Advances in neoadjuvant therapy for locally advanced resectable esophageal cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

KANG Xiaozheng , ZHANG Ruixiang , WANG Zhen , CHEN Xiankai , LI Yong , QIN Jianjun ,  LI Yin

Department of Thoracic Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, P. R. China;

Corresponding author：

LI Yin, Email: liyin@cicams.ac.cn

Keywords：

Esophageal cancer; Neoadjuvant therapy; Esophagectomy; Review

DOI：

10.7507/1007-4848.202408066

Video：

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Abstract Full text Figures/Tables Video References Cited by

Neoadjuvant therapy has become the standard treatment for locally advanced resectable esophageal cancer, significantly improving long-term survival compared with surgery alone. Neoadjuvant therapy has evolved to include various strategies, such as concurrent chemoradiotherapy, chemotherapy, immunotherapy, or targeted combination therapy. This enriches clinical treatment options and provides a more personalized and scientific treatment approach for patients. This article aims to comprehensively summarize current academic research hot topics, review the rationale and evaluation measures of neoadjuvant therapy, discuss challenges in restaging methods after neoadjuvant therapy, and identify the advantages and disadvantages of various neoadjuvant therapeutic strategies.

1.	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2.	Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent, 2024, 4(1): 47-53.
3.	Zhu H, Ma X, Ye T, et al. Esophageal cancer in China: Practice and research in the new era. Int J Cancer, 2023, 152(9): 1741-1751.
4.	He Y, Liang D, Du L, et al. Clinical characteristics and survival of 5 283 esophageal cancer patients: A multicenter study from eighteen hospitals across six regions in China. Cancer Commun (Lond), 2020, 40(10): 531-544.
5.	van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med, 2012, 366(22): 2074-2084.
6.	Eyck BM, van Lanschot JJB, Hulshof MCCM, et al. Ten-year outcome of neoadjuvant chemoradiotherapy plus surgery for esophageal cancer: The randomized controlled CROSS trial. J Clin Oncol, 2021, 39(18): 1995-2004.
7.	Byrd DR, Brierley JD, Baker TP, et al. Current and future cancer staging after neoadjuvant treatment for solid tumors. CA Cancer J Clin, 2021, 71(2): 140-148.
8.	Brierley JD, Greene FL, Sobin LH, et al. The "y" symbol: An important classification tool for neoadjuvant cancer treatment. Cancer, 2006, 106(11): 2526-2527.
9.	Donato BB, Campany ME, Brady JT, et al. Complete pathologic response in esophageal adenocarcinoma: Does it make a difference? Dis Esophagus, 2024, 22: doae068.
10.	Henckens SPG, Liu D, Gisbertz SS, et al. Prognostic value of Mandard score and nodal status for recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma. Br J Surg, 2024, 111(2): znae034.
11.	Cools-Lartigue J, Markar S, Mueller C, et al. An international cohort study of prognosis associated with pathologically complete response following neoadjuvant chemotherapy versus chemoradiotherapy of surgical treated esophageal adenocarcinoma. Ann Surg, 2022, 276(5): 799-805.
12.	de Gouw DJJM, Klarenbeek BR, Driessen M, et al. Detecting pathological complete response in esophageal cancer after neoadjuvant therapy based on imaging techniques: A diagnostic systematic review and meta-analysis. J Thorac Oncol, 2019, 14(7): 1156-1171.
13.	Hu Y, Xie C, Yang H, et al. Assessment of intratumoral and peritumoral computed tomography radiomics for predicting pathological complete response to neoadjuvant chemoradiation in patients with esophageal squamous cell carcinoma. JAMA Netw Open, 2020, 3(9): e2015927.
