Trends in Childhood Cancer Incidence in the U.S. (1992–2004) Amy M. Linabery, MS, MPH 1 Julie A. Ross, PhD 1,2 1 Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota. 2 University of Minnesota Cancer Center, Minnea- polis, Minnesota. BACKGROUND. The etiology of most pediatric neoplasms remains elusive. Exami- nation 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 demo- graphic 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 Surveil- lance, 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, 20.1%–0.8%) was observed for all pedi- atric cancer diagnoses combined. There was a suggestion of an increase in leuke- mia (APC, 0.7%; 95% CI, 20.1%–1.5%), and acute lymphoblastic leukemia in particular (APC, 0.8%; 95% CI, 20.4%–1.9%), whereas rates for central nervous sys- tem tumors overall were stable (APC, 20.1%; 95% CI, 21.1%–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;112:416–32. Ó 2007 American Cancer Society. KEYWORDS: epidemiology, childhood cancer, incidence, trends. I t 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 underscor- ing a need to monitor incidence rates. The last comprehensive reports concerning U.S. incidence trends included data through 1995 7,8 ; 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 Address for reprints: Julie A. Ross, PhD, Depart- ment of Pediatrics, University of Minnesota, 420 Delaware Street SE, MMC 422, Minneapolis, MN 55455; Fax: (612) 626-4842; E-mail: rossx014@ umn.edu Supported by National Institutes of Health Grant T32 CA099936 and the Children’s Cancer Research Fund. Received December 27, 2006; revision received August 14, 2007; accepted August 16, 2007. ª 2007 American Cancer Society DOI 10.1002/cncr.23169 Published online 11 December 2007 in Wiley InterScience (www.interscience.wiley.com). 416 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 nonme- lanoma 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 inci- dence 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 dur- ing the period 1992 through 2004 among those aged 19 years; 95% of diagnoses were confirmed by his- tology. Annual population estimates used in the cal- culation 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. 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 calcu- lated using Joinpoint software 14 to perform weighted least-squares regression, in which the independent variable was calendar year and the dependent vari- able 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 com- parisons 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 ethni- city (Spanish Hispanic-Latino and non-Spanish His- panic-Latino) were evaluated. Trends involving 1 years with <10 cases, as denoted in Table 2, should be interpreted with caution. Cases indicating Ameri- can Indian/Alaskan Native and those with an unknown/unspecified race were excluded from sub- group analysis because there were too few cases to allow for a trend analysis. 