Short-course neoadjuvant radiotherapy combined with chemotherapy and toripalimab for locally advanced esophageal squamous cell carcinoma (SCALE-1): a single-arm phase Ib clinical trial.

BACKGROUND: The optimal dosages, timing, and treatment sequencing for standard-of-care neoadjuvant chemoradiotherapy necessitate re-evaluation when used in conjunction with immune checkpoint inhibitors for patients with resectable, locally advanced esophageal squamous cell carcinoma (RLaESCC). The SCALE-1 phase Ib study aimed to evaluate the safety and efficacy of short-course neoadjuvant radiotherapy combined with chemotherapy and toripalimab in this patient population. METHODS: RLaESCC patients with clinical stages cT3-4aN0M0/cT1-4aN+M0 received neoadjuvant paclitaxel (135 mg/m2), carboplatin (area under the curve=5), and toripalimab (240 mg) every 3 weeks for two cycles. Short-course neoadjuvant radiotherapy (30 Gy in 12 fractions; 5 days per week) was administered between neoadjuvant immune-chemotherapy (nICT) doses. Esophagectomies were scheduled 4-6 weeks after completing neoadjuvant treatment. The primary endpoint was safety, with secondary endpoints including pathological complete response (pCR) rate, postoperative complications, progression-free survival (PFS), and overall survival (OS). Exploratory biomarker analysis used gene expression profiles via the nCounter platform. RESULTS: Of the 23 patients enrolled, all completed neoadjuvant radiotherapy, while 21 cases finished full nICT doses and cycles. Common grade 3/4 adverse events included neutropenia (57%), leukopenia (39%), and skin rash (30%). No grade 3 or higher esophagitis or pneumonitis occured. Twenty patients underwent surgery, and 11 achieved pCR (55%). Two patients (10%) experienced grade IIIb surgical complications. At the database lock, a 2-year PFS rate of 63.8% (95% CI 43.4% to 84.2%) and 2-year OS rate was 78% (95% CI 64.9% to 91.1%) were achieved. Tumor immune microenvironment analysis indicated that tumors with pCR exhibited significantly higher pretreatment T-cell-inflamed score and post-treatment reshaping of antitumor immunity. CONCLUSIONS: Combining short-course neoadjuvant radiotherapy with chemotherapy and toripalimab demonstrated favorable safety and promising efficacy in RLaESCC patients. TRIAL REGISTRATION NUMBER: ChiCTR2100045104.

Quality of life and survival outcomes of patients with inoperable esophageal squamous cell carcinoma after definitive radiation therapy: A multicenter retrospective observational study in China from 2015 to 2016.

Objectives: To investigate the health-related quality of life (HRQL) of long-term survivors of inoperable esophageal squamous cell carcinoma (ESCC) treated with definitive radiation therapy, the real-world trends in the use of advanced radiation techniques, and their impact on the survival outcomes of ESCC patients. Methods: In this multicenter retrospective observational study, the medical records related to demographics and treatment of ESCC patients who were treated with definitive radiation therapy at 14 provincial hospitals in China from 1 January 2015 to 31 December 2016 were analyzed. A HRQL questionnaire was completed by survivors and collected by doctors at the final follow-up. The difference in quality of life between patients with or without recurrence was compared using the Wilcoxon-Mann-Whitney test. Overall survival (OS) was estimated using the Kaplan-Meier method and the group differences were assessed by unstratified log-rank test. The Cox proportional hazards model with Efron's method of tie handling was used to calculate the risk factors for OS. Results: The data of a total of 3,308 patients were collected for this study, 248 were excluded because of missing data, and a final of 3,060 patients were included in the analysis. Most patients (2,901; 94.8%) received intensity-modulated radiotherapy (IMRT)/volumetric-modulated arc therapy (VMAT)/tomotherapy (TOMO). The 5-year OS rate was 30%. Patients who received either two-dimensional radiotherapy (2DRT; HR, 2.43 [95% CI, 1.70-3.47]; P < 0.001) or three-dimensional radiotherapy (3DRT; HR, 1.45 [95% CI, 1.14-1.84]; P = 0.003) had a significantly increased risk of death compared to those who received IMRT/VMAT/TOMO. Of the 716 (23.4%) long-term survivors who completed the HRQL questionnaire, nearly 70% patients were still able to swallow normally or almost normally, and >80% patients did not experience weight loss. Nearly 80% patients found life very enjoyable or were fairly enjoying life. Conclusions: This large, multicenter retrospective study on ESCC patients who received definitive radiation therapy found that most ESCC survivors are satisfied with their quality of life. Most patients received advanced radiation technology. Patients who received either 2DRT or 3DRT had a significantly increased risk of death compared to those who received advanced radiation technology.