Second primary malignancies in patients with clinical T1bN0 esophageal squamous cell carcinoma after definitive therapies: supplementary analysis of the JCOG trial: JCOG0502.

"Declarations Conflict of interestSeiichiro Mitani reports research grants from Taiho Pharmaceutical Co. Ken Kato reports research grants from MSD, Ono Pharmaceutical Co., Merck Serono, Bayer, Beigene, Oncologys Biopharma, Chugai Pharmaceutical Co., and Shionogi. Takashi Kojima reports research grants from Ono Pharmaceutical Co., MSD, Amgen Astellas BioPharma, Chugai Pharmaceutical Co., Shionogi, Parexel, and Taiho Pharmaceutical Co. Yuko Kitagawa is a member of endowed chair from Taiho Pharmaceutical Co., and Chugai Pharmaceutical Co. and reports honorariums from ASAHI KASEI PHARMA Corporation, Taiho Pharmaceutical Co., Ono Pharmaceutical Co., and Chugai Pharmaceutical Co., scholarship grants from Chugai Pharmaceutical Co., Taiho Pharmaceutical Co., Yakult Honsha, ASAHI KASEI PHARMA Corporation, Ohtsuka Pharmaceutical Co., Ltd., and Ono Pharmaceutical Co., trips and other gifts unrelated to research, education, or health care from Ono Pharmaceutical Co. and Bristol Myers Squibb. All remaining authors have declared no conflicts of interest. Conflict of interest Seiichiro Mitani reports research grants from Taiho Pharmaceutical Co. Ken Kato reports research grants from MSD, Ono Pharmaceutical Co., Merck Serono, Bayer, Beigene, Oncologys Biopharma, Chugai Pharmaceutical Co., and Shionogi. Takashi Kojima reports research grants from Ono Pharmaceutical Co., MSD, Amgen Astellas BioPharma, Chugai Pharmaceutical Co., Shionogi, Parexel, and Taiho Pharmaceutical Co. Yuko Kitagawa is a member of endowed chair from Taiho Pharmaceutical Co., and Chugai Pharmaceutical Co. and reports honorariums from ASAHI KASEI PHARMA Corporation, Taiho Pharmaceutical Co., Ono Pharmaceutical Co., and Chugai Pharmaceutical Co., scholarship grants from Chugai Pharmaceutical Co., Taiho Pharmaceutical Co., Yakult Honsha, ASAHI KASEI PHARMA Corporation, Ohtsuka Pharmaceutical Co., Ltd., and Ono Pharmaceutical Co., trips and other gifts unrelated to research, education, or health care from Ono Pharmaceutical Co. and Bristol Myers Squibb. All remaining authors have declared no conflicts of interest."

"Funding This study was supported in part by the National Cancer Center Research and Development Fund (2020-J-3)."

"The details of JCOG0502 have been described elsewhere []. The main eligibility criteria were as follows: (1) histologically proven thoracic esophageal squamous cell, adeno-squamous or basaloid cell carcinoma; (2) clinical stage T1bN0M0 based on the 7th UICC-TNM classification; (3) age from 20 to 75 years; (4) Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1; (5) no prior therapy for esophageal cancer; (6) adequate organ function; and (7) without sever comorbidities. Screening tests for other active malignancies were conducted using upper endoscopy, computed tomography (CT) scans. Positron emission tomography or otolaryngological examination was not mandatory and performed according to investigator’s choice. All patients were informed of the randomized nature of the study. Only when patients refused randomization and consented to non-randomized parts of the trial, they were assigned to surgery or chemo-radiotherapy, as the patients and their oncology team decided. Esophagectomy with 2- or 3-field lymph node dissection was performed in the surgical arm. In the chemo-radiotherapy arm, cisplatin 70 mg/m2 (days 1 and 29) and 5-fluorouracil 700 mg/m2/day (days 1–4, 29–32) combined with 60 Gy/ 30 fr radiotherapy were delivered. Written informed consent was obtained from all the patients prior to enrollment. The study protocol of the trial was approved by the institutional review boards of all institutions. The study was conducted in accordance with the principles of the Helsinki Declaration of 1964 and its later amendments and registered in the clinical trial database (UMIN000000551). Using data from all patients enrolled in JCOG0502, we performed additional analyses for SPMs."