1 / 42

Case

Management of Colorectal Liver Metastasis Bert H. O’Neil, MD Associate Professor of Medicine Director, GI Oncology Research University of North Carolina Lineberger Comprehensive Cacer Center. Case. 22 y/o female college student presents with abdominal pain and BRPBR

galatea
Download Presentation

Case

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Management of Colorectal Liver MetastasisBert H. O’Neil, MDAssociate Professor of MedicineDirector, GI Oncology ResearchUniversity of North CarolinaLineberger Comprehensive Cacer Center

  2. Case • 22 y/o female college student presents with abdominal pain and BRPBR • CT showed intussusception at hepatic flexure, colonoscopy showed fungating mass in same region, mod diff adeno • MRI shows liver mets • Patient undergoes R hemicolectomy prior to visit with medical oncology

  3. Question 1 • Surgeon tells you disease is unresectable, what is the reason? (show MRI again) • Bilobar disease • Greater than 3 metastases • Vascular involvement • Insufficient expected liver reserve

  4. RIGHT HEPATIC LOBECTOMY FOR METASTATIC CARCINOMA OF THE LARGE BOWEL. FIVE-YEAR SURVIVAL. • PEDEN JC Jr, BLALOCK WN. • Cancer. 1963 Sep;16:1133-40.

  5. Hepatic Resection Prognostic Factors 1) Positive margin 2) Extrahepatic disease 3) Node-positive primary 4) Disease-free interval < 12 months 5) Number hepatic tumors > 1 6) Largest hepatic tumor > 5 cm 7) CEA level > 200 ng/mL Fong et al, Ann Surg 230:309, 1999

  6. Hepatic Resection:Survival Score5 Year Survival (%)Median Survival 0 60 74 mo 1 44 51 2 40 47 3 20 33 4 25 20 5 14 22 Fong et al, Ann Surg 230:309, 1999

  7. Resectable Liver Metastasis- Adjuvant Therapy • Precise definition of this entity is difficult, but most would agree that 4 or less mets to a single lobe are readily resectable • Coceptually similar to stage III disease • Prior studies of 5-FU based therapy suggested trend toward OS • Many oncologists have empirically added bevacizumab in this setting

  8. Studies of 5FU in Resected CLM * NS for OS

  9. EORTC 40983- Perioperative FOLFOX vs. Surgery for resectable CLM • Eligibility: • 1-4 Liver metastases that were technically resectable • No extrahepatic (non-primary) disease • No prior oxaliplatin • Design: • Experimental arm: 6 cycles (12 weeks) FOLFOX4 pre- and post surgery Lancet. 2008 Mar 22;371(9617):1007-16

  10. Complications of surgery *P=0.04

  11. Results Lancet. 2008 Mar 22;371(9617):1007-16

  12. Progression-free survival in resected patients HR= 0.73; CI:0.55-0.97, p=0.025 100 90 +9.2%At 3 years 80 Periop CT 70 60 50 42.4% 40 Surgery only 30 33.2% 20 10 0 (years) 0 1 2 3 4 5 6 O N Number of patients at risk : 104 152 85 59 39 24 10 93 151 118 76 45 23 6

  13. Conclusions- Resectable Liver Metastasses • 5FU-based therapy never proven effective • FOLFOX probably standard, but less effective than we would have thought based on stage III results • No evidence that pre-operative therapy is necessary vs. postoperative • Bevacizumab is of unproven benefit in this group of patients, and C08 suggests it may not be helpful as adjuvant therapy • What to do with resectable disease that arises after adjuvant FOLFOX???

  14. Unresectable CLM

  15. Hopital Paul Brousse Experience Response to chemotherapy 69% 7.2 % Complete Path. Response Adam et al, Ann Surg 2004

  16. Hopital Paul Brousse Experience Adam et al, Ann Surg 2004

  17. What Therapy for Initially Unresectable CLM?

  18. FOLFIRI vs. FOLFOXIRI A. Falcone et al, ASCO GI Symposium, Jan 2006, Abstract 227

  19. FOLFIRI vs. FOLFOXIRI A. Falcone et al, ASCO GI Symposium, Jan 2006, Abstract 227

  20. NO16966 (post hoc analysis):Surgery with curative intent ITT population Liver mets only 19.2% 8.4% 12.9% 6.1% Percent of patients n=701 n=699 n=178 n=177 XELOX / FOLFOX4 + placebo XELOX / FOLFOX4 + bevacizumab Cassidy, WCGIC 2007

  21. Retrospective Study of Chemo with or without Bevacizumab Pathologic Response and Toxicity

  22. FOLFIRI alone Cetuximab + FOLFIRI 10 9.8 9 8 7 6 5 Percentage (%) 4 4.5 3 2 1 0 No residual tumor in patients with liver metastases n=134 / n=122 CRYSTAL trial:Surgery with curative intent ITT population(pre-planned) Liver metastases only population(exploratory) p=0.0034* odds ratio 3.0 [95% CI: 1.4 - 6.5] n=599 / group n=599 / group *CMH test

  23. Case Cont’d • Patient was enrolled on CALGB/SWOG 80405, randomized to bev arm (FOLFOX was chosen backbone) • After 3 cycles of therapy (beginning 6 weeks post-op), she developed pain in pelvis and right thigh • MRI: Peripherally enhancing fluid collection tracking along the right intra-pelvic iliopsoas musculature into the anterior right thigh and about the sartorius and gracilis muscles, consistent with abcess. • Yikes!

  24. Question 3 • What do we lose by omitting bevacizumab? • Chance of response decreases by 10% compared with FOLFOX alone • Chance of resectability decreases by 10% compared to FOLFOX alone • Median PFS decreases by 2 months • Median overall survival decreases by 2 months • None of the above is true

  25. SBRT for Unresectable mCRC

  26. Prospective Trials of Stereotactic Body Radiation Therapy for Hepatic Metastases

  27. Local Control by SBRT Rusthoven et al JCO 2009 27 (10) : 1572

  28. Response to CyberKnife

  29. 90-Ytrrium Microspheres

  30. 90Y Microspheres for Refractory LC-mCRC Hendlisz A et al, JCO 2010; 28(23): 3687

  31. 90Y Microspheres for Refractory LC-mCRC 10% PR rate for 90Y spheres + 5FU, 0% for 5FU alone Hendlisz A et al, JCO 2010; 28(23): 3687

  32. RFA

  33. Non-curative Ablation for mCRC:Does it Improve Survival in FOLFOX era? • EORTC 40004 (CLOCC): RPII adding RFA to systemic CT in patients with ≤ 9 unresectable CRC LM and no extrahepatic disease • 119 patients randomized 2002-2007 • CT was FOLFOX (+ bev beginning in 2005) • 30-months OS rate: (primary endpoint) • 61.7% (95% CI, 48.21-73.93) in the RFA +CT • 57.6% (44.07-70.39) in the CT arm (higher than anticipated in study design!) • PFS 16.9 mos vs 9.9 • Conclusion- liver only mets have better prognosis, not clear if RFA changes it

  34. Our patient • Underwent R hepatectomy with biopsy of SBRT site and repair of anastamosis/fistula • Still some viable disease at SBRT site • Now back on FOLFOX (without bevacizumab)

  35. Conclusion • Surgical therapy can be curative of CLM • Adjuvant therapy remains standard, but actual proof is lacking (even after EORTC study) • Modern systemic therapy has allowed for the pool of eligible patients to increase • The best “conversion” therapy remains to be defined • Newer options exist, but more data needed on use • Non-curative RFA does not obviously prolong survival in liver-only CLM, but larger studies may be necessary

More Related