Hideki Ueno1, Megumi Ishiguro2, Eiji Nakatani3,4, Toshiaki Ishikawa5, Hiroyuki Uetake5, Kenta Murotani6, Shigeyuki Matsui7, Satoshi Teramukai8, Tamotsu Sugai9, Yoichi Ajioka10, Hirotoshi Maruo11, Masahito Kotaka12, Masaki Tsujie13, Yoshinori Munemoto14, Takashi Yamaguchi15, Hisashi Kuroda16, Mutsumi Fukunaga17, Naohiro Tomita18, Kenichi Sugihara19. 1. Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, Japan. ueno_surg1@ndmc.ac.jp. 2. Department of Translational Oncology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. 3. Division of Statistical Analysis of Research Support Center, Shizuoka General Hospital, 4-27-1, Kitaando, Aoi-ku, Shizuoka, Japan. 4. Division of Medical Statistics, Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, Japan. 5. Department of Specialized Surgeries, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. 6. Biostatistics Center, Kurume University, 67 Asahi-Machi, Kurume, Fukuoka, Japan. 7. Department of Biostatistics, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, Japan. 8. Department of Biostatistics, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan. 9. Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 2-1-1, Shiwagun, Yahabachou, Iwate, Japan. 10. Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Japan. 11. Department of Surgery, Shizuoka City Shimizu Hospital, 1231 Miyakami, Shimizu-ku, Shizuoka, Japan. 12. Gastrointestinal Cancer Center, Sano Hospital, 2-5-1 Shimizugaoka, Tarumi-ku Kobe, Hyogo, Japan. 13. Department of Surgery, Osaka Prefectural Saiseikai Tondabayashi Hospital, 1-3-36 Koyodai, Tondabayashi, Osaka, Japan. 14. Department of Surgery, Fukui-ken Saiseikai Hospital, 7-1 Funabashi, Wadanaka-cho, Fukui, Japan. 15. Surgery Division, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusa-Mukaihata-cho, Fushimi-ku, Kyoto, Japan. 16. Department of Gastrointestinal Surgery, St. Mary's Hospital, 422 Tsubuku-honmachi, Kurume, Fukuoka, Japan. 17. Department of Surgery, Sakai City Medical Center, 1-1-1 Ebaraji-cho, Nishi-ku, Sakai City, Osaka, Japan. 18. Division of Lower GI Surgery, Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, Japan. 19. Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
Abstract
BACKGROUND: The characterisation of desmoplastic reaction (DR) has emerged as a new, independent prognostic determinant in colorectal cancer. Herein, we report the validation of its prognostic value in a randomised controlled study (SACURA trial). METHODS: The study included 991 stage II colon cancer patients. DR was classified by the central review as Mature, Intermediate or Immature based on the presence of hyalinised collagen bundles and myxoid stroma at the desmoplastic front. All clinical and pathological data, including DR characterisations, were prospectively recorded and analysed 5 years after the completion of the registration. RESULTS: The five-year relapse-free survival (RFS) rate was the highest in the Mature group (N = 638), followed by the Intermediate (N = 294) and Immature groups (N = 59). Multivariate analysis revealed that DR classification was an independent prognostic factor, and based on Harrell's C-index, the Cox model for predicting RFS was significantly improved by including DR. In the conditional inference tree analysis, DR categorisation was the first split factor for predicting RFS, followed by T-stage, microsatellite instability status and budding. CONCLUSIONS: Histological categorisation of DR provides important prognostic information that could contribute to the efficient selection of stage II colon cancer patients who would benefit from postoperative adjuvant therapy.
RCT Entities:
BACKGROUND: The characterisation of desmoplastic reaction (DR) has emerged as a new, independent prognostic determinant in colorectal cancer. Herein, we report the validation of its prognostic value in a randomised controlled study (SACURA trial). METHODS: The study included 991 stage II colon cancerpatients. DR was classified by the central review as Mature, Intermediate or Immature based on the presence of hyalinised collagen bundles and myxoid stroma at the desmoplastic front. All clinical and pathological data, including DR characterisations, were prospectively recorded and analysed 5 years after the completion of the registration. RESULTS: The five-year relapse-free survival (RFS) rate was the highest in the Mature group (N = 638), followed by the Intermediate (N = 294) and Immature groups (N = 59). Multivariate analysis revealed that DR classification was an independent prognostic factor, and based on Harrell's C-index, the Cox model for predicting RFS was significantly improved by including DR. In the conditional inference tree analysis, DR categorisation was the first split factor for predicting RFS, followed by T-stage, microsatellite instability status and budding. CONCLUSIONS: Histological categorisation of DR provides important prognostic information that could contribute to the efficient selection of stage II colon cancerpatients who would benefit from postoperative adjuvant therapy.
Authors: Alexandre Calon; Enza Lonardo; Antonio Berenguer-Llergo; Elisa Espinet; Xavier Hernando-Momblona; Mar Iglesias; Marta Sevillano; Sergio Palomo-Ponce; Daniele V F Tauriello; Daniel Byrom; Carme Cortina; Clara Morral; Carles Barceló; Sebastien Tosi; Antoni Riera; Camille Stephan-Otto Attolini; David Rossell; Elena Sancho; Eduard Batlle Journal: Nat Genet Date: 2015-02-23 Impact factor: 38.330
Authors: Erin S O'Connor; David Yu Greenblatt; Noelle K LoConte; Ronald E Gangnon; Jinn-Ing Liou; Charles P Heise; Maureen A Smith Journal: J Clin Oncol Date: 2011-07-25 Impact factor: 44.544
Authors: Neal W Wilkinson; Greg Yothers; Samia Lopa; Joseph P Costantino; Nicholas J Petrelli; Norman Wolmark Journal: Ann Surg Oncol Date: 2010-04 Impact factor: 5.344
Authors: Alan P Venook; Donna Niedzwiecki; Margarita Lopatin; Xing Ye; Mark Lee; Paula N Friedman; Wendy Frankel; Kim Clark-Langone; Carl Millward; Steven Shak; Richard M Goldberg; Najjia N Mahmoud; Robert S Warren; Richard L Schilsky; Monica M Bertagnolli Journal: J Clin Oncol Date: 2013-03-25 Impact factor: 44.544
Authors: Naohiko Akimoto; Juha P Väyrynen; Melissa Zhao; Tomotaka Ugai; Kenji Fujiyoshi; Jennifer Borowsky; Rong Zhong; Koichiro Haruki; Kota Arima; Mai Chan Lau; Junko Kishikawa; Tyler S Twombly; Yasutoshi Takashima; Mingyang Song; Xuehong Zhang; Kana Wu; Andrew T Chan; Jeffrey A Meyerhardt; Marios Giannakis; Jonathan A Nowak; Shuji Ogino Journal: Front Immunol Date: 2022-03-22 Impact factor: 7.561
Authors: Diederik J Höppener; Jean-Luc P L Stook; Boris Galjart; Pieter M H Nierop; Iris D Nagtegaal; Peter B Vermeulen; Dirk J Grünhagen; Cornelis Verhoef; Michail Doukas Journal: BMC Cancer Date: 2022-08-22 Impact factor: 4.638