Radiotherapy for Patients with Locally Advanced Esophageal Squamous Cell Carcinoma Receiving Neoadjuvant Immunotherapy Combined with Chemotherapy

Abstract

With the success of immunotherapy in advanced esophageal cancer, neoadjuvant chemo-immunotherapy (CIT) is being increasingly used for local staged esophageal cancer, especially in the context of clinical trials, which brings similar pCR with neoadjuvant chemoradiotherapy and shows promising results. However, there is still a part of potentially operable patients can't undergo surgery after neoadjuvant chemo-immunotherapy. The follow-up treatment and prognosis of this population remain unclear. Patients pathologically diagnosed with ESCC, clinical stage T1-3N+M0 or T3-4aNanyM0(AJCC 8th), PS 0-1 were retrospectively enrolled from 1/2020 to 6/2021 in Zhejiang Cancer Hospital. All patients firstly received PD-1 inhibitors (Camrelizumab, Sintilimab or Tislelizumab) plus chemotherapy (albumin paclitaxel,260 mg/m²on day 1 plus carboplatin AUC = 5 on day 1) every 3 weeks for 2-4 cycles. For those patients who did not receive surgery, definitive radiotherapy with 50.4Gy/28F or 50Gy/25F was adopted using VMAT, concurrent with chemotherapy or alone. The concurrent chemotherapy regimens included weekly TC (paclitaxel 50 mg/m 2, d1, carboplatin AUC = 2, d1) or S1 (60mg bid d1-14,29-42). The survival outcomes and treatment toxicity were recorded and analyzed. A total of 56 eligible patients were finally identified from 558 patients who were treated in department of thoracic surgery, 31 patients showed no response to neoadjuvant CIT (6 with PD and 25 with SD), 25 patients achieved PR but did not receive surgery due to poor performance status or refuse to operation. Median age was 66(IQR 56-72) and 55(98.2%) were males. 12(19.6%) were stage II and 44(80.4%) were stage III. Among all the patients,25 (44.6%) received radiotherapy alone, and 31 (55.4%) received chemoradiotherapy after neoadjuvant CIT. The median follow-up was 11.8 months (IQR 8.6-20.1). The median PFS and OS were 16.5 months (95CI 12.9-21.4) and 18.6 months (95CI 11.2-NA), respectively. In the subgroup analysis, the median PFS for patients with PR to CIT was 20.2 moths (95CI:17.23-NA), and 12.9 moths (95CI: 0.68-20.4) for patients with SD or PD, HR was 0.45 (95CI:0.22- 0.93, P = 0.027). No significant difference was observed for patients received radiotherapy alone or chemoradiotherapy with HR = 1.36(95CI:0.69-2.71, P = 0.37). The most common AEs observed during this study were anemia (98.2%), Leukopenia (83.9%), Thrombocytopenia (53.6%). Adverse events of grade≥3 radiation-induced pneumonitis and esophagitis were 12.5% and 32.1%, especially, 6 patients (10.7%) died from esophageal fistula and 2 patients (3.6%) died from grade 5 pneumonitis. For local advanced ESCC patients after neoadjuvant CIT who did not receive surgery, definitive radiotherapy was an optional treatment strategy. However, those patients with no response to CIT also showed poor response to radiotherapy, and particular attention should be paid to treatment related toxicity, especially esophageal fistula.