Correspondence to: Clyde B. Schechter, M.D., Mount Sinai Medical Center, Department of Community and Preventive Medicine, One Gustave L. Levy Place, New York, NY 10029-6574.
The National Cancer Institute's Surveillance, Epidemiology, and End Results1 Program has reported a 35% rise in the incidence of childhood brain cancer since 1972. Legler et al. (1) conclude that increased use of magnetic resonance imaging (MRI) totally accounts for this increase. I believe this claim is erroneous and inconsistent with their own evidence.
The claim that Smith et al. (2) persuasively linked the "rise in brain cancer incidence among children . . . to the increased availability of MRI" is open to different interpretation. That article does not examine the relationship between MRI use and the increase in brain cancer incidence. Rather, statistical modeling techniques were applied to test whether the mid-1980s increase in incidence occurred in a stepwise fashion versus a linear fashion. Smith et al. assumed, without evidence, that an environmental cause would produce a linear increase but that improvements in detection would produce a stepwise change. In fact, the stepwise model is a "straw man" that does not reflect the expected effects of any process. That analysis shows only that the rise in rates was more rapid than graduala conclusion that, absent more specific evidence, is compatible with essentially any cause.
Moreover, the evidence presented by Legler et al. in support of the "better detection" cause is ambiguous and can, in fact, be construed as evidence against it. If increased sensitivity for real disease had caused the increase, the incidence would have risen temporarily and then returned to baseline. The duration of the apparent increase would be approximately equal to the lead time gained by the widespread use of MRI. However, in reality, the incidence rate has not yet subsided. Therefore, under this hypothesis, we would infer that MRI has gained a lead time approaching 15 years. But Legler et al. note that 5-year survival for these children has only increased to 63% from 58% over the same period. If the survival function for these children is exponential, these findings correspond, by standard calculations (3), to mean survival times of approximately 10.8 and 9.2 years, respectively. The increase in mean survival time consists of lead time and whatever real survival benefit results from early detection and from any improved efficacy of treatment during the 1980s and 1990s. Therefore, the gain in lead time is at most 1.6 years. If increased detection sensitivity accounted for the increased incidence, the return to baseline should have occurred long ago. The incidence and survival data thus conclusively exclude increased sensitivity as a cause of the increase in incidence.
Increased detection could account for a sustained increase in incidence of brain cancer, with minimal decreases in mortality only through the detection of substantial numbers of small lesions that are histologically brain cancer but would, if left alone, never surface clinically, as occurs with prostate cancer in the elderly. A typical signature of such "pseudo-disease" is the frequent incidental finding of the lesions in autopsies of people dying of unrelated causes. That phenomenon has never, to my knowledge, been reported.
The evidence presented by the authors is fully compatible with the rapid introduction and persistence of an as yet unidentified neurocarcinogen into the environment. This hypothesis has high a priori plausibility. In 1984, the National Academy of Sciences (4) reported that 15 000 of the 75 000 chemicals registered for commercial use with the U.S. Environmental Protection Agency had moderate to high potential for human exposure. Less than one half of them had been tested for toxicity at all, and fewer than 20% had been tested for toxicity in developing organisms. It would be tragic to delay investigating this type of etiology on the basis of reasoning that is viable only if there is a high prevalence of an unattested indolent form of brain cancer.
NOTES
Editor's note: SEER is a set of geographically defined,
population-based, central cancer registries in the United States, operated by local nonprofit
organizations under contract to the National Cancer Institute (NCI). Registry data are submitted
electronically without personal identifies to the NCI on a biannual basis, and the NCI makes the
data available to the public for scientific research.
REFERENCES
1
Legler JM, Ries LAG, Smith MA, Warren JL, Heineman EF,
Kaplan RS, et al. Brain and other central nervous system cancers: recent trends in incidence and
mortality. J Natl Cancer Inst 1999;91:1382-90.
2
Smith MA, Friedlin B, Ries LA, Simon R. Trends in reported
incidence of primary malignant brain tumors in children in the United States. J Natl Cancer
Inst 1998;90:1269-77.
3 Beck JR, Pauker SG, Gottlieb JE, Klein K, Kassirer JP. A convenient approximation of life expectancy (the "Deale"). II. Use in medical decision making. Am J Med 1982;73:889-97.[Medline]
4 Commission on Life Sciences, National Academy of Sciences. Toxicity testing: strategies to determine needs and priorities. Washington (DC): National Academy Press; 1984.
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