Trends in childhood cancer incidence in the U.S. (1992–2004)

Abstract

BACKGROUND.

The etiology of most pediatric neoplasms remains elusive. Examination of population-based incidence data provides insight regarding etiology among various demographic groups and may result in new hypotheses. The objective of the current study was to present updated information regarding childhood cancer incidence and trends in the U.S. overall and among demographic subgroups, including Asian/Pacific Islanders and Hispanics, for whom to the authors' knowledge trends have not been previously examined.

METHODS.

Data obtained by 13 registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program were evaluated to assess incidence and trends of common primary cancers diagnosed between 1992 and 2004 among children aged birth to 19 years. Frequencies, age-adjusted incidence rates, and joinpoint regression results, including annual percent change (APC) in incidence rates (and 95% confidence intervals [95% CI]), were calculated.

RESULTS.

Between 1992 and 2004, a modest, nonsignificant increase in the average annual incidence rate (APC, 0.4%; 95% CI, −0.1%–0.8%) was observed for all pediatric cancer diagnoses combined. There was a suggestion of an increase in leukemia (APC, 0.7%; 95% CI, −0.1%–1.5%), and acute lymphoblastic leukemia in particular (APC, 0.8%; 95% CI, −0.4%–1.9%), whereas rates for central nervous system tumors overall were stable (APC, −0.1%; 95% CI, −1.1%–1.0%); 2 joinpoints were observed for astrocytoma. Rate increases were noted for hepatoblastoma (APC, 4.3%; 95% CI, 0.2%–8.7%) and melanoma (APC, 2.8%; 95% CI, 0.5%–5.1%). Differences by demographic group (sex, age, and race/ethnicity) are also described.

CONCLUSIONS.

The observed trends reinforce an ongoing need for population-based surveillance and further etiologic studies. Cancer 2008. © 2007 American Cancer Society.

It is estimated that in 2007, approximately 10,400 U.S. children aged birth to 14 years will develop cancer.1 There have been ongoing public concerns regarding pediatric cancers,2–6 underscoring a need to monitor incidence rates. The last comprehensive reports concerning U.S. incidence trends included data through 19957, 8; incidence statistics are publicly available in the National Cancer Institute's (NCI's) annual Cancer Statistics Review (available at URL: http://seer.cancer.gov/publications).9 Herein we provide data regarding recent childhood cancer incidence and trends, including an analysis of trends in several demographic groups.

MATERIALS AND METHODS

Data were obtained from the NCI's Surveillance, Epidemiology, and End Results (SEER) program.10 With an estimated 98% case ascertainment rate,11 the SEER 13 registries capture information regarding demographics, tumor site and morphology, stage at diagnosis, treatment, and vital status, representing approximately 14% of the U.S. population.10 Between 1992 and 2004, SEER actively collected data on all cancer cases (excluding nonmelanoma skin cancers) in Connecticut, Hawaii, Iowa, New Mexico, and Utah; in the metropolitan areas of Atlanta, Detroit, Los Angeles, San Francisco-Oakland, San Jose-Monterey, and Seattle-Puget Sound; and from rural Georgia and the Alaskan Native Tumor Registry. The use of the expanded SEER dataset from 1992 onward permitted the evaluation of the most recent trends and facilitated the calculation of incidence rates among Hispanics and Asian/Pacific Islanders.

Histology and topography codes from the third edition of the International Classification of Diseases for Oncology (ICD-O-3)12 were used in classifying cases of 15 common cancers and 8 subtypes (Table 1). We included all first malignancies diagnosed during the period 1992 through 2004 among those aged ≤19 years; 95% of diagnoses were confirmed by histology. Annual population estimates used in the calculation of incidence rates were obtained by the SEER program from the U.S. Census Bureau. The U.S. 2000 standard population (age <1 year, ages 1–4 years, ages 5–9 years, ages 10–14 years, and ages 15–19 years) was used in direct age standardization.

Table 1. International Classification of Diseases for Oncology, Third Edition Histology and Topography Codes

Disease	Code
ALL indicates acute lymphocytic leukemia; CNS, central nervous system; PNET, primitive neuroectodermal tumor.
Any leukemia	9800–9801, 9805, 9820, 9823, 9826–9827, 9831–9837, 9840, 9860–9861, 9863, 9866–9867, 9870–9876, 9891, 9895–9897, 9910, 9920, 9930–9931, 9940, 9945–9946, 9948
Acute lymphocytic leukemia	9826, 9835–9837
Acute myeloid leukemia	9840, 9861, 9866–9867, 9870–9874, 9891, 9895–9897, 9910, 9920, 9931
Other leukemias (lymphoid leukemias other than ALL/other specified and unspecified leukemias)	9800–9801, 9805, 9820, 9823, 9827, 9831–9834, 9860, 9863, 9875–9876, 9930, 9940, 9945–9946, 9948
Hodgkin disease	9650–9655, 9659, 9661–9665, 9667
Non-Hodgkin lymphoma	9590–9591, 9596, 9670–9671, 9673, 9675, 9678–9680, 9684, 9687, 9689–9691, 9695, 9698–9702, 9705, 9708–9709, 9714, 9716–9719, 9727–9729, 9731–9734, 9760–9762, 9764–9769, 9970
Any CNS tumor	8000–8005(C70.0–C72.9, C75.1–C75.3), 8270–8281, 8300, 9350–9352, 9360–9362, 9380(C70.0–C72.9, C75.1, C75.3), 9381–9384, 9390–9394, 9400–9413, 9420–9424, 9430, 9440–9442, 9444, 9450–9451, 9460, 9470–9474, 9480, 9492–9493, 9500(C71.0–C71.9), 9501–9504(C70.0–C72.9), 9505–9508, 9530–9539, 9582
Ependymoma	9383, 9391–9394
Astrocytoma	9380(C72.3), 9384, 9400–9411, 9420–9424, 9440–9442
PNETs (PNET; medulloblastoma/PNET/pineoblastoma/intracranial neuroblastoma)	9362, 9470–9474, 9480, 9500(C71.0–C71.9)
Other gliomas	9380(C70.0–C72.2, C72.4–C72.9, C75.1, C75.3), 9381–9382, 9430, 9444, 9450–9451, 9460
Other CNS tumors (choriod plexus tumors/medullopithelioma/atypical teratoid/rhabdoid tumors/other specified and unspecified CNS tumors)	8000–8005(C70.0–C72.9, C75.1–C75.3), 8270–8281, 8300, 9350–9352, 9360–9361, 9390, 9412–9413, 9492–9493, 9501–9504(C70.0–C72.9), 9505–9508, 9530–9539, 9582
Extracranial neuroblastoma	9490, 9500(C00.0–C70.9, C72.0–C80.9)
Retinoblastoma	9510–9514
Wilms tumor	8959–8960
Hepatoblastoma	8970
Osteosarcoma	[9180–9187, 9191–9195, 9200](C40.0–C41.9, C76.0–C76.8, C80.9)
Ewing sarcoma	9260(C40.0–C41.9, C76.0–C76.8, C80.9)
Rhabdomyosarcoma	8900–8905, 8910, 8912, 8920, 8991
Nonrhabdomyosarcoma soft tissue sarcoma	8587, 8710–8713, [8800–8805, 8810–8811, 8813–8815, 8821, 8823, 8830, 8834–8835](C00.0–C39.9, C44.0–C76.8, C80.9), 8806, 8820, 8822, 8824–8827, 8831–8833, 8836, 8840–8842, 8850–8858, 8860–8862, 8870, 8880–8881, 8890–8898, 8921, 8963(C00.0–C63.9, C65.9–C69.9, C73.9–C76.8, C80.9), 8982, 8990, 9040–9044, 9120–9125, 9130–9133, 9135–9136, 9140–9142, 9150, 9160–9161, 9170–9175, [9180, 9210, 9220, 9240](C49.0–C49.9), 9231, 9251–9252, 9260(C00.0–C39.9, C47.0–C75.9), 9364(C00.0–C39.9, C47.0–C63.9, C65.9–C69.9, C73.9–C76.8, C80.9), 9365(C00.0–C39.9, C47.0–C63.9, C65.9–C76.8, C80.9), 9373, 9491, 9540–9571, 9580–9581
Germ cell tumors	[8000–8005, 8010–8041, 8050–8075, 8082, 8120–8122, 8130–8141, 8143, 8190–8201, 8210–8211, 8221–8241, 8244–8246, 8260–8263, 8290, 8310, 8313, 8320, 8323, 8380–8384, 8430, 8440, 8480–8490, 8504, 8510, 8550, 8560–8573, 9000, 9014–9015, 9073, 9090–9091](C56.9, C62.0–C62.9), 8441–8444, 8450–8451, 8460–8473, 8590–8671, [9060–9065, 9070–9072, 9080–9085, 9100–9101](C00.0–C55.9, C56.9–C72.9, C73.9–C76.8, C80.9), [9102–9105](C00.0–C55.9, C57.0–C61.9, C63.0–C69.9, C73.9–C75.0, C75.4–C76.8, C80.9)
Thyroid carcinoma	[8010–8041, 8050–8075, 8082, 8120–8122, 8130–8141, 8190, 8200–8201, 8211, 8230–8231, 8244–8246, 8260–8263, 8290, 8310, 8320, 8323, 8430, 8440, 8480–8481, 8510, 8560–8573](C73.9), 8330–8337, 8340–8347, 8350
Malignant melanoma	8720–8780, 8790

