Research status and progress on neoadjuvant therapy for esophageal cancer
Zhu Junge1,2, Li Jianbin2, Zhang Yingjie2
1Department of Graduate,Shandong First Medical University and Shandong Academy of Medical Sciences,Ji’nan 250117,China; 2Department of Chest Radiation Oncology Ⅰ,Shandong Cancer Hospital and Institute,Shandong First Medical University and Shandong Academy of Medical Sciences,Ji’nan 250117,China
Abstract：China is a country with high incidence of esophageal cancer. In recent years, with the deepening research, the value of neoadjuvant therapy in locally advanced resectable esophageal cancer has been widely approved by clinicians, compared with surgery alone or adjuvant therapy. However, the survival results of different neoadjuvant therapy options may be quite different, and many problems remain unresolved. In this article, a systemic literature review was carried out to summarize the radiotherapy target, radiotherapy dose, chemotherapy regimen of neoadjuvant chemoradiotherapy and time to surgery, as well as review the research status and progress on targeted therapy and immunotherapy as neoadjuvant therapy for esophageal cancer.
Zhu Junge,Li Jianbin,Zhang Yingjie. Research status and progress on neoadjuvant therapy for esophageal cancer[J]. Chinese Journal of Radiation Oncology, 2022, 31(4): 389-394.
[1] 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. [2] 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. [3] 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. [4] von Döbeln GA, Klevebro F, Jacobsen AB, et al. Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or gastroesophageal junction:long-term results of a randomized clinical trial[J]. Dis Esophagus, 2019, 32(2) DOI:10.1093/dote/doy078. [5] Ohnuma H, Sato Y, Hayasaka N, et al. Neoadjuvant chemotherapy with docetaxel, nedaplatin, and fluorouracil for resectable esophageal cancer:A phase Ⅱ study[J]. Cancer Sci, 2018, 109(11):3554-3563. DOI:10.1111/cas.13772. [6] Yamashita K, Hosoda K, Moriya H, et al. Prognostic advantage of docetaxel/cisplatin/5-fluorouracil neoadjuvant chemotherapy in clinical stage Ⅱ/Ⅲ esophageal squamous cell carcinoma due to excellent control of preoperative disease and postoperative lymph node recurrence[J]. Oncology, 2017, 92(4):221-228. DOI:10.1159/000455128. [7] Shiraishi O, Yamasaki M, Makino T, et al. Feasibility of preoperative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil versus adriamycin, cisplatin, and 5-fluorouracil for resectable advanced esophageal cancer[J]. Oncology, 2017, 92(2):101-108. DOI:10.1159/000452765. [8] Stahl M, Walz MK, Riera-Knorrenschild J, et al. Preoperative chemotherapy versus chemoradiotherapy in locally advanced adenocarcinomas of the oesophagogastric junction (POET):long-term results of a controlled randomised trial[J]. Eur J Cancer, 2017, 81:183-190. DOI:10.1016/j.ejca.2017.04.027. [9] Al-Batran SE, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4):a randomised, phase 2/3 trial[J]. Lancet, 2019, 393(10184):1948-1957. DOI:10.1016/S0140-6736(18)32557-1. [10] Arnott SJ, Duncan W, Gignoux M, et al. Preoperative radiotherapy for esophageal carcinoma[J]. Cochrane Database Syst Rev, 2005, 2005(4):CD001799. DOI:10.1002/14651858.CD001799.pub2. [11] Czito BG, Palta M, Willett CG. Results of the FFCD 9901 trial in early-stage esophageal carcinoma:is it really about neoadjuvant therapy?