14.	Wang J, Zhu X, Zeng J, et al. Using clinical and radiomic feature-based machine learning models to predict pathological complete response in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation. Eur Radiol, 2023, 33(12): 8554-8563.
15.	Liu Y, Wang Y, Wang X, et al. MR radiomics predicts pathological complete response of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy: A multicenter study. Cancer Imaging, 2024, 24(1): 16.
16.	Eyck BM, Onstenk BD, Noordman BJ, et al. Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal cancer: A systematic review and meta-analysis. Ann Surg, 2020, 271(2): 245-256.
17.	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.
18.	van der Wilk BJ, Eyck BM, Doukas M, et al. Residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer: Locations undetected by endoscopic biopsies in the preSANO trial. Br J Surg, 2020, 107(13): 1791-1800.
19.	van der Wilk BJ, Eyck BM, Wijnhoven BPL, et al. LBA75 Neoadjuvant chemoradiotherapy followed by surgery versus active surveillance for oesophageal cancer (SANO-trial): A phase-Ⅲ stepped-wedge cluster randomised trial. Ann Oncol, 2023, 34(Supplement_3): S1317.
20.	van der Zijden CJ, Lagarde SM, Hermus M, et al. A prospective cohort study on active surveillance after neoadjuvant chemoradiotherapy for esophageal cancer: Protocol of surgery as needed for oesophageal cancer-2. BMC Cancer, 2023, 23(1): 327.
21.	Zhang X, Eyck BM, Yang Y, et al. Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): A prospective multicenter diagnostic cohort study. BMC Cancer, 2020, 20(1): 194.
22.	中华医学会外科学分会腹腔镜与内镜外科学组, 中国研究型医院学会机器人与腹腔镜外科专业委员会, 中国抗癌协会腔镜与机器人外科分会, 等. 腹腔镜胃癌手术操作指南(2023版). 中华消化外科杂志, 2023, 22(4): 425-436.Chinese Society of Laparoscopic and Endoscopic Surgery, Chinese Surgical Society, Chinese Medical Association, Robotic and Laparoscopic Surgery Committee of Chinese Research Hospital Association, et al. Guideline for laparoscopic gastrectomy for gastric cancer (2023 edition). Chin J Pract Surg, 2023, 22(4): 425-436.
23.	Convie L, Thompson RJ, Kennedy R, et al. The current role of staging laparoscopy in oesophagogastric cancer. Ann R Coll Surg Engl, 2015, 97(2): 146-150.
24.	Halle-Smith JM, Bage T, Kamarajah SK, et al. A preoperative predictive tool to assess the need for staging laparoscopy in oesophagogastric cancer patients. Ann R Coll Surg Engl, 2024, 106(4): 369-376.
25.	Krasna MJ, Reed CE, Jaklitsch MT, et al. Thoracoscopic staging of esophageal cancer: a prospective, multiinstitutional trial. Cancer and Leukemia Group B Thoracic Surgeons. Ann Thorac Surg, 1995, 60(5): 1337-1340.
26.	Fujii Y, Daiko H, Kubo K, et al. Non-curative resection for surgical T4b esophageal cancer: Esophagectomy or non-esophagectomy? Langenbecks Arch Surg, 2023, 408(1): 201.
27.	Shapiro J, van Lanschot JJB, Hulshof MCCM, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): Long-term results of a randomised controlled trial. Lancet Oncol, 2015, 16(9): 1090-1098.
28.	Oppedijk V, van der Gaast A, van Lanschot JJ, et al. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J Clin Oncol, 2014, 32(5): 385-391.
29.	Eyck BM, Gao X, Yang Y, et al. Pathological response to neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma: Multicentre East Asian and Dutch database comparison. Br J Surg, 2022, 109(12): 1312-1318.
30.	Yang H, Liu H, Chen Y, et al. Neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus (NEOCRTEC5010): A phase Ⅲ multicenter, randomized, open-label clinical trial. J Clin Oncol, 2018, 36(27): 2796-2803.
31.	Yang H, Liu H, Chen Y, et al. Long-term efficacy of neoadjuvant chemoradiotherapy plus surgery for the treatment of locally advanced esophageal squamous cell carcinoma: The NEOCRTEC5010 randomized clinical trial. JAMA Surg, 2021, 156(8): 721-729.
