Locoregional Therapy for Hepatoma - Axcesor · PDF file© 2013 Virginia Mason Medical Center Locoregional Therapy for Hepatoma Robert D. Crane, MD Interventional Radiology Virginia

© 2013 Virginia Mason Medical Center

Locoregional Therapy for Hepatoma

Robert D. Crane, MDInterventional Radiology

Virginia Mason


How do we know a liver mass is HCC ?


HCC : Bx

• Of pts getting liver transplantonly ~ 5% had Bx to establish Dx of HCC

• Risk of needle tract seeding from Bx estimated to be 2-3%


BCLC staging of HCCBarcelona Clinic Liver Cancer


HCC Tx : Locoregional methods• Percutaneous ethanol injection• Thermal ablation Radiofrequency Microwave

• Irreversible electroporation / IRE• Embolization Bland TACE/chemoembolization Drug eluting beads Y90 radioembolization

• External beam radiation


HCC Tx : Locoregional methods

• Tx Goal RFA/MWA potentially curative TACE/ Y90 palliative

• Downstaging Tx TACE , Y90, or ablation may allow pt to meet Milan

criteria for liver transplant• Bridging Tx Patients with HCC waiting for donor liver and who

have an estimated waiting time of at least 6 months.


Radiofrequency ablation/RFA

• Uses part of electromagnetic spectrum between 3 Hz and 300 GHz


RFA

• RFA probe acts as cathode, circuit is closed by dispersing pads on the patient’s thighs

• Water molecules forced to vibrate with alternating current frictional energy loss heat

• probe itself is not the source of heat• at 55 C, get tissue death in 2 sec• at 45 C, takes 15 minutes


Microwave ablation/MWA• Uses higher frequency part of radiofrequency spectrum• larger ablation zone, less dependent on tissue

thermal conductivity• grounding pads not needed

• Both RFA and MWA can be done percutaneously or with laparoscope

• very little information comparing the 2 modalities in clinical practice


RFA / MWA

• "heat sink effect“ can limit effectiveness of thermal ablation occurs when target tissue abuts or is near a blood

vessel flowing blood acts as radiator

• carries heat away and prevents creation of lethal temperatures


Liver lesion ablation

• Size lesions < 3 cm, ~95-100% complete ablation lesions > 5 cm, complete ablation unlikely

can combine ablation with TACE for lesions up to 7-8 cm

For lesions smaller than 3 cm, RFA has been shown to be equivalent to surgical resection with fewer complications


Liver lesion ablation

• Location avoid central hilar lesions , risk of bile duct or vascular

injury want ablation margin of > 0.5 cm

• diaphragm, heart/pericardium, gut, GB Hydrodissection

• introduction of artificial ascites



Liver lesion ablationrisks

• Liver abscess Altered Sphincter of Oddi, stent, surgical biliary anastomosis

• 40-50% incidence• 10% with pre and extended post antibiotics

May occur late at 1-3 months

RFA complication risk factors

death <1% liver failure, hemorrhage, or recalcitrant abscessliver failure 1‐2% liver reserve and ablation volumehemorrhage 2‐4% abnl coagulation profileinfection/ abscess <5% prior intervention of Sphincter of Oddibowel/GB/biliary injury 1% adjacent to tumortumor lysis syndrome <1% large ablation volumepneumothorax <5% transpleural approach


IRE Irreversible Electroporation

• Strong, short pulsed external electrical field is applied to tissue

• increased cell membrane permeability• cell death due to pores permanently opened• doesn't depend on temperature to kill tissue no heat sink effect

• spares connective tissues (vessels, duct ) Can Tx central lesions

• But, need 6 or more probes within 1-2 cm from each other to Tx a 4 x 4 cm lesion

• IRE not widely available


Embolization methods

• Bland / TAE Particles only, no chemo drug

• Chemoembolization / TACE / cTACE Drugs mixed with particles or Ethiodol

• Drug eluting beads / DEBs / DEBDOX / DEBTACE Beads with chemo, doxorubicin

• Radioembolization / TARE Y90 beads


Embolization

• Liver has 2 blood supplies Normal liver

• Portal vein 90 %• Hepatic artery 10 %

HCC• 90-100 % blood from hepatic artery

• Can cause selective ischemia of HCC• Can preferentially deliver higher concentration of

embolic agent to tumor, relative to adjacent liver


TACE / cTACE

• Multiple different methods of performing TACE• Embolic agent Particles

• 100-500 microns Gelfoam Ethiodol

• Oily contrast agent• ChemoTx drugs Single- doxorubicin, cis platinum Multiple- doxorubicin, cis platinum, mitomycin C


