DC Bead Terumo Workshop GEST 2011 April 27-30 Paris DC Bead Terumo Workshop DEBIRI on colorectal cancer liver metastases: personal experience and tips & tricks Ivan Marri, Camillo Aliberti Unit of Oncological Diagnostic and Interventional Radiology, Delta Hospital AUSL Ferrara, Ferrara Italy camy.ali@libero.it Slide 1

GEST 2011 April 27-30 Paris 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) Slide 2

DEBDOX DEBIRI Cholangiocarcinoma: 54pts Colorectal Cancer: 148pts GEST 2011 April 27-30 Paris DEBDOX DEBIRI Cholangiocarcinoma: 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

1 major complication (acute pancreatitis) GEST 2011 April 27-30 Paris 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 GEST 2011 April 27-30 Paris 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 GEST 2011 April 27-30 Paris 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 Dose + For small lesions or lobar treatment: GEST 2011 April 27-30 Paris Choice of Dose For small lesions or lobar treatment: 100mg of Irinotecan loaded in 2ml of Beads + 100mg Irinotecan

GEST 2011 April 27-30 Paris Choice of Dose For larger lesion or full liver treatment: a maximum of 200mg of Irinotecan loaded in 4ml of Beads + 200mg Irinotecan 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.

Optimizing drug delivery: preferable use of small particles GEST 2011 April 27-30 Paris Choice of DC Bead size Optimizing drug delivery: preferable use of small particles Chemosaturation Size 100-300 μm Size 70-150 μm Deeper penetration into the tumor vascular bed permits to deliver a greater effective dose of drug

Choice of DC Bead size Use of 100-300μm Beads GEST 2011 April 27-30 Paris Choice of DC Bead size Use of 100-300μm Beads for a standard procedure After TACE Before TACE

Choice of DC Bead size Hypovascular metastases GEST 2011 April 27-30 Paris Choice of DC Bead size 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

Treatment of microsatellites GEST 2011 April 27-30 Paris Hypovascular lesions Before TACE Before TACE After TACE Treatment of microsatellites After TACE

Peri-procedural medication GEST 2011 April 27-30 Paris Peri-procedural medication Pain 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 5-10ml of contrast media / ml of DC Bead GEST 2011 April 27-30 Paris 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: GEST 2011 April 27-30 Paris 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!

GEST 2011 April 27-30 Paris Drug administration 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%

GEST 2011 April 27-30 Paris Lobar approach: Place the catheter as selectively as possible in the right or left hepatic artery

Whole liver treatment: GEST 2011 April 27-30 Paris 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 administration GEST 2011 April 27-30 Paris DEBIRI administration Pay attention to identify the origin of cystic and pancreatic artery! Pancreatic artery Cystic artery 19

The aim of TACE with DC Bead is drug delivery not embolotherapy! GEST 2011 April 27-30 Paris Embolization Endpoint Injection should be continued until “near stasis” is observed in the artery directly feeding the tumor The aim of TACE with DC Bead is drug delivery not embolotherapy! AFTER TACE BEFORE TACE Endpoint: FULL DOSE (not stasis) No additional embolization should be performed 20

GEST 2011 April 27-30 Paris Treatment response should be assessed according to modified RECIST (mRECIST)

DEBIRI in Colorectal L.M.: Report of 120 pts GEST 2011 April 27-30 Paris DEBIRI in Colorectal L.M.: Report of 120 pts Median survival time 22,4 months. Median time to progression 8.04 months Median duration of response 5,6 months Aliberti et al. JVIR in press 22

GEST 2011 April 27-30 Paris The association with sistemic therapy increase the response to treatment DEBIRI+Sistemic therapy 63/116 Median survival time 24,6months Median duration of response 8,2months Median time to progression 10,2months Only DEBIRI 53/116 Median survival time 15,7months Median duration of response 3,2months Median time to progression 4,6months 23

DEBIRI Colorectal Liver Metastases treatment algorithm GEST 2011 April 27-30 Paris 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 Partial Response Progression Follow up and other oncological therapy TACE Other oncological therapy Progression TACE

Liver metastases from Uveal Melanoma GEST 2011 April 27-30 Paris 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 25

Liver metastases from Uveal Melanoma GEST 2011 April 27-30 Paris Liver metastases from Uveal Melanoma General report (from May 2007 to March 2011): 78 Patients treated 104 TACE

Liver metastases from Uveal Melanoma GEST 2011 April 27-30 Paris Liver metastases from Uveal Melanoma Treatment Schedule Bead 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

Results: clinical responses GEST 2011 April 27-30 Paris Liver metastases from Uveal Melanoma Results: clinical responses 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. 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

Liver metastases from Uveal Melanoma GEST 2011 April 27-30 Paris Before TACE Liver metastases from Uveal Melanoma After TACE DSA Before TACE After TACE

Advantages of TACE with DEBIRI in Liver Metastases GEST 2011 April 27-30 Paris Advantages of TACE with DEBIRI in Liver Metastases 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