Proton therapy in supradiaphragmatic lymphoma: predicting treatment-related mortality to help optimize patient selection

Abstract

Purpose: In some Hodgkin lymphoma (HL) patients, proton beam therapy (PBT) may reduce the risk of radiation-related cardiovascular disease (CVD) and second cancers (SC) compared with photon radiotherapy (photon-RT). Our aim was to identify those who benefit most from PBT in terms of predicted 30-year absolute mortality risks (AMR30) from CVD and SC, taking into account individual background, chemotherapy, radiation and smoking-related risks. Methods and materials: Eighty patients with supradiaphragmatic HL treated with PBT during 2015-2019 were re-planned using optimal photon-RT. To identify patients predicted to derive the greatest benefit from PBT compared to Photon-RT, doses and AMR30 from CVD and SC of the lung, breast and esophagus were compared for all patients and across patient subgroups. Results: For patients with mediastinal disease below the origin of the left main coronary artery (n=66, 82%), PBT reduced mean dose to heart, left ventricle and heart valves by 1.0, 2.7 and 3.6 Gray (Gy) respectively. Based on US mortality rates, PBT reduced CVD AMR30 by 0.2%, from 5.9% to 5.7%. The benefit was larger if the mediastinal disease overlapped longitudinally with the heart by ≥40% (n=23, 29%), where PBT reduced mean dose to heart, left ventricle and heart valves by 3.2, 5.6, and 5.1Gy respectively, and reduced CVD AMR30 by 0.8%, from 7.0% to 6.2%. For patients with axillary disease (n=25, 31%), PBT reduced mean lung dose by 2.8Gy and lung cancer AMR30 by 0.6%, from 2.7% to 2.1%. Breast and esophageal doses were also lower with PBT but effects on AMR30 were negligible. The effect of smoking on CVD and lung cancer AMR30 was much larger than radiation and chemotherapy and the differences between radiation modalities. Conclusions: The predicted benefit of PBT is not universal and is limited to certain categories of lymphoma patients with lower mediastinal or axillary disease. Smoking cessation should be strongly encouraged in smokers requiring thoracic radiotherapy.