New Strategies in the Management of …...van Lienden KP, et al. Cardiovasc Intervent Radiol....
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New Strategies in the Management of Hepatocellular Carcinoma
Marti Russell, MD, FACSAssistant Professor of Surgery
Emory University Hospital MidtownGrady Memorial Hospital
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2Winship Cancer Institute | Emory University
Outline
• Background• Diagnosis• Surgery• Liver directed therapy• Radiation therapy• Systemic therapy• Treatment strategies to decrease the problem
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3Winship Cancer Institute | Emory University
Incidence• Fifth most common cancer in the world• Leading cause of cancer related mortality • Increasing incidence in the United States
• Hepatitis C induced cirrhosis• Nonalcoholic steatohepatitis/NAFLD
Ferlay J et al. Int J. Cancer. 2015;136:E359-E386.Seer.cancer.gov, accessed 07/07/17.
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4Winship Cancer Institute | Emory University
Risk Factors
Bruix J, et al. Hepatology. 2011;53(3):1020-1022.
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5Winship Cancer Institute | Emory University
Diagnosis
Bruix J, et al. Hepatology. 2011;53(3):1020-1022.
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6Winship Cancer Institute | Emory University
Staging
Dhir M, et al. Ann Surg. 2016;263(6):1112-1125.
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7Winship Cancer Institute | Emory University
Staging
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8Winship Cancer Institute | Emory University
Treatment Options for HCC
Surgery
IR Liver Directed
Radiation
Systemic
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9Winship Cancer Institute | Emory University
Surgical Resection
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10Winship Cancer Institute | Emory University
Surgery
• Degree of cirrhosis• Portal hypertension• Comorbidities• Insurance/citizenship status• Size of Lesions• Number of Lesions
Transplantation Resection
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11Winship Cancer Institute | Emory University
Milan Criteria
Overall Survival Recurrence-free SurvivalCriteria Met 85% 92%Criteria Not Met 50% 59%
Mazzaferro V, et al. N Engl J Med. 1996;334(11):693-699.
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12Winship Cancer Institute | Emory University
Organ Allocation
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13Winship Cancer Institute | Emory University
Proposed Changes 2017
Elwir S, et al. Gastroenterol Hepatol (N Y). 2016;12(3):166-170.
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14Winship Cancer Institute | Emory University
Extended Criteria for Transplant
Sapisochin G, et al. Nat Rev Gastroenterol Hepatol. 2017;14(4):203-217.
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15Winship Cancer Institute | Emory University
Downstaging
Yao FY, et al. Hepatology. 2008;48(3):819-827.
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16Winship Cancer Institute | Emory University
Downstaging
Yao FY, et al. Hepatology. 2008;48(3):819-827.
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17Winship Cancer Institute | Emory University
Downstaging
Gordon-Weeks AN, et al. Br J Surg. 2011;98(9):1201-1208. Pomfret EA, et al. Liver Transpl.2010;16(3):262-278.
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18Winship Cancer Institute | Emory University
Downstaging
Gordon-Weeks AN, et al. Br J Surg. 2011;98(9):1201-1208. Pomfret EA, et al. Liver Transpl.2010;16(3):262-278.
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19Winship Cancer Institute | Emory University
Surgical techniques to increase pool
Sapisochin G, et al. Nat Rev Gastroenterol Hepatol. 2017;14(4):203-217.
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20Winship Cancer Institute | Emory University
Increasing the Organs Available
Living donor transplant must be FLAWLESS.
Sapisochin G, et al. Nat Rev Gastroenterol Hepatol. 2017;14(4):203-217.
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21Winship Cancer Institute | Emory University
Resection• Non-cirrhotic patients• Well-compensated cirrhosis (Child-Pugh A)• No portal hypertension
• Platelet count > 100,000 (150,000)• No splenomegaly• No varices• No patent umbilical vein• Wedge pressure <10mmHg
• MELD < 10
• High recurrence rates
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Resection versus Transplant
Dhir M, et al. Ann Surg. 2016;263(6):1112-1125.