[J]. J Clin Oncol, 2014, 32(23):2398-2400. DOI:10.1200/JCO.2014.55.7231. [12] Hagens E, Künzli HT, van Rijswijk AS, et al. Distribution of lymph node metastases in esophageal adenocarcinoma after neoadjuvant chemoradiation therapy:a prospective study[J]. Surg Endosc, 2020, 34(10):4347-4357. DOI:10.1007/s00464-019-07205-y. [13] Wang X, Miao C, Chen Z, et al. Can involved-field irradiation replace elective nodal irradiation in chemoradiotherapy for esophageal cancer? A systematic review and meta-analysis[J]. Onco Targets Ther, 2017, 10:2087-2095. DOI:10.2147/OTT.S130285. [14] Zhou S, Zhang L, Luo L, et al. Failure pattern of elective nodal irradiation for esophageal squamous cell cancer treated with neoadjuvant chemoradiotherapy[J]. Jpn J Clin Oncol, 2018, 48(9):815-821. DOI:10.1093/jjco/hyy099. [15] Liu T, Ding S, Dang J, et al. Elective nodal irradiationversus involved-field irradiation in patients with esophageal cancer receiving neoadjuvant chemoradiotherapy:a network meta-analysis[J]. Radiat Oncol, 2019, 14(1):176. DOI:10.1186/s13014-019-1388-8. [16] 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. [17] Nilsson K, Klevebro F, Rouvelas I, et al. Surgical morbidity and mortality from the multicenter randomized controlled neores Ⅱ trial:standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for esophageal cancer[J]. Ann Surg, 2020, 272(5):684-689. DOI:10.1097/SLA.0000000000004340. [18] Ordu AD, Nieder C, Geinitz H, et al. Association between radiation dose and pathological complete response after preoperative radiochemotherapy in esophageal squamous cell cancer[J]. Anticancer Res, 2014, 34(12):7255-7261. [19] Thomas M, Borggreve AS, van Rossum P, et al. Radiation dose and pathological response in oesophageal cancer patients treated with neoadjuvant chemoradiotherapy followed by surgery:a multi-institutional analysis[J]. Acta Oncol, 2019, 58(10):1358-1365. DOI:10.1080/0284186X.2019.1646432. [20] Ising MS, Marino K, Trivedi JR, et al. Influence of neoadjuvant radiation dose on patients undergoing esophagectomy and survival in locally advanced esophageal cancer[J]. J Gastrointest Surg, 2019, 23(4):670-678. DOI:10.1007/s11605-019-04141-z. [21] Buckstein M, Rhome R, Ru M, et al. Neoadjuvant chemoradiation radiation dose levels for surgically resectable esophageal cancer:predictors of use and outcomes[J]. Dis Esophagus, 2018, 31(5) DOI:10.1093/dote/dox148. [22] Ajani JA, Correa AM, Walsh GL, et al. Trimodality therapy without a platinum compound for localized carcinoma of the esophagus and gastroesophageal junction[J]. Cancer, 2010, 116(7):1656-1663. DOI:10.1002/cncr.24935. [23] Sanford NN, Catalano PJ, Enzinger PC, et al. A retrospective comparison of neoadjuvant chemoradiotherapy regimens for locally advanced esophageal cancer[J]. Dis Esophagus, 2017, 30(7):1-8. DOI:10.1093/dote/dox025. [24] Xi M, Zhang P, Zhang L, et al. Comparing docetaxel plus cisplatin versus fluorouracil plus cisplatin in esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy[J]. Jpn J Clin Oncol, 2017, 47(8):683-689. DOI:10.1093/jjco/hyx060. [25] Liu SL, Yang H, Zhang P, et al. Neoadjuvant chemoradiotherapy with cisplatin plus vinorelbine versus cisplatin plus fluorouracil for esophageal squamous cell carcinoma:A matched case-control study[J]. Radiother Oncol, 2015, 116(2):262-268. DOI:10.1016/j.radonc.2015.07.020. [26] Jiang DM, Sim HW, Espin-Garcia O, et al. Chemoradiotherapy using carboplatin plus paclitaxel versus cisplatin plus fluorouracil for esophageal or gastroesophageal junction cancer[J]. Oncology, 