En que vamos con el tratamiento neoadyuvante y adyuvante en cáncer de recto?
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Simposio de coloproctología, 26.05.2018. Hotel Intercontinental Medellín (Basado en presentación realizada en el Simposio ACHO Gastrointestinal, 2017).
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En que vamos con el tratamiento neoadyuvante y adyuvante en cáncer de recto?
- 1. Neoadyuvancia y Adyuvancia en Cáncer de Recto: En Qué Estamos. Mauricio Lema Medina MD Clínica de Oncología Astorga / Clínica SOMA, Medellín, Colombia Medellín, 26.05.2018
- 2. @onconerd
- 3. Rectal cancer Stage I Surgery Stage IVb Palliative CT Stage II-IVa XRT CT Surgery Combined- modality
- 4. Rectal cancer Stage I Surgery Stage IVb Palliative CT Stage II-IVa XRT CT Surgery Combined- modality
- 5. Multi-modality is required for rectal cancer
- 6. XRT CT Surgery SurgeryXRT SurgeryCRT CRTSurgery Surgery SurgeryXRT SurgeryCRT CRTSurgery XRT CT CT CT Modality sequence in stage II-IVa rectal cancer Short, or Long RT FU, or Capecitabine Oxaliplatin vs no-oxaliplatin
- 8. XRT CT TME TMEXRT TMECRT CRTTME TME TMEXRT TMECRT CRTTME XRT CT CT CT Modality sequence in stage II-IVa rectal cancer Short, or Long RT FU, or Capecitabine Oxaliplatin vs no-oxaliplatin
- 9. XRT (Radiation therapy) Pre-Op vs Post-Op
- 10. Preoperative or postoperative irradiation in adenocarcinoma of the rectum: final treatment results of a randomized trial and an evaluation of late secondary effects. Frykholm, G. J., Glimelius, B., & Påhlman, L. (1993). Preoperative or postoperative irradiation in adenocarcinoma of the rectum: final treatment results of a randomized trial and an evaluation of late secondary effects. Diseases of the Colon and Rectum, 36(6), 564– 72. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8500374 Short-RT Surgery 25.5 Gy in 5d Surgery Long-RT 60 Gy in 6-7 weeks Stage II/III Rectal cancer Variable Pre-Op XRT Post-Op XRT p Local recurrence rate 11% 22% 0.02
- 11. Preoperative Radiotherapy Combined with Total Mesorectal Excision for Resectable Rectal Cancer Kapiteijn, E., Marijnen, C. A. M., Nagtegaal, I. D., Putter, H., Steup, W. H., Wiggers, T., … van de Velde, C. J. H. (2001). Preoperative Radiotherapy Combined with Total Mesorectal Excision for Resectable Rectal Cancer. New England Journal of Medicine, 345(9), 638–646. https://doi.org/10.1056/NEJMoa010580 Short-RT TME 25.5 Gy in 5d TME Resectable rectal cancer (15 cm) (n=1861) Variable Pre-Op XRT TME alone p Local recurrence rate 2.4 % 8.2 % p<0.05
- 12. XRT CT Surgery TMEShort XRT TMECRT CRTTME Surgery CRTTME TMECRT CRTTME XRT CT CT CT Modality sequence in stage II-IVa rectal cancer Short, or Long RT FU, or Capecitabine Oxaliplatin vs no-oxaliplatin
- 13. Preoperative versus postoperative chemoradiotherapy for rectal cancer. Sauer, R., Becker, H., Hohenberger, W., Rödel, C., Wittekind, C., Fietkau, R., … German Rectal Cancer Study Group. (2004). Preoperative versus Postoperative Chemoradiotherapy for Rectal Cancer. New England Journal of Medicine, 351(17), 1731–1740. https://doi.org/10.1056/NEJMoa040694 Chemo-RT (CRT) TME 5040 cGy, FU 5000 mg/m2 continuous infusion 120 h, week 1 and 5 TME Post-operative Chemotherapy 5040 cGy, FU 5000 mg/m2 continuous infusion 120 h, week 1 and 5 + Boost 540 Gy Locally advanced (T3 or T4 or N+) rectal cancer (823)
- 14. Preoperative versus postoperative chemoradiotherapy for rectal cancer. Sauer, R., Becker, H., Hohenberger, W., Rödel, C., Wittekind, C., Fietkau, R., … German Rectal Cancer Study Group. (2004). Preoperative versus Postoperative Chemoradiotherapy for Rectal Cancer. New England Journal of Medicine, 351(17), 1731–1740. https://doi.org/10.1056/NEJMoa040694
- 15. Preoperative versus postoperative chemoradiotherapy for rectal cancer. Sauer, R., Becker, H., Hohenberger, W., Rödel, C., Wittekind, C., Fietkau, R., … German Rectal Cancer Study Group. (2004). Preoperative versus Postoperative Chemoradiotherapy for Rectal Cancer. New England Journal of Medicine, 351(17), 1731–1740. https://doi.org/10.1056/NEJMoa040694 Chemo-RT (CRT) TME 5040 cGy, FU 5000 mg/m2 continuous infusion 120 h, week 1 and 5 TME Chemo-RT (CRT) Rectal cancer (16 cm) (n=421) Variable Pre-Op CRT Post-Op CRT p Local recurrence rate 6% 13% p=0.006 5040 cGy, FU 5000 mg/m2 continuous infusion 120 h, week 1 and 5
- 16. XRT CT Surgery TMEShort XRT TMECRT CRTTME Surgery CRTTME TMECRT CRTTME XRT CT CT CT Modality sequence in stage II-IVa rectal cancer Short, or Long CRT FU, or Capecitabine Oxaliplatin vs no-oxaliplatin
- 17. Is there a benefit of adjuvant chemotherapy in rectal cancer?