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23Winship Cancer Institute | Emory UniversitySquires MH 3rd, et al. J Surg Oncol. 2014;109(6):533-541.
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24Winship Cancer Institute | Emory UniversitySquires MH 3rd, et al. J Surg Oncol. 2014;109(6):533-541.
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25Winship Cancer Institute | Emory UniversitySquires MH 3rd, et al. J Surg Oncol. 2014;109(6):533-541.
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26Winship Cancer Institute | Emory University
Criteria Transplant Resection P valueWithin Milan Criteria N=131 N=45
5yr OS 65.7% 43.8% P=0.005RFS 85.3% 22.7% P<0.001
Milan + Hep C N=87 N=215yr OS 63.5% 23.3% P=0.001RFS 83.5% 23.7% P<0.001
Milan + MELD <8 N=12 N=305yr OS 62.5% 48.9% P=NSRFS 71.6% 30.8% P=0.08
Milan + Child Pugh A N=37 N=165yr OS 56% 35% P=0.7RFS 71% 37% P=0.04
Squires MH 3rd, et al. J Surg Oncol. 2014;109(6):533-541.
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27Winship Cancer Institute | Emory University
Future Liver Remnant
- 3-D CT reconstruction- TLV (cm3) =
-794.41 + 1267.28 x BSA (m2)- The standardized FLR:
FLR/TLV
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28Winship Cancer Institute | Emory University
• 44 articles with 1791 patients (20% with HCC)
• Technical success rate 99.3%• Clinical success rate 96.1%• Mean hypertrophy after PVE 37.9
+/- 0.1%• Major complications 2.5%• Mortality 0.1%
van Lienden KP, et al. Cardiovasc Intervent Radiol. 2013;36(1):25-34.
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29Winship Cancer Institute | Emory University
Laparoscopic Liver Resections
Nguyen NT, et al. Ann Surg.2009;250(5):631-641.
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30Winship Cancer Institute | Emory University
Laparoscopic Liver Resections
• Mortality 0.3%• Morbidity 10.5%• Negative surgical margins > 82%• Survival after resection HCC
• 50-75% 5 year OS• 31-38.2% 5 year DFS
• In experienced hands is safe with comparable oncologic outcomes
Nguyen NT, et al. Ann Surg.2009;250(5):631-641.
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31Winship Cancer Institute | Emory University
Robotic Liver Resections
Buchs NC, et al. Expert Rev Anticancer Ther. 2017;14(2):237-246.
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32Winship Cancer Institute | Emory University
Robotic Liver Resections
Buchs NC, et al. Expert Rev Anticancer Ther. 2017;14(2):237-246.
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33Winship Cancer Institute | Emory University
Robotic Liver ResectionsPerioperative Outcomes:• Operative Time: 137-507 minutes• Conversion Rate: 5.7-20%• Overall Complications: 7.8-46%• Hospital Stay: 6.1-11.7 days
So is it better than laparoscopy?• Hilum dissection• Biliary reconstruction• More data needed
Buchs NC, et al. Expert Rev Anticancer Ther. 2017;14(2):237-246.
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34Winship Cancer Institute | Emory University
Liver Directed Therapy
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35Winship Cancer Institute | Emory University
Locoregional Therapies
XMeza-Junco J, et al. Cancer Treat Rev. 2012;38(1):54-62.
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36Winship Cancer Institute | Emory University
Ablation
• Most suitable for tumors < 3cm• Recurrence based on size:
• <3cm = 14%• 3-5cm = 25%• >5cm = 58%
Chu KF, et al. Nat Rev Cancer. 2014;14(3):199-208.
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37Winship Cancer Institute | Emory University
Ablation
• Most suitable for tumors < 3cm• Recurrence based on size:
• <3cm = 14%• 3-5cm = 25%• >5cm = 58%
Chu KF, et al. Nat Rev Cancer. 2014;14(3):199-208.
