Tips and tricks. Camillo Aliberti, Massimo Tilli

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1 Tips and tricks Camillo Aliberti, Massimo Tilli Unit of Oncological Diagnostic and Interventional Radiology, Delta Hospital AUSL Ferrara, Ferrara Italy

2 Intra-arterial treatment of liver malignancy with drug eluting beads: General Report of 5-yy experience ( ) 349 patients treated 626 TACE 2 cases of major complications (1 acute pancreatitis and 1 abscess epatic)

3 DEBDOX DEBIRI Cholangiocarcinoma: 54 pts Pancreatic Cancer: 8 pts Breast Cancer: 22 pts Gastric Cancer: 8 Colorectal Cancer: 148 pts Uveal Melanoma: 78 pts Melanoma 12 Carcinoid: 20 Sarcoma:5 Willms Cancer: 2

4 Lessons learned PTS SELECTION PLANNING DOSE OF DRUG SIZE OF BEADS DEB ADMINISTRATION SUPPORTIVE THERAPY EVALUATION OF TUMOR RESPONSE

5 Imaging planning Obtaining a triple-phase CT or MRI of the liver is mandatory to evaluate the indication to treatment of liver 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.

6 Loading Dose of Irinotecan Each vial of DC Bead (2 ml of beads) should be loaded with 50mg Irinotecan (loading dose, 50 mg Irinotecan/ ml of beads). Complete loading achieved within min. Usually prepare the Beads the day before the TACE.

7 Choice of DC Bead Size Use of μm beads For a standard procedure. Before TACE After TACE

8 Choice of Dose For small lesions or lobar treatment: 100 mg of Irinotecan loaded in 2 ml of Beads mg Irinotecan

9 Choice of Dose For larger lesion or full liver treatment : a maximum of 200 mg of Irinotecan loaded in 4 ml of Beads mg Irinotecan Indication to treatment with DC Bead in patients with tumor replacing not more than 70%. In case of replacing more than 50% Interventional and clinical expertise is required to manage patients.

10 DEB Administration 1 Removing the overnatant fluid 2 Mixing beads with a solution of 5-10 ml of contrast media / ml of DC Bead

11 DEB Administration A selective (segmental or lobar) approach should be used. Only in selected cases full liver treatment. Right lobe Lefth lobe Left and Right lobe 116/254 40% 76/254 30% 77/254 30%

12 DEB Administration The use of a microcatheter is advisable: Reduces the vasospasm Permits a optimal distribution of microsphere. Permits the catheterization of difficult arteries. Very Slow infusion of Beads

13 DEB Administration Pay attention to identifying the origin of the cystic and pancreatic artery! pancreatic artery Cystic artery

14 Lobar approach: Place the catheter as selectively as possible in branches of the right or left hepatic artery.

15 Whole Liver Treatment: Place the catheter as selectively as possible in the right or left hepatic branches until chemosaturation. Not infuse bead sin common trunk of hepatic artery! High risk administration of even a few DC Beads into extrahepatic vessels could have dire consequences. 6 months after TACE

16 The Embolization aim of TACE Endpoint wiht DC Injection should be continued until near stasis is Bead observed is in the Drug artery directly delivery feeding the not tumor embolotherapy! BEFORE TACE AFTER TACE End point: FULL DOSE (no stasis) No additional embolization should be performed.

17 Supportive Therapy Intravenous (iv) hydration started Day-1 and continued on Day 0, +1, ml bag/24h infusion (1000ml of saline solution 1000ml of glucose 5%) with the addition of Ranitidine 900mg Prophylactic treatment against pain Morphine 10mg 1 vial iv 30 minutes before DEBIRI and 1vial at +6 hours Intra-arterial Lidocaine 5ml just before DEBIRI Prophylactic treatment against nausea Tropisetron 5mg, 1 vial iv before and 1 vial at +6 hours Prednisone 25mg orally (or Desamethasone 8mgr iv) at am and at pm on day 0,+1,+2,+3,+4,+5 Prophylactic treatment against infection Cefazolin 2000mg iv at am and at pm day 0,+1,+2 The supportive treatment is continued if required on day +3, +4, +5

18 Treatment response Should be assessed according to modified RECIST (mrecist) using morpho-dimensional criteria

19 Treatment response Consider also lack of enhancement

20 RESULTS Liver metastases of Colorectal Cancer (From 2006, March to 2011, March) 148 patients are treated TACE % thecnical success 1 major complication (acute pancreatitis)

