Definitive radiation as a nonsurgical option after chemoimmunotherapy for stage III lung cancer.

8072 Background: The immunotherapy era has led to a resurgence of interest in surgical management of clinical Stage III non-small cell lung cancer (NSCLC). However, patient eligibility or interest in surgery may decline after neoadjuvant treatment, leaving many in need of a non-operative form of local therapy. Here we evaluate outcomes of definitive radiation after chemoimmunotherapy as a potential nonsurgical option for stage III NSCLC patients. Methods: Clinical Stage III lung adenocarcinoma and squamous cell carcinoma patients diagnosed in the National Cancer Database between 2017 and 2021 who received chemoimmunotherapy followed by thoracic radiation within 20 weeks were included. Patients receiving any palliative therapies were excluded. Three-year overall survival was assessed by Cox proportional hazards models and by the Kaplan-Meier method, after landmarking at 10 weeks (median time from immunotherapy to radiation). Propensity-matching was performed 2:1 on year, age, sex, race/ethnicity, Charlson-Deyo score, insurance, region, facility type, histology, and clinical T and N stage. Results: 873 patients were treated with radiation after chemoimmunotherapy. Over 90% received a total radiation dose of at least 50 Gy, and 90-day mortality after initiation of radiation was 4.9%. To evaluate radiation as a local therapy after chemoimmunotherapy, these patients were compared to those who received chemoimmunotherapy only (Table). Patients receiving radiation were less likely to have T4 tumors (37.7% vs. 44.2%, p<0.0001) but had a similar proportion of N3 tumors (28.2% vs. 29.9%, p=0.73) compared to chemoimmunotherapy alone. Three-year overall survival of propensity-matched patients was superior in the radiation group (50.8%) versus chemoimmunotherapy alone (35.9%, p<0.001). In a Cox model, the addition of radiation was associated with lower mortality risk (HR 0.66, 95% 0.58-0.84, p<0.0001) compared to chemoimmunotherapy alone. Conclusions: Radiation after chemoimmunotherapy appears to be a safe and effective regimen for Stage III NSCLC. Further study is indicated to evaluate radiation as a nonsurgical option for clinical stage III patients who begin with chemoimmunotherapy but do not progress to surgery. Characteristics and survival of patients receiving chemoimmunotherapy with or without subsequent radiation. Chemoimmunotherapy followed by radiation(n=873) Chemoimmunotherapy only (n=1408) P (Chi-squared or Wilcoxon rank sum) Age (median, IQR) 67 (60-73) 69 (62-75) <0.0001 Female 369 (42.3%) 667 (47.4%) 0.02 Charlson-Deyo ≥ 2 131 (15.0%) 242 (17.2%) 0.34 Adenocarcinoma 463 (54.0%) 886 (62.9%) <0.0001 Stage 3A 350 (40.1%) 579 (41.1%) 0.78 Stage T4 329 (37.7%) 622 (44.2%) 0.0022 Stage N3 255 (29.2%) 421 (29.9%) 0.73 3-Year Survival* 489 (56.0%) 630 (44.7%) <0.0001 For reference: 3-year survival of immunotherapy after chemoradiation for Stage III NSCLC in the PACIFIC trial was 57%.