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38Winship Cancer Institute | Emory University
Resection versus Locoregional Therapy
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39Winship Cancer Institute | Emory University
• Post op complications worse in surgery group• 1, 2, 3, 4 year overall survival:
• PLAT 95.8, 82.1, 71.4, 67.9%• Resection 93.3, 82.3, 73.4, 64.0%
• 1, 2, 3, 4 year disease free survival• PLAT 85.9, 69.3, 64.1, 46.4%• Resection 86.6, 76.8, 69.0, 51.6%
• Conclusion: no difference in overall or disease free survival; PLAT with fewer complications
High risk of bias secondary to 19 patients randomized to PLAT who withdrew and were treated with surgery.
Chen MS, et al. Ann Surg. 2006;243(3):321-328.
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40Winship Cancer Institute | Emory University
• HCC meeting Milan• Childs A or B• 115 each RFA vs Resection with 7 crossovers from RFA to resection
P=0.001 P=0.017
Huang J, et al. Ann Surg. 2010;252(6):903-912.
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41Winship Cancer Institute | Emory University
• HCC meeting Milan• Childs A or B• 115 each RFA vs Resection with 7 crossovers from RFA to resection
P=0.001 P=0.017
Huang J, et al. Ann Surg. 2010;252(6):903-912.
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42Winship Cancer Institute | Emory University
• HCC meeting Milan• Childs A or B• 115 each RFA vs Resection with 7 crossovers from RFA to resection
P=0.001 P=0.017
Huang J, et al. Ann Surg. 2010;252(6):903-912.
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43Winship Cancer Institute | Emory University
• 2 or less tumors with maximum diameter of 4cm• Childs A or B• Treatment naïve• 84 patients in each group
Feng K, et al. J Hepatol. 2012;57(4):794-802.
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44Winship Cancer Institute | Emory University
• 2 or less tumors with maximum diameter of 4cm• Childs A or B• Treatment naïve• 84 patients in each group
P=0.342 P=0.122
Feng K, et al. J Hepatol. 2012;57(4):794-802.
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45Winship Cancer Institute | Emory University
Radiofrequency vs Microwave AblationRFA
• Temperatures 60-100 C are generated by high frequency alternating current which induces frictional heating causing cell injury
• Cytotoxic temperatures difficult to maintain near major blood vessel secondary to heat sink
MWA• Uses electromagnetic fields to
create rotating molecules that produce heat without electric current
• More suitable for tissues with higher impedance (lung/bone) and solid organs
• Achieves better heating of larger tumor volumes
• Lower susceptibility to heat-sink effect
• Multiple antennae to amplify effectChu KF, et al. Nat Rev Cancer. 2014;14(3):199-208.
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46Winship Cancer Institute | Emory University
• Retrospective Review
• 53 patients/68 lesions• Milan criteria• Unresectable• Child’s A or B
• Conclusion:• No significant difference
Vogl TJ, et al. Abdom Imaging. 2015;40(6):1829-1837.
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47Winship Cancer Institute | Emory University
• 288 patients, 477 lesions• Single lesion ≤ 8cm; ≤ 5 lesions with
max dimension of 6cm per nodule• No pvt or extrahepatic metastases, • PT < 25 seconds, plt > 40,000• Nodules 5mm away from bile duct or
hilum and bowel• Not eligible for surgery
Liang P, et al. Radiology. 2005;235(1):299-307.
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48Winship Cancer Institute | Emory University
• 288 patients, 477 lesions• Single lesion ≤ 8cm; ≤ 5 lesions with
max dimension of 6cm per nodule• No pvt or extrahepatic metastases, • PT < 25 seconds, plt > 40,000• Nodules 5mm away from bile duct or
hilum and bowel• Not eligible for surgery
Liang P, et al. Radiology. 2005;235(1):299-307.
