Patients and methods: A total of 99 patients received age-adapted CT (C5R protocol) followed by radiotherapy. Patients younger than 61 years (group 1, n = 45) received the full C5R with MTX, doxorubicin, vincristine, cyclophosphamide, and cytarabine. Patients aged 61–70 years (group 2, n = 36) received reduced doses. Patients older than 70 years (group 3, n = 18) received four courses of MTX, cyclophosphamide, and etoposide.

Results: Median age was 63 years and 51% of patients had performance status of more than one. Seventeen patients died of toxicity during CT. Complete response was achieved in 56%, 53%, and 28% of patients in groups 1, 2, and 3, respectively. With a median follow-up of 83 months, the 5-year progression-free survival was 31%, 28%, and 11% and the 5-year overall survival 42%, 31%, and 17% for groups 1, 2, and 3, respectively. Leukoencephalopathy occurred in 32% of assessable patients, in both group 1 and groups 2–3.

Conclusion: The C5R protocol was feasible in the multicentric setting with favorable long-term survival in patients younger than 60 years. Despite dose adaptation, results in older patients were disappointing.

Design and methods: To evaluate International Prognostic Index (IPI) score before and after rituximab introduction and to validate the absolute lymphocyte count (ALC)/revised International Prognostic Index (R-IPI) model, we carried out a retrospective analysis on a total of 831 patients with DLBCL.

Results: Our results show that IPI lost its discriminating power with the introduction of rituximab. The analysis of our second set allowed us to validate the ALC/R-IPI model. The R-IPI and ALC/R-IPI could still be used for designing clinical trials, but both have difficulty recognizing a high percentage of poor prognosis patients, though it remains an important goal of a good prognostic model considering the modest impact of salvage treatments on survival.

Conclusions: A new model on the basis of significant variables in the rituximab era and built on a large database of patients treated with rituximab is urgently needed. As prognostic models are changing with the efficacy and mechanisms of action of treatment utilized, looking for a new prognostic score is a never-ending story in which researchers are trying to hit a continuously moving target.

Patients and methods: We conducted a multicentre open-label phase I/II trial of PI-88 in combination with docetaxel. The primary end point was PSA response. Secondary end points included toxicity, radiologic response and overall survival. Doses of PI-88 were escalated to the maximum tolerated dose; whereas docetaxel was given at a fixed 75 mg/m² dose every three weeks

Results: Twenty-one patients were enrolled in the dose-escalation component. A further 35 patients were randomly allocated to the study to evaluate the two schedules in phase II trial. The trial was stopped early by the Safety Data Review Board due to a higher-than-expected febrile neutropenia of 27%. In the pooled population, the PSA response (50% reduction) was 70%, median survival was 61 weeks (6–99 weeks) and 1-year survival was 71%.

Conclusions: The regimen of docetaxel and PI-88 is active in CRPC but associated with significant haematologic toxicity. Further evaluation of different scheduling and dosing of PI-88 and docetaxel may be warranted to optimise efficacy with a more manageable safety profile.

Patients and methods: A total of 43 patients with stage IIIB–IV NSCLC and Eastern Cooperative Oncology Group (ECOG) PS of two or more with good functional status were prospectively recruited. Oral vinorelbine was administered at the dose of 60 mg/m² on days 1–8 every 3 weeks. Primary end points were response rate and safety.

Results: Overall response rate was 18.6% with 8 partial responses; 18 of 43 (41.8%) experienced stable disease lasting >12 weeks and 17 of 43 (39.6%) disease progression for an overall clinical benefit of 60.4%. Median time to progression was 4.0 (range 2–22) months and median overall survival 8.0 (range 3–35) months. Treatment was well tolerated. Of 187 cycles, we did not observe any grade 3/4 toxicity with the exception of a single not-febrile G3 neutropenia. Regardless of severity, main toxic effects observed were nausea in 48.1% and vomiting in 22.9% of patients, anemia in 43.2%, fatigue in 32.6% and leukopenia in 23.2%.

Conclusion: Single-agent oral vinorelbine is extremely safe in elderly patients with advanced NSCLC and ECOG PS of two or more and may represent a valid option in this very special population.

Patients and methods: Patients in complete remission or an unconfirmed complete remission after first-line therapy who received FDG–PET/CT during their follow-up were analyzed retrospectively. Confirmatory biopsy was mandatory in case of recurrence.

Results: Overall, 134 patients were analyzed. Forty-two (31.3%) patients had a recurrence. The positive predictive value of FDG–PET/CT was 0.98. Single-factor analysis identified morphological residual mass [P = 0.0005, hazard ratio (HR) 3.4, 95% confidence interval (CI) 1.7–6.6] and symptoms (P < 0.0001, HR 4.9, 95% CI 2.4–9.9) as significant risk factors for relapse. By multivariate analysis, morphological residual mass was the only significant risk factor for early follow-up (<24 months) (P = 0.0019, HR 7.6, 95% CI 2.1–27.3). Advanced stage (P = 0.0426, HR 3.6, 95% CI 1.1–12.3) and the presence of symptoms (P = 0.0009, HR = 14.6, 95% CI 3.0–69.7) were found to be significant risk factors for later follow-up (>24 months).

Conclusions: Asymptomatic patients without morphological residues and an early stage of disease do not need a routine FDG–PET/CT for follow-up. Asymptomatic patients with morphological residues should receive routine follow-up FDG–PET/CT for the first 24 months. Only patients with advanced initial stage do need a routine follow-up FDG–PET/CT beyond 24 months.

Patients and methods: In 324 BC from patients with long-term follow-up, the TGF-β1 and TGF-βRII transcript and protein expression levels were assessed.

Results: TGF-β1 and TGF-βRII down-expression was significantly associated with BC. Negative TGF-β1 and TGF-βRII protein status was associated with the development of distant metastasis (P = 0.003 and P = 0.029, respectively). In multivariate analysis, TGF-β1-positive tumours were associated with increased disease-free survival (DFS) [hazard ratio (HR) = 0.489, P = 0.003]. TGF-βRII positivity was an independent prognostic factor for DFS (HR = 0.439, P = 0.001) and overall survival (OS) (HR = 0.409, P = 0.003) in human epidermal growth factor receptor-2 (HER2)-negative patients. Absence of TGF-β1 and TGF-βRII proteins in breast tumour cells was significantly associated with metastasis development.

Conclusions: To the best of our knowledge, this is the first report indicating the relevance of HER2 status in discriminating TGF-βRII as a prognostic marker for DFS and OS in human BC. These data indicate that TGF-βRII protein analysis in tumour cells could be introduced in clinical practice as additional prognostic biomarker in HER2-negative BC.

Materials and methods: From October 2002 to January 2004, 62 patients with locally advanced NPC who underwent ¹⁸F-FDG PET/CT scan before and after radiotherapy were reviewed retrospectively. We examined the association of SUV_max and the results of long-term follow-up of the patients.

Results: Patients having tumors with a lower SUV_max had significantly better 5-year overall survival (OS) (P= 0.0187) and disease-free survival (DFS) (P = 0.0163) than patients with a greater SUV_max. The patients who showed with metabolic complete response had a significantly higher 5-year OS (P = 0.0237) and DFS (P = 0.0186) than patients with metabolic partial response. Poor prognosis was found in patients with the SUV_max of neck nodes larger than that at the primary tumor site (SUV_max-N > SUV_max-P) (P = 0.0440).

Conclusions: ¹⁸F-FDG uptake, as measured by the SUV_max before radiotherapy and metabolic response after radiotherapy, may predict the prognosis in locally advanced NPC. High ¹⁸F-FDG uptake before and after radiotherapy may be useful for identifying patients requiring more aggressive treatment.

Patients and methods: Patients had a maximum of three prior chemotherapy lines with no more than two prior platinum-containing regimens and a progression-free interval after the last dose of platinum <12 months. A total dose of 4 mg/m²/cycle (0.8 mg/m²/day from day 1 to day 5) was administered, repeated every 28 days.

Results: From June 2005 to December 2005, 69 assessable patients were enrolled. The best overall response to study treatment by combined CA-125 and RECIST criteria was partial response in 17 patients (24.6%) and disease stabilization in 22 patients (31.9%). The median time to progression and overall survival were 3.8 and 16.2 months, respectively. A total of 312 cycles were administered. Neutropenia grade 4 and thrombocytopenia grade 4 occurred in 17.4% and 7.2% of patients, respectively. Diarrhea grade 4 was never observed. Asthenia and fatigue were reported by 36.2% and 18.8% of patients, but were all grade 2 or less.

Conclusion: Gimatecan is a new active agent in previously treated ovarian cancer with myelosuppression as main toxicity.

Patients and Methods: Previously untreated patients with ABC were randomly assigned to receive docetaxel 75 mg/m² plus epirubicin 75 mg/m² (DE) on day 1 or docetaxel 75 mg/m² on day 1 plus capecitabine 950 mg/m² orally twice daily on days 1–14 (DC) in 21-day cycles. Previous anthracycline-based (neo)-adjuvant chemotherapy was allowed if completed >1 year before enrollment. The primary objective of the study was to compare time to disease progression (TTP).

Results: One hundred and thirty-six women were treated on each arm and median TTP was 10.6 versus 11.0 months (P = 0.7), for DE and DC, respectively. According to RECIST criteria we observed 15 (11%) versus 11 (8%) complete responses and 55 (40%) versus 61 (45%) partial responses (P = 0.8), with DE and DC, respectively. Severe toxicity included grade 3–4 neutropenia (57% versus 46%; P = 0.07), febrile neutropenia (11% versus 8%; P = 0.4), hand–foot syndrome (0% versus 4%; P = 0.02), grade 2–3 anemia (20% versus 7%; P = 0.001) and asthenia (12% versus 6%; P = 0.09) with DE and DC, respectively.

Conclusions: The DE and DC regimens have similar efficacy but different toxicity. Either regimen can be used as front-line treatment of ABC.

Material and methods: We retrospectively investigated the outcome of 122 patients with nodal micrometastases from breast cancer followed up for 60 months.

Results: At univariate analysis, worse DFS was related to features of primary tumor (multifocality P = 0.002; size >2 cm, P = 0.022; grade P = 0.022; absence of estrogen P < 0.001 and progesterone P < 0.001 receptors; HER-2 overexpression P = 0.006; vascular invasion P = 0.039; proliferative fraction ≥20% P = 0.034) and micrometastases (sinusal localization P = 0.010). Among the above-mentioned features, two were strongly associated with worse DFS in the multivariate model, i.e. negative receptorial status [hazard ratio (HR) = 11.24, 95% confidence interval (CI) 4.06–31.09; P < 0.001] and sinusal localization of micrometastasis (HR = 3.66, 1.18–11.36; P = 0.025). The OS was influenced by multifocality (P < 0.001) and receptor status (P = 0.005).

Conclusion: Our results indicate that in patients affected by breast cancer, in addition to the well-known pathological features of primary tumor, sinusal localization of micrometastasis strongly impacts on the prognosis.

Patients and methods: PET scans were carried out in 113 HL patients at the end of therapy and during the follow-up either in regular intervals or in a suspected relapse. Median follow-up of the group was 34 months.

Results: Overall 327 PET scans were evaluated in 113 patients (median three PET scans per patient). At the end of therapy, 94 (83.2%) patients were PET negative and 19 (16.8%) PET positive. Regular follow-up PET scans in 67 of 94 PET-negative patients correctly identified tumor in 6 of 155 PET scans (3.9%). In 27 of 94 patients with clinically suspected relapse, 5 of 27 PET scans (18.5%) confirmed tumor.

Conclusions: Our analysis showed that there is no need for regular follow-up with PET scans in PET-negative patients at the end of therapy: the ratio of true-positive PET scans during the follow-up is low (3.9%). Positive PET at the end of therapy and during follow-up should be evaluated with caution.

Patients and methods: Chemonaive patients with asymptomatic mCRC who did not require immediate chemotherapy-induced tumor reduction received a 400-mg thrice daily loading dose of enzastaurin on day 1 of cycle 1, followed by 500 mg once daily for the remaining 28-day cycles. Progression was assessed on the basis of radiographic imaging, rise in carcinoembryonic antigen or lactate dehydrogenase (LDH) levels or by appearance of clinical symptoms.

Results: Twenty-eight patients received daily enzastaurin. The 6-month PFS rate was 28% [95% confidence interval (CI) 13%–45%] and median PFS was 1.9 months (95% CI 1.8–4.5 months). Twelve (43%) patients had stable disease with a median duration of 6.1 months. The survival rate at 20 months was 77% (95% CI 47%–92%). No grade 4 toxicity was reported and grade 3 toxic effects were observed in three patients with one patient showing probable drug-related elevation of liver transaminases.

Conclusion: The window design in asymptomatic patients with mCRC can be safely applied to assess the activity and safety of novel cytostatic agents like enzastaurin.

Patients and methods: In this single-arm, multicenter phase II study, patients received first-line bevacizumab 15 mg/kg and docetaxel 75 mg/m² on day 1 and capecitabine 825 mg/m² twice per day on days 1–14 every 21 days. Primary and secondary end points were tumor response rate (RR), overall survival (OS), progression-free survival (PFS), and toxicity.

Results: A total of 45 assessable patients received TX-BV for a median of seven cycles. Two complete and 20 partial responses were observed (overall RR 49%); nine patients had stable disease >6 months, for a clinical benefit rate of 69%. Median response duration was 11.8 months. Median OS and PFS were 28.4 and 11.1 months, respectively. Grade 3/4 adverse events included hand–foot syndrome (29%), fatigue (20%), febrile neutropenia (18%), and diarrhea (18%). In cycles 3–10, median dose levels of docetaxel and capecitabine were 60 mg/m² and 660 mg/m², respectively.

Conclusion: TX-BV demonstrated significant activity; dose modifications were required to manage drug-related toxic effects.

Materials and methods: Patients with taxane-sensitive solid tumors were eligible. The main dose escalation foresaw 50% ridaforolimus increments from 25 mg with a fixed PTX dose of 80 mg/m², both given weekly 3 weeks in a 4-week cycle. Collateral levels with a lower dose of either drug were planned upon achievement of the maximum tolerated dose in the main escalation. Pharmacodynamic studies in plasma, peripheral blood mononuclear cells (PBMCs) and skin biopsies and pharmacokinetic (PK) interaction studies at cycles 1 and 2 were carried out.

Results: Two recommended doses were determined: 37.5 mg ridaforolimus/60 mg/m² PTX and 12.5 mg/80 mg/m². Most frequent toxic effects were mouth sores (79%), anemia (79%), fatigue (59%), neutropenia (55%) and dermatitis (48%). Two partial responses were observed in pharyngeal squamous cell and pancreatic carcinoma. Eight patients achieved stable disease ≥4 months. No drug interaction emerged from PK studies. Decrease of eukaryotic initiation factor 4E-binding protein1 (4E-BP1) phosphorylation was shown in PBMCs. Similar inhibition of phosphorylation of 4E-BP1 and mitogen-activated protein kinase was present in reparative epidermis and vascular tissues, respectively.

Conclusion: Potential antiangiogenic effects and encouraging antitumor activity justify further development of the combination.

Materials and methods: PCR–polyacrylamide gel electrophoresis method was used to genotype the NFKB1 –94 insertion/deletion ATTG polymorphism in 233 women with CSCC and 365 ethnicity-matched healthy control women. The genotyping method was confirmed by the DNA sequencing analysis.

Results: The frequency of ATTG₂/ATTG₂ genotype and ATTG₂ allele in the CSCC patients was significantly higher than that of controls, indicating that the –94 insertion/deletion ATTG polymorphism in NFKB1 promoter was associated with CSCC [P = 0.001, odds ratio (OR) = 2.560, 95% confidence interval (CI) 1.459–4.492 and P = 0.001, OR = 1.493, 95% CI 1.168–1.908, respectively]. Results of stratified analyses revealed that this polymorphism is associated with younger age (≤35 years) and positive parametrial invasion but not with tumor differentiation, high clinical stage or lymph node status.

Conclusion: Our results indicate that the functional NFKB1 –94 insertion/deletion ATTG polymorphism is associated with CSCC, especially with younger age (≤35 years) and positive parametrial invasion of CSCC patients.

Patients and methods: This phase I dose-finding study investigated escalating doses of paclitaxel (Taxol) given concurrently with panitumumab, carboplatin and intensity-modulated radiotherapy (IMRT) for stage III–IVB SCCHN. Untreated patients with oral cavity, oropharynx, larynx, hypopharynx or unknown primaries were eligible. Additional eligibility criteria included measurable disease, good performance status and no contraindication to therapy. Patients received weekly fixed doses of panitumumab and carboplatin plus escalating doses of paclitaxel with IMRT.

Results: Nineteen patients were enrolled on to two dose levels (DLs): weekly paclitaxel 15 mg/m² (n = 3) and 30 mg/m² (n = 16). One dose-limiting toxicity occurred in DL 2, which was declared the maximum tolerated dose. All patients experienced mucositis, primarily grade 3 or more. Oral pain, xerostomia, dysphagia, weight loss, dermatitis, nausea and acneiform rash were frequent. All patients had partial response according to RECIST, whereas the overall complete clinical response rate was 95%. At median follow-up of 21 months, 18 of 19 patients (95%) remained disease free.

Conclusions: Panitumumab, carboplatin, paclitaxel and IMRT are well tolerated and appear highly active in the treatment of SCCHN. Further study of this regimen in SCCHN is warranted.

Patients and methods: A total of 158 consecutive patients with PMNSGCT who received platinum-based chemotherapy followed by complete surgical extirpation of residual disease at Indiana University from 1982 to 2007 were retrospectively reviewed. Thirty-five of these 158 patients had rising STM at time of resection.

Results: Thirty-five patients (34 males and 1 female) comprise the basis of this report. Three patients had rising human chorionic gonadotropin, and the remaining 32 patients had rising alpha-fetoprotein at the time of thoracic surgery. Twenty-four of the 35 (69%) pathologically demonstrated viable germ-cell tumor, while 8 patients had teratoma and 3 patients had necrosis only at time of resection, despite the presence of rising STM. Twenty-seven patients normalized their tumor markers postoperatively. Twenty-one of 35 died, 5 were lost to follow-up, and 9 are alive. Of the nine patients alive, seven are continuously disease free with median follow-up of 64 months (range 25–220 months).

Conclusion: The presence of rising STM doesn't preclude successful therapy with surgical resection, especially if carried out by experienced thoracic surgical oncologists.

Patients and methods: Patients with advanced gynecological malignancies received BIBF 1120 twice-daily (b.i.d.) continuously at 100, 150, 200 or 250 mg, combined with paclitaxel (175 mg/m²) and carboplatin (area under the curve 5 min·mg/ml) every 3 weeks. The MTD, safety, pharmacokinetics (PK) and clinical activity were evaluated.

Results: Twenty-two patients were treated. Three experienced dose-limiting toxic effects in the first treatment cycle: 1 of 13 at 200 mg b.i.d. BIBF 1120 [diarrhea, common terminology criteria for adverse events (CTCAE) grade 3]; two of two at 250 mg b.i.d. BIBF 1120 (elevated alanine aminotransferase and aspartate aminotransferase, CTCAE grade 3/4). The MTD was defined as 200 mg b.i.d. Principal adverse events were gastrointestinal disorders. No clinically relevant drug–drug interaction was observed after 20 days treatment with 200 mg b.i.d. BIBF 1120 on the PK of paclitaxel or carboplatin and vice versa.

Conclusions: The MTD of BIBF 1120 in a 20-day continuous dosing regimen with standard-dose paclitaxel and carboplatin was 200 mg b.i.d. This combination had an acceptable safety profile and no clinically relevant drug–drug interactions. Further evaluation of this combination is warranted in this indication.

Materials and methods: All diagnoses of high-grade osteosarcoma were included despite histological varieties, age, site and stage. Of the 1656 cases observed, 198 patients were excluded (41 consultation only, 129 low-grade varieties, and 28 lost to follow-up). Within 1458 included patients, 1032 had characteristics to be enrolled in conventional clinical trials (classic histology, age <41, localized, and extremity disease). Data are also analyzed in subgroups to define patients who benefited most.

Results: With a median follow-up of 12 years (5–25 years), 754 patients (51.7%) are alive, of whom 613 continuously disease free. Survival at 5, 10, and 15 years is 57%, 52%, and 51%, respectively. Patients candidates for clinical trials have a survival rate of 68%, 64%, and 61%, respectively. Survival for the other patients is 30%, 25%, and 24%, respectively. Trend (joinpoint statistical analysis at real 5-year follow-up) shows a yearly statistically significant improvement of 1.31% (95% confidence interval 0.5% to 2.1%) from 51% for patients treated in 1982 to 68% for those treated in 2002. Patients who statistically benefited were those who relapsed or presented with metastatic disease at diagnosis or had axial tumors.

Conclusions: Despite the lack of new drugs for osteosarcoma, survival has statistically improved, especially for those patients with the worst outcome. Aggressive treatments are recommended for all patients including those with poor prognosis.

Patients and methods: A total of 605 patients with LARC who underwent multimodality treatment up to 2005 were studied. The basic treatment principle was preoperative (chemo)radiotherapy, intended radical surgery, IORT and elective adjuvant chemotherapy (aCT). In uni- and multivariate analyses, risk factors for local recurrence (LR), distant metastases (DM) and overall survival (OS) were studied.

Results: Chemoradiotherapy lead to more downstaging and complete remissions than radiotherapy alone (P < 0.001). In all, 42% of the patients received aCT, independent of tumor–node–metastasis stage or radicality of the resection. LR rate, DM rate and OS were 12.0%, 29.2% and 67.1%, respectively. Risk factors associated with LR were no downstaging, lymph node (LN) positivity, margin involvement and no postoperative chemotherapy. Male gender, preoperatively staged T4 disease, no downstaging, LN positivity and margin involvement were associated with a higher risk for DM. A risk model was created to determine a prognostic index for individual patients with LARC.

Conclusions: Overall oncological results after multimodality treatment of LARC are promising. Adding aCT to the treatment can possibly improve LR rates.

Materials and methods: We used the human MCF-7 breast cancer cell line as a model and examined the apoptosis by Hoechst–propidium iodide staining fluorescence imaging and flow cytometry.

Results: Our data indicated that daidzein induces antiproliferative effects in a concentration- and time-dependent manner. We demonstrated that daidzein-induced apoptosis in MCF-7 cells was initiated by the generation of reactive oxygen species (ROS). Furthermore, we showed that this daidzein-induced ROS generation was accompanied by disruption of mitochondrial transmembrane potential, down-regulation of bcl-2, and up-regulation of bax, which led to the release of cytochrome C from the mitochondria into the cytosol, which, in turn, resulted in the activation of caspase-9 and caspase-7, and ultimately in cell death. The induction of the mitochondrial caspase-dependent pathway was confirmed by pretreatment with pan-caspase inhibitor z-VAD-fmk and antioxidant N-acetyl-L-cysteine.

Conclusion: Accordingly, daidzein could induce breast cancer cell apoptosis through the mitochondrial caspase-dependent cell death pathway.