Statistical Analysis

Frequencies and age-adjusted incidence rates were calculated using SEER*STAT software,13 in which incidence rates are reported as the number of cases per 1,000,000 person-years of follow-up. To examine incidence trends the annual percent change (APC) and 95% confidence intervals (95% CIs) were calculated using Joinpoint software14 to perform weighted least-squares regression, in which the independent variable was calendar year and the dependent variable was the natural logarithm of the age-adjusted incidence rate.9 Joinpoint models were employed to determine when the trend changed in magnitude and/or direction during the period 1992 through 2004, allowing a maximum of 3 joinpoints and a minimum of 2 years between consecutive joinpoints and between joinpoints and endpoints.9, 14, 15 The Joinpoint permutation test adjusts for multiple comparisons to ensure an overall type I error rate of 0.05 for a given trend.14

Rates and trends within sex (male and female), age group (age <1 year, ages 1–4 years, ages 5–9 years, ages 10–14 years, and ages 15–19 years), race (white, black, and Asian/Pacific Islander) and ethnicity (Spanish Hispanic-Latino and non-Spanish Hispanic-Latino) were evaluated. Trends involving ≥1 years with <10 cases, as denoted in Table 2, should be interpreted with caution. Cases indicating American Indian/Alaskan Native and those with an unknown/unspecified race were excluded from subgroup analysis because there were too few cases to allow for a trend analysis.

Table 2. Frequencies, Incidence Rates, and Annual Percent Change in 13 SEER Registries From 1992–2004

