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 ) 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

Barcelona Clinic for Liver Cancer (BCLC) staging system and treatment strategy HCC Stage 0 Stage A–C Stage D PST 0–2, Child–Pugh A–B PST 0, Child–Pugh A PST > 2, Child–Pugh C End stage (D) Very early stage (0) Early stage (A) Intermediate stage (B) Advanced stage (C) 1 HCC < 2 cm 1 HCC or 3 nodules Multinodular, Portal invasion, Carcinoma in situ < 3 cm, PST 0 PST 0 N1, M1, PST 1–2 1 HCC 3 nodules ≤ 3 cm Portal pressure/ bilirubin Increased Associated diseases Normal No Yes Resection Liver transplantation PEI/RFA TACE Sorafenib Best supportive care Curative treatments (30%) Target: 20% Target: 40% Target: 10% Median OS > 60 mo; 5-year survival (40–70%) OS 20 mo (45-14) OS 11 mo (6-14) OS < 3 months AASLD = American Association for the Study of Liver Diseases; PEI = percutaneous ethanol injection; PST = Performance Status test; RFA = radiofrequency ablation.

� 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 Relative Absolute Indication contraindications contraindications • Tumor size ≥ 10 cm Treatment of Decompensated cirrhosis � � • Comorbidities intermediate including: involving � jaundice stage (BCLC B) compromised organ � clinical encephalopathy HCC function � refractory ascites • Untreated varices at � hepatorenal syndrome high risk of bleeding Extensive tumor with massive � • Bile-duct occlusion or replacement of both entire incompetent papilla lobes due to stent or Severely reduced portal vein � surgery flow Technical contraindications to � hepatic intra-arterial treatment Renal insufficiency (creatinine ≥ � 2 mg/dL 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 B O E F D O O R L E U T A P C T E A K 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

TACE: an evolving technique toward improving the treatment of HCC From From Non-selective “Homemade” drug- treatment of the in-oil emulsions and entire liver embolic agents parenchyma (“conventional” TACE) To To Selective treatment Drug-eluting bead (segmental (calibrated embolic approaches with microsphere) microcatheters) Lencioni R. Personal communication. Hong K, et al. Clin Cancer Res. 2006;12:2563-7. www.biocompatibles.com.

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

After DEBDOX Before DEBDOX M, 54y – Child-Pugh B 6 weeks Follow-up after DEB-DOX – HCC sg. VII

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

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

Pre TACE Post TACE Pre TACE Post TACE 2 months NO LESIONS 4 PROCEDURES Segment IV Segment I Post TACE 4 months Pre TACE

� 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 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