© 2005 Oxford University Press
IN THIS ISSUE
Recommendations for Tumor Marker Prognostic StudiesPublished tumor marker study articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results. To improve the quality of marker research reporting, McShane et al. (p. 1180) have developed guidelines for the reporting of tumor marker studies, as recommended by the National Cancer Institute–European Organization for Research and Treatment of Cancer First International Meeting on Cancer Diagnostics in 2000. The guidelines identify information about the study design, pre-planned hypotheses, patient and specimen characteristics, assay methods, and statistical methods that should be included in marker study reports. The goal of the guidelines, the authors conclude, is to encourage complete reporting so that relevant information will be available to help others judge the usefulness of the data and understand the context in which the conclusions apply.
Role of Detection in Predicting Breast Cancer Survival
Screening mammography detects breast cancers at an earlier stage of development than breast cancers detected symptomatically—the so-called stage shift—so mammographically detected breast cancers tend to have better prognoses. To investigate the benefits of breast cancer screening beyond stage shift, Shen et al. (p. 1195) analyzed data from three large randomized breast cancer screening trials. They found that method of detection was an independent predictor of disease-specific survival. The authors conclude that there is an apparent survival benefit beyond stage shift for patients with screen-detected breast cancers compared with those with breast cancers detected otherwise and that method of detection appears to be an important prognostic factor. The clinical implication is that for two women with seemingly identical disease, the one whose cancer was detected mammographically has a much better prognosis. The research implication is that method of detection should be collected routinely in clinical trials.
In an editorial, Krzyzanowska and Tannock (p. 1170) discuss these results, whose endpoint was cancer-specific survival, and results of another recent study, whose endpoint was distant disease-free survival; both studies reported better survival associated with screen-detected cancers. They conclude, however, that knowing the method of detection might add limited prognostic value beyond that of well-established prognostic factors.
Differential Effects of Gefitinib and Cetuximab in NSCLC
The epidermal growth factor receptor (EGFR) is overexpressed in many cancers, and several targeted therapies aimed at inhibiting EGFR signaling have been developed. Many patients with non–small cell lung cancer (NSCLC) who show radiographic responses to gefitinib, a small-molecule inhibitor of the tyrosine kinase domain, have somatic mutations in the EGFR gene, but whether such mutations are associated with responsiveness to cetuximab, a monoclonal antibody directed against the extracellular domain, is unknown. In this issue, Mukohara et al. (p. 1185) report on their analysis of the effects of gefitinib and cetuximab on NSCLC cell lines carrying wild-type or mutant EGFR. Both agents had similar, and relatively weak, effects on growth and apoptosis of cells with wild-type EGFR. However, cells with mutant EGFR were much more sensitive to gefitinib than to cetuximab, possibly because only gefitinib was able to inhibit phosphorylation of the mutant EGFR.
In an editorial, Minna et al. (p. 1168) note that the findings have important clinical implications because both agents should, in theory, block EGFR signaling. They point out that evidence from other studies suggests that cetuximab may still have a role to play in the context of EGFR mutant NSCLC.
Cancer in Men With Klinefelter Syndrome
Men with Klinefelter syndrome have one or more extra X chromosomes and have endocrine abnormalities. Case reports have led to suggestions that men with Klinefelter syndrome have elevated risks of several cancers. Swerdlow et al. (p. 1204) followed a cohort of 3518 men who had been diagnosed with Klinefelter syndrome and compared their cancer incidence and mortality with that of men in the national population. They found that, compared with the general population, men with Klinefelter syndrome had higher mortality from lung cancer, breast cancer, and non-Hodgkin lymphoma and lower mortality from prostate cancer. Especially high were mortality from breast cancer among men with 47,XXY mosaicism and mortality from non-Hodgkin lymphoma among men with a 48,XXYY constitution. The cancer incidence data corroborated these associations. The authors conclude that these results support a hormonal etiology for breast cancer in men and for prostate cancer.
Disparities in the Receipt of Treatment for Colon Cancer
To determine why disparities in receipt of colon cancer treatment among black and white patients exist, Baldwin et al. (p. 1211) analyzed data on chemotherapy receipt of 5294 black and white Medicare-insured patients aged 66 years and older. The authors found that although black and white patients with resection of stage III cancer were equally likely to consult with an oncologist, black patients were less likely to receive chemotherapy. The disparity was highest among patients aged 66–70 years. Patient, physician, hospital, and environmental factors accounted for approximately 50% of the disparity, with 27% related to surgical length of stay and neighborhood socioeconomic status, 12% to health systems. The authors conclude that more qualitative research is needed to understand the factors that contribute to lower chemotherapy receipt by black patients.
Cetuximab Therapy and Symptomatic Hypomagnesemia
Schrag et al. (p. 1221) report that patients treated with cetuximab, a monoclonal antibody against the epithelial growth factor receptor (EGFR), occasionally develop a magnesium wasting syndrome with inappropriate urinary excretion. They first observed this phenomenon in a 34-year-old male patient with metastatic colorectal cancer who developed profound fatigue and symptomatic hypocalcemia and hypomagnesemia while receiving cetuximab plus irinotecan therapy. This problem prompted a review of serum chemistry reports for 154 consecutive colorectal cancer patients treated with cetuximab, of whom 34 had at least one serum magnesium measurement, and eight of the 34 patients had grade 3 or 4 hypomagnesemia. The authors suggest that, when fatigue or hypocalcemia is encountered during cetuximab therapy, serum magnesium level should be measured and repleted as necessary.
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