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

Seiichiro Mitani, Ken Kato, Hiroyuki Daiko, Yoshinori Ito, Isao Nozaki, Takashi Kojima, Masahiko Yano, Satoru Nakagawa, Masaki Ueno, Masaya Watanabe, Shigeru Tsunoda, Tetsuya Abe, Shigenori Kadowaki, Tomohiro Kadota, Keita Sasaki, Ryunosuke Machida, Yuko Kitagawa

Research output: Contribution to journalArticlepeer-review

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Abstract

Background: Previous studies have suggested that patients with esophageal squamous cell carcinoma (ESCC) are still at a high risk of developing second primary malignancies (SPMs) after definitive therapies. We evaluated the development of SPMs and explored its risk factors in patients with clinical T1bN0 ESCC. Methods: JCOG0502 prospectively compared esophagectomy with definitive chemo-radiotherapy for clinical T1bN0 ESCC. Here, we reviewed all JCOG0502 patients’ data for SPMs and investigated the risk factors for SPMs using uni-variable and multivariable analyses by Fine and Gray model. Results: Among 379 enrolled patients, 213 underwent esophagectomy and 166 received chemo-radiotherapy. Patient characteristics were male (85%); median age [63 (range 41–75) years; location of the primary tumor (upper/middle/lower thoracic esophagus, 11%/63%/27%, respectively]; alcohol consumption history (79%); smoking history (66%); prevalence of no/several/many/unknown Lugol-voiding lesions (LVLs) (45%/36%/8%/11%, respectively). In a median follow-up of 7.1 years, 118 SPMs occurred in 99 (26%) patients. Cumulative incidences of SPMs after 3, 5, and 10 years were 9%, 15%, and 36%, respectively. The most common primary tumor sites were the head and neck (35%), stomach (20%) and lungs (14%). In multivariable analyses, compared to no LVLs, several LVLs [hazard ratio (HR) 2.24, 95% confidential interval (CI) 1.32–3.81] and many LVLs (HR 2.88, 95% CI 1.27–6.52) were significantly associated with the development of SPMs. Sixteen patients died due to the SPMs. Conclusion: The incidence of SPMs was high. The presence of LVLs, which was a predictive factor for SPMs, may be useful for surveillance planning.

Original languageEnglish
Pages (from-to)455-463
Number of pages9
JournalJournal of gastroenterology
Volume57
Issue number7
DOIs
Publication statusPublished - 2022 Jul

Keywords

  • Definitive chemoradiotherapy
  • Esophageal cancer
  • Esophagectomy
  • Second malignancies

ASJC Scopus subject areas

  • Gastroenterology

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