Total Cases
	1992–2004
Cancer	No. (%)	Incidence rate*	Years	APC1† (95% CI)	Years	APC2† (95% CI)	Years	APC3† (95% CI)	Years	APC4† (95% CI)
APC indicates annual percentage change; 95% CI, 95% confidence interval; ALL, acute lymphocytic leukemia; AML, acute myeloid leukemia; CNS, central nervous system; PNET, primitive neuroectodermal tumor. Bold type indicates statistical significance at the .05 level. * Incidence rate per 1,000,000 person-years, age-adjusted to the 2000 US Standard population. † The APC was calculated via weighted least-squares regression. ‡ The frequencies and percentages in a column will not sum to those found in the “Total” row because only the most common cancers are reported. § Excludes 266 Alaskan Natives and 310 cases with race unknown. ‖ Trend calculation involves ≥1 years with <10 cases and should be interpreted with caution.
Total‡	22,694 (100%)	157.9	1992–2004	0.4 (−0.1–0.8)
Leukemias	6129 (27%)	41.9	1992–2004	0.7 (−0.1–1.5)
ALL	4697 (21%)	31.9	1992–2004	0.8 (−0.4–1.9)
AML	1085 (5%)	7.5	1992–2004	1.0 (−0.4–2.4)
Other/unspecified leukemias	347 (2%)	2.4	1992–1996	−18.6 (−31.6–−3.2)	1996–2004	7.0 (0.1–14.3)
Hodgkin disease	1611 (7%)	11.7	1992–2004	−0.8 (−2.4–0.7)
Non-Hodgkin lymphoma	1472 (6%)	10.4	1992–2004	1.4 (−0.1–3.0)
CNS tumors	4004 (18%)	27.6	1992–2004	−0.1 (−1.1–1.0)
Ependymoma	308 (1%)	2.1	1992–2004	−0.5 (−4.1–3.3)
Astrocytoma	1920 (8%)	13.3	1992–1999	−2.9 (−5.2–−0.5)	1999–2002	7.8 (−9.1–27.9)	2002–2004	−8.3 (−23.1–9.4)
PNET	971 (4%)	6.6	1992–2004	−1.2 (−3.1–0.7)
Other gliomas	664 (3%)	4.6	1992–2004	1.5 (−0.9–4.0)
Other/unspecified CNS tumors	141 (0.6%)	0.9	1992–2004	5.4 (0.8–10.3)‖
Neuroblastoma (extracranial)	1107 (5%)	7.3	1992–2004	−0.6 (−2.9–1.7)
Retinoblastoma	514 (2%)	3.4	1992–2004	0.3 (−1.5–2.1)
Wilms tumor	804 (4%)	5.3	1992–2004	−2.1 (−4.6–0.4)
Hepatoblastoma	216 (1%)	1.4	1992–2004	4.3 (0.2–8.7)
Osteosarcoma	660 (3%)	4.7	1992–2004	0.2 (−1.4–1.8)
Ewing sarcoma	327 (1%)	2.3	1992–2004	−3.4 (−7.0–0.3)
Rhabdomyosarcoma	643 (3%)	4.4	1992–2004	0.8 (−1.8–3.4)
Nonrhabdomyosarcoma soft tissue sarcoma	925 (4%)	6.6	1992–2004	0.8 (−1.3–2.9)
Germ cell tumors	1607 (7%)	11.5	1992–2004	0.8 (−0.7–2.4)
Thyroid carcinoma	764 (3%)	5.6	1992–2004	1.5 (−0.7–3.6)
Malignant melanoma	672 (3%)	4.9	1992–2004	2.8 (0.5–5.1)
Sex	Male
	1992–2004
Cancer	No. (%)	Incidence rate*	Years	APC1† (95% CI)	Years	APC2† (95% CI)	Years	APC3† (95% CI)	Years	APC4† (95% CI)
Total‡	12,316 (100%)	167.0	1992–2004	0.4 (−0.1–1.0)
Leukemias	3456 (28%)	46.1	1992–2004	0.7 (−0.4–1.9)
ALL	2678 (22%)	35.6	1992–2004	0.6 (−0.9–2.0)
AML	579 (5%)	7.8	1992–2004	1.9 (0.2–3.7)
Other/unspecified leukemias	199 (2%)	2.7	1992–1997	−18.4 (−30.5–−4.1)‖	1997–2004	14.0 (2.4–26.9)
Hodgkin disease	818 (7%)	11.5	1992–2004	1.0 (−1.4–3.5)
Non-Hodgkin lymphoma	997 (8%)	13.8	1992–2004	0.8 (−1.3–3.0)
CNS tumors	2224 (18%)	29.9	1992–2004	−0.4 (−2.1–1.2)
Ependymoma	177 (1%)	2.4	1992–2004	−3.8 (−7.6–0.2)‖
Astrocytoma	1023 (8%)	13.9	1992–2004	−0.6 (−2.5–1.4)
PNET	584 (5%)	7.8	1992–2004	−1.3 (−4.5–2.0)
Other gliomas	356 (3%)	4.8	1992–2004	1.7 (−1.2–4.6)
Other/unspecified CNS tumors	84 (0.7%)	1.1	1992–2004	5.3 (−1.2–12.2)‖
Neuroblastoma	598 (5%)	7.7	1992–2004	−1.6 (−4.9–1.9)
Retinoblastoma	270 (2%)	3.4	1992–1994	14.3 (−41.6–123.6)	1994–1997	−23.0 (−66.2–75.3)	1997–2000	36.3 (−33.3–178.3)	2000–2004	−5.7 (−22.2–14.2)
Wilms tumor	367 (3%)	4.7	1992–2004	−2.3 (−4.0–−0.5)
Hepatoblastoma	122 (1%)	1.6	1992–2004	5.5 (1.1–10.0)‖
Osteosarcoma	385 (3%)	5.4	1992–2004	−0.4 (−3.5–2.8)
Ewing sarcoma	202 (2%)	2.8	1992–2004	−4.7 (−9.9–0.8)‖
Rhabdomyosarcoma	372 (3%)	5.0	1992–2004	0.2 (−3.1–3.5)
Nonrhabdomyosarcoma soft tissue sarcoma	502 (4%)	6.9	1992–2004	2.0 (−0.6–4.7)
Germ cell tumors	984 (8%)	13.8	1992–2004	1.6 (−0.3–3.6)
Thyroid carcinoma	130 (1%)	1.8	1992–2004	0.4 (−6.6–8.0)‖
Melanoma	282 (2%)	4.0	1992–2004	3.8 (0.2–7.6)
Sex	Female
	1992–2004
Cancer	No. (%)	Incidence rate*	Years	APC1† (95% CI)	Years	APC2† (95% CI)	Years	APC3† (95% CI)	Years	APC4† (95% CI)
Total‡	10,378 (100%)	148.2	1992–2004	0.3 (−0.3–0.9)
Leukemias	2673 (26%)	37.4	1992–2004	0.6 (−0.8–2.0)
ALL	2019 (19%)	28.0	1992–2004	1.1 (−0.6–2.8)
AML	506 (5%)	7.2	1992–2004	−0.1 (−1.9–1.8)
Other/unspecified leukemias	148 (1%)	2.1	1992–2004	−3.3 (−7.7–1.4)‖
Hodgkin disease	793 (8%)	11.9	1992–2004	−2.4 (−4.5–−0.3)
Non-Hodgkin lymphoma	475 (5%)	6.9	1992–2004	2.8 (−0.3–6.0)
CNS tumors	1780 (17%)	25.1	1992–2004	0.4 (−0.8–1.6)
