mugur grasumd, phd

Mugur Grasu MD, PhDRadiology, Medical Imaging and Interventional Radiology – Fundeni Clinical

Institute

University of Medicine and Pharmacy - Carol Davila – Bucharest

� depends on a variety of factors:

� the size, number, distribution (unilobar vs. bilobar )

of tumors

� the relationship of the tumor to hepatic vasculature

� the status of distant metastases

� the severity of liver disease (Child-Pugh score)

� the suitability of the patient for liver transplantation

� the functional status of the patient

� local expertise

Memeo, R., de Blasi, V., Cherkaoui, Z. et al. J Gastrointest Canc (2016) 47: 239. doi:10.1007/s12029-016-9840-6

Portal pressure/

bilirubin

HCC

PEI/RFA Sorafenib

Stage 0

PST 0, Child–Pugh A

Very early stage (0)

1 HCC < 2 cm

Carcinoma in situ

Early stage (A)

1 HCC or 3 nodules

< 3 cm, PST 0

End stage (D)

Liver transplantation TACEResection

Target: 10%

OS < 3 months

Curative treatments (30%)

Median OS > 60 mo; 5-year survival (40–70%)Target: 20%

OS 20 mo (45-14)

Associated diseases

YesNo

3 nodules ≤ 3 cm

Increased

Normal

1 HCC

Stage D

PST > 2, Child–Pugh C

Intermediate stage (B)

Multinodular,

PST 0

Advanced stage (C)

Portal invasion,

N1, M1, PST 1–2

Stage A–C

PST 0–2, Child–Pugh A–B

Barcelona Clinic for Liver Cancer (BCLC)

staging system and treatment strategy

AASLD = American Association for the Study of Liver Diseases; PEI = percutaneous ethanol injection;

PST = Performance Status test; RFA = radiofrequency ablation.

Target: 40%

OS 11 mo (6-14)

Best supportive care

� BCLC – B class – multinodular, asymptomatic,

without an invasive pattern

� Untreated patients – median survival 16 mo

or 49% at 2 year

� 11 mo – worst scenario of untreated patients

(placebo arm of SHARP trial)

� TACE extends survival – median up to 19-20

mo

� Best responders to TACE 36-45 mo

� Ascites is the worst prognostic factor for this

subclass

Llovet, Lancet 2002 Lo, Hepatology 2002

Llovet JM, et al. Lancet. 2002;359:1734-9. Lo CM, et al. Hepatology. 2002;35:1164-71.

Treatment Patients 1 year 2 years 3 years

TACE 40 57 % 31 % 26 %

Control 39 32 % 11 % 3 %

Lo CM, et al. Hepatology. 2002;35:1164-71.

Intermediate stage HCC population:

indication and contraindications for TACE

� Treatment of

intermediate

stage (BCLC B)

HCC

� Decompensated cirrhosis

including:

� jaundice

� clinical encephalopathy

� refractory ascites

� hepatorenal syndrome

� Extensive tumor with massive

replacement of both entire

lobes

� Severely reduced portal vein

flow

� Technical contraindications to

hepatic intra-arterial treatment

� Renal insufficiency (creatinine ≥

2 mg/dL

IndicationAbsolute

contraindications

Relative contraindications

• Tumor size ≥ 10 cm

• Comorbiditiesinvolving compromised organ function

• Untreated varices at high risk of bleeding

• Bile-duct occlusion or incompetent papilla due to stent or surgery

Raoul JL, Sangro B, Forner A, Mazzaferro V, Piscaglia F, Bolondi L, et al. – Evolving strategies for the management of intermediate-stage hepatocellularcarcinoma: Available evidence and expert opinion on the use of transarterial chemoembolization. Cancer Treat Rev 2011;37:212–220.

� IMAGING - preferably within 4 weeks of the planned TACE (max 8 weeks), not only for the purpose of patient triage to proper therapy, but also to accurately evaluate response to the treatment.� MRI

� CT (at least 3 phases postcontrast)

� STAGING (thorax, abdomen and pelvis)

� BONE SCAN� BLOOD TESTS (bilirubin < 2 mg/dl !)� INFORMATION FOR THE PATIENT

� Palliative treatment

� 5-7% complications, 1-4% periprocedural death

� Femoral approach– 4-5F catheter

� Diagnostic angiograpphy

� Mesenteric artery evaluation

� Indirect portal vein evaluation

� Selective catheterization of lobar or

segmental hepatic artery

� Inject – Lipiodol and Doxorubicin

� EMBOLISATION

Hepatic angiography – Hepatic artery with origin from SMA

Right Hepatic angiography – HCC in segment VI

L

I

P

I

O

D

O

L

U

P

T

A

K

E

B

E

F

O

R

E

T

A

C

E

1 MONTH FOLLOW-UP

M, 64y –

Child-Pugh

A

HCC right

lobe

27 Jul 2016

M, 64y –

Child-Pugh

A

HCC right

lobe

27 Jul 2016

M, 64y –

Child-Pugh

A

HCC right

lobe

27 Jul 2016

M, 64y – Child-Pugh A HCC right lobe - 19 Jan 2017

Lencioni R. Personal communication.