Materials and methods: Nude mice, bearing human pancreatic carcinoma xenografts, were treated with either combined anti-EGFR (cetuximab) and anti-HER2 (trastuzumab) or gemcitabine, and tumor growth was observed.

Results and conclusion: In first-line therapy, mice survival was significantly longer in the 2mAbs group compared with gemcitabine (P < 0.0001 for BxPC-3, P = 0.0679 for MiaPaCa-2 and P = 0.0019 for Capan-1) and with controls (P < 0.0001). In second-line therapy, tumor regressions were observed after replacing gemcitabine by 2mAbs treatment, resulting in significantly longer animal survival compared with mice receiving continuous gemcitabine injections (P = 0.008 for BxPC-3, P = 0.05 for MiaPaCa-2 and P < 0.001 for Capan-1). Therapeutic benefit of 2mAbs was observed despite K-Ras mutation. Interestingly, concerning the mechanism of action, coinjection of F(ab')₂ fragments from 2mAbs induced significant tumor growth inhibition, compared with controls (P = 0.001), indicating that the 2mAbs had an Fc fragment-independent direct action on tumor cells. This preclinical study demonstrated a significant improvement of survival and tumor regression in mice treated with anti-EGFR/anti-HER2 2mAbs in first- and second-line treatments, compared with gemcitabine, independently of the K-Ras status.

Patients and methods: In 1005 patients, paraffin-embedded tissues of transurethral resection or cystectomy were evaluated by immunohistochemistry (IHC), using antibodies against HER2. All samples with a 2+ or 3+ HER2 overexpression were evaluated by FISH.

Results: HER2 overexpression was observed in 93 (9.2%) tumors (2+: 42 tumors and 3+: 51 tumors). Using FISH, all HER2 3+ tumors had a gene amplification, whereas no amplification was found in 2+ tumors. Intratumoral heterogeneity was observed in 35% of cases. These tumors showed the same heterogeneous pattern, with adjacent 3+ positive and negative areas by both IHC and FISH.

Conclusions: This study showed that 5.1% of invasive bladder carcinomas had a HER2 gene amplification. These findings may have clinical implications for the management of patients with HER2-positive locally advanced or metastatic bladder cancer, as they could be potential candidates for targeted therapy.

Patients and methods: We retrospectively analyzed the efficacy and toxicity of MINE (mesna, ifosfamide, mitoxantrone, and etoposide) alternated with ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) in the treatment of 61 relapsed or refractory HL patients after ABVD-based chemotherapy.

Results: Overall, 25 patients (41%) achieved a complete response (CR), 23 (38%) a partial response (PR), 4 (7%) a stable disease, and 8 (13%) progressed for an overall response rate of 79%. Response to first-line chemotherapy was the most important prognostic factor for response to MINE–ESHAP (P = 0.041). No grade 4 extrahematologic toxic effects or toxic deaths were observed. Adequate peripheral blood stem-cell collection was achieved in 56 of 59 (95%) mobilized patients. Overall survival and event-free survival after HDT and ASCT were significantly higher for patients achieving CR/PR in comparison with those refractory to MINE–ESHAP (46% and 35% versus 74% and 69%, respectively).

Conclusion: MINE–ESHAP results in a high response rate with acceptable toxicity in patients with HL having failed ABVD-based treatment.

Patients and methods: The location and degree of LVD/BVD were analysed in primary tumours (n = 138/140) and in their subgroups of non-RT (n = 74) and RT (n = 64/66). Further, the degree of LVD/BVD was examined in the corresponding distant normal mucosa (n = 35/31) and adjacent normal mucosa (n = 72/91). All sections were immunohistochemically examined by using D2-40 and CD34 antibodies.

Results: In the whole series of the patients, a higher LVD at the periphery was related to negative p53 expression (P = 0.03) and favourable survival independent of tumour–node–metastasis stage, differentiation and p53 expression (P = 0.03). LVD was increased in p53-negative tumours after RT (P = 0.01).

Conclusion: LVD at the periphery of the tumour was an independent prognostic factor in rectal cancer patients.

Materials and methods: Clinicopathologic features and immunohistochemical expression of Skp2 and p27 were studied retrospectively in 671 patients treated with cyclophosphamide, vincristine, doxorubicin and prednisolone (CHOP) or cyclophosphamide, vincristine, doxorubicin and prednisolone plus rituximab (R-CHOP). The median follow-up periods were 43.2 months in the CHOP group (n = 425) and 24.0 months in the R-CHOP group (n = 246).

Results: High Skp2 or low p27 expression correlated significantly with poor overall survival (OS) and progression-free survival (P < 0.001) in both treatment groups. The prognostic value of Skp2 or p27 expression was independent of the parameters included in the International Prognostic Index by multivariate analysis. Patients with high Skp2 expression in combination with low p27 expression showed the worst survival.

Conclusions: Addition of rituximab to the CHOP regimen did not provide a beneficial outcome to patients with diffuse large B-cell lymphoma with high Skp2 expression and low p27 expression. Skp2 and p27 may be useful prognostic markers in the rituximab era.

Patients and methods: In 334 mRCC patients treated with sunitinib, we tested thresholds from –45% to +10%. We classified patients as ‘responders’ when the best relative variation of the sum of longest diameters (SLD) reached the tested threshold and as ‘nonresponders’ otherwise. For each tested threshold, the median PFS of the two groups were compared. Receiver operating characteristic (ROC) analysis was also carried out among the 103 patients that progressed during follow-up. Finally, the ‘optimal’ threshold was retested on an independent cohort of 39 patients.

Results: The SLD threshold of –10% gave the most significant difference. It divided patients into 256 responders and 78 nonresponders (median PFS 11.1 and 5.6 months). The same –10% threshold was found using the ROC analysis. Results were confirmed on the external validation cohort.

Conclusion: A variation of –10% in the SLD accurately and rapidly identifies mRCC patients benefiting from sunitinib.

Methods: Analyses were based on the Asia Pacific Cohort Studies Collaboration of 506 648 study participants (408 381 Asia, 98 267 Australasia) drawn from 38 population-based cohort studies. Cox proportional hazards regression was used to estimate the relationship between height and cancer rates.

Results: A total of 3 272 600 person-years of follow-up gave rise to 7497 cancer deaths (4415 in Asia; 3082 in Australasia). After multiple adjustments and left censoring, taller individuals experienced increased rates of carcinoma of the intestine (men and women); all cancers, liver, lung, breast, ‘other’ malignancies (all women); and cancers of the prostate and bladder (men). No consistent regional (Asia versus Australasia) or sex differences were observed.

Conclusions: In the present study, taller men and women had an elevated risk of selected malignancies. These associations did not differ appreciably between Asian and Caucasian populations.

Methods: We systematically reviewed studies assessing the prevalence of mental health conditions in acute care hospitals with comprehensive structured clinical interviews.

Results: Of 46 retrieved manuscripts, eight were deemed eligible for this meta-analysis. Within the studies, 1448 cancer patients had been assessed, whereby 456 were diagnosed having a mental health disorder. The prevalence rates ranged from 23% (breast cancer patients in Turkey) to 53% (elderly cancer patients in Uganda). The combined prevalence estimate is 32% (95% confidence interval 27% to 37%).

Conclusion: One-third of the cancer patients in acute care hospitals is suffering from mental health disorders and need appropriate treatment.

Patients and methods: We evaluated AR using immunohistochemistry from 413 whole sections from January 2008 to March 2009 and analyzed the relationship between AR and clinicopathological parameters. Tumors with ≥10% nuclear-stained cells were considered to be positive for AR. The differences among variables were calculated by chi-square test.

Results: The expression rate of AR was 72.9% higher than those of estrogen receptors (ER) and progesterone receptors. AR expression was significant in patients with no elevated preoperative serum cancer antigen 15-3 levels, smaller tumor size, lower histologic grade and hormone receptor-positive and non-triple-negative breast cancer. However, AR expression was observed in 35% of triple-negative cancers. Metaplastic, medullary and mucinous types of carcinomas showed less AR expression. In the ER-negative subgroup, AR was significantly correlated with human epidermal growth factor receptor type 2 (HER-2) overexpression.

Conclusions: AR is expressed in a significant number of breast cancers and is associated with lower tumor burden and favorable differentiation. There are many issues to be further investigated such as whether AR is an independent prognostic factor, whether it is a therapeutic target for the triple-negative breast cancers and whether it is associated with HER-2 signaling in ER-negative tumors.

Methods: A retrospective pooled analysis incorporating three phase III studies was conducted: Multicenter International Study of Oxaliplatin, 5-Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) (adjuvant treatment; stage II/III colon cancer), EFC4584 (second-line treatment; metastatic CRC), and EFC2962 (first-line treatment; metastatic CRC). Patients were ineligible for the studies if they had known PSN (EFC4584) or PSN grade ≥1 (MOSAIC and EFC2962) at baseline. The incidence of PSN was evaluated retrospectively in patient subgroups with or without DM at baseline that received FOLFOX. Kaplan–Meier curves were used to assess the probability of PSN with increasing cumulative oxaliplatin dose.

Results: Of 1587 patients enrolled across the three studies, 135 (8.5%) had DM at baseline. The incidence of PSN (non-DM/DM) was 45.0%/46.7% (grade 1), 28.6%/26.7% (grade 2), and 13.0%/12.6% (grade 3). The probability of PSN by cumulative dose of oxaliplatin was similar in DM and non-DM patients.

Conclusions: This retrospective analysis indicates that oxaliplatin-based therapy does not influence the incidence, severity, or time to onset of PSN in asymptomatic DM patients with CRC who meet eligibility criteria for clinical trials.

Patients and methods: From May 1997 to September 2007, 39 pretreated MF and PTCLU patients received gemcitabine. Inclusion criteria were as follows: histologic diagnosis of MF or PTCLU; relapsed/refractory disease; age ≥18 years; and World Health Organization performance status of two or less. Nineteen patients had MF and 20 PTCLU. All patients with MF had a T3–T4, N0, and M0 disease and patients with PTCLU had stage III–IV disease. Gemcitabine was given on days 1, 8, and 15 on a 28-day schedule (1200 mg/m²/day) for a total of three to six cycles.

Results: Overall response rate was 51% (20 of 39 patients); complete response (CR) and partial response (PR) rates were 23% (9 of 39 patients) and 28% (11 of 39 patients), respectively. Patients with MF had a CR rate of 16% and a PR rate of 32% compared with a CR rate of 30% and a PR rate of 25% of PTCLU patients. Among the CR patients, 7 of 9 are in continuous complete response with a variable disease-free interval (15–120 months).

Conclusion: In our experience, gemcitabine proved to be effective in pretreated MF and PTCLU patients, even in the long term.

Patients and methods: One hundred and thirty-six DLBCL patients who were treated with R-CHOP from 2003 to 2007 were analyzed in the present study.

Results: ALC ≥1.0 x 10⁹/l predicted a longer 3-year progression-free survival (PFS) and 3-year overall survival (OS) versus ALC <1.0 x 10⁹/l (82.6% versus 60.0%, P = 0.005 and 87.2% versus 62.0%, P < 0.001, respectively). Non-GC type had similar PFS and OS to germinal center type (68.2% versus 80.0%, P = 0.074 and 72.7% versus 82.9%, P = 0.111, respectively). However, considering clinical influence of the ALC according to immunophenotype, low ALC in non-GC type DLBCL was associated with lower PFS and OS compared with others (PFS, P = 0.002; OS, P < 0.001). Multivariate analysis revealed that low ALC in non-GC type had lower PFS [hazard ratio (HR) = 3.324, P = 0.001] and OS (HR = 4.318, P < 0.001), independent of international prognostic index.

Conclusion: A low ALC in non-GC type DLBCL counteracted the beneficial effect of rituximab on survival.

Patients and methods: A total of 385 patients with invasive primary breast carcinomas and paired lymph nodes (n = 211) were assessed for ER, PR and HER2 expression using quantitative immunofluorescence. Cut-points were defined by comparison with tumours scored by immunohistochemistry (IHC) and FISH. Differences in expression for each of the markers and molecular phenotype were analysed.

Results: Quantitative receptor expression shows a wide dynamic range compared with IHC. Overall, 46.9% cases had disparate breast/node receptor status of at least one receptor. Many of the differences in expression between primary tumour and node are large magnitude (greater than fivefold) changes. Triple-negative phenotype changes in 23.1% of cases.

Conclusions: A significant number of patients show discordant quantitative expression of molecular markers between primary and nodal disease. Appropriately measured, lymph node receptor status could be a more accurate measurement for guiding adjuvant therapy, which requires testing in a clinical trial.

Patients and methods: We conducted a retrospective study investigating the effects of statins on the prognosis of diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). Newly diagnosed DLBCL patients were analyzed (n = 256), including 35 patients taking statins.

Results: The 3-year progression-free survival rates were 84% and 73% (P = 0.38), while the overall survival rates were 89% and 78% (P = 0.28) for those patients treated with and without statins, respectively. After adjusting for the International Prognostic Index and serum cholesterol level, statin use was not associated with prognosis.

Conclusions: These results indicate that statins do not influence the clinical prognosis of DLBCL treated with RCHOP. Further studies with larger numbers of patients are warranted to confirm the prognostic significance of statins for patients with DLBCL receiving rituximab-containing chemotherapy.

Patients and methods: LEAP opened globally and enrollment continued until lapatinib received regulatory approval in each participating country. Patients were assessed for progression-free survival (PFS) and overall survival (OS) and monitored for serious adverse events (SAEs).

Results: As of 30 September 2008, 4283 patients from 45 countries enrolled in LEAP. The median treatment duration was 24.7 weeks. The most common drug-related SAEs were diarrhea (9.7%), vomiting (4.3%), and nausea (2.4%) and were mainly grade 3 or higher. The incidences of special interest SAEs were decreased left ventricle ejection fraction (0.5%), interstitial lung disease/pneumonitis (0.2%), and serious hepatobiliary events (0.4%). This safety profile is consistent with the overall lapatinib program. The median PFS and OS were 21.1 [95% confidence interval (CI) = 20.1–22.3] and 39.6 (95% CI = 37.7–40.7) weeks, respectively (n = 4006). Subgroup analysis showed longer PFS and OS in patients who had not received prior capecitabine.

Conclusions: These results demonstrate the safety and efficacy of lapatinib in a broader patient population compared with a clinical trial.

Patients and methods: A total of 52 patients with advanced solid tumors received a 30-min infusion of escalating doses of sagopilone (0.6–29.4 mg/m²) every 3 weeks. Nine additional patients were recruited to a 3-h infusion arm (16.53- or 22.0-mg/m² dose) to assess the incidence of neuropathy with prolonged infusion.

Results: The MTD was established as 22.0 mg/m². DLTs comprised peripheral sensory neuropathy (PNP), infection, hyponatremia, diarrhea, and central ataxia. PNP was the most common grade 3 event, with a similar incidence in the 30-min and 3-h arms. Hematologic adverse events were rare and of low intensity. One confirmed partial response (PR) and one unconfirmed PR were reported in the 30-min arm, and a further unconfirmed PR was observed in the 3-h arm. Eleven patients achieved disease stabilization. Sagopilone showed high levels of tissue binding and no obvious serum accumulation in both arms.

Conclusions: These data demonstrate that sagopilone therapy is feasible and well tolerated. The recommended dose for phase II studies is 16.53 mg/m², once every 3 weeks.

Patients and methods: We retrospectively collected data from 147 patients treated with a doxorubicin-containing regimen from 1998 to 2008.

Results: Progression-free survival (PFS) was 6.5 months (range 1–141 months). We did not identify an independent prognostic factor for PFS. Planned dose of doxorubicin was the sole parameter improving PFS [hazard ratio (HR) = 0.13, P = 0.023]. Overall survival (OS) was 17 months (range 1–115 months). The sole identified prognostic factor for OS was the interval between initial diagnosis and metastatic relapse. After adjustment to this prognostic factor, metastasectomy improved OS (HR = 0.52, P = 0.012) and the addition of ifosfamide seemed to worsen OS (HR = 1.42, P = 0.028).

Conclusion: In our analysis, combined regimens did not improve the outcome. Maintenance of the doxorubicin dose was associated with improved PFS. Metastasectomy favorably influenced OS.

Patients and methods: Seventy-seven patients with low-grade or mantle cell lymphoma received autologous stem-cell transplantation (ASCT) on a phase II study. Rituximab 375 mg/m² was administered 3 days before mobilization-dose cyclophosphamide, then weekly for four doses after count recovery from ASCT. Immune reconstitution was assessed.

Results: Sixty percent of transplants occurred in first remission. Actuarial event-free survival (EFS) and overall survival (OS) were 60% and 73%, respectively, at 5 years, with 7.2-year median follow-up for OS in surviving patients. Median EFS was 8.3 years. Older age and transformed lymphomas were independently associated with inferior EFS, whereas day 60 lymphocyte counts did not predict EFS or late infections. Early and late transplant-related mortality was 1% and 8%, with secondary leukemia in two patients. B-cell counts recovered by 1–2 years; however, the median IgG level remained low at 2 years. Late-onset idiopathic neutropenia, generally inconsequential, was noted in 43%.

Conclusion: ASCT with rituximab can produce durable remissions on follow-up out to 10 years. Major infections do not appear to be significantly increased or to be predicted by immune monitoring.

Patients and methods: A total of 15 patients were enrolled in the first stage of phase II study. All patients received CAP-GEM every 3 weeks. The primary end point was objective response rate (RR); secondary end points were toxicity, progression-free survival (PFS) and overall survival.

Results: Complete responses (CR) and partial responses were observed in three (20%) and three (20%) patients for a 40% RR, respectively. Grade 1–2 neutropenia, anemia and thrombocytopenia were the most common side-effects, noted in seven (46.7%), five (33.3%) and five (33.3%) patients, respectively. The most common grade 3 toxicity was neutropenia in three patients (20%). Median PFS was 11 months (95% confidence interval 4–17). The 1- and 2-year survival rates were 80% and 67%, respectively.

Conclusion: We have decided to publish the preliminary results because this regimen was more active than that expected. Although our results are preliminary, CAP-GEM shows activity and safety in pretreated TETs. Furthermore, multicenter trials, also in first-line setting, are necessary to confirm our results.

Methods: All patients diagnosed with primary colon cancer stage III from 2001 to 2007 in the area of the Eindhoven Cancer Registry were included (N = 1637). We examined determinants of the administration of adjuvant chemotherapy and their relation to survival.

Results: The proportion of patients receiving adjuvant chemotherapy decreased with increasing age from 85% for patients <65 years to 68% for those 65–74 years and 17% for patients ≥75 years, with large interhospital variation. Elderly patients {odds ratio (OR) 0.1 [95% confidence interval (CI) 0.1–0.1]} and those with comorbidity [OR 0.6 (95% CI 0.5–0.8)] received adjuvant chemotherapy less often. Patients with an intermediate [OR 1.4 (95% CI 1.1–1.9)] or high socioeconomic status [OR 1.5 (95% CI 1.1–2.0)] or stage IIIC [OR 1.5 (95% CI 1.1–2.0)] received adjuvant chemotherapy more often. Adjuvant chemotherapy was the most important predictor of survival. In a multivariable analysis, older age was no longer a significant negative predictor of survival, in contrast to comorbidity, higher tumor stage, poor tumor grade, and male gender. The improvement in survival from 2001 to 2006 did not reach statistical significance.

Conclusion: Adherence to guidelines for adjuvant chemotherapy was still suboptimal in 2007, especially for elderly patients, and differed widely between hospitals.

Patients and methods: One hundred and sixty-two patients with a range of cancers were recruited. QOL and fatigue were measured by Functional Assessment of Cancer Therapy—General and Functional Assessment of Cancer Therapy—Fatigue, respectively, and mood status by Profile of Mood State. The inflammatory marker serum C-reactive protein (CRP) was monitored serially.

Results: Regression analysis indicated that the MQ group significantly improved overall QOL (t₁₄₄ = –5.761, P < 0.001), fatigue (t₁₅₃ = –5.621, P < 0.001), mood disturbance (t₁₂₂ =2.346, P = 0.021) and inflammation (CRP) (t₉₉ = 2.042, P < 0.044) compared with usual care after controlling for baseline variables.

Conclusions: This study indicates that MQ can improve cancer patients’ overall QOL and mood status and reduce specific side-effects of treatment. It may also produce physical benefits in the long term through reduced inflammation.

Materials and methods: The study comprised 32 patients with operable hormone receptor-negative breast cancer and a control group with 43 healthy women. Variables included presence and absence of breast cancer, clinical and histopathology findings, and overall survival.

Results: Plasma D-dimer level was normal in the control group and significantly higher in breast cancer patients (P = 0.001), as well as in nonsurvivors compared with survivors (P = 0.025). The results showed that plasma D-dimer levels were not correlated with clinical and histopathology findings (P > 0.213).

Conclusions: The results taken together indicate the presence of a hypercoagulability state in women with operable hormone receptor-negative breast cancer given the increased levels of D-dimer in this group. Therefore, considering higher levels of D-dimer in patients with a poor outcome, its evaluation may be a promising tool for prognosis in women with operable hormone receptor-negative breast cancer.

Methods: Phase III trials reporting INV and IRC assessments were identified. The difference in end point assessment (IRC – INV) across all study arms was determined. A random-effects model was used to calculate the mean difference between INV and IRC RR as well as PFS. Differences in estimated benefits of treatment (experimental – control) between IRC and INV were determined.

Results: Twenty-one trials were included (18 RR, 8 PFS). The estimated mean difference between IRC- and INV-determined RR was 4.57% [95% confidence interval (CI) 2.95% to 6.19%]. For median PFS, the estimated mean difference was –0.19 (95% CI –0.68 to 0.29) months. The difference in estimated benefits of treatment ranged from –7.0% to 7.2% for RR and –2.0 to +2.4 months for PFS; there was no evidence of systemic bias by INV (P = 0.54 for RR and 0.31 for PFS).

Conclusion: INV overestimate RR compared with IRC. Given the variability in assessing RR and PFS between INV and IRC, an IRC should be considered if the primary end point is on the basis of assessments of changes in tumor lesions.

Materials and methods: All patients with CSI-NSGCT referred from 1998 to 2007 to the British Columbia Cancer Agency and the Oregon Testis Cancer Program were retrospectively reviewed. A total of 233 patients were identified, of which 223 chose active surveillance.

Results: Vascular invasion (VI) was absent, present and unknown in 66%, 27% and 7% of cases, respectively. Overall, 49% of patients had embryonal predominant disease. Fifty-nine patients (26%) relapsed, all but one with good prognosis disease. VI was present in 30 relapsed patients. Most patients relapsed within 2 years (88%). Only 7 of 223 patients (3%) relapsed beyond 2 years. All relapses were in long-term remission following chemotherapy with or without retroperitoneal lymph node dissection (RPLND). Only 17 of 223 patients (8%) required postorchiectomy surgery. Disease-specific survival is 100% after a median follow-up of 52 months (3–136). No patient has required second-line chemotherapy.