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, 20.1%–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 sub- stantially 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, 22.9%; 95% CI, 25.2%–20.5%) followed by a rapid increase (1999–2002: APC, 7.8%; 95% CI, 29.1%–27.9%) and a subsequent decline (2002–2004: APC, 28.3%; 95% CI, 223.1%–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, 218.6%; 95% CI, 231.6%–23.2%) 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, 20.1%; 95% CI, 21.1%–1.0%). The observed and expected rates, as determined by join- Childhood Cancer Incidence Trends/Linabery et al. 417 TABLE 1 International Classification of Diseases for Oncology, Third Edition Histology and Topography Codes Disease Code 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 ALL indicates acute lymphocytic leukemia; CNS, central nervous system; PNET, primitive neuroectodermal tumor. 418 CANCER January 15, 2008 / Volume 112 / Number 2 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 APC 1 y (95% CI) Years APC 2 y (95% CI) Years APC 3 y (95% CI) Years APC 4 y (95% CI) Total { 22,694 (100%) 157.9 1992–2004 0.4 (20.1–0.8) Leukemias 6129 (27%) 41.9 1992–2004 0.7 (20.1–1.5) ALL 4697 (21%) 31.9 1992–2004 0.8 (20.4–1.9) AML 1085 (5%) 7.5 1992–2004 1.0 (20.4–2.4) Other/unspecified leukemias 347 (2%) 2.4 1992–1996 218.6 (231.6–23.2) 1996–2004 7.0 (0.1–14.3) Hodgkin disease 1611 (7%) 11.7 1992–2004 20.8 (22.4–0.7) Non-Hodgkin lymphoma 1472 (6%) 10.4 1992–2004 1.4 (20.1–3.0) CNS tumors 4004 (18%) 27.6 1992–2004 20.1 (21.1–1.0) Ependymoma 308 (1%) 2.1 1992–2004 20.5 (24.1–3.3) Astrocytoma 1920 (8%) 13.3 1992–1999 22.9 ( 25.2–20.05) 1999–2002 7.8 (29.1–27.9) 2002–2004 28.3 (223.1–9.4) PNET 971 (4%) 6.6 1992–2004 21.2 (23.1–0.7) Other gliomas 664 (3%) 4.6 1992–2004 1.5 (20.9–4.0) Other/unspecified CNS tumors 141 (0.6%) 0.9 1992–2004 5.4 (0.8–10.3) k Neuroblastoma (extracranial) 1107 (5%) 7.3 1992–2004 20.6 (22.9–1.7) Retinoblastoma 514 (2%) 3.4 1992–2004 0.3 (21.5–2.1) Wilms tumor 804 (4%) 5.3 1992–2004 22.1 (24.6–0.4) Hepatoblastoma 216 (1%) 1.4 1992–2004 4.3 (0.2–8.7) Osteosarcoma 660 (3%) 4.7 1992–2004 0.2 (21.4–1.8) Ewing sarcoma 327 (1%) 2.3 1992–2004 23.4 (27.0–0.3) Rhabdomyosarcoma 643 (3%) 4.4 1992–2004 0.8 (21.8–3.4) Nonrhabdomyosarcoma soft tissue sarcoma 925 (4%) 6.6 1992–2004 0.8 (21.3–2.9) Germ cell tumors 1607 (7%) 11.5 1992–2004 0.8 (20.7–2.4) Thyroid carcinoma 764 (3%) 5.6 1992–2004 1.5 (20.7–3.6) Malignant melanoma 672 (3%) 4.9 1992–2004 2.8 (0.5–5.1) Sex Male 1992–2004 Cancer No. (%) Incidence rate* Years APC 1 y (95% CI) Years APC 2 y (95% CI) Years APC 3 y (95% CI) Years APC 4 y (95% CI) Total { 12,316 (100%) 167.0 1992–2004 0.4 (20.1–1.0) Leukemias 3456 (28%) 46.1 1992–2004 0.7 (20.4–1.9) ALL 2678 (22%) 35.6 1992–2004 0.6 (20.9–2.0) AML 579 (5%) 7.8 1992–2004 1.9 (0.2–3.7) Other/unspecified leukemias 199 (2%) 2.7 1992–1997 218.4 (230.5–24.1) k 1997–2004 14.0 (2.4–26.9) (continued ) Childhood Cancer Incidence Trends/Linabery et al. 419 TABLE 2 (continued ) Sex Male 1992–2004 Cancer No. (%) Incidence