32.	Liu S, Wen J, Yang H, et al. Recurrence patterns after neoadjuvant chemoradiotherapy compared with surgery alone in oesophageal squamous cell carcinoma: Results from the multicenter phase Ⅲ trial NEOCRTEC5010. Eur J Cancer, 2020, 138: 113-138.
33.	Kato K, Machida R, Ito Y, et al. Doublet chemotherapy, triplet chemotherapy, or doublet chemotherapy combined with radiotherapy as neoadjuvant treatment for locally advanced oesophageal cancer (JCOG1109 NExT): A randomised, controlled, open-label, phase 3 trial. Lancet, 2024, 404(10447): 55-66.
34.	Tang H, Wang H, Fang Y, et al. Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: A prospective multicenter randomized clinical trial. Ann Oncol, 2023, 34(2): 163-172.
35.	Reynolds JV, Preston SR, O'Neill B, et al. Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): An open-label, randomised, phase 3 trial. Lancet Gastroenterol Hepatol, 2023, 8(11): 1015-1027.
36.	Hoeppner J, Brunner T, Lordick F, et al. Prospective randomized multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (ESOPEC trial). J Clin Oncol, 2024, 42(17_suppl): LBA1-LBA1.
37.	康晓征, 张瑞祥, 王镇, 等. 从肿瘤异质性视角看局部进展期食管鳞癌围手术期治疗策略的优化. 中华胃肠外科杂志, 2023, 26(4): 334-338.Kang XZ, Zhang RX, Wang Z, et al. Optimization of perioperative treatment strategies for locally advanced esophageal squamous cell carcinoma from the perspective of tumor heterogeneity. Chin J Gastrointest Surg, 2023, 26(4): 334-338.
38.	Qin J, Xue L, Hao A, et al. Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: The randomized phase 3 ESCORT-NEO/NCCES01 trial. Nat Med, 2024.
39.	Shitara K, Rha SY, Wyrwicz LS, et al. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): An interim analysis of the multicentre, double-blind, randomised phase 3 study. Lancet Oncol, 2024, 25(2): 212-224.
40.	Lorenzen S, Götze TO, Thuss-Patience P, et al. Perioperative atezolizumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable esophagogastric cancer: interim results from the randomized, multicenter, phase Ⅱ/Ⅲ DANTE/IKF-s633 trial. J Clin Oncol, 2024, 42(4): 410-420.
41.	Janjigian YY, Al-Batran SE, Wainberg ZA, et al. LBA73 pathological complete response (pCR) to durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Interim results of the global, phase Ⅲ MATTERHORN study. Ann Oncol, 2023, 34(2_suppl): S1315-S1316.
42.	Eads JR, Graham N, Gibson MK, et al. A phase Ⅱ/Ⅲ study of peri-operative nivolumab (NIVO) and ipilimumab (IPI) in patients (PTS) with locoregional esophageal (E) and gastroesophageal junction (GEJ) adenocarcinoma: Results of the neoadjuvant pathologic complete response (pCR) rate (ECOG-ACRIN EA2174). J Clin Oncol, 2024, 42(16_suppl): 4000-4000.
43.	Safran HP, Winter K, Ilson DH, et al. Trastuzumab with trimodality treatment for oesophageal adenocarcinoma with HER2 overexpression (NRG Oncology/RTOG 1010): A multicentre, randomised, phase 3 trial. Lancet Oncol, 2022, 23(2): 259-269.
44.	Clements HA, Underwood TJ, Petty RD. Total neoadjuvant therapy in oesophageal and gastro-oesophageal junctional adenocarcinoma. Br J Cancer, 2024, 130(1): 9-18.
45.	国家癌症中心, 中国医师协会胸外科医师分会, 中华医学会胸心血管外科学分会, 等. 食管癌及食管胃交界部癌外科持续质量改进目标中国专家共识(2024版). 中华医学杂志, 2024, 104(20): 1804-1811.National Cancer Center Chinese Association of Thoracic Surgeons, Chinese Society for Thoracic and Cardiovascular Surgery, Chinese Society for Diseases of the Esophagus, et al. Chinese expert consensus on surgical continuous quality improvement goals in esophageal cancer and esophagogastric junction cancer (2024 edition). Nat Med J China, 2024, 104(20): 1804-1811.

