chemosaturation: indication, technique and outcome · liver malignancies: arterial therapies...

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

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

Liver Malignancies: Treatment Decision-making is a Complex Task

Institute of Diagnostic and Interventional Radiology, Goethe University, Frankfurt/Main

Individualized

therapy

Receptor status

Mutation status

Krankheitsfreies Intervall

Previous

therapiesNebenwirkungspe

Metastasenlokalistion

Symptome

Biomarkers

Disease-free interval

Symptoms

Localization of tumor

Spectrum ofside effects

Patientpreference

Liver Malignancies: Check List


1. Unilobar – bilobar

2. Resectable – unresectable

resection combined withcontralateral ablation

peritoneum lymph nodes lung (bone tumors)

3. Synchronous – metachronous

4. No extrahepatic manifestation – extrahepatic manifestation

5. Symptomatic – asymptomatic

Liver Malignancies: Arterial Therapies


Definition: 1. Intraarterial hepatic chemotherapy (IAHC)Transarterial chemoperfusion (TACP)

2. Transarterial chemoembolization (TACE)

- conventional TACE

- TACE with DC beads

3. Radioembolization4. Isolated liver perfusion

Indications: 1. Salvage therapy: response when systemictherapy inefficient

2. First line therapy (induction therapy): convertnonsurgical patient to surgical patient

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

Liver Malignancies: Clinical Classification

Intensified therapy:FOLFOX + Cet

FOLFIRI + Cet

FOLFOXIRI

CT + Bev ? HAI, TACE

Surgery

or

FOLFOX

Group 3Liver metastasesthat are unlikelyto become resectable

Group 1Primarilyresectablemetastases

Group 2Potentiallyresectablemetastases

symptomaticrapid progression

asymptomaticslow

progression

primary goal:

QoL, survival time

TACE, HAI, SIRT


Isolated Hepatic Perfusion


IHP is a regional therapy which isolates the hepatic vascular inflow and outflow surgically1

The liver is then perfused with chemotherapy via a closed extracorporeal circuit1:

first tested at Roswell Park Institute in 19612

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 reports3,4

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;16:132-41

2. Ausman RK. N Y State J Med 1961;61:3393-7

3. Van Iersel LB, et al. Ann Oncol 2008;19:1127-43

4. Alexander HR Jr, et al. Ann Surg Oncol 2009;16:1852-9

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


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

Isolation

Chemosaturation withPercutaneous Hepatic Perfusion



German Melanoma Trial: Frankfurt

Study period: 2012 - 2015

Patients: n = 18 with hepatic metastasesfrom uveal melanoma

Chemosaturation therapy: 1 – 3 sessions

Evaluation: n = 17 patients RECIST criteria

survival time analysis

adverse events and complications


German Melanoma Trial: Frankfurt

Median overall survival after first chemosaturation:

9.6 months

range: 4 – 29.8 months

Time to progression: n = 2 patients with PD

n = 1 patient 3.6 months

n = 1 patient deceased 1.7 months after

chemosaturation

Results


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


1st Staging

Before Vemurafenib therapy

1st staging Pat. 2


MRI Before Melphalan Chemosaturation

Pat. 2


5th Staging: No Evidence of Disease

After 2nd MWA (3 months after chemosaturation)

After 1st MWA (2 months after chemosaturation)

Pat. 2


Chemosaturation Therapy

Before Chemosaturation Therapy

20/02/2013

After Chemosaturation Therapy

17/04/2013


Conclusion

Chemosaturation is a potential option for patients

with non-resectable hepatic metastases

from uveal melanoma.

Interventional Radiologist

Perfusionist

Anaesthetist

Pharmacist

Interventional radiology staff

Intensivist/critical care specialist Oncologist

(surgical & medical)*must commit to managing the patient


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


Focus – Phase III 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

FOCUS Clinical Trial for Patients with Hepatic Dominant Ocular Melanoma (the FOCUS Trial)


Protocol 202 – European StudyHepatocellular 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


GermanyGerman 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

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

chemosaturation: indication, technique and outcome · liver malignancies: arterial therapies...

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