Conclusions: Active surveillance for all CSI-NSGCT patients is associated with excellent outcomes comparable with the best results reported with primary RPLND or adjuvant chemotherapy. Nearly 75% of patients are spared any therapy after orchiectomy.

Materials and methods: The clonality of bilateral breast cancer was evaluated through the X-inactivation analysis using the human androgen receptor gene (HUMARA) polymorphism and the histopathologic and molecular results were compared. A different or an identical pattern of X inactivation was considered as indicator of a second primary cancer or not informative, respectively. We considered morphological indicators of a new primary cancer the absence of concordance in the histological type or a better histological differentiation.

Results: Ten patients with bilateral breast cancer were evaluated. Morphological criteria indicated that eight were second primary, a conclusion confirmed by the X-inactivation analysis. Two cases classified as recurrence according to morphological criteria were classified as second tumor by molecular analysis.

Conclusion: Our results show that the HUMARA clonality assay can improve the histological parameters in differentiating metastatic cancer from second primary cancer.

Patients and methods: Oxaliplatin was administered i.v. (100 mg/m²) on day 1, while S-1 was administered orally (80 mg/m²/day, b.i.d.) for 14 days followed by a 7-day rest. This schedule was repeated every 3 weeks.

Results: Among 55 patients enrolled, one patient received oxaliplatin for the other study, and three patients were considered unsuitable against the inclusion criteria. Accordingly, 51 patients were assessable for efficacy. The response rate was 59%, and the disease control rate was 84%. The median progression-free survival time was 6.5 months, the 1-year survival rate was 71%, and the median survival time was 16.5 months. In 54 patients assessed for safety, the major grade 3/4 toxic effects were neutropenia (22%), thrombocytopenia (13%), anemia (9%), anorexia (6%), fatigue (6%), and sensory neuropathy (4%).

Conclusion: These findings indicate that SOX regimen with oxaliplatin at a dose of 100 mg/m² is feasible and shows promising efficacy against advanced gastric cancer.

Patients and methods: Tissue microarrays were constructed from archived tissue obtained from patients on three sequential Southwest Oncology Group (SWOG) trials for FL. All three trials included anthracycline-based chemotherapy. Anti-CD20 monoclonal antibodies were included for patients in the latter two trials. Immunohistochemistry was used to study the number and distribution of cells staining for forkhead box protein P3 (FOXP3) and lymphoma-associated macrophages (LAMs) and the number of lymphoma cells staining for myeloma-associated antigen-1 (MUM-1). Cox proportional hazards regression was used to evaluate the association between marker expression and overall survival (OS).

Results: The number or pattern of infiltrating FOXP3 cells and LAMs did not correlate with OS in sequential SWOG studies for FL. The presence of MUM-1 correlated with lower OS for patients who received monoclonal antibody but not for those treated with chemotherapy alone.

Conclusions: Immune cell composition of lymph nodes did not correlate with OS in this analysis of trials in FL. The mechanism of the observed correlation between MUM-1 expression and adverse prognosis in patients receiving monoclonal antibody therapy requires confirmation.

Materials and methods: A large (n = 205) clinically annotated tissue microarray (TMA) was constructed and immunostained for several tumor-related markers. Staining was scored via an automated Ariol image analysis system; data were statistically analyzed to evaluate the correlation of clinicopathological and molecular variables with overall survival (OS) and local recurrence.

Results: Multivariable analysis identified older age [hazard ratio (HR) 1.62, P < 0.0001], nonextremity location (HR 2.95, P = 0.001), high tumor grade (HR 2.5, P = 0.02), and increased matrix metalloproteinase (MMP) 2 expression (HR 1.74, P = 0.04) as predictors for poor OS. Similarly, older age (HR 1.51, P = 0.008), nonextremity location (HR 4.09, P = 0.001), and increased MMP2 expression (HR 6.28, P = 0.006) were all found to correlate with shorter local recurrence-free interval. High nuclear p53 expression was associated with shorter STS local recurrence-free interval, with a trend toward significance.

Conclusions: Data presented indicate that a clinically annotated TMA can be utilized to identify STS-related prognostic markers. Specifically, MMP2 and nuclear p53 should be further evaluated for their potential inclusion in complex karyotype STS staging systems.

Patients and methods: The databases of the University of Texas M.D. Anderson Cancer Center (MDACC) Tumor Registry, Department of Breast Medical Oncology, and Department of Laboratory Medicine were cross-referenced for patients with breast cancer, who were also identified as having HCV. Eligible patients had a diagnosis of invasive breast cancer, breast cancer treatment at MDACC, and a diagnosis of HCV.

Results: During chemotherapy, 25% of patients experienced elevations in aminotransferases and 44% of patients required dose reductions/delays in chemotherapy. More than 60% of the patients who received chemotherapy demonstrated a grade 2 or greater complication. However, 92% of patients were able to complete the number of cycles specified in the initial chemotherapy plan.

Conclusions: As the majority of these breast cancer patients completed the initial chemotherapy plan, this study indicates that breast cancer patients with HCV can be treated with cytotoxic therapy. Comparison with historical controls showed similar rates of hepatic toxicity in the presence (or absence) of HCV, indicating that incidence of transaminitis may not be significantly affected by HCV.

Methods, materials and patients: The current study investigated the impact of four vascular endothelial growth factor type A (VEGFA) and three vascular endothelial growth factor receptor type 2 (VEGFR2) gene polymorphisms on the outcomes of 228 CML patients following imatinib therapy. VEGFA genotypes such as –2578C>A (rs699947), –460T>C (rs833061), +405G>C (rs2010963) and +936C>T (rs3025039) loci and VEGFR2 genotypes (rs1531289, rs1870377 and rs2305948) were analyzed using matrix-assisted laser desorption/ionization time-of-flight-based method.

Results: In single marker analyses, strong correlations were noted between complete cytogenetic response (CCyR) and VEGFR2 genotypes (rs1531289/rs1870377), between treatment failure and VEGFR2 genotype (rs1870377) and between progression to advanced disease and VEGFA genotypes (rs699947/rs833061). Three haplotypes of VEGFR2 gene were generated as follows: GT (46.1%), AT (27.9%) and GA (25.7%). Haplotype analyses showed good correlations between VEGFR2 haplotype and CCyR and treatment failure to imatinib. Multivariate analyses confirmed strong correlations of VEGFR2 polymorphisms (especially rs1531289, rs1870377 or VEGFR2 haplotype) with CCyR, treatment failure and of VEGFA genotype (rs699947) with progression to advanced disease.

Conclusion: The VEGFR2 gene polymorphism correlates with cytogenetic response, treatment failure following imatinib therapy for CML, while VEGFA genotype correlates with progression to advanced disease.

Patients and methods: Clinical experience data from 10 treatment centres were pooled. Postmenopausal patients with predominantly hormone receptor-positive and HER2-positive disease were included. Clinical benefit (CB) was defined as the proportion of patients achieving a response to treatment (partial or complete) or stable disease lasting ≥6 months.

Results: Data for 102 patients were analysed. Fulvestrant resulted in an overall CB rate of 42% (43/101) in HER2-positive patients and 40% (25/63) in patients with visceral disease. Median duration of treatment was 14.5 months (range 6–44 months). Fulvestrant showed activity up to the fourth line of endocrine therapy and up to the seventh line of overall therapy.

Conclusions: Results indicate that fulvestrant may be a suitable treatment option in extensively pre-treated patients with HER2-positive, hormone receptor-positive ABC. Further exploration of its use in this patient population is warranted.

Methods: Clinicopathological characteristics, carried out local treatment strategies and adjuvant chemotherapy data were collected.

Results: From 2001 to January 2006, 2754 Dutch patients were randomised to the study. Mean age of patients was 65 years (standard deviation 9). Tumours were ≤2 cm in 46% (within CCCRs 39%–50%), node-negative disease varied from 25% to 45%, and PgR status was determined in 75%–100% of patients. Mastectomy was carried out in 55% (45%–70%), sentinel lymph node procedure in 68% (42%–79%) and axillary lymph node dissections in 77% (67%–83%) of patients, all different between CCCRs (P < 0.0001). Adjuvant chemotherapy was given in 15%–70% of eligible patients (P < 0.001).

Discussion: In spite of national guidelines, breast cancer treatment on specific issues widely varied between the various Dutch regions. These data provide valuable information for breast cancer organisations indicating (lack of) guideline adherence and areas for breast cancer care improvement.

Materials and methods: From 1995 to 2007, 202 patients had received a pulmonary metastasectomy from colorectal cancer at our institution. Over a median follow-up of 28.9 months, 48 patients received second metastasectomy (29 wedge resections, 5 segmentectomies, 13 lobectomies, and 1 completion pneumonectomy). The median disease-free interval was 9.6 months. Among these 48 patients, 28 showed pulmonary recurrence again and of those, 10 patients received third metastasectomy (two wedge resections, two segmentectomies, four lobectomies, and two completion pneumonectomies).

Results: There was no postoperative mortality. Of the 48 patients who underwent second metastasectomy, overall and disease-free 5-year survivals were 79% and 49%, respectively, after second operation. Of the 10 patients who received third metastasectomy, overall survival was 78% at 5 years after last operation.

Conclusions: Repeated resection after initial metastasectomy can be carried out safely and provides long-term survival in patients with recurrent pulmonary metastasis from colorectal cancer. Our findings indicate that close follow-up for the early detection of recurrence and parenchyma-saving resection can improve the results after repeated resection.

Materials and methods: CTC were determined at baseline and at different time points during treatment. Patients were stratified into low (less than three CTC per 7.5 ml of blood) or high CTC (three or more CTC per 7.5 ml of blood).

Results: A total of 467 patients were assessable for CTC analysis. Among them, 129 patients (29%) with high baseline CTC had a significantly decreased progression-free survival [PFS; hazard ratio (HR) 1.5] and overall survival (OS; HR 2.2) compared with 322 patients with low baseline CTC. This difference remained statistically significant during treatment. The sensitivity and specificity of high CTC at baseline for the prediction of progressive disease on CT imaging were 16.7% and 70.1%, respectively, and of high CTC at 1–2 weeks after the start of treatment 20.0% and 95.1%, respectively. The combined analysis of CTC and CT imaging provided a more accurate outcome assessment than either modality alone.

Conclusions: The CTC count before and during treatment independently predicts PFS and OS in ACC patients treated with chemotherapy plus targeted agents and provides additional information to CT imaging.

Patients and methods: We report our monocentric experience in the treatment of seven adult patients with multisystem (MS) LCH (n = 3) or single-system multifocal (SS-m) LCH (n = 4) with the short-course intensive chemotherapy regimen methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomicin (MACOP-B).

Results: The overall response rate was 100% [five complete response (CR), two partial response (PR)]. After a median follow-up of 6.5 years, four patients are in first continuous CR and three patients relapsed after 5, 8 and 62 months, respectively. Four patients were evaluated with positron emission tomography (PET) scan: all three PET-negative patients at the end of treatment had a long-lasting response with only one patient relapsing after 5 years. PET scan detected additional bone lesions at diagnosis in two of four patients, changing the treatment program in one of them.

Conclusions: MACOP-B regimen seems to be very active in the treatment of adult MS or SS-m LCH, with long-lasting responses in five of seven patients. PET scan merits further evaluation in the initial staging and in the evaluation of the response to chemotherapy.

Patients and methods: MBC patients with metastatic disease and those treated with AIs were selected from the breast cancer database of the Centre Antoine-Lacassagne (Nice, France). Sex hormone levels were retrospectively assessed on serum samples from our institutional serum bank.

Results: Fifteen patients entered the study. Two patients (13%) had complete response, four patients (27%) had partial response, two patients (13%) had stable disease and seven patients (47%) had progressive disease. The median progression-free survival and overall survival were 4.4 months [95% confidence interval (CI) 0.1–8.6] and 33 months (95% CI 18.4–47.6), respectively. All assessable patients (n = 6) had E₂ levels less than the lower limit of the assay during AI treatment. Among them, three had partial response, one had stable disease and two had progressive disease. A large increase in follicle-stimulating hormone, luteinizing hormone and E₂ levels was observed in one responding patient at progression.

Conclusions: AIs are active in MBC patients. This activity is correlated with a significant reduction in E₂ levels. Secondary resistance is in part related to a deleterious feedback loop resulting in a significant increase in substrate for aromatization.

Patients and methods: Patients with histologically proven advanced colorectal cancer undergoing first-line chemotherapy with three or more serial CEA measurements (one at baseline and two or more during treatment) were included. Patients were grouped according to CEA kinetic as flare (F), decreasing CEA, normal baseline CEA, stable CEA and increasing CEA (I).

Results: From January 2000 to February 2008, 837 patients were screened of whom 670 were eligible. CEA flare occurred in 78 (11.6%) patients. On multivariate analysis, compared with patients with increasing CEA, patients with CEA flare had a significantly better ORR [I versus F: 11% versus 73%; risk ratio (RR): 27.96; 95% confidence interval (CI): 9.55–81.88; P < 0.001], PFS (median 3.1 versus 8.3 months; RR: 0.38; 95% CI: 0.26–0.56; P < 0.001) and OS (median 10.9 versus 17.7 months; RR: 0.53; 95% CI: 0.34–0.82; P < 0.001).

Conclusions: Compared with patients with rising CEA, flare was an independent favourable predictive and prognostic factor for tumour response and survival.

Methods: Patients with DLBCL diagnosed from 1 September 1999 to 14 January 2005 at the British Columbia Cancer Agency (BCCA) were identified. Patients were included if they were ≥16 years old with advanced stage or any stage with testicular involvement and were treated with CHOP (1999–2001) or R-CHOP (2001–2005) with curative intent.

Results: Four hundred and thirty-five patients were identified; 126 (29%) were treated with CHOP and 309 (71%) with R-CHOP. With a median follow-up of 5.7 years, there were 31 CNS relapses in total with a trend to a reduced likelihood of CNS relapse in R-CHOP-treated patients (3-year risk 9.7% versus 6.4, P = 0.085). In multivariate analysis, the use of rituximab significantly reduced the risk of CNS relapse [hazard ratio (HR) 0.45, P = 0.034]; this benefit was more striking in patients who achieved a complete response (HR 0.18, P = 0.005).

Conclusion: The use of R-CHOP appears to reduce the overall risk of CNS relapse in patients with DLBCL particularly in patients who achieve a complete response.

Materials and methods: A series of 12 HCV-positive patients presenting with subcutaneous nodules that revealed lymphoma infiltration at biopsy. Molecular analysis of immunoglobulin heavy chain (IGH) gene rearrangement and FISH investigations for t(11;18)(q21;q21) and t(14;18)(q32;q21) were carried out in nine patients.

Results: The 12 patients (median age 69.5 years), all with positive HCV serology, presented with single or multiple subcutaneous nodules resembling lipomas. Histologically the lesions showed lymphoid infiltrates, consistent with extranodal MZL of mucosa-associated lymphoid tissue (MALT). Functional IGH gene rearrangements were identified in nine tested patients, with somatic mutations in 82%, indicating a histogenesis from germinal center-experienced B cells. The t(11;18) was found in two of nine cases. Staging did not show any other lymphoma localization. In two patients, a response was achieved with antiviral treatment. Extracutaneous spread to MALT sites occurred in a case.

Conclusions: Our observations expand the spectrum of HCV-associated lymphomas to include a subset of extranodal MZL characterized by a novel primary ‘lipoma-like’ subcutaneous presentation and indolent clinical course.

Materials and methods: We retrospectively evaluated outcomes in 147 patients with occult invasive cervical cancer.

Results: Forty-eight patients with IA1 lesions (IA1 group) did not receive further treatment. Of the 99 patients with IA2–IIA lesions, 26 received no definitive treatment (observation group), 44 received RT or CCRT (RT/CCRT group), and 29 underwent RP (RP group). After a median follow-up of 116 months (range 3–235 months), recurrent disease was observed in 0%, 34.6%, 6.8%, and 0% of patients in the IA1, observation, RT/CCRT, and RP groups, respectively. In the RT/CCRT group, treatment was delayed due to severe diarrhea in 4 patients (9%) and 12 patients (27%) had late complications related to RT requiring further management (including two surgical interventions). Five patients in the RP group (17%) experienced perioperative complications which were easily managed, intraoperatively or conservatively. Late complications were not observed in the RP group.

Conclusion: Although RP and RT/CCRT had similar therapeutic efficacy, the lower rate of late complications observed with RP makes it preferable to RT/CCRT.

Patients and methods: Six-hundred and forty-seven patients were included in this cross-sectional cohort study and had to fill in questionnaires [health-related quality of life (QoL) (Functional Assessment of Cancer Therapy—General Scale), depression and anxiety (Hospital Anxiety and Depression Scale), fatigue (Multidimensional Fatigue Inventory) and expectancies toward treatment]. Clinical data were extracted from medical records. This study presents the comparison of both cohorts.

Results: Patients in the homeopathy cohort are younger, better educated and more often employed than patients in the CC cohort. The most pronounced differences indicate longer disease histories and different diagnostic and clinical pretreatment variables. Despite the clinical differences, QoL as well as anxiety, depression and fatigue was similar in both the groups.

Conclusions: Homeopathic treatment is sought by cancer patients at a different phase during the course of the disease, which has particular implications for research. However, expectancies toward the benefit of the treatment as well as QoL data are similar.

Patients and methods: Age-adjusted incidence rates, gender and age predilection and geographic differences were analyzed, comprising data from the Austrian National Cancer Registry.

Results: A total of 5333 cases were registered; male-to-female ratio was 0.8. The most common histotypes were sarcoma not otherwise specified (36%), leiomyosarcoma (24%), liposarcoma (12%), malignant fibrous histiocytoma (9%) and fibrosarcoma (5%). Age-adjusted incidence rate was 2.4 per 100 000 per year. Analysis of annual incidence rates and 3-year periods showed no increase (annual increasing gradient = –0.0025).

Conclusions: This study has analyzed the most recent data from a European population in comparison with seven international studies. An increase, as postulated elsewhere, could not be confirmed. The incidence rate of STS in Austria ranges in the lower half of the international incidence rates (1.8–5.0 per 100 000 per year). Different inclusion criteria (Kaposi’s sarcoma and dermatofibrosarcoma) and classifications in the various studies explain the increase of incidence in some studies rather than true increase of STS due to new or accumulated risk factors.

Patients and methods: A total of 309 patients with DIN received low-dose tamoxifen as part of institutional guidelines and were compared with 371 patients with DIN who received no systemic treatment after surgery.

Results: Women with estrogen receptor (ER)/progesterone receptor (PgR) >50% DIN who were not treated had a higher incidence of breast events than women on tamoxifen [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.00–3.12] or women with ER/PgR <50% DIN (HR 1.72; 95% CI 1.14–2.58). Among untreated patients with ER >50% DIN, recurrence was higher in PgR ≥50% DIN than in PgR <50% DIN, whereas it was similar among low PgR (<50%) DIN against which tamoxifen had no effect. No difference in endometrial cancer incidence was noted.

Conclusions: High ER and especially high PgR expression is a significant adverse prognostic indicator of DIN, and low-dose tamoxifen appears to be an active treatment. Women with low-expression ER or PgR DIN do not seem to benefit from tamoxifen. A definitive clinical trial is warranted.

Patients and methods: Patients with stage II/III breast cancer received four cycles of XT (capecitabine 1650 mg/m² on days 1–14 and docetaxel 60 mg/m² on day 8 every 3 weeks), followed by four cycles of FEC (5-fluorouracil 500 mg/m², epirubicin 90 mg/m², and cyclophosphamide 500 mg/m² on day 1 every 3 weeks). Primary end points were the pathological complete response (pCR) rate and adverse drug reactions.

Results: Seventy-four patients were enrolled and 71 patients were assessable for clinical and pathological responses. The overall response rate was 91.5%. The pCR rate was 14.1% (10 of 71). Grade 3/4 neutropenia was observed in 32.4% of patients. The most common grade 3/4 non-hematologic adverse event was hand–foot syndrome, observed in 11.3% of patients. With 29 months median follow-up, 2-year disease-free survival was estimated 85% for all patients.

Conclusion: These data indicate that the sequential combination of XT followed by FEC is a well-tolerated, effective neoadjuvant treatment of stage II/III breast cancer.

Patients and methods: Capillary density, assessed by sidestream dark field imaging of the mucosal surface of the lip, was measured at baseline, after 6 weeks of bevacizumab treatment and >3 months after discontinuation. Additional measurements included blood pressure (BP) measurements, flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD) and aortic pulse wave velocity (PWV).

Results: Fourteen patients were included. Seven patients completed measurements at all three predefined time points. Capillary density significantly decreased after 6 weeks of bevacizumab treatment and was reversible after discontinuation of bevacizumab (P = 0.00001 using a general linear model repeated measures test). BP, FMD and NMD remained unchanged. Mean PWV increased after 6 weeks of treatment (P = 0.027) and decreased after bevacizumab discontinuation. Among the six patients with the best response were the three patients showing the clearest decrease in capillary density after 6 weeks of bevacizumab treatment.

Conclusions: Bevacizumab-induced decrease in capillary density is reversible. Noninvasive assessment of capillary density during treatment with antiangiogenic drugs may be useful as a marker of treatment efficacy.

Methods: A Medline and Cochrane library search was carried out using the search terms ‘CHOP’, ‘lymphoma’ and ‘randomized trials’. Eligible trials had CHOP as a control arm and any regimen administering doxorubicin at a higher DI (16.6 mg/m²/week) as the investigational arm. Pooling of data was carried out using the mixed effect model.

Results: Eight trials were eligible. Patients receiving DI doxorubicin-based regimens had a significantly better overall survival [summary hazard ratio (SHR) 0.82; 95% confidence interval (CI) 0.71–0.96], event-free survival (SHR 0.86; 95% CI 0.75–0.99) and higher complete response rate (summary odds ratio 0.91; 95% CI 0.67–0.97).

Conclusion: High DI doxorubicin based should be considered in patients with aggressive NHL.

Patients and methods: We retrospectively analyzed 172 patients (22 with ANKL and 150 with ENKL). The ENKLs consisted of 123 nasal and 27 extranasal (16 cutaneous, 9 hepatosplenic, 1 intestinal and 1 nodal) lymphomas.

Results: Complete remission rate for ENKL was 73% in stage I, but 15% in stage IV, which was consistent with that for ANKL (18%). The prognosis of ENKL was better than that of ANKL (median survival 10 versus 1.9 months, P < 0.0001) but was comparable when restricted to stage IV cases (4.0 months, P = 0.16). Multivariate analysis showed that four factors (non-nasal type, stage, performance status and numbers of extranodal involvement) were significant prognostic factors. Using these four variables, an NK prognostic index was successfully constructed. Four-year overall survival of patients with zero, one, two and three or four adverse factors were 55%, 33%, 15% and 6%, respectively.

Conclusion: The current prognostic model successfully stratified patients with NK cell neoplasms with different outcomes.