1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2. Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent, 2024, 4(1): 47-53.
3. Zhu H, Ma X, Ye T, et al. Esophageal cancer in China: Practice and research in the new era. Int J Cancer, 2023, 152(9): 1741-1751.
4. He Y, Liang D, Du L, et al. Clinical characteristics and survival of 5 283 esophageal cancer patients: A multicenter study from eighteen hospitals across six regions in China. Cancer Commun (Lond), 2020, 40(10): 531-544.
5. van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med, 2012, 366(22): 2074-2084.
6. Eyck BM, van Lanschot JJB, Hulshof MCCM, et al. Ten-year outcome of neoadjuvant chemoradiotherapy plus surgery for esophageal cancer: The randomized controlled CROSS trial. J Clin Oncol, 2021, 39(18): 1995-2004.
7. Byrd DR, Brierley JD, Baker TP, et al. Current and future cancer staging after neoadjuvant treatment for solid tumors. CA Cancer J Clin, 2021, 71(2): 140-148.
8. Brierley JD, Greene FL, Sobin LH, et al. The "y" symbol: An important classification tool for neoadjuvant cancer treatment. Cancer, 2006, 106(11): 2526-2527.
9. Donato BB, Campany ME, Brady JT, et al. Complete pathologic response in esophageal adenocarcinoma: Does it make a difference? Dis Esophagus, 2024, 22: doae068.
10. Henckens SPG, Liu D, Gisbertz SS, et al. Prognostic value of Mandard score and nodal status for recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma. Br J Surg, 2024, 111(2): znae034.
11. Cools-Lartigue J, Markar S, Mueller C, et al. An international cohort study of prognosis associated with pathologically complete response following neoadjuvant chemotherapy versus chemoradiotherapy of surgical treated esophageal adenocarcinoma. Ann Surg, 2022, 276(5): 799-805.
12. de Gouw DJJM, Klarenbeek BR, Driessen M, et al. Detecting pathological complete response in esophageal cancer after neoadjuvant therapy based on imaging techniques: A diagnostic systematic review and meta-analysis. J Thorac Oncol, 2019, 14(7): 1156-1171.
13. Hu Y, Xie C, Yang H, et al. Assessment of intratumoral and peritumoral computed tomography radiomics for predicting pathological complete response to neoadjuvant chemoradiation in patients with esophageal squamous cell carcinoma. JAMA Netw Open, 2020, 3(9): e2015927.
14. Wang J, Zhu X, Zeng J, et al. Using clinical and radiomic feature-based machine learning models to predict pathological complete response in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation. Eur Radiol, 2023, 33(12): 8554-8563.
15. Liu Y, Wang Y, Wang X, et al. MR radiomics predicts pathological complete response of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy: A multicenter study. Cancer Imaging, 2024, 24(1): 16.
16. Eyck BM, Onstenk BD, Noordman BJ, et al. Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal cancer: A systematic review and meta-analysis. Ann Surg, 2020, 271(2): 245-256.
17. 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.
18. van der Wilk BJ, Eyck BM, Doukas M, et al. Residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer: Locations undetected by endoscopic biopsies in the preSANO trial. Br J Surg, 2020, 107(13): 1791-1800.
19. van der Wilk BJ, Eyck BM, Wijnhoven BPL, et al. LBA75 Neoadjuvant chemoradiotherapy followed by surgery versus active surveillance for oesophageal cancer (SANO-trial): A phase-Ⅲ stepped-wedge cluster randomised trial. Ann Oncol, 2023, 34(Supplement_3): S1317.
20. van der Zijden CJ, Lagarde SM, Hermus M, et al. A prospective cohort study on active surveillance after neoadjuvant chemoradiotherapy for esophageal cancer: Protocol of surgery as needed for oesophageal cancer-2. BMC Cancer, 2023, 23(1): 327.
21. Zhang X, Eyck BM, Yang Y, et al. Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): A prospective multicenter diagnostic cohort study. BMC Cancer, 2020, 20(1): 194.
22. 中华医学会外科学分会腹腔镜与内镜外科学组, 中国研究型医院学会机器人与腹腔镜外科专业委员会, 中国抗癌协会腔镜与机器人外科分会, 等. 腹腔镜胃癌手术操作指南(2023版). 中华消化外科杂志, 2023, 22(4): 425-436.Chinese Society of Laparoscopic and Endoscopic Surgery, Chinese Surgical Society, Chinese Medical Association, Robotic and Laparoscopic Surgery Committee of Chinese Research Hospital Association, et al. Guideline for laparoscopic gastrectomy for gastric cancer (2023 edition). Chin J Pract Surg, 2023, 22(4): 425-436.
23. Convie L, Thompson RJ, Kennedy R, et al. The current role of staging laparoscopy in oesophagogastric cancer. Ann R Coll Surg Engl, 2015, 97(2): 146-150.
24. Halle-Smith JM, Bage T, Kamarajah SK, et al. A preoperative predictive tool to assess the need for staging laparoscopy in oesophagogastric cancer patients. Ann R Coll Surg Engl, 2024, 106(4): 369-376.
25. Krasna MJ, Reed CE, Jaklitsch MT, et al. Thoracoscopic staging of esophageal cancer: a prospective, multiinstitutional trial. Cancer and Leukemia Group B Thoracic Surgeons. Ann Thorac Surg, 1995, 60(5): 1337-1340.
