Selection Criteria and Insertion of SIRT into HCC Treatment Guidelines

Selection Criteria and Insertion of SIRT into HCC Treatment Guidelines 2 nd Asia Pacific Symposium on Liver- Directed Y-90 Microspheres Therapy 1st November 2014, Singapore

Pierce Chow FRCSE PhD SIRT in the Treatment of HCC 1. Indications a. APPLE Guidelines b. National Cancer Center Guidelines 2. Contra-indications 1. Relative 2. absolute 2

Pierce Chow FRCSE PhD Asia-Pacific Primary Liver Cancer Expert (APPLE) conference 2014 3

Pierce Chow FRCSE PhD APPLE 2014 Consensus Workshop Apple 2014 Consensus Workshop Report 4

Pierce Chow FRCSE PhD APPLE recommendations for SIRT 2014 first- line therapy in Advanced HCC with vascular invasion and/or which are liver dominant with bilirubin <2 mg/dl and which are Child-Pugh A or <B7 1-3. (Level B1). In this context sorafenib may be added in patients with extra-hepatic disease4. (Level B2) first-line therapy in multi-focal or bilobar HCC with high disease burden5,6. (Level B1) second-line therapy in patients with multi-focal HCC who has progressed on TACE1-3. (Level B1) bridging therapy in patients on the waiting list for cadaveric transplantation7,8. (Level B1) 5

90 Y microspheres in Patients with HCC and PVT

90 Y microspheres in Patients with HCC and PVT Data from SGH/NCC Number of SIRT administrations - single : 82.5% Khor et al 2014

Chow et al 2014

Pierce Chow FRCSE PhD Comparative Median Survival Study AHCC05 2014 (Phase II multicenter study) Asian Patients Khor 2013 (Retrospec tive study) Cheng 2009 (Prospective Study) European Patients Sangro 2011 (Retrospective study) US Patients Salem 2010 (Prospective study) Y-90 + Sorafenib Y-90 Sorafenib Placebo Y-90 Y-90 BCLC B 20.3mo 23.8mo 14.3 mo 8 mo 16.9 mo 17.2 mo BCLC C 8.6mo 11.8mo 5.6 mo 4.1 mo 10.0 mo 7.3 mo SIRSA 1 patient down-staged to transplantation, 2 to RFA

Patient Outcomes According to Suitability for TACE in the ENRY Series Median Survival (months) not reached No difference n = 52 n = 32 n = 39 n = 55 n = 48 n = 31 (unresectable) Candidates for TACE Poor Candidates for TACE Failed TACE Sangro et al., Hepatology 2011;54:868-878

Overall Survival by BCLC Stage Data from SGH/NCC Number of SIRT administrations - single : 82.5%

Pierce Chow FRCS, PhD Downstaging for HCC: Chemoembolization VS Y90 SIRT Downstaged patients stratified according to size/distribution Table for follow-up/survivals Lewandowski, 2009 14

Tumor size changes after 3 months T3 to T2 30 20 10 0-10 -20-30 -40-50 -60-70 PD SD PR Retrospective analysis of 86 UNOS T3 patients (2000-2008; indication by MDT) TACE (43) RE (43) TACE (43) RE (43) +32 mo +8 mo Portal HT 77% 74% Single 53% 47% Child A 53% 56% BCLC B 85% 79% Selective Treat 56% 46% G3/4 Bil Toxicity 26% 7% MELD Pre/Post 9/9 8/9.5 Ds T3 T2 31% 58% Med. time to prog 12.8 33.3 Transplanted 26% 21% RFA 23% 42% Med Surv (cens) 18.7 35.7 Med Surv (uncens) 19.2 41.6 Recurrence 18% 22% Lewandowski, RJ, et al. Am J Transpl. 2009;9:1920-8.

