Chemosaturation: Indication, Technique and Outcome

Transcription

1 Chemosaturation: Indication, Technique and Outcome Thomas J Vogl, S Koch, B Gebauer, W Willinek, C Engelke, R Bruening, F Wacker, A Enk I D I R: Institute of Diagnostic and Interventional Radiology Goethe University Frankfurt, Germany

2 Disclosure Speaker name: Thomas Vogl I have the following potential conflicts of interest to report: Consulting Employment in industry Stockholder of a healthcare company Owner of a healthcare company Other: travel grant I do not have any potential conflict of interest

3 Liver Malignancies: Treatment Decision-making is a Complex Task Localization Metastasenlokalistion of tumor Krankheitsfreies Disease-free interval Intervall Receptor status Symptoms Symptome Individualized therapy Mutation status Biomarkers Spectrum of Nebenwirkungspe side effects Patient preference Previous therapies

4 Liver Malignancies: Check List 1. Unilobar bilobar 2. Resectable unresectable resection combined with contralateral ablation 3. Synchronous metachronous 4. No extrahepatic manifestation extrahepatic manifestation peritoneum lymph nodes lung (bone tumors) 5. Symptomatic asymptomatic

5 Liver Malignancies: Arterial Therapies Definition: 1. Intraarterial hepatic chemotherapy (IAHC) Transarterial chemoperfusion (TACP) 2. Transarterial chemoembolization (TACE) - conventional TACE - TACE with DC beads 3. Radioembolization 4. Isolated liver perfusion Indications: 1. Salvage therapy: response when systemic therapy inefficient 2. First line therapy (induction therapy): convert nonsurgical patient to surgical patient

6 Liver Malignancies: Treatment Options When resection is not possible, treatment options include: tumor-focused or local ablative therapy whole organ or regional therapy systemic therapy

7 Liver Malignancies: Clinical Classification Group 1 Primarily resectable metastases Group 2 Potentially resectable metastases Group 3 Liver metastases that are unlikely to become resectable Surgery or FOLFOX symptomatic rapid progression Intensified therapy: FOLFOX + Cet FOLFIRI + Cet FOLFOXIRI CT + Bev? HAI, TACE asymptomatic slow progression primary goal: QoL, survival time TACE, HAI, SIRT

8 Isolated Hepatic Perfusion IHP is a regional therapy which isolates the hepatic vascular inflow and outflow surgically 1 The liver is then perfused with chemotherapy via a closed extracorporeal circuit 1 : first tested at Roswell Park Institute in Studies over the last decade show response rates of 60-70% in a variety of tumor types with liver-limited metastases: colorectal cancer data include large institutional reports 3,4 ocular melanoma several small studies neuroendocrine tumors limited data Major disadvantages are: highly invasive open surgical procedure with associated morbidity it can only be performed once 1. Alexander RH & Butler CC. Cancer J 2010;16: Ausman RK. N Y State J Med 1961;61: Van Iersel LB, et al. Ann Oncol 2008;19: Alexander HR Jr, et al. Ann Surg Oncol 2009;16:1852-9

9 Chemosat Procedure: Overview CHEMOSAT utilizes 3 primary principles: o ISOLATION isolates hepatic blood flow o SATURATION chemotherapeutic agent delivered to liver o FILTRATION chemo-rich blood is filtered outside the body

10 Isolation Inflate and wedge cephalad balloon of isolation aspiration catheter at the junction of the atrium and the superior vena cava Inflate caudal balloon of isolation aspiration catheter to complete hepatic venous isolation

11 Chemosaturation with Percutaneous Hepatic Perfusion

12 German Melanoma Trial: Frankfurt Study period: Patients: n = 18 with hepatic metastases from uveal melanoma Chemosaturation therapy: 1 3 sessions Evaluation: n = 17 patients RECIST criteria survival time analysis adverse events and complications

13 German Melanoma Trial: Frankfurt Results Median overall survival after first chemosaturation: 9.6 months range: months Time to progression: n = 2 patients with PD n = 1 patient 3.6 months n = 1 patient deceased 1.7 months after chemosaturation

14 Chemosaturation Therapy Patient name: MP Age: 53 years Primary disease: malignant melanoma History: malignant melanoma with liver metastases 2 chemoembolizations radiochemotherapy for breast cancer adrenalectomy, adnexectomy, partial liver resection systemic chemotherapy with Vemurafenib cyclic systemic chemotherapy with Carboplatin and Taxol monochemotherapy with Dacarbazin (DTIC) Latest treatment: chemosaturation therapy of the liver with Melphalan Pat. 2

15 1 st Staging Before Vemurafenib therapy 1 st staging Pat. 2

16 MRI Before Melphalan Chemosaturation Pat. 2

17 5 th Staging: No Evidence of Disease After 1 st MWA (2 months after chemosaturation) After 2 nd MWA (3 months after chemosaturation) Pat. 2

18 Chemosaturation Therapy Before Chemosaturation Therapy 20/02/2013 After Chemosaturation Therapy 17/04/2013

19 Conclusion Interventional Radiologist Intensivist/critical care specialist Interventional radiology staff Oncologist (surgical & medical) *must commit to managing the patient Perfusionist Anaesthetist Pharmacist Chemosaturation is a potential option for patients with non-resectable hepatic metastases from uveal melanoma.

20 Clinical Development Programme 1. FOCUS Phase III Global Trial: o Clinical Trial for Patients with Hepatic Dominant Ocular Melanoma (the FOCUS Trial) 2. Phase II Trial - Hepatocellular Carcinoma (HCC) & Intrahepatic Cholangiocarcinoma (ICC) Programme: o Protocol 201 US Study o Protocol 202 European Study

21 Focus Phase III Trial FOCUS Clinical Trial for Patients with Hepatic Dominant Ocular Melanoma (the FOCUS Trial) Study objective: To evaluate the safety, efficacy and pharmacokinetic profile of chemosaturation therapy versus best alternative care (BAC) in 240 patients with hepatic dominant OM Primary endpoint: Comparison of overall survival between the two study arms Secondary endpoints: Overall progression-free survival Overall response rate Hepatic progression-free survival Hepatic response rate Quality of Life (QoL) assessment

22 Protocol 202 European Study Hepatocellular Carcinoma (HCC) & Intrahepatic Cholangiocarcinoma (ICC) Programme Study objective: To assess the safety and efficacy of chemosaturation therapy in HCC and ICC patients Primary endpoint: Objective response rate via modified response Evaluation Criteria in solid tumors (mrecist) Secondary endpoints: Progression-free survival Systemic exposure of chemosaturation therapy Quality of Life assessment

23 Germany German centres that have preformed CHEMOSAT 1. Charité Hospital, Berlin 2. University of Bonn 3. Goethe University Frankfurt 4. University Hospital Göttingen 5. Asklepios Klinik Barmbek, Hamburg 6. Hannover MHH 7. University of Heidelberg 8. University of Jena 9. University of Leipzig 10. University Clinic Regensburg 11. University Clinic Tübingen CHEMOSAT TREATMENTS (Dec 2016) PATIENTS TREATED 209 TOTAL TREATMENTS 378 PTs TREATED 2X 114 PTs TREATED 3X 38 PTs TREATED 4X 13 PTs TREATED 5X 4 PTs TREATED 6X 1

24 Chemosaturation: Indication, Technique and Outcome Thomas J Vogl, S Koch, B Gebauer, W Willinek, C Engelke, R Bruening, F Wacker, A Enk I D I R: Institute of Diagnostic and Interventional Radiology Goethe University Frankfurt, Germany