Comparison of short-term efficacy of neoadjuvant immunotherapy combined with chemotherapy and neoadjuvant chemoradiation for locally advanced resectable esophageal squamous cell carcinoma_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHANG Hai ¹ , LI Jingpei ² , WEN Zunbei ¹ , CAI Maode ¹ , ZHANG Kunqiang ¹ , LI Zhuoyi ² , HE Jianxing ² , LIU Jun ² ,  LIN Wanli ¹

1. Department of Thoracic Surgery, Gaozhou People's Hospital, Gaozhou, 525200, Guangdong, P. R. China;
2. Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510282, P. R. China;

Corresponding author：

LIN Wanli, Email: gdgzgg@21cn.com

Keywords：

Esophageal squamous cell carcinoma; immunotherapy; chemoradiation; pathological remission rate; neoadjuvant therapy

DOI：

10.7507/1007-4848.202105005

Video：

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Objective To investigate the short-term therapeutic effect of neoadjuvant immunotherapy combined with chemotherapy in the locally advanced esophageal squamous cell carcinoma. Methods The clinical data of patients with esophageal squamous cell carcinoma treated with neoadjuvant treatment in Gaozhou People's Hospital from August 2019 to October 2020 were retrospectively analyzed. According to the different treatments, the patients were divided into two groups: a neoadjuvant immunotherapy combined with chemotherapy group (NIC group) and a neoadjuvant chemoradiotherapy group (NC group). The baseline data, incidence of adverse events during treatment, perioperative indicators, postoperative pathological remission rate and incidence of postoperative complications were compared between the two groups. Results Totally 33 patients were enrolled, including 15 males and 18 females, with an average age of 62.37±7.99 years. There were 17 patients in the NIC group and 16 patients in the NC group. In the NIC group, the carcinoma was mainly located in the middle and lower esophagus, with 5 paitents in stage Ⅱ, 9 patients in stage Ⅲ, and 3 patients in stage Ⅳa. In the NC group, the carcinoma was mainly located in the upper-middle esophagus, with 1 patient in stage Ⅱ and 15 patients in stage Ⅲ. During the neoadjuvant treatment, there was no significant difference in the occurrence of bone marrow suppression or gastrointestinal reactions between the two groups (P>0.05). There were 4 immune-related rashes in the NIC group and 1 esophageal perforation in the NC group. Fourteen (82.35%) patients in the NIC group and 12 (75.00%) patients in the NC group completed the operation on schedule. The postoperative ICU stay time and chest tube indwelling time in the NIC group were shorter than those in the NC group (P<0.05). There were 5 patients of complete remission in the NIC group, and 6 patients in the NC group. There was no significant difference in the pathological regression grade or residual tumor cells between the two groups (P>0.05). There was no significant difference in the incidence of anastomotic fistula, thoracic gastric fistula, bronchial mediastinal fistula, abdominal distension, pulmonary infection, stroke, or hoarseness during the perioperative period between the two groups of patients who completed the operation (P>0.05). In the NC group, 2 patients died during the perioperative period because of thoracic gastric fistula complicated by severe infection. Conclusion Neoadjuvant immunotherapy combined with chemotherapy dose not significantly increase the occurrence of adverse events and shows a good rate of pathological remission, which indicates that the neoadjuvant immunotherapy combined with chemotherapy is a safe, feasible and potential new treatment model.

Citation： ZHANG Hai, LI Jingpei, WEN Zunbei, CAI Maode, ZHANG Kunqiang, LI Zhuoyi, HE Jianxing, LIU Jun, LIN Wanli. Comparison of short-term efficacy of neoadjuvant immunotherapy combined with chemotherapy and neoadjuvant chemoradiation for locally advanced resectable esophageal squamous cell carcinoma. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2023, 30(9): 1261-1266. doi: 10.7507/1007-4848.202105005 Copy

