1Department of Pathology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China; 2Department of Radiation Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China; 3Department of Thoracic Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China; 4Department of Image, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China
AbstractObjective To explore the pathological differences of surgically resected specimens of advanced esophageal squamous cell carcinoma (ESCC) to different neoadjuvant therapies (neoadjuvant radiochemotherapy and toripalimab combined with neoadjuvant radiochemotherapy). Methods Thirty patients diagnosed with advanced ESCC who underwent surgical operation after neoadjuvant therapy in Jiangsu Cancer Hospital from October 2020 to September 2021 were included. Among them, 15 patients received neoadjuvant radiochemotherapy (radiochemotherapy group) and 15 patients were treated with toripalimab combined with radiochemotherapy (immunotherapy combined with radiochemotherapy group). Surgically resected specimens were collected. The histopathological features of primary esophageal lesions and the responses of involved lymph nodes were analyzed and compared between two groups. Results The major pathological response (MPR) rate in the radiochemotherapy group was 10/15, and 14/15 in the immunotherapy combined with radiochemotherapy group (P=0.17). The pathological complete response (pCR) rate of the primary lesions in the radiochemotherapy group was 7/15, and 10/15 in the immunotherapy combined with radiochemotherapy group (P=0.46). In the radiochemotherapy group, the incidence rate of tertiary lymphoid structure (TLS) was 7/15, and 12/15 in the immunotherapy combined with radiochemotherapy group (P=0.02). The incidence rate of necrosis in the radiochemotherapy group was 6/15, and 1/15 in the immunotherapy combined with radiochemotherapy group (P=0.03). In addition, the incidence rate of foam cell infiltration in the radiochemotherapy group was 6/15, and 13/15 in the immunotherapy combined with radiochemotherapy group (P=0.01). Furthermore, the pCR rate of involved lymph nodes in the radiochemotherapy group was 7/33, and 11/12 in the immunotherapy combined with radiochemotherapy group (P<0.001). Conclusion Compared with the radiochemotherapy group, the incidence of TLS and foam cell infiltration is higher, the incidence of necrosis is lower and clinical efficacy of involved lymph nodes is higher in the immunotherapy combined with radiochemotherapy group, prompting that toripalimab combined with neoadjuvant radiochemotherapy exert higher synergistic immune effect.
Wu Yi'nan,Zhang Jingyuan,Jiang Ning et al. Pathological evaluation of 30 cases of esophageal squamous cell carcinoma after two neoadjuvant therapies[J]. Chinese Journal of Radiation Oncology, 2023, 32(1): 15-21.
Wu Yi'nan,Zhang Jingyuan,Jiang Ning et al. Pathological evaluation of 30 cases of esophageal squamous cell carcinoma after two neoadjuvant therapies[J]. Chinese Journal of Radiation Oncology, 2023, 32(1): 15-21.
[1] Abnet CC, Arnold M, Wei WQ.Epidemiology of esophageal squamous cell carcinoma[J]. Gastroenterology, 2018,154(2):360-373. DOI: 10.1053/j.gastro.2017.08.023. [2] Erratum to "Cancer statistics, 2021"[J]. CA Cancer J Clin, 2021,71(4):359. DOI: 10.3322/caac.21669. [3] Sung H, Ferlay J, Siegel RL, et al.Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021,71(3):209-249. DOI: 10.3322/caac.21660. [4] van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer[J]. N Engl J Med, 2012,366(22):2074-2084. DOI: 10.1056/NEJMoa1112088. [5] 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]. J Clin Oncol, 2018,36(27):2796-2803. DOI: 10.1200/JCO.2018.79.1483. [6] Ni W, Yang J, Deng W, et al.Patterns of recurrence after surgery and efficacy of salvage therapy after recurrence in patients with thoracic esophageal squamous cell carcinoma[J]. BMC Cancer, 2020,20(1):144. DOI: 10.1186/s12885-020-6622-0. [7] Benitez JC, Remon J, Besse B.Current panorama and challenges for neoadjuvant cancer immunotherapy[J]. Clin Cancer Res, 2020,26(19):5068-5077. DOI: 10.1158/1078-0432.CCR-19-3255. [8] van den Ende T, de Clercq NC, van Berge Henegouwen MI, et al. Neoadjuvant chemoradiotherapy combined with atezolizumab for resectable esophageal adenocarcinoma: a single-arm phase II feasibility trial (PERFECT)[J]. Clin Cancer Res, 2021,27(12):3351-3359. DOI: 10.1158/1078-0432.CCR-20-4443. [9] Kelly RJ, Smith KN, Anagnostou V, et al. Neoadjuvant nivolumab plus concurrent chemoradiation in stage II/III esophageal/gastroesophageal junction cancer[J]. J Clin Oncol, 2019, 37(4_suppl):142-142. DOI: 10.1200/JCO.2019.37.4_suppl.142. [10] Kelly RJ, Ajani JA, Kuzdzal J, et al.Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer[J]. N Engl J Med, 2021,384(13):1191-1203. DOI: 10.1056/NEJMoa2032125. [11] Jiang N, Jiang M, Zhu X.Short course neoadjuvant chemo-radiotherapy plus anti-PD-1 antibody (toripalimab) for locally advanced squamous cell carcinoma of esophagus, a phase IB clinical trial (SCALE)[C]. Beijing: Chinese Society of Clinical Oncology (CSCO) Annual Meeting, 2021. [12] Travis WD, Dacic S, Wistuba I, et al.IASLC multidisciplinary recommendations for pathologic assessment of lung cancer resection specimens after neoadjuvant therapy[J]. J Thorac Oncol, 2020,15(5):709-740. DOI: 10.1016/j.jtho.2020.01.005. [13] Martin-Romano P, Sola JJ, Diaz-Gonzalez JA, et al.Role of histological regression grade after two neoadjuvant approaches with or without radiotherapy in locally advanced gastric cancer[J]. Br J Cancer, 2016,115(6):655-663. DOI: 10.1038/bjc.2016.252. [14] Eyck BM, van Lanschot J, Hulshof M, et al. Ten-year outcome of neoadjuvant chemoradiotherapy plus surgery for esophageal cancer: the randomized controlled CROSS trial[J]. J Clin Oncol, 2021,39(18):1995-2004. DOI: 10.1200/JCO.20.03614. [15] 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[J]. Eur J Cancer, 2020,138:113-121. DOI: 10.1016/j.ejca.2020.08.002. [16] Li C, Zhao S, Zheng Y, et al.Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1)[J]. Eur J Cancer, 2021,144:232-241. DOI: 10.1016/j.ejca.2020.11.039. [17] Yin L, Xue J, Li R, et al.Effect of low-dose radiation therapy on abscopal responses to hypofractionated radiation therapy and anti-PD1 in mice and patients with non-small cell lung cancer[J]. Int J Radiat Oncol Biol Phys, 2020,108(1):212-224. DOI: 10.1016/j.ijrobp.2020.05.002. [18] Ling Y, Li N, Li L, et al.Different pathologic responses to neoadjuvant anti-PD-1 in primary squamous lung cancer and regional lymph nodes[J]. NPJ Precis Oncol, 2020,4(1):32. DOI: 10.1038/s41698-020-00135-2. [19] Cottrell TR, Thompson ED, Forde PM, et al.Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC)[J]. Ann Oncol, 2018,29(8):1853-1860. DOI: 10.1093/annonc/mdy218. [20] Tian L, Goldstein A, Wang H, et al.Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming[J]. Nature, 2017,544(7649):250-254. DOI: 10.1038/nature21724. [21] Fleming CA, McCarthy K, Ryan C, et al. Evaluation of discordance in primary tumor and lymph node response after neoadjuvant therapy in breast cancer[J]. Clin Breast Cancer, 2018,18(2):e255-e261. DOI: 10.1016/j.clbc.2017.11.016. [22] Wang H, Mao X.Evaluation of the efficacy of neoadjuvant chemotherapy for breast cancer[J]. Drug Des Devel Ther, 2020,14:2423-2433. DOI: 10.2147/DDDT.S253961. [23] Liu J, Yang Y, Liu ZC, et al.Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma[J]. J Immunother Cancer. 2022, 10(3):e004291. DOI:10.1136/jitc-2021-004291. [24] Liu J, Li J, Lin W, et al.Neoadjuvant camrelizumab plus chemotherapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2019): a multicenter, phase 2 study[J]. Int J Cancer, 2022,151(1):128-137. DOI: 10.1002/ijc.33976.