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SGH – Surgery
Guidelines for SIRT in HCC
An Evolution
2nd Asia Pacific Symposium on Liver-
Directed Y-90 Microspheres Therapy
1st November 2014, Singapore
SGH – Surgery
Pierce Chow FRCSE PhD
2
Surgery is potentially curative in early HCC
But 80% are inoperable at time of diagnosis
Median survival of untreated inoperable HCC 3 – 8 months
High recurrence rates after surgical resection
The challenge of HCC
Clinical Presentation Treatment Options
LOCALLY ADVANCED HEPATOCELLULAR CARCINOMA
Locally Advanced HCC
Consider Clinical Trial
Present for evaluation
by multi-disciplinary
team
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)
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 multi-
disciplinary tumour board [43,44] (level – 2b)
Good liver function
- Palliative treatment - Consider Clinical Trial
- Transplant within UCSF
Surgical resection for carefully selected cases after
multidisciplinary board evaluation
Poor liver function
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)
*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
SGH – Surgery
Main Loco-regional Therapies
• Trans-arterial chemo-embolisation (TACE):
• widely used - disease control approx 40%
• used mainly in HCC, NETs (includes DC Beads)
• Selective Internal Radiation Therapy (SIRT):
• higher disease control (approx 80%)
• SIR-Sphere®, Thera-Sphere®
Pierce Chow FRCSE PhD
4
SGH – Surgery
Hepatology 2008; 47(1): 71-81
SGH – Surgery
Guidelines for SIRT
1) ESMO Guidelines
2) NCCN Guidelines
3) APPLE Guidelines
4) National Cancer Center Guidelines
Pierce Chow FRCSE PhD
6
SGH – Surgery
European Society of
Medical Oncology
Pierce Chow FRCSE PhD
7
SGH – Surgery
ESMO Guidelines (2010)
BCLC Staging for HCC
Pierce Chow FRCSE PhD
8
Summary of Treatment
Options and
Recommendations
according to BCLC
S. Jelic, 2010
SGH – Surgery
ESMO Guidelines (2010)
• “… Yttrium-90 microsphere
radioembolization is a recently FDA-
approved, non-surgical procedure used to
treat inoperable HCC……”
Pierce Chow FRCSE PhD
9
SGH – Surgery
ESMO Guidelines (2012)
Pierce Chow FRCSE PhD
10 C.Verslype, 2012
SGH – Surgery
Pierce Chow FRCSE PhD
11
Hepatocellular carcinoma: ESMO–ESDO Clinical Practice
Guidelines for diagnosis, treatment and follow-up Annals of Oncology 23 (Supplement 7): vii41–vii48, 2012
SGH – Surgery
National Comprehensive
Cancer Network
Pierce Chow FRCSE PhD
12
SGH – Surgery
NCCN Guidelines (2009)
Pierce Chow FRCS, PhD
SGH – Surgery
NCCN Guidelines (2009)
Pierce Chow FRCS, PhD
“………randomized, controlled studies on the use of
radioembolization therapy in the treatment of patients
with HCC are needed………..”
SGH – Surgery
NCCN Guidelines (2012)
Pierce Chow FRCSE PhD
SGH – Surgery
NCCN Guidelines (2012)
Pierce Chow FRCSE PhD
“… may be amenable to embolization
(chemoembolization, bland
embolization, radioembolization)
provided that the arterial blood supply
to the tumor may be isolated….”
SGH – Surgery
NCCN Guidelines (2014)
Pierce Chow FRCSE PhD
17
SGH – Surgery
NCCN Guidelines (2014)
Pierce Chow FRCSE PhD
18
*Arterially directed therapies include transarterial embolization (TAE), chemoembolization
(transarterial chemoembolization[TACE] and TACE with drug-eluting beads [DEB-TACE] )and
radioembolization with yttrium-90 microspheres.