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11.	Kudo T, Hamamoto Y, Kato K, et al. Nivolumab treatment for oesophageal squamous-cell carcinoma: An open-label, multicentre, phase 2 trial. Lancet Oncol, 2017, 18(5): 631-639.
12.	Kelly RJ, Smith KN, Anagnostou V, et al. Neoadjuvant nivolumab plus concurrent chemoradiation in stage Ⅱ/Ⅲ esophageal/gastroesophageal junction cancer. J Clin Oncol, 2019, 37: 142.
13.	Noordman BJ, Spaander MCW, Valkema R, et al. Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): A prospective multicentre, diagnostic cohort study. Lancet Oncol, 2018, 19(7): 965-974.
14.	Gray JE, Villegas A, Daniel D, et al. Three-year overall survival with durvalumab after chemoradiotherapy in stage Ⅲ NSCLC: Update from PACIFIC. J Thorac Oncol, 2020, 15(2): 288-293.
15.	Alsaab HO, Sau S, Alzhrani R, et al. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: Mechanism, combinations, and clinical outcome. Front Pharmacol, 2017, 8: 561.
16.	Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer, 2012, 12(4): 252-264.
17.	Shu CA, Gainor JF, Awad MM, et al. Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: An open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol, 2020, 21(6): 786-795.
18.	Van Der Kraak L, Goel G, Ramanan K, et al. 5-Fluorouracil upregulates cell surface B7-H1 (PD-L1) expression in gastrointestinal cancers. J Immunother Cancer, 2016, 4: 65.
19.	Kim JH, Park HE, Cho NY, et al. Characterisation of PD-L1-positive subsets of microsatellite-unstable colorectal cancers. Br J Cancer, 2016, 115(4): 490-496.
20.	Vanderwalde A, Spetzler D, Xiao N, et al. Microsatellite instability status determined by next-generation sequencing and compared with PD-L1 and tumor mutational burden in 11348 patients. Cancer Med, 2018, 7(3): 746-756.
21.	Vivaldi C, Catanese S, Massa V, et al. Immune checkpoint inhibitors in esophageal cancers: Are we finally finding the right path in the mist? Int J Mol Sci, 2020, 21(5): 1658.
22.	Watanabe M, Otake R, Kozuki R, et al. Recent progress in multidisciplinary treatment for patients with esophageal cancer. Surg Today, 2020, 50(1): 12-20.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. 张思维, 郑荣寿, 左婷婷, 等. 中国食管癌死亡状况和生存分析. 中华肿瘤杂志, 2016, 38(9): 709-715.
3. Lagergren J, Smyth E, Cunningham D, et al. Oesophageal cancer. Lancet, 2017, 390(10110): 2383-2396.
4. Kojima T, Shah MA, Muro K, et al. Randomized phase Ⅲ KEYNOTE-181 study of pembrolizumab versus chemotherapy in advanced esophageal cancer. J Clin Oncol, 2020, 38(35): 4138-4148.
5. Kato K, Shah MA, Enzinger P, et al. KEYNOTE-590: Phase Ⅲ study of first-line chemotherapy with or without pembrolizumab for advanced esophageal cancer. Future Oncol, 2019, 15(10): 1057-1066.
6. Thompson JA, Schneider BJ, Brahmer J, et al. NCCN guidelines insights: Management of immunotherapy-related toxicities, version 1. 2020. J Natl Compr Canc Netw, 2020, 18(3): 230-241.
7. Schwartz LH, Litière S, de Vries E, et al. RECIST 1. 1-Update and clarification: From the RECIST committee. Eur J Cancer, 2016, 62: 132-137.
8. Zanoni A, Verlatoa G, Minicozzi A, et al. Prognostic significance of the mandard TRG classification after induction therapy in carcinoma of the oesophagus and cardia. Chir Ital, 2009, 61(4): 419-425.
9. Doi T, Piha-Paul SA, Jalal SI, et al. Safety and antitumor activity of the anti-programmed death-1 antibody pembrolizumab in patients with advanced esophageal carcinoma. J Clin Oncol, 2018, 36(1): 61-67.
10. Shah MA, Kojima T, Hochhauser D, et al. Efficacy and safety of pembrolizumab for heavily pretreated patients with advanced, metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: The phase 2 KEYNOTE-180 study. JAMA Oncol, 2019, 5(4): 546-550.
11. Kudo T, Hamamoto Y, Kato K, et al. Nivolumab treatment for oesophageal squamous-cell carcinoma: An open-label, multicentre, phase 2 trial. Lancet Oncol, 2017, 18(5): 631-639.
12. Kelly RJ, Smith KN, Anagnostou V, et al. Neoadjuvant nivolumab plus concurrent chemoradiation in stage Ⅱ/Ⅲ esophageal/gastroesophageal junction cancer. J Clin Oncol, 2019, 37: 142.
13. Noordman BJ, Spaander MCW, Valkema R, et al. Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): A prospective multicentre, diagnostic cohort study. Lancet Oncol, 2018, 19(7): 965-974.
14. Gray JE, Villegas A, Daniel D, et al. Three-year overall survival with durvalumab after chemoradiotherapy in stage Ⅲ NSCLC: Update from PACIFIC. J Thorac Oncol, 2020, 15(2): 288-293.
15. Alsaab HO, Sau S, Alzhrani R, et al. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: Mechanism, combinations, and clinical outcome. Front Pharmacol, 2017, 8: 561.
16. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer, 2012, 12(4): 252-264.
17. Shu CA, Gainor JF, Awad MM, et al. Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: An open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol, 2020, 21(6): 786-795.
18. Van Der Kraak L, Goel G, Ramanan K, et al. 5-Fluorouracil upregulates cell surface B7-H1 (PD-L1) expression in gastrointestinal cancers. J Immunother Cancer, 2016, 4: 65.
19. Kim JH, Park HE, Cho NY, et al. Characterisation of PD-L1-positive subsets of microsatellite-unstable colorectal cancers. Br J Cancer, 2016, 115(4): 490-496.
20. Vanderwalde A, Spetzler D, Xiao N, et al. Microsatellite instability status determined by next-generation sequencing and compared with PD-L1 and tumor mutational burden in 11348 patients. Cancer Med, 2018, 7(3): 746-756.
21. Vivaldi C, Catanese S, Massa V, et al. Immune checkpoint inhibitors in esophageal cancers: Are we finally finding the right path in the mist? Int J Mol Sci, 2020, 21(5): 1658.
22. Watanabe M, Otake R, Kozuki R, et al. Recent progress in multidisciplinary treatment for patients with esophageal cancer. Surg Today, 2020, 50(1): 12-20.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Comparison of short-term efficacy of neoadjuvant immunotherapy combined with chemotherapy and neoadjuvant chemoradiation for locally advanced resectable esophageal squamous cell carcinoma

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