Ependymoma	131 (1%)	1.8	1992–1995	45.8 (9.3–94.5)‖	1995–1998	−27.3 (−55.4–18.4)	1998–2001	35.9 (−16.4–121.0)	2001–2004	−7.0 (−24.6–14.7)
Astrocytoma	897 (9%)	12.7	1992–2004	−0.2 (−2.0–1.7)
PNET	387 (4%)	5.4	1992–2004	−1.3 (−4.4–1.9)
Other gliomas	308 (3%)	4.4	1992–2004	1.4 (−1.9–4.9)
Other/unspecified CNS tumors	57 (0.5%)	0.8	1992–2004	3.9 (−5.0–13.8)‖
Neuroblastoma	509 (5%)	6.9	1992–2004	0.6 (−2.2–3.5)
Retinoblastoma	244 (2%)	3.3	1992–2004	−1.9 (−4.9–1.3)
Wilms tumor	437 (4%)	5.9	1992–2004	−2.1 (−5.9–1.8)
Hepatoblastoma	94 (0.9%)	1.3	1992–2004	2.9 (−3.7–10.0)‖
Osteosarcoma	275 (3%)	4.0	1992–1996	−11.7 (−24.4–3.0)	1996–2004	6.3 (1.1–11.8)
Ewing sarcoma	125 (1%)	1.8	1992–2004	−1.2 (−6.2–4.1)‖
Rhabdomyosarcoma	271 (3%)	3.8	1992–2004	1.7 (−1.5–5.0)
Nonrhabdomyosarcoma soft tissue sarcoma	423 (4%)	6.2	1992–1999	5.1 (0.1–10.5)	1999–2002	−16.9 (−43.4–21.9)	2002–2004	19.0 (−18.8–74.4)
Germ cell tumors	623 (6%)	9.1	1992–2004	−0.3 (−2.6–2.2)
Thyroid carcinoma	634 (6%)	9.5	1992–2004	1.6 (−0.2–3.5)
Melanoma	390 (4%)	5.9	1992–2004	2.2 (−0.9–5.5)
Age Group	< 1 Year
	1992–2004
Cancer	No. (%)	Incidence rate*	Years	APC1† (95% CI)	Years	APC2† (95% CI)	Years	APC3† (95% CI)	Years	APC4† (95% CI)
Total‡	1677 (100%)	225.9	1992–2004	0.1 (−1.3–1.4)
Leukemias	296 (18%)	39.9	1992–2004	0.8 (−2.5–4.2)
ALL	139 (8%)	18.7	1992–2004	−0.4 (−5.3–4.7)‖
AML	109 (6%)	14.7	1992–2004	3.2 (−1.8–8.3)‖
Other/unspecified leukemias	48 (3%)	6.5	1992–2004	−2.5 (−9.1–4.6)‖
Hodgkin disease	1 (0.06%)	0.1		—
Non-Hodgkin lymphoma	12 (0.7%)	1.6		—
CNS tumors	225 (13%)	30.3	1992–2004	0.3 (−2.9–3.5)
Ependymoma	23 (1%)	3.1		—
Astrocytoma	79 (5%)	10.6	1992–2004	2.1 (−2.6–7.1)‖
PNET	76 (5%)	10.2	1992–2004	−4.5 (−10.6–2.1)‖
Other gliomas	16 (1%)	2.2		—
Other/unspecified CNS tumors	31 (2%)	4.2	1992–2004	5.2 (−2.7–13.7)‖
Neuroblastoma	402 (24%)	54.1	1992–2004	−1.9 (−5.5–1.9)
Retinoblastoma	196 (12%)	26.4	1992–2004	−1.1 (−3.1–0.8)
Wilms tumor	107 (6%)	14.4	1992–2004	−4.0 (−10.2–2.5)‖
Hepatoblastoma	78 (5%)	10.5	1992–2004	4.2 (−1.9–10.7)‖
Osteosarcoma	1 (0.06%)	0.1		—
Ewing sarcoma	1 (0.06%)	0.1		—
Rhabdomyosarcoma	39 (2%)	5.3		—
Nonrhabdomyosarcoma soft tissue sarcoma	76 (5%)	10.2	1992–2004	10.4 (4.9–16.3)‖
Germ cell tumors	156 (9%)	21.0	1992–2004	0.3 (−5.0–5.9)‖
Thyroid carcinoma	0 (0%)	0.0		—
Melanoma	5 (0.3%)	0.7		—
Age Group	1–4 Years
	1992–2004
Cancer	No. (%)	Incidence rate*	Years	APC1† (95% CI)	Years	APC2† (95% CI)	Years	APC3† (95% CI)	Years	APC4† (95% CI)
Total‡	5913 (100%)	199.6	1992–2004	0.3 (−0.5–1.1)
Leukemias	2526 (43%)	85.3	1992–2004	0.6 (−0.9–2.0)
ALL	2169 (37%)	73.2	1992–2004	0.4 (−1.4–2.3)
AML	279 (5%)	9.4	1992–2004	1.5 (−2.9–6.2)
Other/unspecified leukemias	78 (1%)	2.6	1992–2004	2.7 (−5.6–11.8)‖
Hodgkin disease	25 (0.4%)	0.8		—
Non-Hodgkin lymphoma	181 (3%)	6.1	1992–2004	−2.2 (−5.4–1.1)‖
CNS tumors	1,140 (19%)	38.5	1992–1996	−4.8 (−10.6–1.3)	1996–2001	5.7 (−0.7–12.6)	2001–2004	−5.1 (−13.9–4.5)
Ependymoma	130 (2%)	4.4	1992–2004	−1.2 (−5.3–3.2)‖
Astrocytoma	493 (8%)	16.6	1992–2004	1.9 (−0.3–4.2)
PNET	326 (6%)	11.0	1992–2004	−2.2 (−5.8–1.5)
Other gliomas	136 (2%)	4.6	1992–2004	0.1 (−6.0–6.5)‖
Other/unspecified CNS tumors	55 (0.9%)	1.9		—
Neuroblastoma	557 (9%)	18.8	1992–2004	−0.7 (−3.0–1.7)
Retinoblastoma	296 (5%)	10.0	1992–2004	1.6 (−1.6–4.8)
Wilms tumor	510 (9%)	17.2	1992–2004	−1.5 (−4.0–1.1)
Hepatoblastoma	120 (2%)	4.1	1992–2004	4.8 (0.9–8.8)‖
Osteosarcoma	9 (0.2%)	0.3		—
Ewing sarcoma	17 (0.3%)	0.6		—
Rhabdomyosarcoma	200 (3%)	6.8	1992–2004	−1.7 (−5.6–2.5)‖
Nonrhabdomyosarcoma soft tissue sarcoma	70 (1%)	2.4	1992–2004	1.0 (−7.0–9.7)‖
Germ cell tumors	117 (2%)	3.9	1992–2004	0.7 (−5.1–6.7)‖
Thyroid carcinoma	1 (0.02%)	0.0		—
Melanoma	20 (0.3%)	0.7		—
Age Group	5–9 Years
	1992–2004
Cancer	No. (%)	Incidence rate*	Years	APC1† (95% CI)	Years	APC2† (95% CI)	Years	APC3† (95% CI)	Years	APC4† (95% CI)
Total‡	3926 (100%)	107.4	1992–2004	0.3 (−0.7–1.4)
Leukemias	1395 (36%)	38.2	1992–1999	2.8 (−0.2–5.8)	1999–2004	−3.9 (−8.5–0.9)
ALL	1176 (30%)	32.2	1992–1999	3.6 (0.5–6.8)	1999–2004	−4.0 (−8.6–0.9)
AML	169 (4%)	4.6	1992–2004	−0.9 (−5.3–3.7)‖
Other/unspecified leukemias	50 (1%)	1.4	1992–2004	−6.9 (−15.2–2.3)‖
Hodgkin disease	141 (4%)	3.9	1992–2004	0.9 (−2.2–4.0)‖
Non-Hodgkin lymphoma	302 (8%)	8.3	1992–2004	2.0 (−0.7–4.8)
CNS tumors	1087 (28%)	29.7	1992–2004	0.6 (−1.2–2.4)
Ependymoma	63 (2%)	1.7	1992–2004	4.9 (−3.8–14.4)‖
Astrocytoma	515 (13%)	14.1	1992–2004	−0.9 (−3.8–2.1)
PNET	271 (7%)	7.4	1992–2004	1.3 (−3.2–6.0)
Other gliomas	219 (6%)	6.0	1992–2004	3.1 (−3.0–9.7)‖
