Neoadjuvant Immune Checkpoint Inhibitors Plus Chemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: Perioperative and Survival Outcomes

Xiao Ma; Weixin Zhao; Bin Li; Yongfu Yu; Yuan Ma; Mathew Thomas; Yawei Zhang; Jiaqing Xiang; Yiliang Zhang

doi:10.3389/fonc.2022.810898

Neoadjuvant Immune Checkpoint Inhibitors Plus Chemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: Perioperative and Survival Outcomes

Front Oncol. 2022 Jun 10:12:810898. doi: 10.3389/fonc.2022.810898. eCollection 2022.

Authors

Xiao Ma^{1

2}, Weixin Zhao^{2

3}, Bin Li^{1

2}, Yongfu Yu⁴, Yuan Ma⁵, Mathew Thomas⁶, Yawei Zhang^{1

2}, Jiaqing Xiang^{1

2}, Yiliang Zhang^{1

2}

Affiliations

¹ Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Institute of Thoracic Oncology, Fudan University, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
³ Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai Key Laboratory of Radiation Oncology, Shanghai, China.
⁴ Department of Biostatistics, The Key Laboratory of Public Health Safety of Ministry of Education, School of Public Health, Fudan University, Shanghai, China.
⁵ Chinese Institute for Brain Research, Beijing, China.
⁶ Department of Cardiothoracic Surgery, Mayo Clinic, Jacksonville, FL, United States.

Abstract

Background: Immune checkpoint inhibitors (ICI) improve survival in patients with late-stage esophageal squamous cell carcinoma (ESCC) but have not been fully evaluated in locally advanced ESCC.

Method: We retrospectively assessed outcomes of consecutive, treatment-naïve locally advanced ESCC (stage III or IVA) adults treated with neoadjuvant ICI plus chemotherapy followed by surgery, who refused or lacked access to radiotherapy, with regards to surgery feasibility, pathological response, and relapse-free survival (RFS).

Results: We uneventfully treated 34 patients with the combined regimen in 2020. None reported grade III or higher toxic effects. All underwent surgery as planned: 32 received complete (R0) resections and 2 had microscopically positive margins (R1). Tumor downstaging occurred in 33 (97.1%) patients and 11 (32.4%) had pathologically complete response of the primary lesion. Median postoperative length of stay was 12 days (interquartile range: 11 to 17). All patients resumed a semi-liquid diet on discharge. The 90-day postoperative morbidity rate was 20.6% (7/34) with no mortalities. The 1-year RFS was 77.8% [95% CI, 64.2-94.2].

Conclusion: Neoadjuvant ICI plus chemotherapy was safe and resulted in significant downstaging, rendering inoperable tumors operable, relieving symptoms of dysphagia and prolonging survival for locally advanced ESCC patients who refused or lacked access to radiotherapy.

Keywords: esophageal squamous cell carcinoma; esophagectomy; immune checkpoint inhibitor; neoadjuvant therapy; perioperative outcomes; survival outcomes.