rate* Years APC 1 y (95% CI) Years APC 2 y (95% CI) Years APC 3 y (95% CI) Years APC 4 y (95% CI) Hodgkin disease 818 (7%) 11.5 1992–2004 1.0 (21.4–3.5) Non-Hodgkin lymphoma 997 (8%) 13.8 1992–2004 0.8 (21.3–3.0) CNS tumors 2224 (18%) 29.9 1992–2004 20.4 (22.1–1.2) Ependymoma 177 (1%) 2.4 1992–2004 23.8 (27.6–0.2) k Astrocytoma 1023 (8%) 13.9 1992–2004 20.6 (22.5–1.4) PNET 584 (5%) 7.8 1992–2004 21.3 (24.5–2.0) Other gliomas 356 (3%) 4.8 1992–2004 1.7 (21.2–4.6) Other/unspecified CNS tumors 84 (0.7%) 1.1 1992–2004 5.3 (21.2–12.2) k Neuroblastoma 598 (5%) 7.7 1992–2004 21.6 (24.9–1.9) Retinoblastoma 270 (2%) 3.4 1992–1994 14.3 (241.6–123.6) 1994–1997 223.0 (266.2–75.3) 1997–2000 36.3 (233.3–178.3) 2000–2004 25.7 (222.2–14.2) Wilms tumor 367 (3%) 4.7 1992–2004 22.3 (24.0–20.05) Hepatoblastoma 122 (1%) 1.6 1992–2004 5.5 (1.1–10.0) k Osteosarcoma 385 (3%) 5.4 1992–2004 20.4 (23.5–2.8) Ewing sarcoma 202 (2%) 2.8 1992–2004 24.7 (29.9–0.8) k Rhabdomyosarcoma 372 (3%) 5.0 1992–2004 0.2 (23.1–3.5) Nonrhabdomyosarcoma soft tissue sarcoma 502 (4%) 6.9 1992–2004 2.0 (20.6–4.7) Germ cell tumors 984 (8%) 13.8 1992–2004 1.6 (20.3–3.6) Thyroid carcinoma 130 (1%) 1.8 1992–2004 0.4 (26.6–8.0) k Melanoma 282 (2%) 4.0 1992–2004 3.8 (0.2–7.6) Sex Female 1992–2004 Cancer No. (%) Incidence rate* Years APC 1 y (95% CI) Years APC 2 y (95% CI) Years APC 3 y (95% CI) Years APC 4 y (95% CI) Total { 10,378 (100%) 148.2 1992–2004 0.3 (20.3–0.9) Leukemias 2673 (26%) 37.4 1992–2004 0.6 (20.8–2.0) ALL 2019 (19%) 28.0 1992–2004 1.1 (20.6–2.8) AML 506 (5%) 7.2 1992–2004 20.1 (21.9–1.8) Other/unspecified leukemias 148 (1%) 2.1 1992–2004 23.3 (27.7–1.4) k Hodgkin disease 793 (8%) 11.9 1992–2004 22.4 (24.5–20.3) Non-Hodgkin lymphoma 475 (5%) 6.9 1992–2004 2.8 (20.3–6.0) CNS tumors 1780 (17%) 25.1 1992–2004 0.4 (20.8–1.6) Ependymoma 131 (1%) 1.8 1992–1995 45.8 (9.3–94.5) k 1995–1998 227.3 (255.4–18.4) 1998–2001 35.9 (216.4–121.0) 2001–2004 27.0 (224.6–14.7) Astrocytoma 897 (9%) 12.7 1992–2004 20.2 (22.0–1.7) PNET 387 (4%) 5.4 1992–2004 21.3 (24.4–1.9) (continued ) 420 CANCER January 15, 2008 / Volume 112 / Number 2 TABLE 2 (continued ) Sex Female 1992–2004 Cancer No. (%) Incidence rate* Years APC 1 y (95% CI) Years APC 2 y (95% CI) Years APC 3 y (95% CI) Years APC 4 y (95% CI) Other gliomas 308 (3%) 4.4 1992–2004 1.4 (21.9–4.9) Other/unspecified CNS tumors 57 (0.5%) 0.8 1992–2004 3.9 (25.0–13.8) k Neuroblastoma 509 (5%) 6.9 1992–2004 0.6 (22.2–3.5) Retinoblastoma 244 (2%) 3.3 1992–2004 21.9 (24.9–1.3) Wilms tumor 437 (4%) 5.9 1992–2004 22.1 (25.9–1.8) Hepatoblastoma 94 (0.9%) 1.3 1992–2004 2.9 (23.7–10.0) k Osteosarcoma 275 (3%) 4.0 1992–1996 211.7 (224.4–3.0) 1996–2004 6.3 (1.1–11.8) Ewing sarcoma 125 (1%) 1.8 1992–2004 21.2 (26.2–4.1) k Rhabdomyosarcoma 271 (3%) 3.8 1992–2004 1.7 (21.5–5.0) Nonrhabdomyosarcoma soft tissue sarcoma 423 (4%) 6.2 1992–1999 5.1 (0.1–10.5) 1999–2002 216.9 (243.4–21.9) 2002–2004 19.0 (218.8–74.4) Germ cell tumors 623 (6%) 9.1 1992–2004 20.3 (22.6–2.2) Thyroid carcinoma 