Yttrium-90 Radioembolization for Hepatocellular Carcinoma:
Comprehensive Analysis of Long-term Outcomes in 291 Patients
Robert J. Lewandowski, Ahsun Riaz, Robert K. Ryu, Ramona
Gupta, Vanessa L. Gates, Kent T. Sato, Reed Omary,
Riad Salem
Northwestern Memorial Hospital
Chicago, IL
Disclosures
Consultant, Advisory Boards, Research Support
• MDS Nordion, Sirtex Medical
Y90 Radioisotope
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100% pure beta emitter, 0.9367 MeV
Physical half-life of 64.2 h
Irradiates tissue with average range of 2.5 mm
Maximum penetration of approx. 1.0 cm
A constituent of an insoluble glass matrix
Microsphere diameter 25µ - 35µ
Methodical Approach to Y90:
10 year experience
•
Investigated each concept
– Safety
– Angiographic Technique
– Dosimetry
– Niche Applications
• Portal vein thrombosis
• Radiation Lobectomy
• Radiation Segmentectomy
– Lung dose, Distribution
– Liver Metastases
• CRC
• NET
• Cholangiocarcinoma
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Imaging criteria
Pathologic analyses  comparison with TACE
Biomarkers
Long term Survival
Combination with Systemic Agents
• Capecitabine
• Sorafenib
Northwestern 5-yr Experience
291-Patient Cohort
• December 2003  December 2008
– Open label protocol: Y90 glass microspheres
• All baseline CT/MR
– 1250 CT/MRI scans, total 4.3 scans per patient
– Strict imaging definition of metastases at baseline
– Comprehensive review at each stage in time for
development of metastases (CT chest, bone scans)
– Prospectively followed all patients
RECIST (Uni-dimensional) Guideline
System
Response
Evaluation Criteria in
Solid Tumors
(RECIST)
Classification
Definition
CR
100% decrease in maximum diameter of
target lesion
PR
≥30% decrease in maximum diameter of
target lesion
SD
<30% decrease to ≤20% increase in
maximum diameter of target lesion
PD
>20% increase from maximum response of
target lesion
Clinical Outcomes
• TTP: Progression defined as any of the
following: progression by WHO, EASL, UNOS
stage or appearance of new lesions
• Survival: from first treatment
• Univariate (Kaplan-Meier with Logrank) and
Multivariate (Cox Regression Model) were
used
Baseline Demographics
N (%)
Age (years)
Gender
Ethnicity
< 65
138 (47)
≥ 65
153 (53)
≥ 75
63 (22)
Male
223 (77)
Female
68 (23)
Caucasian
208 (71)
African American
37 (13)
Asian
29 (10)
Hispanic
17 (6)
Etiology
N (%)
Etiology
HCV
100 (34)
Alcohol
56 (19)
Cryptogenic
54 (19)
HBV
26 (9)
HCV + Alcohol
23 (8)
NASH
6 (2)
Autoimmune
4 (1.3)
Hemochromatosis
4 (1.3)
HCV + HBV
3 (1)
PBC
1 (0.6)
Unknown
14 (5)
Imaging Characteristics
N (%)
Distribution
Tumor location
Morphology
Tumor Burden
Solitary
78 (27)
Multifocal
213 (73)
Bilobar
139 (48)
Unilobar
152 (52)
Uninodular & <50%
73 (25)
Multinodular & <50%
180 (62)
Massive or >50%
38 (13)
0-25%
223 (76.6)
26-50%
48 (16)
51-75%
19 (7)
76-100%
1 (0.4)
Imaging Characteristics
