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

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 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.

Risk of subsequent colorectal cancers after a solid tumor in childhood: Effects of radiation therapy and chemotherapy

“…The observed increased crude risk ratio and the statistically nonsignificant higher adjusted risk ratio for MOPP could be attributable to procarbazine (Table : model 2). Procarbazine which is administered orally and is fully absorbed in the gastrointestinal tract has been linked with gastrointestinal carcinogenesis in previous papers . Based on our novel findings, we believe that the monitoring guidelines for CRC need to update, and childhood cancer survivors who received < 30 Gy radiation doses (ranging from 5 to 29.99 Gy) to the abdomen should also be prioritized for colorectal cancer screening for many years after childhood cancer treatment.…”

High prevalence of advanced colorectal neoplasia and serrated polyposis syndrome in Hodgkin lymphoma survivors

“…14,[17][18][19] We, therefore, now include advanced serrated lesions within the definition of advanced colorectal neoplasia. 9 In the current study, we did not have sufficient patient numbers to evaluate the prevalence of advanced colorectal neoplasia before the age of 40 years. 25,26 Based on the results of this interim analysis, sufficient evidence is provided to currently consider a colonoscopy surveillance program for HL survivors.…”

“…22,24 Recent literature and recent guidelines of both the European Society of Gastrointestinal Endoscopy and the US Multi-Society Task Force on Colorectal Cancer acknowledge that similarly to advanced adenomas, serrated lesions that have dysplasia and/or are at least 10 mm in size should be approached as high-risk lesions. [3][4][5]9 Because HL survivors have an increased risk of advanced colorectal neoplasia from the age of 40 years and CRC risk is especially increased in HL patients treated before the age of 35 years, we recommend that surveillance start not later than the age of 40 years. 16,20 The current Dutch CRC screening program with biennial fecal immunochemical testing has insufficient sensitivity for advanced adenomas and especially for advanced serrated lesions for this high-risk group.…”

Second cancers in Hodgkin's lymphoma long-term survivals: A 60-year single institutional experience with real-life cohort of 871 patients

“…Modern radiotherapy (with so called involved‐node and involved‐site RT) considers multimodal imaging as well as anatomic changes during therapy . With these new approaches, comparing to some older techniques as mantel filed technique or inverted‐Y irradiation, one may expect reduced risk of radiotherapy induced SC in the future . Reduced dose to 20 Gy comparing to 30 Gy in early stage HL was also shown noninferior is some randomised clinical trials .…”

“…16 Current renaissance in immunotherapy will subsequently influence the treatment results and possibly the risk of SC, similarly as in novel treatment approaches in solid cancers. 5,17,18 On the basis of our initial analysis of HL survivors, 19 we suggested special follow-up schema for patients after initial HL treatment and utilised this approach in last decade finding it possible, effective and 21 one may expect reduced risk of radiotherapy induced SC in the future. 6,14,15,22,23 Reduced dose to 20 Gy comparing to 30 Gy in early stage HL was also shown noninferior is some randomised clinical trials.…”