Mugur Grasu MD, PhD Radiology, Medical Imaging and Interventional - - PowerPoint PPT Presentation

Mugur Grasu MD, PhD

Radiology, 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 )

• f 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 TACE Resection 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 Yes No 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

• r 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

Indication Absolute contraindications Relative contraindications

• Tumor size ≥ 10 cm
• Comorbidities

involving 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 hepatocellular carcinoma: 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 TACE 6 weeks Post TACE 3 months Pre TACE Pre TACE M, 54y – Child-Pugh B 6 weeks Follow-up after DEB-DOX II – HCC sg. IV

Pre TACE Post TACE 2 months Pre TACE Post TACE 4 months Pre TACE Post TACE Segment I Segment 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

• f 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 RECIST

A 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