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49Winship Cancer Institute | Emory University
• 288 patients, 477 lesions• Single lesion ≤ 8cm; ≤ 5 lesions with
max dimension of 6cm per nodule• No pvt or extrahepatic metastases, • PT < 25 seconds, plt > 40,000• Nodules 5mm away from bile duct or
hilum and bowel• Not eligible for surgery
Liang P, et al. Radiology. 2005;235(1):299-307.
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50Winship Cancer Institute | Emory University
• 80 patients/117 lesions• No more than 3 lesions• 3-8cm• Child’s A or B w/o extrahepatic mets or vascular invasion• Not amenable or refused surgery
Liu Y, et al. Clin Radiol. 2013;68(1):21-26.
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51Winship Cancer Institute | Emory University
• 80 patients/117 lesions• No more than 3 lesions• 3-8cm• Child’s A or B w/o extrahepatic mets or vascular invasion• Not amenable or refused surgery
Liu Y, et al. Clin Radiol. 2013;68(1):21-26.
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52Winship Cancer Institute | Emory University
• 80 patients/117 lesions• No more than 3 lesions• 3-8cm• Child’s A or B w/o extrahepatic mets or vascular invasion• Not amenable or refused surgery
Liu Y, et al. Clin Radiol. 2013;68(1):21-26.
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53Winship Cancer Institute | Emory University
• 80 patients/117 lesions• No more than 3 lesions• 3-8cm• Child’s A or B w/o extrahepatic mets or vascular invasion• Not amenable or refused surgery
Liu Y, et al. Clin Radiol. 2013;68(1):21-26.
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54Winship Cancer Institute | Emory University
• 80 patients/117 lesions• No more than 3 lesions• 3-8cm• Child’s A or B w/o extrahepatic mets or vascular invasion• Not amenable or refused surgery
Multivariate analysis identified tumor size as the only independent prognosis factor (p=0.008).Risk of death for patients with tumors 5-8cm was 2.3x higher than those with tumors 3-5cm.
Liu Y, et al. Clin Radiol. 2013;68(1):21-26.
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55Winship Cancer Institute | Emory University
TransArterial ChemoEmbolization (TACE)Indications:• Unresectable Child Pugh A or B multifocal HCC w/o vascular invasion
Contraindications:• Resectable tumors• Decompensated cirrhosis (Child-Pugh ≥8) including jaundice,
encephalopathy and refractory ascites• AFP > 1000/uL• Tumor replacement of both lobes• Intractable infection• Uncorrectable bleeding disorder
Graf D, et al. Eur J Intern Med. 2014;25(5):430-437.
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56Winship Cancer Institute | Emory University
TACE/cTACE/DEB TACE
Dhir M, et al. Ann Surg. 2016;263(6):1112-1125. Nishikawa H, et al. Anticancer Res. 2014;34(12):6877-6886.
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57Winship Cancer Institute | Emory University
TACE/cTACE/DEB TACE
Dhir M, et al. Ann Surg. 2016;263(6):1112-1125. Nishikawa H, et al. Anticancer Res. 2014;34(12):6877-6886.
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58Winship Cancer Institute | Emory University
Preoperative TACEAuthor Number Design Results
Wu et al - 24 preop TACE28 control
Large HCC Prior to resection
Preoperative TACE delays surgery, increases difficulty without survival benefit
Yamasaki et al 50 preop TACE47 control
Solitary hcc, 2-5cmPrior to resection
No survival advantage
Zhou et al 52 preop TACE56 control
Prior to resection No difference in recurrence, DFS or OS but did result in lower resection rate (p=0.017)
Kaibori et al 42 preop TACE39 TACE + lipiodolization43 control
Prior to resection No change in DFS or OS
Nicolini et al16 cTACE22 DEB-TACE
Prior to liver transplant 3 year RFS (p=0.0493)61.5%87.4%Significant increase inflammatory reaction
Frenette et al 76 cTACE35 DEB-TACE
Prior to liver transplant No difference in necrosis, recurrence or dropout
Nishikawa H, et al. Anticancer Res. 2014;34(12):6877-6886. Wu CC, et al. Br J Surg.1995;82(1):122-126. Yamasaki S, et al. Jpn J Cancer Res. 1996;87(2):206-211. Zhou WP, et al. Ann Surg. 2009;249(2):195-202. Kaibori M, et al. Dig Dis Sci. 2012;57(5):1404-1412. Nicolini D, et al. World J Gastroenterol. 2013;19(34):5622-5632. Frenette CT, et al. Transplantation. 2014;98(7):781-787.