634 (6%) 9.5 1992–2004 1.6 (20.2–3.5) Melanoma 390 (4%) 5.9 1992–2004 2.2 (20.9–5.5) Age Group <1 Year 1992–2004 Cancer No. (%) Incidence rate* Years APC 1 y (95% CI) Years APC 2 y (95% CI) Years APC 3 y (95% CI) Years APC 4 y (95% CI) Total { 1677 (100%) 225.9 1992–2004 0.1 (21.3–1.4) Leukemias 296 (18%) 39.9 1992–2004 0.8 (22.5–4.2) ALL 139 (8%) 18.7 1992–2004 20.4 (25.3–4.7) k AML 109 (6%) 14.7 1992–2004 3.2 (21.8–8.3) k Other/unspecified leukemias 48 (3%) 6.5 1992–2004 22.5 (29.1–4.6) k 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 (22.9–3.5) Ependymoma 23 (1%) 3.1 — Astrocytoma 79 (5%) 10.6 1992–2004 2.1 (22.6–7.1) k PNET 76 (5%) 10.2 1992–2004 24.5 (210.6–2.1) k Other gliomas 16 (1%) 2.2 — Other/unspecified CNS tumors 31 (2%) 4.2 1992–2004 5.2 (22.7–13.7) k Neuroblastoma 402 (24%) 54.1 1992–2004 21.9 (25.5–1.9) Retinoblastoma 196 (12%) 26.4 1992–2004 21.1 (23.1–0.8) Wilms tumor 107 (6%) 14.4 1992–2004 24.0 (210.2–2.5) k (continued ) Childhood Cancer Incidence Trends/Linabery et al. 421 TABLE 2 (continued ) Age Group <1 Year 1992–2004 Cancer No. (%) Incidence rate* Years APC 1 y (95% CI) Years APC 2 y (95% CI) Years APC 3 y (95% CI) Years APC 4 y (95% CI) Hepatoblastoma 78 (5%) 10.5 1992–2004 4.2 (21.9–10.7) k 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) k Germ cell tumors 156 (9%) 21.0 1992–2004 0.3 (25.0–5.9) k Thyroid carcinoma 0 (0%) 0.0 — Melanoma 5 (0.3%) 0.7 — Age Group 1–4 Years 1992–2004 Cancer No. (%) Incidence rate* Years APC 1 y (95% CI) Years APC 2 y (95% CI) Years APC 3 y (95% CI) Years APC 4 y (95% CI) Total { 5913 (100%) 199.6 1992–2004 0.3 (20.5–1.1) Leukemias 2526 (43%) 85.3 1992–2004 0.6 (20.9–2.0) ALL 2169 (37%) 73.2 1992–2004 0.4 (21.4–2.3) AML 279 (5%) 9.4 1992–2004 1.5 (22.9–6.2) Other/unspecified leukemias 78 (1%) 2.6 1992–2004 2.7 (25.6–11.8) k Hodgkin disease 25 (0.4%) 0.8 — Non-Hodgkin lymphoma 181 (3%) 6.1 1992–2004 22.2 (25.4–1.1) k CNS tumors 1,140 (19%) 38.5 1992–1996 24.8 (210.6–1.3) 1996–2001 5.7 (20.7–12.6) 2001–2004 25.1 (213.9–4.5) Ependymoma 130 (2%) 4.4 1992–2004 21.2 (25.3–3.2) k Astrocytoma 493 (8%) 16.6 1992–2004 1.9 (20.3–4.2) PNET 326 (6%) 11.0 1992–2004 22.2 (25.8–1.5) Other gliomas 136 (2%) 4.6 1992–2004 0.1 (26.0–6.5) k Other/unspecified CNS tumors 55 (0.9%) 1.9 — Neuroblastoma 557 (9%) 18.8 1992–2004 20.7 (23.0–1.7) Retinoblastoma 296 (5%) 10.0 1992–2004 1.6 (21.6–4.8) Wilms tumor 510 (9%) 17.2 1992–2004 21.5 (24.0–1.1) Hepatoblastoma 120 (2%) 4.1 1992–2004 4.8 (0.9–8.8) k Osteosarcoma 9 (0.2%) 0.3 — Ewing sarcoma 17 (0.3%) 0.6 — Rhabdomyosarcoma 200 (3%) 6.8 1992–2004 21.7 (25.6–2.5) k Nonrhabdomyosarcoma soft tissue sarcoma 70 (1%) 2.4 1992–2004 1.0 (27.0–9.7) k Germ cell tumors 117 (2%) 3.9 1992–2004 0.7 (25.1–6.7) k (continued ) 422 CANCER January 15, 2008 / Volume 112 / Number 2 TABLE 2 (continued ) Age Group 1–4 Years 1992–2004 Cancer No. (%) Incidence rate* Years APC 1 y (95% CI) Years APC 2 y (95% CI) Years APC 3 y (95% CI) Years APC 4 y (95% CI) 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 