Patients and methods: We investigated a single-centre cohort of 500 adult survivors (228 females) of childhood cancer, median age 28 years (range 18–59 years) and median follow-up time 19 years (range 6–49 years). We measured total cholesterol, high-density lipoprotein–cholesterol, systolic and diastolic blood pressure, body mass index and the prevalence of diabetes mellitus. Data from the epidemiological Monitoring van Risicofactoren en Gezondheid in Nederland (MORGEN) study were used to calculate standard deviation scores as normative values.

Results: The criteria of the metabolic syndrome were met in 13% of the total cohort. Acute lymphoblastic leukaemia (ALL) survivors treated with cranial irradiation had an increased risk of developing the metabolic syndrome compared with ALL survivors not treated with cranial irradiation (23% versus 7%, P = 0.011), probably determined by higher prevalence of overweight and hypertension.

Conclusion: Adult survivors of childhood cancer, especially those treated with cranial irradiation, are at increased risk of developing the metabolic syndrome.

Patients and methods: We analyzed 208 patients to study the clinical features and outcomes of CNS disease in extranodal NK/T-cell lymphoma.

Results: Twelve patients (5.76%, 12/208) experienced CNS disease during treatment or follow-up period (median 11.62 months, range 0.2–123.2 months). The clinical variables associated with CNS disease were Ann Arbor stage III/IV (15.87%, P <0.001), regional lymph node involvement (10.41%, P = 0.006), group III/IV of NK/T-cell lymphoma prognostic index (NKPI; 10.20%, P = 0.003), high/high–intermediate international prognostic index (9.30%, P = 0.072) and extra-upper aerodigestive primary sites (9.75%, P = 0.008). In multivariate analysis, NKPI retained the strongest statistical power to predict CNS disease (P = 0.007, relative risk 9.289, 95% confidence interval 1.828–47.212) in extranodal NK/T-cell lymphoma.

Conclusions: Despite extranodal NK/T-cell lymphoma frequently involves paranasal sinus, a routine CNS evaluation and prophylaxis do not seem to be necessary in NKPI group I or II patients due to a very low incidence. Nevertheless, CNS prophylaxis should be considered in NKPI groups III and IV.

Patients and methods: Patients enrolled in TARGET at two centres (Institut Gustave Roussy, Villejuif, France, n = 85; Central Clinical Hospital of Military Medical Academy, Warsaw, Poland, n = 54) made up the current subgroup, who were retrospectively evaluated for the incidence of brain metastases during follow-up. The association between treatment (sorafenib versus placebo) and occurrence of brain metastases was evaluated by univariate analysis.

Results: The overall incidence of brain metastases in patients receiving sorafenib was 3% (2 of 70 patients) compared with 12% (8 of 69 patients) in patients receiving placebo (P < 0.05). The incidence of brain metastases was also significantly lower in the sorafenib group after 1 (P = 0.0447) and 2 years (P = 0.005) of treatment compared with the placebo group.

Conclusions: In this subpopulation, sorafenib may reduce the occurrence of brain metastases. Antiangiogenic therapy, such as sorafenib, could be an effective preventive therapy for brain metastases in advanced RCC.

Patients and methods: We carried out a population-based study to investigate incidence rates (IRs) and time trends of EN-MZL diagnosed in the province of Modena (Italy) from 1997 to 2007.

Results: One hundred and sixty-five cases were identified from the Modena Cancer Registry that corresponded to an age-standardized IR of 2.3 cases per 100 000. A bimodal distribution of age was shown with the group of young patients mostly represented by males with cutaneous lymphoma. No time trends were observed for the IR; the incidence of gastric mucosa-associated lymphoid tissue (g-MALT) lymphomas (N = 51) markedly declined during the study period, dropping from 1.4 in 1997 to 0.2 in 2002 and then remaining stable until 2007; the calculated annual percent change for g-MALT was –17.0% (95% confidence interval –26.6% to –6.2%). We also observed a significant decrease in the rate of g-MALT associated with Helicobacter pylori (HP) infection from 61% to 17% of patients diagnosed before and after 2002 (P = 0.007; P for trend = 0.016).

Conclusion: This population-based study provides new insights into recent changes in the epidemiology of EN-MZL, mainly represented by the sharp reduced incidence of HP-positive g-MALT lymphomas.

Patients and methods: In 115 nonmetastatic patients diagnosed with large operable or locally advanced breast cancer, we prospectively detected CTC using the CellSearch system before and after neoadjuvant chemotherapy in a phase II trial (REMAGUS02).

Results: At baseline, 23% of patients were CTC positive, but only 10% had >1 CTC/7.5 ml of blood. After a median follow-up of 36 months, CTC detection before chemotherapy was an independent prognostic factor for both distant metastasis-free survival [DMFS; P = 0.01, relative risk (RR) = 5.0, 95% confidence interval (CI) 1.4–17] and overall survival (OS; P = 0.007, RR = 9, 95% CI 1.8–45). CTC detection after chemotherapy was of less significance (P = 0.07 and 0.09, respectively). Moreover, CTC detection showed interesting characteristics as an individual predictive test for metastatic relapses (sensibility 55%, specificity 81%, and global accuracy 77%).

Conclusions: Detection of ≥1 CTC/7.5 ml before neoadjuvant chemotherapy can accurately predict OS. Our findings may change the clinical management of nonmetastatic breast cancer and indicate that the metastatic efficiency of CTC could be higher than previously reported.

Materials and methods: Patients with recurrent and/or metastatic HNSCC were enrolled on a phase II bortezomib/docetaxel trial (bortezomib 1.6 mg/m² and docetaxel 40 mg/m² on days 1 and 8 of a 21-day cycle). Response was assessed using RECIST. Tissue specimens were evaluated for the presence of human papillomavirus (HPV) and expression of NF-B-associated genes.

Results: Twenty-one of 25 enrolled patients were assessable for response; one partial response (PR, 5%), 10 stable disease (SD, 48%) and 10 progressive disease (PD, 48%). Patients with PR/SD had significantly longer survival compared with patients with PD and the regimen was well tolerated. Only one of 20 tumors was positive for HPV. Patients with PD had higher expression of NF-B and epidermal growth factor receptor-associated genes in their tumors by gene expression analysis.

Conclusion: Further understanding of treatment resistance and interactions between bortezomib and docetaxel may provide novel approaches in managing HNSCC.

Materials and methods: We included 68 patients treated with first-line XELOX. Polymorphism analyses were carried out on pretreatment blood samples. Response was evaluated according to the RECIST. Survival analysis was described by the Kaplan–Meier method and log-rank testing.

Results: The overall response rate was 38% and the median overall survival 19.4 months. A favorable outcome was seen in patients with the EGF61A/G genotype compared with the combined group of A/A and G/G, with response rates of 57% and 18%, respectively (P = 0.001). There was a significantly different progression-free survival (P = 0.018) in favor of the A/G group. The TS and ERCC1 genotypes failed to provide any significant impact on the outcome.

Conclusion: Polymorphism analysis of a simple blood sample is a feasible approach to biomarker analysis and the EGF61A>G polymorphism may influence the effect of first-line XELOX. Consequently, this marker deserves further investigation.

Patients and methods: This report describes the wide spectrum of clinical presentation, difficulty with correct clinical diagnosis, complications of treatment and pathologic findings of one of the largest series of primary cardiac lymphomas at a specialist UK centre. Our series comprised five males and one female with an age range of 10–81 years.

Results: Most cases involved at least two chambers with the ventricles being the most common site. Clinical presentation included arrhythmias, valve incompetence, cardiac failure, pericardial effusion, embolic stroke and sudden death. Our study, in contrast to other series, included both B- and T-cell lymphomas.

Conclusions: All six cases illustrate the wide spectrum of clinical presentation of lymphomas presenting primarily in the heart and emphasise that histology of all mass lesions is essential. Other series are small like ours highlighting the rarity of these tumours in the heart with the emphasis on imaging, early diagnosis and treatment.

Patients and methods: This was an open-labelled, phase I, dose-escalation study. Proprietary form of green-lipped mussel lipid extract (GLMLE), 260-mg capsule, was administered on a twice-daily schedule, orally. Patients remained on study until disease progression or unacceptable toxicity.

Results: From December 1999 to May 2003, 17 patients were enrolled. Fifteen of them were male with advanced prostate cancer and two were female with advanced breast cancer. The median age of the patients was 74 years (range 56–85 years). Sixteen patients were assessable for adverse events and dose-limiting toxicity (DLT). Reason for withdrawal from the study included progressive disease (n = 12), death (n = 1) and DLT (n = 3). Two patients had evidence of grade 4 hepatic dysfunction. The MTD was not reached. There were no objective tumour responses noted.

Conclusions: GLMLE appears to be a well-tolerated compound in this setting. There appears to be no objective benefit. However, grade 3/4 hepatic toxicity noted in two patients is of concern and should be considered while evaluating patients taking GLMLE or while designing studies with this agent.

Materials and methods: The group of 222 breast cancer patients with brain metastasis was divided into three biological subgroups. The propensity of biological subtypes for metastases to the brain and survivals depending on biological subtype, recursive partitioning analysis of Radiation Therapy Oncology Group (RPA RTOG) prognostic class and the use of systemic treatment after whole-brain radiotherapy were assessed.

Results: The rate of patients with triple-negative, human epidermal growth factor receptor 2 (HER2)-positive and luminal breast cancer with brain metastases was 28%, 53% and 19%, respectively. Median survival from brain metastases in triple-negative, HER2-positive and luminal subtype was 3.7, 9 and 15 months, respectively. Median survival from brain metastases in RPA RTOG prognostic class I, II and III was 15, 11 and 3 months, respectively. In the luminal and in the triple-negative subtype, systemic therapy prolonged survival from 3 to 14 months and from 3 to 4 months, respectively. In HER2-positive subtype, median survival without further treatment, after chemotherapy and after chemotherapy with targeted therapy were 3, 8 and 11 months, respectively.

Conclusions: HER2-positive and triple-negative breast cancers have special predilection for metastases to the brain. Survival from brain metastases depended on performance status and the use of systemic treatment.

Materials and methods: We developed a Markov model to describe health states in the 5 years after CRT for HNC in a 50-year-old man. We compared three strategies: dissect all patients, dissect patients with RD on CT, and dissect patients with RD on PET-CT. Probabilistic sensitivity analyses were carried out to model uncertainty in PET-CT performance, up-front and salvage dissection costs, and patient utilities.

Results: ND only for patients with RD on PET-CT was the dominant strategy over a wide range of realistic and exaggerated assumptions. Probabilistic sensitivity analyses confirmed that the PET-CT strategy was almost certainly cost-effective at a societal willingness-to-pay threshold of $500 000/quality-adjusted life year.

Conclusion: Adjuvant ND reserved for patients with RD on PET-CT is the dominant and cost-effective strategy.

Patients and methods: We analyzed 2784 women treated for early-stage breast cancer by quadrantectomy and whole-breast irradiation in a single institution. We evaluated the prognostic factors associated with local, regional and distant recurrences and the prognostic value of local and regional recurrences on systemic progression.

Results: After a median follow-up of 72 months, we observed 33 local events, 35 regional events and 222 metastases or deaths as first events (5-year cumulative incidence 1.1%, 1.2% and 7.6%, respectively). Size, estrogen receptor status, Her2/Neu and Ki-67 were associated with all three types of events, while axillary status and vascular invasion were associated only with the occurrence of metastases or death. Young age increased the risk of local recurrence. Local and regional recurrences were associated with an increased risk of systemic progression: hazard ratios 2.5 [95% confidence interval (CI) 1.1–5.8] and 5.3 (95% CI 3.0–9.5), respectively.

Conclusions: Local and regional recurrences after breast-conserving surgery are rare events. They are markers of tumor aggressiveness and indicators of an increased likelihood of distant metastases.

Patients and methods: This retrospective study included 233 unselected patients with stage III colon cancer treated by FL (n = 124) or FOLFOX (n = 109). The impact of p53 expression and MSI on disease-free survival (DFS) was defined using univariate and multivariate analyses. A Cox proportional hazards model was specifically designed to evaluate the interaction between chemotherapy and these genetic alterations.

Results: In univariate analyses, addition of oxaliplatin significantly improved DFS provided that tumour overexpressed p53 [hazard ratio (HR) 0.39; 95% confidence interval (CI) 0.19–0.82; P = 0.01] or displayed MSI phenotype (HR 0.17; 95% CI 0.04–0.68; P = 0.01). In multivariate analyses, p53 was confirmed as an independent factor predictive of benefit from FOLFOX (P = 0.03), while the interaction of MSI with chemotherapy could not be determined in the absence of relapse in the MSI group treated with FOLFOX.

Conclusion: Our observations indicate that MSI status and p53 expression may influence the impact of oxaliplatin on adjuvant treatment of stage III colon cancer patients.

Materials and methods: Sixty patients with histologically proven GEP-NETs were treated with DOTATATE Y-90. Clinical responses were assessed 6 weeks after completing therapy and then after each of the 3- to 6-month intervals. The radiological response was classified according to RECIST criteria.

Results: At 6 months after final treatment, radiological partial response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions) was observed in 13 patients (23%), and the remaining patients had stable disease (SD; less than 30% decrease in the sum of the longest diameter of target lesions or less than 20% increase in the sum of the longest diameter of target lesions) (77%). Clinical PR at 6 months was in 43 patients (72%), nine patients had SD and progressive disease (PD) was noted in eight patients. Median progression-free survival (PFS) was 17 months, while the median overall survival (OS) was 22 months. In eight patients with early PD, the PFS was 4.5 and OS 9.5 months, while in those with SD or PR, PFS and OS were 19.5 and 23.5 months, respectively. After 12 months of follow-up, five patients had World Health Organization (WHO) grade 2 or 3 renal toxicity. Haematological toxicity (WHO grade 3 and 4) was noted during therapy in 10% of patients and persisted in 5%.

Conclusions: DOTATATE Y-90 therapy is effective and relatively safe in patients with GEP-NET. Standard doses of DOTATATE Y-90 result in a relatively low risk of myelotoxicity. However, due to ongoing risk of renal toxicity, careful monitoring of the kidney is recommended.

Patients and methods: A total of 1135 chemonaive patients with stage IIIB or IV NSCLC were randomly allocated to receive gemcitabine 1000 mg/m² on days 1 and 8 plus carboplatin area under the concentration–time curve (AUC) 5.5 on day 1 (GC), gemcitabine 1000 mg/m² on days 1 and 8 plus paclitaxel 200 mg/m² on day 1 (GP), or paclitaxel 225 mg/m² plus carboplatin AUC 6.0 on day 1 (PC). Stratification was based on disease stage, baseline weight loss, and presence or absence of brain metastases. Cycles were repeated every 21 days for up to six cycles or disease progression.

Results: Median survival (months) with GC was 7.9 compared with 8.5 for GP and 8.7 for PC. Response rates (RRs) were as follows: GC, 25.3%; GP, 32.1%; and PC, 29.8%. The GC arm was associated with a greater incidence of grade 3 or 4 hematologic events but a lower rate of neurotoxicity and alopecia when compared with GP and PC.

Conclusions: Non-platinum and non-paclitaxel gemcitabine-containing doublets demonstrate similar overall survival and RR compared with the standard PC regimen. However, the treatment arms had distinct toxicity profiles.

Methods: In the SWiss Venous ThromboEmbolism Registry, 257 cancer patients (61 ± 15 years) with acute VTE and prior hospitalization for acute medical illness or surgery within 30 days (91% were at high risk with Geneva VTE risk score ≥3) were enrolled.

Results: Overall, 153 (60%) patients received prophylaxis (49% pharmacological and 21% mechanical) before the onset of acute VTE. Outpatient status at the time of VTE diagnosis [odds ratio (OR) 0.31, 95% confidence interval (CI) 0.18–0.53], ongoing chemotherapy (OR 0.51, 95% CI 0.31–0.85), and recent chemotherapy (OR 0.53, 95% CI 0.32–0.88) were univariately associated with the absence of VTE prophylaxis. In multivariate analysis, intensive care unit admission within 30 days (OR 7.02, 95% CI 2.38–20.64), prior deep vein thrombosis (OR 3.48, 95% CI 2.14–5.64), surgery within 30 days (OR 2.43, 95% CI 1.19–4.99), bed rest >3 days (OR 2.02, 95% CI 1.08–3.78), and outpatient status (OR 0.38, 95% CI 0.19–0.76) remained the only independent predictors of thromboprophylaxis.

Conclusions: Although most hospitalized cancer patients were at high risk, 40% did not receive any prophylaxis before the onset of acute VTE. There is a need to improve thromboprophylaxis in cancer patients, particularly in the presence of recent or ongoing chemotherapy.

Patients and methods: Forty-one women who had undergone menopause as a result of chemotherapy and 57 healthy women who had undergone recent natural menopause were evaluated on two occasions 1 year apart. The primary end point was the summed score of the self-report Functional Assessment of Cancer Therapy, endocrine symptoms (FACT-ES) scale. Quality of life was evaluated by the FACT-G questionnaire and fatigue by the FACT-F subscale.

Results: There was a strong trend for patients to report worse FACT-ES scores than controls at the first (P = 0.05) and second (P = 0.04) time points. More patients had moderate/severe hot flashes than controls undergoing natural menopause (51% versus 19%, P = 0.003). Patients reported worse fatigue than controls at the first assessment (P = 0.04), with no difference at the second. Menopausal symptoms were associated with fatigue for both groups. There was no difference between patients and controls in the quality-of-life scale, although assessment of patients is likely subject to adaptation and response-shift bias.

Conclusions: Women undergoing chemotherapy-induced menopause may experience worse symptoms than women undergoing natural menopause.

Methods: Cox-adjusted models were used to further analyze a randomized phase III study in 1725 chemonaive patients with stage IIIB or IV NSCLC and Eastern Cooperative Oncology Group performance status (PS) of zero or one who received cisplatin plus pemetrexed (CP; C, 75 mg/m² and P, 500 mg/m²) or cisplatin plus gemcitabine (CG; C, 75 mg/m² and G, 1250 mg/m²) every 21 days.

Results: Histology was confirmed to be predictive of CP efficacy and may also be prognostic. Gender, ethnicity, disease stage, smoking status, and PS were not predictive in either treatment arm but were shown to be prognostic in the nonsquamous population, consistent with the results in the overall NSCLC population.

Conclusions: NSCLC histology significantly predicts efficacy outcomes for patients receiving pemetrexed. Several other factors are prognostic for the overall study population as well as a subset of patients with advanced nonsquamous NSCLC.

Patients and methods: S-1 was given orally twice daily for two consecutive weeks at a daily dose of 80–120 mg, followed by a 2-week rest period, within a 4-week cycle. LV was given orally twice a day at a daily dose of 50 mg, simultaneously with S-1.

Results: Of the 56 patients with previously untreated mCRC, 32 (57%) had partial responses. The median follow-up period was 27.2 months. The median time to progression was 6.7 months (95% confidence interval 5.4–7.9). The median survival time was 24.3 months. There was no treatment-related death or grade 4 toxicity. The most common grade 3 toxic effects were diarrhea (32%), anorexia (21%), stomatitis (20%), and neutropenia (14%).

Conclusion: S-1 combined with LV therapy demonstrated promising efficacy and acceptable safety in chemotherapy-naive patients with mCRC without the concurrent use of irinotecan, oxaliplatin, or molecular-targeted drugs.

Patients and methods: Data on 906 women diagnosed with pT_1–2pN₀ breast cancer from 1986 to 1992 with known HER2 status and treated with a modified radical mastectomy without adjuvant radiotherapy or adjuvant trastuzumab were analyzed with respect to local relapse-free survival (LRFS), regional relapse-free survival (RRFS) and distant relapse-free survival (DRFS). Log-rank statistics were used to compare 10-year Kaplan–Meier curves of LRFS, RRFS and DRFS in HER2+ and HER2– patients.

Results: Median follow-up was 12.8 years. HER2+ patients had a worse DRFS (P = 0.028) but there was no statistically significant difference in LRFS or RRFS between HER2+ and HER2– patients (P = 0.32 and 0.24 for LRFS and RRFS, respectively). Ten-year LRFS estimates among HER2+ patients was 91.3% and 86.9% for HER2– patients. Ten-year RRFS estimates for HER2+ and HER2– patients were 88.0% and 93.0%, respectively.

Conclusion: HER2 overexpression was not associated with higher local or regional recurrence risk in subjects with pT_1–2pN₀ breast cancer following mastectomy and nodal dissection after a median follow-up of >12 years.

Patients and methods: Fifty SMZL patients were treated with cladribine with or without anti-CD20 mAb.

Results: Forty-six of 50 patients were assessable for response. Overall response rate was 87%: 24 of 46 patients (52%) achieved a complete hematological response (CR), 16 of 46 (35%) a partial response and 6 (13%) were unresponsive. Interestingly, 15 of 24 cases (62%) in CR also achieved a molecular remission.

Conclusions: The present results indicate that this schedule is a valid therapeutic approach in SMZL. Addition of rituximab significantly improved quality of response and consequently the outcome of the disease.

Methods: Frozen tumor samples from 148 patients aged 55–70 years were selected (T1–2, N0) and classified by the 70-gene prognosis signature (MammaPrint^TM) into good or poor prognosis. Eighteen percent received hormonal therapy.

Results: Breast cancer-specific survival (BCSS) at 5 years was 99% for the good-prognosis signature versus 80% for the poor-prognosis signature group (P = 0.036). The 70-gene prognosis signature was a significant and independent predictor of BCCS during the first 5 years of follow-up with an adjusted hazard ratio of 14.4 (95% confidence interval 1.7–122.2; P = 0.01) at 5 years.

Conclusion: The 70-gene prognosis signature can accurately select postmenopausal patients at low risk of breast cancer-related death within 5 years of diagnosis and can be of clinical use in selecting postmenopausal women for adjuvant chemotherapy.

Methods: Chemotherapy-naive elderly patients with SCLC received amrubicin (35 mg/m², days 1–3) and carboplatin [area under the curve (AUC) 4.0, day1] every 3 weeks. The primary end point was overall response rate (ORR), and secondary end points were progression-free survival (PFS), overall survival and toxicity profile.

Results: From January 2005 to November 2007, 36 patients were enrolled [median age 76 (range 70–83); ECOG performance status of zero and one in 17 and 19 patients, respectively]. One complete response and 31 partial responses were observed (ORR 89%). Median PFS was 5.8 months and median survival time was 18.6 months. Grade 3–4 neutropenia was observed in 97% of the patients and six patients (17%) suffered from grade 3–4 febrile neutropenia. Other toxic effects were moderate and treatment-related death was not observed.

Conclusions: Amrubicin combined with carboplatin is quite effective for SCLC with acceptable toxic effects even for the elderly population. Further evaluation of this regimen is warranted.

Methods: Review of available literature with focus on presenting the epidemiological, histological and immunohistochemical arguments against an association between HPV and aggressive glossal neoplasm in younger populations.

Conclusion: HPV is not associated with the recent surge in the incidence of biologically aggressive oral cavity cancer in young populations.

Patients and methods: AZD5438 was administered four times daily, once every 7 days (study 1), for 14 consecutive days followed by 7 days of rest (study 2), or continuously (study 3), to patients with advanced solid tumours. Dose escalation proceeded until the emergence of dose-limiting toxic effects.

