TOPICAL TOPICSBrain Cancer Incidence in Children: Time to Look Beyond the Trends

James G. Gurney, PhD*

Key words: brain neoplasms; CNS cancer; children; trends; epidemiology; magneticresonance imaging

Primary malignant tumors of the brain, because of therelatively poor prognosis and the substantial morbidityamong many who survive, constitute a particularly omi-nous group of neoplasms. CNS malignancies, of whichover 93% are located in the brain, represent 21% of allmalignancies in children younger than 15 years of age inthe United States (U.S.). The annual age-adjusted inci-dence rate is currently about 32 per million children[1,2]. Nonmalignant intracranial neoplasms, such as cra-niopharyngiomas, benign meningiomas, pituitary tumors,and choroid plexus papillomas, increase the annual CNStumor burden among children by an additional 7 permillion [2]. Public and scientific concern about risingincidence rates of malignant brain tumors (hereaftercalled “brain cancer”) has been heightened in recentyears [3–8]. Indeed, data from the United States [9,10],Europe [11–13], and Australia [14] have shown thatbrain cancer incidence rates have increased substantiallyin children over the past two to three decades. What issometimes not appreciated, however, is that increasingincidence ratesof brain cancer do not necessarily equateto increasingoccurrenceof brain cancer.

As many fear, brain cancer trends could be reflectingincreased exposure to etiologically relevant environmen-tal toxins or hazardous life style choices. They could,however, also reflect changes in a variety of factors re-lated to improved case ascertainment. In a recently pub-lished report [15], Malcolm Smith and several colleaguesfrom the U.S. National Cancer Institute explored the lat-ter conjecture. They conducted a statistical analysis ofchildhood brain cancer incidence rates using nationaldata from the population-based SEER [1] cancer surveil-lance system. Their a priori hypothesis was that the in-troduction and dissemination of magnetic resonance im-aging (MRI) technology in the mid–1980s resulted inimproved detection and reporting of pediatric brain can-cer, thus largely explaining the observed U.S. trends.They did not average yearly rate changes over the 1973–1994 time period of their study using a linear model witha constant annual rate of increase, as others have done.Rather, they accounted for a sharp increase in rates that

occurred in 1984 and 1985 using a step function(“jump”) model. The jump model provided a statisticallysignificantly better fit to the temporal incidence data thandid the linear model. Their results showed that incidencerates of childhood brain cancer varied little from 1973–1984, a jump in rates occurred in 1984–1985, and a newbaseline rate was established after 1985 that remainedessentially stable through 1994. In other words, the av-erage annual increase in childhood brain cancer rates thatwas calculated in previous reports using linear modelswas explained primarily by the sharp rate increases thatoccurred in 1984 and 1985.

Figure 1 illustrates childhood brain cancer trendsbased on SEER data using the modeling approach em-ployed by Smith et al. [15]. The estimated average per-centage change (EAPC) from 1975–1995 using a linearmodel was +1.5% per year. The jump model provided abetter fit than the linear model (P 4 0.003) and showedthat the EAPCs from 1975–1984 and 1986–1995 wereboth −0.1%, respectively. These data are consistent withstable age-adjusted annual rates of 24 per million chil-dren in the earlier period, and 30 per million children inthe later period.

The Smith et al. report [15], and an accompanyingeditorial by William Black [16], presented evidence insupport of the MRI-detection effect, in addition to thestatistical analysis. This included: 1) the timing of MRIintroduction in the U.S.; 2) the rapid nature of the diffu-sion and application of MRI technology in the U.S.; 3)the fact that focal low grade malignancies, especially ofthe brain stem and cerebrum for which MRI has consid-erable detection benefits over CT scans, substantially ac-counted for the increased rates; and 4) that mortality rates

Division of Pediatric Epidemiology/Clinical Research, Department ofPediatrics, University of Minnesota; and University of Minnesota Can-cer Center, Minneapolis, Minnesota*Correspondence to: James G. Gurney, Division of Pediatric Epide-miology, University of Minnesota, 1300 S. 2nd St., Suite 300, Min-neapolis, MN 55454-1015. E-mail: gurney@epi.umn.edu

Received 26 January 1999; Accepted 5 March 1999

Medical and Pediatric Oncology 33:110–112 (1999)

© 1999 Wiley-Liss, Inc.

did not mirror the increase in incidence rates, despite thelack of substantial improvement in brain cancer survivalover the same time period. Changes in the mid–1980s inother diagnostic capabilities, such as stereotactic biopsy,may also have accounted for some portion of the ob-served rise in incidence rates.

