Annals of Oncology 2008 19(4):603; doi:10.1093/annonc/mdn065
© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
In this issue
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Proliferation identifies high-risk patients amongst small, low-grade breast cancers
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Approximately 20–30% of patients with lymph-node negative
breast cancers die from recurrent disease. Relative survival
improvement of 15–20% at 10 years resulting from adjuvant
systemic therapy can be expected, but with this level of improvement,
the survival benefits and side effects of adjuvant systemic
therapy must be considered simultaneously. Consequently, there
is a need for accurate and reliable prognostic markers to help
identify high-risk patients. Patients with rapidly proliferating
tumors, as measured by mitotic activity index (MAI), significantly
benefit from adjuvant systemic therapy, in contrast to those
with low proliferation. The question remains open as to whether
this also holds for "favourable prognosis" subgroups. In this
issue, Baak et al. [649–654] report the results of a multicentre
prospective analysis of the MAI for recurrence-free survival
and overall cancer-related survival of grade, MAI, and other
prognosticators in long-term follow-up, T1-3N0M0 breast cancer
patients under 71 years. These authors report that in these
patients an MAI of 10 or more accurately identifies those at
high risk.
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Clinical impact of mutations in GISTs
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KIT and platelet-derived growth factor receptor-
(PDGFR
) are
two transmembrane receptors, whose intracellular region is subdivided
into a juxtamembrane domain and two tyrosine kinase domains.
Mutations in these genes, resulting in constitutively phosphorylated
and activated receptors, are responsible for 90% of gastrointestinal
stromal tumors (GISTs). The prognostic role of different types
of mutations has been studied but remains controversial. In
this issue, Braconi et al. [706–710] report the results
of a study of 104 patients diagnosed with GIST by KIT immunoreactivity.
Tumor DNA was sequenced for the presence of mutations in KIT
exons 9, 11, 13 and 17 and in PDGFR
exons 12 and 18. Disease-free
survival was analyzed in 85 radically resected patients. These
authors report that point mutations and duplications in KIT
exon 11 are associated with a better clinical trend in disease-free
survival, and that PDGFR -mutated GISTs are preferentially localized
in the stomach and seem to have a favorable clinical behavior.
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Prognostic factors for hematotoxicity of chemotherapy in aggressive NHL
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It is a common practice that chemotherapy for cancer treatment
is dosed proportional to the body surface, but this is not ideal.
Dose-limiting hematotoxicity (DLHT) regularly occurs in some
patients who experience severe infections or bleeding disorders.
To reduce these risks, dose reduction or postponement strategies
are usually recommended in subsequent treatment cycles once
DLHT has occurred, but this kind of dose erosion often compromises
treatment outcome. It is therefore desirable to identify prognostic
factors for hematotoxicities. In this issue, Ziepert et al.
[752–762] report the results of a study that analyzed
data of 1399 patients with aggressive lymphoma from trials using
CHOP (combination chemotherapy with cyclophosphamide, doxorubicin,
vincristine and prednisone)-like therapies, with the aim of
identifying prognostic factors for hematotoxicities. These authors
report the development of an online tool, the Haematotoxcalculator,
http://www.toxcalculator.com/.
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Compassionate use of bevacizumab in children and young adults
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Targeted therapies for the most common adult malignancies have
become available over the last decade, but little progress has
been made on the introduction of such therapies for children
with malignant solid tumors. Bevacizumab is a humanized antibody
against vascular endothelial growth factor (VEGF), which by
specific binding to VEGF-A and its isoforms counteracts angiogenic
effects induced by VEGF and allows for a normalization of tumor
vasculature. In 2004, the USA FDA approved bevacizumab as a
first-line treatment of patients with metastatic colorectal
cancer, and it is currently being tested for various other adult
malignancies such as renal cell carcinoma, metastatic breast
cancer, and advanced pancreatic cancer. Nevertheless, clinical
experiences with bevacizumab in pediatric patients are limited.
In this issue, Benesch et al. [807–813] report the results
of the compassionate use of bevacizumab in 15 children and young
adults with refractory or recurrent solid tumors. These authors
report that bevacizumab seems to have a good acute safety profile
and some antitumor activity in these heavily pretreated children
and young adults. They argue that prospective clinical trials
are urgently needed to further evaluate the safety and efficacy
of bevacizumab in pediatric patients.
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Quote
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"What good men most biologists are, the tenors of the scientific
world-temperamental, moody, lecherous, loud-laughing, and healthy.
Your true biologist will sing you a song as loud and off-key
as will a blacksmith, for he knows that morals are too often
diagnostic of prostatitis and stomach ulcers."
John Steinbeck, who knew male biologists, writing in The log from the Sea of Cortez
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