SGH – Surgery
Asia-Pacific Primary Liver
Cancer Expert (APPLE)
conference 2014
Pierce Chow FRCS, PhD
19
SGH – Surgery
APPLE 2014 Consensus Workshop
Pierce Chow FRCS, PhD
20 Apple 2014 Consensus
Workshop Report
SGH – Surgery
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)
Pierce Chow FRCSE PhD
21
90Y microspheres in Patients with HCC and PVT
SGH – Surgery
90Y microspheres in Patients with HCC and PVT
• Number of SIRT administrations - single : 82.5%
Khor et al 2014
Data from SGH/NCC
SGH – Surgery Chow et al 2014
SGH – Surgery
Pierce Chow FRCSE PhD
Comparative Median Survival
Asian Patients
European
Patients
US
Patients
Study
AHCC05
2014
(Phase II
multicenter
study)
Khor 2013
(Retrospec
tive study)
Cheng 2009
(Prospective
Study)
Sangro 2011
(Retrospective
study)
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
SGH – Surgery
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)
Pierce Chow FRCSE PhD
26
SGH – Surgery
Med
ian
Su
rviv
al (
mo
nth
s)
Candidates for TACE
Poor Candidates for TACE
Failed TACE
not reached
(unresectable)
n = 52 n = 32 n = 39 n = 55 n = 48 n = 31
Patient Outcomes According to Suitability for TACE in the ENRY Series
Sangro et al., Hepatology 2011;54:868-878
No difference
SGH – Surgery
Overall Survival by BCLC Stage
• Number of SIRT administrations - single : 82.5%
Data from SGH/NCC
SGH – Surgery
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)
Pierce Chow FRCSE PhD
29
SGH – Surgery
Downstaging for HCC:
Chemoembolization VS Y90 SIRT
Pierce Chow FRCS, PhD
30
Downstaged patients stratified according
to size/distribution
Lewandowski, 2009
Table for follow-up/survivals
SGH – Surgery
T3 to T2
Lewandowski, RJ, et al. Am J Transpl. 2009;9:1920-8.
Tumor size changes after 3 months
-70
-60
-50
-40
-30
-20
-10
0
10
20
30PD
SD
PR +32 mo +8 mo
Retrospective analysis of 86 UNOS T3 patients (2000-2008; indication by MDT)
TACE (43) RE (43)
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
TACE (43) RE (43)
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%
SGH – Surgery
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† 2nd–4th 4 R0 2 CCC; CRC; OeC
Lau 71 SIR-Spheres† 1st–2nd 4 R0 HCC
Iñarrairaegui 72‡ SIR-Spheres† >1st 3 R0, 2 LT HCC
of which 21‡ SIR-Spheres† >1st 3 R0, 2 LT, 1 RF UNOS stage T3
Chow 29 SIR-Spheres† + sorafenib >1st 2 RF, 1 LT HCC
Barakat 1‡ SIR-Spheres† 1st 1 R0 HCC
Ettorre 1‡ SIR-Spheres† 1st 1 LT HCC
Miglioresi 4‡ SIR-Spheres† 1st 4 LT HCC
Gramenzi 63‡ SIR-Spheres† nr 2 LT HCC
Saxena 25 SIR-Spheres† >1st 1 R0 CCC
Coldwell 23‡ SIR-Spheres† >3rd 1 RF CCC
Högberg 2 SIR-Spheres† 1st 2 R0 CCC
Gaba 1‡ SIR-Spheres† 2nd 1 RL CCC ‡ retrospective data; † SIR-Spheres microspheres; R0: complete surgical resection; LT: transplant; RF: radiofrequency ablation; RL: radiation lobectomy
SGH – Surgery
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)
Pierce Chow FRCSE PhD
33
SGH – Surgery
APPLE 2014 Consensus Workshop
Pierce Chow FRCS, PhD
34 Apple 2014 Consensus
Workshop Report
SGH – Surgery
National Cancer Center
Singapore
Pierce Chow FRCSE PhD
35
Clinical Presentation Treatment Options
LOCALLY ADVANCED HEPATOCELLULAR CARCINOMA
Locally Advanced HCC
Consider Clinical Trial
Present for evaluation
by multi-disciplinary
team
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)
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 multi-
disciplinary tumour board [43,44] (level – 2b)
Good liver function
- Palliative treatment - Consider Clinical Trial
- Transplant within UCSF
Surgical resection for carefully selected cases after
multidisciplinary board evaluation
Poor liver function
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)
*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
SGH – Surgery
Pierce Chow FRCSE PhD
37
Thank
You!