| 描述信息 |
Background: In locally advanced oral squamous cell carcinoma (LAOSCC) patients, pathological response to induction therapy may translate into improved survival, and major pathologic response (MPR) is important evaluate index for pathological response. The neoadjuvant immunochemotherapy (NAICT) using combination of anti-PD-1 and chemotherapy has not been well issued in LAOSCC. Methods: The prospective single arm trial (NCT04473716) has been performed to evaluate the induction therapy of anti-PD-1 (Toripalimab) and Paclitaxel/Cisplatin in LAOSCC patients at clinical stage III and IV A (AJCC 2018). The patients received two cycles of intravenous Albumin Paclitaxel (260mg/m2), Cisplatin (75mg/m2) and Toripalimab (240mg) on day 1 and day 22. Radical surgery was performed on day 43-56 (within two weeks of induction therapy). Post-operative radiotherapy or chemoradiotherapy was planned on within 1.5 months after surgery, based on clinical and pathological stage. The primary endpoints of the trial were MPR and safety. Primary tumors were assessed for the percentage of residual viable tumor that was identified on HE staining, and tumor with no more than 10% viable tumor cell were considered as MPR. The second endpoints were the rates of 2-year survival, local recurrence and adverse events. Targeted NGS and MIF were performed to assess the clinical molecular characteristics and tumor immune microenvironment in the pre- and post-NAICT tumor samples, respectively. This study has been approved by institutional ethics committee at Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. Results: From November 2020 to April 2021, 20 LAROSCC patients were enrolled, including 16 males and 4 females, aged from 19 to 75 years. NAICT was well-tolerated with low incidence of grade 3-4 adverse events (AEs) in three patients (15%), including neutropenia, leukopenia, hypokalemia, vomiting, and rash. All AEs were relieved after expectant treatment, without delay of surgery. Using pathological evaluation for NAICT, the MPR rate was 60% (12/20), including 30% (6/20) pCR. MPR was archived in all 4 patients with combined positive score of PD-L1>10. Using radiographical evaluation, there were 10% of CR and 50% of PR. The pathological and radiographical response was consistent in linear regression analysis (P<0.001). The pathological response pattern to NAICT was scatter pattern in 92.9% (13/14) of patients, with multiple residual foci. Patients with higher TMB and more immune activation cells in biopsies tended to show higher MPR rate, respectively. More tertiary lymphoid structure was found in the post-NAICT surgical specimens than pre-NAICT biopsies (P=0.03), especially in the MPR group (P=0.009). During 18 months median follow-up, the disease-free survival was 90% and overall survival was 95%. Conclusions: NAICT with TTP protocol in LAROSCC is feasible and well tolerated, with a promising MPR. It should be cautious to narrow the scope of tumor resection when archiving MPR. This trial is provocative to support further personalized randomized trials using NAICT in LAROSCC. |