Hong K, et al. Clin Cancer Res. 2006;12:2563-7.

www.biocompatibles.com.

From

Non-selective

treatment of the

entire liver

parenchyma

To

Selective treatment

(segmental

approaches with

microcatheters)

From

“Homemade” drug-

in-oil emulsions and

embolic agents

(“conventional”

TACE)

To

Drug-eluting bead

(calibrated embolic

microsphere)

TACE: an evolving technique toward

improving the treatment of HCC

M, 54y – Child-Pugh B – 4 HCCs - May 2016

M, 54y – Child-Pugh B – DEB-DOX – HCC sg. VII - May 2016

M, 54y – Child-Pugh B – DEB-DOX – HCC sg. VII - May 2016

M, 54y – Child-Pugh B – DEB-DOX – HCC sg. VII - May 2016

M, 54y – Child-Pugh B

6 weeks Follow-up after DEB-DOX – HCC sg. VII

Before DEBDOX After DEBDOX

M, 54y – Child-Pugh B – DEB-DOX II – HCC sg. IV - May 2016

Post TACE

Post TACE6 weeks

Post TACE3 months

Pre TACE

Pre TACE

M, 54y – Child-Pugh B

6 weeks Follow-up after DEB-DOX II – HCC sg. IV

Pre TACE Post TACE2 months

Pre TACE

Post TACE4 months

Pre TACE Post TACE

Segment ISegment IV

NO LESIONS

4 PROCEDURES

� An important limitation of conventional TACE

has been the inconsistency in the technique and

the treatment schedules.

� This limitation has greatly hampered the acceptance

of TACE as a standard oncology treatment.

� DEBDOX provides levels of consistency and

repeatability not available with conventional

TACE, and offers the opportunity to implement a

standardized approach to HCC treatment.

Consensus Meeting – European Conference on Interventional Oncology in Florence, Italy

Technical recommendations for the use of DEBDOX in HCC treatment.

� Intra-arterial administration of chemotherapy associated with� nausea

� vomiting

� bone marrow depression

� alopecia

� potential renal failure

� Post-embolization syndrome occurs in 60-80% of patients� consists of fever, abdominal pain, and a moderate degree of ileus

� fasting for 24 hours and i.v. rehydration are mandatory

� prophylactic antibiotics not routinely used (?!)

� usually self-limited in < 48 hours and patients can be discharged from hospital

� fever reflective of tumor necrosis

� minority of patients may develop severe infectious complications such as hepatic abscess or cholecystitis

� in a multicenter study including 201 European

patients (PRECISION V), use of DEBDOX

resulted in a marked and statistically

significant reduction in liver toxicity and

drug-related adverse events compared with

conventional TACE with lipiodol and

doxorubicin

SAE Comparison : Conventional TACE vs PRECISION TACE

� Water-in-oil emulsion of Doxorubicin (30-100

mg) and Lipiodol (10-15 ml.)

� 1 volume Doxo+contrast / 2 volume Lipiodol

� Selective / ultraselective embolization with

microcatheters (2.8-2.0F) – improves survival

� CBCT – add-on tool for a more targeted

procedure

� A set of 2 sequential TACE procedures are

usually performed 2-8 weeks apart

� CT – after 1 month - mRECIST

� Lipiodol UPTAKE

� Residual tumoral tissue

� MRI – after 3 months

� New lesions ?

� Residual tumoral tissue

Raoul JL, Sangro B, Forner A, Mazzaferro V, Piscaglia F, Bolondi L, et al. – Evolving strategies for the

management of intermediate-stage hepatocellular carcinoma: Available evidence and expert opinion on

the use of transarterial chemoembolization. Cancer Treat Rev 2011;37:212–220.

Schematic diagram showing variable mRECIST objective response, with stable disease by RECISTA radiologist’s guide to the modified Response Evaluation Criteria in Solid Tumours (mRECIST) assessment of therapy for hepatocellular carcinoma – ECR 2011 C2120

HCC in segment VIII

1 mo FU – partial response mRECIST 18 moFU – partial response RECIST

1 mo follow-up

HCC in segment VII

NO Arterial enhancement

mRECIST - CR

� 376 TACE 2016

� 207 DEB-TACE (TANDEM and PearLife)

� 123 cTACE hyperselective

� 46 lobar cTACE

� TACE is the GOLD standard of care for patients with

intermediate stage HCC – BCLC-B

� However, only a limited patient population derives

maximum benefit from TACE

� DEB-TACE – increases overall survival – 36-45 months

� is generally well tolerated and effective

� may offer a benefit to patients with more advanced

disease within the intermediate stage of HCC

compared with cTACE

� Guidelines and expert opinion articles indicate that not

all intermediate HCC patients are suitable candidates

for TACE