Second malignant tumors following treatment during childhood and adolescence for cancer

Green, Daniel M.; Zevon, Michael A.; Reese, Peter A.; Lowrie, Geoffrey S.; Gaeta, John F.; Pearce, J.; Michalek, Arthur M.; Stephens, Elizabeth

doi:10.1002/mpo.2950220102

Cited by 84 publications

(40 citation statements)

References 47 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: 53%

“…Previous studies differ on the importance of age and gender as risk factors. 22,26,27,29 For example, Neglia et al 22 found female gender to be a significant risk factor, whereas Olsen et al 29 reported that male gender was a risk factor. In addition, de Vathaire et al 26 reported that older age was a risk factor, whereas a younger age was found to be a risk factor in the Neglia et al study.…”

Section: Discussionmentioning

confidence: 99%

“…22 Yet another study showed that neither age nor gender was a significant risk factor. 27 Therefore, the significance of age and gender as risk factors for the development of SNs remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…However, others have demonstrated an association between chemotherapy administration and the development of SNs. 5,15,26,27,30,31 Tucker et al 15 showed that treatment of pediatric patients with alkylating agents increased their risk of secondary bone sarcomas. Our findings support that study.…”

Section: Discussionmentioning

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: 53%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Second neoplasms after megavoltage radiation for pediatric tumors

Gold¹,

Neglia²,

Dusenbery³

2003

Cancer

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“…[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: 82%

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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Treatment of children with stage IV favorable histology Wilms tumor: A report from the National Wilms Tumor Study Group

Green

Breslow

Evans

et al. 1996

Med. Pediatr. Oncol.

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The purpose of this study was to evaluate the effect of the sequential addition of doxorubicin and cyclophosphamide to the combination of vincristine and actinomycin D on the relapse‐free survival of children with stage IV/favorable histology Wilms tumor. We reviewed the clinical courses of all randomized patients from National Wilms Tumor Study (NWTS)‐2 and 3 with stage IV/favorable histology (FH) Wilms tumor. We determined the four‐year relapse‐free survival percentage for patients treated on NWTS‐2 with the combination of vincristine (VCR) and actinomycin D (AMD) with (regimen D) or without (regimen C) doxorubicin (DOX), and for patients treated on NWTS‐3 with the combination of VCR + AMD + DOX with (regimen J) or without (regimen DD‐RT) cyclophosphamide (CTX). All children received whole lung radiation therapy. The four‐year relapse‐free survival percentage for children with stage IV/FH Wilms tumor treated with regimen C was 53.3%, compared to 57.7% for those treated with regimen D (P = 0.63). The four‐year relapse‐free survival percentage for children with stage IV/FH Wilms tumor treated with regimen DD‐RT was 79.0%, compared to 80.9% for those treated on regimen J (P = 0.79). The four‐year relapse‐free survival for children with lung metastases only treated with regimen D on NWTS‐2 was significantly lower than that of children treated with the related regimen DD‐RT on NWTS‐3 (P = 0.03). We conclude that the addition of doxorubicin to the combination of vincristine and actinomycin D and pulmonary irradiation did not clearly improve the four‐year relapse‐free survival percentage of children with stage IV/FH Wilms tumor, although the benefit may have been masked by the greater frequency of death due to toxicity in NWTS‐2. There was no evidence that the addition of CTX to the three‐drug treatment regimen improved the four‐year relapse‐free survival percentage of children with stage IV/FH Wilms tumor. The data with only two drugs derived from NWTS‐2 suggest that there is a population of children with stage IV/FH Wilms tumor who can be successfully treated without an anthracycline. The goal of future research will be to identify this subgroup at the time of initial diagnosis. © 1996 Wiley‐Liss, Inc.

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Second malignant tumors following treatment during childhood and adolescence for cancer

Cited by 84 publications

References 47 publications

Second neoplasms after megavoltage radiation for pediatric tumors

Second neoplasms after megavoltage radiation for pediatric tumors

Second malignancy after treatment of childhood acute myeloid leukemia

Treatment of children with stage IV favorable histology Wilms tumor: A report from the National Wilms Tumor Study Group

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