Transarterial Kelly W. Burak Chemoembolization · 2020. 5. 19. · Kelly W. Burak Disclosures (past...
Transcript of Transarterial Kelly W. Burak Chemoembolization · 2020. 5. 19. · Kelly W. Burak Disclosures (past...
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Transarterial Chemoembolization
Kelly W. BurakMD, FRCPC, MSc (Epid)Associate Professor of MedicineUniversity of CalgaryDepartments of Medicine & Oncology
Director, Calgary Liver Unitand Southern Alberta Liver Transplant Clinic
Chair, IR Guidelines CommitteeAHS Provincial GI Tumour Group
@kwburak
Research support from:Bayer Bristol-Myers-SquibbGenentechSalixGlaxo-Smith-Kline
Consulting / Advisory Boards / Honorarium from:AstellasGileadJanssenNovartis
Kelly W. BurakDisclosures (past 24 months)
Overview
1) Evidence for TACE
2) DEBs vs cTACE
3) Bridging to LT
4) Combination with Sorafenib
5) When to abandon TACE?
median survival from ~ 16 20 months
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Systematic Review
• Technique
– No consensus chemo or particles
– Role of Lipiodol controversial
• Survival
– 1 yr = 62 20% / 3 yr = 30 15%
• Complications
– Post-embolization syndrome 60 – 80%
– Liver failure 0 – 49%
– Procedure related death 2.4% (0 – 9%)
Marelli L, et al. Cardiovasc Intervent Radiol 2007;30:6-25.
DEBs
DC-Bead [DEBDOX]100-300µM
HepaSphere
30-60µM
Doxorubicin Exposure
Varela M, et al. J Hepatol 2007;46:474-81.
DC-Bead
DEB versus cTACE
• Post-embolization syndrome similar
• Fewer liver toxicity
SAEs (9 vs 3)
• Less cardiotoxicity
LVEF DEB cTACE
No decrease 37% 29%
Non-substantial 18% 24%
Substantial 0% 6%
Not known 45% 42%
Vogel TJ, et al. Am J Roentgenol 2011;197:562-570.
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Better Survival with DEBs
• 104 pts (103 cirrhotic) treated with DEB
– 95% CP A, 63% HCV +
– 41 BCLC A / 63 BCLC B
• 24.5 mo median FU
– 2 LT / 24 sorafenib
• Median survival
– BCLC A = 54.2 mo
– BCLC B = 47.7 mo
– Censoring at LT / sorafenib = 47.7 mo
Burrel M, et al. J Hepatol 2012;56:1330-35.
Calgary TACE (2002-2010)
Characteristics cTACE (n=140) DEB (n=62) p value
Patients 65 34
# TACE/pt, median [range] 2 [1-6] 1 [1-5] NS
Male 73.9% 73.5% NS
Age, mean SE 66.7 1.4 59.4 1.9 0.003
HCV / HBV 38.5% / 21.5% 41.1% / 38.2% NS
LT performed 9.2% 8.8% NS
BCLC A / B 38.5% / 61.5% 41.2% / 58.6% NS
CP class A / B 58.7% / 41.3% 50% / 44.1% NS
Size largest lesion, mean 5.0cm 4.2cm NS
TTV, mean 393.9cm3 109.2cm3 NS
AFP, median 36.8ng/mL 28.5ng/mL NS
Overall Survival
Median OS [95%CI]
Overall cohort: 21.7 mo [15.8-30.9]
CP class A: 30.0 mo [20.1-42.0]
CP class B: 15.3 mo [12.0-18.7]
DEB: 26.5 mocTACE: 21.7 mo
Days after initial TACE
Pro
po
rtio
n S
urv
ivin
g
p=0.55
Survival Analysis
• Female sex associated with survival after TACE
– HR 3.7 [1.8-7.4], p<0.001– Adjusting for AFP, TTV, CP, age, LT listing, type & # of TACE
mortality HR [95% CI] mortality HR [95% CI]
TTV >115cm3 1.75 [1.00-3.07] Multiple TACE 0.51 [0.29-0.88]
AFP >400ng/mL 1.95 [1.08-3.52] Listing for LT 0.32 [0.12-0.89]
Ascites 2.37 [1.11-5.08] CP class A 0.51 [0.29-0.88]
ECOG PS 1 2.39 [1.36-4.21] Albumin 0.93 [0.87-0.99]
Male sex 0.33 [0.19-0.60]
Univariate analysis
Multivariate analysis
Complications & LOS
Characteristics cTACE (n=140) DEB (n=62) p value
Any Complication 86.2% 67.6% 0.029
Post-Embolization Syndrome 73.9% 23.5% <0.0001
Major Complications* 32.3% 11.8% 0.026
Death within 30 days 3 0# <0.001
Length of Stay, median [IQR] 3 days [2-5] 2 days [2-4] 0.011
*Major complications = Death within 30d, GI bleed, new ascites, SBP, encephalopathy, severe PES, vascular complications.
# Does not include 1 death in SPACE study and 1 death in 2012.
DEBs are Cost-Effective
Burak KW, et al. Can J Gastroenterol 2013; 27(Suppl A): 72A-73A.
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DEB vs cTACEOverall Survival
Song MJ, et al. J Hepatol 2012; 57: 1244-50.
Doxorubicin Exposure
HepaSphere
30-60µM
Malagari K, et al. Cardiovasc Intervent Radiol 2014; 37: 165-75.
Bridging to LT
Maggs JR, et al. Aliment Pharmacol Ther 2012; 35: 1113-1134.
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Combination Studies SPACE Study
Lencioni R, et al. J Clin Oncol 2012; Suppl 4: LBA154.
TTP
Lencioni R, et al. J Clin Oncol 2012; Suppl 4: LBA154.
Overall Survival
Lencioni R, et al. J Clin Oncol 2012; Suppl 4: LBA154.
Japan – Korea Study
• 458 CP A pts with unresectable HCC
• 25% tumour 1-3mo after 1st or 2nd TACE
• 1:1 sorafenib or placebo
• >50% started >9 wks after TACE
• Sorafenib dosing
• median = 386mg
• 73% dose reductions
• 91% dose interruptions
Kudo M, et al. Eur J Cancer 2011;37:212-20.
Japan – Korea Study
TTP
OS
Kudo M, et al. Eur J Cancer 2011;37:212-20.
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Japan – Korea Study
Kudo M, et al. Eur J Cancer 2011;37:212-20.
Median sorafenib
16 vs 31 wks
When to Abandon TACE?
Expert Recommendations
Adapted from Raoul JL, et al. Cancer Treat Rev 2011;37:212-20.
OPTIMIS
Study
SHARP Subgroup Analysis
p=NS
Bruix J, et al. J Hepatol 2012;57:821-829.
p=NS
BCLC Stage B Prior TACE
Sorafenibor
RCTs evaluatingSorafenib± TARESorafenib± SBRT
Conclusions
• TACE provides survival advantage for carefully selected patients (Level 1a)
• DEBs are a more standardized technique and are better tolerated (Level 1b)
– DEBs may offer a survival advantage (Level 2b)
• Bridging to LT may recurrence (Level 3b)
• Combination with sorafenib is not recommended (Level 1b)
• When to abandon TACE remains an area of controversy and requires further study
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Transarterial Chemoembolization
Kelly W. BurakMD, FRCPC, MSc (Epid)Associate Professor of MedicineUniversity of CalgaryDepartments of Medicine & Oncology
Director, Calgary Liver Unitand Southern Alberta Liver Transplant Clinic
Chair, IR Guidelines CommitteeAHS Provincial GI Tumour Group
@kwburak