Results: Sixty-four patients were included across the three studies (19, 17 and 28, respectively). Nausea and vomiting were the most common adverse events. When dosed continuously, 40 mg four times daily was considered intolerable, and due to safety issues, all studies were terminated prematurely. Consequently, no intolerable dose was identified during the weekly schedule. Pharmacokinetics demonstrated dose-proportional exposure, high interpatient variability and accumulation after multiple doses. Skin biopsies indicated reduced retinoblastoma protein phosphorylation at cdk2 phospho-sites; other pharmacodynamic assessments did not reveal consistent trends.

Conclusions: AZD5438 was generally well tolerated in a weekly dosing schedule, but not in continuous schedules. The clinical development programme for AZD5438 was discontinued owing to tolerability and exposure data from these studies.

Patients and methods: JCV and EBV DNA were assessed by PCR, and FISH technique was used to localize viral infection and to estimate chromosomal instability (rogue cells, ‘chromosomal aberrations’) throughout evolution. The influence of viral infection and chromosomal instability on freedom from progression (FFP) was investigated in HL patients.

Results: PCR product sequencing of PBL identified JCV in 42 (57%) circulating lymphocytes of HL patients. FISH analysis revealed that the presence of cells with a high JCV genome copy number—associated to the presence of rogue cells and ‘higher frequency of chromosomal aberrations’—increased from 15% before treatment to 52% (P < 10^–5) after. The co-activation of JCV and EBV was independent of known prognostic parameters and associated with a shorter FFP (JCV and EBV co-activation P < 0.001, rogue cells P < 0.002).

Conclusion: In HL, JCV activation and chromosomal instability have been identified in PBL and associated with a poorer prognosis, especially in EBV+.

Materials and methods: A total of 448 patients with prostate cancer received EBRT alone (n = 361, group 1) or ADT followed by EBRT (n = 87, group 2). In group 2, ADT was initiated 3 months before EBRT. After baseline prostate-specific antigen (PSA) determination (PSA_preRT), PSA was assessed during the 6th week of the EBRT course (PSA_6wRT) in group 1. In group 2, PSA was measured again 3 months after the start of ADT, before EBRT (PSA_ADT-preRT).

Results: In group 1, median PSA_6wRT/PSA_preRT was 0.72 and median prostate-specific antigen velocity (PSAV) was –1.5 ng/ml/month. In the multivariate analysis, prognostic groups and PSA_6wRT/PSA_preRT (or PSAV) independently predicted biochemical failure (BF), clinical failure (CF), and prostate cancer-specific survival. In group 2, the median PSA_ADT-preRT was 1.3 ng/ml. In the high-risk group, an undetectable PSA_ADT-preRT (≤0.2 ng/ml) predicted BF (P < 0.01) and CF (P = 0.007).

Conclusion: A PSA decline 6 weeks after the start of EBRT when used as monotherapy and 3 months after the start of ADT in patients treated with combined ADT and EBRT is predictive of progression and specific survival.

Patients and methods: We enrolled 1922 women aged ≥50 years with histologically confirmed invasive breast cancer treated at the University of Ulm from 1992 to 2005. Adherence to guidelines and effects on OAS and DFS for women aged ≥70 years was compared with that for younger women (50–69 years).

Results: Women >70 years less often received recommended breast-conserving therapy (70–79 years: 74%–83%; >79 years: 54%) than women aged ≤69 years (93%). Non-adherence to the guidelines on radiotherapy (<70 years: 9%; 70–79 years: 14%–27%; >79 years: 60%) and chemotherapy (<70 years: 33%; 70–79 years: 54%–77%; > 79 years: 98%) increased with age. Omission of radiotherapy significantly decreased OAS [≤69 years: hazard ratio (HR) = 3.29; P <0.0001; ≥70 years: HR = 1.89; P = 0.0005] and DFS (≤69 years: HR = 3.45; P <0.0001; ≥70 years: HR = 2.14; P <0.0001). OAS and DFS did not differ significantly for adherence to surgery, chemotherapy, or endocrine therapy.

Conclusion: Our study confirms that substandard treatment increases considerably with age. Omission of radiotherapy had the greatest impact on OAS and DFS in the elderly population.

Patients and methods: Three groups of men were recruited from three major cancer centers in Israel: 185 married colon and rectal cancer patients, 54 single (unmarried) colon and rectal cancer patients, and 153 male spouses of female cancer patients. Participants were evaluated on four standardized instruments measuring psychological distress, coping, and social support.

Results: About 42.6% of the participants reported on a clinical level of psychological distress, with the highest rates (61.1%) among the single (unmarried) patients. Distress was negatively correlated to Karnofsky score and coping variables among all study groups. Distress was significantly and negatively correlated to social support variables among the spouses and married patients but not among the single patient groups.

Conclusions: Social support received by male cancer patients from friends and family may be mediated by spouse support. As a result, single male patients are at higher risk for psychological distress. Male spouses were also found to have high rates of distress. These two groups need special attention by oncologists.

Patients and methods: Existing databases in Berlin and Marburg of HDCT trials from 1989 to 2008 were retrospectively screened. Among 534 patients, 71 of 534 (13%) patients were scheduled for HDCT having failed previous conventional-dose first-line and first-salvage chemotherapy regimens; those 49 patients who had received at least cisplatin plus etoposide first-line as well as conventional-dose cisplatin-based first-salvage regimens and were diagnosed after 1 January 1990 were further analyzed.

Results: Median age at SST was 32 years (range 19–52 years). Median follow-up for surviving patients was 4 years (range 1.7–8.5 years). Three of 49 (6%) patients either progressed or died before scheduled HDCT; the remaining 46 of 49 (94%) received either single or sequential HDCT. The rate of favorable responses to HDCT was 27 of 49 (55%). Nine patients remain alive and free of progression. One additional patient was lost to follow without progression at 4 years. The projected overall survival rate at 5 years was 17% (95% confidence intervals 7% to 30%).

Conclusion: HDCT can induce remissions in patients with multiple relapsed GCTs with a long-term survival rate of ~17%.

Patients and methods: Women diagnosed with advanced breast cancer were randomly allocated to receive 3-weekly docetaxel (group D) or 3-weekly docetaxel alternating with 3-weekly gemcitabine (group D/G) until treatment failure as first-line chemotherapy. The primary end point was TTF.

Results: Two hundred and thirty-seven subjects were assigned to treatment (group D, 115; group D/G, 122). The median TTF was 5.6 and 6.2 months in groups D and D/G, respectively (hazard ratio 0.85, 95% confidence interval 0.63–1.16; P = 0.31). There was no significant difference in time-to-disease progression, survival, and response rate between the groups. When adverse events were evaluated for the worst toxicity encountered during treatment, there was little difference between the groups, but when they were assessed per cycle, alternating treatment was associated with fewer severe (grade 3 or 4) adverse effects (P = 0.013), and the difference was highly significant for cycles when gemcitabine was administered in group D/G (P < 0.001).

Conclusion: The alternating regimen was associated with a similar TTF as single-agent docetaxel but with fewer adverse effects during gemcitabine cycles.

Materials and methods: We reviewed phase II and III clinical trials evaluating new cancer drugs, which were registered from January to June 2008. Correlations were sought between the number of clinical trials and incidence, mortality and prevalence of the cancers studied (obtained from GLOBOCAN 2002) and stratified by region of the world.

Results: We identified 399 newly registered trials. Most trials (N = 229, 57%) were sponsored by industry. The most common types of cancer studied were breast 73 (18%), lung 57 (14%), prostate 44 (11%) and colorectal 28 (7%). In MDR, incidence, mortality and prevalence correlated significantly (Pearson r = 0.80, 0.73 and 0.63; P ≤ 0.01) with the number of all registered clinical trials, whereas in LDR, only prevalence showed significant association (Pearson r = 0.55; P = 0.03) with the number of trials for a given type of cancer.

Conclusion: Lethal cancers that are common in the LDR (e.g. stomach, liver and esophageal cancers) deserve greater emphasis for drug development.

Patients and methods: Elderly patients (age ≥70 years) with advanced NSCLC were randomly assigned to either the weekly arm {70 mg/m² paclitaxel on days 1, 8, and 15 and carboplatin [area under the curve (AUC) = 6] on day 1} or the standard arm [200 mg/m² paclitaxel and carboplatin (AUC = 6) on day 1]. The primary end point was the overall response rate (ORR).

Results: Eighty-two patients were enrolled. The ORR and median progression-free survival were 55% and 6.0 months for the weekly arm and 53% and 5.6 months for the standard arm. Grade 3/4 neutropenia and peripheral neuropathy were observed in 41% and 0% of the patients in the weekly arm and in 88% and 25% in the standard arm, respectively.

Conclusions: This is the first randomized study that compares the platinum doublet designed specifically for the elderly. Regarding the safety, the weekly regimen was less toxic than the standard regimen and seems to be preferable for elderly patients with advanced NSCLC.

Methods: The effects of treatment, pathologically documented response (pathological response), pre- and post-treatment biomarkers on relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) are analysed.

Results: At a median follow-up of 74 (range 48–105 months) months, the 5-year RFS, DMFS, and OS were 64 % versus 53% (P = 0.11), 73% versus 55% (P = 0.04), and 82% versus 69% (P = 0.07) in PET and ET, respectively. At multivariate analysis, after adjusting treatment effect for pretreatment biomarkers, PET independently predicted better DMFS (P = 0.018) and OS (P = 0.03), whereas the impact on RFS was of borderline significance (0.057). PET treatment was significantly better than ET treatment only in high-grade or highly proliferating tumours. The better outcome in PET arm was the results of both the higher rate of patients with optimal pathological response and the lower rate of patients with biologically aggressive residual tumour.

Conclusions: The PET weekly regimen significantly improves both DMFS and OS in LABC patients, compared with the triweekly ET combination. The therapeutic advantage is limited to patients with highly aggressive tumours.

Materials and methods: Anticancer effects of echinoside A were evaluated in vitro and in vivo. TUNEL and DNA fragmentation assays were applied to examine its ability to induce apoptosis. A series of biochemical assays were applied to investigate the inhibition of echinoside A on topoisomerase2 (Top2). Molecular docking analyses were used to demonstrate the direct interaction between echinoside A and Top2.

Results: Echinoside A inhibited the growth of tumors in mouse models and human prostate carcinoma xenografts in nude mouse models. Echinoside A shows the unique characteristics of inhibiting the noncovalent binding of Top2 to DNA by competing with DNA for the DNA-binding domain of the enzyme and of interfering predominantly with the Top2-mediated prestrand passage cleavage/religation equilibrium over with the poststrand passage one. These features distinguish echinoside A from other known Top2 inhibitors. As a result, echinoside A-induced DNA double-strand breaks in a Top2-dependent manner.

Conclusion: Echinoside A targets Top2 by unique interference with the binding of Top2 to DNA and by imparing the Top2-mediated DNA cleavage and religation, exerting potent in vitro and in vivo antitumor activities.

Patient characteristics and methods: This retrospective study was conducted in 369 stage I–II–IIIA, surgically resected, NSCLC patients. Patients exposed to anti-epidermal growth factor receptor (EGFR) agents were excluded. IGF1R expression was evaluated by immunohistochemistry in tissue microarray sections.

Results: A positive IGF1R expression (score ≥ 100) was observed in 282 cases (76.4%) and was significantly associated with squamous cell histology (P = 0.04) and with grade III differentiation (P = 0.02). No difference in survival was observed between the positive and negative group when score 100 was used as cut-off for discriminating a positive versus a negative IGF1R result (52 versus 48 months, P = 0.99) or when median value of IGF1R expression was used (45 versus 55 months, P = 0.36). No difference in survival was observed between IGF1R-positive and -negative patients in a subgroup of stage I–II adenocarcinoma (n = 137) with known EGFR mutation and copy number status.

Conclusions: IGF1R expression does not represent a prognostic factor in resected NSCLC patients. Patients with squamous cell carcinoma overexpress IGF1R more frequently than patients with nonsquamous histology, justifying the different sensitivity to anti-IGF1R agents observed in clinical trials.

Methods: Eligible patients had bidimensionally measurable brain metastases from histologically/cytologically confirmed melanoma, breast cancer (BC), or non-small-cell lung cancer (NSCLC). Prior chemotherapy, radiotherapy, and whole-brain radiotherapy (WBRT) were allowed. Patients received temozolomide 150 mg/m²/day (days 1–7 and 15–21 every 28- or 35-day cycle).

Results: In the intent-to-treat population (N = 157; 53 melanoma, 51 BC, and 53 NSCLC), one patient had complete response, nine (6%) had partial responses, and 31 (20%) had stable disease in the brain. Median progression-free survival was 56, 58, and 66 days for melanoma, BC, and NSCLC, respectively. Median overall survival was 100 days for melanoma, 172 days for NSCLC, and not evaluable in the BC group. Thrombocytopenia was the most common adverse event causing dose modification or treatment discontinuation. Grade 4 toxic effects were rare.

Conclusions: This alternating weekly, dose-dense temozolomide regimen was well tolerated and clinically active in heavily pretreated patients with brain metastases, particularly in patients with melanoma. Combining temozolomide with WBRT or other agents may improve clinical outcomes.

Materials and methods: This study included 42 336 men and 32 168 women aged ≥20 years who took health examination and were followed up for 5.6 years. Mortality data were analyzed according to the metabolic syndrome.

Results: The relative risk (RR) and 95% confidence interval (CI) of cancer mortality in subjects with metabolic syndrome compared with subjects without metabolic syndrome was 1.41 (1.08–1.84) after adjustment for possible confounding factors. The association is significant only among men [RR 1.52 (1.10–2.10)], but not among women. The RRs and 95% CIs for cancer deaths in subjects with elevated body mass index, blood pressure, fasting glucose, and triglycerides were 1.36 (1.07–1.71), 1.34 (1.07–1.69), 1.45 (1.14–1.86), and 1.60 (1.26–2.02) after mutual adjustment, respectively. Upon increasing the number of metabolic risk factors to 1, 2–3, and 4–5, the RRs and 95% CIs of death from cancer were 1.32 (0.83–1.48), 1.47 (1.10–1.96), and 2.42 (1.25–4.68), respectively, with a graded fashion (P for trend < 0.005).

Conclusion: Our results indicate that metabolic syndrome is a risk factor for cancer-related death in Korean adults. Prevention and management of the metabolic syndrome would be needed to reduce cancer mortality.

Design: This article evaluates CD26/dipeptidyl peptidase-IV expression on mobilised peripheral blood stem cell (PBSC) harvest of donors and its correlation with engraftment in HSCT. We have analysed CD26 expression on cells in various gates, that is, lymphocytes, monocytes, neutrophils and all populations using flow cytometry tool.

Results: Ours is the first study on human mobilised PBSC harvest from cancer patients or allogeneic related donors (n = 28) to demonstrate that increased CD26 expression leads to early engraftment in transplanted cancer patients. Correlation of CD26 expression with WBC engraftment was statistically significant (lymphocyte gate: P < 0.00001; monocyte gate: P < 0.00001; neutrophil gate: P < 0.00001; all populations: P < 0.00001). CD34 expression is a known predictor of engraftment. Nevertheless, there was no correlation between CD34 and CD26 expression in these cases.

Conclusions: This study has given important leads indicating that CD26 expression may be an independent predictor of engraftment. Further study with large number of patients as well as study on circulatory CD26 may add valuable information towards improving current knowledge on CD26.

Patients and methods: In the Fédération Francophone de Cancérologie Digestive (FFCD) 9203 trial, 742 eligible patients were randomly assigned to receive preoperative radiotherapy with or without concurrent chemotherapy. Surrogacy was evaluated using Prentice criteria and the proportion of treatment effect (PTE) explained by each potential surrogate.

Results: None of the candidate surrogates fulfilled all Prentice criteria. Data analyses did not provide interpretable PTE measures for OS. Regarding LC, the highest PTE was reached by TRG, which explained 12% of the effect on local recurrence. This proportion may not exceed 41% [95% confidence interval (CI) –1% to 41%]. PTE explained by the CRM status was associated with a wide uncertainty (95% CI –81% to 105%), which does not exclude a potentially high degree of surrogacy.

Conclusion: In the FFCD 9203 trial, pathological parameters were not surrogate for OS or LC.

Materials and methods: Three hundred and ninety-seven consecutive patients with curatively resected colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tissue and 14 polymorphisms of DNA repair genes determined using a real-time PCR genotyping assay.

Results: The median age of the patients was 63 years, and 218 (54.9%) patients had colon cancer, while 179 (45.1%) patients had rectal cancer. A multivariate survival analysis, including age, differentiation, carcinoembryonic antigen level, and stage, revealed a better survival for the patients with the combined IVS10+12AG and GG genotype than for the patients with the IVS10+12AA genotype [disease-free survival: hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.30–0.75, P = 0.002; overall survival: HR 0.50, 95% CI 0.26–0.98, P = 0.042]. None of the other polymorphisms was associated with survival.

Conclusion: The IVS10+12A>G polymorphism in the hMSH2 gene was found to be an independent prognostic marker for patients with colorectal cancer.

Patients and methods: From June 1995 to May 2002, 126 patients with either locally extensive or advanced HL were treated with the 12-week Stanford V chemotherapy program followed by 36-Gy involved-field radiotherapy to sites initially ≥5 cm and/or to macroscopic splenic disease. Overall, 26% had stage IV disease and 20% had international prognostic score (IPS) ≥4. Overall survival (OS), disease-specific survival, progression-free survival (PFS), FFS, and freedom from second relapse (FF2R) were determined.

Results: The 5- and 7-year OS were 90% and 88%, respectively. The 5-year FFS was 78%. IPS ≥4 was a significant independent predictor of worse OS and PFS. The FF2R was 64% at 3 years.

Conclusion: Stanford V with appropriate radiotherapy is a highly effective regimen for locally extensive and advanced HL.

Materials and methods: A series of 218 lung NETs [24 metastatic typical carcinoids (TCs), 73 atypical carcinoids (ACs), 60 LCNECs and 61 surgically resected small-cell lung carcinomas] were investigated for SSTR types 2A and 3 tissue distribution using immunohistochemistry, in correlation with clinicopathologic parameters, outcome, scintigraphy and treatment.

Results: SSTRs were heterogeneously distributed with a significant progressive decrease from low- to high-grade forms. SSTR type 2A was strikingly overexpressed in metastatic TCs as compared with ACs and clinically benign TCs. SSTR tissue immunolocalization correlated with octreotide scintigraphy in 20 of 28 cases.

Conclusion: The immunohistochemical determination of SSTRs, with special reference to low-grade/intermediate-grade tumours, may assist the clinical approach with somatostatin analogue-based diagnostic and therapeutic procedures in clinically aggressive pulmonary NETs.

Materials and methods: Immunohistochemical staining for fascin1 was carried out on paraffin-embedded tissue sections from 161 patients with NPC. Data were subjected to statistical analysis with respect to clinicopathological variables and survival. Small interfering RNA (siRNA) approach was used to knockdown fascin1 expression in NPC cells to determine whether fascin1 contributes to tumor cell invasion.

Results: Immunohistochemical analysis showed that fascin1 was highly expressed in 95 (59.0%) of 161 paraffin-embedded NPC tissues. Fascin1 expression was significantly correlated with clinical stage (P < 0.001) and N classification (P < 0.001). Statistical analysis showed that fascin1 expression was inversely correlated with both overall and disease-free survival of NPC patients. Multivariate analysis showed that fascin1 expression was an independent prognostic indicator for patient's survival. Moreover, disruption of endogenous fascin1 expression in NPC cells using siRNA technique suppressed NPC cell invasiveness and decreased cell filopodia and lamellopodia.

Conclusion: The present study indicates that fascin1 expression is inversely correlated with NPC patient survival and directly correlated with the malignant status of NPC.

Patients and methods: Sonographic uterine effects of the steroidal AI exemestane were studied in 219 women participating in the Intergroup Exemestane Study: a large trial in postmenopausal women with estrogen receptor-positive (or unknown) early breast cancer, disease free after 2–3 years of tamoxifen, randomly assigned to continue tamoxifen or switch to exemestane to complete 5 years adjuvant treatment. The primary end point was the proportion of patients with abnormal (≥5 mm) endometrial thickness (ET) on transvaginal ultrasound 24 months after randomisation.

Results: The analysis included 183 patients. Two years after randomisation, the proportion of patients with abnormal ET was significantly lower in the exemestane compared with tamoxifen arm (36% versus 62%, respectively; P = 0.004). This difference emerged within 6 months of switching treatment (43.5% versus 65.2%, respectively; P = 0.01) and disappeared within 12 months of treatment completion (30.8% versus 34.7%, respectively; P = 0.67).

Conclusion: Switching from tamoxifen to exemestane significantly reverses endometrial thickening associated with continued tamoxifen.

Design: This review considers evidence from preclinical and clinical studies examining the value of continuing trastuzumab treatment in patients who develop mCNS disease. A wealth of data from clinical studies showed that trastuzumab prolonged survival in patients with mCNS disease, compared with no trastuzumab treatment, by effectively controlling their non-CNS disease. Trastuzumab has also been shown to penetrate an impaired blood–brain barrier to a limited degree, such as during radiotherapy, and intrathecal delivery of trastuzumab to the central nervous system (CNS) has shown promise. Research efforts are focussing on improving the delivery of trastuzumab to the CNS.

Conclusion: Evidence indicates that patients with mCNS disease from HER2-positive breast cancer should continue to receive trastuzumab to control HER2-positive metastases outside the CNS and receive established therapies to control the mCNS disease.

Methods: After stratifying abstracts according to category of presentation (oral, poster, and ‘publication only’), we took a random sample of 10% of the studies presented at years 2001–2003 and 2006–2008. We assigned abstract nationality using the affiliation of authors. For multinational studies, we developed an algorithm to assign nationality.

Results: Of the 22 045 eligible abstracts, 2206 were analyzed and represented 71 countries: 905 (41%) abstracts were from a single institution, 969 (44%) were multicenter, uninational studies, and 332 (15%) were multinational studies. United States nationality was assigned to 49% of all abstracts and the next 14 countries with a higher number of studies accounted for 41%. There was a statistically significant temporal trend in the proportion of multinational studies. Also, multinational studies and abstracts with United States nationality were more frequently presented in oral and poster fashion and had more frequent involvement of the pharmaceutical industry.

Conclusion: This study provides a geographic overview of clinical cancer research and indicates that multinational collaboration is increasing.

Patients and methods: The ‘neoadjuvant response index’ (NRI) was calculated by adding a breast response score (a number from a five-point scale) to an axillary response score (a number from a three-point scale) and dividing this by the score that would have been obtained in case of a pCR in both breast and axilla. Consequently, the NRI is a number between 0 (representing no response) and 1 (a pCR of both breast and axilla).

Results: The NRI was calculated in 267 patients who had received neoadjuvant chemotherapy. The average NRI was 0.48 (median 0.40). Forty-one patients (15%) had an NRI of 0; 55 patients (21%) had an NRI of 1 (pCR). ‘Highly endocrine responsive’ tumors responded substantially less than ‘incompletely endocrine responsive’ ones. In triple negatives, an NRI of >0.70 was associated with a better recurrence-free survival than a lower NRI.

