Locoregional Therapy for Hepatoma Robert D. Crane, MD Interventional Radiology Virginia Mason
How do we know a liver mass is HCC?
HCC : Bx Of pts getting liver transplant only ~ 5% had Bx to establish Dx of HCC Risk of needle tract seeding from Bx estimated to be 2-3%
BCLC staging of HCC Barcelona 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 ablation RFA complication risks risk factors death <1% liver failure, hemorrhage, or recalcitrant abscess liver failure 1 2% liver reserve and ablation volume hemorrhage 2 4% abnl coagulation profile infection/ abscess <5% prior intervention of Sphincter of Oddi bowel/gb/biliary injury 1% adjacent to tumor tumor lysis syndrome <1% large ablation volume pneumothorax <5% transpleural approach 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
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 / ctace results ctace better than best supportive care ctace not better than bland embolization / TAE No clear consensus on methods or procedural techniques
TACE / ctace results 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. ctace Precision 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 in HCC at 3-20 x background liver 95% radiation discharged within 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 Tx summary 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
-»» Lammer CVIR 2010
UNOS/OPTN United 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 candidate HCC 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 board Hepatology HPB surgery Interventional radiology Oncology Radiation oncology
Lammer CVIR 2010