Ben M Eyck1, J Jan B van Lanschot1,2, Maarten C C M Hulshof3, Berend J van der Wilk1, Joel Shapiro1, Pieter van Hagen1, Mark I van Berge Henegouwen4, Bas P L Wijnhoven1, Hanneke W M van Laarhoven5, Grard A P Nieuwenhuijzen6, Geke A P Hospers7, Johannes J Bonenkamp8, Miguel A Cuesta9, Reinoud J B Blaisse10, Olivier R Busch4, Geert-Jan M Creemers11, Cornelis J A Punt12,13, John Th M Plukker14, Henk M W Verheul15,16, Ernst J Spillenaar Bilgen17, Maurice J C van der Sangen18, Tom Rozema19,20, Fiebo J W Ten Kate21, Jannet C Beukema22, Anna H M Piet23, Caroline M van Rij24, Janny G Reinders25, Hugo W Tilanus26, Ewout W Steyerberg27,28, Ate van der Gaast29. 1. Department of Surgery, Erasmus Medical Center Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands. 2. Formerly at Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands. 3. Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands. 4. Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 5. Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands. 6. Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands. 7. Comprehensive Cancer Center, University of Groningen-University Medical Center Groningen, Groningen, the Netherlands. 8. Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands. 9. Department of Surgery, Amsterdam University Medical Centers, Location VUmc, Amsterdam, the Netherlands. 10. Department of Medical Oncology, Rijnstate Hospital, Arnhem, the Netherlands. 11. Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands. 12. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. 13. Formerly at Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands. 14. Department of Surgery, University of Groningen-University Medical Center Groningen, Groningen, the Netherlands. 15. Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands. 16. Formerly at Department of Medical Oncology, Amsterdam University Medical Centers, Location VUmc, Amsterdam, the Netherlands. 17. Department of Surgery, Rijnstate Hospital, Arnhem, the Netherlands. 18. Department of Radiation Oncology, Catharina Hospital, Eindhoven, the Netherlands. 19. Verbeeten Institute, Tilburg, the Netherlands. 20. Formerly at Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands. 21. Formerly at Department of Pathology, Erasmus MC-University Medical Center Rotterdam, the Netherlands. 22. Department of Radiation Oncology, University of Groningen-University Medical Center Groningen, Groningen, the Netherlands. 23. Department of Radiation Oncology, Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands. 24. Department of Radiation Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands. 25. Arnhem Radiotherapeutic Institute ARTI, Arnhem, the Netherlands. 26. Formerly at Department of Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands. 27. Department of Public Health, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands. 28. Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands. 29. Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.
Abstract
PURPOSE: Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen. METHODS: From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone. Follow-up data were collected through 2018. Cox regression analyses were performed to compare overall survival, cause-specific survival, and risks of locoregional and distant relapse. The effect of neoadjuvant chemoradiotherapy beyond 5 years of follow-up was tested with time-dependent Cox regression and landmark analyses. RESULTS: The median follow-up was 147 months (interquartile range, 134-157). Patients receiving neoadjuvant chemoradiotherapy had better overall survival (hazard ratio [HR], 0.70; 95% CI, 0.55 to 0.89). The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent (P value for interaction, P = .73), and landmark analyses suggested a stable effect on overall survival up to 10 years of follow-up. The absolute 10-year overall survival benefit was 13% (38% v 25%). Neoadjuvant chemoradiotherapy reduced risk of death from esophageal cancer (HR, 0.60; 95% CI, 0.46 to 0.80). Death from other causes was similar between study arms (HR, 1.17; 95% CI, 0.68 to 1.99). Although a clear effect on isolated locoregional (HR, 0.40; 95% CI, 0.21 to 0.72) and synchronous locoregional plus distant relapse (HR, 0.43; 95% CI, 0.26 to 0.72) persisted, isolated distant relapse was comparable (HR, 0.76; 95% CI, 0.52 to 1.13). CONCLUSION: The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years.
PURPOSE: Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen. METHODS: From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone. Follow-up data were collected through 2018. Cox regression analyses were performed to compare overall survival, cause-specific survival, and risks of locoregional and distant relapse. The effect of neoadjuvant chemoradiotherapy beyond 5 years of follow-up was tested with time-dependent Cox regression and landmark analyses. RESULTS: The median follow-up was 147 months (interquartile range, 134-157). Patients receiving neoadjuvant chemoradiotherapy had better overall survival (hazard ratio [HR], 0.70; 95% CI, 0.55 to 0.89). The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent (P value for interaction, P = .73), and landmark analyses suggested a stable effect on overall survival up to 10 years of follow-up. The absolute 10-year overall survival benefit was 13% (38% v 25%). Neoadjuvant chemoradiotherapy reduced risk of death from esophageal cancer (HR, 0.60; 95% CI, 0.46 to 0.80). Death from other causes was similar between study arms (HR, 1.17; 95% CI, 0.68 to 1.99). Although a clear effect on isolated locoregional (HR, 0.40; 95% CI, 0.21 to 0.72) and synchronous locoregional plus distant relapse (HR, 0.43; 95% CI, 0.26 to 0.72) persisted, isolated distant relapse was comparable (HR, 0.76; 95% CI, 0.52 to 1.13). CONCLUSION: The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years.
Authors: Go Nishikawa; Pratyusha Banik; Rajat Thawani; Adel Kardosh; Stephanie G Wood; Nima Nabavizadeh; Emerson Y Chen Journal: J Gastrointest Oncol Date: 2022-06