Safety And Tolerability Of Neoadjuvant Chemoradiotherapy Combined With Pembrolizumab For Local Advanced, Resectable Esophageal Cancer: Preliminary Results Of A Prospective Phase IB Trial

Abstract Background Nowadays, it has emerged that conventional neoadjuvant chemotherapy for locally borderline resectable esophageal cancer is not effective. However, it still remains controversial which treatment is best. We aimed to evaluate neoadjuvant chemoradiotherapy for locally borderline resectable esophageal cancer. Methods Twenty six patients (23 men, 3 women) who underwent esophagectomy after neoadjuvant chemoradiotherapy between January 2011 and December 2016 were subjected. Radiotherapy was administered at 40 Gy with concurrent chemotherapy which consisted of 5-fluorouracil and cisplatin for all 26 patients. The therapeutic effect of neoadjuvant chemoradiotherapy and surgical outcomes including rates of curative resection and pathological complete response, and postoperative complications were retrospectively reviewed. Postoperative complications were defined as any event requiring specific medical or surgical treatment, which were assessed by the Clavien-Dindo classification. The evaluation criteria of neoadjuvant chemoradiotherapy were assessed by the RECIST guideline (ver.1.1). Results For primary tumor, 24 patients showed partial response and 2 showed stable disease. Therefore, the response rate to the primary tumor was 92.3%. For metastatic lymph nodes, on the other hand, 11 patients showed partial response and 8 showed stable disease and 1 showed progressive disease, and the response rate was 55%. Two patients were unresectable, three patients had R2 resection, and the remaining 21 patients (81%) had curative resection (R0). In the R0 resected group, the 5-year survival rate was 57%. The median operative time, bleed loss, and postoperative hospital stays were 546 minutes (178–963), 720ml (262–5170) and 34days (17–99), respectively. Postoperative complications were observed in 22 patients. The incidences of more than grade2 postoperative pneumonia, vocal cord palsy, and anastomosis leakage were 8/26 (31%), 8/26 (31%) and 3/26 (12%). There were treatment-related mortality in 2 patients. Seven patients (27%) achieved histologically complete response. Conclusion Neoadjuvant chemoradiotherapy for locally borderline resectable esophageal cancer is effective in increasing curative resection rate. In addition, patients who underwent curative resection can expect long-term survival. Disclosure All authors have declared no conflicts of interest.

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Preoperative chemoradiation and cetuximab for resectable, locally advanced esophageal cancer: Preliminary results of a prospective phase Ib/II trial.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e14571 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e14571-e14571

Author(s):

Baruch Brenner ◽

Yulia Kundel ◽

Ofer Purim ◽

Gal Medalia ◽

Liran Olshinka ◽

...

Keyword(s):

Esophageal Cancer ◽

Phase Ii ◽

Local Control ◽

Locally Advanced ◽

Preoperative Chemoradiation ◽

Advanced Esophageal Cancer ◽

Phase Ib ◽

Preliminary Results ◽

Prospective Phase ◽

Locally Advanced Esophageal Cancer

e14571 Background: This prospective phase IB/II study evaluated the safety and efficacy of the addition of cetuximab to standard preoperative chemoradiation (CRT) in locally advanced esophageal cancer (LAEC). We hereby report its preliminary results. Methods: Patients (pts) with potentially resectable LAEC, defined as T2-4N0-1M0, T1-4N1M0 or T1-4N0-1M1A tumors, received an induction cycle of cisplatin 100 mg/m2, day 1, and 5-FU 1000 mg/m2/day as a continuous infusion (CI), days 1–5, followed 4 weeks later by 50.4 Gy radiotherapy (RT) given concurrently with 2 cycles of cisplatin 75 mg/m2 and escalating doses of CI 5-FU, days 1–4 and 29-32. Pts received also 10 weekly infusions of cetuximab, 250 mg/m2, with a loading dose of 400 mg/m2, starting from the induction. The phase II part of the study started when the 5-FU dose during CRT was defined. Surgery was planned 6-8 weeks after CRT. Results: Thirty-six pts have been enrolled to date and 32 completed CRT. The median age was 65 years and 60% were males. The ratio of squamous/adeno histologies was 53%/47%. Pts had very advanced tumors: 95% T3-T4, 63% N1 and 28% M1A. In the absence of dose limiting toxicity, 31 pts received the phase II dose of 5-FU, defined as 1000 mg/m2/day. The most common grade >3 toxicities were leucopenia (51% of pts) and neutropenia (48%). There was one toxic death, due to neutropenic sepsis. Among the 27 operated pts, R0 resection was achieved in 24 (89%). There were 4 cases (15%) of postoperative mortality, due to infection (3 pts) or respiratory failure (1). Downstaging was noted in 83% of pts and pathological complete response (pCR) in 32%. Pts with squamous histology had a higher pCR rate (53% vs 7%, p=0.007). At the time of the analysis, 14 pts (40%) remain free of disease and the local control rate is 92%. Updated results will be presented at the meeting. Conclusions: Preliminary results from this prospective study suggest that the addition of cetuximab to standard CRT is safe. The R0, pCR and local control rates are encouraging. Squamous cell tumors may gain more benefit from the addition of cetuximab.

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The Optimal Treatment for Resectable Esophageal Cancer: A Network Meta-Analysis of 6168 Patients

Frontiers in Oncology ◽

10.3389/fonc.2021.628706 ◽

2021 ◽

Vol 11 ◽

Author(s):

Meng Yuan ◽

Yongxing Bao ◽

Zeliang Ma ◽

Yu Men ◽

Yang Wang ◽

...

Keyword(s):

Esophageal Cancer ◽

Meta Analysis ◽

Neoadjuvant Chemoradiotherapy ◽

Disease Free Survival ◽

Optimal Treatment ◽

Cochrane Library ◽

Neoadjuvant Radiotherapy ◽

Free Survival ◽

Resectable Esophageal ◽

Resectable Esophageal Cancer

The optimal treatment for resectable esophageal cancer remains unclear. This network meta-analysis compares the efficacy of different treatments. PubMed, Embase, and the Cochrane library were systematically screened. Randomized controlled trials comparing the efficacy of different treatments for resectable esophageal cancer were included. Hazard ratios (HR) for overall survival (OS), progression-free survival, or disease-free survival, and odds ratios for locoregional recurrence and distant metastasis rates were identified as the measurements of efficacy. A Bayesian network meta-analysis was performed. In this study, 26 studies were included. Patients received either surgery alone; neoadjuvant chemotherapy (CT), neoadjuvant radiotherapy (RT), or neoadjuvant chemoradiotherapy (CRT) followed by surgery; or surgery followed by adjuvant CT, adjuvant RT, or adjuvant CRT. Neoadjuvant CRT followed by surgery (pooled HR = 0.76, 95% credible interval: 0.67–0.85) and neoadjuvant CT followed by surgery compared with surgery alone were the only two showing statistically confident improvement on OS. Ranking analysis showed that neoadjuvant CRT with surgery was likely to be the best option in terms of efficacy. Therefore, for patients with resectable esophageal cancer, neoadjuvant CRT with surgery is the optimal treatment. Future studies should focus on the optimization of neoadjuvant CRT regimens.

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