William Lo, HMS MD/PhD candidate, MS III Gillian Lieberman, MD <05/17> State-of-the-art minimally invasive interventions for liver tumors William Lo, HMS MD/PhD candidate, MS III Gillian Lieberman, MD
Agenda Introduction to IR interventions for HCC IR Cases Limitations of RFA State-of-the-art research 2
Introduction Hepatocellular carcinoma: aggressive tumor (median survival 6-20 months) Current treatment options: Surgical: resection, orthotopic liver transplantation Nonsurgical: radiofrequency ablation (RFA), microwave ablation, cryoablation, transarterial chemoembolization (TACE), Y-90 radioembolization, radiation therapy, systemic therapy IR interventions play a key role in the management of unresectable HCC and as a bridge to transplant 3
Radiofrequency ablation Radiofrequency ablation: heats up tumor using RF energy (typically ~500 khz) causing ionic agitation. Cool-tip electrode: larger lesion size (avoids charring tissue) Image credit: http://www.medtronic.com/covidien/products/ablation-systems/cool-tip-rf-ablation-system-andswitching-controller 4
Lesion formation Image credit: http://www.medtronic.com/content/dam/covidien/library/us/en/product/ablationsystems/cool-tip-ablation-zone-lesion-size-chart.pdf 5
Outcomes Complete radiographic response rates: 80-90% for tumors <3 cm Long-term outcome: 3-yr survival: Large lesions (>5 cm): 59% Medium-sized (2-5 cm): 74% Small (<2 cm): 91% Tateishi, Ryosuke, et al. "Percutaneous radiofrequency ablation for hepatocellular carcinoma." Cancer 103.6 (2005): 1201-1209. Choi, Dongil, et al. "Percutaneous radiofrequency ablation for early-stage hepatocellular carcinoma as a first-line treatment: long-term results and prognostic factors in a large single-institution series." European radiology 17.3 (2007): 684-692 6
Transarterial chemoembolization (TACE) Infuse chemotherapeutic agent into hepatic artery followed by particle embolization to block off blood supply to the tumor. Indications: unresectable, encapsulated HCC lesions that are too large or multifocal for RFA, or too close to major vessels or dome of liver. Image credit: https://www.mtvir.com/transarterial-chemoembolization-tace-is-a-nonsurgical-wayto-treat-certain-tumors-in-the-liver/ 7
Transarterial chemoembolization (TACE) Complications: 1) Postembolization syndrome (3-4 days) in 60-80% of patients RUQ pain Nausea Fatigue Transient elevation of ALT, AST and bilirubin Self-limited (full recovery in ~1 wk) 2) Systemic toxicity from chemo Image credit: https://www.mtvir.com/transarterial-chemoembolization-tace-is-a-nonsurgical-wayto-treat-certain-tumors-in-the-liver/ 8
Transarterial chemoembolization (TACE) Drug-eluting beads (DEB- TACE): reduces systematic toxicity of chemotherapy by slowly releasing the drug locally Example: Doxorubicineluting beads (LC beads) Image credit: http://www.angiodynamics.com/uploads/pdf/03-25-10-02-07-17-mlc%20344%20us.pdf 9
Y-90 radioembolization Intra-arterial injection of Yttrium-90 (90-Y)-labeled microspheres [TheraSphere, SIR-Spheres]: 20-30 µm in diameter SIRT: Selective Internal Radiation Treatment Particularly useful in cases of main portal vein thrombus or obstruction (where TACE is contraindicated) Milder postembolization syndrome Image credit: http://diiradiology.com/services/interventionalradiology/therasphere.php 10
Pt #1: Presentation 57 year old man with cirrhosis and HCC who presents with a suspicious 2.0 cm segment VI lesion 11
A useful tool to teach segmental liver anatomy Pauli EM, Staveley-O'Carroll KF, Brock MV, Efron DT, Efron G. A Handy Tool to Teach Segmental Liver Anatomy to Surgical Trainees. Arch Surg. 2012;147(8):692-693. doi:10.1001/archsurg.2012.689 12
Pt #1: Pre-procedural MRI Early enhancement in arterial phase Washout in portal venous phase with pseudocapsule Portal vein Segment VI lesion Segment VI lesion Kidney Aorta Spleen Kidney Aorta Spleen Courtesy of Dr. Ahmed and Dr. Redmond 13
Pt #1: Peri-procedural US Hypoechoic mass in the liver Courtesy of Dr. Ahmed and Dr. Redmond 14
Pt #1: Post-RFA US Hyperechoic lesion due to coagulation necrosis Courtesy of Dr. Ahmed and Dr. Redmond 15
Pt #1: Needle track RFA needle probe Courtesy of Dr. Ahmed and Dr. Redmond 16
Pt #1: Post-RFA C+ CT Hypodense lesion due to coagulation necrosis Courtesy of Dr. Ahmed and Dr. Redmond 17
