We also estimated the SIR in different periods over 30 years. Sanctuary therapy: a randomized trial of 724 children with previously untreated acute lymphoblastic leukemia . International incidence of childhood cancer. Administrative, technical or material support: Hijiya, Hudson, Lensing, Zacher. Patients treated with radiation therapy are overrepresented in this study population as compared with the populations of current studies. 1. Five of these were isolated relapses in the central nervous system, and two were isolated marrow relapses. et al. The median age of patients with these solid tumors in our cohort was 26.2 years (range, 12.6-39.7 years), considerably younger than the expected ages for the development of most carcinomas and sarcomas. Cancer 1986;58:40713. Cancer 1983;51:10419. The content of this site is intended for health care professionals. Cancer 1986;57:197985. Prognostic factors and therapy in acute lymphoblastic leukemia of childhood: CCG-141 . In 30 of these 36, therapy had been completely discontinued by the time the second neoplasm was diagnosed. Stratification according to age at the diagnosis of ALL did not yield any additional associations. Ortega JA, Nesbit ME Jr, Donaldson MH, et al. Distribution of Second Neoplasms According to the Patient's Age at the Diagnosis of ALL. As expected, this ratio was highest for overall tumors in the first 5 years of follow-up (SIR, 335.1; 95% CI, 232.8-436.7), reflecting the overwhelming impact of myeloid leukemias (SIR, 3951.7; 95% CI, 2782.9-5448.9). Compared with the results from the Children's Cancer Group (CCG)10 or Berlin-Frankfurt-Mnster (BFM) study group,11 in which meningioma and basal cell carcinoma accounted for less than 4% of all secondary neoplasms, the proportion of such tumors is considerably higher (approximately 15%) in our patient population. PuiCH, MahmoudHH, RiveraGK. et al. The estimated cumulative risk for radiation exposure is shown in Figure 4 (with the patients irradiated at the time of relapse being transferred to the exposed group as of the time of radiation). ConclusionsThe cumulative incidence of secondary neoplasms increases steadily over 30 years after treatment of acute lymphoblastic leukemia. Tumors of the central nervous system were the most common, followed by hematopoietic cancers. Among the 2169 patients who achieved complete remission without additional therapy, 879 had relapse as a first event and 1290 patients remained in complete remission. Second malignant neoplasms in children: an update from the Late Effects Study Group . All Rights Reserved. Previous Presentation: This study was presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 14, 2005, Orlando, Fla. When the patients were stratified into 2 groups (those who did vs did not receive cranial/craniospinal irradiation), the addition of cranial/craniospinal irradiation had a significant impact on the SIR for CNS tumors and other solid tumors (SIRs, 45.8 vs 4.3 and 5.1 vs 2.5, respectively) but not on the SIR for lymphomas or myeloid malignancies (Table 3). Cancer 1987;59:15068. Additionally, in the recent era, our survivors had a shorter duration of follow-up (median, 15.9 years [range, 2.4-26.2 years]). There was no association with exposure to cyclophosphamide or anthracyclines. This association held for carcinoma incidence (2.14% [SE, 0.72%] for men vs 5.52% [SE, 1.35%] for women; P=.07). Kreissman SG(1), Gelber RD, Cohen HJ, Clavell LA, Leavitt P, Sallan SE. The observed number of events including all patients was significantly higher than the expected number of secondary neoplasms, representing myeloid malignancies, lymphomas, brain tumors, and other solid tumors (SIR, 13.5; 95% CI, 10.9-16.8). Secondary Neoplasms Observed in First Complete Remission and After Relapse of Acute Lymphoblastic Leukemia, Latency From Diagnosis of Acute Lymphoblastic Leukemia to Development of a Secondary Neoplasm in First Complete Remission, Cumulative Incidence of Secondary Neoplasms in First Complete Remission Over 30 Years, Late-Occurring Secondary Neoplasms in Patients in First Complete Remission, Incidence of Secondary Neoplasms in First Complete Remission vs General US Population, Risk Factors Associated With Development of Secondary Neoplasms. Cumulative assigned doses were calculated for the anthracyclines (daunorubicin and doxorubicin) and for cyclophosphamide. JAMA. Nineteen new secondary neoplasms were diagnosed in these groups since publication of the studies, but in each analysis the risk factors retained their original importance. The histologic subtypes of CNS tumors other than meningioma, carcinomas excluding basal cell carcinoma, and soft-tissue sarcomas in first complete remission or after relapse are noted in Table 1. 20. Initial symptoms can be nonspecific, particularly in children. RellingMV, RubnitzJE, RiveraGK. Role of the Sponsor: The funding agencies/sponsors had no involvement in the design and conduct of the study; in the collection, management, analysis, or interpretation of the data; or in the preparation, review, and approval of the manuscript. . Patterns of second malignant neoplasms in children . Meadows AT, Baum E, Fossati-Bellani F, et al. Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and 5-year survival rates in the United States have exceeded 70% for over two decades. There is a substantial excess of second neoplasms, especially of the central nervous system, among children treated for ALL. 29. Malkin E, Li FP, Strong LC, et al. 40. Acknowledgment: We thank John Gilbert for scientific editing (compensated for his work). Five, 10, and 15 years after diagnosis, the actuarial estimated cumulative proportions of patients with a second neoplasm were 0.3 percent (95 percent confidence limits, 0.19 percent and 0.48 percent), 1.52 percent (95 percent confidence limits, 1.11 percent and 2.11 percent), and 2.53 percent (95 percent confidence limits, 1.74 percent and 3.38 percent), respectively. In this cohort of 9720 patients with newly diagnosed ALL, the overall estimated proportion of patients with a second neoplasm was approximately 2.5 percent 15 years after diagnosis. Two patients had undergone bone marrow transplantation. Risk of a Second Neoplasm According to the Patient's Age at the Diagnosis of ALL. For example, a second cancer may mark a particularly susceptible host, as a result of a combination of age, genetics, and possibly therapy. Secondary acute lymphoblastic leukemia (s-ALL) is rare and poorly defined and data regarding outcomes post-transplant are lacking. Vertical bars are 95 percent confidence limits. Among the 1290 patients who remained in complete remission, 123 (9.5%) developed a secondary neoplasm as their first event, 1099 (85.2%) remained alive without events, and 68 (5.3%) died in complete remission. However, even with exclusion of basal cell carcinomas, there remains an impressive increase in carcinoma incidence between 25 and 30 years after induction, reflecting cases of more aggressive malignant neoplasms (Figure 3). Among 41 patients, 4 (9.8%) died. Cancer. Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research Hospital. 24. Nonparametric estimation from incomplete observations . For patients whose treatment was unclear, this approach was combined with a chart review. 3). It is associated with "success" and with relief at no longer having to 16. StrojanP, PopovicM, JerebB. Proc Am Soc Clin Oncol 1991;10:221. abstract. Secondary neoplasms subsequent to Berlin-Frankfurt-Mnster therapy of acute lymphoblastic leukemia in childhood: significantly lower risk without cranial radiotherapy. Some limitations to the current study should be noted. NegliaJP, MeadowsAT, RobisonLL. In: Murphy SB, Gilbert JR, eds. For cancer doesn t get another cancer neoplasms occurring in 24 of the analysis, the cohort limit! Children with leukemia as their first cancer.31 member institutions are required to periodic Whose treatment was unclear, this approach was combined with a chart review patients. The incidence of second neoplasms according to age at the time of the late-occurring . System relapse in children treated with radiation therapy, and support needed to approach -. 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