Trends in Brain Cancer Incidence and Survival in the United States: Surveillance, Epidemiology, and End Results Program, 1973 to 2001.

Sundeep Deorah, M.A.; Charles F. Lynch, M.D., Ph.D.; Zita A. Sibenaller, Ph.D.; Timothy C. Ryken, M.D.

Disclosures

Neurosurg Focus. 2006;20(4):E3 

In This Article

Discussion

Our review of 38,453 cases of malignant brain tumor reported to the SEER registry from 1973 to 2001 involves one of the largest collections of data on these patients. Using the US population in the year 2000 as a reference for standardization, we report an overall incidence rate of 6.1 cases per 100,000 person-years. The SEER data include only malignant CNS tumors (that is, those with an ICD-O behavior code of 3) and exclude nonmalignant CNS tumors (behavior codes of 0 and 1), despite their potential for causing death or significant morbidity. A more recently established centralized database, CBTRUS, collects data on all primary CNS tumors. An annual incidence of 14.1 cases per 100,000 person-years (based on the 2000 population standard) for all primary CNS tumors was noted in the CBTRUS statistical report for 2004. Meningiomas, pituitary tumors, and nerve sheath tumors accounted for approximately 24, 8, and 6.5%, respectively, of all CNS tumors, thus largely explaining the differences in incidence rates produced by the two registries.[18]

In accordance with previous studies, we found that very young adults have the lowest risk of brain cancer and that the risk continues to rise with age. Higher incidence for those in older age groups suggests a possible role for bioaccumulation from environmental toxic exposure in the cause of malignant brain tumor. Our results also confirm previous observations of a higher incidence of brain cancer in men compared with women. Although some investigators have suggested that female sex hormones have a protective effect against brain cancer, others have suggested innate differences in the susceptibility of X and Y chromosomes to tumorigenic stimuli.[11]

There have been several reports on the association between race and the incidence of malignant brain tumor. In our study, Caucasians had a relative risk of 1.86 compared with African-Americans for malignant brain tumor. This is less than that reported by Robertson, et al.,[17] who found the relative risk for African-Americans to be 6.2 for GBM, 3.5 for astrocytoma, and 4.3 for oligodendroglioma. Others have reported that Caucasians have a relative risk of 2.3 to 2.5 compared with African-Americans for GBM.[5,12] At least a portion of this difference is related to socioeconomic differences and better access to health care for Caucasians rather than a difference in genetic susceptibility. Residents of metropolitan counties (used as surrogates for urban residence) were 1.35 times at higher risk of malignant brain tumor compared with residents of nonmetropolitan counties (used as surrogates for rural residence). Although farming and pesticide exposure have been suggested as potential risk factors, either their effects are small or there are larger risk factors operating in urban areas. Differences in access to medical care may also be a reason for this discrepancy between urban and rural incidence rates. At the same time, there is a possibility of nondifferential misclassification of exposure (for example, residence) due to mobility of the study population, because SEER obtains information on the patient's residence at the time of diagnosis but does not collect data on prior residences.

Several studies have addressed the issue of the incidence trend for primary malignant brain tumor in recent decades. Although they generally concur that the incidence of primary malignant brain tumor has been rising, some are based on a relatively small number of cases, and others have used statistical sampling methods to arrive at this conclusion. We have used a population-based approach to calculate incidence trend, and we report that the incidence of malignant brain tumor is decreasing in the US. By using regression analysis, we found that the incidence rate increased until 1987, and has been declining, albeit modestly, since then.

During the period of rising incidence rate, from 1973 to 1987, the elderly population experienced the greatest increase (EAPC 3.87%). This period also corresponds to the period of the introduction and widespread use of CT and MR imaging, which increased the sensitivity of brain cancer diagnosis. However, some investigators believe that the increased incidence of brain cancer in this time period was not entirely due to an artifact of increased case identification. By retrospective review of medical records, Desmeules, et al.,[2] determined that approximately 20% of CNS tumors remained undiagnosed without the use of CT or MR imaging studies. Therefore, they argued that CT or MR imaging should account for only a 20% increase in the incidence among the elderly. Because the increase was much larger, there were reasons to believe that factors besides CT and MR imaging were important in creating the observed increase in the incidence rate of brain tumor. Technological advances related to stereotactic brain biopsy procedures and the increased understanding and knowledge of physicians could also have affected the incidence trend during this period.[13] Because the rising trend was seen across both sexes and all ages, races, and places of residence, it appears less plausible that a specific risk factor was operating in that time period that affected everyone alike.

