Second malignancy risk after treatment of hodgkin lymphoma

Abstract

Second cancers are among the most serious sequelae of HL treatment because they cause substantial morbidity as well as mortality. Compared to the general population, HL survivors experience substantially increased relative risks (6- to 15-fold) of leukemia, non-Hodgkin lymphoma (NHL), sarcoma, and thyroid cancer and moderately increased risks (two- to sixfold) for a variety of other (solid) tumors, such as cancers of the lung, breast, stomach, esophagus, and cervix and melanoma. Overall, HL patients treated in the 1960s–1980s experience about 45–90 excess malignancies per 10,000 patients per year. Solid cancers account for the large majority of excess cancers. The relative risk of solid tumors rises with increasing follow-up time from 5 to 20 years after treatment and stabilizes thereafter. The absolute excess risk of solid malignancy strongly increases with time, as the background rate of cancer rises with age. Elevated risks of solid cancers are largely attributable to extended-field radiotherapy. The risks of lung, breast, and stomach cancer after HL increase with higher radiation doses and radiation volume. Consequently, with prescribed dose and treated volumes decreasing with modern radiotherapy, risks in more recently treated patients appear to be lower. Procarbazine-containing chemotherapy also increases the risk of solid malignancy, in particular lung and stomach cancer. By contrast, alkylator-based chemotherapy appears to decrease the risk of radiation-associated breast cancer, through its effect on premature menopause. Smoking multiplies treatment-associated risks of lung cancer. Therefore, all HL patients should be advised to stop smoking. HL survivors should be screened for second malignancy when effective screening methods are available; early initiation of breast cancer and colorectal cancer screening is recommended after radiotherapy to the chest or abdomen, respectively.