The risk of second cancers (SCs) was assessed in 744 patients with Hodgkin's 
disease (HD) admitted to The Netherlands Cancer Institute from 1966 to 1983. 
Sixty-nine SCs were observed one month or more after start of first treatment. 
These included 14 cases of lung cancer, nine cases of non-Hodgkin's lymphoma 
(NHL), 16 cases of leukemia, and six cases of the myelodysplastic syndrome 
(MDS). The median interval between the diagnosis of HD and that of second lung 
cancer, NHL, and leukemia was 8.1, 13.3, and 5.7 years, respectively. The 
overall relative risks (RR) (observed/expected [O/E] ratios) of developing lung 
cancer, NHL, and leukemia were 4.9 (95% confidence limit [CL], 2.7 to 8.2), 31.0 
(95% CL, 14.2 to 58.9) and 45.7 (95% CL, 26.1 to 74.2), respectively. At 15 
years the cumulative risk of developing an SC amounted to 20.6% +/- 2.9%. The 
15-year estimates of lung cancer, NHL, and leukemia were 6.2% +/- 1.9%, 5.9% +/- 
2.1% and 6.3% +/- 1.7%, respectively. Increased lung cancer risk following HD 
has not frequently been clearly demonstrated before; that we were able to 
demonstrate such risk may be due to the completeness of follow-up over long 
periods that could be achieved in this study. Excess lung cancer risk was only 
noted in treatment regimens with radiotherapy (RT); also, all lung cancers arose 
in irradiation fields. Excess risk of leukemia was only found in treatment 
regimens involving chemotherapy (CT). For NHL, combined modality treatment was 
shown to be the most important risk factor. Risk of lung cancer and NHL 
increased with time since diagnosis. A time-dependent covariate analysis (Cox 
model) performed on leukemia and MDS showed an increasing risk with intensity of 
CT, age (greater than 40 years), and a splenectomy.