Pt #2: Summary 68 year old man with compensated HCV cirrhosis c/b multifocal hepatocellular carcinoma (biopsy proven) s/p CyberKnife on 3/24/16 and RFA x 3, most recently on 12/15/16. 18
Pt #2: Pre-procedural MRI Band of enhancement in arterial phase Portal venous phase Segment VIII lesion Segment VIII lesion Aorta Spleen Aorta Spleen Courtesy of Dr. Faintuch and Dr. Wang 19
Pt #2: Pre-procedural MRI Hepatic arterial phase Portal venous phase Prior segment V ablation zone Prior segment V ablation zone Prior segment VI/VII ablation zone Prior segment VI/VII ablation zone Courtesy of Dr. Faintuch and Dr. Wang 20
Pt #2: Peri-procedural CT RFA needle probe Courtesy of Dr. Faintuch and Dr. Wang 21
Pt #2: Post-RFA C+ CT Hypodense lesion (coagulation necrosis) Courtesy of Dr. Faintuch and Dr. Wang 22
Limitations of RFA Peri-procedural localization of tumor margin on CT Limited efficacy in large tumors Heat sink effect: dissipation of heat through major vessels (under treatment of tumor and recurrence) Rates of complete necrosis for tumors with nonperivascular location: 88%; perivascular locations: 47% (heat sink effect!) Lu, David SK, et al. "Radiofrequency ablation of hepatocellular carcinoma: treatment success as defined by histologic examination of the explanted liver 1." Radiology 234.3 (2005): 954-960. 23
NIH-PA Author Manuscript NIH-PA Author Manuscrip Navigational guidance through image fusion Krücker et al. Page 19 Figure 8. Needle positioning using navigation relative to a prior PET scan registered and fused with the pre-procedural CT. The target location, a lymphoma directly adjacent to the heart, was clearly visible in the PET scan but was occult in CT. Krücker, Jochen, et al. "Clinical utility of real-time fusion guidance for biopsy and ablation." Journal of Vascular and Interventional Radiology 22.4 (2011): 515-524. Dr. Brad Wood, Director of the NIH Center for Interventional Oncology and Chief of IR, NIH Clinical Center 24
New form of combination RFA + Heat-Deployed Liposomal Doxorubicin Goal: Improve RFA treatment of larger lesions (>3 cm) by augmenting thermal effects with local heatdeployed chemo (and to treat microscopic disease) therapy Hong, Cheng William, et al. "Imaging features of radiofrequency ablation with heat-deployed liposomal doxorubicin in hepatic tumors." Cardiovascular and interventional radiology 39.3 (2016): 409-416. 25
Irreversible electroporation IRE: non-thermal tissue ablation technique that uses short electric pulses to create pores in the cell membrane (leading to necrosis) Typical treatment parameters: 90 pulses, 20-100 ms, 1500-3000V Advantage: ability to treat tumors near blood vessels Contraindications: Patients with pacemakers/arrhythmia NanoKnife (AngioDynamics) Narayanan, Govindarajan. "Irreversible electroporation for treatment of liver cancer." Gastroenterology & hepatology 7.5 (2011): 313. Deipolyi, Amy, et al. "Irreversible electroporation: evolution of a laboratory technique in interventional oncology." Diagnostic and Interventional Radiology 20.2 (2014): 147. Image Credit: http://www.angiodynamics.com/products/ nanoknife 26
Microscopic image guidance: real-time thermal therapy monitoring for epithelial lesions Novel contrast-free imaging technique to directly visualize the thermal coagulation zone at high resolution in an integrated optical imaging (OCT) and RFA clinical balloon catheter Treatment zone visualization using complex differential variance (at low and high energy setting) demonstrates a treatment depth (red bar) of ~700 μm and ~1000 μm (a, c), respectively, in porcine esophagus, consistent with the NBTC-negative (pink) region (b, d) indicative of thermal injury. e, epithelium; lp, lamina propria; mm, muscularis mucosa; sm, submucosa; mp, muscularis propria. Scale bars = 1 mm. Lo, W. C. Y., et al., "Microscopic image guidance: real-time radiofrequency ablation monitoring for Barrett s esophagus." Journal of Vascular and Interventional Radiology 2.28 (2017): S199-S200. Lo, W. C. Y., et al., Laser thermal therapy monitoring using complex differential variance in optical coherence tomography (Featured article in January 2017 issue), Journal of Biophotonics (2017), 10(1): 84-91. 27
Acknowlegements BIDMC Department of Interventional Radiology Dr. Gillian Lieberman, MD Dr. Sahil Mehta, MD Dr. Yifei Wang, MD Dr. Salomao Faintuch, MD Dr. Muneeb Ahmed, MD Dr. Fady El-Gabalawy, MD All the friendly nursing staff and technicians in the angio and CT suites 28