Conclusions: The NRI proposed here may be useful to better reflect the efficacy of neoadjuvant systemic regimens than the binary pCR–‘no pCR’ system.

Materials and methods: Tissue microarrays containing 638 primary breast cancer specimens with 15-year patient follow-up were employed to assess Grb7 expression using our Automated QUantitative Analysis method; cytokeratin defines pixels as breast cancer (tumor mask) within the histospot, and Grb7 expression within the mask is measured with Cy5-conjugated antibodies.

Results: High Grb7 expression was strongly associated with decreased survival in the entire cohort and in the node-positive subset (P = 0.0034 and P = 0.0019, respectively). On multivariable analysis, it remained an independent prognostic marker (P = 0.01). High Grb7 was strongly associated with high HER2/neu, and coexpression of these molecules was associated with worse prognosis than HER2/neu overexpression alone.

Conclusions: High Grb7 defines a subset of breast cancer patients with decreased survival, indicating that Grb7 might be a valuable prognostic marker and drug target. Coexpression with HER2/neu indicates that cotargeting these molecules might be an effective approach for treating HER2/neu-positive breast cancers. Future studies using Grb7-targeting agents should include assessment of Grb7 levels.

Methods: We searched PubMed for eligible articles and on-line databases for abstracts of major oncology meetings.

Results: Eight studies reported on the frequency of DDIs: six evaluated the frequency of potential DDIs, while two studies reported on real DDIs, i.e. interactions that had clinical consequences. Studies of potential DDIs found that approximately one-third of patients are exposed to dangerous drug doublets, with the most common ones involving warfarin and anticonvulsants. One study of real DDIs found that 2% of hospitalized cancer patients had a DDI as the cause of admission.

Conclusions: Drug interactions comprise an important issue in oncology, with approximately one-third of ambulatory cancer patients being at risk of DDIs. Data are limited on the clinical consequences of drug interactions among cancer patients.

Patients and methods: Patients aged ≥70 years were randomly assigned to receive CAPOX [oxaliplatin 65 mg/m² intravenously (i.v.) days 1 and 8 and capecitabine 1000 mg/m² orally b.i.d. days 1–14; q21d] or CAPIRI (irinotecan 80 mg/m² i.v. days 1 and 8 and capecitabine 1000 mg/m² orally b.i.d. days 1–14; q21d). The primary study end point was overall response rate (ORR).

Results: Ninety-four patients were enrolled. In an intent-to-treat analysis, 2 complete responses (CRs) and 16 partial responses (PRs) were reported with CAPOX (ORR 38%), and 2 CRs and 15 PRs with CAPIRI (ORR 36%; P = 0.831). Median time to progression was 8 months for CAPOX and 7 months for CAPIRI (P = 0.195), with median survival times of 19.3 months and 14.0 months (P = 0.165), respectively. Global health status was improved in 45% and in 21% of patients in the CAPOX and CAPIRI arms, respectively. The most common treatment-related grade 3–4 adverse events in CAPIRI versus CAPOX patients were diarrhea (32% versus 15%; P = 0.052) and neutropenia (23% versus 6%; P = 0.021).

Conclusion: CAPOX and CAPIRI had similar efficacy in elderly patients, although CAPOX seemed to be better tolerated.

Patients and methods: We evaluated the rate of genetic testing among young breast cancer survivors identified through the Young Survival Coalition (YSC), an advocacy group for young women with breast cancer. Items regarding family history and genetic testing were included in a Web-based cross-sectional survey.

Results: A total of 701 women were eligible based on a history of breast cancer diagnosed ≤40 years. Mean age at diagnosis was 32.9 years and mean age at survey 35.7 years. About 41% reported a first- or second-degree relative with breast or ovarian cancer. About 24% had undergone genetic testing, and 26% of those tested reported that a mutation was found. By multivariate logistic regression, likelihood of having undergone testing was higher in women who were younger at diagnosis, were more educated, had a first- or second-degree relative with breast or ovarian cancer, had a mastectomy rather than breast conservation, and considered themselves at high risk for a cancer-predisposing mutation.

Conclusion: Most women diagnosed with breast cancer ≤40 years do not undergo genetic testing.

Patients and methods: In a prospective observational study (January 2003 and February 2006), 199 GI (82 women/117 men; age range, 26–84 years) and 182 breast (180 women/2 men; age range, 29–85 years) cancer patients were enrolled and followed-up for symptomatic VTE during adjuvant chemotherapy. The effect of acquired (i.e. age, chemotherapy, tumour histotype, history of thrombosis, body mass index and smoking) and inherited risk factors [i.e. antithrombin, protein C (PC), protein S, homocysteine, activated PC resistance, factor V Leiden (FVL) and prothrombin (PT) mutations) was prospectively evaluated.

Results: Overall, 30 VTE events (7.87%) were recorded: 28 (7.35%) during treatment and 2 (0.52%) during the subsequent follow-up. Among all the 381 cancer patients, FVL was detected in 14 cases (3.67%) and PT mutation in 10 cases (2.62%). Multivariate analysis showed a significant association between the development of VTE and both thrombocytosis [hazard ratio (HR) 1.65; 95% confidence interval (CI), 1.04–2.637, P <0.0341] and a prior episode of thrombosis (HR 7.6; 95% CI, 1.77–33.1, P <0.006). FVL and PT mutations were not associated with the risk for VTE.

Conclusion: The present data indicate thrombocytosis and history of thrombosis as risk factors for development of a thrombotic event during adjuvant chemotherapy in patients with malignant diseases.

Patients and methods: We identified 1245 women, the majority with breast-conserving surgery, irradiated for primary node-negative breast cancer from 1980 to 2004 registered at the Geneva Cancer Registry. We compared breast cancer-specific and cardiovascular mortality between inner-quadrant (n = 393) versus outer-quadrant tumors (n = 852) by multivariate Cox regression analysis.

Results: After a mean follow-up of 7.7 years, 28 women died of cardiovascular disease and 91 of breast cancer. Patients with inner-quadrant tumors had a more than doubled risk of cardiovascular mortality compared with patients with outer-quadrant tumors (adjusted hazard ratio 2.5; 95% confidence interval 1.1–5.4). Risk was particularly increased in the period with higher boost irradiation. Patients with left-sided breast cancer had no excess of cardiovascular mortality compared with patients with right-sided tumors.

Conclusions: Radiotherapy of inner-quadrant breast cancer is associated with an important increase of cardiovascular mortality, a possible result of higher irradiation of the heart. For patients with inner-quadrant tumors, the heart should be radioprotected.

Patients and methods: After R0 or R1 resection, treatment initiated with capecitabine 1000 mg/m² b.i.d. for 2 weeks and 1-week rest. Subsequently, patients received capecitabine (575–650 mg/m² orally b.i.d., 5 days/week) and cisplatin (20–25 mg/m² i.v., once weekly) according to a predefined dose-escalation schedule concurrent with radiation. Radiotherapy was given to a fixed total dose of 45 Gy in 25 fractions.

Results: Thirty-one patients were eligible and started treatment. During chemoradiotherapy, seven patients developed 10 items of grade III and one episode of grade IV (mainly hematological) toxicity (National Cancer Institute—Common Toxicity Criteria version 3.0). The maximum tolerable dose was determined to be for cisplatin 20 mg/m² i.v. weekly and for capecitabine 575 mg/m² b.i.d. orally.

Conclusions: This phase I–II study demonstrated that postoperative chemoradiotherapy with weekly cisplatin and daily capecitabine is feasible in gastric cancer at the defined dose level. This schedule is currently being tested as the experimental arm in a phase III multicenter study (CRITICS: chemoradiotherapy after induction chemotherapy in cancer of the stomach; Clinicaltrials.gov NCT 00407186).

Patients and methods: Three-hundred and eighty patients randomly assigned to receive standard doxorubicin, bleomycin, vinblastine and dacarbazine who underwent at least two cycles of treatment were studied. With a median follow-up of 6.9 years, progression-free survival (PFS) from the end of cycle 2 was analysed according to DI during those cycles.

Results: During the first two cycles, 25% of patients received >97% of planned DI, 37% received between 86% and 97% and 38% received <86%. DI during the first two cycles was correlated with DI during the remainder of the course, but there was no evidence that early DI influenced PFS (hazard ratio 0.87, 95% confidence interval 0.67–1.11; P = 0.265). Multivariate analysis also failed to confirm the influence of early DI on PFS or overall survival.

Conclusions: At the range of DI delivered in a multicentre trial using conventional therapy, there is no clear evidence that early DI influences outcome. This should be tested in a prospective study.

Methods: Individual patient data from six randomized phase II/III chemotherapy trials, from the Manchester Lung Group and UK Medical Research Council, were pooled for analysis. End points included overall survival, response rate, toxicity, dose intensity (DI) and transfusion rates.

Results: Of 1707 patients analyzed, 44% were women. At baseline, women had poorer performance status (PS) (57% versus 67% Eastern Cooperative Oncology Group PS 0–1/Karnofsky PS 80–100, P = 0.0004) and more were of normal weight or underweight (57% versus 48%, P = 0.003), but fewer were anemic (25% versus 62%, P < 0.0001). Response rates between women and men were similar (77% versus 76%, P = 0.64). In univariate [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.76–0.96, P = 0.006] and multivariate (HR 0.88, 95% CI 0.79–0.99, P = 0.04) analyses, female sex predicted for longer survival. Women experienced more grade 3/4 emesis (18% versus 9%, P < 0.0001) and grade 3/4 mucositis (13% versus 8%, P = 0.005) than men. There were no differences in DI, infections, transfusions or treatment-related deaths.

Conclusion: Data from >1700 patients in randomized SCLC chemotherapy trials confirm that women survive modestly longer than men but may experience greater toxicity.

Method: The history, accreditation criteria and implementation of the DC incentive program is described.

Results: Since 2004, 75 centers have applied for designation and 48 have been accredited including 34 comprehensive cancer centers (CCCs) in general hospitals and seven freestanding CCCs. Perceived benefits accrued from the accreditation included the following: improved status and role identification of the center, positive impact on daily work, positive impact on business activity and positive impact on funding for projects.

Conclusions: The accreditation of DCs has been a central to the ESMO initiative to improve the palliative care provided by oncologists and oncology centers. It is likely that many other oncology departments and cancer centers already meet the criteria and ESMO strongly encourages them to apply for accreditation.

Materials and methods: Eighty-one patients with MPM observed in 14 Italian oncology institutions from 1982 to 2007 have been examined with the aim of delineating the history of MPM.

Results: Presentation symptoms were ascites, abdominal pain, asthenia, weight loss, anorexia, abdominal mass, fever, diarrhea and vomiting in various associations. Computed tomography scan and echotomography signs were ascites, abdominal mass and peritoneal thickening. Peritoneal fluid cytology (61 cases) was positive for mesothelioma in 31 and for malignancy, not mesothelioma, in 13. Laparoscopy was carried out in 40 cases and laparotomy in 36. Thrombocytosis was present in 59 cases. Associated tumors diagnosed during the lifetime were colorectal cancer in two cases and cheek carcinoma, thyroid carcinoma, tongue carcinoma, bladder carcinoma and testicular seminoma. Thirty patients were treated with surgery and 45 with chemotherapy. The median survival time from diagnosis is 13 months. Ascites, fever and vomiting were significative variables at presentation; only vomiting holds significance in a multivariate analysis.

Conclusions: MPM is a disease with various types of presentation, frequently associated with thrombocytosis, sometimes with other tumors. Survival and diagnosis time can differ in various types of MPM. Prognosis is poor.

Patients and methods: An on-site review was carried out by the study coordinators of the individual charts of all patients participating in the Capecitabine-Irinotecan-Oxaliplatin (CAIRO) study who had died within 30 days of the last administration of study drugs when death was accompanied by any other event than disease progression. The relationship between treatment and death was categorized as unrelated, remote, possible, or probable and submitted to an independent data monitoring committee (IDMC). These results were then compared with the initial assessment of the local investigator.

Results: Forty of 820 patients qualified for review. The relationship between cause of death and study drugs was changed in 26 patients (65%). A major protocol violation (MPV) was identified in 12 of 14 patients with a probable relationship between cause of death and study treatment.

Conclusions: There was little agreement between the relation as assessed by the local investigator compared with the IDMC. A quality control improves the assessment of safety results and the observed MPVs underscore the importance of educating medical staff and patients.

Patients and methods: The incidence of EM disease, its relationship with prior exposure to HDT or novel agents, and its prognostic impact were analyzed in 1003 MM patients. Based on the different therapies available, three periods were considered: 1971–1993, conventional-dose chemotherapy; 1994–1999, HDT for younger patients; and 2000–2007, introduction of novel agents.

Results: Overall, 13% of patients had EM disease, 7% at diagnosis and 6% later. In the 2000–2007 period, there was a significant increase of EM involvement, at diagnosis (P = 0.02) and during follow-up (P = 0.03). The risk of EM spread was not significantly increased after HDT [hazard ratio (HR 0.6)], bortezomib (HR 1.62), or thalidomide/lenalidomide (HR 1.07). EM disease was associated with shorter overall (HR 3.26, P < 0.0001) and progression-free (HR 1.46, P = 0.04) survival.

Conclusions: The incidence of EM disease has increased, probably due to the availability of more sensitive imaging techniques and the prolongation of patients’ survival. HDT or novel agents seem not to increase the risk of EM disease. EM involvement confers a poor prognosis.

Patients and methods: Patients with metastatic CRPC progressing following one to two chemotherapy regimens including docetaxel were included. The primary end point was progression-free survival (PFS) per radiographic and clinical evaluations. Oral sunitinib was administered 50 mg/day 4-weeks on followed by 2-weeks off per cycle up to a maximum of eight cycles or until clinical progression or intolerable toxicity.

Results: Thirty-six patients with a median age of 69.5 years were accrued. The median PFS was 19.4 weeks with a 12-week PFS of 75.8%. Four patients (12.1%) had a ≥50% prostate-specific antigen (PSA) decline and seven (21.2%) had a ≥30% PSA decline. Two of 18 patients (11.1%) with measurable disease demonstrated 30% declines by RECIST and eight (44.4%) displayed some shrinkage. A decline in pain score ≥2 points occurred in 13.6% of 22 assessable patients. Drug discontinuation due to toxic effects occurred in 52.8% of patients.

Conclusion: Sunitinib malate demonstrated promising activity in metastatic CRPC progressing after prior docetaxel.

Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years).

Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy.

Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy.

Materials and methods: Patients (N = 24) refractory to previous chemotherapy received Genexol-PM as an 1-h infusion on a weekly basis for 3 weeks followed by a resting week. The starting dose was 80 mg/m² and the maximum administered dose was 200 mg/m².

Results: The majority of patients had lung, nasopharyngeal and breast cancers and in eleven patients (46%), taxane-based chemotherapy had previously failed. The MTD was defined at 180 mg/m². The most common grade 3 non-hematologic adverse events in cycle 1 were fatigue (4%) and neuropathy (4%) occurring mainly at 200 mg/m². Five (21%) patients had partial response, nine (38%) had stable disease and seven (29%) had disease progression. Five of 11 previously taxane-refractory patients showed clinical benefit to Genexol-PM. The pharmacokinetics of Genexol-PM displayed dose-proportionality, with both the maximum concentration (C_max) and the area under the concentration-time curve from zero to infinity (AUC_0–) increasing by approximately four- and threefold, respectively, as the dose of Genexol-PM was escalated from 80 to 200 mg/m². The median total-body clearance of Genexol-PM for all patients was 43.9 l/h.

Conclusion: The weekly regimen of Genexol-PM was well tolerated and responses were observed in patients with refractory tumors, including patients who had failed taxane-based chemotherapy previously.

Methods: A total of 109 patients were stratified into high- and low-level EpCAM expression by immunohistochemical staining of primary tumors and subsequently randomly assigned to receive monotherapy with either high- (6 mg/kg every two weeks (q2w)) or low-dose adecatumumab (2 mg/kg/ q2w) until disease progression.

Results: No complete or partial tumor responses could be confirmed by central RECIST assessment. The probability for tumor progression was significantly lower in patients receiving high-dose adecatumumab and expressing high levels of EpCAM (hazard ratio 0.43; P = 0.0057 versus low dose and low EpCAM). Three of 18 patients with highest EpCAM expression treated with adecatumumab developed new metastases up to week 6, compared with 14 of 29 patients with low EpCAM. Most frequent treatment-related adverse events (high dose/low dose) were chills (59%/20%), nausea (55%/18%), fatigue (39%/23%) and diarrhea (43%/7%).

Conclusions: Single-agent adecatumumab shows dose- and target-dependent clinical activity in EpCAM-positive MBC, albeit no objective tumor regression. Further investigation of adecatumumab in patients with EpCAM-overexpressing tumors and lower tumor burden is warranted.

Methods: In a population-based study, 691 of 907 (76%) men in Sweden who lost a wife to cancer 4–5 years earlier answered an anonymous questionnaire about their preparedness at the time of their wife's death as well as potential predictors for preparedness.

Results: A final logistic regression model indicates following predictors for preparedness, among others: the length of the widower's intellectual awareness time before his wife's death [relative risk (RR) 4.1, confidence interval (CI) 2.7–6.1], the widower could take in the information that his wife's disease could not be cured (RR 3.5, CI 2.3–5.2), the couple had arranged their economical affairs (RR 1.5, CI 1.3–1.7), the wife had stayed at a palliative care unit during her last months of life (RR 1.2, CI 1.1–1.4) and health care personnel supported the husband to participate in his wife's care (RR 1.6, CI 1.3–2.1).

Conclusions: We identified several care-related factors that may influence the preparedness of men before their wife's death to cancer. These factors can be considered in future intervention studies aiming at influencing preparedness before the death of a loved one.

Patients and methods: Patients received docetaxel (60–75 mg/m²) i.v. on day 1 and ABT-751 (100–200 mg) orally daily for 14 days, repeated every 3 weeks for up to 10 times on four escalating dose levels (DLs).

Results: Thirty-two patients received a median of 8.5 treatment cycles (range 1–10). One of six patients on DL 3 (D 60 mg/m² + A 200 mg) and 4 (D 75 mg/m² + A 200 mg) experienced dose-limiting toxicity, and both DLs were expanded. Overall, severe adverse events occurred more commonly on DL 4 than 3 (47% versus 18% of patients). PK data for docetaxel and ABT-751 were similar to reported literature. Best post-treatment prostate-specific antigen decline of ≥50% occurred in 60% and objective responses occurred in 45% of patients. Median overall survival was 24 months (95% confidence interval 8.3–37.7 months).

Conclusions: The combination of ABT-751 and docetaxel is safe and active in CRPC. Based on the cumulative safety analysis, the recommended phase II dose of ABT-751 is 200 mg daily with docetaxel 60 mg/m² for this patient population.

Methods: Using data from the 1973–2005 database of the Surveillance, Epidemiology, and End Results Program, we empirically validated a novel model-based method to project 5- and 10-year relative survival of AML patients and we applied the method to project relative survival of AML patients in the United States diagnosed during 2006–2010.

Results: Empirical evaluation indicated that the modeling approach provides more accurate estimates of currently diagnosed patients than standard methods of survival analysis, such as cohort analysis or period analysis, in the majority of cases. Projected figures for 2006–2010 show 5- and 10-year relative survival estimates of 21.4% and 18.7% for all ages combined, 62.2% and 57.4% for ages 25–34, and 60.6% and 58.1% for ages 35–44. These estimates are substantially higher than the most up-to-date estimates obtained by standard survival analysis.

Conclusion: Patients diagnosed with AML during 2006–2010 at younger ages have much higher long-term survival expectations than indicated by previously available survival statistics.

Patients and methods: Individual patient data (n = 310) were obtained from seven trials using TEC chemotherapy. Prostate-specific antigen (PSA) response was defined as ≥50% post-therapy decline from baseline. Overall survival was defined from baseline to death from any cause. Logistic and Cox regression were used to investigate heterogeneity in outcome to TEC by patient and disease characteristics. Predicted survival probabilities were calculated from the Halabi Cancer and Leukemia Group B (CALGB) nomogram.

Results: The pooled PSA response proportion was 69% [95% confidence interval (CI) 56% to 80%]. There was no evidence of differential PSA response by disease characteristics. Established prognostic factors were associated with survival. The pooled 12-month survival estimate of 79% (95% CI 71% to 84%) was higher than the median 59% 12-month nomogram-predicted survival.

Conclusions: TEC chemotherapy has significant clinical activity in CRPC. A randomized, controlled trial evaluating the addition of carboplatin to taxane-based chemotherapy is needed to elucidate the value of carboplatin in CRPC.

Materials and methods: We examined the effects of Calbiochem (CL)-387,785, HER2 tyrosine kinase inhibitor, and trastuzumab on cell growth and HER2 signaling in eight breast cancer cell lines showing HER2 amplification and trastuzumab-conditioned BT474 (BT474-TR).

Results: Four cell lines with PIK3CA mutations (E545K and H1047R) were more resistant to trastuzumab than the remaining four without mutations (mean percentage of control with 10 µg/ml trastuzumab: 58% versus 92%; P = 0.010). While PIK3CA-mutant cells were more resistant to CL-387,785 than PIK3CA-wild-type cells (mean percentage of control with 1 µM CL-387,785: 21% versus 77%; P = 0.001), CL-387,785 retained activity against BT474-TR. Growth inhibition by trastuzumab and CL-387,785 was more closely correlated with changes in phosphorylation of S6K (correlation coefficient, 0.811) than those of HER2, Akt, or ERK1/2. Growth of most HER2-amplified cells was inhibited by LY294002, regardless of PIK3CA genotype.

Conclusions: PIK3CA mutations are associated with resistance to HER2-targeted agents. PI3K inhibitors are potentially effective in overcoming trastuzumab resistance caused by PIK3CA mutations. S6K phosphorylation is a possibly useful pharmacodynamic marker in HER2-targeted therapy.

Materials and methods: This phase 1, dose escalation study assessed the safety, tolerability, pharmacokinetics (PKs) and immunogenicity of lexatumumab administered i.v. every 14 days in patients with advanced solid tumors.

Results: Thirty-one patients received lexatumumab over five dose levels (0.1–10 mg/kg). Most (26 of 31) received four or more cycles of treatment. One patient at 10 mg/kg experienced a possibly related dose-limiting toxicity of grade 3 hyperamylasemia. Nine patients achieved stable disease. One patient with chemotherapy-refractive Hodgkin's disease experienced a mixed response. Lexatumumab PKs were linear up to 10 mg/kg. At the 10 mg/kg dose, the mean (±standard deviation) t_1/2b was 13.67 ± 4.07 days, clearance was 4.95 ± 1.93 ml/day/kg, V₁ was 45.55 ml/kg and V_ss was 79.08 ml/kg, indicating that lexatumumab distributes outside the plasma compartment. No human antihuman antibodies were detected.