Other/unspecified CNS tumors	19 (0.5%)	0.5		—
Neuroblastoma	108 (3%)	3.0	1992–2004	1.6 (−3.5–7.0)‖
Retinoblastoma	19 (0.5%)	0.5		—
Wilms tumor	164 (4%)	4.5	1992–2004	−3.5 (−8.4–1.6)‖
Hepatoblastoma	15 (0.4%)	0.4		—
Osteosarcoma	90 (2%)	2.5	1992–2004	−0.6 (−5.5–4.5)‖
Ewing sarcoma	58 (1%)	1.6	1992–2004	−1.6 (−8.8–6.1)‖
Rhabdomyosarcoma	161 (4%)	4.4	1992–2002	3.5 (0.3–6.9)‖	2002–2004	−26.7 (−55.1–19.5)
Nonrhabdomyosarcoma soft tissue sarcoma	118 (3%)	3.2	1992–2004	−1.1 (−7.3–5.5)‖
Germ cell tumors	80 (2%)	2.2	1992–2004	1.7 (−4.2–7.9)‖
Thyroid carcinoma	41 (1%)	1.1		—
Melanoma	38 (1%)	1.0		—
Age Group	10–14 Years
	1992–2004
Cancer	No. (%)	Incidence rate*	Years	APC1† (95% CI)	Years	APC2† (95% CI)	Years	APC3† (95% CI)	Years	APC4† (95% CI)
Total‡	4346 (100%)	121.1	1992–2004	0.4 (−0.6–1.5)
Leukemias	990 (23%)	27.6	1992–2004	0.5 (−0.7–1.9)
ALL	695 (16%)	19.4	1992–2004	0.7 (−1.0–2.6)
AML	231 (5%)	6.4	1992–2004	1.2 (−1.9–4.4)
Other/unspecified leukemias	64 (1%)	1.8	1992–2004	−3.7 (−8.6–1.5)‖
Hodgkin disease	409 (9%)	11.4	1992–2004	−0.4 (−3.2–2.4)
Non-Hodgkin lymphoma	404 (9%)	11.3	1992–2004	1.7 (−1.1–4.6)
CNS tumors	906 (21%)	25.2	1992–2004	−1.1 (−3.0–1.0)
Ependymoma	52 (1%)	1.4	1992–2002	−2.5 (−6.9–2.1)‖	2002–2004	−52.2 (−84.3–45.1)
Astrocytoma	483 (11%)	13.5	1992–2004	−1.9 (−4.4–0.8)
PNET	190 (4%)	5.3	1992–2004	−2.0 (−5.4–1.6)
Other gliomas	159 (4%)	4.4	1992–2004	4.3 (−2.4–11.5)‖
Other/unspecified CNS tumors	22 (0.5%)	0.6		—
Neuroblastoma	29 (0.7%)	0.8		—
Retinoblastoma	1 (0.02%)	0.0		—
Wilms tumor	19 (0.4%)	0.5		—
Hepatoblastoma	3 (0.07%)	0.1		—
Osteosarcoma	267 (6%)	7.4	1992–2004	0.2 (−2.5–3.0)
Ewing sarcoma	109 (3%)	3.0	1992–2004	−4.3 (−7.7–−0.7)‖
Rhabdomyosarcoma	117 (3%)	3.3	1992–2004	1.5 (−4.8–8.3)‖
Nonrhabdomyosarcoma soft tissue sarcoma	276 (6%)	7.7	1992–2004	0.0 (−3.3–3.4)
Germ cell tumors	266 (6%)	7.4	1992–2004	2.1 (−1.3–5.5)
Thyroid carcinoma	160 (4%)	4.5	1992–2004	−0.6 (−5.3–4.3)‖
Melanoma	108 (2%)	3.0	1992–2004	6.7 (1.8–11.9)‖
Age Group	15–19 Years
	1992–2004
Cancer	No. (%)	Incidence rate*	Years	APC1† (95% CI)	Years	APC2† (95% CI)	Years	APC3† (95% CI)	Years	APC4† (95% CI)
Total‡	6832 (100%)	200.8	1992–2004	0.4 (−0.4–1.3)
Leukemias	922 (13%)	27.1	1992–2004	2.0 (−0.3–4.5)
ALL	518 (8%)	15.2	1992–2004	3.3 (0.4–6.4)
AML	297 (4%)	8.7	1992–2004	0.9 (−3.1–5.1)
Other/unspecified leukemias	107 (2%)	3.1	1992–2004	0.1 (−7.0–7.8)‖
Hodgkin disease	1035 (15%)	30.4	1992–2004	−1.3 (−2.7–0.2)
Non-Hodgkin lymphoma	573 (8%)	16.8	1992–2004	2.3 (−0.8–5.4)
CNS tumors	646 (9%)	19.0	1992–2004	−1.3 (−4.1–1.5)
Ependymoma	40 (0.6%)	1.2	1992–2004	2.0 (−9.0–14.4)‖
Astrocytoma	350 (5%)	10.3	1992–2004	−1.2 (−5.0–2.7)
PNET	108 (2%)	3.2	1992–1997	−19.3 (−38.5–5.9)‖	1997–2001	34.0 (−22.6–132.2)	2001–2004	−28.5 (−59.8–27.1)
Other gliomas	134 (2%)	3.9	1992–2004	−1.4 (−7.0–4.6)‖
Other/unspecified CNS tumors	14 (0.2%)	0.4		—
Neuroblastoma	11 (0.2%)	0.3		—
Retinoblastoma	2 (0.03%)	0.1		—
Wilms tumor	4 (0.06%)	0.1		—
Hepatoblastoma	0 (0%)	0.0		—
Osteosarcoma	293 (4%)	8.6	1992–2004	0.7 (−3.1–4.5)
Ewing sarcoma	142 (2%)	4.2	1992–2004	−4.1 (−8.9–0.9)‖
Rhabdomyosarcoma	126 (2%)	3.7	1992–2004	2.8 (−1.5–7.2)‖
Nonrhabdomyosarcoma soft tissue sarcoma	385 (6%)	11.3	1992–2004	0.4 (−3.6–4.5)
Germ cell tumors	988 (14%)	29.0	1992–2004	0.7 (−1.2–2.7)
Thyroid carcinoma	562 (8%)	16.5	1992–2004	2.1 (−0.4–4.7)
Melanoma	501 (7%)	14.7	1992–2004	1.3 (−1.4–4.1)
Race§	White
	1992–2004
Cancer	No. (%)	Incidence rate*	Years	APC1† (95% CI)	Years	APC2† (95% CI)	Years	APC3† (95% CI)	Years	APC4† (95% CI)
Total‡	17,977 (100%)	168.3	1992–2004	0.6 (0.0–1.3)
Leukemias	4948 (28%)	45.5	1992–2004	1.0 (0.1–2.0)
ALL	3890 (22%)	35.6	1992–2004	1.1 (0.0–2.3)
AML	808 (4%)	7.5	1992–2004	1.4 (−0.7–3.6)
Other/unspecified leukemias	250 (1%)	2.3	1992–1996	−19.1 (−33.6–−1.5)‖	1996–2004	6.5 (−1.5–15.1)
Hodgkin disease	1354 (8%)	13.2	1992–2004	−1.0 (−3.0–1.0)
Non-Hodgkin lymphoma	1125 (6%)	10.8	1992–2004	1.4 (−0.5–3.2)
CNS tumors	3179 (18%)	29.5	1992–2004	0.1 (−1.3–1.4)
Ependymoma	241 (1%)	2.2	1992–2004	−1.1 (−5.5–3.6)
Astrocytoma	1548 (9%)	14.4	1992–2004	−0.3 (−1.9–1.4)
PNET	783 (4%)	7.2	1992–2004	−1.0 (−3.1–1.2)
Other gliomas	498 (3%)	4.7	1992–2004	2.0 (−0.6–4.7)
Other/unspecified CNS tumors	109 (0.6%)	1.0	1992–2004	6.6 (0.2–13.4)‖
Neuroblastoma	864 (5%)	7.6	1992–2004	−0.3 (−2.6–2.2)
Retinoblastoma	373 (2%)	3.3	1992–2004	1.0 (−1.5–3.6)
Wilms tumor	621 (3%)	5.5	1992–2004	−2.4 (−4.7–0.0)
Hepatoblastoma	163 (0.9%)	1.4	1992–2004	5.3 (−0.8–11.7)‖