TACE / cTACEresults

• cTACE better than best supportive care• cTACE not better than bland embolization / TAE• No clear consensus on methods or procedural

techniques


TACE / cTACEresults

survival

# pts 1 yr 3 yr 5 yr

Atanaka 2159 65% 36% 18%

Savastano 57 75% 9%‐

Shijo 110 79% 38% 14%

Ukida 1075 61% 15%‐

Grosso 340 59% 27% 17%


Drug eluting beads DEBs / DEBDOX

• Negatively charged polymer• Interacts with positively charged drugs such as

doxorubicin • ChemoTx released over days

T1/2 = 6 days

• Minimal systemic chemo levels


Drug eluting beads / DEBs

• Hydrated size 100-300 micron 300-500 micron Newly released 75-150 micron

• Superior results with 100-300 vs 300-500• Dose of doxorubicin 50-75mg / vial


DEBDOX vs. cTACEPrecision V study

• Lammer et al CVIR 2010 • Multicenter , randomized, DEBDOX vs cTACE• 212 pts w Child-Pugh A/B cirrhosis, and large and/or

multinodular, unresectable HCC• tumor response at 6 months following blinded review of

MRI studies

79% DEBDOX vs 66% cTACE




DEBDOX Tx


DEB embolization

• Cone beam CT CT performed at the time of angiographic procedure Can identify vascular supply to HCC with greater

precision


Y 90 / Yttrium 90• Two Y90 products available• Therasphere is the only Y90 product approved for use

with HCC• glass microsphere embedded w radiation• 20-30 microns (1/3 diam of human hair)• Beta radiation, penetrates 2-3 mm• Half life is 2.7 days• Relies on Rad Tx, not embolic Tx

Non embolic / microembolic

• Can be used w portal vein invasion cases


Y 90

Y90 spheres accumulate inHCC at 3-20 x background liver• 95% radiation dischargedwithin 2 weeks

Sangro (Hepatology 2012)


Y 90 : planning & embo

• Planning angiogram Arterial anatomy defined Any at risk vessels leading to gut are pre-emptively

occluded, to avoid radiation ulcers• Nuclear Medicine Lung shunt study Tc-MAA injected in hepatic artery

• Want lung shunt to be less than 20%

• Lung dose to be < 30 Gray


Y 90 : Tx

• Tx dose calculated based on liver volume to be treated and tumor size Volumes from CT or MR

• Target 120 Grey to planned tx area• Calculated rad Tx dose ordered for specific day and time• Angiographic injection into target vessel Out pt procedure Lobar, segmental, or whole liver


Y 90 : results

• No randomized studies with direct comparison of Y90 to cTACE or DEBs

• Retrospective single institution analysis showed similar results comparing Y 90 to cTACE


Y 90 : results• Salem et al Gastroenterology 2010• 291 pts treated with Y90 • single-center, prospective, longitudinal cohort study• Response rate 57% based on EASL criteria


Y 90 : results

• Sangro et al (Hepatology 2011)• Multicenter European study, RCT• 325 pts• overall survival was 12.8 mo

varied significantly by disease stage• BCLC A, 24.4 months • BCLC B, 16.9 months • BCLC C, 10.0 months


Y 90 : results

• Y90 Tx well tolerated by pts Outpt procedure with minimal side effects Mild fatigue for 1 week

• Improvement of HCC by CT or MR tends to be more gradual than DEB or TACE Tumor shrinkage seen after 3-6 months May have confusing appearance on imaging

prior to 3 months


Locoregional HCC Txsummary

• Don’t bx mass suspected to be HCC unless needed after evaluation by multidisciplinary liver tumor

board

• RFA/MWA preferred when feasible• IRE promising, but has limited role now• DEBDOX superior to cTACE and bland embolization• Y90 and DEBDOX Best embolization methods available now No direct RCT comparison studies



Y 90

• Radiation segmentectomy Subselective injection of Y 90 with intent to ablate

entire segment of liver including the target HCC


• Lammer CVIR 2010


Y 90 : results• Salem et al Gastroenterology 2010


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» Lammer CVIR 2010


UNOS/OPTNUnited Network for Organ Sharing / Organ Procurement and Transplantation Network


BCLC staging of HCC


HCC Tx

• Surgical resection• Transplantation• Locoregional Tx• Chemotherapy• Best supportive care


HCC : Transplant candidateHCC size matters

• Milan criteria basis for selecting patients with cirrhosis and

hepatocellular carcinoma for liver transplantation. one lesion smaller than 5 cm up to 3 lesions smaller than 3 cm no extrahepatic manifestations no vascular invasion

• MELD score pts w HCC within Tx criteria get 22 MELD points ,

increasing q 3 months lesion needs to be 2 cm or greater to qualify


Y90 : results

• Salem et al Gastroenterology 2010


HCC

• VMMC Liver tumor boardHepatologyHPB surgeryInterventional radiologyOncologyRadiation oncology


• Lammer CVIR 2010

Documents

Locoregional Therapy for Hepatoma - Axcesor · PDF file© 2013 Virginia Mason Medical Center Locoregional Therapy for Hepatoma Robert D. Crane, MD Interventional Radiology Virginia