DEB-TACE vs Conventional TACE in Intermediate HCC: Best Candidates for DEB-TACE?

Transcription

1 DEB-TACE vs Conventional TACE in Intermediate HCC: Best Candidates for DEB-TACE? Ho Jong Chun, MD., PhD Seoul St. Mary s Hospital, The Catholic University of Korea

2 Why Drug-eluting Beads? Clear Rationale - Maximize drug delivery - Consistent/better reproducibility of the method - Long-lasting effect/slow release - Lower systemic side effect

3 DC Beads TM Comparison with Intraarterial Injection in Rabbit Hong K et al. Clin Cancer Res 2006;12:

4 DC Beads TM Pharmacokinetics Varela M et al.j Hepatol Mar;46(3):474-81

5 DEB-TACE Possible Advantages over c-tace Localized delivery of drugs Controlled/sustained release of drugs More chemotherapeutic agent in the tumor higher tumor objective response Less chemotherapeutic agent in blood stream less systemic toxicity or adverse effect

6 Seoul St. Mary s Hospital Typical Imaging Course on CT Pre Cone beam CT after TACE 1 day 1 month 3 month contrast saturation

7 DEB-TACE vs ctace RCT (2010) p = 0.11 Lammer J et al. CVIR 2010;33:41-52

8 DEB-TACE vs ctace RCT (2010) DC Bead showed significant advantage in patients with negative prognostic factors Patients for with objective negative response prognostic (p=0.038) factors and disease control (p=0.026) Lammer J et al. CVIR 2010;33:41-52

9 DEB-TACE vs ctace RCT (2014) 177 patients RCT (Precision Italia Study Group) DEB-TACE (n=89) vs ctace (n=88) 1- and 2-year survival (p=0.949) % and 56.8% after DEB-TACE % and 55.4% after ctace Objective tumor response (p>0.05) R Golfieri, et al. British Journal of Cancer 2014;111:

10 DEB-TACE vs ctace RCT (2014) Adverse events Subgroup analysis R Golfieri, et al. British Journal of Cancer 2014;111:

11 DEB-TACE vs ctace Meta-analysis (2014) Objective tumor response for DEB-TACE Huang K, et al. J Gastroenterol Hepatol. 2014;29:

12 DEB-TACE vs ctace Meta-analysis (2014) Disease control for DEB-TACE Complications for DEB-TACE Han S, et al. PLoS One 2014;9(8):e102686

13 DEB-TACE vs ctace Meta-analysis (2015) Overall survival Objective tumor response Xie Z, et al. Hepatology Research 2015;45:

14 DEB-TACE vs ctace Pathologic Comparison (2014) 111 consecutive HCC before OLT DEB-TACE (n=35) vs ctace (n=76) Complete necrosis after OLT % for ctace % for DEB-TACE No significant differences of necrosis rate, tumor recurrence, drop-out and tolerability. Frenette CT, et al. Transplantation. 2014;987:

15 DEB-TACE vs ctace Summary Two RCTs, Three Meta-anaslysis, One Pathologic Comparison Tumor response DEB-TACE ctace Survival DEB-TACE ctace Safety DEB-TACE ctace

16 DEB-TACE vs ctace Embolization Characteristics DEB-TACE ctace material PVA microsphere Lipiodol+gelfoam duration permanent transient vessel damage severe mild size 100~300 μm liquid level catheter technique only within or just before tumor avoid wedge the catheter (catheter<feeding artery) can pass thru portal vein can wedge the catheter (catheter feeding artery)

17 Predictive Factors for Complete Response after DEB-TACE 172 patients with 315 tumors Imaging response evaluation with mrecist 1 month after DEB-TACE Tumor size > 5 cm CR Median location (S1/S4) CR common intrahepatic collaterals & anastomosis Total extinction blush CR Vesselle G, et al. Eur Radiol Oct 11

18 Predictive Factors for Histologic Necrosis after DEB-TACE 23 patients with 27 tumors within Milan criteria Imaging response evaluation with mrecist Explant pathology comparison after DEB-TACE Odisio BC, et al. CVIR 2014;37:

19 Predictive Factors for Histologic Necrosis after DEB-TACE 23 patients with 27 tumors within Milan criteria Imaging response evaluation with mrecist Explant pathology comparison after DEB-TACE Mean overall initial lesion diameter (p=0.030) - group 1 (> 50% necrosis) 3.2 cm - group 2 ( 50% necrosis) 2.1 cm Presence of capsule (p=0.0027) - group 1 (> 50% necrosis) 78% - group 2 ( 50% necrosis) 22% Odisio BC, et al. CVIR 2014;37:

