Julio Garcia-Aguilar1, Sujata Patil2, Marc J Gollub3, Jin K Kim1, Jonathan B Yuval1, Hannah M Thompson1, Floris S Verheij1, Dana M Omer1, Meghan Lee1, Richard F Dunne4, Jorge Marcet5, Peter Cataldo6, Blase Polite7, Daniel O Herzig8, David Liska9, Samuel Oommen10, Charles M Friel11, Charles Ternent12, Andrew L Coveler13, Steven Hunt14, Anita Gregory15, Madhulika G Varma16, Brian L Bello17, Joseph C Carmichael18, John Krauss19, Ana Gleisner20, Philip B Paty1, Martin R Weiser1, Garrett M Nash1, Emmanouil Pappou1, José G Guillem21, Larissa Temple22, Iris H Wei1, Maria Widmar1, Sabrina Lin2, Neil H Segal23, Andrea Cercek23, Rona Yaeger23, J Joshua Smith1, Karyn A Goodman24, Abraham J Wu25, Leonard B Saltz23. 1. Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, NY. 2. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY. 3. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY. 4. Department of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY. 5. Division of Colon and Rectal Surgery, Department of Surgery, University of South Florida, Tampa, FL. 6. Division of General Surgery, Department of Surgery, University of Vermont, Burlington, VT. 7. Department of Medicine, Comprehensive Cancer Center, University of Chicago, Chicago, IL. 8. Division of Gastrointestinal and General Surgery, Oregon Health and Science University, Portland, OR. 9. Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH. 10. Division of Gastrointestinal Oncology, John Muir Cancer Institute, John Muir Health, Walnut Creek, CA. 11. Division of General Surgery, Department of Surgery, University of Virginia, Charlottesville, VA. 12. Department of Surgery, Colorectal Service at Bergan Mercy Medical Center, Omaha, NE. 13. Department of Medicine, Fred Hutch Cancer Center, University of Washington, Seattle, WA. 14. Department of Surgery, Washington University School of Medicine, St Louis, MO. 15. Department of Surgery, St Joseph Hospital Orange County, Orange, CA. 16. Section of Colon and Rectal Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA. 17. Division of Colorectal Surgery, Department of Surgery, Medstar Washington Hospital Center, Washington, DC. 18. Division of Colon and Rectal Surgery, Department of Surgery, University of California, Irvine, Irvine, CA. 19. Department of Medicine, Rogel Cancer Center at the University of Michigan, Ann Arbor, MI. 20. Division of Surgical Oncology, Department of Surgery, University of Colorado, Denver, CO. 21. Division of Gastrointestinal Surgery, Department of Surgery, University of North Carolina, Chapel Hill, NC. 22. Division of Colorectal Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, NY. 23. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. 24. Department of Radiation Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY. 25. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
Abstract
PURPOSE: Prospective data on the efficacy of a watch-and-wait strategy to achieve organ preservation in patients with locally advanced rectal cancer treated with total neoadjuvant therapy are limited. METHODS: In this prospective, randomized phase II trial, we assessed the outcomes of 324 patients with stage II or III rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and either total mesorectal excision (TME) or watch-and-wait on the basis of tumor response. Patients in both groups received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation combined with either continuous infusion fluorouracil or capecitabine during radiotherapy. The trial was designed as two stand-alone studies with disease-free survival (DFS) as the primary end point for both groups, with a comparison to a null hypothesis on the basis of historical data. The secondary end point was TME-free survival. RESULTS: Median follow-up was 3 years. Three-year DFS was 76% (95% CI, 69 to 84) for the INCT-CRT group and 76% (95% CI, 69 to 83) for the CRT-CNCT group, in line with the 3-year DFS rate (75%) observed historically. Three-year TME-free survival was 41% (95% CI, 33 to 50) in the INCT-CRT group and 53% (95% CI, 45 to 62) in the CRT-CNCT group. No differences were found between groups in local recurrence-free survival, distant metastasis-free survival, or overall survival. Patients who underwent TME after restaging and patients who underwent TME after regrowth had similar DFS rates. CONCLUSION: Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME, and postoperative chemotherapy.
PURPOSE: Prospective data on the efficacy of a watch-and-wait strategy to achieve organ preservation in patients with locally advanced rectal cancer treated with total neoadjuvant therapy are limited. METHODS: In this prospective, randomized phase II trial, we assessed the outcomes of 324 patients with stage II or III rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and either total mesorectal excision (TME) or watch-and-wait on the basis of tumor response. Patients in both groups received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation combined with either continuous infusion fluorouracil or capecitabine during radiotherapy. The trial was designed as two stand-alone studies with disease-free survival (DFS) as the primary end point for both groups, with a comparison to a null hypothesis on the basis of historical data. The secondary end point was TME-free survival. RESULTS: Median follow-up was 3 years. Three-year DFS was 76% (95% CI, 69 to 84) for the INCT-CRT group and 76% (95% CI, 69 to 83) for the CRT-CNCT group, in line with the 3-year DFS rate (75%) observed historically. Three-year TME-free survival was 41% (95% CI, 33 to 50) in the INCT-CRT group and 53% (95% CI, 45 to 62) in the CRT-CNCT group. No differences were found between groups in local recurrence-free survival, distant metastasis-free survival, or overall survival. Patients who underwent TME after restaging and patients who underwent TME after regrowth had similar DFS rates. CONCLUSION: Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME, and postoperative chemotherapy.
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Authors: J Joshua Smith; Oliver S Chow; Marc J Gollub; Garrett M Nash; Larissa K Temple; Martin R Weiser; José G Guillem; Philip B Paty; Karin Avila; Julio Garcia-Aguilar Journal: BMC Cancer Date: 2015-10-23 Impact factor: 4.430
Authors: Markus Diefenhardt; Anke Schlenska-Lange; Thomas Kuhnt; Simon Kirste; Pompiliu Piso; Wolf O Bechstein; Guido Hildebrandt; Michael Ghadimi; Ralf-Dieter Hofheinz; Claus Rödel; Emmanouil Fokas Journal: Cancers (Basel) Date: 2022-07-27 Impact factor: 6.575
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