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

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. In a Dutch cohort of 3121...

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Bibliographic Details
Published in:	British journal of cancer 2017-07, Vol.117 (3), p.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:	Article
Language:	eng
Subjects:	Adult Antineoplastic Agents - administration & dosage Antineoplastic Combined Chemotherapy Protocols - therapeutic use Bleomycin - therapeutic use Cancer therapies Chemotherapy Clinical Study Colon Colon cancer Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - epidemiology Colorectal Neoplasms - etiology Diaphragm Doxorubicin - therapeutic use Female Follow-Up Studies Health risks Hodgkin Disease - drug therapy Hodgkin Disease - radiotherapy Hodgkin's lymphoma Humans Incidence Irradiation Lymphoma Male Mechlorethamine - therapeutic use Middle Aged Neoplasms, Radiation-Induced - epidemiology Neoplasms, Radiation-Induced - etiology Neoplasms, Second Primary - epidemiology Neoplasms, Second Primary - etiology Netherlands - epidemiology Prednisone - therapeutic use Procarbazine Procarbazine - administration & dosage Procarbazine - therapeutic use Radiation Radiation therapy Rectum Risk Factors Survivors Vinblastine - therapeutic use Vincristine - therapeutic use Young Adult
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Summary:	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. 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. 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 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 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 =0.004). Colorectal cancer surveillance should be considered for HL survivors who received Infradiaphragmatic radiotherapy and a high cumulative procarbazine dose.
ISSN:	0007-0920 1532-1827