© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 3, 155,
February 6, 2002
© 2002 Oxford University Press
IN THIS ISSUE |
Disease-specific mortality is the most widely accepted end point in randomized cancer screening trials. The validity of this end point requires that the cause of death be accurately determined. An alternative end point, all-cause mortality, requires only that the death and the date be accurately ascertained. Black et al. (p. 167) compared disease-specific and all-cause mortality in 12 published randomized trials of cancer screening with information on both end points. They found major inconsistencies in the results for these end points in seven of the 12 trials. Because all-cause mortality is not affected by problems associated with misclassifying the cause of death, the authors recommend that all-cause mortality be examined when interpreting the results of randomized cancer screening trials.
In an accompanying editorial, Juffs and Tannock (p. 156) note that, in this comparison of all-cause mortality and disease-specific mortality, the net effect of misclassifying the cause of death has favored screening. They suggest that, although population-based screening trials with the improved design of an all-cause mortality end point will require very large numbers of patients, a lengthy follow-up time, and great expense, implementation of costly screening programs cannot be justified if we are not certain of their true benefit.
Platinum-Based Therapy in Elderly Lung Cancer Patients
Although many newly diagnosed cancer patients are elderly, clinicians often view even relatively healthy elderly patients as unfit for aggressive treatment. In particular, older patients are often not treated with combination or platinum-based therapy. To investigate whether advanced age reduces responsiveness to cisplatin or exacerbates toxicity, Langer et al. (p. 173) analyzed data from an Eastern Cooperative Oncology Group (ECOG) study that had compared outcomes among non-small cell lung cancer (NSCLC) patients randomly assigned to cisplatin plus either etoposide or paclitaxel. Response rates, toxicity, and survival in fit, elderly NSCLC patients (i.e., those 70 years of age or older) were similar to those in younger patients, although the older patients had a higher incidence of comorbid conditions and experienced more leukopenia and neuropsychiatric toxicity. The authors conclude that there is no good reason to deny fit elderly NSCLC patients access to protocol therapy.
Lung Cancer After Treatment for Hodgkin’s Disease
Lung cancer is a frequent cause of death in patients cured of Hodgkin’s disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described. Travis et al. (p. 182) quantified the risk of treatment-associated lung cancer, taking into account tobacco use. Treatment with alkylating agents without radiotherapy was associated with a fourfold increased risk of lung cancer, and a radiation dose of 5 Gy or more without alkylating agents increased the risk more than fivefold. Lung cancer risk increased with both increasing number of cycles of alkylating agents and increasing radiation dose. Risk after treatment with alkylating agents and radiotherapy together was as expected if the individual excess risks were summed. Tobacco use increased lung cancer risk more than 20-fold. The authors underscore that the precise estimates of risk resulting from treatment should be interpreted with caution given the possible residual and enhancing effects of tobacco.
Cost-Effectiveness of Cervical Cancer Screening Policies
Recommended policies for cervical cancer screening differ widely among countries with respect to targeted age range, screening interval, and total number of scheduled Pap smears. In this issue, van den Akker-van Marle et al. (p. 193) used a microsimulation screening analysis program to perform a cost-effectiveness analysis that compared the efficiency of cervical cancer screening policies of almost 500 cervical cancer screening policies. The authors identified 15 efficient screening policies, with age ranges of 40–52 years (for two Pap smears) and of 20–80 years (for 40 scheduled Pap smears). The average cost-effectiveness ratios increased from $6700 (for the 12-year screening interval) to $23,900 (for the 1.5-year screening interval) per life-year gained. The authors note that the cost-effectiveness ratios could be improved for some countries. The authors conclude that the diversity in cervical cancer screening policies among high-income countries does not appear to relate to the cost-effectiveness ratio of the screening policy.
ATM Mutations in Breast Cancer Families
The ATM gene is mutated in ataxia-telangiectasia, an autosomal recessive disorder that predisposes carriers to various cancers, but controversy exists as to whether ATM mutations increase the risk of breast cancer. Chenevix-Trench et al. (p. 205) examined two ATM mutations that may be associated with an increased risk for breast cancer in a population-based, case–control series of breast cancer patients and in multiple-case breast cancer families. They found one case patient who carried one of these ATM mutations, but no patients or control subjects carried the other mutation. In three multiple-case families, one of the mutations segregated with breast cancer. They recommend that a full mutation analysis of the ATM gene in multiple-case breast cancer families may clarify the role of ATM in breast cancer susceptibility.
Allelic Imbalances in Bladder Cancer
Bladder cancers have high rates of genomic instability. Primdahl et al. (p. 216) investigated whether genome-wide screening with single-nucleotide polymorphism (SNP) arrays could detect allelic imbalance (loss of gain of at least one allele) in bladder cancers. Using DNA from microdissected bladder tumors and leukocytes, they detected allelic imbalances in known areas of imbalance on chromosomes 6, 8, 9, 11, and 17 and in a new area on the short arm of chromosome 6. They detected more imbalances in TP53-mutated tumors, in both muscle-invasive tumors and noninvasive tumors. The authors conclude that SNP arrays are feasible for high-throughput, genome-wide scanning for allelic imbalances in bladder cancer.
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