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59Winship Cancer Institute | Emory University
Radioembolization• Either resin or glass microspheres• Loaded with y90 – high energy radiation source with half life of 2.67
days and a short tissue penetration (2.5mm)• Patients with non-metastatic unresectable disease who are not
candidates for transplant or ablation• Can be used in patient with portal vein thrombosis• Bridge to transplant and downstaging• Criteria:
• Good performance status• Adequate pulmonary reserve• Creatinine <2mg/dL• Plt > 50,000• Child-Pugh ≤7
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60Winship Cancer Institute | Emory University
Radioembolization
Salem R, et al. Hepatology. 2013;58(6):2188-2197. Edeline J, et al. Liver Cancer. 2015;4(1):16-25.
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61Winship Cancer Institute | Emory University
TARE versus TACE
P=0.7803
Conclusions:• Abdominal pain and increased
transaminase activity more frequent in chemoembo group (p<0.05)
• Time to progression longer following radioembo (13.3mo versus 8.4mo; p=0.046)
• Median Survival 20.5 vs 17.4 (p=0.232)
Salem R, et al. Gastroenterology. 2011;140(2):497-507.
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62Winship Cancer Institute | Emory University
Cochrane Review
Abdel-Rahman OM, et al. Cochrane Database Syst Rev. 2016;2:CD011313.
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63Winship Cancer Institute | Emory University
Cochrane Review
Abdel-Rahman OM, et al. Cochrane Database Syst Rev. 2016;2:CD011313.
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64Winship Cancer Institute | Emory University
Cochrane Review
Abdel-Rahman OM, et al. Cochrane Database Syst Rev. 2016;2:CD011313.
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65Winship Cancer Institute | Emory University
Cochrane Review
Abdel-Rahman OM, et al. Cochrane Database Syst Rev. 2016;2:CD011313.
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66Winship Cancer Institute | Emory University
Cochrane Review
Abdel-Rahman OM, et al. Cochrane Database Syst Rev. 2016;2:CD011313.
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67Winship Cancer Institute | Emory University
Cochrane Review
Abdel-Rahman OM, et al. Cochrane Database Syst Rev. 2016;2:CD011313.
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68Winship Cancer Institute | Emory University
Potential advantages of TARE• Less toxicity, no inpatient stay, no pain management, improved quality
of life over TACE • Radiation segmentectomy – applying radiation to small sectors of the
liver• Radiation lobectomy – used for right lobe disease that is potentially
resectable but small FLR• Treats tumor while liver grows• As tumor treated, right sided atrophy and left sided hypertrophy• Wait time of 6-12 weeks allows biologic test of time
• Potential “downstaging” to transplant• 56% downstaging rate• Better downstaging than TACE (58% vs 31%; p<0.05)• Improved response rate (49% vs 36%; p=0.052)
Salem R, et al. Gastroenterology. 2011;140(2):497-507. Gilbertsen P, et al. J Vasc Interv Radiol. 2011;22:s79. Lewandowski RJ, et al. Am J Transplant. 2009;9(8):1920-1928. Kulik LM, et al. J Surg Oncol. 2006;94(7):572-586.
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69Winship Cancer Institute | Emory University
High Intensity Focused Ultrasound (HIFU)
• Under MRI or US, the ultrasound beam is directed a the target tissue resulting in a rapid local temperature increase followed by protein denaturation inducing coagulative necrosis
• Advantages: through the skin• Cons:
• Only available at a few centers• High cost (MRI guidance)• Time consuming • General or epidural anesthesia
• Limited data
Diana M, et al. Hepatobiliary Surg Nutr.2016;5(4):329-344.