Conclusions: Lexatumumab can be safely administered every 14 days at 10 mg/kg. The PK profile supports this schedule. Further evaluation of lexatumumab at this dose schedule is warranted, including combination trials with other agents.

Patients and methods: Formalin-fixed paraffin-embedded tissues were obtained from 137 patients with localized gastric cancer at University of Southern California and Memorial Sloan-Kettering Cancer Center medical facilities. DNA was extracted and genotyping was carried out using PCR–restriction fragment length polymorphism-based protocols.

Results: In false discovery rate-adjusted univariate analysis, PAR-1 –506 ins/del (P < 0.001), ES +4349 G>A (P = 0.004), and IL-8 –251 T>A (P < 0.0001) were associated with time to tumor recurrence (TTR). Further, PAR-1 –506 ins/del and IL-8 –251 were associated with overall survival (OS). After adjusting for covariates, IL-8 remained significantly associated with TTR (adjusted P = 0.003) and OS (adjusted P = 0.049), whereas ES was significantly associated with TTR (adjusted P = 0.026).

Conclusions: Polymorphisms in PAR-1, ES, and IL-8 may serve as independent molecular prognostic markers in patients with localized gastric adenocarcinoma. The assessment of the patients’ individual risk on the basis of interindividual genotypes may therefore help to identify patient subgroups at high risk for poor clinical outcome.

Patients and methods: Premenopausal women with EBC, any hormone receptor status, after surgery received standard adjuvant chemotherapy [doxorubicin (adriamycin)/cyclophosphamide, cyclophosphamide/methotrexate/5-fluorouracil, or cyclophosphamide/epirubicin/5-fluorouracil] followed by randomization to tamoxifen or placebo for 5 years. Outcomes were overall survival (OS), disease-free survival (DFS), toxicity, and compliance with therapy.

Results: Median follow-up for 672 women was 9.7 years. Multivariate analysis showed improved DFS [78.2% versus 71.3% at 5 years; hazard ratio (HR) 0.77; P = 0.056] and a trend for improved OS (86.6% versus 82.1% at 5 years; HR 0.78; P = 0.12). There was no evidence of greater benefit for the receptor-positive subgroup. Compliance with treatment was suboptimal in both arms, with 103 (31%) women on tamoxifen and 70 (21%) on placebo-stopping therapy early because of toxicity, refusal, or other choices.

Conclusions: Adjuvant tamoxifen, given after chemotherapy to premenopausal women with EBC, improved 5-year DFS. Poor compliance may have reduced treatment efficacy.

Materials and methods: We analyzed 80 patients who underwent surgery for metastatic GIST after imatinib therapy from July 2002 to October 2007. Patients were divided into those with surgery at best clinical response (group A, n = 49) and those with surgery at focal progression (group B, n = 31). Primary end points were progression-free survival (PFS) and disease-specific survival (DSS).

Results: Two-year postoperative PFS was 64.4% in group A and 9.7% in group B (P < 0.01). In group A, median PFS was not reached; in group B, it was 8 months. Median DSS from the time of imatinib onset was not reached in either group. Five-year DSS was 82.9% in group A and 67.6% in group B (P < 0.01). Multivariate analysis confirmed a significantly shorter PFS and DSS in group B. Surgical morbidity occurred in 13 patients (16.3%).

Conclusions: Surgery for focal progressive lesions could be considered as part of the second-line/third-line armamentarium in selected cases. Surgery of residual disease upon best clinical response seems associated with survival benefit compared with historical controls in similar patient collectives treated with imatinib alone. However, evidence from prospective randomized trials is needed to make definite recommendations.

Patients and methods: Tumor tissue samples from 335 resected patients with stage I–IIIA non-small-cell lung cancer (NSCLC) were obtained and tissue microarrays were constructed from duplicate cores of tumor cells and tumor-related stroma from each specimen. Immunohistochemistry was used to evaluate the expression of the molecular markers PDGF-A, PDGF-B, PDGF-C, PDGF-D, PDGFR-, PDGFR-β, VEGFR-3 and D2-40.

Results: There were 232 N0 and 103 N+ patients (76 N1 and 27 N2). In multivariate analyses, high tumor cell PDGF-A expression (P = 0.017) correlated with LNM. Tumor cell co-expression of VEGFR-3 and PDGF-B correlated with nodal metastasis and was an independent indicator of poor prognosis (hazard ratio 4.8, confidence interval 95% 2.80–8.31, P < 0.001).

Conclusion: Tumor cell PDGF-A expression correlates with LNM, and the co-expression of PDGF-B and VEGFR-3 is strongly associated with poor survival in NSCLC patients.

Methods: In 2007, the French Association of Residents in Oncology conducted a nationwide study of all medical oncology residents in France.

Results: The strongest factors that had influenced their decision to become a medical oncology specialist were an interest in medical oncology (98%), exposure to this branch of medicine during graduate training as a medical student (83%), interest in research (81%), and the diversity of the activity (75%). The mean score for the quality of training was 6 (0–10). More time for reading during working hours as well as for attending staff meetings and greater availability of teaching oncologists would improve the quality of training. The most popular career choice was working in a public hospital but most residents stated that they had not received adequate information about the different career plans.

Conclusions: No data are available regarding how training in medical oncology is perceived. This study provides useful data for future policies to boost the number of oncologists.

Materials and methods: A total of 564 premenopausal women were entered into a randomised study independent of ER status. Using a tissue microarray, AIB1 and ER were analysed by immunohistochemistry.

Results: AIB1 scores were obtained from 349 women. High AIB1 correlated to factors of worse prognosis (human epidermal growth factor receptor 2, Nottingham histological grade 3, and lymph node metastases) and to ER negativity. In the control arm, high AIB1 was a negative prognostic factor for recurrence-free survival (RFS) (P = 0.02). However, ER-positive patients with high AIB1 responded significantly to tamoxifen treatment (P = 0.002), increasing RFS to the same level as for systemically untreated patients with low AIB1. Although ER-positive patients with low AIB1 had a better RFS from the beginning, this was not further improved by tamoxifen (P = 0.8).

Conclusions: In the control group, high AIB1 was a negative prognostic factor. However, ER-positive patients with high AIB1 responded significantly to tamoxifen. This implicates high AIB1 to be an independent predictive factor of improved response to tamoxifen and not, as has previously been discussed, a factor predicting tamoxifen resistance.

Patients and methods: Single-stage phase 2 study of irinotecan and docetaxel to evaluate tumor response, toxicity, time to progression, and overall survival was carried out. Regimen of docetaxel (25 mg/m²) and irinotecan (70 mg/m²) was administered on days 1 and 8 of each 3-week cycle. Patients had histologically confirmed breast adenocarcinoma and metastatic cancer measurable with RECIST.

Results: Of 70 patients enrolled, 64 were assessable. Prior treatment with an anthracycline and a taxane was required. Eighteen (28%) patients [95% confidence interval (CI) 15% to 31%] had tumor response, plus four patients had stable disease (less than 30% decrease in sum of longest diameter and less than 20% increase) for >6 months. The clinical benefit rate was 34% overall. Median duration of tumor response was 6.7 months (95% CI 4.2–37.7 months); median follow-up was 18.6 months (range 8.5–37.7 months). The most common severe adverse events included fatigue [n = 16 (25%)] and neutropenia [n = 13 (20%)].

Conclusions: Weekly dosing of combination of irinotecan and docetaxel is active against MBC. However, the response rate to our regimen was not significantly better than single-agent docetaxel. Other schedules of irinotecan plus docetaxel should be considered for future studies.

Methods: Sixty-one patients receiving initial therapy with fludarabine-based regimens were categorised according to the presence of post-treatment cytopenias (haemoglobin <110–130 g/l depending on sex and age, neutrophils <2.0 x 10⁹/l, or platelets <140 x 10⁹/l) lasting >3 months.

Results: Persistent cytopenias unrelated to persistent disease were found in 43% of patients. Cytopenias were associated with clinically important rates of infection and transfusion requirement (P = 0.03) and predicted for worse overall survival (61% versus 96% at 60 months, P = 0.05). Increasing age predicted for persistent cytopenias (P = 0.02), but the presence of pretreatment cytopenias and delivered dose intensity were not predictive. The median times to resolution of anaemia, neutropenia, and thrombocytopenia were 7, 9, and 10 months, respectively.

Conclusions: Cytopenias often persist >3 months after first-line fludarabine combination therapy and can lead to important clinical sequelae. Although cytopenias generally resolve over time, treating physicians should be aware of these factors when considering fludarabine combination chemotherapy and when documenting treatment response status in chronic lymphocytic leukaemia.

Materials and methods: A total of 2954 consecutive patients have been included; multivariate analyses of distant metastasis-free survival (DMFS) and overall survival (OS) were carried out to ascertain the independent prognostic role of vitiligo as a time-dependent covariate.

Results: Vitiligo was demonstrated in 83 of 2954 melanoma patients (2.8%). A significantly higher percentage of autoimmune diseases was demonstrated in vitiligo patients (7 of 83) with respect to patients without vitiligo (80 of 2871) (P = 0.004). Multivariate analyses selected the time-dependent covariate vitiligo as the favourable independent prognostic variable associated to a longer DMFS in stage III and a higher OS in both stage III and stage IV.

Conclusion: Melanoma-associated vitiligo should be considered as a distinct clinical entity, separate from vitiligo vulgaris, and identifies a subgroup of patients characterised by a high prevalence of immune-mediated diseases and by a favourable prognosis.

Patients and methods: Twenty patients receiving weekly docetaxel were evaluated. Forty eyes were double-blind randomized: AT in one eye and CS in the other eye were administered, six times daily, throughout the docetaxel administration. Patients were assessed for tearing and stenosis at weeks 3, 6, 9 and 26. The primary end point was the incidence of dacryostenosis in each group at 9 weeks.

Results: At 9 weeks, punctal or canalicular stenosis was observed in 9 of 20 (45%) of the CS eyes and 9 of 20 (45%) of the AT eyes. Dacryostenosis was mild in 37 of 40 eyes (93%) and severe in 3 of 40 eyes (8%), with equal distribution in the CS and AT group. Tearing was present in 9 of 20 (45%) of the CS eyes and 8 of 20 (40%) of the AT eyes, of which two eyes without stenosis in each group.

Conclusions: The incidence of dacryostenosis in patients receiving weekly docetaxel was not different for the AT- and the CS-treated eyes. The dacryostenosis was predominantly mild, not leading to surgical interventions.

Materials and methods: Age-standardized mortality rates were calculated by the direct method using age-specific mortality rates at 5-year age intervals and weights based on the age distribution of the standard world population. The joinpoint regression model was used to describe changes in trends.

Results: For all cancers combined, the mortality rate at age 65–84 years during 2000–2007 was 1145.13 (per 100 000 population) for men and 461.93 (per 100 000) for women. Mortality rates have declined in the past 10 years in both sexes. These favorable trends were driven largely by decreases in mortality for three leading cancers in the elderly men [lung, stomach and colorectal cancer (CRC)] and for two of the three most common cancers in the elderly women (stomach and CRC), combined with a leveling off of death rate from lung cancer in women.

Conclusion: The population-based data in the current study underscore the importance of cancer research and prevention for the older segment in Japan to reduce the additional cancer burden among the growing number of elderly persons.

Patients and methods: In all, 1118 RPS patients were evaluated at our institution (1996–2006). Patients with resectable, nonmetastatic disease were selected (n = 343) and baseline, treatment and outcome variables were retrieved. A nomogram was created and its performance was evaluated by calculating its discrimination (concordance index) and calibration and by subsequent internal validation.

Results: Median follow-up and OS were 50 and 59 months, respectively. Independent predictors of OS were included in the nomogram: age (≥65), tumor size (≥15 cm), type of presentation (primary versus recurrent), multifocality, completeness of resection and histology. The concordance index was 0.73 [95% confidence interval (CI) 0.71–0.75] and the calibration was excellent, with all observed outcomes within the 95% CI of each predicted survival probability.

Conclusions: A RPS-specific postoperative nomogram was developed. It improves RPS staging by allowing a more dynamic and robust disease-specific risk stratification. This prognostic tool can help in patient counseling and for selection of high-risk patients that may benefit from adjuvant therapies or inclusion into clinical trials.

Patients and methods: Patients with gastric adenocarcinoma treated in Los Angeles County from 1988 to 2006 were identified from the Los Angeles County Cancer Surveillance Program. Patients were categorized by race and ethnicity as White, Asian, Hispanic and Black.

Results: Of 13 084 patients, 39% were White, 22% Asian, 28% Hispanic, 11% Black and 2% other. Asian patients demonstrated higher survival than Whites, Hispanics and Blacks [median survival (MS) 16.3 versus 8.4, 8.7 and 7.9 months, respectively; log-rank P values < 0.001]. Multivariate Cox regression analysis showed that Asians had improved probability of survival [hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.72–0.82; P < 0.001]. In patients who underwent curative-intent surgery, Asian patients demonstrated higher survival than Whites, Hispanics and Blacks (MS 32.7 versus 18.8, 19.9 and 18.9 months, respectively; log-rank P values < 0.001). Multivariate Cox regression analysis showed that Asians had improved probability of survival after surgery (HR 0.79, 95% CI 0.71–0.88; P < 0.001).

Conclusions: Asians with gastric adenocarcinoma have superior outcomes in Los Angeles County. These outcomes verify disparities in gastric cancer survival among different races and ethnicities independent of established clinical and pathologic factors.

Methods: Forty-seven multi-specialty health care providers from the New York Metropolitan Area attended a communication skills module at a Comprehensive Cancer Care Center about how to conduct clinical interviews utilizing interpreters. The development of this module was on the basis of current literature and followed the Comskil model previously utilized for other doctor–patient CSTs. Participants were given pre- and post-surveys to evaluate their own confidence as well as the helpfulness of the module.

Results: On the basis of a retrospective pre–post measure, participants reported an increase in their confidence about interviewing patients via translators. In addition, at least 80% of participants reported their satisfaction with the various components of the module by either agreeing or strongly agreeing with the different statements.

Conclusions: We have developed a module that trains clinicians in effective collaboration with professional medical interpreters and shown its ability to increase the confidence of clinician's to work with limited English proficiency patients. Our approach intends to minimize not only the language barrier but also the cultural barriers that could potentially interfere with patients’ care.

Practice implications: This work has important practice implications in the oncology setting, where cultural sensitivity is paramount and empathic exchange with the patient optimizes their sense of being well supported by their health care team. We believe that this model is generalizable to many other medical settings where use needs to be made of a professional interpreter.

Methods: The 5-year age group, date and site of first and subsequent CRC diagnoses as well as death dates were obtained from the NSW Central Cancer Registry. The time to SPCRC and standardised incidence ratios (SIRs) were generated.

Results: Six hundred and sixty patients (2.1%) developed SPCRCs and the cumulative incidence at 18 years was 5.5%, 95% confidence interval (CI) 4.9% to 6.3%. The risk of SPCRC was increased in patients with a CRC history compared with the general population (SIR = 1.5, 95% CI 1.4–1.6) and inversely related to age at first diagnosis (30–49 years, SIR = 5.1, 95% CI 3.6–7.1 versus ≥80 years, SIR = 1.1, 95% CI 0.9–1.4). The excess absolute risk of SPCRC was greater for females aged 50–69 years at first diagnosis than for males in the same age group. SPCRC was also increased in individuals with right-sided first primaries (SIR = 2.0, 95% CI 1.6–2.4).

Conclusions: The SPCRC rate was increased during the first 5 years after first diagnosis but remained increased for up to 10 years in females, in patients with right-sided cancers and in patients <60 years at first diagnosis. These findings support active surveillance up to 10 years in these risk groups.

Methods: We searched Medline (PubMed), Excerpta Medica database, and the Cochrane Review in October 2007.

Results: Among 3327 articles searched, 31 articles on 22 randomized controlled trials, which included 161 045 total subjects, 88 610 in antioxidant supplement groups and 72 435 in placebo or no-intervention groups, were included in the final analyses. In a fixed-effects meta-analysis of all 22 trials, antioxidant supplements were found to have no preventive effect on cancer [relative risk (RR) 0.99; 95% confidence interval (CI) 0.96–1.03). Similar findings were observed in 12 studies on primary prevention trials (RR 1.00; 95% CI 0.97–1.04) and in nine studies on secondary prevention trials (RR 0.97; 95% CI 0.83–1.13). Further, subgroup analyses revealed no preventive effect on cancer according to type of antioxidant, type of cancer, or the methodological quality of the studies. On the other hand, the use of antioxidant supplements significantly increased the risk of bladder cancer (RR 1.52; 95% CI 1.06–2.17) in a subgroup meta-analysis of four trials.

Conclusions: The meta-analysis of randomized controlled trials indicated that there is no clinical evidence to support an overall primary and secondary preventive effect of antioxidant supplements on cancer. The effects of antioxidant supplements on human health, particularly in relation to cancer, should not be overemphasized because the use of those might be harmful for some cancer.

Methods: Clinical and pathological data of 694 patients <61 years with primary unilateral T1–4N0M0 breast cancer were analysed. Grade, estrogen receptor (ER) status and human epidermal growth factor receptor 2 (HER2) status were first assessed locally; subsequent central re-evaluation of these parameters was carried out. Clinicopathological low or high risk was assessed using national Dutch guidelines and the Adjuvant! Online (www.adjuvantonline.com).

Results: The local pathological examination was discordant with central review for grade, ER and HER2 in 28% (kappa 0.56; grade 2 tumours 35% discordant), 5% (kappa 0.85) and 4% (kappa 0.81) of patients, respectively. If clinical risk were assessed based on Dutch guidelines or Adjuvant! Online, respectively, 15% (one of seven patients; kappa 0.70) or 8% (kappa 0.83) of patients would have been assigned to a different clinical risk group.

Conclusion: Inter-observer variation in pathological examination of breast carcinomas results in significant differences in grade, ER status, HER2 status, clinicopathological risk and subsequently in adjuvant systemic treatment advice.

Patients and methods: One hundred and forty-one patients with unresectable mCRC were enrolled in a randomized study comparing standard XELOX (XELOX₃₀), arm A, and XELOX_30Chron, arm B—both with short-time infusion of oxaliplatin—with the primary aim of reducing overall toxicity.

Results: Overall toxicity grade 2–4 was 90% versus 85%, P = 0.47 and grade 3–4 was 31% versus 37%, P = 0.6 in arm A and B, respectively. We found no significant differences in median overall survival (17.6 versus 15.5 months; P = 0.068) and median progression-free survival (8.9 versus 8.8 months; P = 0.7). The incidence of grade 3 neuropathy was 16% in arm A and 19% in arm B (P = 0.7) after a cumulative dose of oxaliplatin of 1000 mg/m².

Conclusion: XELOX_30Chron does not reduce toxicity or improve efficacy. A 30-min infusion of oxaliplatin is safe and does not increase the severity of chronic neuropathy.

Methods: From April to August 2007, a double-blind questionnaire with 13 common items graduated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events was completed by clinicians and nurses for outpatients undergoing chemotherapy at our Medical Oncology Day Hospital Unit. Patients completed a modified questionnaire with simplified terms. They were requested to specify seriousness of symptoms with a subjective scale varying from 1 to 4. Every patient–nurse–clinician questionnaire was registered for the statistical analysis. Agreement was evaluated by Cohen's kappa coefficient.

Results: Eighty-five paired questionnaires were completed. Patients, nurses and clinicians agreed on most symptoms and toxicity grade. Agreements between patients and nurses were stronger than those between patients and physicians for the six most common symptoms: asthenia (kappa 75% versus 37%), constipation (83% versus 45%), neuropathy (82% versus 55%), mucositis (78% versus 46%) and diarrhoea (90% versus 77%). These differences mainly reflected differences in the proportion of positive agreement: nurses were more able to detect symptoms self-reported by patients than physicians. The only exception was nausea, as kappa coefficient was very good for both health professionals (91% versus 89%). When considering the different grade of toxicity by the weighted kappa coefficient, we scored again the highest agreement between patient and nurse, with weighted kappa ranging from 55% (asthenia) to 86% (diarrhoea), and the lowest agreement between patient and physician, with weighted kappa ranging from 32% (asthenia) to 74% (nausea). The agreement between physician and nurse slightly improved, with weighted kappa ranging from 41% (constipation) to 77% (nausea).

Conclusion: Our results support the validity of nurse toxicity reporting and that the nurse staff could be successfully employed in collecting toxicity data because of a greater ability to elicit information from patients than the medical staff.

Patients and methods: Forty-five newly diagnosed patients with advanced-stage HL and International Prognostic Score ≥3 received two initial cycles of escBEACOPP and then were evaluated by positron emission tomography (PET)/computed tomography scan. If a good imaging response was obtained, they were treated by four cycles of ABVD.

Results: Following the first two cycles of escBEACOPP, the overall response was 100% and at the end of all therapy, 40 (89%) patients were in complete response (disappearance of all clinical evidence of disease and PET negativity), three (7%) in partial response (PET-positive residual lesions and a size reduction of the majority of large masses by >50%), while two (4%) had progressive disease. After a median follow-up of 48 months, progression-free survival (PFS) and overall survival at 4 years were 78% and 95%, respectively. The 4-year PFS for early PET-negative patients (n = 31) and early PET-positive patients (n = 13) were 87% and 53%, respectively (P = 0.01).

Conclusions: These data indicate that combined escBEACOPP–ABVD may improve the outcome in patients with high-risk advanced HL. The potential benefit of early-interim PET activity as a guide to continuing therapy in these patients merits further study in the future.

Patients and methods: A dose of 13 mg/m² was administered i.v. over 4 h on days 1, 8 and 15 every 28 days. The primary end point was rate of disease control defined as no evidence of radiological progression at 6 months. A sample size of 16 assessable patients in stage 1 and nine assessable patients in stage 2 was selected; progression to stage 2 required one or more patients with disease control in stage 1 (H_o = 0.10, H_a = 0.30; and β = 0.10).

Results: Thirty-five patients were enrolled. Two patients achieved a confirmed radiological partial response (RECIST) lasting ≥6 months, along with a confirmed prostate-specific antigen decline of ≥50%. Eleven patients experienced toxicity necessitating early discontinuation. The commonest adverse events were nausea (30 patients; 85.7%), fatigue (28 patients; 80.0%), vomiting (23 patients; 65.7%) and anorexia (20 patients; 57.1%). There was no significant cardiac toxicity.

Conclusions: At the dose and schedule selected, romidepsin demonstrated minimal antitumor activity in chemonaive patients with CRPC. Further studies of improved HDACi, alone and in combination with other therapies, should nevertheless be investigated.

Materials and methods: From 1969 to 2006, 41 patients were treated conservatively for an advanced-stage serous borderline ovarian tumor. Patient outcomes were reviewed.

Results: Twenty patients had undergone a unilateral salpingo-oophorectomy, 18 a unilateral cystectomy and two bilateral cystectomy (unknown for one patient). Three patients had invasive implants. The median duration of follow-up was 57 months (range 4–235). The recurrence rate was high (56%), but overall survival remained excellent (100% at 5 years, 92% at 10 years). One death had occurred due to an invasive ovarian recurrence. Eighteen pregnancies (nine spontaneous) were observed in 14 patients.

