Transarterial therapy:

how to choose

cTACE vs. DEB-TACE vs.Y90-SIRT

台大醫院影醫部 梁博欽

TLAC 2015.12.27

TLCA Guideline 2015

TLCA Guideline 2015

Precision V Design

• Randomised phase II study

• Control arm of conventional transarterial chemoembolisation

(cTACE) with doxorubicin

• 200 patients (100 per arm)

• 23 European centres in Austria, France, Germany, Greece, and

Switzerland

• Patients receive up to 3 treatments (baseline, 2 and 4 months)

• Follow-up period: 6 months

Patients

randomised

1:1

(n=212)

TACE with DC BeadDoxorubicin dose = 150mg

Conventional TACE Doxorubicin dose = 50–75mg/m2

(maximum 150mg)

TACE repeated at 2 and 4 months

• Primary endpoint: tumor response at 6 months (by blinded independent

review of MR images)

• Secondary endpoints included safety

TACE repeated at 2 and 4 months

International multicentre, randomised phase II study of DC Bead uploaded

with doxorubicin versus conventional Lipiodol TACE with doxorubicin

Lencioni R et al. ASCO 2009; Lammer J et al. Cardiovasc Intervent Radiol 2010 (e-pub)

TACE with DC Bead vs conventional TACE:

a randomized trial (“PRECISION V”)

Main Exclusion Criteria

• Severe liver dysfunction

- Child C

- Bilirubin level >3mg/dl

• Advanced tumour stage

- tumor involvement > 50%

of the whole liver

- Portal vein invasion

- extrahepatic spread

• Patient previously treated with

chemo- or radiotherapy

Main Inclusion Criteria

• Patient with large / multinodular

HCC without vascular invasion or

extrahepatic spread

• Patient not suitable for curative

resection / ablation

• ECOG performance status 0 or 1

• Child Pugh A or B

• Recurrent tumor after resection or

ablation

• Patients on the transplant list who

may not receive a transplant within

6 months

TACE with DC Bead vs conventional TACE:

enrolment criteria

Lencioni R et al. ASCO 2009; Lammer J et al. Cardiovasc Intervent Radiol 2010 (e-pub)

PRECISION TACE with DC Bead

• 2 x 2 ml vials of DC Bead (total 4ml) for total doxorubicin dose of 150mg

• 1 vial 300-500µm plus 1 vial 500-700µm

Conventional TACE

• Doxorubicin dose of 50-75mg/m2 to maximum of 150mg, lipiodol, embolic

Technique (both groups)

• Unifocal tumours: segmental approach

• Bilobar disease: both lobes treated within a 3-week period

• Embolisation to stasis in 2nd or 3rd order branches, additional unloaded

beads (Bead Block, Biocompatibles) if needed

TACE with DC Bead vs conventional TACE: treatment

Lencioni R et al. ASCO 2009; Lammer J et al. Cardiovasc Intervent Radiol 2010 (e-pub)

CharacteristicsDC Bead (n=102) cTACE (n=110)

n % n %

Child Pugh A 83 81.4 91 82.7

B 19 18.6 19 17.3

ECOG0 78 76.5 81 73.6

1 24 23.5 29 26.4

Bilobar DiseaseNo 54 52.9 63 57.3

Yes 48 47.1 47 42.7

Recurrent

Disease

No 91 89.2 97 88.2

Yes 11 10.8 13 11.8

TACE with DC Bead vs conventional TACE: baseline

stratification allows for balanced statistical evaluation

Lencioni R et al. ASCO 2009; Lammer J et al. Cardiovasc Intervent Radiol 2010 (e-pub)

6-Month Response in More Advanced Patients

DC BeadTM Demonstrated Statistically Significant Advantage in Advanced Patients

Objective Response (p=0.038) and Disease Control (p=0.026)

DC Bead shows a significant (p<0.05)

response benefit in More Advanced patients

Serious Adverse Events – Advanced Disease

*per 100 patients, events within 30 days of treatment

The significant (p<0.05) response benefit in More Advanced patients

with DC Bead is delivered with an improved safety profile

Summary

Overall, DC BeadTM has

• Greater objective response (p=0.11)

• Lower related SAEs and AEs

DC Bead has a significant (p<0.05) advantage in

• Objective response in more advanced patients (p=0.038)

• Disease control in more advanced patients (p=0.026)

DC Bead has a highly significant (p<0.01) advantage in the

• Reduction of doxorubicin associated side effects (p=0.0001) in all

patients

• Reduction of disturbance in liver enzymes, AST and ALT (p<0.01)

TLCA Guideline 2015

Transarterial therapy: how to choose cTACE vs. DEB-TACE vs.Y90-SIRT

TLCA Guideline 2015

NCI level of evidence

GRADE System(Grading of Recommendations, Assessment, Development and Evaluation)

GRADE system(Grading of Recommendations, Assessment, Development and Evaluation)

5th APPLE 2014 Recommendation for SIRT

• In early stage HCC, SIRT can be considered for bridging treatment for cadaveric liver transplantation (evidence level B1).

• In intermediate stage HCC, SIRT can be considered for bilobar, multinodular or large tumour burden HCC, and also for HCC after conventional TACE has failed. There is limited data that SIRT may be used as neoadjuvant treatment (evidence level B1).

• In advanced stage HCC, SIRT can be used for patients with vascular invasion and liver-dominant metastatic HCC (evidence level B1).

5th APPLE 2014 Recommendation for SIRT

• In early stage HCC, SIRT can be considered for bridging treatment for cadaveric liver transplantation (evidence level B1).

