Session Item

Hodgkin lymphoma (HL) is a highly curable hematological neoplasia. Consolidation radiation therapy techniques have made significant progresses to reduce late radiation-induced toxicity. Recent technical breakthroughs notably include intensity modulated proton therapy (IMPT), which has demonstrated a major dosimetric benefit at the cardiac level for mediastinal HL patients. However, its implementation in clinical practice is still challenging due to the current shortage of proton therapy facilities and the increased cost of this technique. In this context. The purpose of this study is to propose a general frame for mediastinal HL patient selection strategy for IMPT, taking into account patient clinical characteristics and overall IMPT treatment availability.

We included 20 HL patients treated with VMAT. IMPT plans were generated on initial simulation scans. Dose to the heart, to the left ventricle and to the valves were retrieved to calculate the relative risk (RR) of ischemic heart disease (IHD), congestive heart failure (CHF) and valvular disease (VD). Composite relative risk reduction (cRRR) of late cardiotoxicity between IMPT and VMAT were calculated as weighted means of relative risk reduction for IHD, CHF and VD, across a wide range of cardiovascular risk factors, using the initial RR with VMAT as ponderations factors. The proportion of mediastinal HL patients who could benefit from IMPT was estimated in European countries, based on the population and the number of active gantries, to propose country-specific cRRR threshold for patient selection.

Twenty patients were treated between January 2018 and May 2020 at Institut Curie (Paris, France). Compared with VMAT, IMPT significantly reduced mean dose to the heart (1.79 Gy vs 0.88 Gy, p<0.01), to the left ventricle (0.59 Gy vs 0.02, p<0.01) and to the valves (1.36 Gy vs. 0.03, p<0.01). For a HL patient without cardiovascular risk factor treated with anthracycline, the relative risks of late cardiovascular complication were significantly higher after VMAT compared with IMPT for ischemic heart disease (median 1.13 vs. 1.07, p<0.01), for congestive heart failure (2.98 vs. 2.84, p=0.01), and for valvular disease (1.03 vs. 1.01, p=0.05). Considering all possible combination of cardiovascular risk factor, the median cumulative relative risk reduction (cRRR) with IMPT was 4.2%, ranging between 0.1% and 30.3%. The estimation of the proportion of HL patients currently treatable with IMPT in European countries (with proton therapy centers) ranged between 8% for Italy and 100% for Denmark, corresponding to cRRR threshold between 20% and 0%.

This multi-parameter selection strategy for HL protontherapy, taking simultaneously into consideration patient clinical characteristics and national treatment capacity, allows flexible patient selection in case of IMPT availability shortage and might be readily implemented for other tumor types.