Annals of Oncology 2005 16(11):1717; doi:10.1093/annonc/mdi374
© 2005 European Society for Medical Oncology
In this issue
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CNS metastases in HER2-positive breast cancer
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Trastuzumab, a humanized monoclonal antibody that recognizes
the extracellular domain of HER2, has been studied in a variety
of clinical settings, including a randomized trial of chemotherapy
with or without trastuzumab as first-line treatment for HER2-positive
metastatic breast cancer. That study showed that the addition
of trastuzumab improved response rate, and progression-free
and overall survival. Recently, HER2 overexpression and trastuzumab-based
therapy has been suggested to be associated with increased rates
of brain metastases. Retrospective analyses of women with HER2-overexpressing
breast cancer receiving trastuzumab-based treatment indicated
that approximately one-third had developed CNS metastases. In
this issue, Burstein et al. report on a study that aimed to
assess the clinical frequency and time course of isolated brain
metastases among women receiving trastuzumab in combination
with chemotherapy for advanced breast cancer. These authors
conclude that patients with HER2-overexpressing metastatic breast
cancer are at risk of CNS progression, reflecting improved peripheral
tumor control and patient survival through use of trastuzumab.
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Imatinib in patients with c-Kit-expressing relapsed SCLC
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Although standard combination cytotoxic chemotherapy of small-cell
lung cancer (SCLC) has shown antitumor activity, long-term survival
is low and most patients eventually develop progressive disease.
Even patients achieving a complete response show a high rate
of relapse. High level expression of c-Kit and its ligand, stem
cell factor (SCF), has been found widely in SCLC, and the role
of the c-Kit autocrine loop in SCLC has been well studied. This
autocrine loop not only functions cooperatively with other SCLC
autocrine loops, but also seems to confer a tumor survival advantage
in SCLC. Imatinib mesylate is an orally bioavailable inhibitor
of several tyrosine kinases including c-Kit. In a pivotal study,
pretreatment of H526 cells with imatinib was shown to inhibit
SCF-mediated Kit activation. In this issue, Dy et al. report
the results of a phase II study that aimed to evaluate the clinical
activity of imatinib mesylate in patients with recurrent and
refractory c-Kit-expressing SCLC. These authors report that
imatinib showed no clinical activity in spite of patient selection
for c-Kit-expressing SCLC.
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Prognostic significance of bone marrow magnetic resonance imaging in previously untreated multiple myeloma
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Conventional radiographs of the skeleton are routinely obtained
during the work-up of patients with suspected myeloma, with
abnormal radiographs being detected in more than 80% of patients.
However, the prognostic value of radiographic findings is controversial
and in some series, patients with normal appearing skeletal
surveys actually had a worse prognosis than patients with minimal
lytic changes. Recently, the International Myeloma Working Group
proposed an International Staging System (ISS) based on serum
albumin and ß
2-microglobulin. However, magnetic resonance
imaging (MRI) can sample a large volume of bone marrow and depicts
bone marrow abnormalities in multiple myeloma with greater sensitivity
than conventional radiographs. In this issue, Moulopoulos et
al. report a study that aimed to correlate MRI patterns with
the ISS and the outcome of patients with previously untreated,
symptomatic multiple myeloma. These authors report that diffuse
marrow replacement on MRI added to the evaluation and management
of these patients.
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Molecular staging of the sentinel lymph node in melanoma patients
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The number of metastatic nodes and tumor burden of nodal metastasis
are the two major predictors of outcome in patients with melanoma
of equivalent T classification. Therefore, accurate classification
of the nodal status is of compelling prognostic value for patients
with early stage melanoma. In this issue, Romanini et al. report
a study that aimed to assess the prognostic value of using reverse
transcriptase (RT)–PCR to determine positivity in melanoma
patients'sentinel lymph node (SLN) previously shown to be negative
by conventional histopathology. These authors report that RT–PCR
was more sensitive than conventional histopathology for the
detection of SLN positivity and that it was a reliable predictor
of disease relapse in stage I–II melanoma patients.
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Quote
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‘Also, the high standard held up to the public mind by
the College of Physicians, which gave its peculiar sanction
to the expensive and highly rarefied medical instruction obtained
by graduates of Oxford and Cambridge, did not hinder quackery
from having an excellent time of it; for since professional
practice chiefly consisted in giving a great many drugs, the
public inferred that it might be better off with more drugs
still, if they could only be got cheaply, and hence swallowed
large cubic measures of physic prescribed by unscrupulous ignorance
which had taken no degrees.’
Dr Lydgate considers the problems of his profession in George Eliot's Middlemarch.
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