Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors
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
(2017) British Journal of Cancer, volume 117, issue 3, pp. 306 - 314
(Article)
Abstract
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
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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 (Padditivity=0.004). CONCLUSIONS: Colorectal cancer surveillance should be considered for HL survivors who received Infradiaphragmatic radiotherapy and a high cumulative procarbazine dose.
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Keywords: Adult, Antineoplastic Agents/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Bleomycin/therapeutic use, Colon, Colorectal Neoplasms/epidemiology, Diaphragm, Doxorubicin/therapeutic use, Female, Follow-Up Studies, Hodgkin Disease/drug therapy, Humans, Male, Mechlorethamine/therapeutic use, Middle Aged, Neoplasms, Radiation-Induced/epidemiology, Neoplasms, Second Primary/epidemiology, Netherlands/epidemiology, Prednisone/therapeutic use, Procarbazine/administration & dosage, Rectum, Risk Factors, Survivors, Vinblastine/therapeutic use, Vincristine/therapeutic use, Young Adult, Taverne
ISSN: 0007-0920
Publisher: Nature Publishing Group
(Peer reviewed)