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70Winship Cancer Institute | Emory University
High Intensity Focused Ultrasound (HIFU)
• Under MRI or US, the ultrasound beam is directed a the target tissue resulting in a rapid local temperature increase followed by protein denaturation inducing coagulative necrosis
• Advantages: through the skin• Cons:
• Only available at a few centers• High cost (MRI guidance)• Time consuming • General or epidural anesthesia
• Limited data
Diana M, et al. Hepatobiliary Surg Nutr.2016;5(4):329-344.
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71Winship Cancer Institute | Emory University
Radiation Therapy
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72Winship Cancer Institute | Emory University
3D Conformal RT/IMRT
• Allows profile shaping of the beam of radiation to match the profile of the tumor
• Modification of Intensity-Modulated Radiation Therapy – highly conformal doses to target structures with decreased scatter – further improvement of CRT
• Image guidance and breathing motion management have made it possible to deliver ablative doses of radiation
• Increased dose to target tissue with less surrounding toxicity
Dhir M, et al. Ann Surg. 2016;263(6):1112-1125.
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73Winship Cancer Institute | Emory University
Stereotactic Body Radiation
• Multiple highly accurate and precise beams to deliver radiation with rapid fall off doses away from the target
• Objective responses 37-90% with 2-year survival 43-82%• Complete path responses in 14-27% of patients• Risk for radiation induced liver disease, as well as progression of Child-
Pugh class, chest wall toxicity and biliary toxicity• Can be used as a bridge to transplant
Dhir M, et al. Ann Surg. 2016;263(6):1112-1125.
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74Winship Cancer Institute | Emory University
SBRT
Klein J, et al. Int J Radiat Oncol Biol Phys. 2013;87(1):22-32.
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75Winship Cancer Institute | Emory University
Protons?
Skinner HD, et al. Semin Radiat Oncol. 2011;21(4):278-286.
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76Winship Cancer Institute | Emory University
Protons?
Considerations:• Portal vein invasion• Centrally located tumors• Not suitable for RFA – close to diaphragm
or major blood vessels• Locally advanced tumors Child Pugh B or C
Skinner HD, et al. Semin Radiat Oncol. 2011;21(4):278-286.
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77Winship Cancer Institute | Emory University
Systemic Therapy
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78Winship Cancer Institute | Emory University
Median Survival:6.5mo vs 4.2moP=0.014
Time to Progression2.8mo vs 1.4moP=0.0005
Cheng AL, et al. Lancet Oncol. 2009;10(1):25-34.
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79Winship Cancer Institute | Emory University
Median OSSorafenib 10.7 moPlacebo 7.9 moP<0.001
Llovet JM, et al. N Engl J Med. 2008;359(4):378-390.
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80Winship Cancer Institute | Emory University
Median OSSorafenib 10.7 moPlacebo 7.9 moP<0.001
Median timeSorafenib 4.1moPlacebo 4.9moP=0.77
Llovet JM, et al. N Engl J Med. 2008;359(4):378-390.
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81Winship Cancer Institute | Emory University
Median OSSorafenib 10.7 moPlacebo 7.9 moP<0.001
Median timeSorafenib 4.1moPlacebo 4.9moP=0.77
TTPSorafenib 5.5moPlacebo 2.8moP<0.001
Llovet JM, et al. N Engl J Med. 2008;359(4):378-390.
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82Winship Cancer Institute | Emory University
Signaling Pathways and Potential Targets
Siegel AB, et al. Hepatology. 2010;52(1):360-369. Finn RS. Semin Liver Dis. 2013;33 Supple 1: S11-19.
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83Winship Cancer Institute | Emory UniversityFinn RS. Semin Liver Dis. 2013;33 Supple 1: S11-19.
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84Winship Cancer Institute | Emory University
Additional Trials
Finn RS. Semin Liver Dis. 2013;33 Supple 1: S11-19.