Osteosarcoma	473 (3%)	4.6	1992–2004	0.1 (−1.6–1.9)
Ewing sarcoma	299 (2%)	2.9	1992–2004	−3.4 (−7.2–0.6)
Rhabdomyosarcoma	477 (3%)	4.4	1992–2004	1.7 (−1.5–4.9)
Nonrhabdomyosarcoma soft tissue sarcoma	699 (4%)	6.7	1992–2004	2.0 (−0.7–4.7)
Germ cell tumors	1276 (7%)	12.3	1992–2004	1.1 (−0.7–2.9)
Thyroid carcinoma	619 (3%)	6.1	1992–2004	2.0 (−0.3–4.4)
Melanoma	602 (3%)	5.9	1992–2004	4.2 (2.2–6.3)
Race§	Black
	1992–2004
Cancer	No. (%)	Incidence rate*	Years	APC1† (95% CI)	Years	APC2† (95% CI)	Years	APC3† (95% CI)	Years	APC4† (95% CI)
Total‡	2228 (100%)	116.8	1992–2004	−0.4 (−1.5–0.8)
Leukemias	471 (21%)	24.2	1992–2004	−0.6 (−2.8–1.6)
ALL	292 (13%)	14.8	1992–2004	−2.1 (−5.7–1.7)
AML	125 (6%)	6.6	1992–2004	3.5 (−0.9–8.1)‖
Other/unspecified leukemias	54 (2%)	2.8		—
Hodgkin disease	167 (7%)	9.3	1992–1999	−9.1 (−15.7–−2.0)‖	1999–2004	9.4 (−2.8–23.3)
Non-Hodgkin lymphoma	163 (7%)	8.7	1992–2004	3.3 (−0.4–7.1)‖
CNS tumors	431 (19%)	22.1	1992–2004	−1.0 (−2.6–0.6)
Ependymoma	34 (2%)	1.7		—
Astrocytoma	194 (9%)	10.0	1992–2004	−3.4 (−6.5–−0.3)‖
PNET	93 (4%)	4.7	1992–2004	−0.6 (−5.5–4.5)‖
Other gliomas	94 (4%)	4.8	1992–2004	0.0 (−5.6–5.8)‖
Other/unspecified CNS tumors	16 (0.7%)	0.8		—
Neuroblastoma	131 (6%)	6.6	1992–2004	−1.3 (−8.0–5.9)‖
Retinoblastoma	68 (3%)	3.4	1992–2004	2.1 (−4.0–8.6)‖
Wilms tumor	128 (6%)	6.3	1992–2004	−2.5 (−8.1–3.4)‖
Hepatoblastoma	13 (0.6%)	0.6		—
Osteosarcoma	97 (4%)	5.3	1992–2004	4.0 (0.0–8.1)‖
Ewing sarcoma	6 (0.3%)	0.3		—
Rhabdomyosarcoma	106 (5%)	5.5	1992–2004	−1.7 (−6.5–3.3)‖
Nonrhabdomyosarcoma soft tissue sarcoma	123 (6%)	6.7	1992–2004	1.2 (−4.5–7.3)‖
Germ cell tumors	118 (5%)	6.4	1992–2004	−2.1 (−7.5–3.7)‖
Thyroid carcinoma	33 (1%)	1.8		—
Melanoma	7 (0.3%)	0.4		—
Race§	Asian/Pacific Islander
	1992–2004
Cancer	No. (%)	Incidence rate*	Years	APC1† (95% CI)	Years	APC2† (95% CI)	Years	APC3† (95% CI)	Years	APC4† (95% CI)
Total‡	1913 (100%)	127.5	1992–2004	−0.6 (−2.2–1.0)
Leukemias	567 (30%)	37.3	1992–2004	−0.8 (−3.7–2.2)
ALL	406 (21%)	26.6	1992–2004	0.1 (−2.8–3.1)
AML	127 (7%)	8.4	1992–2004	−3.5 (−9.0–2.4)‖
Other/unspecified leukemias	34 (2%)	2.3	1992–2004	−0.5 (−10.0–9.9)‖
Hodgkin disease	70 (4%)	4.8	1992–2004	4.6 (−2.9–12.6)‖
Non-Hodgkin lymphoma	152 (8%)	10.3	1992–2004	1.2 (−3.4–6.0)‖
CNS tumors	307 (16%)	20.5	1992–2004	0.7 (−2.4–4.0)
Ependymoma	25 (1%)	1.7		—
Astrocytoma	135 (7%)	9.0	1992–2004	2.6 (−3.5–9.1)‖
PNET	75 (4%)	5.0	1992–2004	−2.0 (−5.6–1.8)‖
Other gliomas	61 (3%)	4.1	1992–2004	1.4 (−4.3–7.4)‖
Other/unspecified CNS tumors	11 (0.6%)	0.7		—
Neuroblastoma	93 (5%)	5.9	1992–2004	−2.9 (−7.2–1.5)‖
Retinoblastoma	51 (3%)	3.2	1992–2004	−1.4 (−8.3–6.1)‖
Wilms tumor	33 (2%)	2.1		—
Hepatoblastoma	27 (1%)	1.7		—
Osteosarcoma	80 (4%)	5.5	1992–2004	−4.4 (−10.1–1.5)‖
Ewing sarcoma	15 (0.8%)	1.0		—
Rhabdomyosarcoma	44 (2%)	2.9		—
Nonrhabdomyosarcoma soft tissue sarcoma	76 (4%)	5.2	1992–2004	−9.6 (−16.3–−2.4)‖
Germ cell tumors	182 (10%)	12.3	1992–2004	0.6 (−3.9–5.3)‖
Thyroid carcinoma	87 (5%)	6.0	1992–2004	−4.0 (−9.0–1.3)‖
Melanoma	18 (0.9%)	1.2		—
Ethnicity	Spanish/Hispanic/Latino
	1992–2004
Cancer	No. (%)	Incidence rate*	Years	APC1† (95% CI)	Years	APC2† (95% CI)	Years	APC3† (95% CI)	Years	APC4† (95% CI)
Total‡	5532 (100%)	149.0	1992–2004	0.7 (−0.3–1.7)
Leukemias	1968 (36%)	51.6	1992–2004	0.6 (−0.5–1.8)
ALL	1576 (28%)	40.9	1992–2004	0.7 (−0.7–2.0)
AML	295 (5%)	8.1	1992–2004	1.4 (−1.1–3.9)
Other/unspecified leukemias	97 (2%)	2.6	1992–2004	−1.7 (−7.2–4.2)‖
Hodgkin disease	337 (6%)	10.0	1992–2004	−1.4 (−4.8–2.2)
Non-Hodgkin lymphoma	305 (6%)	8.6	1992–2004	1.7 (−1.3–4.7)
CNS tumors	847 (15%)	22.3	1992–2004	0.8 (−0.9–2.5)
Ependymoma	72 (1%)	1.8	1992–2004	−0.6 (−5.7–4.7)‖
Astrocytoma	371 (7%)	9.9	1992–2004	0.1 (−2.3–2.5)
PNET	245 (4%)	6.3	1992–2004	−2.2 (−6.5–2.3)
Other gliomas	122 (2%)	3.3	1992–2004	7.7 (1.9–13.8)‖
Other/unspecified CNS tumors	37 (0.7%)	0.9		—
Neuroblastoma	222 (4%)	5.2	1992–2004	1.0 (−2.6–4.8)
Retinoblastoma	143 (3%)	3.3	1992–2004	2.6 (−2.0–7.5)‖
Wilms tumor	183 (3%)	4.4	1992–2004	−0.7 (−4.4–3.2)
Hepatoblastoma	52 (0.9%)	1.2	1992–2004	1.5 (−6.4–10.1)‖
Osteosarcoma	166 (3%)	4.9	1992–2004	0.4 (−3.7–4.6)‖
Ewing sarcoma	67 (1%)	1.9	1992–2000	−10.4 (−17.2–−3.0)‖	2000–2004	21.8 (0.2–48.1)
Rhabdomyosarcoma	135 (2%)	3.5	1992–2004	1.6 (−2.3–5.7)‖
Nonrhabdomyosarcoma soft tissue sarcoma	209 (4%)	5.9	1992–2004	2.4 (−2.2–7.3)
Germ cell tumors	434 (8%)	12.6	1992–2004	0.8 (−1.1–2.8)
Thyroid carcinoma	158 (3%)	4.8	1992–2004	0.3 (−3.6–4.3)‖
Melanoma	34 (0.6%)	1.0	1992–2004	7.5 (0.4–15.0)‖