21 Probability of continued response RESULTS DEBIRI Colorectal L.M: Report of 120 pts Duration of response (months) Median survival time is 22,4 months. Median time to progression is 8.04 months Median duration of response 5,6 months Aliberti et al JVIR in press

22 RESULTS Only DEBIRI 56/116 Median survival time 15,7 months Median duration of response 3,2 months Median time to progression 4,6 months DEBIRI+ Sistemic therapy 66/116 The association to sistemic Median survival time 24,6 months therapy increase the Median duration. of treatment response response 8,2 months Median time to progression 10,2 months

23 DEBIRI Colorectal Liver Metastases treatment algorithm DEBIRI TACE 2/4 ml of Beads Loaded with mg od Drug 4 week CT/MR ot PET Complete Response Partial Response Progression Follow up and other oncological therapy Progression TACE TACE Other oncological therapy

24 RESULTS Liver metastases from Uveal Melanoma: Report (From 2007, May to 2011, March) 78 Patients treated 104 TACE

25 Treatment Schedule Bead size RESULTS Dose of Drug mg (when is possible use the maximum dose) Segmental or Lobar approach; if necessary is possible to treat whole liver. Peri-Procedure Medication Similar strategy of DEB in Colorectal Metastases

26 Clinical Responses We observed an overall Response Rate of 45/52 pts (86%) followed RECIST-modified criteria at 3 months. A month after TACE we observed: A significant reduction (>50%) of the lesional contrast enhancement in 93% of patients. 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 RESULTS 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 slowrelease irinotecan-eluting beads. Early results of a phase II clinical study. In Vivo; 2009 Jan- Feb;23(1):131-7

27 Before TACE RESULTS Liver metastases from Uveal Melanoma After TACE DSA Before TACE After TACE

28 ENDPOINT: Full dose of drug Sometimes we induce blood stasis before complete infusion of IRI planned dose Injection of beads until stasis

29 What s new? Size μm New DC Bead Size designed to optimize Drug Delivery

30 Number of microspheres per vial => 6 times more microspheres in the DC Bead M1 vial than in DC Bead µm

31 Rationale Develop a product that is best suited to treating the different type of metastatic disease, exspecially hypovascular mets Deeper penetration into the tumour bed Avoid premature proximal occlusion of tumor feeding vessels

32 Optimizing Drug Delivery: Importance of Particle Size SMALL Size μm Size μm Chemosaturation Deeper penetration of the tumour bed and permitting to deliver a consistent dose of drug.

33 Ability to deliver a consistent dose ( mg irinotecan) Deliver consistent dose of drug that compliments systemic Cht Treatment of microsatellites not visible on DSA or CT scans Within the current size/safety profile of M1: Larger than 70 micron to minimise the risk of shunting Larger than 40 micron to eliminate the need for MAA mapping

34 INDICATIONS CE Marked for use ONLY with Irinotecan Hypo-vascularisated tumors Treatment of microsatellites lesions Treatment of residual vial tissue after first TACE Treatment of recurrent lesions

35 Hypo-vascularisated lesions Before TACE Before TACE Treatment of microsatellites After TACE After TACE

36 Higher rate of necrosis Detecting of necrotic areas in micrometastases not seen at baseline CT

37 LM from CRC Microsatellite of LM

38 Large necrosis and progressive dimensional reduction at 1 month CT at 24h LM from CRC CT at 1month

39 Necrosis in many microsatellite and hypovascular LM from uveal melanoma not shown in baseline CT

40 NOT SUITABLE FOR M1 A/P Fistula in LM from uveal melanoma (risk oh hepatic infarction) Prolonged DSA study before injection!!!

41 Since November 2010 we performed 81 TACE using M1 treating 48 patients 11 colorectal mets 29 uveal melanoma 4 breast cancer 2 esophageal cancer 2 small cell lung cancer

42 All pts presented not large hypovascular metastases or recurrence after first DEBIRI cycle In 10 patients, short lasting alopecia was observed at 3 to 4 weeks MDCT at 24 hours extended to obtain also pulmonary angiography (performed in all pts) don t detect mayor complications or radiological signs of pulmonar embolism In all pts we injected maximal dose of IRI (100 to 200mg) Imaging after TACE seems to show higher tumor necrosis (also in microlesions not visible at baseline imaging) than DC Bead µm

43 Conclusion The use of DC Bead M1 is well tolerated and safe In our experience, it increase the efficacy of DEBIRI treatment Larger studies are needed to confirm these promising results

44 Thanks for attention