Current Treatment of Colorectal Metastases. Dr. Thavanathan Surgical Grand Rounds February 1, 2005

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1 Current Treatment of Colorectal Metastases Dr. Thavanathan Surgical Grand Rounds February 1, 2005

2 25% will have metastases at initial presentation 25-50% 50% will develop metastases later 40% of potentially curative bowel resections will develop mets.

3 Natural History of Mets. 1. Turk & Wanebo studied 2581 patients - median survival was 10.6 months. 2. Rougier et al. - median survival 8.4 months 3. Farnell - Pulmonary mets. - 44% died within 1 yr - 91% died within 2 yr

4 Options Palliative Chemotherapy Radiotherapy Local Ablative Procedures Surgery

5 Chemotherapy Either A) Intravenous B) Intraarterial

6 Chemotherapy Intravenous 1) 5 Fu, Leucovorin Response rate Median of survival months 2) 5 Fu, Leucovorin & Irinotecan Response rate Median survival 14.8 months 3) 5Fu, Leucovorin & Oxaliplatin Response rate Median of Survival 16.2 months

7 Chemotherapy Recent Study with same drugs at higher dose (5Fu 2.6 g/m 2 ) response rate = 56% However: in 24% of patients dose had to be reduced due to toxicity. Overall survival 22 months.

8 Chemotherapy Intraarterial Tumour derives 90% of blood supply from hepatic artery (normal liver 30%) Drug Metabolism FuDR 5Fu 95% removed first pass - 40% removed first pass

9 Chemotherapy Techniques of intraarterial catheter placement A) open surgery B) laparoscopy C) Percutaneous w/ infusion pumps or ports.

10 Chemotherapy Principles of catheter placement Perfuse whole liver May need more than one catheter Avoid perfusing G.I. tract.

11 Chemotherapy Complications of intraarterial chemotherapy 1. Catheter problems 2. Biliary sclerosis 3. GI ulcerations and bleeding

12 Chemotherapy Results of Intraarterial Chemotherapy Meta-analysis analysis -> > Response rate of 41% (IV chemo 15-20%) -> > no survival benefit Recent French study: Oxaliplatin Intraarterially with IV 5Fu Leucovorin (every two weeks.) Response rate 64% 1 yr survival 82% 2 yr survival 63%

13 Chemotherapy Adjuvant intraarterial chemotherapy 3 randomized trials Kemeney study and Eastern cooperative group study criticized. Several patients excluded. German multi-institutional institutional study 226 patients Median survival 40.8 months for control group Median survival 34.5 months for treated group

14 Chemotherapy Transarterial chemoembolization Doxorubicin, Mitomycin C or Cisplatin Response rate 29% All transient Median time to progression = 8 months.

15 Radiotherapy Liver very sensitive to radiotherapy Dose limited to Gy. Systemic internal radiation therapy = SIRT Microspheres of Yttrium in resin - Injected intraarterially Tumour dose of radiation Gy Liver dose of radiation Gy Response - all are transient. Median Survival 9.8 months

16 Local Ablative Therapy 1. Perc.. Ethanol 2. Cryotherapy 3. Radioablation 4. Microwave ablation

17 Local Ablative Therapy Perc.. Ethanol under ultrasound or CT. Volume depends on size Once or twice a week. Complications fever, pleural effusion, cholangitis,, hepatic abscess, portal vein thrombosis and death. Giovannini 40 patients 58% complete necrosis 29% partial necrosis Mean survival 19 Months

18 Local Ablative Therapy Cryotherapy Liquid N 2 through probe - placed under U/S, open surgery, or laparoscopy Freeze for 15 min, thaw 5 min freeze/thaw cycles until ice ball extends 1 cm beyond the margin Mortality 1.6% Complication 6-29% 6 - biliary fistulae, liver subphrenic abscess, myoglobinuria, thrombocytopaenia, coagulapathy, multiorgan failure, cracked liver. Local recurrence 9-44% 9 Median survival 8-43 months.

19 Local Ablative Therapy Radioablation Applicable to lesions away from major blood vessels. Usually <3 cm diam and <3 in number. Estimated median survival 36 months. Cryotherapy felt to be more effective for larger lesions (>3cm) but more complications.

20 Surgery Surgery is only treatment with potential for cure/long-term survival. 5 yr mortality up to 47% - although most studies at 36% Principles Complete resection Adequate amount of residual liver Therefore, number, size and location of mets. critical.

21 Surgery Usual criteria employed for surgery: 1) Fit for major surgery 2) No extrahepatic unresectable disease 3) Number of mets.. 4 or less - recent studies show that no. of mets.. Is immaterial as long as safe, complete resection can be done. 4) Able to resect with 1 cm margin. 5) Adequate residual healthy liver > 40% failure risk minimal 30-40% moderate risk. < 30% risk is high.

22 Surgery Preoperative Tests: Bloodwork Chest X-rayX Colonoscopy CT Less routine tests include - chest CT, MRI, PET scan, CT portogram. - not standard, but may be necessary.

23 Surgery Type of Surgery (intraoperative U/S) Extended Lobectomy Lobectomy Segmentectomy Wedge Resection Extended Resections diaphragm, abd.. wall, lymphadenectomy,, IVC resection. - Can be combined with local ablative proc. s - Individualize according to patient.

24 Surgery Results mortality 0-5% complications 20-40% 5 yr survival 36% 10yr survival 25% Extended hepatic resections w/ IVC resection have mortality of 25% (no long term follow-up yet)

25 Surgery Postoperative treatment Chemotherapy not standard - IV or intraarterial Recurrrences that are resectable would have 2 nd and even 3 rd resections with equally good results.

26 New Trends To improve resectability 1) Neoadjuvant chemotherapy 2) Portal venous embolization 3) 2 stage hepatectomy

27 Neoadjuvant Chemotherapy Adam, Bismuth Paris. 701 patients unresectable (size, bad location, extrahepatic diseases) Neoadjuvant IV chemotherpy - w/ 5Fu, leucovorin and oxaliplatin - chronomodulated - reassess after 3 treatments 95 (13.5%) of them became resectable Mortality = 0, complication rate = 26% 5 yr survival 35% from resection 39% from start of chemo.

28 Portal Venous Embolization Principles Adam & Bismuth Surgery is feasible technically, but residual liver volume can be <40%. With PVE liver volume can increase 10-12% 12% And resection rate can increase 19% (Complication rate of 3%)

29 Two-Stage Hepatectomy Adam & Bismuth 398 unresectable patients After 1 st stage hepatectomy/chemo, 16 (4%) became eligible for curative second stage resection. Mortality 1 st stage = 0 Mortality 2 nd stage = 0 3 yr survival of 35% (long term results not available)

30 Colorectal Lung Mets. Similar considerations as liver mets. Surgery is a option when only a limited no. of mets.. are resected,, while leaving adequate functional lung parenchyma Mansel et al. - Median survival 3.5 years - 5 yr survival 45%

31 Resection of Lung and Liver Mets. Murota,, Sugihara Japan Studied 30 patients with lung and liver mets.. (12 of them synchronously) No. of lung nodules: 18 patients 1 nodule 5 patients 2 nodules 3 patients 3 nodules 2 patients 4 nodules 2 patients > 4 nodules

32 Resection of Lung and Liver Mets. Performed video assisted lung resection or thoracotomy Mortality = 0 1 yr survival = 86% 3 yr survival = 49% 5 yr survival = 43%

33 Conclusion Treatment of colorectal metastases: Surgery is most effective, but in a minority of patients. In future, progress on some systemic treatment is the answer

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