1. Medical College of Wisconsin, Milwaukee, WI
A Systematic Review and Meta-Analysis of Hepatic Artery Based Therapy for Intrahepatic Cholangiocarcinoma
Boehm L PharmD, Jayakrishnan T MD, Muira J MD, Johnston F MD MHS, Turaga KK MD MPH, Gamblin TC MD MS
Medical College of Wisconsin, Milwaukee, WI

2. Author Disclosure T Clark Gamblin, MD MS
Consultant, Angiodynamics and Covidien
Kiran K Turaga, MD
Honorarium, Castle Biosciences Inc
Other Authors
No relevant financial or other relevant disclosures

3. Background
Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary tumor of the liver arising from biliary epithelium with typical survival times ranging from 5-13 months with standard systemic chemotherapies.
Hepatic artery based therapies (HAT) have been shown to prolong survival in unresectable hepatic malignancies.
HAT includes hepatic artery infusion (HAI), transcatheter arterial chemoembolization (TACE), drug-eluding bead TACE (DEB-TACE), and Yttrium90 radioembolization (Y90).
Figure 1.
Cross sectional CT image of a patient with ICC demonstrating lesion between right and left lobes of the liver
Figure 1.
Cross sectional CT image of a patient with ICC demonstrating lesion between right and left lobes of the liver

4. Purpose and Methods Purpose Methods: Outcomes:
The objective was to perform a qualitative and semi-quantitative systematic review and meta-analysis of hepatic artery directed therapies for patients with unresectable ICC.
Methods:
The study was prospectively registered at PROSPERO
Outcomes:
Primary Outcome: Cumulative Median Overall Survival (OS) in months
Secondary Outcomes: Tumor response to therapy (RECIST criteria) and toxicities

5. Results Records identified through database searching (n = 790)
Screening
Included
Eligibility
Identification
Additional records identified through other sources (n = 3)
Records after filters applied (n = 385)
Records screened (n = 385)
Records excluded on the basis of title and abstract screening
(n = 343)
Full-text articles assessed for eligibility (n = 42)
Full-text articles excluded, with reasons (n = 22)
-Concomitant systemic chemotherapy
-Concomitant radiotherapy
-Results not stratified by cancer type
-Patients had resectable disease
-Outcomes of interest not reported
Studies included in qualitative synthesis (n = 20)
Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews
and Meta-Analyses: The PRISMA Statement. PLoS Med 6(6): e doi: /journal.pmed

6. Baseline Characteristics
The mean age of subjects across all four HAT treatment arms was 62.5 years (SD ± 4.65).
Of the patients evaluated 54.6% had an ECOG performance status of 0.
The median KPI of patients in the DEB-TACE treatment arm was 100 (70-100).
HAI
TACE
DEB-TACE
Y-90
Number of Articles 4 10 2 5
Number of Patients (n)
n=64
n=399
n=37
n=127
Mean Age (Years)
58.5 (±3.34)
61.8 (±5.07)
67.5 (±1.06)
63.7(±4.06)
Performance Status
ECOG 1 3
n=25
19 (76%)
5 (20%)
1 (4%)
n=200
116 (58%)
71 (35.5%)
12 (6%)
1 (0.5%) NR
n=101
43 (42.6%)
40 (39.6%)
18 (17.8%)
KPI
Median (range)
n=28
80 (40-90)
n=10
100 (70-100)
n=26
Extrahepatic Disease (%)
21.9%
29.2%
42%
37%

7. Results Cumulative median OS was highest for HAI (21 months, 11-31).
Tumor response per RECIST was highest for HAI with 87.3% of patients exhibiting either a partial response or stable disease.
Y-90 therapy had a similar tumor response profile (85.1%)
HAI
TACE
DEB-TACE
Y-90
Cumulative Median OS (Months) 21 13 12 14
RECIST Tumor Response
Complete Response
Partial Response
Stable Disease
Progressive Disease
n=63
26 (41.3%)
29 (46%)
8 (12.7%)
n=333
1 (0.3%)
41 (12.3%)
206 (61.9%)
85 (25.5%)
n=34
1 (2.9%)
10 (29.4%)
16 (47%)
7 (20.6%)
n=121
32 (26.4%)
71 (58.7%)
18 (14.9%)

8. Results
Grade I/II complication rates were highest among those treated with HAI therapy (2.84 per patient)
Grade III/IV complication rates were low across all treatment groups in general.
Highest for HAI (0.35 per patient)
Lowest for TACE (0.26 per patient)
Rates of hepatic complications were highest among those treated with HAI therapy
Complication Rates per Patient Treated

9. Conclusion
Hepatic artery infusion reported the best outcomes in terms of:
Median overall survival
Overall response to therapy
TACE was associated with lowest incidence of complications

10. THANK YOU
I would like to thank you for your patience and I am open to any questions