Subsequent Malignancies in Children Treated for Hodgkin's Disease: Associations With Gender and Radiation Dose

Louis S. Constine, Nancy Tarbell, Melissa M. Hudson, Cindy Schwartz, Susan G. Fisher, Ann G. Muhs, Swati K. Basu, Larry E. Kun, Andrea Ng, Peter Mauch, Ajay Sandhu, Eva Culakova, Gary Lyman, Nancy Mendenhall

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Abstract

Purpose: Subsequent malignant neoplasms (SMNs) are a dominant cause of morbidity and mortality in children treated for Hodgkin's disease (HD). We evaluated select demographic and therapeutic factors associated with SMNs, specifically gender and radiation dose. Methods and Materials: A total of 930 children treated for HD at five institutions between 1960 and 1990 were studied. Mean age at diagnosis was 13.6 years, and mean follow-up was 16.8 years (maximum, 39.4 years). Treatment included radiation alone (43%), chemotherapy alone (9%), or both (48%). Results: We found that SMNs occurred in 102 (11%) patients, with a 25-year actuarial rate of 19%. With 15,154 patient years of follow-up, only 7.18 cancers were expected (standardized incidence ratio [SIR] = 14.2; absolute excess risk [AER] = 63 cases/10,000 years). The SIR for female subjects, 19.93, was significantly greater than for males, 8.41 (p < 0.0001). After excluding breast cancer, the SIR for female patients was 15.4, still significantly greater than for male patients (p = 0.0012). Increasing radiation dose was associated with an increasing SIR (p = 0.0085). On univariate analysis, an increased risk was associated with female gender, increasing radiation dose, and age at treatment (12-16 years). Using logistic regression, mantle radiation dose increased risk, and this was 2.5-fold for female patients treated with more than 35 Gy primarily because of breast cancer. Conclusions: Survivors of childhood HD are at risk for SMNs, and this risk is greater for female individuals even after accounting for breast cancer. Although SMNs occur in the absence of radiation therapy, the risk increases with RT dose.

Original languageEnglish (US)
Pages (from-to)24-33
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume72
Issue number1
DOIs
StatePublished - Sep 1 2008

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neoplasms
Hodgkin Disease
Radiation
dosage
radiation
incidence
cancer
breast
Neoplasms
Incidence
Breast Neoplasms
Child Mortality
mortality
logistics
chemotherapy
Survivors
regression analysis
radiation therapy
Earth mantle
Radiotherapy

Keywords

  • Age
  • Breast cancer
  • Gender
  • Pediatric Hodgkin's disease
  • Subsequent malignancy

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Subsequent Malignancies in Children Treated for Hodgkin's Disease : Associations With Gender and Radiation Dose. / Constine, Louis S.; Tarbell, Nancy; Hudson, Melissa M.; Schwartz, Cindy; Fisher, Susan G.; Muhs, Ann G.; Basu, Swati K.; Kun, Larry E.; Ng, Andrea; Mauch, Peter; Sandhu, Ajay; Culakova, Eva; Lyman, Gary; Mendenhall, Nancy.

In: International Journal of Radiation Oncology Biology Physics, Vol. 72, No. 1, 01.09.2008, p. 24-33.

Research output: Contribution to journalArticle

Constine, LS, Tarbell, N, Hudson, MM, Schwartz, C, Fisher, SG, Muhs, AG, Basu, SK, Kun, LE, Ng, A, Mauch, P, Sandhu, A, Culakova, E, Lyman, G & Mendenhall, N 2008, 'Subsequent Malignancies in Children Treated for Hodgkin's Disease: Associations With Gender and Radiation Dose', International Journal of Radiation Oncology Biology Physics, vol. 72, no. 1, pp. 24-33. https://doi.org/10.1016/j.ijrobp.2008.04.067
Constine, Louis S. ; Tarbell, Nancy ; Hudson, Melissa M. ; Schwartz, Cindy ; Fisher, Susan G. ; Muhs, Ann G. ; Basu, Swati K. ; Kun, Larry E. ; Ng, Andrea ; Mauch, Peter ; Sandhu, Ajay ; Culakova, Eva ; Lyman, Gary ; Mendenhall, Nancy. / Subsequent Malignancies in Children Treated for Hodgkin's Disease : Associations With Gender and Radiation Dose. In: International Journal of Radiation Oncology Biology Physics. 2008 ; Vol. 72, No. 1. pp. 24-33.
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abstract = "Purpose: Subsequent malignant neoplasms (SMNs) are a dominant cause of morbidity and mortality in children treated for Hodgkin's disease (HD). We evaluated select demographic and therapeutic factors associated with SMNs, specifically gender and radiation dose. Methods and Materials: A total of 930 children treated for HD at five institutions between 1960 and 1990 were studied. Mean age at diagnosis was 13.6 years, and mean follow-up was 16.8 years (maximum, 39.4 years). Treatment included radiation alone (43{\%}), chemotherapy alone (9{\%}), or both (48{\%}). Results: We found that SMNs occurred in 102 (11{\%}) patients, with a 25-year actuarial rate of 19{\%}. With 15,154 patient years of follow-up, only 7.18 cancers were expected (standardized incidence ratio [SIR] = 14.2; absolute excess risk [AER] = 63 cases/10,000 years). The SIR for female subjects, 19.93, was significantly greater than for males, 8.41 (p < 0.0001). After excluding breast cancer, the SIR for female patients was 15.4, still significantly greater than for male patients (p = 0.0012). Increasing radiation dose was associated with an increasing SIR (p = 0.0085). On univariate analysis, an increased risk was associated with female gender, increasing radiation dose, and age at treatment (12-16 years). Using logistic regression, mantle radiation dose increased risk, and this was 2.5-fold for female patients treated with more than 35 Gy primarily because of breast cancer. Conclusions: Survivors of childhood HD are at risk for SMNs, and this risk is greater for female individuals even after accounting for breast cancer. Although SMNs occur in the absence of radiation therapy, the risk increases with RT dose.",
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AU - Tarbell, Nancy