20 Predictive Factors for Histologic Necrosis after DEB-TACE 23 patients with 27 tumors within Milan criteria Imaging response evaluation with mrecist Explant pathology comparison after DEB-TACE Mean overall initial lesion diameter (p=0.030) - group 1 (> 50% necrosis) 3.2 cm - group 2 ( 50% necrosis) 2.1 cm Presence of capsule (p=0.0027) - group 1 (> 50% necrosis) 78% - group 2 ( 50% necrosis) 22% Smaller (<2 cm) and non-encapsulated tumor necrosis Odisio BC, et al. CVIR 2014;37:

21 Predictive Factors for Histologic Necrosis after DEB-TACE 61 patients before OLT Explant pathology comparison after DEB-TACE Smaller (<2 cm) and non-encapsulated tumor necrosis Fasarella PM, et al. CIRSE 2015

22 Small HCCs M/61 HCC(B)/Child A Two small HCCs: ~1.5 cm, probably encapsulated, some hypervascular Peripheral location, fine feeding arteries

23 Small HCCs M/61 HCC(B)/Child A Two small HCCs: ~1.5 cm, probably encapsulated, some hypervascular Peripheral location, fine feeding arteries DEB-TACE ( μm+doxorubicin 50 mg)

24 Small HCCs M/61 HCC(B)/Child A Two small HCCs: ~1.5 cm, probably encapsulated, some hypervascular Peripheral location, fine feeding arteries DEB-TACE ( μm+doxorubicin 50 mg) CR/SD on 1 month FU

25 Small HCCs M/75 HCC(B)/Child A/Recurrent nodule after TACE small HCC: 1.3 cm probably encapsulated hypervascular one feeding artery less than catheter diameter wedging the catheter

26 Small HCCs M/75 HCC(B)/Child A/Recurrent nodule after TACE small HCC: 1.3 cm probably encapsulated hypervascular one feeding artery less than catheter diameter wedging the catheter limited in DEB TACE due to smaller feeding artery than the microcatheter early or proximal plugging

27 DEB-TACE Small HCCs vs Intermediate/Large HCCs 90 patients with HCCs (n=119) Imaging response evaluation with mrecist 1 month follow-up after DEB-TACE Size # CR PR SD PD 2 cm (68%) 5 (10%) 11 (22%) 0 (0%) > 2 cm 5 cm (67.3%) 12 (23.1%) 4 (7.7) 1 (1.9%) > 5 cm 17 7 (41.2%) 9 (53%) 1 (5.8%) 0 (0%) P= > 5 cm tumor was significantly lower in CR than 5 cm tumor on 1 month FU after DEB TACE. Subgroup analysis from Oh JS, Chun HJ, et al. J Vasc Interv Radiol 2013; 24:

28 DEB-TACE Small HCCs vs Intermediate/Large HCCs 90 patients with HCCs (n=119) Imaging response evaluation with mrecist 1 month follow-up after DEB-TACE Size # OR SD PD 2 cm (78%) 11 (22%) 0 (0%) > 2 cm 5 cm 52 47(90.4%) 4 (7.7) 1 (1.9%) > 5 cm (94.2%) 1 (5.8%) 0 (0%) P= > 5 cm tumor was significantly lower in CR than 5 cm tumor on 1 month FU after DEB TACE. 2 cm tumor was significantly lower in OR than > 2 cm tumor. Subgroup analysis from Oh JS, Chun HJ, et al. J Vasc Interv Radiol 2013; 24:

29 Better Response Factors for DEB-TACE 1. Tumor size Smaller < Intermediate/Large

30 Better Response Factors for DEB-TACE 1. Tumor size Smaller < Intermediate/Large 2. Tumor location

31 Central/Median lobe HCCs M/57 HCC(B)/Child A Single intermediate-size HCC: ~4.1 cm, encapsulated, hypervascular Central location, multiple fine feeding arteries only segmental treatment (DEB-TACE)

32 Central/Median lobe HCCs M/57 HCC(B)/Child A Single intermediate-size HCC: ~4.1 cm, encapsulated, hypervascular Central location, multiple fine feeding arteries only segmental treatment (DEB-TACE) PR on 1 month FU feeding artery damage limited in repeated TACE