APC 1 y (95% CI) Years APC 2 y (95% CI) Years APC 3 y (95% CI) Years APC 4 y (95% CI) Total { 3926 (100%) 107.4 1992–2004 0.3 (20.7–1.4) Leukemias 1395 (36%) 38.2 1992–1999 2.8 (20.2–5.8) 1999–2004 23.9 (28.5–0.9) ALL 1176 (30%) 32.2 1992–1999 3.6 (0.5–6.8) 1999–2004 24.0 (28.6–0.9) AML 169 (4%) 4.6 1992–2004 20.9 (25.3–3.7) k Other/unspecified leukemias 50 (1%) 1.4 1992–2004 26.9 (215.2–2.3) k Hodgkin disease 141 (4%) 3.9 1992–2004 0.9 (22.2–4.0) k Non-Hodgkin lymphoma 302 (8%) 8.3 1992–2004 2.0 (20.7–4.8) CNS tumors 1087 (28%) 29.7 1992–2004 0.6 (21.2–2.4) Ependymoma 63 (2%) 1.7 1992–2004 4.9 (23.8–14.4) k Astrocytoma 515 (13%) 14.1 1992–2004 20.9 (23.8–2.1) PNET 271 (7%) 7.4 1992–2004 1.3 (23.2–6.0) Other gliomas 219 (6%) 6.0 1992–2004 3.1 (23.0–9.7) k Other/unspecified CNS tumors 19 (0.5%) 0.5 — Neuroblastoma 108 (3%) 3.0 1992–2004 1.6 (23.5–7.0) k Retinoblastoma 19 (0.5%) 0.5 — Wilms tumor 164 (4%) 4.5 1992–2004 23.5 (28.4–1.6) k Hepatoblastoma 15 (0.4%) 0.4 — Osteosarcoma 90 (2%) 2.5 1992–2004 20.6 (25.5–4.5) k Ewing sarcoma 58 (1%) 1.6 1992–2004 21.6 (28.8–6.1) k Rhabdomyosarcoma 161 (4%) 4.4 1992–2002 3.5 (0.3–6.9) k 2002–2004 226.7 (255.1–19.5) Nonrhabdomyosarcoma soft tissue sarcoma 118 (3%) 3.2 1992–2004 21.1 (27.3–5.5) k Germ cell tumors 80 (2%) 2.2 1992–2004 1.7 (24.2–7.9) k Thyroid carcinoma 41 (1%) 1.1 — Melanoma 38 (1%) 1.0 — (continued ) Childhood Cancer Incidence Trends/Linabery et al. 423 TABLE 2 (continued ) Age Group 10–14 Years 1992–2004 Cancer No. (%) Incidence rate* Years APC 1 y (95% CI) Years APC 2 y (95% CI) Years APC 3 y (95% CI) Years APC 4 y (95% CI) Total { 4346 (100%) 121.1 1992–2004 0.4 (20.6–1.5) Leukemias 990 (23%) 27.6 1992–2004 0.5 (20.7–1.9) ALL 695 (16%) 19.4 1992–2004 0.7 (21.0–2.6) AML 231 (5%) 6.4 1992–2004 1.2 (21.9–4.4) Other/unspecified leukemias 64 (1%) 1.8 1992–2004 23.7 (28.6–1.5) k Hodgkin disease 409 (9%) 11.4 1992–2004 20.4 (23.2–2.4) Non-Hodgkin lymphoma 404 (9%) 11.3 1992–2004 1.7 (21.1–4.6) CNS tumors 906 (21%) 25.2 1992–2004 21.1 (23.0–1.0) Ependymoma 52 (1%) 1.4 1992–2002 22.5 (26.9–2.1) k 2002–2004 252.2 (284.3–45.1) Astrocytoma 483 (11%) 13.5 1992–2004 21.9 (24.4–0.8) PNET 190 (4%) 5.3 1992–2004 22.0 (25.4–1.6) Other gliomas 159 (4%) 4.4 1992–2004 4.3 (22.4–11.5) k 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 (22.5–3.0) Ewing sarcoma 109 (3%) 3.0 1992–2004 24.3 (27.7–20.7) k Rhabdomyosarcoma 117 (3%) 3.3 1992–2004 1.5 (24.8–8.3) k Nonrhabdomyosarcoma soft tissue sarcoma 276 (6%) 7.7 1992–2004 0.0 (23.3–3.4) Germ cell tumors 266 (6%) 7.4 1992–2004 2.1 (21.3–5.5) Thyroid carcinoma 160 (4%) 4.5 1992–2004 20.6 (25.3–4.3) k Melanoma 108 (2%) 3.0 1992–2004 6.7 (1.8–11.9) k Age Group 15–19 Years 1992–2004 Cancer No. (%) Incidence rate* Years APC 1 y (95% CI) Years APC 2 y (95% CI) Years APC 3 y (95% CI) Years APC 4 y (95% CI) Total { 6832 (100%) 200.8 1992–2004 0.4 (20.4–1.3) Leukemias 922 (13%) 27.1 1992–2004 2.0 (20.3–4.5) ALL 518 (8%) 15.2 1992–2004 3.3 (0.4–6.4) AML 297 (4%) 