Risk of pneumonitis and outcomes after mediastinal proton therapy for relapsed/refractory lymphoma: A PTCOG and PCG collaboration


Int J Radiat Oncol Biol Phys. 2020 Aug 28:S0360-3016(20)34202-4. doi: 10.1016/j.ijrobp.2020.08.055. Online ahead of print.


PURPOSE: Despite high response rates, there has been reluctance to use radiotherapy for patients with relapsed/refractory (r/r) Hodgkin (HL) or aggressive non-Hodgkin lymphoma (NHL) given concerns for subacute and late toxicities. Symptomatic pneumonitis, a subacute toxicity, has an incidence of 17-24% (>=grade 2) even with intensity modulated radiotherapy. Proton therapy (PT), which has no exit radiation dose, is associated with lower dose to lung compared to other radiation techniques. As risk of radiation pneumonitis is associated with lung dose, we evaluated whether pneumonitis rates are lower with PT.

METHODS AND MATERIALS: Within an international, multi-institutional cohort, we retrospectively evaluated the incidence and grade of radiation pneumonitis (CTCAEv4) among patients with r/r HL or NHL treated with PT.

RESULTS: 85 patients with r/r lymphoma (66% HL, 34% NHL; 46% primary chemorefractory) received thoracic PT from 2009-2017 in the consolidation (45%) or salvage (54%) setting. Median dose was 36 Gy(RBE). Prior to PT, patients underwent a median of 1 salvage systemic therapy (range 0-4); 40% received PT within 4 months of transplant. With a median follow-up of 26.3 months among living patients, 11 patients developed symptomatic (grade 2) pneumonitis (12.8%). No grade 3 or higher pneumonitis was observed. Dose to lung, including mean lung dose, lung V5 and V20, significantly predicted risk of symptomatic pneumonitis, but not receipt of brentuximab, history of bleomycin toxicity, gender, or peri-transplant radiation.

CONCLUSIONS: PT for relapsed/refractory lymphoma was associated with favorable rates of pneumonitis compared to historical controls. We confirm that among patients treated with PT, pneumonitis risk is associated with mean lung and lung V20 dose. These findings highlight how advancements in radiation delivery may improve the therapeutic ratio for patients with relapsed/refractory lymphoma. PT may be considered as a treatment modality for patients with relapsed/refractory lymphoma in the

consolidation or salvage setting.