Risk of second tumors in survivors of childhood cancer

Li, Frederick P.; Cassady, J. Robert; Jaffe, Norman

doi:10.1002/1097-0142(197504)35:4<1230::aid-cncr2820350430>3.0.co;2-q

Cited by 258 publications

(64 citation statements)

References 21 publications

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“…Actuarial rates have ranged from 3-13% at 20 -30 years of follow-up. 6,8,10,18,22,[25][26][27] Higher rates are associated with single-institution studies, as is ours, whereas lower rates are associated with larger studies involving multiple institutions. Additional reasons may account for the higher risk estimate in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…Although a genetic predisposition for cancer and previous chemotherapy may be contributing causes to the development of SNs, 5 various reports have highlighted the significant contribution of radiotherapy to the development of SNs in childhood cancer survivors. 3,[5][6][7][8][9][10][11][12][13][14][15][16][17][18] A radiation dose-effect relationship has been noted for some SNs such as bone sarcomas. 15 Children are particularly susceptible to the carcinogenic effects of radiation, possibly due to the increased rapidity of cell division in various tissues associated with the normal growth and development process.…”

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confidence: 99%

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Second neoplasms after megavoltage radiation for pediatric tumors

Gold¹,

Neglia²,

Dusenbery³

2003

Cancer

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BACKGROUNDBecause ionizing radiation is a known carcinogen, diligent long‐term follow‐up in children exposed to therapeutic radiation is required. The authors updated an earlier study on the nature and risk of second neoplasms (SN) in patients treated with megavoltage radiotherapy as children.METHODSThe authors followed 446 children who were treated for a primary malignancy with megavoltage radiotherapy between January 16, 1954 and December 31, 1980. These children survived a minimum of 5 years. The nature and incidence of SNs were evaluated in this population. Patients with bilateral retinoblastoma or neurofibromatosis were excluded from the study due to their large genetically based predisposition for developing an SN.RESULTSThe Kaplan–Meier actuarial survival rate was 80% (95% confidence interval [CI] 74–85%) at 30 years for all patients. Thirty‐seven (8.3%) patients developed SNs, most of which occurred within the original radiation treatment field, 3.8–31.8 years (median, 15.5 years) after radiotherapy. The cumulative risk of developing an SN was 13% (95% CI 9–19%) at 30 years and the standardized incidence ratio for the development of any SN was 5.2 (95% CI 3.4–7.6%). The most common SNs were breast carcinoma (n = 8), skin carcinoma (five basal cell carcinomas, two malignant melanomas, and one dermatosarcoma), and meningiomas (n = 6). All eight breast carcinomas occurred after the treatment of childhood Hodgkin disease. Of the 37 patients with SNs, 12 died of either the SN (n = 10) or of recurrent disease (n = 2). Risk factors associated with developing a SN included initial diagnosis of Hodgkin disease (P = 0.0003), female gender (P = 0.008), and an initial diagnosis of acute lymphoblastic leukemia (P = 0.02).CONCLUSIONSPatients in the radiation‐treated cohort experienced increased mortality, were at an increased risk of developing an SN, and should undergo increased medical surveillance as adults. The cumulative probability of developing an SN has increased substantially at 30 years, largely due to an increase in follow‐up time. In addition, the cumulative probability curve does not show evidence of plateau after increased duration of follow‐up. Finally, the emergence of secondary breast carcinoma in the current study was not noted in the previous analysis. Cancer 2003;10:2588–96. © 2003 American Cancer Society.DOI 10.1002/cncr.11356

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Second neoplasms after megavoltage radiation for pediatric tumors

Gold¹,

Neglia²,

Dusenbery³

2003

Cancer

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“…With this cohort, and excluding basocellular carcinomas of the skin, Tucker, for the Late Effect Study Group (LESG), found a constant standardised incidence ratio of 16, in agreement with our estimation of 13 (Tucker et al, 1984). Li, studying 410 5-year survivors from the Sidney Farber Cancer Institute, found a standardised incidence ratio of 20, not significantly different from our estimation (Li et al, 1975;Li, 1977). However, standardised incidence ratios by time periods after FPC diagnosis were not published.…”

