Bi-Institutional Report on Consolidative Proton Therapy after Initial Chemotherapy for Mediastinal Diffuse Large B-Cell and Primary Mediastinal Large B-Cell Lymphomas

Abstract

Combined modality therapy with R-CHOP (rituximab, cyclophosphamide, vincristine, prednisone) and radiation is a standard treatment option for mediastinal aggressive non-Hodgkin lymphomas (MANHL), however very intense “radiation-free” chemotherapy is gaining in use, in part due to concern over radiation toxicity. We investigated early outcomes for patients receiving chemotherapy followed by consolidative proton therapy (PT) in these pts with mediastinal lymphoma, a group of patients that have been shown to derive dosimetric benefit from PT compared to photon-based techniques. From 2011-2017, 24 adult patients with MANHL (either primary mediastinal large B cell lymphomas or mediastinal diffuse large B cell lymphoma) enrolled on either institutional review board-approved outcomes tracking protocols or registry studies received consolidative PT after first-line chemotherapy with R-CHOP (16 pts) or R-CHP-brentuximab vedotin (8 pts) at two academic institutions. Six cycles were given in 22 pts, and 4 cycles in 2 pts. Patients with relapsed disease at the time of PT were excluded. The majority were male (58%) with a median age of 36 [range 22-72]. Stage distribution included 10 stage I, 9 stage II, 3 stage III, and 2 Stage IV with 42% with B symptoms and 33% with extranodal involvement. The majority (87.5%) had disease that measured at least 7.5 cm before chemotherapy, with a median maximum dimension of 12 cm [range 4-23 cm]. Involved-site radiotherapy target volumes were used for all patients. Pts received a median dose of 30.6 Gy(RBE) [range 30–39.6 Gy(RBE)]. Pencil beam scanning was used in 33%, deep inspiratory breath hold was used in 33%, and both were used in 12.5%. Follow-up time was defined as time from start of PT to event or last follow-up. The median follow-up was 28 months (range, 1.2–76 months). The majority (75%) of pts were in complete metabolic response before PT with Deauville Score (DS) of 1 or 2, however 21% had DS4, none of whom relapsed. Of the 24 pts, there was only 1 local failure that occurred 19 months after PT within the high dose region in a pt with DS1. One patient relapsed below the diaphragm at 20 months. The one pt who had DS5 after chemotherapy died 11 months after PT with relapse in the hilum (out of field) and infradiaphragmatic. Consolidative PT was given 3 months after chemotherapy in this patient. The median mean lung dose was 6.7 Gy(RBE) [range 2.3-16.8], median lung V5 was 30% [range 12-59], median lung V20 was 16% [range 4-40]. The median mean heart dose was 10.9 Gy(RBE) [range 0.01-16.9]. None had grade 2 or higher radiation pneumonitis. Consolidative involved site PT following standard chemotherapy in aggressive mediastinal B cell lymphomas results in excellent local control (96%) with minimal toxicity in this bi-institutional early report.