Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

Background: Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens. Methods: In a Dutch cohort of 3121 5-year HL survivors treated between 1965 and 1995, subsite-specific CRC incidence was compared with general population rates. Treatment effects were quantified by Cox regression analyses. Results: After a median follow-up of 22.9 years, 55 patients developed CRC. The standardized incidence ratios (SIR) was 2.4-fold increased (95% confidence interval (95% CI) 1.8-3.2), leading to 5.7 excess cases per 10 000 patient-years. Risk was still increased 30 years after HL treatment (SIR: 2.8; 95% CI: 1.6-4.6). The highest (SIR: 6.5, 95% CI: 3.3-11.3) was seen for transverse colon cancer (15.0 (95% CI: 4.3-40.8) after inverted-Y irradiation). A prescribed cumulative procarbazine dose >4.2 g (-)2 was associated with a 3.3-fold higher CRC risk (95% CI: 1.8-6.1) compared to treatment without procarbazine. Patients receiving >4.2 gm(-2) procarbazine and infradiaphragmatic radiotherapy had a hazard ratio of 6.8 (95% CI: 3.0-15.6) compared with patients receiving neither treatment, which is significantly higher than an additive joint effect (P-additivity = 0.004). Conclusions: Colorectal cancer surveillance should be considered for HL survivors who received Infradiaphragmatic radiotherapy and a high cumulative procarbazine dose.