HEPATIC ARTERIAL INFUSION PUMP CHEMOTHERAPY IN HCC AND IHCC.pptx

Hepatic arterial Infusion pump chemotherapy- techniques, rationale, results and evidences....

1. HEPATIC ARTERIAL INFUSION PUMP CHEMOTHERAPY IN HCC AND IHCC PRESENTER DR HARSHAVARDHANA H P DNB RESIDENT GEM HOSPITAL MODERATOR DR RAJIV MAHARAJ CONSULTANT HPB UNIT GEM HOSPITAL Centre for HPB Surgery & Liver Transplantation, GEM Hospital & Research centre, presents PG Academic series

2. Contents of todays topic

3. WHAT IS HEPATIC ARTERIAL INFUSION (HAI)? Liver – directed therapy… What’s old is New…Again..? Fong Y Atlas UGI & HPB surgery Springer 2007 MAXIMUM LIVER TREATMENT MINIMUM SYSTEMIC SIDE EFFECTS

4. Rationale of HAI for unresectable or Multifocal ICC THE POWER OF FIRST- PASS METABOLISM Intrahepatic cholangiocarcinoma (ICC) is a primary tumor. ICC is often locally advanced , but not metastatic , at the time of presentation. ICC derives its blood supply from the hepatic arterial system . Surgically implantable HAI pump with programmable flow rate over 2 weeks . Can be used in combination with systemic therapy.

5. Rationale of HAI for unresectable or Multifocal ICC THE POWER OF FIRST- PASS METABOLISM Based on higher liver extraction of floxuridine (FUDR) vs 5-FU during intra-arterial therapy ( 94-99% VS 19-55%) - FUDR + Dexamethasone FUDR follows linear kinetics without response saturation at high doses. Drugs with a high total-body clearance are more useful for hepatic infusion.

6. Drug levels after injection into Hepatic artery or Portal vein FUDR is a 5- flurouracil precursor that has high “first pass” liver uptake and has efficacy against ICC. Labelled H3- FUDR uptake Tumor (nmol/ g) Normal Liver (nmol/g) Hepatic artery 12.0 24.0 Portal vein 0.8 18.0

7. Clinical pharmacology of Hepatic arterial chemotherapy

8. INTRAHEPATIC CCA Shifting focus to unresectable / Multifocal liver only Rizvi S et al. Rev Clin Onc . 2017

9. FEASIBILITY IT TAKES A TEAM ….

10. TECHNIQUE

11. ABERRENT HEPATIC ARTERIAL ANATOMY PREFERRED TECHNIQUE LIGATION OF ISOLATED VESSEL. PLACEMENT OF CATHETER IN GDA. PRINCIPLE- INTRAHEPATIC COLLATERAL DEVELOPMENT & CROSS PERFUSION DURATION 4 WEEKS EXCEPTION – CENTRAL TUMORS BULKY TUMOURS

12. POSTOPERATIVE ASSESSMENT MALPERFUSION 5 to 7 % cases ANGIOGRAPHY OR SURGICAL INTERVENTION Tc labelled MAA SCAN

13. COMPLICATIONS OF HEPATIC ARTERY INFUSION PUMP PLACEMENT

14. Generalized operative morbidity 25%

15. PUMP RELATED MALFUNCTION 544 Hepatic Artery Infusion Pump Placements 25%

16. M ost common complications- Thrombosis Haemorrhage 3. Perfusion Abnormalities

17. HAI was discontinued for pump related complications in only 9% of cases. PUMP FAILURE RATE 6 MONTHS 5% 1 YEAR 9% 2 YEAR 16% 3 YEAR 26%

18. EXTRA HEPATIC PERFUSION PRESENTATION GI ULCERATION PANCREATITIS INVESTIGATIONS Tc MAA ANGIOGRAPHY TREATMENT ANGIOGRAPHIC EMBOLIZATION SURGICAL LIGATION

19. Incomplete Hepatic Perfusion – 2% CAUSES included failure to ligate a replaced or accessory hepatic artery Failure to achieve cross-perfusion after ligation of an accessory artery TREATMENT E mbolization or Surgical ligation of the accessory vessel