26. Fujii Y, Daiko H, Kubo K, et al. Non-curative resection for surgical T4b esophageal cancer: Esophagectomy or non-esophagectomy? Langenbecks Arch Surg, 2023, 408(1): 201.
27. Shapiro J, van Lanschot JJB, Hulshof MCCM, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): Long-term results of a randomised controlled trial. Lancet Oncol, 2015, 16(9): 1090-1098.
28. Oppedijk V, van der Gaast A, van Lanschot JJ, et al. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J Clin Oncol, 2014, 32(5): 385-391.
29. Eyck BM, Gao X, Yang Y, et al. Pathological response to neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma: Multicentre East Asian and Dutch database comparison. Br J Surg, 2022, 109(12): 1312-1318.
30. Yang H, Liu H, Chen Y, et al. Neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus (NEOCRTEC5010): A phase Ⅲ multicenter, randomized, open-label clinical trial. J Clin Oncol, 2018, 36(27): 2796-2803.
31. Yang H, Liu H, Chen Y, et al. Long-term efficacy of neoadjuvant chemoradiotherapy plus surgery for the treatment of locally advanced esophageal squamous cell carcinoma: The NEOCRTEC5010 randomized clinical trial. JAMA Surg, 2021, 156(8): 721-729.
32. Liu S, Wen J, Yang H, et al. Recurrence patterns after neoadjuvant chemoradiotherapy compared with surgery alone in oesophageal squamous cell carcinoma: Results from the multicenter phase Ⅲ trial NEOCRTEC5010. Eur J Cancer, 2020, 138: 113-138.
33. Kato K, Machida R, Ito Y, et al. Doublet chemotherapy, triplet chemotherapy, or doublet chemotherapy combined with radiotherapy as neoadjuvant treatment for locally advanced oesophageal cancer (JCOG1109 NExT): A randomised, controlled, open-label, phase 3 trial. Lancet, 2024, 404(10447): 55-66.
34. Tang H, Wang H, Fang Y, et al. Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: A prospective multicenter randomized clinical trial. Ann Oncol, 2023, 34(2): 163-172.
35. Reynolds JV, Preston SR, O'Neill B, et al. Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): An open-label, randomised, phase 3 trial. Lancet Gastroenterol Hepatol, 2023, 8(11): 1015-1027.
36. Hoeppner J, Brunner T, Lordick F, et al. Prospective randomized multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (ESOPEC trial). J Clin Oncol, 2024, 42(17_suppl): LBA1-LBA1.
37. 康晓征, 张瑞祥, 王镇, 等. 从肿瘤异质性视角看局部进展期食管鳞癌围手术期治疗策略的优化. 中华胃肠外科杂志, 2023, 26(4): 334-338.Kang XZ, Zhang RX, Wang Z, et al. Optimization of perioperative treatment strategies for locally advanced esophageal squamous cell carcinoma from the perspective of tumor heterogeneity. Chin J Gastrointest Surg, 2023, 26(4): 334-338.
38. Qin J, Xue L, Hao A, et al. Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: The randomized phase 3 ESCORT-NEO/NCCES01 trial. Nat Med, 2024.
39. Shitara K, Rha SY, Wyrwicz LS, et al. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): An interim analysis of the multicentre, double-blind, randomised phase 3 study. Lancet Oncol, 2024, 25(2): 212-224.
40. Lorenzen S, Götze TO, Thuss-Patience P, et al. Perioperative atezolizumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable esophagogastric cancer: interim results from the randomized, multicenter, phase Ⅱ/Ⅲ DANTE/IKF-s633 trial. J Clin Oncol, 2024, 42(4): 410-420.
41. Janjigian YY, Al-Batran SE, Wainberg ZA, et al. LBA73 pathological complete response (pCR) to durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Interim results of the global, phase Ⅲ MATTERHORN study. Ann Oncol, 2023, 34(2_suppl): S1315-S1316.
42. Eads JR, Graham N, Gibson MK, et al. A phase Ⅱ/Ⅲ study of peri-operative nivolumab (NIVO) and ipilimumab (IPI) in patients (PTS) with locoregional esophageal (E) and gastroesophageal junction (GEJ) adenocarcinoma: Results of the neoadjuvant pathologic complete response (pCR) rate (ECOG-ACRIN EA2174). J Clin Oncol, 2024, 42(16_suppl): 4000-4000.
43. Safran HP, Winter K, Ilson DH, et al. Trastuzumab with trimodality treatment for oesophageal adenocarcinoma with HER2 overexpression (NRG Oncology/RTOG 1010): A multicentre, randomised, phase 3 trial. Lancet Oncol, 2022, 23(2): 259-269.
44. Clements HA, Underwood TJ, Petty RD. Total neoadjuvant therapy in oesophageal and gastro-oesophageal junctional adenocarcinoma. Br J Cancer, 2024, 130(1): 9-18.
45. 国家癌症中心, 中国医师协会胸外科医师分会, 中华医学会胸心血管外科学分会, 等. 食管癌及食管胃交界部癌外科持续质量改进目标中国专家共识(2024版). 中华医学杂志, 2024, 104(20): 1804-1811.National Cancer Center Chinese Association of Thoracic Surgeons, Chinese Society for Thoracic and Cardiovascular Surgery, Chinese Society for Diseases of the Esophagus, et al. Chinese expert consensus on surgical continuous quality improvement goals in esophageal cancer and esophagogastric junction cancer (2024 edition). Nat Med J China, 2024, 104(20): 1804-1811.

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