Conclusions: This study demonstrates that spontaneous pregnancies can be achieved after conservative treatment of advanced-stage borderline ovarian tumors (with noninvasive implants) but the recurrence rate is high. Nevertheless, this high rate has no impact on survival. Conservative surgery can be proposed to patients with a borderline tumor of the ovary and noninvasive peritoneal implants. Should infertility persist following treatment of the borderline tumor, an in vitro fertilization procedure can be cautiously proposed.

Patients and methods: Patients were randomly assigned to receive 3-week cycles of capecitabine 1000 mg/m², twice daily for 14 days, with on day 1 either irinotecan 250 mg/m² (XI) or cisplatin 80 mg/m² (XP). The primary end point was overall response rate (ORR) and secondary end points included progression-free survival (PFS), overall survival (OS) and safety.

Results: Of 118 patients recruited, 112 were eligible for safety analysis and 103 for efficacy analysis. In the XI and XP treatment arms, there were no marked differences in ORR, 37.7% versus 42.0%, and median PFS, 4.2 versus 4.8 months, although median OS was longer, 10.2 versus 7.9 months, respectively. Grade 3/4 toxicity was higher in the XP regimen for thrombocytes (18.2% versus 1.8%), nausea (23.6% versus12.3%) and vomiting (16.4% versus 1.8%) and in the XI arm for diarrhea (22.8% versus 7.3%).

Conclusion: The comparable activity and safety of the XI and XP regimens establish XI as a relevant platinum-free first-line treatment choice for patients with mGC.

Methods: A multicenter phase II trial was conducted by the Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies (MITO) Group. Patients with advanced/recurrent measurable carcinoma of the cervix that had failed one prior chemotherapy regimen in association or not with radiotherapy were treated with pemetrexed at a dose of 500 mg/m² every 21 days. All the patients had a measurable lesion according to RECIST criteria in a not previously irradiated field.

Results: From November 2006 to September 2008, 43 patients were entered by seven member institutions of the MITO-Group. A total of 164 cycles (median 2, range 1–9) were administered. The treatment was well tolerated. More serious toxic effects (grades 3 and 4) included leukopenia in 27.9% and neutropenia in 30.2% of patients. No treatment-related deaths were reported. Six patients (13.9%) had partial responses (at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) with a median response of 7 weeks (range 3–27). Twenty-three patients (53.4%) had stable disease (less than a 50% reduction and less than a 25% increase in the sum of the products of two perpendicular diameters of all measured lesions and the appearance of no new lesions) and fourteen (32.5%) patients had progressive disease. Median progression-free survival was 10 weeks and overall survival was 35 weeks.

Conclusion: Pemetrexed showed moderate activity against advanced/recurrent cervical cancer that had failed prior chemotherapy.

Patients and methods: In all patients with metastatic NSGCT who started chemotherapy at our center from April 2001 to April 2007, thyroid function was analyzed. The association between thyroid function and HCG level was examined and the frequency of hyperthyroidism in patients with low (<5000 IU/l), intermediate (≥5000 but <50 000 IU/l) and high (≥50 000 IU/l) serum HCG was assessed.

Results: For 144 of 148 eligible patients, thyroid function tests were available. Five patients with hyperthyroidism (3.5%) were identified, who all had high-serum HCG (mean 1 325 147 IU/l). Fifty percent of the patients with high HCG levels had hyperthyroidism versus 0% of the patients with HCG <50 000 IU/l (P < 0.001). Free thyroxin levels normalized within 26 days after starting chemotherapy in all patients.

Conclusions: Hyperthyroidism frequently accompanies NSGCT with highly elevated HCG. Since its symptoms overlap with those of extensive metastatic disease, it may not be recognized. Thyroid function should be assessed in patients with high HCG levels and symptomatic hyperthyroidism should be treated temporarily with beta-blockade or antithyroidal medication.

patients and methods: In all, 897 patients with primary MDS treated with supportive care only were examined in a retrospective multicenter study. A Cox model was developed to determine the prognostic impact of age and gender on survival and to examine their modulating influence on IPSS results. Based on main effects and interactions of these variables, we established an individualized age- and gender-adapted scoring system to improve prognostication in MDS.

Results: While the risk of a patient in the IPSS is best represented by the values 0 (low), +1 (intermediate-1), +2 (intermediate-2), and +3 (high), these values were found to vary between –1.9 and +3.5 in the same patients when including age and gender. Whereas in low-risk MDS, male patients were found to have a less favorable survival, a particularly high risk (+3.5) was found in younger (≤66 years) high-risk female patients.

Conclusion: The inclusion of age and gender and their respective interactions contribute to improved and individualized prognostication in MDS.

Patients and methods: Gastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. PTX was administered i.v. at 50 mg/m² and i.p. at 20 mg/m² on days 1 and 8. S-1 was administered at 80 mg/m²/day for 14 consecutive days, followed by 7 days rest. The primary end point was the 1-year overall survival (OS) rate. Secondary end points were the response rate, efficacy against malignant ascites and safety.

Results: Forty patients were enrolled, including 21 with primary tumors with peritoneal dissemination, 13 with peritoneal recurrence and six with positive peritoneal cytology only. The median number of courses was 7 (range 1–23). The 1-year OS rate was 78% (95% confidence interval 65% to 90%). The overall response rate was 56% in 18 patients with target lesions. Malignant ascites disappeared or decreased in 13 of 21 (62%) patients. The frequent grade 3/4 toxic effects included neutropenia (38%), leukopenia (18%) and anemia (10%).

Conclusion: Combination chemotherapy of i.v. and i.p. PTX with S-1 is well tolerated and active in gastric cancer patients with peritoneal metastasis.

Patients and methods: In the present study, the influence of comorbidity on survival and acute myeloid leukemia (AML) evolution was analyzed retrospectively in 419 patients with de novo myelodysplastic syndromes (MDS) (observation period: 1985–2007). The median age was 71 years (range 24–91 years). Two different scoring systems, the hematopoietic stem-cell transplantation-specific comorbidity index (HCT-CI) and the Charlson comorbidity index (CCI) were applied.

Results: The HCT-CI was found to be a significant prognostic factor for overall survival (OS, P < 0.05) as well as event-free survival (EFS, P < 0.05) in our patients, whereas the CCI was of prognostic significance for OS (P < 0.05), but not for EFS. For AML-free survival, neither the HCT-CI nor the CCI were of predictive value. A multivariate analysis including age, lactate dehydrogenase, ferritin, karyotype, number of cytopenias, French–American–British groups, and comorbidity was applied. Comorbidity was found to be an independent prognostic factor in patients with low- or int-1-risk MDS (P < 0.05) regarding OS and EFS.

Conclusions: Together, our data show that comorbidity is an important risk factor for OS and EFS in patients with MDS.

Materials and methods: CRPC patients with progression after docetaxel (Taxotere) therapy received pemetrexed (500 mg/m²) i.v. every 3 weeks. The primary end point was prostate-specific antigen (PSA) response. A pharmacogenetic analysis of the reduced folate carrier-1 gene (RFC1) G80A polymorphism was also carried out.

Results: Forty-nine patients were enrolled: median age 68 years, median baseline PSA 72 ng/ml, and median Karnofsky performance status of 90. Grade 3 or 4 toxicity occurred in 20 (43%) and four patients (8%), respectively. Confirmed >50% PSA decline occurred in four patients (8%), stable PSA lasting at least 12 weeks in 10 patients (20%). A significant relationship was observed between time from prior docetaxel therapy and overall survival. Pharmacogenetic analyses of RFC1 G80A genotype frequencies showed no relationship between genotypes and clinical efficacy.

Conclusions: Pemetrexed treatment of CRPC patients after docetaxel therapy was associated with only modest clinical activity. Further investigation of pemetrexed as a single agent in a nonenriched CRPC population is unlikely to add significant clinical benefit over that seen with traditional second-line chemotherapy agents such as mitoxantrone.

Patients and methods: We retrospectively reviewed 80 patients treated with CRT for head and neck cancers. The pharyngeal constrictors (PCs), supraglottic larynx (SGL), and glottic larynx (GL) were contoured and the mean radiation doses and the volumes of each receiving >40, 50, 60, and 70 Gy (V40, V50, V60, and V70) were determined.

Results: A total of 33 of 80 patients required a FT either before or during the course of CRT. Fifteen patients required the FT for ≥6 months. On univariate analysis, significant factors associated with a prolonged FT requirement were mean PC dose, PC-V60, PC-V70, SGL dose, SGL-V70, and advanced T3–T4 disease. Multivariate analyses found both PC-V70 and T3-T4 disease as significant factors .The proportions of patients requiring a FT ≥6 months were 8% and 28% for treatment plans with PC-V70 <30% and ≥30%, respectively.

Conclusions: Increased radiation dose to the PCs is associated with a higher risk of a prolonged FT need. Dose sparing of the PC muscles may reduce this risk.

Patients and methods: From May 2004 to January 2008, 195 patients with relapsed/progressive MBC underwent whole-body FDG–PET/CT and provided blood samples for assessment of CTC count.

Results: Higher CTC numbers were detected in patients with bone metastases relative to those with no bone lesions (mean 65.7 versus 3.3, P = 0.0122) and in patients with multiple bone metastases relative to those with one or two bone lesions (mean 77.7 versus 2.6, P < 0.001). CTCs predicted overall survival (OS) in 108 patients with multiple sites of metastases including bone (P = 0.0008) but not in 58 without bone metastases (P = 0.4111) and in 29 with bone involvement only (P = 0.3552). All 15 patients but one with human epidermal growth factor receptor 2 (HER-2) positive tumors who were treated with trastuzumab-based regimens had <5 CTCs at progression. In multivariate analysis, CTCs, but not bone metastases, remained a significant predictor of OS.

Conclusion: Presence of extensive bone metastases as detected by FDG–PET/CT is associated with increased CTC numbers in MBC.

Methods: A total of 789 patients with recurrent breast cancer were studied. ER, PR, and HER2 status were determined by immunohistochemistry (IHC) and/or FISH. Repeat markers for ER, PR, and HER2 were available in 28.9%, 27.6%, and 70.0%, respectively. Primary and recurrent tumors were classified as triple receptor-negative breast cancer (TNBC) or receptor-positive breast cancer (RPBC, i.e. expressing at least one receptor). Discordance was correlated with clinical/pathological parameters.

Results: Discordance for ER, PR, and HER2 was 18.4%, 40.3%, and 13.6%, respectively. Patients with concordant RPBC had significantly better post-recurrence survival (PRS) than discordant cases; patients with discordant receptor status had similarly unfavorable survival as patients with concordant TNBC. IHC scores for ER and PR showed weak concordance between primary and recurrent tumors. Concordance of HER2–FISH scores was higher.

Conclusions: Concordance of quantitative hormone receptor measurements between primary and recurrent tumors is modest consistent with suboptimal reproducibility of measurement methods, particularly for IHC. Discordant cases have poor survival probably due to inappropriate use of targeted therapies. However, biological change in clinical phenotype cannot be completely excluded.

Patients and methods: Cases comprised 37 patients who underwent RIC allo-HCT. Haemopoietic cell grafts were harvested from HLA-matched siblings (27) and unrelated donors (7). Controls consisted of 43 patients from the same institutions who received conventional therapy only. Matching variables were age at diagnosis and time to first CLL-specific therapy.

Results: Both patient groups were well balanced in terms of cytogenetics by FISH, CD38 and ZAP-70 expression, and immunoglobulin heavy-chain variable region mutational status. Median overall survival was 113 months for HCT patients and 85 months for controls when calculated from time of diagnosis (P = 0.072) and 103 and 67 months, respectively, when calculated from time of first therapy (P = 0.041).

Conclusion: RIC allo-HCT is a reasonable option for patients with high-risk CLL. However, these results require confirmation before the procedure can be recommended outside clinical trials.

Materials and methods: After confirming the absence of safety issues in phase 1, a total of 33 cases were registered up to and including phase 2. Safety and efficacy were evaluated by National Cancer Institute—Common Toxicity Criteria version 2 and Visual Analogue Scale (VAS) at 1 week after PVP. Based on VAS score decreases, efficacy was classified into significantly effective (SE; ≥5 or reached 0–2), moderately effective (ME; 2–4), or ineffective (NE; <2 or increase).

Results: Procedures were completed in all 33 patients (42 vertebrae). Thirty days after PVP, two patients died of primary disease progression, but no major adverse reactions (>grade 2) were observed. Response rate was 70% (95% confidence interval 54% to 83%) [61% (n = 20) with SE, 9% (n = 3) with ME, and 30% (n = 10) with NE] and increased to 83% at week 4. Median time to response was 1 day (mean 2.4). Median pain-mitigated survival period was 73 days.

Conclusion: For PMVCF, PVP is a safe and effective treatment modality with immediate onset of action.

Patients and methods: Patients with histologically proven, previously untreated follicular or marginal-zone PBL (MZL PBL) diagnosed from 1980 to 2003 were included in the study. Major end points were progression-free survival (PFS), overall survival (OS) and potential prognostic factors.

Results: We collected data on 60 cases of PBL [36 follicular and 24 marginal-zone lymphoma (MZL)]. Stage was I_E or II_E in 57 patients and IVE in three patients due to bilateral breast involvement. Surgery, chemotherapy and radiotherapy (RT), alone or in combination, were used as first-line treatments in 67%, 42% and 52% of patients, respectively. Overall response rate was 98%, with a 93% complete response rate. Five-year PFS were 56% for MZL and 49% for follicular PBL (P = 0.62). Relapses were mostly in distant sites (18 of 23 cases); no patients relapsed within RT fields.

Conclusions: Our data showed an indolent behaviour of MZL PBL, comparable to other primary extranodal MZL. Conversely, patients with follicular PBL had inferior PFS and OS when compared with limited-stage nodal follicular non-Hodgkin's lymphomas, suggesting an adverse prognostic role of primary breast localisation in this histological subgroup.

Patients and methods: Patients with EBC presenting to The Royal Marsden Hospital from June 2005 to September 2007 who had CNB and subsequent EB were included. ER and PgR were determined by immunohistochemistry (IHC) and graded from 0 to 8 (Allred score). HER2 was determined by IHC and scored from 0 to 3+. FISH analysis was carried out in HER2 2+ cases and in discordant cases.

Results: In all, 336 pairs of samples were compared. ER was positive in 253 CNBs (75%) for 255 EBs (76%) and was discordant in six patients (1.8%). PgR was positive in 221 CNBs (66%) and 227 (67.6%) EBs being discordant in 52 cases (15%). HER2 was positive in 41 (12.4%) of the 331 CNBs in which it was determined compared with 44 (13.3%) EBs and discordant in four cases (1.2%).

Conclusions: CNB can be used with confidence for ER and HER2 determination. For PgR, due to a substantial discordance between CNB and EB, results from CNB should be used with caution.

Design and methods: We treated patients <61 years with high-risk aggressive lymphoma with four to six courses of dose-escalated CHOP plus etoposide (MegaCHOEP) necessitating repeated ASCT. Outcomes of patients with mature T-NHL (excluding anaplastic lymphoma kinase-positive anaplastic large cell lymphoma) and aggressive B-NHL were compared using multivariate Cox regression analysis.

Results: Compared with 84.4% of B-NHL patients, 66.7% of T-NHL patients were able to receive all treatments; the rates of progressive disease were 27.3% in T-NHL and 16.3% in B-NHL patients. At 3 years, event-free survival (EFS) and overall survival were significantly worse for T-NHL [25.9% confidence interval (CI) 10.4% to 41.4% and 44.5% CI 26.5% to 62.5%) than for B-NHL patients (60.1% CI 52.1% to 68.1%; P < 0.001 and 63.4% CI 55.4% to 71.4%; P = 0.016). In multivariate analysis, T-NHL was a strongly significant adverse risk factor for EFS (relative risk 2.2, P = 0.001).

Conclusions: MegaCHOEP for T-NHL patients was no better than other high-dose regimens and was unable to address the major problems of HDT/ASCT: neither early progressions nor early relapses were reduced. This study sheds some doubt on expectations that HDT/ASCT will significantly improve outcomes for patients with T-NHL.

Materials and methods: Four hundred and seventy-six patients <60 years old with newly diagnosed CD20+ DLBCL were randomised to induction with ACE or ACVBP. Three hundred and thirty responders received HDT followed by ASCT. After ASCT, 269 patients were re-randomised to receive either maintenance rituximab or observation alone. Randomisation was stratified by the quality of response to ASCT. The primary end point of this study was event-free survival (EFS).

Results: At a median of 4 years’ follow-up from the second randomisation, there was a trend (P = 0.1) towards increased EFS for patients who received rituximab compared with observation.

Conclusion: The type of induction therapy (ACVBP or ACE) did not significantly affect overall survival at a median 51 months’ follow-up.

Patients and methods: LMCRC patients were randomized to receive every 14 days, FA, 400 mg/m² infused over 2 h, followed by 5-FU as a 400 mg/m² i.v. bolus, followed by continuous 5-FU infusion, 2400 mg/m² over 46 h (LV5FUs) with or without irinotecan: 180 mg/m² infusion (FOLFIRI). The primary end point was disease-free survival (DFS); secondary end points included overall survival (OS) and safety.

Results: Treated patients (n = 306) were balanced for critical prognostic factors in each arm. Median DFS in patients receiving LV5FUs was 21.6 versus 24.7 months for FOLFIRI [hazard ratio (HR) 0.89, log-rank P = 0.44]. No significant differences were found in OS. A trend was observed for improved DFS in patients receiving FOLFIRI within 42 days of surgery (HR 0.75, P = 0.17). Grade 3/4 toxic effects were more common in patients treated with FOLFIRI versus LV5FUs (47% versus 30%) with neutropenia being most common (23% versus 7%).

Conclusion: FOLFIRI in the adjuvant treatment of LMCRC showed no significant improvement in DFS compared with LV5FUs.

Patients and methods: Consecutive cancer patients scheduled for chemotherapy randomly received: acenocumarine 1 mg/day for 3 days before and 8 days after central vein catheter (CVC) insertion; dalteparin 5000 IU 2 h before and daily for 8 days after CVC insertion; no anticoagulant treatment (NT). All patients underwent venography on days 8 and 30, some of them on days 90, 150 and 210 after CVC.

Results: A total of 450 patients were randomized, 348 underwent at least two venography. Both acenocumarine and dalteparin reduced venography-detected CVCrT rate [21.9% acenocumarine versus 52.6% NT, odds ratio (OR) 0.3, P < 0.01; 40% dalteparin versus 52.6% NT, OR 0.6, P = 0.05]. Acenocumarine was more effective than dalteparin (OR 0.4, P = 0.01). The rate of occlusive CVCrT was not different in the three groups (0.9% acenocumarine, 3.3% dalteparin, 1.8% NT; P = 0.40). Most CVCrTs (95.6%) were observed on day 8 after CVC insertion and were non-occlusive.

Conclusions: In this study of early and short-term prophylaxis, acenocumarine was more effective than dalteparin on non-occlusive and asymptomatic CVCrT events. The first days following CVC insertion represent the highest risk for CVCrT.

Patients and methods: Patients referred to our institution during a 5-year period for treatment of acute leukemia/myelodysplasia and who had received adjuvant chemotherapy for breast cancer are included. Leukemia-free survival for the whole group and for patients who underwent hematopoietic stem cell transplantation (HSCT) was estimated.

Results: Fifteen women (14 with acute leukemia and one with myelodysplasia) were identified. Seven of 15 patients had received an anthracycline, cyclophosphamide and a taxane. Ten patients developed acute leukemia/myelodysplasia with a latency period of 2 years or less from initiation of chemotherapy. Although mixed-lineage leukemia (MLL) rearrangement was the commonest chromosomal abnormality (8 of 15 patients), various other chromosomal abnormalities were also detected. Twelve of 15 patients underwent HSCT (11 allogeneic and one autologous). Eleven of these 12 patients who underwent HSCT were in remission at a median follow-up of 20.4 months (range 4.4–53.3 months).

Conclusion: Durable remissions can be achieved in patients who develop acute leukemia/myelodysplasia secondary to adjuvant chemotherapy for breast cancer and are able to undergo allogeneic HSCT. Our results indicate that HSCT should be an early consideration in the management of such patients who are suitable candidates for the procedure.

Patients and methods: Forty-eight of 127 (37.8%) lymphoma patients were HBsAg negative and HBcAb positive, and 24 of these patients were then given liver function tests and HBsAg tests monthly and serum HBV DNA every 3 months.

Results: HBV reactivation was observed in two patients (4.1%) who had received intensive chemotherapy including steroid and rituximab. Immediate administration of entecavir therapy after elevation of HBV DNA level was conducted, and this resulted in reduction of it and improvement of liver function test.

Conclusions: Rituximab plus steroid-containing regimens may increase the risk of HBV reactivation in HBsAg-negative and HBcAb-positive lymphoma patients. More ambitious prospective studies are required to establish clinically useful or cost-effective follow-up methods for control of HBV reactivation in lymphoma patients with occult HBV infection.

Patients and methods: MBC patients were enrolled to receive six cycles of PLD 35 mg/m² (day 1) and docetaxel 40 mg/m² (days 1 and 15), every 28 days (group A). Because of unacceptable toxic effects, doses were modified to PLD 30 mg/m² (day 1) and docetaxel 75 mg/m² (day 2), every 3 weeks (group B). The primary end point was clinical benefit.

Results: Sixty-seven patients were included (group A, 53; group B, 14). In both groups, the median number of cycles delivered was 4 and the overall dose intensity was 82% for docetaxel and 71% for PLD. In group A, main toxic effects were hematologic, palmar–plantar erythrodysesthesia (PPE), and stomatitis. In group B, higher rates of grade 3–4 PPE, febrile neutropenia, and hematologic toxic effects were reported. The rate of clinical benefit was 47%. Among patients with a measurable disease, 49% achieved a partial response, 27% had a stable disease, and 13% progressed, according to RECIST criteria.

Conclusion: The combination of PLD and docetaxel delivered at planned doses in this study yields unacceptable toxicity and should not be used routinely in patients with MBC.

Methods: From 1999 to 2003, the vital status of 9051 cases of invasive breast cancer was identified in the Eastern Region of England. Survival analysis was by Cox proportional hazards regression. Data were analysed separately for patients aged <70 years and those older due to differences in treatment policies.

Results: Overall 5-year survival was 78%. In patients aged <70 years, significant differences in survival lost their formal significance after adjustment for detection mode and node status, although this remained close to statistical significance with some residual differences between relative hazards. There was significant negative ecological correlation between proportion with nodes positive or not examined and 9-year survival rates. Patients with estrogen receptor (ER) status unknown were at significantly higher risk of dying than ER-positive patients. There was a clear trend of increasing hazard of dying with increasing deprivation. Survival differences in women aged ≥70 years were related to whether surgery was included as part of treatment.

Conclusion: This variation in treatment and survival may be attributed to lack of information, in particular nodal and ER status, thereby impacting on staging and prescription of adjuvant therapy.