N (%)
PVT
Metastases
None
166 (57)
Branch
58 (20)
Main
67 (23)
None
245 (84)
LN
29 (10)
Other
17 (6)
Tumor Size
N
Mean (Range)
Overall
291
7
(1.2-22)
< 5 cm
116 (40)
3.4
(1.2-4.9)
5-10 cm
123 (42)
7.1
(5-10)
> 10 cm
52 (18)
14.9
(10.1-22)
Size
Baseline Stage
N (%)
Child Pugh
A
131 (45)
B
152 (52)
C
8 (3)
A
(n=39)
BCLC
A1
3 (1)
A2
22 (8)
A3
8 (2)
A4
6 (2)
B
66 (23)
C
178 (61)
D
8 (3)
Treatment Characteristics
Location
Number of
Treatments
(N)
Median dose
(Gy)
Mean dose
(Gy) [Range]
Liver
526
103
112
(18-1693)
Lung (per
treatment)
526
5.4
8.8
(0.09-89.9)
Lung
(cumulative)
291
9.3
15.7
(0.09-110)
Clinical Toxicities
Adverse Event
No. of Patients
%
Fatigue
167
57
Abdominal Pain
67
23
Nausea/Vomiting
57
20
Anorexia
45
15
Fever/Chills
10
3
Diarrhea
7
2
Weight Loss
4
1
Liver-only disease
Child’s
Class
PVT
N
EASL
PR
N (%)
WHO PR
N (%)
TTP
Median
(95% CI)
Overall Survival
Median
(95% CI)
116 (113)
78 (69)
59 (52)
10.8 (7.4-14)
17.2 (14.9-24)
Overall
81 (79)
61 (77)
42 (53)
15.5 (10.7-25.9)
22.1 (17.2-32.5)
T1/T2
27 (25)
22 (88)
13 (52)
27.1 (8, -)
20.5 (14.9-27.4)
T3
27 (27)
24 (89)
17 (63)
21.9 (10.9-25.8)
35.7 (18.3-44.4)
T4a
27 (27)
15 (56)
12 (44)
8.6 (6, -)
14.9 (7.3-22.2)
T4b
35 (34)
17 (50)
17 (50)
5.6 (2.3-7.6)
10.4 (7.2-16.6)
122 (114)
59 (52)
44 (39)
8.4 (5.9-12.3)
7.7 (6.5-11.2)
Overall
65 (64)
43 (67)
30 (47)
13.0 (8.4-18.1)
14.8 (11.8-29.1)
T1/T2
22 (22)
15 (68)
8 (36)
13.0 (6.3-25)
29.1 (17.1, -)
T3
21 (21)
18 (86)
12 (57)
17.4 (8.4-33.9)
38.3 (6.9-41.7)
T4a
22 (21)
10 (48)
10 (48)
8.8 (3.6-18.1)
11.8 (6.2-19)
T4b
57 (50)
16 (32)
14 (28)
5.9 (4.2-7.9)
5.6 (4.5-6.7)
UNOS
Overall CP A
A
PVT Absent
PVT
Present
Overall CP B
B
PVT Absent
PVT
Present
Northwestern 5-yr Experience
291-Patient Cohort
• Significant findings:
– 273/291 (94%) of patients had FU imaging
– All as outpatients
– 58% downstaged T3 T2
– 32 transplanted
– No GI ulcers
AFP 8.0
AFP 800
Pre treatment
AFP  2200
6 months post
treatment
AFP  4.5
After 2 treatments
Pre treatment
22 months
Pre Tx: AFP 1368
36 months post
Tx: AFP 9.5
Northwestern 5-yr Experience
291-Patient Cohort
• Continues to be evolving role of Y90 in HCC
• Cohort data permits
– Exploratory subgroup analyses
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Who benefits
Who doesn’t
Where should research be focused?
Downstaged to potential cures (transplant/resection)
Treatment in portal vein thrombosis patients
• Next considerations
– Y90 vs chemoembolization
– Y90 +/- Sorafenib (various combinations)
Acknowledgements
Radiology:
Robert Lewandowski
Reed Omary
Bob Ryu
Kent Sato
Paul Nikolaidis
Frank Miller
MR Physicists:
Andrew Larson
Post-Doc Fellows:
Saad Ibrahim
Ahsun Riaz
Nurses:
Karen Marshall
Sharon Coffey
Krystina Salzig
Peggy Gilbertsen
Jennifer Karp
Elizabeth Gonda
Hepatology/Oncology:
Laura Kulik
Mary Mulcahy
William Small
Al Benson
Michael Abecassis
Daniel Ganger
Steve Flamm