Session Item

Hodgkin lymphoma (HL) survivors have an increased risk of colorectal cancer (CRC), which may be due to abdominal radiotherapy (RT) and/or chemotherapy, particularly alkylating agents. This study aimed to quantify CRC risk according to estimated radiation dose to colon segments and dose of specific chemotherapeutic agents.

We conducted a nested case-control study among five-year HL survivors diagnosed before age 51, treated between 1965 and 2000. Patient and treatment information was abstracted from hospital records for 78 CRC cases and 238 matched controls. Patients were typically treated using megavoltage parallel opposed fields, with slipzones between sequentially treated supra- and infra-diaphragmatic fields. Mean radiation dose to colon segments (caecum, ascending, hepatic flexure, transverse, splenic flexure, descending, sigmoid and rectum) was estimated by reconstruction of individual RT treatments on representative computed tomography datasets. Relative risks (RRs) were estimated using conditional logistic regression.

The median interval between HL and CRC diagnosis was 25.7 years (range 5.3-41.9). Patients who received infradiaphragmatic RT (48 (62%) cases, 97 (41%) controls) had a 2.4-fold (95% confidence interval (CI) 1.4-4.1) increased risk of CRC. The mean dose to the affected colon segment was 12.6Gy in cases compared to 7.6Gy to matched locations in controls (P_difference 0.005). Increased CRC risks were also seen for patients who received >5.6g/m² procarbazine (RR 2.6, 95% CI 1.4-4.7). Risk of CRC increased linearly with increasing radiation dose to the affected colon segment, with an excess relative risk (ERR) per Gy of 0.075  (95% CI 0.023-0.18). The association between radiation dose and CRC risk was modified by procarbazine dose; the ERR/Gy was 0.022 for patients who received no procarbazine and increased 17% per 1g/m² increase in cumulative dose (Figure 1). Treatment with anthracyclines (RR 1.0, 95% CI 0.5-2.0), any alkylating chemotherapy (RR 1.6, 95% CI 0.9-2.9) or splenectomy (RR 1.1, 95% CI 0.6-2.0) was not associated with increased CRC risk. 

This is the first time that a dose-response relationship linking radiation dose and cumulative procarbazine dose with risk of CRC  has been demonstrated. The effect of RT was modified by procarbazine, with a significantly elevated risk of CRC only seen in those who received higher radiation dose to the colon in addition to high doses of procarbazine. Our dose-response relationships will enable individualised estimation of CRC risk for people treated for HL in the modern era. Such data can inform discussions about the risks of RT and chemotherapy, and allow selection of the optimal treatment strategy for individual patients, as well as characterisation of high risk survivors.