P40.07 Immunotherapy Toxicity in Lung Cancer & the Impact of Thoracic Radiation Therapy

Abstract

Immunotherapy is increasingly utilized either alone or in combination with chemotherapy and/or radiation therapy (RT) with improved survival. Immunotherapy related toxicity can appear similar to radiation induced toxicity. The contribution of concurrent or sequential thoracic radiation to immunotherapy related cardiopulmonary toxicity is not well understood. Current literature suggests that combination of immunotherapy and thoracic radiation does not result in an increase in high-grade toxicities, however clinicians continue to approach this combination with caution. All patients that received immunotherapy for non-small cell lung cancer (NSCLC) between 2011 and 2020 were included in the analysis. The electronic medical records were used to collect demographic, treatment, and toxicity data. RTOG toxicity scale was used to grade pneumonitis and CTCAE was used for all other toxicities. The first course of radiation therapy was used for analysis if patients received more than one course. The relationship between thoracic RT and the incidence of cardiopulmonary toxicities was evaluated through pairwise comparisons using Barnard’s exact test of three groups including: patients who received thoracic RT ³ 45 Gy, thoracic RT < 45 Gy, and those who did not receive thoracic RT. To account for the three pairwise comparisons for each toxicity class, Bonferroni adjusted p-values were utilized. Additionally, the impact of RT type (thoracic vs. nonthoracic) and total dose (³ 45 Gy vs. < 45 Gy) over multiple courses of treatment was examined. The cause specific hazard ratios for toxicity outcomes were modeled using the Cox proportional hazards model, with time of treatment initiation designated as the time of origin. Candidate variables for inclusion included: receipt of any thoracic vs. non-thoracic RT, thoracic vs. nonthoracic RT received as most recent therapy relative to time of toxicity, total thoracic RT dose (³ 45 Gy or < 45 Gy), and total non-thoracic RT dose. The toxicity outcomes (all grade occurrences and grade 3-5 events) evaluated included cardiopulmonary toxicities of any type, pleural effusions, and pneumonitis events. 251 patients met the inclusion criteria and were included in the analysis. The majority of patients were locally advanced or metastatic at presentation; 33.5% stage III & 56.6% stage IV. RT was given in 83.3% of patients and 63.7% of patients received thoracic RT. An elevated risk of grade 3-5 pleural effusions was found in patients who received thoracic RT and cumulative dose < 45 Gy, however, the group that received ³ 45 Gy did not reveal an increased risk of grade 3-5 pleural effusions. Overall, the remaining candidate variables were not found to significantly impact the evaluated toxicity outcomes (p > 0.05). An increased risk of pleural effusions was found in patients who received a prior cumulative RT dose of <45 Gy. However, overall, the results of this large single-institution retrospective review do not show an association with thoracic RT and increased risk of cardiopulmonary toxicity in patients receiving immunotherapy for NSCLC. Further dosimetric analysis will be conducted to better characterize cardiopulmonary toxicity outcomes relative to radiation dose to the heart and lung.