20. GASTRODUODENAL ULCERS Most frequent anomaly -small branch to the lesser curve of the stomach. Do not respond to standard antiulcer therapy DIAGNOSIS- ANGIOGRAPHY TREATMENT – ANGIOGRAPHIC EMBOLIZATION OR SURGERY

21. Arterial or Catheter Thrombosis – 2% Cause- technical errors Not filling the pump frequently or Allowing back bleeding into the catheter during sideport manipulation. First step- empty the pump and replace the chemotherapy with heparinized saline. Salvage rate with anticoagulation or lytic therapy – 31% First sign -abdominal pain occurring with chemotherapy. Delayed thrombosis was more common than early. Confirmation- extrahepatic perfusion on 99mTc MAA scan.

22. INFECTIOUS COMPLICATIONS Pneumonia UTI Wound infections Pump pocket infections Any sign of pump-pocket erythema should be treated early and aggressively with parenteral antibiotics.

23. BILIARY SCLEROSIS - 5.5 % Most frequent site – Common hepatic duct (87.5%) Causative factors- Larger dose of FUDR, Addition of Bevacizumab Post op surgical complications Salvaged by stenting or dilation Median survival was not compromised.

24. RESULTS AND EVIDENCES

25. Conclusion: HAIP chemotherapy with floxuridine for patients with unresectable iCCA was associated with a 3-year OS of 39.5% , which is favorable compared with systemic chemotherapy for which no 3-year survivors were reported in the Advanced Biliary Cancer (ABC) trials.

26. nine studies representing 478 patients HAI PUMP SYSTEMIC CHEMOTHERAPY 1 YEAR OS 86.4 62.5 2 YEAR OS 55.5 24.5 3 YEAR OS 39.5 5 YEAR OS 9.7 CURATIVE INTENT RESECTION <10%

27. Limitations:

28. Based on pooled analysis, the overall weighted median survival was 15.5 months .

29. 1- and 2-year OS of 69.7 and 46.5% respectively. This treatment could be considered in patients with small lesions in whom a complete resection is not possible.

30. HAI IN HCC

31. Conclusion:  Based on the present data, HAIC showed benefit effect in HCC patients, with pronged OS and DFS , as well as increased ORR and DCR . These benefit effects were more obvious in CRLM or advanced HCC patients . However, considering the potential limitations, more large-scale, randomized trials are needed to verify our findings.

32. Conclusion:  HAIC improved long-term survival for both resectable and unresectable HCC patients in comparison with other therapies. However, the clinical effect of HAIC needs to be ascertained by large-scale well-designed studies.

33. Conclusions:  This systematic review demonstrated that HAIC is superior to SORF in HCC with PVTT with respect to OS, PFS, and DCR, especially in HCC with types III-IV PVTT. HAIC caused more myelosuppression , whereas SORF is associated with diarrhea and hand-foot syndrome . Further randomized controlled trials are warranted.

34. Conclusion:  FOLFOX-HAIC significantly improved overall survival over TACE in patients with unresectable large hepatocellular carcinoma. MEDIAN OVERALL SURVIVAL – 23.1 vs 16.1

35. Conclusions:  This meta-analysis indicated that SoraHAIC seems to be efficient and safe for advanced HCC patients. However, additional large-scale randomized controlled trials are needed to further investigate the clinical benefit.

36. Conclusion:  HAIC offers a safe and effective alternative to Sorafenib with better tumor response and longer overall survival and progression-free survival, H ence, HAIC should be recommended for the patients with advanced HCC.

37. Conclusion:  To some degree, HAIC may be a better therapeutic method in patients with unresectable HCC than TACE.

38. Our meta-analysis showed that adjuvant HAIC improves overall and disease-free survival after resection, especially in tumors ≥7 cm .

39. CONCLUDING REMARKS HAIP chemotherapy with floxuridine has shown favorable 3-year OS of 39.5% and 50% to 70% response rate compared with systemic chemotherapy where no patients surviving beyond three years were observed in the ABC trials. HAIC improved long-term survival for both resectable and unresectable HCC patients in comparison with other therapies Proper surgical technique. Close follow up with Serial monitoring LFT. Even though these results are quite impressive, external validation of these results is necessary besides a well structured randomized controlled trials to optimally determine efficacy.

40. TEAM EFFORT

41. THANK YOU