2021, 99(1):49-56. DOI:10.1159/000510446. [27] Odawara S, Kitajima K, Katsuura T, et al. Tumor response to neoadjuvant chemotherapy in patients with esophageal cancer assessed with CT and FDG-PET/CT-RECIST 1.1 vs. PERCIST 1.0[J]. Eur J Radiol, 2018, 101:65-71. DOI:10.1016/j.ejrad.2018.02.009. [28] Song T, Yao Q, Qu J, et al. The value of intravoxel incoherent motion diffusion-weighted imaging in predicting the pathologic response to neoadjuvant chemotherapy in locally advanced esophageal squamous cell carcinoma[J]. Eur Radiol, 2021, 31(3):1391-1400. DOI:10.1007/s00330-020-07248-z. [29] Kurokawa Y, Shibata T, Ando N, et al. Which is the optimal response criteria for evaluating preoperative treatment in esophageal cancer:RECIST or histology?[J]. Ann Surg Oncol, 2013, 20(9):3009-3014. DOI:10.1245/s10434-013-2946-1. [30] Fanelli GN, Loupakis F, Smyth E, et al. Pathological tumor regression grade classifications in gastrointestinal cancers:role on patients' prognosis[J]. Int J Surg Pathol, 2019, 27(8):816-835. DOI:10.1177/1066896919869477. [31] Takeda FR, Tustumi F, de Almeida Obregon C, et al. Prognostic value of tumor regression grade based on ryan score in squamous cell carcinoma and adenocarcinoma of esophagus[J]. Ann Surg Oncol, 2020, 27(4):1241-1247. DOI:10.1245/s10434-019-07967-8. [32] Liu Y, Zhang KC, Huang XH, et al. Timing of surgery after neoadjuvant chemotherapy for gastric cancer:impact on outcomes[J]. World J Gastroenterol, 2018, 24(2):257-265. DOI:10.3748/wjg.v24.i2.257. [33] Bausys A,Ümarik T, Luksta M, et al. Correction to:impact of the interval between neoadjuvant chemotherapy and gastrectomy on short-and long-term outcomes for patients with advanced gastric cancer[J]. Ann Surg Oncol, 2021, 28(Suppl 3):889. DOI:10.1245/s10434-021-10462-8. [34] Wang Y, Liu Z, Shan F, et al. Optimal timing to surgery after neoadjuvant chemotherapy for locally advanced gastric cancer[J]. Front Oncol, 2020, 10:613988. DOI:10.3389/fonc.2020.613988. [35] Mukherjee S, Hurt CN, Gwynne S, et al. NEOSCOPE:A randomised phase Ⅱ study of induction chemotherapy followed by oxaliplatin/capecitabine or carboplatin/paclitaxel based pre-operative chemoradiation for resectable oesophageal adenocarcinoma[J]. Eur J Cancer, 2017, 74:38-46. DOI:10.1016/j.ejca.2016.11.031. [36] Franko J, Voynov G, Goldman CD. Esophagectomy timing after neoadjuvant therapy for distal esophageal adenocarcinoma[J]. Ann Thorac Surg, 2016, 101(3):1123-1130. DOI:10.1016/j.athoracsur.2015.09.044. [37] Klevebro F, Nilsson K, Lindblad M, et al. Association between time interval from neoadjuvant chemoradiotherapy to surgery and complete histological tumor response in esophageal and gastroesophageal junction cancer:a national cohort study[J]. Dis Esophagus, 2020, 33(5) DOI:10.1093/dote/doz078. [38] Tie H, He F, Shen J, et al. Prolonged interval between neoadjuvant chemoradiotherapy and esophagectomy does not benefit the outcome in esophageal cancer:a systematic review and meta-analysis[J]. Dis Esophagus, 2018, 31(1):1-9. DOI:10.1093/dote/dox116. [39] Qin Q, Xu H, Liu J, et al. Does timing of esophagectomy following neoadjuvant chemoradiation affect outcomes? A meta-analysis[J]. Int J Surg, 2018, 59:11-18. DOI:10.1016/j.ijsu.2018.09.013. [40] Haisley KR, Laird AE, Nabavizadeh N, et al. Association of intervals between neoadjuvant chemoradiation and surgical resection with pathologic complete response and survival in patients with esophageal cancer[J]. JAMA Surg, 2016, 151(11):e162743. DOI:10.1001/jamasurg.2016.2743. [41] Stroes CI, Schokker S, Creemers A, et al. Phase Ⅱ feasibility and biomarker study of neoadjuvant trastuzumab and pertuzumab with chemoradiotherapy for resectable human epidermal growth factor receptor 2-positive esophageal adenocarcinoma:TRAP study[J]. J Clin Oncol, 2020, 38(5):462-471. DOI:10.1200/JCO.19.01814. [42] Liu T, Qin Y, Li J, et al. Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer:a subpopulation analysis of the JACOB trial[J]. Cancer Commun (Lond), 2019, 39(1):38. DOI:10.1186/s40880-019-0384-6. [43] Ku GY, Bains MS, Park DJ, et al. Phase Ⅱ study of bevacizumab and preoperative chemoradiation for esophageal adenocarcinoma[J]. J Gastrointest Oncol, 2016, 7(6):828-837. DOI:10.21037/jgo.2016.08.09. [44] Cunningham D, Stenning SP, Smyth EC, et al. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK medical research council ST03):primary analysis results of a multicentre, open-label, randomised phase 2-3 trial[J]. Lancet Oncol, 2017, 18(3):357-370. DOI:10.1016/S1470-2045(17)30043-8. [45] Lockhart AC, Reed CE, Decker PA, et al. Phase Ⅱ study of neoadjuvant therapy with docetaxel, cisplatin, panitumumab, and radiation therapy followed by surgery in patients with locally advanced adenocarcinoma of the distal esophagus (ACOSOG Z4051)[J]. Ann Oncol, 2014, 25(5):1039-1044. DOI:10.1093/annonc/mdu091. [46] Brenner B, Purim O, Gordon N, et al. The addition of cetuximab to preoperative chemoradiotherapy for locally advanced esophageal squamous cell carcinoma is associated with high rate of long term survival:mature results from a prospective phase Ib/Ⅱ trial[J]. Radiother Oncol, 2019, 134:74-80. DOI:10.1016/j.radonc.2019.01.013. [47] Ruhstaller T, Thuss-Patience P, Hayoz S, et al. Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer:a randomized, open-label, phase Ⅲ trial (SAKK 75/08)[J]. Ann Oncol, 2018, 29(6):1386-1393. DOI:10.1093/annonc/mdy105. [48] Liu D, Zhang Q, Zhu J, et al. Phase-Ⅱ study of toripalimab combined with neoadjuvant chemotherapy for the treatment of resectable esophageal squamous cell carcinoma[J]. J Clin Oncol, 2021, 39(15s):abstr e16029. DOI:10.1200/JCO.2021.39.15_suppl.e16029. [49] Takiguchi S, Shitara K, Takiguchi N, et al. Neoadjuvant nivolumab monotherapy in patients with resectable gastric cancer:Preliminary results from a multicenter study[J]. J Clin Oncol, 2021, 39(15s):abstr 4026. DOI:10.1200/JCO.2021.39.15_suppl.4026. [50] Liu N, Liu Z, Zhou Y, et al. Efficacy and safety of camrelizumab combined with FLOT versus FLOT alone as neoadjuvant therapy in patients with resectable locally advanced gastric and gastroesophageal junction adenocarcinoma who received D2 radical gastrectomy[J]. J Clin Oncol, 2021, 39(15s):abstr e16020. DOI:10.1200/JCO.2021.39.15_suppl.e16020. [51] Cheng C, Yang W, Chen W, et al. Neoadjuvant PD-1 blockade in combination with chemotherapy for patients with resectable esophageal squamous cell carcinoma[J]. J Clin Oncol, 2021, 39(3s):abstr 220. DOI:10.1200/JCO.2021.39.3_suppl.220. [52] Li J, Liu J, Li Z, et al. Camrelizumab plus chemotherapy as neoadjuvant therapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2019):a multicenter, open-label, single-arm, phase 2 study[J]. J Clin Oncol, 2021, 39(15s):abstr 4028. DOI:10.1200/JCO.2021.39.15_suppl.4028. [53] 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. [54] 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.
2022, Vol. 31 
