ivan marri, camillo aliberti unit of oncological diagnostic and interventional radiology,

Ivan Marri, Camillo Aliberti

Unit of Oncological Diagnostic and Interventional Radiology,

Delta Hospital AUSL Ferrara, Ferrara Italy

[email protected]

GEST 2011 April 27-30 Paris

DC Bead Terumo Workshop

DEBIRI on colorectal cancer liver metastases: personal

experience and tips & tricks

Intra-arterial treatment of liver malignancy with drug eluting Beads:

Global Report of five years of experience (from March 2006 to March 2011)

• 357 patients treated • 626 TACE• 2 cases of major complications(1 acute pancreatitis and 1 liver abscess)


DEBIRIDEBDOX CholangiocarcinomaCholangiocarcinoma: 54pts

Pancreatic Cancer: 8pts

Breast Cancer: 22pts

Gastric Cancer: 8pts

Carcinoid: 20pts

Sarcoma: 5pts

Willms Cancer: 2pts

Colorectal Cancer: 148pts

Uveal Melanoma: 78pts

Melanoma: 12pts


Liver metastases of Colorectal Cancer: General Report (From 2006 to 2011)

• 148 patients treated • 254 TACE• 100% technical success• 1 major complication (acute pancreatitis)


Pre-Treatment Imaging

Obtaining a triple-phase CT or MRI of the liver is mandatory to evaluate the indication to the treatment of metastases with DC-Bead

• Site and number of LM• % of liver substitution• Vascular map of the liver• Feeding vessels of the lesions• Morphologic evaluation of ileo-femoral arteries

Additional imaging examinations to rule out extrahepatic disease should be performed as appropriate.


Loading dose of Irinotecan

Each vial of DC Bead (2ml of Beads) can load 100mg of Irinotecan (loading dose 50mg Irinotecan/ml of Beads)

Complete loading achieved within 60-120min: we usually load Beads the day before the TACE.


Choice of DoseFor small lesions or lobar treatment:

100mg of Irinotecan loaded in 2ml of Beads

+100mg

Irinotecan


Choice of DoseFor larger lesion or full liver treatment: a maximum

of 200mg of Irinotecan loaded in 4ml of Beads

Indication to treatment with DC Bead in patients with liver replacing less than 70% .In case of replacing more than 50% interventional and clinical expertise is required to manage patients.

+200mg

Irinotecan


Choice of DC Bead size Optimizing drug delivery: preferable use

of small particles

Deeper penetration into the tumor vascular bed permits to deliver a greater effective dose of drug

ChemosaturationSize 100-300 μm Size 70-150 μm


Before TACE After TACE


Choice of DC Bead size Use of 100-300μm Beads for a standard procedure

CE Marked for use ONLY with Irinotecan

•Hypovascular metastases•Treatment of microsatellites lesions•Treatment of residual viable tissue after first TACE•Treatment of recurrent lesions


Choice of DC Bead size

Hypovascularlesions

Treatment of microsatellites

Before TACE Before TACE

After TACE

After TACE


Peri-procedural medicationPain treatment: •1 vial (10mg) of Morphine/100ml of physiological solution e.v. 30min. before the procedure•1 vial of Morphine/100ml of physiological solution e.v. slow infusion during the TACE•1 vial of Morphine/100ml of physiological solution very slow infusion afther the procedure

Prophylactic treatment against nausea: 1 vial (5mg) of Tropisetron/100ml of phs.sol. e.v. before TACE and at +6 hours

Antibiotic prophylaxis and gastric protection should be administered from day 0 to day 5


Drug administration

1 Remove the overnatant fluid

2 Mix Beads with a solution of 5-10ml of contrast media / ml of DC Bead


The use of microcatheter is advisable:•Reduces the vasospasm•Permits the catheterization of difficult arteries•Permits an optimal distribution of microspheres

Very Slow infusion of Beads!


A selective (segmental or lobar) approach should be used; only in selected cases full liver treatment.

