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Paired whole exome and transcriptome analyses for the Immunogenomic changes during concurrent chemoradiotherapy in esophageal squamous cell carcinoma.

ABSTRACT: BACKGROUND:The immunogenomic changes triggered by concurrent chemoradiation therapy (CCRT), a standard neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (ESCC), are unknown. We aimed to analyze the early immunogenomic changes in ESCC induced by CCRT and to correlate them with clinical outcomes. METHODS:We collected biopsy samples from 40 patients with ESCC and the surgical candidates were treated with 5-fluorouracil (5-FU)/Cisplatin and concurrent radiation therapy. Endoscopic biopsy was performed before and after one treatment cycle of 5-FU/Cisplatin and 5 to 18 fractions of radiation. We analyzed immunogenomic changes using paired whole-exome sequencing (n?=?29) and paired whole-transcriptome sequencing (WTS, n?=?23). Multiplex immunohistochemistry (IHC) was conducted in four representative pair samples. RESULTS:Fourteen out of 23 WTS samples (60.8%) showed increased immune scores after CCRT, as calculated by ESTIMATE. The rate of progression-free survival was higher in patients with increased immune scores compared with the remaining patients (83.1% vs. 57.1%, p?=?0.25). Tumor mutation burden and neoantigen load were significantly reduced after CCRT (p?

SUBMITTER: Park S

PROVIDER: S-EPMC6524245 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Paired whole exome and transcriptome analyses for the Immunogenomic changes during concurrent chemoradiotherapy in esophageal squamous cell carcinoma.

Park Sehhoon S Joung Je-Gun JG Min Yang Won YW Nam Jae-Yong JY Ryu Daeun D Oh Dongryul D Park Woong-Yang WY Lee Se-Hoon SH Choi Yoon La Y Ahn Jin Seok JS Ahn Myung-Ju MJ Park Keunchil K Sun Jong-Mu JM

Journal for immunotherapy of cancer 20190516 1

<h4>Background</h4>The immunogenomic changes triggered by concurrent chemoradiation therapy (CCRT), a standard neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (ESCC), are unknown. We aimed to analyze the early immunogenomic changes in ESCC induced by CCRT and to correlate them with clinical outcomes.<h4>Methods</h4>We collected biopsy samples from 40 patients with ESCC and the surgical candidates were treated with 5-fluorouracil (5-FU)/Cisplatin and concurrent radia ...[more]

PMID: 31097034

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Project description:BackgroundThis study aims to investigate the efficacy and safety of postoperative intensity-modulated radiotherapy (IMRT) covering partial regional lymph node areas combined with chemotherapy for locally advanced thoracic esophageal squamous cell carcinoma patients.MethodsThis was a single-center, single-arm phase II clinical trial that began in 2014. Patients who underwent radical transthoracic resection within 3 months and were histologically confirmed esophageal squamous cell carcinoma (pT3-4 or N+, M0 determined according to AJCC Guidelines, Edition 7) were recruited. Postoperative radiotherapy was performed with a total dose of 50.4Gy in 28 fractions using IMRT. Clinical target volumes (CTVs) included tumor bed, anastomosis, bilateral supraclavicular region, and superior mediastinal lymph nodes. Synchronous chemotherapy for 2 cycles (paclitaxel 150mg/m2, day1; Cisplatin 25mg/m2, day1-3; every 4 weeks), followed by 2 cycles of consolidation chemotherapy with the same regimen. The primary endpoint was the 2-year local control rate, and the secondary endpoints were overall survival (OS) and adverse events (AEs).ResultsA total of 75 eligible patients were included from 2014 to 2017. The 2-year LRFS rate, as the primary endpoint, was 73.3%. The 1-year and 3-year OS rates were 88.0% and 68.0%, respectively. Local recurrence occurred in 13/75 (17.4%) patients, of which 2.7% (2/75) were extra-target lymph nodes. Grade 4 adverse events reported in this study included 10 cases (13.3%) of neutropenia, 1 case (1.3%) of anemia, and 2 cases (2.7%) of thrombocytopenia, without toxic-related deaths. Almost all (96%) patients completed the entire postoperative radiotherapy course, and 62 (82.7%) patients completed at least 2 cycles of chemotherapy.ConclusionPostoperative IMRT (clinical target volume including tumor bed, anastomosis, bilateral supraclavicular region, and superior mediastinal lymph nodes) combined with synchronous chemotherapy in patients with locally advanced thoracic esophageal squamous cell carcinoma was well tolerated, with a high local control rate and a low probability of recurrence outside the irradiation field.Clinical trial registrationhttps://clinicaltrials.gov/ChiCTR1900022689.

Dataset Information

Paired whole exome and transcriptome analyses for the Immunogenomic changes during concurrent chemoradiotherapy in esophageal squamous cell carcinoma.

Publications

Paired whole exome and transcriptome analyses for the Immunogenomic changes during concurrent chemoradiotherapy in esophageal squamous cell carcinoma.

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