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85Winship Cancer Institute | Emory University
Additional Trials
Finn RS. Semin Liver Dis. 2013;33 Supple 1: S11-19.
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86Winship Cancer Institute | Emory UniversityBruix J, et al. Lancet Oncol. 2015;16(13):1344-1354.
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87Winship Cancer Institute | Emory UniversityBruix J, et al. Lancet Oncol. 2015;16(13):1344-1354.
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88Winship Cancer Institute | Emory UniversityBruix J, et al. Lancet Oncol. 2015;16(13):1344-1354.
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89Winship Cancer Institute | Emory University
Immunotherapy
Hong YP, et al. World J Hepatol. 2015;7(7):980-992.
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90Winship Cancer Institute | Emory University
Immunotherapy in HCC
Hong YP, et al. World J Hepatol. 2015;7(7):980-992. Sangro B, et al. J Hepatol. 2013;59(1):81-88.
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91Winship Cancer Institute | Emory University
Immunotherapy in HCC
Trememlimumab:PR – 17.6%Disease control 76%TTP 6 months
Hong YP, et al. World J Hepatol. 2015;7(7):980-992. Sangro B, et al. J Hepatol. 2013;59(1):81-88.
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92Winship Cancer Institute | Emory UniversityEl-Khoueiry AB, et al. Lancet. 2017;389(10088):2492-2502.
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93Winship Cancer Institute | Emory UniversityEl-Khoueiry AB, et al. Lancet. 2017;389(10088):2492-2502.
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94Winship Cancer Institute | Emory University
Immunotherapy
Harding JJ, et al. Cancer. 2016;122(3):367-377. Kudo M. Oncology. 2017;92(Suppl 1):50-61.
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95Winship Cancer Institute | Emory University
Immunotherapy
Harding JJ, et al. Cancer. 2016;122(3):367-377. Kudo M. Oncology. 2017;92(Suppl 1):50-61.
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96Winship Cancer Institute | Emory University
Future Combination Therapy
Chu KF, et al. Nat Rev Cancer. 2014;14(3):199-208.
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97Winship Cancer Institute | Emory University
Future Combination TherapyGALNT14 genotype-guided, sorafenib in combination with transarterial chemoembolization in hepatocellular carcinoma: An interim report of a prospective randomized controlled trial.
Chu KF, et al. Nat Rev Cancer. 2014;14(3):199-208.
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98Winship Cancer Institute | Emory University
Future Combination TherapyGALNT14 genotype-guided, sorafenib in combination with transarterial chemoembolization in hepatocellular carcinoma: An interim report of a prospective randomized controlled trial.
A phase II study of sorafenib and yttrium-90 glass microspheres for advanced hepatocellular carcinoma, BCLC stage C.
Chu KF, et al. Nat Rev Cancer. 2014;14(3):199-208.
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99Winship Cancer Institute | Emory University
Future Combination TherapyGALNT14 genotype-guided, sorafenib in combination with transarterial chemoembolization in hepatocellular carcinoma: An interim report of a prospective randomized controlled trial.
A phase II study of sorafenib and yttrium-90 glass microspheres for advanced hepatocellular carcinoma, BCLC stage C.
Efficacy and safety of localized concurrent chemoradiation therapy and sorafenib sequential therapy in advanced hepatocellular carcinoma: A prospective phase II trial.
Chu KF, et al. Nat Rev Cancer. 2014;14(3):199-208.
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100Winship Cancer Institute | Emory University
Future Combination TherapyGALNT14 genotype-guided, sorafenib in combination with transarterial chemoembolization in hepatocellular carcinoma: An interim report of a prospective randomized controlled trial.
A phase II study of sorafenib and yttrium-90 glass microspheres for advanced hepatocellular carcinoma, BCLC stage C.
Efficacy and safety of localized concurrent chemoradiation therapy and sorafenib sequential therapy in advanced hepatocellular carcinoma: A prospective phase II trial.