- 18. Postoperative adjuvant chemotherapy in rectal cancer operated for cure Petersen, S. H., Harling, H., Kirkeby, L. T., Wille-Jørgensen, P., & Mocellin, S. (2012). Postoperative adjuvant chemotherapy in rectal cancer operated for cure. In S. H. Petersen (Ed.), Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd. https://doi.org/10.1002/14651858.CD004078.pub2
- 19. CT XRT CT Surgery TMEShort XRT TMECRT CRTTME Surgery CRTTME TMECRT CRTTME XRT CT CT CT Short, or Long CRT FU, or Capecitabine Oxaliplatin vs no-oxaliplatin No actual trial of this sort
- 20. Can capecitabine substitute for FU?
- 21. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Hofheinz, R.-D., Wenz, F., Post, S., Matzdorff, A., Laechelt, S., Hartmann, J. T., … Hochhaus, A. (2012). Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. The Lancet Oncology, 13(6), 579–588. https://doi.org/10.1016/S1470-2045(12)70116-X CRT (Capec) TME Two cycles of capecitabine (2500 mg/m(2) days 1-14, repeated day 22), followed by chemoradiotherapy (50·4 Gy plus capecitabine 1650 mg/m(2) days 1-38), then three cycles of capecitabineT Stage II/III Rectal cancer (n=401) Variable Capecitabine FULV p 5-yr OS 76% 67% p=0.05 (post-hoc) Capec. x3-5 Capeci. x2 CRT (FULV) TME two cycles of bolus fluorouracil (500 mg/m(2) days 1-5, repeated day 29), followed by chemoradiotherapy (50·4 Gy plus infusional fluorouracil 225 mg/m(2) daily), then two cycles of bolus fluorouracil FULV. x2-4 FULV. x2
- 22. XRT CT Surgery TMECRT CRTTME Surgery CRTTME TME CRT (FULV or Capec) CRTTME XRT CT FULV or Capec. CT Modality sequence in stage II-IVa rectal cancer Short, or Long CRT FU, or Capecitabine Oxaliplatin vs no-oxaliplatin FULV or Capec. TMEShort XRT
- 24. Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. Hong, Y. S., Nam, B.-H., Kim, K., Kim, J. E., Park, S. J., Park, Y. S., … Kim, T. W. (2014). Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. The Lancet Oncology, 15(11), 1245–1253. https://doi.org/10.1016/S1470-2045(14)70377-8 CRT TME FU/Capecitabine + RT CRT TME Stage II/III Rectal cancer (n=321) Variable FOLFOX FULV p 3-yr DFS 71.6 % 62.9 % p=0.04 FU/Capecitabine + RT FOLFOX (4 mo) FU/LV (4 mo)
- 25. XRT CT Surgery TMECRT CRTTME Surgery CRTTME CRTTME XRT CT CT Short, or Long CRT FU, or Capecitabine Oxaliplatin vs no-oxaliplatin TME CRT (FULV or Capec) FOLFOX or CAPOX Modality sequence in stage II-IVa rectal cancer FOLFOX or CAPOX TMEShort XRT Based on Phase II data Based on Phase II data
- 27. Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non- blinded, phase 3, non-inferiority trial. 2017). Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-in Short-RT TME 25.5 Gy in 5d Long-RT 25 x 2 Gy in 6-7 weeks Stage II/III Rectal cancer Variable Short without delay Short with delay Long with delay Local recurrence rate 7 (of 357) 10 (of 358) 7 (of 128) Within 1 week TME After 4-8 weeks TMEShort-RT 25.5 Gy in 5d After 4-8 weeks
- 28. XRT CT Surgery TMECRT CRTTME Surgery CRTTME CRTTME XRT CT CT Short, or Long CRT FU, or Capecitabine Oxaliplatin vs no-oxaliplatin TME CRT (FULV or Capec) FOLFOX or CAPOX Modality sequence in stage II-IVa rectal cancer FOLFOX or CAPOX TMEShort XRT
- 29. Non-standard
- 30. Cercek, Proc ASCO, 2017
- 31. Cercek, Proc ASCO, 2017
- 32. Total neoadjuvant therapy TNT +/- TME CRT (FULV or Capec) FOLFOX or CAPOX % Surgery % No surgery TNT 78.2 21.8 Conventional 94.0 6.0 Cercek, Proc ASCO, 2017 RETROSPECTIVE
- 33. Gu, J. Proc ASCO, 2017
- 34. Gu, J. Proc ASCO, 2017
- 35. Conclusions • Multimodality is essential for optimal outcomes in rectal cancer • Pre-operative radiation improves loco-regional control (but does not affect survival) • Both Short-course and Long-course RT are beneficial • Pre-operative chemo-radiation ALSO improves loco-regional control (but does not affect survival) • FU-based or Capecitabine-based are acceptable. • Type of surgery is settled: MUST be a TME. • Timing of surgery is evolving • A few days, to never. • Adjuvant chemotherapy appears to improve OS in rectal cancer • At least with FU (or Capecitabine) • Some evidence of benefit with Oxaliplatin + FP • TNT, Watch and Wait, Trametinib + CRT, are areas of intense scientific inquiry.
- 36. @onconerd