BackgroundNeoadjuvant immunotherapy with anti-PD-1 was proved promising in resectable non-small cell lung cancer (NSCLC). Immune-related adverse events (irAEs) have been preliminarily implicated their association with treatment efficacy. Here we elucidated the early onset of irAEs associated with better clinical outcomes in a prospective study (Renaissance study).MethodsWe conducted the prospective study of NSCLC patients treated by neoadjuvant Toripalimab (240mg, every 3 weeks) plus double platinum-based chemotherapy from December 2020 to March 2022 at Peking University Cancer Hospital. Patients were enrolled if they have resectable IIB-IIIB NSCLC without EGFR/ALK mutation. Data were analyzed to explore the relationship between clinical outcome and irAEs after neoadjuvant treatment. A multidisciplinary team including physicians, surgeons, and radiologists, confirmed the irAEs according to the clinical manifestation. The relationship between irAEs and pathological outcomes was analyzed. The Renaissance study was approved by the Peking University Ethic board (2020YJZ58) and registered athttps://clinicaltrials.gov/as NCT04606303.ResultsFifty-five consecutive patients were enrolled with a male-to-female ratio of 10:1, the median age was 62 years old (IQR: 45-76), of which 44 patients (80%) were diagnosed with squamous cell carcinoma. Forty-eight of 55 patients finally received thoracic surgery with a median preoperative waiting time of 67 days (IQR 39-113 days). Pathological results demonstrated that 31 (64.6%) patients achieved major pathological response (MPR) and 24 (50.0%) achieved complete pathological response (pCR). Among 48 patients who received R0 resection, immunotherapy-related thyroid dysfunction, rash/pruritus and enteritis occurred in 11 patients (22.9%), 7 patients (14.6%), and 1 patient (2.1%), respectively. Six patients (54.5%) with thyroid dysfunction achieved MPR with 5 (45.5%) achieved pCR, and a median time to onset was 45 days (IQR 21-91 days). Six patients (85.7%) with rash or pruritus achieved MPR and 5 patients (71.4%) achieved pCR, with median time to onset being 8 days (IQR 6-29 days). Furthermore, irAEs had no significant influence on operation time (170.6 min vs 165.7 min, P=0.775), intraoperative blood loss (67.4 mL vs 64.3 mL, P=0.831) and preoperative waiting time (93 days vs 97 days, P=0.630) when comparing with patients without irAEs (Figure 1).Figure 1Comparison of operation time(A), intraoperative blood loss(B), and preoperative waiting time(C)between “with irAEs” and “without irAEs”.ConclusionThe immunotherapy-related rash is potentially associated with pathological outcomes in NSCLC patients after neoadjuvant chemo-immunotherapy, suggesting easy-to-find irAEs, such as rash, can be used as indicators to predict response to neoadjuvant chemo-immunotherapy.Clinical trial registrationclinicaltrials.gov/, identifier NCT04606303.