Nivolumab (nivo) in sorafenib (sor)-naive and -experienced pts with advanced hepatocellular carcinoma (HCC): CheckMate 040 study.
Chu KF, et al. Nat Rev Cancer. 2014;14(3):199-208.
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101Winship Cancer Institute | Emory University
Future Combination TherapyGALNT14 genotype-guided, sorafenib in combination with transarterial chemoembolization in hepatocellular carcinoma: An interim report of a prospective randomized controlled trial.
A phase II study of sorafenib and yttrium-90 glass microspheres for advanced hepatocellular carcinoma, BCLC stage C.
Efficacy and safety of localized concurrent chemoradiation therapy and sorafenib sequential therapy in advanced hepatocellular carcinoma: A prospective phase II trial.
Nivolumab (nivo) in sorafenib (sor)-naive and -experienced pts with advanced hepatocellular carcinoma (HCC): CheckMate 040 study.
Phase I/II study of durvalumab and tremelimumab in patients with unresectable hepatocellular carcinoma (HCC): Phase I safety and efficacy analyses.
Chu KF, et al. Nat Rev Cancer. 2014;14(3):199-208.
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102Winship Cancer Institute | Emory University
Future Combination TherapyGALNT14 genotype-guided, sorafenib in combination with transarterial chemoembolization in hepatocellular carcinoma: An interim report of a prospective randomized controlled trial.
A phase II study of sorafenib and yttrium-90 glass microspheres for advanced hepatocellular carcinoma, BCLC stage C.
Efficacy and safety of localized concurrent chemoradiation therapy and sorafenib sequential therapy in advanced hepatocellular carcinoma: A prospective phase II trial.
Nivolumab (nivo) in sorafenib (sor)-naive and -experienced pts with advanced hepatocellular carcinoma (HCC): CheckMate 040 study.
Phase I/II study of durvalumab and tremelimumab in patients with unresectable hepatocellular carcinoma (HCC): Phase I safety and efficacy analyses.
BBI608-503-103HCC: A phase Ib/II clinical study of napabucasin(BBI608) in combination with sorafenib or amcasertib (BBI503) in combination with sorafenib (Sor) in adult patients with hepatocellular carcinoma (HCC).
Chu KF, et al. Nat Rev Cancer. 2014;14(3):199-208.
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103Winship Cancer Institute | Emory University
So what about prevention?
STOP
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104Winship Cancer Institute | Emory University
An ounce of CURE . . .
Slide courtesy of Dr. Lesley Miller
Hepatitis C is Deadly
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105Winship Cancer Institute | Emory University
And Hepatitis C is potentially curable!
Slide courtesy of Dr. Lesley Miller
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106Winship Cancer Institute | Emory University
Routine HCV Screening at Grady
Slide courtesy of Dr. Lesley Miller
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107Winship Cancer Institute | Emory University
12,419tested
871HCV Ab +
• 7% prevalence
714 HCV RNA tested
• 82% tested
471 HCV RNA positive
• 66% viremic
400 linked to care
• 85% linked
Grady HCV Care CascadeOctober 2012-September 2016
Slide courtesy of Dr. Lesley Miller
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108Winship Cancer Institute | Emory University
Current HCV medications
Slide courtesy of Dr. Lesley Miller
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109Winship Cancer Institute | Emory University
Over 400 patients predicted cured 2015-16
Slide courtesy of Dr. Lesley Miller
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110Winship Cancer Institute | Emory University
Conclusion• Surgery offers the best long term survival benefit but ablation for early
stage tumors may be very reasonable and considered curative.• Local regional treatments are considered palliative but can produce
long term results. • Exact role for Y-90 pending.
• Radiation is likely underutilized in HCC because of past toxicity but as it becomes more precise and with the development of proton therapy, still is a reasonable option.
• Like all cancers right now, we are looking for answers in the targeted therapy and immunotherapy realm with many trials pending.
• One mode of treatment may be prevention – the role of HCV treatment continues to evolve.