Endoscopy 2020; 52(12): 1066-1074
DOI: 10.1055/a-1198-5232
Original article

Endoscopic submucosal dissection with additional radiotherapy in the treatment of T1a esophageal squamous cell cancer: randomized controlled Trial

Yuhang Zhang*
1   Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
,
Ling Liu*
1   Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
,
Qiming Wang
1   Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
,
Linjie Guo
1   Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
,
Liansong Ye
1   Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
,
Hongze Zeng
1   Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
,
Xianhui Zeng
1   Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
,
Xianglei Yuan
1   Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
,
Yan Li
1   Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
,
Yuyan Zhang
1   Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
,
Elinor Zhou
2   Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
,
Bing Hu
1   Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
› Author Affiliations
Trial Registration: Chinese Clinical Trial Registry Registration number (trial ID): ChiCTR-ICR-15006192 Type of study: prospective, randomized study


Abstract

Background Endoscopic submucosal dissection (ESD) is effective for treating T1a early esophageal squamous cell carcinoma (ESCC). However, occasional recurrences are inevitable. This trial was designed to clarify the efficacy of combining ESD with additional radiotherapy in the treatment of T1a ESCC.

Methods Between January 2015 and September 2018, patients with early ESCC (T1aN0M0) following ESD were randomly assigned (1:1) to the radiotherapy group or non-radiotherapy group. Patients in the radiotherapy group received a median radiation dose of 59.4 Gy within 2 months after ESD. In the non-radiotherapy group, patients underwent regular follow-up only. Recurrence-free survival, cancer-specific survival, overall survival, and complications were evaluated.

Results 70 patients completed the per-protocol treatment. Three patients in the non-radiotherapy group experienced intraluminal mucosal recurrence compared with none in the radiotherapy group. No local lymph node or distant metastases occurred in either group. The 3-year cumulative recurrence-free survival was 100 % in the radiotherapy group and 85.3 % in the non-radiotherapy group (P = 0.04; hazard ratio 0.08, 95 % confidence interval [CI] 0.01 – 0.86). However, there was no significant difference in RFS between the treatments within the T1a invasion subgroups (P > 0.05). No patient died in either group. Mucosal defects of more than three-quarters of the esophageal circumference were positively correlated with stenosis (P < 0.01; odds ratio 23.26, 95 %CI 4.04 – 133.86). No severe radiation toxicities were recorded.

Conclusions Radiotherapy after ESD might be a safe and effective optional therapeutic strategy to prevent recurrence of T1a ESCC.

* These authors contributed equally to this work.


