Second cancer after the treatment for Hodgkin's disease: a report from the International Database on Hodgkin's Disease

Abstract

Twenty institutions/cooperative groups tabulated second cancers among 12,411 patients diagnosed with Hodgkin's disease between 1960 and 1987, giving 82,850 person-years of observation. Overall, 631 second cancers were observed, as compared with 223.25 expected (observed (O) to expected (E) ratio 2.83, p<0.001) at least one year after the diagnosis of Hodgkin's disease. Second cancers were acute leukaemia.s (AL) in 158 cases as compared with 5.75 expected (O/E = 27.48, p <0.001), non-Hodgkin's lymphomas (NHL.) in 106 cases as compared with 3.34 expected (O/E 31.77, p<0.001), and solid tumors (ST) in 367 cases as compared with 214.16 expected (O/E = 1.71, p<0.001), with no differences between males and females. Excess of ST was observed for the following anatomic sites: salivary gland, small intestine, colon, bronchus, pleura, bone, skin other than melanoma and thyroid in males; salivary gland, bronchus, pleura, skin other than melanoma and breast in females. While the excess of second AL and NHL was significant over the 1–14 year period after the start of initial therapy, that of second ST became apparent after the fifth year, increasing with time. Overall, the 15-year cumula tive incidence rate of second cancer was 11.2%. It was 2.2%, 1.8% and 7.5% for second AL, NHL and ST, respectively. While the cumulative incidence of AL and NHL plateaued after 17 years, that of ST was still increasing. To analyse whether a particular treatment category was associated with an increased risk of second cancer, a prognostic study was performed on the 11,241 patients who achieved a complete remission and were continuously disease-free. Overall, 87 patients developed an AL, 68 a NHL, and 231 a ST. Combined modality treatments including MOPP or MOPP-like chemotherapy were associated with the higher risk of second AL (Relative risk (RR) = 17.11; p4.50; p2.50; p<0.001), splenectomy (RR = 1.65; p<0.05) and MOPP or MOPP-like chemotherapy used alone (RR = 2.20; p3.5; p<0.001), male gender (RR 1.82; p<0.05) and clinical stage III (RR 1.70; p2.80; p<0.001), as did extended field radiation therapy (RR = 1.84; p<0.001) and combined modality treatment including MOPP or MOPP like chemotherapy (RR = 1.67; p <0.01). We conclude that combination of MOPP or MOPP-like chemotherapy and ir radiation for Hodgkin's disease greatly increases the risk of AL far above older age, advanced stage and splenectomy. In contrast, only age above 30 highly correlates with an in creased risk of NHL, while age above 40 and extended field radiation therapy greatly increase the risk of ST. Because the development of second cancer represents the most serious consequence of the curative therapy of Hodgkin's disease, the treatment decision should be balanced between the short, and long-term consequences of each competitive strategy available.