AU - Hudson, Melissa M.

AU - Schwartz, Cindy

AU - Fisher, Susan G.

AU - Muhs, Ann G.

AU - Basu, Swati K.

AU - Kun, Larry E.

AU - Ng, Andrea

AU - Mauch, Peter

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N2 - Purpose: Subsequent malignant neoplasms (SMNs) are a dominant cause of morbidity and mortality in children treated for Hodgkin's disease (HD). We evaluated select demographic and therapeutic factors associated with SMNs, specifically gender and radiation dose. Methods and Materials: A total of 930 children treated for HD at five institutions between 1960 and 1990 were studied. Mean age at diagnosis was 13.6 years, and mean follow-up was 16.8 years (maximum, 39.4 years). Treatment included radiation alone (43%), chemotherapy alone (9%), or both (48%). Results: We found that SMNs occurred in 102 (11%) patients, with a 25-year actuarial rate of 19%. With 15,154 patient years of follow-up, only 7.18 cancers were expected (standardized incidence ratio [SIR] = 14.2; absolute excess risk [AER] = 63 cases/10,000 years). The SIR for female subjects, 19.93, was significantly greater than for males, 8.41 (p < 0.0001). After excluding breast cancer, the SIR for female patients was 15.4, still significantly greater than for male patients (p = 0.0012). Increasing radiation dose was associated with an increasing SIR (p = 0.0085). On univariate analysis, an increased risk was associated with female gender, increasing radiation dose, and age at treatment (12-16 years). Using logistic regression, mantle radiation dose increased risk, and this was 2.5-fold for female patients treated with more than 35 Gy primarily because of breast cancer. Conclusions: Survivors of childhood HD are at risk for SMNs, and this risk is greater for female individuals even after accounting for breast cancer. Although SMNs occur in the absence of radiation therapy, the risk increases with RT dose.

AB - Purpose: Subsequent malignant neoplasms (SMNs) are a dominant cause of morbidity and mortality in children treated for Hodgkin's disease (HD). We evaluated select demographic and therapeutic factors associated with SMNs, specifically gender and radiation dose. Methods and Materials: A total of 930 children treated for HD at five institutions between 1960 and 1990 were studied. Mean age at diagnosis was 13.6 years, and mean follow-up was 16.8 years (maximum, 39.4 years). Treatment included radiation alone (43%), chemotherapy alone (9%), or both (48%). Results: We found that SMNs occurred in 102 (11%) patients, with a 25-year actuarial rate of 19%. With 15,154 patient years of follow-up, only 7.18 cancers were expected (standardized incidence ratio [SIR] = 14.2; absolute excess risk [AER] = 63 cases/10,000 years). The SIR for female subjects, 19.93, was significantly greater than for males, 8.41 (p < 0.0001). After excluding breast cancer, the SIR for female patients was 15.4, still significantly greater than for male patients (p = 0.0012). Increasing radiation dose was associated with an increasing SIR (p = 0.0085). On univariate analysis, an increased risk was associated with female gender, increasing radiation dose, and age at treatment (12-16 years). Using logistic regression, mantle radiation dose increased risk, and this was 2.5-fold for female patients treated with more than 35 Gy primarily because of breast cancer. Conclusions: Survivors of childhood HD are at risk for SMNs, and this risk is greater for female individuals even after accounting for breast cancer. Although SMNs occur in the absence of radiation therapy, the risk increases with RT dose.

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KW - Gender

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KW - Subsequent malignancy

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