Section: Discussionmentioning

confidence: 99%

Long-term risk of second malignant neoplasm after a cancer in childhood

Vathaire

Schweisguth²,

Rodary³

et al. 1989

Br J Cancer

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Summary The risk of subsequent second malignant neoplasm was studied in a cohort of 634 patients, treated for a childhood cancer at the Gustave Roussy Institute between 1942 and 1969, and in complete remission five years after diagnosis. The most frequent types of first primary cancers (FPC) were Wilms' tumours (28% of the children), neuroblastomas (16%), lymphomas (12%) and soft tissue sarcomas (11%). Median follow-up duration after FPC was 19 years. Thirty-two patients (obs=32) developed a total of 35 second cancers. Bone, thyroid, connective tissues and skin were the most frequent types of second cancer, with six patients for each type. The average annual incidence of second cancer was 0.36%. The average annual incidence for the periods 5-9, 10-14, 15-19, 20-24 and 25+ years after FPC was respectively 0.16%, 0.34%, 0.36%, 0.71% and 1.18%. The cumulative incidence of second cancer for the periods 5-20, 5-25 and 5-30 years after FPC was, respectively, 4.3% (95% Cl: 2.8-6.6%), 7.8% (95% Cl: 5.1-11.8%) and 13.0% (95% CI: 8.2-20.0%). The expected number of cancers in the cohort, computed from Danish cancer incidence data, was exp=2.2. When compared to this expected number, the average annual excess incidence of second cancer, defined as obs-exp divided by the number of person years of observation, was 0.33%. This rose from 0.15% for the period 5-9 years after FPC to 1.09% for the period beginning 25 years after FPC. The standardised incidence ratio of second cancer (i.e. obs/exp) was 15 (95% CI: 10-21), and was fairly constant in the period extending from 15 to 20 years after FPC diagnosis. Obs/exp was equal to 25 for the patients who had had chemotherapy and equal to 9 for those who had not. Cyclophosphamide seemed less carcinogenic than the other alkylating agents. Obs/exp was similar for the patients who had received radiotherapy and for those who had not. The risk of cancer increased with age in the reference population and increased faster in the cohort, because the standardised incidence ratio is constant over a long period.

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“…Some of these prior studies did not include patients with a primary diagnosis of AML, while others did not distinguish the primary diagnosis of ALL from that of AML. [17][18][19][20][21][22][23][24] We found only four studies that reported the number of patients with a primary diagnosis of AML who were in the cohort; either no second cancer or only one second cancer was reported for these four studies with a small number of patients (38 to 163 patients). [25][26][27][28] Comparison of the findings of these four studies with those of our study is not possible because information about the person-years at risk or the cumulative incidence of second cancer in the survivors of AML was not reported.…”

Section: Leukemiamentioning

confidence: 92%

Second malignancy after treatment of childhood acute myeloid leukemia

et al. 2001

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To investigate the cumulative incidence of second malignancy and the competing risk of death due to any other cause in patients who were treated for childhood acute myeloid leukemia (AML), we analyzed the outcomes in a cohort of 501 patients who were treated at St Jude Children's Research Hospital between 1970 and 1996. Five patients developed a second cancer (two carcinomas of the parotid gland, one non-Hodgkin's lymphoma, one supratentorial primitive neuroectodermal tumor, one acute lymphoblastic leukemia) as compared with 0.47 expected in the general population (standardized incidence ratio, 10.64; 95% confidence interval, 3.28 to 22.34). A third neoplasm (meningioma) developed in one patient. At 15 years after the diagnosis of AML, the estimated cumulative incidence of second malignancy was 1.34% ± 0.61%, whereas the cumulative incidence of death due to any other cause was 72.96% ± 2.14%. We concluded that although a more than 10-fold increased risk of development of cancer was found in survivors of childhood AML as compared to the general population, the risk of this late complication is small when compared to the much larger risk of death because of the primary leukemia or the early complications of its treatment. Future studies should focus on improving treatments for primary AML while preventing second malignancies. Leukemia (2001) 15, 41-45.

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Risk of second tumors in survivors of childhood cancer

Cited by 258 publications

References 21 publications

Second neoplasms after megavoltage radiation for pediatric tumors

Second neoplasms after megavoltage radiation for pediatric tumors

Long-term risk of second malignant neoplasm after a cancer in childhood

Second malignancy after treatment of childhood acute myeloid leukemia

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