This study was approved by the University of Minnesota Institutional Review Board.

RESULTS

Overall

Between 1992 and 2004, 22,694 incident malignant neoplasms were reported among those patients aged <20 years within the 13 SEER registries examined (Table 2). The average annual age-adjusted incidence rate was 158 per 1,000,000 person-years and there was a suggestion of a positive trend (APC, 0.4%; 95% CI, −0.1%–0.8%) (Table 2).

Frequencies, incidence rates, and results of the best≥ fit joinpoint regression models for each of the cancer subtypes examined are provided in Table 2. None of the rates changed in a strictly monotonic fashion because each of the cancer diagnoses is rare and subject to random fluctuation; trends are best described by joinpoint results. Rates increased substantially over the time period for melanoma (APC, 2.8%; 95% CI, 0.5%–5.1%), hepatoblastoma (APC, 4.3%; 95% CI, 0.2%–8.7%), and other/unspecified central nervous system (CNS) tumors (APC, 5.4%; 95% CI, 0.8%–10.3%). Two joinpoints were found for astrocytoma; the rate decreased initially (1992–1999: APC, −2.9%; 95% CI, −5.2%–−0.5%) followed by a rapid increase (1999–2002: APC, 7.8%; 95% CI, −9.1%–27.9%) and a subsequent decline (2002–2004: APC, −8.3%; 95% CI, −23.1%–9.4%). A change in the magnitude and direction of the trend was observed for other/unspecified leukemias; a significant decrease was observed between 1992 and 1996 (APC, −18.6%; 95% CI, −31.6%–−3.2%) and a significant increase was detected thereafter (APC, 7.0%; 95% CI, 0.1%–14.3%). The trends for other cancer subgroups were indistinguishable from a slope of 0, although the data indicate a possible increase for leukemia overall (acute lymphoblastic leukemia [ALL] and acute myeloid leukemia [AML]) and non-Hodgkin lymphoma (NHL), and suggest a decrease for Wilms tumor and Ewing sarcoma. Notably, the rate of CNS tumors overall remained steady over the time period examined (APC, −0.1%; 95% CI, −1.1%–1.0%). The observed and expected rates, as determined by joinpoint regression, for leukemias and CNS tumors are shown in Figure 1.

Figure 1. Observed (data points) and expected (joinpoint regression lines) incidence rates from Surveillance, Epidemiology, and End Results (SEER) 13 registries from 1992 through 2004 for (A) leukemias and (B) central nervous system (CNS) tumors. ALL indicates acute lymphoblastic leukemia; AML, acute myeloid leukemia; PNET, primitive neuroectodermal tumor.

Frequencies, incidence rates, and joinpoint results for the demographic subgroups for each of the cancers analyzed are listed in Table 2. The trends were generally similar across strata of demographic variables examined; noteworthy trends are discussed.

Sex

A significantly positive trend (APC, 1.9%; 95% CI, 0.2%–3.7%) for AML was observed among males, whereas no concomitant trend was apparent among females. For other/unspecified leukemias, the rate in males decreased sharply between 1992 and 1997 (APC, −18.4%; 95% CI, −30.5%–−4.1%) and then increased between 1997 and 2004 (APC, 14.0%; 95% CI, 2.4%–26.9%). Similarly, rapid changes punctuated by 3 joinpoints were observed with respect to retinoblastoma rates in males; these patterns were not observed in females.

Hodgkin disease (HD) declined in females (APC, −2.4%; 95% CI, −4.5%–−0.3%), but not in males. Joinpoints resulting in a shift in the direction of the trend also were observed among females for osteosarcoma (1 joinpoint), nonrhabdomyosarcoma soft tissue sarcomas (2 joinpoints), and ependymoma (3 joinpoints); these changes were not detected among males. An increase in thyroid carcinoma was suggested in females only.

Age Group

The incidence rate of ALL was stable, with the exception of those ages 5 through 9 years, in whom an increase was initially observed (1992–1999: APC, 3.6%; 95% CI, 0.5%–6.8%), followed by a decline similar in magnitude, and in those patients ages 15 to 19 years, in whom a substantial increase was detected (APC, 3.3%; 95% CI, 0.4%–6.4%). Rates of HD may also be declining among patients ages 15 to 19 years.

For CNS tumors overall, an initial decline was observed among those ages 1 to 4 years (1992–1996: APC, −4.8%; 95% CI, −10.6%–1.3%), with a subsequent rise and fall in rates; rates appeared stable in other age groups. The early decline observed in the rate of ependymomas in patients ages 10 to 14 years was more rapid later in the period; this pattern was restricted to this age group and was based on few cases (N = 52). Astrocytoma rates increased in the younger age groups (aged <5 years) and declined in older age groups, although rates were imprecise in all groups. No change was observed in the incidence of primitive neuroectodermal tumor, except in patients ages 15 to 19 years, in whom 2 joinpoints were identified, resulting in sharp changes in the direction of the trend.

A significant increase occurred in the 1990s for rhabdomyosarcoma among those ages 5 to 9 years (APC, 3.5%; 95% CI, 0.3%–6.9%), followed by a sharp decline. For other soft tissue sarcomas, a significant rise was found in infants (APC, 10.4%; 95% CI, 4.9%–16.3%), with little or no change noted in other groups. An increase in patients ages 15 to 19 years was suggested for thyroid carcinoma.

Race

For leukemias overall and ALL, increases were observed in whites (leukemias: APC, 1.0%; 95% CI, 0.1%–2.0%; ALL: APC, 1.1%; 95% CI, 0.0%–2.3%), whereas there was no evidence of change in blacks and Asian/Pacific Islanders. The trend for other leukemias and other CNS tumors among the white group paralleled those observed overall. A decrease in Wilms tumor (APC, −2.4%; 95% CI, −4.7%–0.0%) and an increase in melanoma (APC, 4.2%; 95% CI, 2.2%–6.3%) were detected only among the white group. There was also a suggestion of an increase in thyroid cancers in whites over the period examined.

