Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Chemoradiation vs Surgery for rectal cancer

1,067 views

Published on

Chemoradiation vs Surgery for rectal cancer. Dr. Chris Crane

Published in: Education
  • Be the first to comment

  • Be the first to like this

Chemoradiation vs Surgery for rectal cancer

  1. 1. Under what Circumstances would chemoradiation +/- LE be comparable to radical surgery? Christopher H. Crane, M.D. Program Director, GI SectionProgram Director, GI Section Department of Radiation OncologyDepartment of Radiation Oncology
  2. 2. No Disclosures
  3. 3. GI Mucosa Limits the XRT Dose • Many other tumors: definitive doses possible – Lung, head and neck, prostate, liver, anal ca • Luminal GI tumors: esophageal, gastric, rectal – The tumor resides within a serial organ at risk – Limits the dose to 54Gy or so.
  4. 4. Complications of Radical Rectal Surgery • Permanently altered bowel function – Often colostomy • Urinary dysfunction from 7-68% • Impotence 15-100% • Retrograde ejaculation 3-35%
  5. 5. NCDB LE Special Study (1994-96) Local Recurrence – T2 5- Year LE RR T2 22% 15% T2: p=0.01 You et al. Ann Surg 245(5):726-33, 2007 N=164 N=866
  6. 6. German Trial (CAO / ARO / AIO) Pre-operative vs Postoperative CXRT • Significantly lower acute toxicity rate – 27% vs 40%, p=0.001 • LR improved with preoperative CXRT – 5 yr: 6% vs 13%, p=0.001 • SP higher in preoperative CXRT – 39% vs 19%, p=0.006 – Subjective need for APR, not whole group • Significantly lower late toxicity – 14% vs 24%, p=0.01 • anastamotic stricture (12% vs 4%) • Diarrhea, SBO (9% vs 15%) Sauer, R NEJM, 351, 2004
  7. 7. CXRT / Mesorectal resection- cT3 N0 pts ypN+ according to ypT stage Crane, pESTRO 2004 ypT0 in T3 NX (including clinically node +) = 4/45 = 9% Bedrosian, J Gastroint Surg, 2004 Pathologic T Stage Institution 1 Institution 2 Institution 3 Total ypT0 0/27 (0%) 0/14 (0%) 1/43 (2%) 1/84(1%) ypT1 2/29 (7%) 0/12 (0%) 4/17 (24%) 6/58 (10%) ypT2 15/95 (16%) 12/97 (12%) 4/60 (7%) 31/252 (12%) ypT3 54/166 (33%) 62/164 (38%) 15/68 (22%) 131/398 (33%) ypT4 0 5/5 (100%) 2/2 (100%) 7/7 (100%)
  8. 8. Can Radical Surgery Be Avoided in Selected Rectal Cancer Patients?
  9. 9. *Responding patients Chemoradiation Followed by Local Excision*
  10. 10. Local Excision of T3 tumors after Preoperative XRT Study # Patients % pCR/mRD % LF (5-yr act) Median FU Mohiuddin, TJU, 1994 15 Downstaged 0 40 Kim, USF, 2001 17 100/0 0 19 Bonnen, MDACC, 2004 26 54/35 6 51 Lezoche, Italy 2005 46 0/23 5 55 Meadows, UF, 2006 16 56/44 21 (3 yr) 9 (with salvage) 27
  11. 11. Local Excision of T2 tumors after Preoperative XRT Study # Patients % pCR % LF Median FU Lezoche, Italy 2005 54 16(30%) 5 (5 yr) 55 Meadows, UF, 2006 16 T1/T2 4(25%) 9 (3 yr) 27
  12. 12. ypT stage All patients -seven studies LR T0 0/53 (0%) T1 1/45 (2%) T2 6/85 (7%) T3 7/33 (21%) Total 17/237 (7%) Cumulative recurrence rates based on ypT Stage CXRT/LE (cT2/cT3) Modified from Table 5, Borschitz, et al Ann Surg Onc, 2008
  13. 13. Randomized Trial - T2 Rectal Cancer CXRT then TAE vs Laparoscopic Resection • 40 pts • 50.4 Gy + PVI 5-FU (200 mg/m2 ) – 20 TAE – 20 LAP Resection • One recurrence in each group (5%) • Median FU 56 mo Lezoche, et al Surgical Oncology, 2005
  14. 14. ACOSOG Z6041 Study Design uT2 rectal cancer (EUS- MRI) CXRT Cape (850mg/m2 bid) oxali (50 mg/m2/wk) 54 Gy Local excision T0-T2 R0: Observation T3 or R+: radical resection F o l l o w <8 cm from anal verge <4 cm size Primary Obj: 3 yr DFS in uT2N0 Chan, ASTRO 2010
  15. 15. ACOSOG Z6041 Study Design uT2 rectal cancer (EUS- MRI) CXRT Cape (650mg/m2 bid) oxali (50 mg/m2/wk) 50.4Gy Local excision T0-T2 R0: Observation T3 or R+: radical resection F o l l o w <8 cm from anal verge <4 cm size Primary Obj: 3 yr DFS in uT2N0 Chan, ASTRO 2010
  16. 16. Conclusions Neoadjuvant CRT with CAPOX • 44% pCR • Only 5% of patients needed radical surgery • Long term follow-up is needed for LC endpoint • High GI toxicity rates Chan, ASTRO 2010
  17. 17. Author Wound dehiscence Transient incontinence Kim et al 1/26 (4%) 1/26 (4%) Ruo et al 1/10 (10%) None Schell et al None 2/11 (18%) Hershman et al NS NS Bonnen et al NS NS Stipa et al None 1/26 (4%) Lezoche et al 11/100 (11%) 2/100 (2%) NS, not specified; nCRT, neoadjuvant chemoradiation; LE, local excision. Complications, CXRT / TAE Modified from Table 3, Borschitz, et al Ann Surg Onc, 2008 •Wound complications do not appear to be a limitation •Diverting iliostomy could be perfomed
  18. 18. Non-operative Management in Complete Responders? • University of São Paulo, Brazil • Pre-op Chemoradiation (50.4 Gy + FU/LV) • 265 pts – Clinical CR = observation (n=71, 26%) • 2 endorectal failures, 5y OS 100% – Incomplete CR / radical surgery, pCR (n=22%, 8.3%) • 2 DOD, 5y OS 88% • Median follow-up 57.3 months Habr-Gama, Ann Surg. 240(4):711-718, 2004
  19. 19. Organ Preservation Model Locally Advanced Rectal Ca • Clinical selection will affect success – Tumor size, nodal status, tumor grade, others • Neoadjuvant CXRT – Endoscopic CR • Full thickness local excision = excisional biopsy of tumor bed – ypT0, no further surgery • Radical surgery only for non-responders: – Gross residual disease or ypT3 • What about microscopic residual disease? Crane, Annals of Surg Onc, (3) p288-90, 2006
  20. 20. Response of Primary Tumor to CXRT • Observing response of primary key to organ preserving strategy • Predicts Control of Microscopic Mesorectal Disease • Could predicting response help? – Only if it leads to personalized therapy – Increase the pool of responders • Pair agents to patients – Proteomics, genomics • Change agents during therapy (PET)?
  21. 21. The Message Regarding Pre-op/LE • Promising strategy, especially in responding patients • Better long term GI and sexual function • Salvage rates of LR 50-70% – Close FU is critical • Multidisciplinary team has to be on the same page

×