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Interventional Oncology vs. Liver Tumors: Whats in the quiver? Howard M. Richard, III, MD.

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Presentation on theme: "Interventional Oncology vs. Liver Tumors: Whats in the quiver? Howard M. Richard, III, MD."— Presentation transcript:

1 Interventional Oncology vs. Liver Tumors: Whats in the quiver? Howard M. Richard, III, MD

2 Disclosures None

3 Overview Explain the various modalities utilized in the treatment of liver tumors Discuss the nature of clinical evidence for the various interventional oncology options for treating liver tumors Discuss the rationale for choosing between the various options based on the varied clinical presentations of liver tumors

4 History Liver resection for cure Only 20% of patients are candidates for curative resection Liver transplant – Scarcity of livers > up to 30% of candidates will have disease progression and fall off transplant list Liver resection – Lobectomy, segmentectomy...

5 Resection for cure Milan criteria for liver transplantation – One lesion smaller than 5cm – Three lesions smaller than 3cm – No extra-hepatic disease – No vascular invasion Partial liver resection – Functional liver remnant

6 Resection for cure 26% functional liver reserve for patients with normal liver function 40% high grade steatosis and after oxaliplatin- or irinotecan-based neoadjuvant chemotherapy >50% of the total liver volume for cirrhotic

7 Pathology Primary – Hepatocellular carcinoma Secondary – Colorectal liver (most common) – Neuroendocrine Carcinoid – Breast, melanoma, etc...

8 Modalities Resection – Bridging treatment – Prior to OLT or hepatectomy Resection after down-staging – Portal vein embolization Palliative – Ablation – Embolization – Adjuvant medications

9 Resection for cure Extended resection Staged resection Preoperative portal vein embolization to increase future remnant liver volume Resection combined with tumor ablation

10 Portal vein embolization Patients with marginal or insufficient functional liver reserve Ipsilateral hepatic atrophy Contralateral hepatic hypertrophy In non cirrhotic patients % hypertrophy of contralateral lobe

11 Portal vein embolization Ipsilateral access into portal veins Limits any iatrogenic damage to the eventually resected portion of the liver

12 Portal vein embolization PVA N-butyl cyanoacrylate Fibrin glue/Lipiodol Gelfoam and thrombin Coils Gentamycin Ethanol

13 Portal vein embolization Can increase the size of the liver remnant % More effective in enlarging the left lobe Using Ethanol requires balloon occlusion

14 Ablation Thermal – RF, Laser, Microwave, HiFUS, Cryo Chemical – Alcohol, acetic acid, other Irreversible Electroporation

15 Ablation Thermal vs Non thermal Thermal – RFA is predominant – Laser, Microwave, HiFUS, and Cryo are much less popular Non thermal – Ethanol is inexpensive – Proven inferior to RFA – IRE is emerging as an option

16 Embolization Bland Chemoinfusion Chemoembolization Radio embolization Adjuvant medications

17 Bland embolization Concept of hepatic arterial embolization 1950s Tumors derive 90% of blood from hepatic artery while portal vein provides majority of flow to liver Goal is terminal arterial blockade 40 um particles optimally block tumor neo- vascular network

18 Bland embolization Fistulas allow systemic non-target embolization Tumor ischemia > Hypoxia Stimulation of angiogenesis – Up-regulate pro-angiogenic factors – Provide mechanism for resisting apoptosis Associated with metastasis – Poor outcomes

19 Bland embolization Benefits – Inexpensive – Repeatable Disadvantages – Non target embolization of gallbladder, pancreatitis, liver failure – Liver abscess

20 Chemo infusion Infuse drug alone no embolization Infuse chemotherapeutics with first pass hepatic metabolism – Maximize tumor exposure to drug – Minimize systemic toxicity

21 Chemo infusion First premise > liver can clear the drug at first pass even at high dose Second premise > increased drug concentration in liver leads to increased response Third premise > regional drug delivery leads to decreased systemic exposure to drug

22 Chemo infusion Colorectal cancer – Floxuridine FUDR Increase response rate when compared to systemic chemo Usual referral is for patients who progress on traditional chemo HCC no improvement in survival when compared to systemic chemo

23 Chemo embolization Drugs and Gelfoam embolization introduced in the 1970s by Yamada Currently defined as – Infusion of a mixture of chemotherapeutics with or without iodized oil followed by particle embolization Purpose – Prevent washout of drug – Induce tumor ischemia

24 Chemo embolization Higher local drug concentrations Lower systemic drug exposure – Compared to systemic treatment Lipiodol is believed to increase intra-tumoral retention of the chemotherapeutics Worldwide > single agent Doxyrubicin US > Doxyrubicin, Cisplatin and Mitomycin C

25 Chemo embolization 2002 Lo and Llovet reported RCT vs HCC – Survival benefit for TX of HCC – When compared to standard supportive treatment 2006 Geschwind reported RCT vs CRC – Survival benefit for TX of CRC Effective in generating tumor response – Neuroendocrine, breast, cholangiocarcinoma...

