Subsequent malignancies in children treated for Hodgkin's disease: associations with gender and radiation dose.
OBJECTIVE
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
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.
Constine
Louis S
LS
Department of Radiation Oncology, University of Rochester, Rochester, NY 14642, USA. louis_constine@urmc.rochester.edu
Tarbell
Nancy
N
Hudson
Melissa M
MM
Schwartz
Cindy
C
Fisher
Susan G
SG
Muhs
Ann G
AG
Basu
Swati K
SK
Kun
Larry E
LE
Ng
Andrea
A
Mauch
Peter
P
Sandhu
Ajay
A
Culakova
Eva
E
Lyman
Gary
G
Mendenhall
Nancy
N
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000453:epidemiology / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology / Q000401:mortality; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000401:mortality; D011879:Radiotherapy Dosage; D012008:Recurrence; D012737:Sex Factors; D013223:Statistics as Topic; D017741:Survivors; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000401:mortality