The report by Smith et al. [15] lends strong support tothe contention that recent increases of childhood braincancer incidence rates in the U.S. are due, at least to alarge extent, to improved detection and reporting coinci-dent with the advent of MRI in the mid–1980s. If correct,then some consolation can be taken that the rise in ratesdid not likely represent an increase in the exposure toenvironmental or behavioral hazards resulting in morebrain cancers in children. This consolation must be bal-anced, however, by our continuing lack of knowledgeabout what specific factors are causally related to child-hood brain cancer [17,18]. This remains the case despiterecent research efforts to reveal the role of likely candi-dates [19–25].

The controversy related to the increasing childhoodbrain cancer rates points out an important issue: Inter-pretation of temporal trends is often a tricky business. Ananalysis of incidence rates over time will reflect not onlytrue increases or decreases. Also to be considered aretemporal changes in population characteristics, the accu-racy of census estimates, screening practices, diagnostictechnology, morphology classifications, and other prac-

tices influencing case ascertainment. One or more ofthese elements can effectively conspire to show increas-ing incidence rates over time that is not reflective of morecancer, but rather of better case identification. Because ofthe relative rarity of childhood cancers, especially whenstratified by site or histology, incidence rates are consid-erably more sensitive to changes in case identificationthan are most adult cancers.

The difficulty in properly understanding the contribu-tion of confounding factors when looking for truechanges in disease occurrence, however, certainly doesnot mean surveillance efforts should be stopped. Publichealth surveillance systems are essential tools for quan-tifying and tracking changes in the burden of diseasewithin a defined population. Rather, the example citedhere serves to reinforce the need for a cautious andthoughtful approach to the interpretation of all data. AsBlack points out in his editorial [16], the report by Smithet al. [15] should lead us to other questions that need tobe answered in relation to childhood brain cancer. Blackincludes these: “How many children have unrecognizeddisease, what is the full spectrum of the disease, howshould the disease be managed, and what signs or symp-toms should prompt an MRI examination in the firstplace?” I would add that we also need concerted researchefforts toward identifying both exogenous and geneticfactors that increase the susceptibility to brain cancer inchildren.

Fig. 1. Average annual incidencerates of brain cancer in childrenyounger than 15 years in the UnitedStates, SEER 1975–1995. Rateswere adjusted to the 1970 U.S. stan-dard population. From 1975–1995,the rates increased an average of1.5% per year (long continuous line).The average rate change for both pe-riods 1975–1984 and 1986–1995(short lines) was −0.1% per year.The incidence rates averaged 24 permillion children from 1975–1984,and 30 per million children from1986–1995.

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ACKNOWLEDGMENTS

Parts of this article were published previously in theChildren’s Cancer Research Fund’s “C3 Causes ofChildhood Cancer Newsletter” (Vol. 9, No. 5, October1998; Oie@epivax.epi.umn.edu). The author thanksLynn Ries and Malcolm Smith of the U.S. National Can-cer Institute for providing the information contained inFigure 1.

REFERENCES

1. Ries LAG, Kosary CL, Hankey BF, et al., editors. SEER cancerstatistics review, 1973–1995. Bethesda, MD: National Cancer In-stitute; 1998.

2. Gurney JG, Wall DA, Jukich PJ, et al. The contribution of non-malignant tumors to CNS tumor incidence rates among children inthe United States. Cancer Causes Control (in press).

3. Cushman J. U.S. reshaping cancer strategy as incidence in chil-dren rises: increase may be tied to new chemicals in the environ-ment. The New York Times, September 29, 1997, p A1.