26 Chemo embolization 2009 Vogl retrospective TACE with – Mitomycin C vs Mitomycin C and Gemcitabine for neuroendocrine liver mets Combination therapy Improved local control Improved five year survival

27 Chemo embolization Breast cancer mets to liver – Local control can be established Sarcoma mets to liver – Significant tumor necrosis – Improved survival

28 Drug eluting Beads Chemoembolization with special beads Load PVA based beads with various types of chemo and deliver to hepatic artery Once on location, beads release drug Sustained and controlled release Improve local delivery and minimize systemic exposure

29 Drug eluting beads DC beads Biocompatibles Yellow Blue Red

30 Drug eluting beads Quadraspheres Biosphere/Meritt Beads swell upon exposure to ionic fluids – Conforms to vessels Studies as a bland agent Can absorb Doxyrubicin

31 Drug eluting beads Doxyrubicin-capable or DC beads – Load with doxyrubicin 25mg/ml by immersion in drug solution for minutes. – Requires drug compounding in the pharmacy DC beads have been loaded with Irinotecan for use against colorectal liver mets Quadraspheres can be loaded with Doxyrubicin

32 Drug eluting beads Tumor response rates for DC beads vs HCC – 10-20% total response – 40-60% partial response rates Irinotecan vs CRC mets – 19 month overall survival in patients who had progressed on systemic chemo Safe and effective Expensive

33 Radio embolization

34 Yttrium-90 microsphere Glass sphere Yttrium-89 is converted to Yttrium-90 Beta decay to Zirconium-90

35 100 Gy HCC study Objectives : Define activity of Yttrium-90 microspheres in previously untreated patients with HCC Evaluate treatment response and survival of patients treated with Yttrium-90 microspheres Survival benefit Dancey, JE, Shepherd, FA, Paul, K, Sniderman, KW, Houle, S, Gabrys, J, Hendler, AL, & Goin, JE. Treatment of Nonresectable Hepatocellular Carcinoma with Intrahepatic 90 Y-Microspheres J Nucl Med 2000; 41:

36 100 Gy HCC study DAYS > 104 Gy (N = 10) Median Survival = 635 days < 104 Gy (N = 10) Median Survival = 323 days Survival of Patients Receiving TheraSphere By Liver Dose

37 TheraSphere ®

38 SIR-Spheres Initially developed in micron spheres Impregnated with yttrium-90 Particles emit beta radiation

39 SIR Sphere Characteristics 35 m 100% ß emitter MeV Half-life of 64.2 h 2.5 mm av (max 11) Glass/Ceramic matrix

40 SIR-Spheres Selective Internal Radiation Particles lodge in capillaries of tumor Size and number of tumors does not matter

41 SIR-Spheres 90Y-microspheres do not undergo any biologic degradation Activity decays to infinity at a mean life of 3.86 d Beta particle decay – average range in tissue is 2.5 mm – with a maximum range of < 11mm

42 Trans-Arterial Hepatic LDR Brachytherapy T ARGETED D ELIVERY L ETHALITY

43 Radioembolization Response rate 90% * – Falling tumor markers and serial 3-monthly CT scans HCC can be down-staged to OLT, resection or ablation Increased survival, tumor response time and time to progression when compared to 5-FU vs CRC * Hepatogastroenterology Mar-Apr;48(38):333-7.

44 Dose Distribution and Effect PET Before TheraSphere ® PET After TheraSphere ® MAA

45 Adjuvant chemotherapy Sorafenib (Nexavar, Bayer) – MultiKinase inhibitor (anti VEGF) – Can be used to decrease intratumoral arteriovenous fistulas and enable SIR Bevacizumab (Avastin, Genentech) – Monoclonal antibody to vascular endothelial growth factor – Augments efficacy of TACE vs HCC

46 Discussion Radioembolization vs HCC – Treatment can down stage patients to become eligible for transplant, resection or ablation Radioembolization vs CRC – Compared to hepatic artery chemotherapy Decreased time to progression Increased survival Radioembolization vs neuroendocrine – Increased survival compared to systemic treatment

47 Discussion Lo and llovet RCT for HCC – Chemoembolization is superior to best supportive care DEB vs embolization – DEB is superior to bland embolization – Longer time to progression

48 Discussion DEB vs chemoembolization – DEB higher rate of response – DEB fewer adverse events – DEB has yet to show a survival benefit Radioembolization vs Chemoembolization – SIR better at downstaging HCC – SIR less toxicity – SIR has yet to show survival benefit

49 Discussion Surgery compared to embolization and ablation for HCC up to 7cm – Five year survival 56 to 54% Chemoembolization vs CE and ablation for HCC 3-5cm – CE & RFA is more effective Radio embolization & 5-FU vs 5-FU for CRC – SIR & 5-FU is well tolerated, improved time to progression

50 Conclusions Ablation with RFA is choice for small tumors when surgery or transplantation is not feasible IRE is a choice when ablation target is adjacent to large vessels (Heat Sink) or central bile ducts Ethanol or cryoablation can be used if target is in sensitive location ie. Near the dome of the diaphragm or heart

51 Conclusions Chemoembolization is standard for intermediate/ advanced unresectable HCC CE can help select patients for OLT (bridge) Combination of CE and Ablation is effective with limited toxicity Drug eluting bead will replace oil based chemoembolization

52 Conclusions Y-90 is safe and effective as outpatient TX Y-90 for HCC – Downstaging / bridging to transplantation or resection – Portal vein thrombosis – Advanced disease

53 Decisions decisions Milan criteria for resection – If close consider portal vein embolization, CE, SIR Few lesions – Ablation Moderate disease – CE Extensive disease – SIR


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