Table 1s – 3s, Fig. 1s, Fig. 2s



Publication History

Received: 11 September 2019

Accepted: 22 May 2020

Article published online:
15 July 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 World cancer report 2014. Stewart BW, Wild C. Lyon, France: International Agency for Research on Cancer; 2014
  • 2 Chen W, Zheng R, Baade PD. et al. Cancer statistics in China, 2015. CA Can J Clin 2016; 66: 115-132
  • 3 Takubo K, Aida J, Sawabe M. et al. Early squamous cell carcinoma of the oesophagus: the Japanese viewpoint. Histopathology 2007; 51: 733-742
  • 4 Shimizu M, Zaninotto G, Nagata K. et al. Esophageal squamous cell carcinoma with special reference to its early stage. Best Pract Res Clin Gastroenterol 2013; 27: 171-186
  • 5 Das A, Singh V, Fleischer DE. et al. A comparison of endoscopic treatment and surgery in early esophageal cancer: an analysis of surveillance epidemiology and end results data. Am J Gastroenterol 2008; 103: 1340-1345
  • 6 Min YW, Lee H, Song BG. et al. Comparison of endoscopic submucosal dissection and surgery for superficial esophageal squamous cell carcinoma: a propensity score-matched analysis. Gastrointest Endosc 2018; 88: 624-633
  • 7 Ikeda A, Hoshi N, Yoshizaki T. et al. Endoscopic submucosal dissection (ESD) with additional therapy for superficial esophageal cancer with submucosal invasion. Intern Med 2015; 54: 2803-2813
  • 8 Hisano O, Nonoshita T, Hirata H. et al. Additional radiotherapy following endoscopic submucosal dissection for T1a-MM/T1b-SM esophageal squamous cell carcinoma improves locoregional control. Radiat Oncol 2018; 13: 14
  • 9 Tsujii Y, Nishida T, Nishiyama O. et al. Clinical outcomes of endoscopic submucosal dissection for superficial esophageal neoplasms: a multicenter retrospective cohort study. Endoscopy 2015; 47: 775-783
  • 10 Kitagawa Y, Uno T, Oyama T. et al. Esophageal cancer practice guidelines 2017 edited by the Japan Esophageal Society: part 1. Esophagus 2019; 16: 1-24
  • 11 Mochizuki Y, Saito Y, Tsujikawa T. et al. Combination of endoscopic submucosal dissection and chemoradiation therapy for superficial esophageal squamous cell carcinoma with submucosal invasion. Exp Ther Med 2011; 2: 1065-1068
  • 12 Kawaguchi G, Sasamoto R, Abe E. et al. The effectiveness of endoscopic submucosal dissection followed by chemoradiotherapy for superficial esophageal cancer. Radiat Oncol 2015; 10: 31
  • 13 Oyama T, Inoue H, Arima M. et al. Prediction of the invasion depth of superficial squamous cell carcinoma based on microvessel morphology: magnifying endoscopic classification of the Japan Esophageal Society. Esophagus 2017; 14: 105-112
  • 14 National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology. Esophageal and esophagogastric junction cancers, Version 1.2014. Plymouth Meeting, PA: NCCN; 2014
  • 15 Muto M, Hironaka S, Nakane M. et al. Association of multiple Lugol-voiding lesions with synchronous and metachronous esophageal squamous cell carcinoma in patients with head and neck cancer. Gastrointest Endosc 2002; 56: 517-521
  • 16 Uno K, Koike T, Kusaka G. et al. Risk of metachronous recurrence after endoscopic submucosal dissection of esophageal squamous cell carcinoma. Dis Esophagus 2017; 30: 1-8
  • 17 Udagawa H, Ueno M. Comparison of two major staging systems of esophageal cancer – toward more practical common scale for tumor staging. Ann Transl Med 2018; 6: 76
  • 18 Ishikawa H, Sakurai H, Tamaki Y. et al. Radiation therapy alone for stage I (UICC T1N0M0) squamous cell carcinoma of the esophagus: indications for surgery or combined chemoradiotherapy. J Gastroenterol Hepatol 2006; 21: 1290-1296
  • 19 Yamada K, Murakami M, Okamoto Y. et al. Treatment results of chemoradiotherapy for clinical stage I (T1N0M0) esophageal carcinoma. Int J Radiat Oncol Biol Phys 2006; 64: 1106-1111
  • 20 Goense L, Meziani J, Borggreve AS. et al. Role of adjuvant chemoradiotherapy after endoscopic treatment of early-stage esophageal cancer: a systematic review. Minerva Chir 2018; 73: 428-436
  • 21 Huh CW, Lee HH, Kim BW. et al. Predictive factors of submucosal fibrosis before endoscopic submucosal dissection for superficial squamous esophageal neoplasia. Clin Transl Gastroenterol 2018; 9: 159
  • 22 Hong L, Huang YX, Zhuang QY. et al. Survival benefit of re-irradiation in esophageal cancer patients with locoregional recurrence: a propensity score-matched analysis. Radiat Oncol 2018; 13: 171
  • 23 van Hagen P, Hulshof MC, van Lanschot JJ. et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012; 366: 2074-2084
  • 24 Liu M, Shi X, Guo X. et al. Long-term outcome of irradiation with or without chemotherapy for esophageal squamous cell carcinoma: a final report on a prospective trial. Radiat Oncol 2012; 7: 142
  • 25 Atsumi K, Shioyama Y, Arimura H. et al. Esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer: frequency and prediction. Int J Radiat Oncol Biol Phys 2012; 82: 1973-1980
  • 26 Ono S, Fujishiro M, Niimi K. et al. Predictors of postoperative stricture after esophageal endoscopic submucosal dissection for superficial squamous cell neoplasms. Endoscopy 2009; 41: 661-665
  • 27 Miwata T, Oka S, Tanaka S. et al. Risk factors for esophageal stenosis after entire circumferential endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma. Surg Endosc 2016; 30: 4049-4056
  • 28 Gaspar LE, Winter K, Kocha WI. et al. A phase I/II study of external beam radiation, brachytherapy, and concurrent chemotherapy for patients with localized carcinoma of the esophagus (Radiation Therapy Oncology Group Study 9207): final report. Cancer 2000; 88: 988-995