4. Burcum J. A medical enigma: a rise in brain tumors sets off searchfor a reason. The Minneapolis Star Tribune, January 6, 1999, pA12.

5. Larsen NS. Brain tumor incidence rising: researchers ask why(news). J Natl Cancer Inst 1993;85:1024–1025.

6. Davis DL, Ahlbom A, Hoel D, et al. Is brain cancer mortalityincreasing in industrial countries? Am J Ind Med 1991;19:421–431.

7. Workshop Group on Brain Cancer. Increasing incidence of braincancer. Can Med Assoc J 1992;146:847–848.

8. U.S. EPA Conference on Preventable Causes of Cancer in Chil-dren (minutes). Washington, DC: U.S. Environmental ProtectionAgency, Office of Children’s Health Protection; September 15–16, 1997.

9. Gurney JG, Davis S, Severson RK, et al. Trends in cancer inci-dence in children in the U.S. Cancer 1996;78:532–541.

10. Bunin GR, Feuer EJ, Witman PA, et al. Increasing incidence ofchildhood cancer: report of 20 years experience from the GreaterDelaware Valley Pediatric Tumor Registry. Paediatr PerinatalEpidemiol 1996;10:319–338.

11. Blair V, Birch JM. Patterns and temporal trends in the incidenceof malignant disease in children: II. Solid tumours of childhood.Eur J Cancer 1994;30A:1498–1511.

12. McKinney PA, Ironside JW, Harkness EF, et al. Registration qual-ity and descriptive epidemiology of childhood brain tumours inScotland, 1975–90. Br J Cancer 1994;70:973–979.

13. Kaatsch P, Haaf G, Michaelis J. Childhood malignancies in Ger-many—methods and results of a nationwide registry. Eur J Cancer1995;31A:993–999.

14. McWhirter WR, Petroeschevsky AL. Incidence trends in child-hood cancer in Queensland, 1973–1988. Med J Aust 1991;154:453–455.

15. Smith MA, Feidlin B, Ries LAG, et al. Trends in reported inci-dence of primary malignant brain tumors in children in the UnitedStates. J Natl Cancer Inst 1998;90:1269–1277.

16. Black WC. Increasing incidence of childhood primary malignantbrain tumors—enigma or no-brainer? J Natl Cancer Inst 1998;90:1249–1251.

17. Davis FG, Preston-Martin S. Epidemiology: incidence and sur-vival. In: Bigner DD, McLendon RE, Bruner JM, editors. Russell& Rubinstein’s pathology of tumours of the nervous system, VolI, 6th ed. London: Arnold, 1998, p 5–45.

18. Kuijten RR, Bunin GR. Risk factors for childhood brain tumors.Cancer Epidemiol Biomarkers Prev 1993;2:277–288.

19. Preston-Martin S, Pogoda JM, Mueller BA, et al. Maternal con-sumption of cured meats and vitamins in relation to pediatric braintumors. Cancer Epidemiol Biomarkers Prev 1996;5:599–605.

20. Gurney JG, Mueller BA, Davis S, et al. Childhood brain tumoroccurrence in relation to residential power line configurations,electric heating sources, and electric appliance use. Am J Epide-miol 1996;143:120–128.

21. Bunin GR, Kuijten RR, Buckley JD, et al. Relation between ma-ternal diet and subsequent primitive neuroectodermal brain tumorsin young children. N Engl J Med 1993;329:536–541.

22. Bunin GR, Buckley JD, Boesel CP, et al. Risk factors for astro-cytic glioma and primitive neuroectodermal tumor of the brain inyoung children: a report from the Children’s Cancer Group. Can-cer Epidemiol Biomarkers Prev 1994;3:197–204.

23. Pogoda JM, Preston-Martin S. Household pesticides and risk ofpediatric brain tumors. Environ Health Perspect 1997;105:1214–1229.

24. Gurney JG, Mueller BA, Preston-Martin S, et al. A study of pe-diatric brain tumors and their association with epilepsy and anti-convulsant use. Neuroepidemiology 1997;16:248–256.

25. Biegel JA. Genetics of pediatric central nervous system tumors. JPediat Hematol Oncol 1997;19:492–501.

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