“Second Malignant Neoplasms Among Long-Term Survivors of Hodgkin's Disease

Abstract

Survivors of Hodgkin's disease are at significantly increased risk of second cancers across all age groups, according to the results of this largest population-based study of Hodgkin's disease patients to date. Cancers of the stomach, female breast, and uterine cervix remained at significantly elevated risk over 25 years, while solid tumors at other sites showed an apparent decrease in relative and absolute excess risk. No second cancers occurred significantly below expectations. An increased risk of breast cancer continues or more than 25 years after a diagnosis of Hodgkin's disease. A significant increase in bladder cancer after Hodgkin's disease was an unexpected finding of the study. The authors analyzed data collected on 32,591 Hodgkin's disease patients (57.4% male) from 16 population-based cancer registries in North America and Europe, including 1,111 25-year survivors and 2,800 20-year survivors. There were 2,153 second cancers; of these, 1,726 were solid tumors. Age emerged as an important factor. The relative risk of solid neoplasms decreased with increasing age at diagnosis. Patients who were diagnosed at older ages carried the greatest second cancer burden. Patients aged 51 to 60 at Hodgkin's disease diagnosis had the highest incidence of cancer. Age at diagnosis was a factor in determining the site of a second cancer. After a progressive rise in risk of developing solid tumors over time, there was an apparent reduction of risk at 25 years. Cancers of the lung, digestive tract, and female breast made up the largest number of subsequent malignancies. A radiogenic effect was suggested by the temporal trends and treatment group distribution for cancers of the esophagus, stomach, rectum, female breast, bladder, thyroid, and bone/connective tissue. Significant two- to six-fold increased risks were seen for cancers of the lip, tongue salivary gland, gum and mouth, pharynx, esophagus, stomach, lung, female breast, uterine cervix, thyroid, bone, and connective tissue. Relative and absolute risks were similar for men and women. Patients treated with chemotherapy alone had a significantly elevated relative risk for solid tumors only within the first 15 years of follow-up. The increased risk of breast cancer continues for more than 25 years after Hodgkin's disease diagnosis. A significant increase in bladder cancer after Hodgkin's disease was an unexpected finding. The authors cautioned that their results may underestimate the actual risks due to possible underreporting of second cancers.