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

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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

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SGH – Surgery

European Society of

Medical Oncology

Pierce Chow FRCSE PhD

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SGH – Surgery

ESMO Guidelines (2010)

BCLC Staging for HCC

Pierce Chow FRCSE PhD

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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

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SGH – Surgery

ESMO Guidelines (2012)

Pierce Chow FRCSE PhD

10 C.Verslype, 2012

SGH – Surgery

Pierce Chow FRCSE PhD

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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

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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

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SGH – Surgery

NCCN Guidelines (2014)

Pierce Chow FRCSE PhD

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*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

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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

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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

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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

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SGH – Surgery

Downstaging for HCC:

Chemoembolization VS Y90 SIRT

Pierce Chow FRCS, PhD

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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!