Abstract 1488P
Background
Genomic alternations in esophageal squamous cell carcinoma (ESCC) have not been fully evaluated, and the association between gene alternations and prognosis is unknown. We evaluated the frequency of gene alternations and the prognostic factors in 127 patients with stage I ESCC.
Methods
JCOG0502 is a parallel-group controlled trial of esophagectomy versus chemoradiotherapy for clinical stage T1bN0M0 ESCC (UMIN000000551). In this analysis, we performed whole-exosome sequencing (WES) using DNA extracted from formalin-fixed paraffin-embedded ESCC and normal samples (normal tissue or blood). We then identified single nucleotide variants (SNVs), insertions/deletions (indels), and copy number alterations (CNAs). We evaluated the association of each gene with a frequency ≥10% with progression-free survival (PFS), using a Cox model including age (≤64years old / ≥65 years old) and tumor diameter (≤4 cm / >4 cm). We controlled for family-wise error at 0.05 by Bonferroni method.
Results
We enrolled 379 patients to JCOG0502 and here analyzed samples from 127 patients by WES. The median patient age was 63 years (IQR 57-67 years). All patients were PS0 and 78.0% of patients ultimately underwent surgery. The 3-year PFS rate was 76.3%. We detected 125 genes with SNVs, indels or CNAs with a frequency of ≥10%. Of these, genomic alterations in FGF4 and FGF19 were significantly associated with PFS: FGF4 (HR 3.7, 95%CI 2.0-7.0, p=0.000066) and FGF19 (HR 3.6, 95%CI 1.9-6.9, p=0.00015). Genomic alterations in CTTN showed a marginal association with PFS (HR 2.5, 95%CI 1.3-4.7, p=0.007). The FGF4, FGF19 and CTTN alterations were all CNAs at chr 11q13.3 and were detected in 20.5%, 16.5% and 18.9% of the patients, respectively.
Conclusions
We have identified new genomic alterations associated with ESCC (T1bN0M0) prognosis. These findings open avenues for developing new, potential therapeutic options for patients with ESCC.
Clinical trial identification
JCOG0502A1.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The National Cancer Center Research and Development Funds (grant number 29-A-3), AMED (grant number JP15km0305012).
Disclosure
K. Kato: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): ONO; Advisory/Consultancy, Research grant/Funding (institution): Beigine; Advisory/Consultancy, Research grant/Funding (institution): MSD; Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Speaker Bureau/Expert testimony: Taiho; Speaker Bureau/Expert testimony: Eli Lilly; Research grant/Funding (institution): Shionogi; Research grant/Funding (institution): Merck Bio; Research grant/Funding (institution): Chugai. T. Kojima: Advisory/Consultancy, Research grant/Funding (institution): Ono; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy: Oncolys BioPharma; Advisory/Consultancy: Merck Biopharma; Advisory/Consultancy: BMS; Research grant/Funding (institution): Shionogi; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Chugai; Research grant/Funding (institution): Merck Serono. Y. Toh: Officer/Board of Directors: Japan Esophageal Society; Officer/Board of Directors: Japan Broncho-esophageal Society; Officer/Board of Directors: Japanese Board of Cancer Therapy; Officer/Board of Directors: Member, Science Council of Japan. M. Okada: Research grant/Funding (institution): ONO; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Chugai; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Daiichi Sankyo. S. Hironaka: Honoraria (self): Nihonkayaku; Honoraria (self): Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono pharmaceutical; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Yakult Honsha; Honoraria (self): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Chugai Pharmaceutical; Honoraria (self): Tsumura & Co; Honoraria (self), Research grant/Funding (institution): Sanofi; Honoraria (self): Merck; Honoraria (self): Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: MSD; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Boehringer; Research grant/Funding (institution): ToyamaKagaku; Research grant/Funding (institution): KyowaHakkoKirin; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Shionogi; Research grant/Funding (institution): Takeda. Y. Komatsu: Honoraria (self): Asahi Kasei Pharma Corporation; Honoraria (self), Research grant/Funding (institution): Bayer Yakuhin, Ltd; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Daiichi Sankyo Company, Limited.; Honoraria (self): Eli Lilly Japan K.K.; Honoraria (self): Kyowa Kirin Co.,Ltd; Honoraria (self): Merck Biopharma Co., Ltd.; Honoraria (self): Sanofi K.K.; Honoraria (self): Shire Japan K.K.; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Yakult Honsha Co.,Ltd.; Honoraria (self): Nippon Kayaku Co.,Ltd.; Honoraria (self): Novartis Pharma K.K.; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd.; Honoraria (self): Pfizer Japan Inc.; Honoraria (self): Takeda Pharmaceutical Company Limited; Honoraria (self): Bristol-Myers Squibb Co.; Honoraria (self): Mitsubishi Tanabe Pharma Corporation.; Honoraria (self): Nipro Corporation; Honoraria (self): Otsuka Pharmaceutical Factory, Inc.; Research grant/Funding (institution): A2 Healthcare Corp.; Research grant/Funding (institution): Astellas Pharma Inc.; Research grant/Funding (institution): Dainippon Sumitomo Pharma Co., Ltd.; Research grant/Funding (institution): Eisai Co., Ltd.; Research grant/Funding (institution): MSD K.K.; Research grant/Funding (institution): NanoCarrier Co., Ltd.; Research grant/Funding (institution): Parexel International Corporation.; Research grant/Funding (institution): Sanofi-aventis S.A; Research grant/Funding (institution): Incyte Corporation.; Research grant/Funding (institution): IQVIA Inc.; Research grant/Funding (institution): syneos health clinical k.k.; Research grant/Funding (institution): Sysmex Corporation. A. Kuchiba: Honoraria (self): Chugai Pharmaceutical Co., Ltd . K. Nakamura: Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Otsuka; Research grant/Funding (institution): Ono; Research grant/Funding (institution): Kyorin; Research grant/Funding (institution): Daiichi-Sankyo; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer. Y. Kitagawa: Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Taiho Pharmaceutical Co., Ltd; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Yakult Honsha Co. Ltd.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Daiichi Sankyo Company, Limited; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck Serono Co., Ltd.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): AsahiKasei Co., Ltd.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): EA Pharma Co., Ltd.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Otsuka Pharmaceutical Co., Ltd.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Takeda Pharmaceutical Co., Ltd.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Otsuka Pharmaceutical Factory Inc.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Shionogi & Co., Ltd.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Kaken Pharmaceutical Co.,Ltd.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Astellas Pharma Inc.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Medicon Inc.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Dainippon Sumitomo Pharma Co., Ltd.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Taisho Toyama Pharmaceutical Co., Ltd.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Kyouwa Hakkou Kirin Co., Ltd.; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Nihon Pharmaceutical Co., Ltd.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Japan Blood Products Organization; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Sanofi K.K.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Eisai Co., Ltd.; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Tsumura & Co.; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Olympus Corporation; Research grant/Funding (institution): Kowa Pharmaceutical Co., Ltd.; Research grant/Funding (institution): Pfizer Japan Inc.; Research grant/Funding (institution): Medtronic Japan Co., Ltd.; Research grant/Funding (institution): KCI Licensing, Inc.; Research grant/Funding (institution): Abbott Japan Co., Ltd.; Research grant/Funding (institution): Fujifilm Toyama Chemical Co., Ltd. All other authors have declared no conflicts of interest.