A notable finding in this study is the falling incidence trend of malignant brain tumor in the US after 1987. Using SEER data, Gurney and Kadan-Lottick[3] reported that incidence rates for CNS cancer had stabilized after 1991 in all age groups, including the very elderly. However, concerns over changes in environmental toxicants, such as radio-frequency exposure, pesticides, N-nitroso compounds, and ionizing radiation, as well as several epidemiological studies linking them to brain tumor, have continued to fuel interest in the close monitoring of incidence trends for brain cancer. Cellular phones were introduced in the 1980s and became widespread by the early 1990s. There is growing concern among the public that exposure to radiofrequency fields from cellular phones might increase the risk of brain cancer.[9] Recently, investigators have reported in large case–control studies that there is no association between cellular phone use and risk of brain cancer.[7,14] Likewise, our results do not support the hypothesis relating cellular phone use and brain cancer at the population level. If anything, the incidence of brain cancer declined during the period of cellular phone use. Of particular interest is the observation that the incidence rates are declining in the urban counties, which are expected to contain heavy users of cellular phones. However, being a population-based observation study, our study suffers from ecological fallacy, and consequently it contributes only modestly to causality. In addition, concerns, including potentially long induction periods, persist for long-term, heavy users of cellular phones.

Several findings specific to certain tumor types are noted in the study. Of particular concern is the continued rising incidence of GBM. Although its increase in the 1970s and 1980s can be explained on the basis of increased case identification due to improved imaging techniques, its rising trend in the late 1980s and 1990s can, in part, be explained by a falling trend for astrocytoma NOS. A shift between diagnostic categories may not reflect a real change in the incidence, but rather, changes in pathologic diagnostic practice, such as better techniques to obtain and store biopsy specimens and the expertise of neuropathologists in making a specific diagnosis.

Consistent with earlier reports, survival for patients with brain cancer has improved over the last three decades. The population-based data suggest that either cases are being diagnosed at an earlier stage or that improvements in treatment have, at least partially, been transferred to the general population. As reported earlier, the 5-year relative survival rate differs only minimally by sex, race, and place of residence. As in several clinical and population-based studies, we noted a pattern of decreasing survival rates corresponding with increasing age of the patients. Responses to both radiotherapy and chemotherapy have been correlated with the age of patients and are thought, at least partially, to explain the importance of age in the prognosis of patients with brain tumor. Unlike those for patients with malignant brain tumor in general, survival rates for patients with GBM have not shown any improvement after the 1980s. There is a need to develop more innovative and effective therapies to deal with this lethal cancer.

The statistics reported in this study reflect the experience of approximately 10% of the US population, which has been oversampled for ethnic and rural population. Because SEER maintains very high standards in terms of data collection and the study includes a very large number of cases, the incidence rates and survival estimates reported in this study are robust for several categories, including relatively small population or histologic subgroups. By having a large number of cases in each year of diagnosis after 1973, we had meaningful trend data to test the effect of changes in environmental risk factors on brain cancer risk at the population level. However, being a population-based study, the results contribute only in a limited manner to causal inference. In addition, there is no uniform microscopic review; cases reported to the registries are based upon diagnoses rendered by multiple pathologists with varying levels of expertise. Another limitation of our study is that we included only malignant brain tumors. Because several brain tumor subtypes may have benign and malignant entities or may progress from benign to malignant, this limits our understanding of etiologic factors of tumor subtypes and their trends over time.

The advantage of using SEER data for calculating patient survival rate is that it is a population-based estimate and it reflects the end results of research, clinical trials, and diffusion of therapy to the general population. The individual case series and clinical trials have motivated patients and physicians, and the survival experiences shown by them are generally larger than what is finally seen at the population level. However, by excluding benign CNS tumors, which show better survival rates, SEER data underestimate survival rates for patients with brain tumors.

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