SIR-Spheres microspheres in down-sizing primary liver cancers to resection, ablation or radiation lobectomy Investigator n Tx line # Outcomes Tumour Type(s) Whitney 44 SIR-Spheres 2 nd 4 th 4 R0 2 CCC; CRC; OeC Lau 71 SIR-Spheres 1 st 2 nd 4 R0 HCC Iñarrairaegui 72 SIR-Spheres >1 st 3 R0, 2 LT HCC of which 21 SIR-Spheres >1 st 3 R0, 2 LT, 1 RF UNOS stage T3 Chow 29 SIR-Spheres + sorafenib >1 st 2 RF, 1 LT HCC Barakat 1 SIR-Spheres 1 st 1 R0 HCC Ettorre 1 SIR-Spheres 1 st 1 LT HCC Miglioresi 4 SIR-Spheres 1 st 4 LT HCC Gramenzi 63 SIR-Spheres nr 2 LT HCC Saxena 25 SIR-Spheres >1 st 1 R0 CCC Coldwell 23 SIR-Spheres >3 rd 1 RF CCC Högberg 2 SIR-Spheres 1 st 2 R0 CCC Gaba 1 SIR-Spheres 2 nd 1 RL CCC retrospective data; SIR-Spheres microspheres; R0: complete surgical resection; LT: transplant; RF: radiofrequency ablation; RL: radiation lobectomy

Pierce Chow FRCS, PhD APPLE 2014 Consensus Workshop Apple 2014 Consensus Workshop Report 18

Pierce Chow FRCSE PhD National Cancer Center Singapore 19

LOCALLY ADVANCED HEPATOCELLULAR CARCINOMA Clinical Presentation Treatment Options Consider Clinical Trial Locally Advanced HCC Good liver function Poor liver function Present for evaluation by multi-disciplinary team - Palliative treatment - Consider Clinical Trial - Transplant within UCSF Surgical resection for carefully selected cases after multidisciplinary board evaluation LOCOREGIONAL THERAPY No Vascular Invasion* Transarterial chemoembolisation (TACE) + DC-Beads [32,33] (level 1b) Selective Internal Radiation Therapy (SIRT) [34-36] (level 2b) External beam RT (alone or as part of combined modality) Sorafenib [32-35] (level 1b) With Vascular Invasion Sorafenib [37-40] (level 1b) Selective Internal Radiation Therapy (SIRT) [34-36] (level 2b) External beam RT (alone or as part of combined modality) [41,42] (level 2a) Transplantation is a consideration for HCC within the USCF expanded criteria (single tumours < 6.5cm or 2-3 tumours < 4.5cm at the most, with a total tumour diameter < 8cm) after assessment by a multidisciplinary tumour board [43,44] (level 2b) *Sorafenib may also be considered when local regional therapy is not feasible or fails [40] (level - 2b) National Cancer Center Singapore Consensus Guidelines on Liver Cancer http://www.nccs.com.sg/patientcare/comprehensivelivercancerclinic/documents/clcc guideline Final Ver to upload PDF 26092014.pdf

Contra-indications to SIRT RELATIVE CONTRA-INDICATIONS 1. Inadequate haematological, renal and hepatic function as follows: Platelets < 80,000/μL Haemoglobin < 9.5 g/dl Total bilirubin < 2.0 mg/dl INR > 2 ALP >5 x institutional upper limit of normal AST and ALT > 5 x institutional upper limit of normal Creatinine 2.0 mg/dl 2. Life expectancy of at least 3 months without any active treatment. 3. Have had systemic chemotherapy for HCC within the last 3 months 4. Metastatic disease. In this context local-regional lymph nodes measuring > 2 cm in greatest diameter or lung nodules measuring > than 1 cm - Sorafenib must be added Pierce Chow FRCS, PhD 21

Contra-indications to SIRT ABSOLUTE CONTRA-INDICATIONS 1. Has clinical ascites (in spite of optimal diuretic treatment) or any other clinical signs of liver failure, on physical examination. 2. i. If the Body Surface Area (BSA) method is used for dose calculation and the percentage lung shunting exceeds 20% of the hepatic artery blood flow, as determined by TC-99 MAA scan. In the event that the lung shunt study indicates that pulmonary shunt exceeds 20%, the partition model (ii below) may be used to adjust the prescribed activity so that radiation absorbed dose to the lungs does not exceed 20 Gy. 3. ii. Partition model (pre-assessment dosimetry) calculations based on Tc-99m MAA and CT scans show that any of the following radiation dose limits are exceeded: 1. radiation absorbed dose to the lungs > 20Gy 2. radiation absorbed dose to cirrhotic liver > 50Gy 3. radiation absorbed dose to non-cirrhotic liver > 70Gy 4. Pre-assessment angiogram and Tc-99 MAA scan that demonstrates significant and un-correctable activity in the stomach, pancreas or bowel. 5. Complete main portal vein thrombosis. 6. Hepatic arterial anatomy not suitable for implantation of SIR-Spheres, as assessed by hepatic angiogram. Pierce Chow FRCS, PhD 22

Pierce Chow FRCSE PhD Thank You! 23