Predicting Early Tumor Recurrence in Patients With Esophageal Squamous Cell Carcinoma

Official title

Predicting Postoperative Early Tumor Recurrence in Patients With Esophageal Squamous Cell Carcinoma

Overview

The prognosis of patients with esophageal squamous cell carcinoma (ESCC) who develop post-operative early tumor recurrence is often relatively poor. Therefore, biomarker that can detect micro metastases before the start of treatment is required. Epigenomic alterations such as DNA methylation have attracted attention as promising biomarkers. The investigators aim to predict early recurrence based on whole genome DNA methylation analysis of esophageal cancer.

Detailed description

Prognosis for patients with esophageal squamous cell carcinoma (ESCC) remains poor. Surgery is one of the standard treatments for patients with ESCC who are considered to have a curative resection, however, approximately 40% of patients develop tumor recurrence within two years after surgery. The main cause of poor prognosis in ESCC patients undergoing surgery is postoperative tumor recurrence due to the presence of latent micro-metastases at the time of surgery. Even with today's advances in preoperative diagnostic techniques, predicting early tumor recurrence remains difficult due to the lack of established methods. Epigenetic markers, especially DNA methylation, are considered ideal markers for predicting cancer metastasis due to their cancer-specific methylation patterns, biological stability, and technical reproducibility. Our study aims to evaluate methylation of surgical specimens to assess residual disease and predict early recurrence.

Interventions

• Procedure Surgery
  Esophagectomy

Primary outcome measures

• Recurrence-free Survival（RFS) [Time frame: Up to 60 months]

Eligibility criteria

Inclusion criteria

• Patients who had histologically confirmed ESCC.
• Patients who had undergone only complete esophagectomy with radical lymph node dissection without chemotherapy or radiotherapy before or after surgery.
• Patients for whom tissue samples are available
• Patients who were followed-up completely, with information on observation periods of at least 2 years after surgery.
• Written informed consent following full study information is provided to the patient.

Exclusion criteria

• Patients lacking clinical information within 2 years of surgery.
• Patients with multiple cancers.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Study design

Observational model

Case-control

Study locations

Japan · 2 centers

• Nagoya University — Nagoya
• Yamanashi Universiy — Chūō

Publications

• Brown LM, Devesa SS, Chow WH. Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age. J Natl Cancer Inst. 2008 Aug 20;100(16):1184-7. doi: 10.1093/jnci/djn211. Epub 2008 Aug 11. PMID 18695138
• Sawada G, Niida A, Uchi R, Hirata H, Shimamura T, Suzuki Y, Shiraishi Y, Chiba K, Imoto S, Takahashi Y, Iwaya T, Sudo T, Hayashi T, Takai H, Kawasaki Y, Matsukawa T, Eguchi H, Sugimachi K, Tanaka F, Suzuki H, Yamamoto K, Ishii H, Shimizu M, Yamazaki H, Yamazaki M, Tachimori Y, Kajiyama Y, Natsugoe S, Fujita H, Mafune K, Tanaka Y, Kelsell DP, Scott CA, Tsuji S, Yachida S, Shibata T, Sugano S, Doki PMID 26873401
• Cui Y, Chen H, Xi R, Cui H, Zhao Y, Xu E, Yan T, Lu X, Huang F, Kong P, Li Y, Zhu X, Wang J, Zhu W, Wang J, Ma Y, Zhou Y, Guo S, Zhang L, Liu Y, Wang B, Xi Y, Sun R, Yu X, Zhai Y, Wang F, Yang J, Yang B, Cheng C, Liu J, Song B, Li H, Wang Y, Zhang Y, Cheng X, Zhan Q, Li Y, Liu Z. Whole-genome sequencing of 508 patients identifies key molecular features associated with poor prognosis in esophageal PMID 32398863
• Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Yang H, Li T, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J. 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 Aug 1; PMID 34160577
• Leng X, He W, Yang H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Liu H, Yang H, Li T, Zhang X, Li Q, Wang G, Mao T, Guo X, Lin T, Liu M, Fu J, Han Y. Prognostic Impact of Postoperative Lymph Node Metastases After Neoadjuvant Chemoradiotherapy for Locally Advanced Squamous Cell Carcinoma of Esophagus: From the Results of NEOCRTEC5010, a Randomized Multicen PMID 31855875
• Guo H, Zhu H, Xi Y, Zhang B, Li L, Huang Y, Zhang J, Fu Z, Yang G, Yuan S, Yu J. Diagnostic and prognostic value of 18F-FDG PET/CT for patients with suspected recurrence from squamous cell carcinoma of the esophagus. J Nucl Med. 2007 Aug;48(8):1251-8. doi: 10.2967/jnumed.106.036509. Epub 2007 Jul 13. PMID 17631554
• Shuto K, Kono T, Shiratori T, Akutsu Y, Uesato M, Mori M, Narushima K, Imanishi S, Nabeya Y, Yanagawa N, Okazumi S, Koda K, Matsubara H. Diagnostic performance of diffusion-weighted magnetic resonance imaging in assessing lymph node metastasis of esophageal cancer compared with PET. Esophagus. 2020 Jul;17(3):239-249. doi: 10.1007/s10388-019-00704-w. Epub 2019 Dec 9. PMID 31820208
• Ajani JA, D'Amico TA, Bentrem DJ, Cooke D, Corvera C, Das P, Enzinger PC, Enzler T, Farjah F, Gerdes H, Gibson M, Grierson P, Hofstetter WL, Ilson DH, Jalal S, Keswani RN, Kim S, Kleinberg LR, Klempner S, Lacy J, Licciardi F, Ly QP, Matkowskyj KA, McNamara M, Miller A, Mukherjee S, Mulcahy MF, Outlaw D, Perry KA, Pimiento J, Poultsides GA, Reznik S, Roses RE, Strong VE, Su S, Wang HL, Wiesner G, W PMID 37015332

Identifiers

NCT: NCT06476067 · 23228/ESCC-Erec

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