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

• Published in: British journal of cancer Vol. 117; no. 3; pp. 306 - 314
• Main Authors: van Eggermond, Anna M, Schaapveld, Michael, Janus, Cécile PM, de Boer, Jan Paul, Krol, Augustinus DG, Zijlstra, Josée M, van der Maazen, Richard WM, Kremer, Leontien C, van Leerdam, Monique E, Louwman, Marieke WJ, Visser, Otto, De Bruin, Marie L, Aleman, Berthe MP, van Leeuwen, Flora E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.07.2017; Nature Publishing Group
• Subjects: 692/4028/67/1059/485; 692/4028/67/1504/1885; 692/4028/67/1990/291/1556; 692/499; Adult; Antineoplastic Agents - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomedical and Life Sciences; Biomedicine; Bleomycin - therapeutic use; Cancer Research; Cancer therapies; Chemotherapy; Clinical Study; Colon; Colon cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - etiology; Diaphragm; Doxorubicin - therapeutic use; Drug Resistance; Epidemiology; Female; Follow-Up Studies; Hodgkin Disease - drug therapy; Hodgkin Disease - radiotherapy; Hodgkin's lymphoma; Humans; Lymphoma; Male; Mechlorethamine - therapeutic use; Middle Aged; Molecular Medicine; Neoplasms, Radiation-Induced - epidemiology; Neoplasms, Radiation-Induced - etiology; Neoplasms, Second Primary - epidemiology; Neoplasms, Second Primary - etiology; Netherlands - epidemiology; Oncology; Prednisone - therapeutic use; Procarbazine; Procarbazine - administration & dosage; Procarbazine - therapeutic use; Radiation therapy; Rectum; Risk Factors; Survivors; Vinblastine - therapeutic use; Vincristine - therapeutic use; Young Adult; colorectal cancer; radiation therapy; chemotherapy; procarbazine; second malignant neoplasm; long-term complications; Hodgkin lymphoma
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/bjc.2017.177

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 m −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 g m −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.