33 Central/Median lobe HCCs M/83 HCC(B)/Child A Multiple HCCs: ~3.8 cm, encapsulated, hypervascular Central location, multiple fine feeding arteries only lobar treatment

34 Central/Median lobe HCCs M/83 HCC(B)/Child A Multiple HCCs: ~3.8 cm, encapsulated, hypervascular Central location, multiple fine feeding arteries only lobar treatment limited in DEB-TACE due to mandatory lobar treatment for multiple/central HCC

35 Better Response Factors for DEB-TACE 1. Tumor size Smaller < Intermediate/Large 2. Tumor location Median/central < Peripheral/subcapsular

36 Better Response Factors for DEB-TACE 1. Tumor size Smaller < Intermediate/Large 2. Tumor location Median/central < Peripheral/subcapsular 3. Tumor vascularity - Enhancement degree on CT/MR - Angiographic staining degree - Perfusion volume on CT/DSA - Diffuse-weighted MR (DWMR)

37 Predictors for Response after DEB-TACE on DWMR 57 patients with HCCs Diffuse-weighed MR (DWMR) study before/after DEB-TACE Imaging response evaluation with mrecist Low ADC value High cellularity/non-necrosis/high vascularity At baseline, lesions with OR at 1 and 3 months showed more restricted diffusion compared with others (p=0.031) A baseline ADC < mm 2 /s is a predictor of survival. Kokabi N, et al. J Vasc Interv Radiol 2015;26:

38 Better Response Factors for DEB-TACE 1. Tumor size Smaller < Intermediate/Large 2. Tumor location Median/central < Peripheral/subcapsular 3. Tumor vascularity Hypervascular 4. Can be treated with superselective approach

39 DEB-TACE vs ctace Liver/Biliary Injury 237 patients with NET (n=134), HCC (n=103) CT/ MR evaluation after ctace (n=294), DEB-TACE (n=182) DEB-TACE is independently associated with liver/biliary injuries (OR=6.62). Biloma/parenchymal infarct strongly associated with DEB-TACE (OR=9.78;p=0.002) and underlying noncirrhotic liver (OR=8.13;p=0.04). Guiu B, et al. Journal of Hepatology 2012;56:

40 DEB-TACE ctace Limitations of DEB-TACE 1. Limited embolization effect in small HCC - Difficulty to target the tumor/small feeding artery - Weak arterial supply/large portal vein flow supply 2. Limited in hypovascular tumor TACE 3. Limited in non-superselective embolization - More parenchymal/bile duct damage - Non-feeding artery damage/early feeding artery occlusion 4. Limited in repeated TACE - Feeding artery permanent occlusion/damage

41 Previous Suggested Indications of DEB-TACE Patients with heart problem (Excellent pharmacokinetics) Patients with advanced clinical stage (Better tumor response) Patients with larger tumor (Excellent pharmacokinetics) Same with ctace Non-resectable tumor Down-stage or bridge for surgery Recurrent tumor after surgery Better tumor response Early detection of residual/recurrent tumor prolonged overall survival

42 Current Suggested Indications of DEB-TACE Think the advantages - Excellent pharmacokinetics - Less post-embolization syndrome - Better tumor response?

43 Current Suggested Indications of DEB-TACE Think the advantages - Excellent pharmacokinetics - Less post-embolization syndrome - Better tumor response? Think the limitations first - Not too small ( 2 cm) or not too large tumor (< 5 cm) (large tumor repeated TACE or additional embolization) - Hypervascular/encapsulated tumor - Non-median/central liver location - Can be treated with superselective approach

44 DEB-TACE in Future Advances Relatively large particles (100~300 μm) - Cannot pass through small feeding artery or into portal vein - Limited efficacy in small/early HCC or hypovascular tumor Smaller 40 μm-sized microsphere Permanent embolization particles (PVA-based) - Severe vessel damage - Bile duct complication/limited in repeated TACE or lobar treatment Biodegradable drug-eluting microsphere

45 Summary Drug-eluting beads (DEB) have excellent pharmacokinetics with improving antitumor efficacy. However, DEB-TACE did not demonstrate significant superiority in tumor response or overall survival so far. DEB-TACE has some limitations in clinical practice, related to larger-sized particles and permanent embolic effect. Therefore, DEB-TACE may demonstrate better result than before in controlled indications; intermediate sized, hypervascular, encapsulated, peripherally located, single tumors. Future advanced technology will overcome the limitations of current DEB and may bring superiority of DEB-TACE over conventional TACE.

46 감사합니다.