HD declined substantially in the black group in the 1990s (APC, −9.1%; 95% CI, −15.7%–2.0%) and subsequently rose as sharply, whereas an increase in NHL was suggested in both whites and blacks. Astrocytomas decreased (APC, −3.4%; 95% CI, −6.5%–−0.3%) and osteosarcoma notably increased (APC, 4.0%; 95% CI, 0.0%–8.1%) among the black group. A statistically significant decrease was observed in nonrhabdomyosarcoma soft tissue sarcomas among Asian/Pacific Islanders only (APC, −9.6%; 95% CI, −16.3%–−2.4%). The trends described among blacks and Hispanics were each based on relatively few cases (N ≤ 194).

Ethnicity

Trends among the non-Spanish/Hispanic/Latino (non-Hispanic) subgroup were very similar to those observed in the white racial group (data not shown). An overall increase in all childhood cancers was suggested among Hispanics, as well as a modest increase in leukemias. Unlike the fluctuating trend observed in the non-Hispanic group, no change in other leukemias was detected in the Hispanic group. There was a statistically significant increase in other gliomas among Hispanic children (APC, 7.7%; 95% CI, 1.9%–13.8%) and a substantial increase in melanomas (APC, 7.5%; 95% CI, 0.4%–15.0%), which was also observed in non-Hispanic children. Rates of Ewing sarcoma decreased between 1992 and 2000 (APC, −10.4%; 95% CI, −17.2%–−3.0%) and increased thereafter (APC, 21.8%; 95% CI, 0.2%–48.1%); this trend was based on a very small number of cases (N = 67).

DISCUSSION

Recent reports from the U.S. and Europe16, 17 indicate that rates of childhood cancers are increasing between 0.6% to 1.1% annually; however, these reports include data beginning in the 1970s, and therefore described trends may be due in large part to rate increases in previous decades. The current analysis indicates a modest, nonsignificant increase (0.4% annually) in all childhood cancers diagnosed since the early 1990s, with evidence of increases in select malignancies and shifting trends in others.

The results of the current study corroborate those from prior SEER reports, in which the overall rates of CNS tumors stabilized after 1986.8, 18 Although not significant, there is a suggestion of an overall increase in leukemia, especially ALL. Changes in the rates of other/unspecified leukemias and CNS tumors, respectively, account for relatively few cases and may primarily reflect changes in classification, rather than actual decreases. On further inspection of individual ICD-O-3 codes, the decline in other leukemias between 1992 and 1996 is attributable to decreases in acute leukemia, not otherwise specified [NOS], and chronic myeloid leukemia, but the increase noted between 1996 and 2004 is not easily explained. Fluctuations in astrocytoma were characterized by a decrease in astrocytoma, NOS; an increase in pilocytic astrocytoma; and an initial increase in fibrillary astrocytoma between 1992 and 2002, followed by a sharp drop. The observed pattern may be attributable to random variation. The increase in other/unspecified CNS tumors is not due to the 2001 inclusion of benign tumors in the SEER registries9 because our analysis included malignant neoplasms only; a nonsignificant increase in the diagnosis of chorioid plexus carcinomas contributed mostly to the observed increase.

The rise in the rate of hepatoblastoma coincides with an increase in the frequency of low or very low weight births19 and there is convincing evidence that the 2 may be etiologically related.20 Increases in malignant melanomas have been previously reported21 and parallel increases have been observed in adults.22, 23

The differences by demographic subgroup are unlikely explained by changes in classification or diagnosis because changes should have been applied equally across demographic subgroups. The significant increase in AML among males, but not females, is of interest and should be followed closely to determine whether this pattern continues. The decrease in HD noted among females contradicts prior reports of increasing rates among adolescents and young adults, but is consistent with results observed in older adults.24–26 A concomitant increase in NHL was suggested; however, a corresponding decline in males was not detected, ruling out changes in classification as a likely explanation. The dramatic increase in ependymomas noted between 1992 and 1995 occurring among females involved a small number of cases (N = 131), and therefore may be due to chance. Categorizing ependymomas as borderline benign or malignant can be difficult27; however, there is no reason to suspect classification differences by sex and across different registries. A positive trend in infantile fibrosarcoma accounts for the rise in nonrhabdomyosarcoma soft tissue sarcomas noted among infants, but trend fluctuations for all CNS tumors among patients ages 1 to 4 years is not explained by specific subtypes.

Care must be exercised in analyzing and interpreting data across racial groups because there were relatively few cases in the black and Asian/Pacific Islander groups for the rare cancer diagnoses. Trends among white children were similar to those described overall, although the increase in ALL and decline in Wilms tumor are of interest. If real, these trends may reflect changes in environmental exposures. Glazer et al.28 found no evidence for trends in cancer incidence among Hispanic children in California between 1988 and 1994. The current study results demonstrated a significant increase in other gliomas, which appears to be driven by an increase in gliomas, NOS. This may be a ‘jump’ analogous to that observed between 1984 and 1986 for other sections of the population,18 reflecting a lag in access to improved diagnostic methods in lower socioeconomic strata. The observed rise in melanoma rates is consistent with a prior report among Hispanics of all ages in California.29

Observed differences in trends across demographic subgroups provide starting points for etiologic research. Testable hypotheses, including birth characteristics and environmental/exogenous exposures, can be investigated in relation to specific cancers via rigorous case-control studies. The development of a national pediatric cancer registry, such as that being implemented by the Children's Oncology Group,30 may facilitate such studies.

The principal strength of SEER is the high rate of case ascertainment and high data quality. Our analysis provides current trends in childhood cancer incidence, and to our knowledge represents the first report from the 13 SEER registries and the first report regarding trends in Asian/Pacific Islanders and Hispanics. One limitation of the current study is that important demographic and/or etiologic differences could potentially exist between the population monitored by the 13 SEER registries and the 86% not under surveillance simply by chance.31 Furthermore, childhood cancers represent a heterogeneous group of diseases with specific etiologies. Because each cancer diagnosis is rare, random fluctuations may erroneously appear as noteworthy trends; a large number of statistical tests, using an overall type I error rate of 5% per trend, were performed in the joinpoint regression analyses and the results therefore may include spurious associations. Trends involving <10 cases/year are noted in Table 2; these trends, as well as those with wide 95% CIs, should be interpreted cautiously. Changes in classification, such as the introduction of the International Classification of Childhood Cancer (ICCC) in 199627 and ICD-O-3 in 2001,12 or detection of malignancies may have influenced incidence trends. Classification by ICD-O-3 codes should limit the impact of the ICCC; however, the third edition of the ICD-O brought about minor changes in coding that may have impacted trends slightly beginning in 2001.

The results of the current study indicate that incidence rates for pediatric cancers overall have marginally increased since 1992, whereas rates for select diagnoses have significantly increased. Some intriguing differences by sex, age, and race/ethnicity exist. The trends described herein, in concert with the paucity of information regarding underlying causes of disease, necessitate an ongoing need for population-based surveillance and further etiologic studies.