• In intermediate stage HCC, SIRT can be considered for bilobar, multinodular or large tumour burden HCC, and also for HCC after conventional TACE has failed. There is limited data that SIRT may be used as neoadjuvant treatment (evidence level B1).

• In advanced stage HCC, SIRT can be used for patients with vascular invasion and liver-dominant metastatic HCC (evidence level B1).

5th APPLE 2014 Recommendation for SIRT

• In early stage HCC, SIRT can be considered for bridging treatment for cadaveric liver transplantation (evidence level B1).

• In intermediate stage HCC, SIRT can be considered for bilobar, multinodular or large tumour burden HCC, and also for HCC after conventional TACE has failed. There is limited data that SIRT may be used as neoadjuvant treatment (evidence level B1).

• In advanced stage HCC, SIRT can be used for patients with vascular invasion and liver-dominant metastatic HCC (evidence level B1).

SIRTEX ongoing clinical studyTitle Setting Sponsor Study ID Treatment Arm(s) Location

SIRveNIBhttp://www.sirvenib.com/Study to compare selective internal radiation therapy (SIRT) versus sorafenib in locally advanced hepatocellular carcinoma

HCC

Collaborative Group Study

NCT01135056Sorafenib versus SIR-Spheres microspheres

Asia-Pacific

SARAHSorafenib versus radioembolizationin advanced hepatocellular carcinoma

HCC

Collaborative Group Study

NCT01482442Sorafenib versus SIR-Spheres microspheres

France

SORAMICwww.soramic.de Sorafenib and micro-therapy guided by primovist-enhanced MRI in patients with inoperable liver cancer

HCC

Investigator-Initiated Research Study

NCT01126645Sorafenib versus SIR-Spheres microspheres > Sorafenib

Europe

TRYPHON -- terminatedY90 radioembolization prior to surgical resection or radiofrequency for hepatocellular carcinoma in cirrhotic liver

HCC

Investigator-Initiated Research Study

NCT01686880 SIR Spheres microspheres Belgium

Selective internal radiation therapy (SIRT) versus transarterial chemoembolisation (TACE) for the treatment of cholangiocellular carcinoma (CCC)

CCC

Investigator-Initiated Research Study

NCT01798147SIR Spheres microspheres versus transarterial chemoembolisation (TACE)

Germany

Guidelines for management of HCC

Peipei Song, Liver International 2012;32(7): 1053-1063

Guidelines for management of HCC

Peipei Song, Liver International 2012;32(7): 1053-1063

AASLD/BCLC staging and treatment strategy 2010

Hepatology 2011(53;3): 1020-1022 Lancet 2012; 379: 1245-1255

Substaging of BCLC stage B

Luigi Bolondi et al. Semin Liver Dis 2012; 32: 348-359

Milan criteria for Liver Txp

• A solitary lesion of < 5 cm, or 2 to 3 nodules, all < 3 cm and without microscopic vascular invasion or extrahepatic disease.

• 5-year post-transplant survival exceeding 70%

• 5-year tumor recurrence rate below 15%

Mazzaferro et al. N Engl J Med 1996; 334: 693-699

UCSF criteria for Liver Txp

University of California San Francisco criteria

• 1 lesion ≤ 6.5cm in diameter or 2 to 3 lesions, each ≤ 4.5 cm in diameter, with a total diameter of ≤ 8 cm.

• 2-year survival of 86%

Yao et al. Hepatology 2001; 33: 1394-1403

New Milan criteria(Up-to-seven criteria, Ut-7 criteria) • hepatocellular carcinomas with seven as the sum of

the size of the largest tumor (in cm) and the number of tumors.

• 5-year overall survival rate 71.2%.

Mazzaferro et al. Lancet Oncol 2009; 10: 35-43

NCCN Guidelines Version2.2014

• All arterial directed therapies are relatively contraindicated in patients bilirubin > 3 mg/dL unless segmental injection can be performed.

• Radioembolization with Yttrium-90 microspheres has an increased risk of radiation induced liver disease in patients with bilirubin over 2 mg/dL

• Arterial directed therapies are relatively contraindicated in patients with main portal vein thrombosis and Child C

NCCN Guidelines Version2.2015

ESMO Strategy for staging and treatment 2012

Annals of Oncology 23 (Supplement 7): vii41–vii48, 2012

EASL-EORTC recommendation for treatment 2012

Journal of Hepatology 2012(56): 908-943

NCI level of evidence

GRADE System(Grading of Recommendations, Assessment, Development and Evaluation)

APASL treatment algorithm 2010

Omata M, et.al Hepatol Int 2010 4:439–474

Kudo 2010 APASL

J-HCC 2009 Evidence-based treatment guideline

J Gastroenterol. 2009;44 Suppl 19:119-21.

JSH-LCSGJ 2011Consensus-Based Treatment Algorithm

Dig Dis 2011;29:339–364

TLCA Guideline 2015

National Cancer Center Singapore Consensus Guideline 2014

TPVGH Guideline 3rd Version

NTUH Guideline 2015

APASL treatment algorithm 2010

Omata M, et.al Hepatol Int 2010 4:439–474

Transarterial therapy: how to choose cTACE vs. DEB-TACE vs.Y90-SIRT

Conclusion

•Transarterial therapy: how to choose cTACE vs. DEB-TACE vs.Y90-SIRT

TLCA Guideline 2015

DEB-TACE

Thanks for your attention !!

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