Right lobe Lefth lobe L+R lobe

101/254 40% 75/254 30% 76/254 30%


Drug administration

Lobar approach: Place the catheter as selectively as possible in the right or left hepatic artery


Whole liver treatment:Place the catheter as selectively as possible in tumors feeding arteries in right and left lobe Do not infuse Beads in common trunk of hepatic artery! High risk of administration of even a few DC Beads into extra-hepatic vessels

6 months after TACE


DEBIRI administrationPay attention to identify the origin of

cystic and pancreatic artery!

Cystic artery

Pancreatic artery


Embolization EndpointInjection should be continued until “near stasis” is observed in the artery directly feeding the tumor

No additional embolization should be performed

BEFORE TACE AFTER TACE

Endpoint: FULL DOSE (not stasis)

The aim of TACE with DC Bead is drug delivery not embolotherapy!


Treatment response should be assessed according to modified RECIST (mRECIST)


DEBIRI in Colorectal L.M.: Report of 120 pts

Median survival time 22,4 months.

Median time to progression 8.04 months

Duration of response (months)121086420

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Median duration of response 5,6 months

Aliberti et al. JVIR in press


Only DEBIRI 53/116•Median survival time 15,7months•Median duration of response 3,2months•Median time to progression 4,6months

DEBIRI+Sistemic therapy63/116 •Median survival time 24,6months•Median duration of response 8,2months•Median time to progression 10,2months

The association with sistemic therapy increase the response to treatment


DEBIRI Colorectal Liver Metastases treatment algorithm

DEBIRI TACE 2/4 ml of Beads Loaded with 100-200mg od Drug

4 week CT/MR or PET

Complete Response

Follow up and other oncological therapy

Partial Response

TACE

Progression

Other oncological therapy

Progression

TACE


Liver metastases from Uveal Melanoma• 60-70% Intrahepatic diffuse, 30-40% oligonodular

• Surgery is feasible in only a minority of patients (30%) .

• Systemic chemotherapy (nitrosureas, DITC, Cisplatin and Interferons) has achieved a low median survival (range 5-7 months)

• Conventional TACE showed slightly better median survival (10 months)

• Other therapeutic approaches (Photodynamic, RT, HIFU) are still investigational and require further supporting data.

Palliative therapies have not been shown to significantly improve survival


General report(from May 2007 to March 2011):

• 78 Patients treated • 104 TACE


Liver metastases from Uveal Melanoma

Treatment ScheduleBead size 100-300μm

Dose of drug 75-150mg (when is possible use the maximum dose)

Segmental or lobar approch if necessary is possible to treat whole liver.

Peri-procedural medication is the same of colorectal metastases



One month after TACE we observed a significant reduction (>50%) of the lesional contrast enhancement in 93% of patients

We observed an overall Response Rate of 45/52 pts (86%) followed RECIST-modified criteria at 3 months f.u.

Results: clinical responses

37 patients out 52 are alive at time of analysis, with a median time to progression of 7,5 months and median follow-up of 10 months (range 1-24 months)

40% of entire population are alive at 15 months

Fiorentini G, Aliberti C, Del Conte A, Tilli M, Rossi S, Ballardini P, Turrisi G, Benea G: Intra-arterial hepatic chemoembolization (TACE) of liver metastases from ocular melanoma with slow-release irinotecan-eluting beads. Early results of a phase II clinical study. In Vivo; 2009 Jan-Feb;23(1):131-7



After TACE

After TACEBefore TACE

Before TACE

DSA



• Absence of systemic toxicity

• Good treatment option for patients with toxicity of chemotheraphy waiting for further therapy (Chemo-Holiday)

• Effective palliation in preminent hepatic metastatic disease from various tumors

• Probably the best treatment in ocular melanoma patients


Advantages of TACE with DEBIRI in Liver Metastases

ivan marri, camillo aliberti unit of oncological diagnostic and interventional radiology,

Documents

liver treatment

treatment of metastases

pts breast cancer

pts pancreatic cancer

pts gastric cancer

pts willms cancer

dcbead site

lobar treatment