8.7 1992–2004 0.9 (23.1–5.1) Other/unspecified leukemias 107 (2%) 3.1 1992–2004 0.1 (27.0–7.8) k Hodgkin disease 1035 (15%) 30.4 1992–2004 21.3 (22.7–0.2) Non-Hodgkin lymphoma 573 (8%) 16.8 1992–2004 2.3 (20.8–5.4) (continued ) 424 CANCER January 15, 2008 / Volume 112 / Number 2 TABLE 2 (continued ) Age Group 15–19 Years 1992–2004 Cancer No. (%) Incidence rate* Years APC 1 y (95% CI) Years APC 2 y (95% CI) Years APC 3 y (95% CI) Years APC 4 y (95% CI) CNS tumors 646 (9%) 19.0 1992–2004 21.3 (24.1–1.5) Ependymoma 40 (0.6%) 1.2 1992–2004 2.0 (29.0–14.4) k Astrocytoma 350 (5%) 10.3 1992–2004 21.2 (25.0–2.7) PNET 108 (2%) 3.2 1992–1997 219.3 (238.5–5.9) k 1997–2001 34.0 (222.6–132.2) 2001–2004 228.5 (259.8–27.1) Other gliomas 134 (2%) 3.9 1992–2004 21.4 (27.0–4.6) k 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 (23.1–4.5) Ewing sarcoma 142 (2%) 4.2 1992–2004 24.1 (28.9–0.9) k Rhabdomyosarcoma 126 (2%) 3.7 1992–2004 2.8 (21.5–7.2) k Nonrhabdomyosarcoma soft tissue sarcoma 385 (6%) 11.3 1992–2004 0.4 (23.6–4.5) Germ cell tumors 988 (14%) 29.0 1992–2004 0.7 (21.2–2.7) Thyroid carcinoma 562 (8%) 16.5 1992–2004 2.1 (20.4–4.7) Melanoma 501 (7%) 14.7 1992–2004 1.3 (21.4–4.1) Race § White 1992–2004 Cancer No. (%) Incidence rate* Years APC 1 y (95% CI) Years APC 2 y (95% CI) Years APC 3 y (95% CI) Years APC 4 y (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 (20.7–3.6) Other/unspecified leukemias 250 (1%) 2.3 1992–1996 219.1 (233.6–21.5) k 1996–2004 6.5 (21.5–15.1) Hodgkin disease 1354 (8%) 13.2 1992–2004 21.0 (23.0–1.0) Non-Hodgkin lymphoma 1125 (6%) 10.8 1992–2004 1.4 (20.5–3.2) CNS tumors 3179 (18%) 29.5 1992–2004 0.1 (21.3–1.4) Ependymoma 241 (1%) 2.2 1992–2004 21.1 (25.5–3.6) Astrocytoma 1548 (9%) 14.4 1992–2004 20.3 (21.9–1.4) PNET 783 (4%) 7.2 1992–2004 21.0 (23.1–1.2) Other gliomas 498 (3%) 4.7 1992–2004 2.0 (20.6–4.7) Other/unspecified CNS tumors 109 (0.6%) 1.0 1992–2004 6.6 (0.2–13.4) k Neuroblastoma 864 (5%) 7.6 1992–2004 20.3 (22.6–2.2) (continued ) Childhood Cancer Incidence Trends/Linabery et al. 425 [...]... 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... Ethnicity TABLE 2 (continued ) 428 January 15, 2008 / Volume 112 / Number 2 Childhood Cancer Incidence Trends/ Linabery et al 429 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, 22.4%; 95% CI, 24.5%–20.3%), but not in males Joinpoints resulting in a shift in the direction of the trend also... malignancies may have 431 influenced incidence trends Classification by ICD-O3 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... were performed in the joinpoint regression analyses and the results therefore may include spurious associations Trends involving . performed in the joinpoint regression analyses and the results there- fore may include spurious associations. Trends invol- ving <10 cases/year are noted in. childhood cancers diagnosed since the early 199 0s, with evidence of increases in select malignancies and shifting trends in others. The results of the current study