Pneumonitis after Palliative Thoracic Radiotherapy +/- Immunotherapy: A Retrospective Propensity-Matched Cohort Study

Abstract

Patients (pts) with advanced lung cancer often receive combined palliative thoracic radiotherapy (RT) and immune checkpoint inhibitors (ICI). There are limited data assessing the toxicities of combined ICI-RT in this setting. We sought to compare the rates of clinically significant pneumonitis among pts with lung cancer receiving palliative thoracic RT with or without recent or concomitant ICI. We hypothesized there would be a higher rate of grade 2+ pneumonitis among RT pts who received recent or concomitant ICI compared to those who did not. We retrospectively identified consecutive pts with advanced/recurrent lung cancer from a tertiary academic center who received palliative thoracic RT with recent (defined as within 95 days of RT start) or concomitant ICI (ICI-RT group) between January 2014 and February 2020. Pts were propensity matched in a 1:1 manner (by age, sex, ECOG, RT modality, and RT dose) to lung cancer pts who received palliative thoracic RT without any history of ICI receipt (RT-only group). The presence and grade (CTCAE v5.0) of pneumonitis were independently assessed by two investigators. The primary endpoint was grade 2+ pneumonitis, estimated using the cumulative incidence function and compared between the ICI-RT and RT-only groups using Gray's test. The secondary endpoint was overall survival, estimated using the Kaplan-Meier method and compared between groups using the log-rank test. A total of 146 pts were included in the study (73 in each group). There were no statistically significant differences between the ICI-RT and RT-only groups with respect to age (median 67.7 vs. 67.6, p = 0.97), sex (52% vs. 52% female, p = 1.00), pre-treatment ECOG 0-1 (74% vs 75%, p = 0.85), or biologically effective dose greater than 45 (48% vs. 48%, p = 1.00). The most common RT regimens were 30 Gy in 10 fractions (33 pts, 23%) and 20 Gy in 5 fractions (18 patients, 12%). A plurality of cases utilized 3DCRT (67 pts, 46%). In the ICI-RT group, the median time from last dose of ICI to the start of palliative RT was 16 days; three pts in this group-initiated ICI while receiving RT treatment. The most common ICI was pembrolizumab (36 pts, 49%). A total of eleven grade 2+ pneumonitis events (nine grade 2 and two grade 3 events) were observed. The ICI-RT group had a higher cumulative incidence of grade 2+ pneumonitis compared with the RT-only group (1-year rate, 12.3% vs. 2.7%, p = 0.029); grade 3 pneumonitis occurred in 1/73 (1.4%) in each group. There was no difference in overall survival between groups (median 239 vs. 218 days, p = 0.76). In pts with advanced lung cancer treated with palliative thoracic RT, recent or concomitant ICI use was associated with a higher cumulative incidence of grade 2+ pneumonitis. However, the incidence of grade 3+ pneumonitis was low (1.4%) regardless of ICI receipt.