1. Northwestern Memorial Hospital
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 1

2. Consultant, Advisory Boards, Research Support
Disclosures
Consultant, Advisory Boards, Research Support
MDS Nordion, Sirtex Medical 2

3. Y90 Radioisotope 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 3

4. 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
Imaging criteria
Pathologic analyses  comparison with TACE
Biomarkers
Long term Survival
Combination with Systemic Agents
Capecitabine
Sorafenib 4

5. 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

6. RECIST (Uni-dimensional) Guideline
System
Classification
Definition
Response Evaluation Criteria in Solid Tumors (RECIST) 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 6

7. 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

8. Baseline Demographics
Age (years)
< 65
138 (47)
≥ 65
153 (53)
≥ 75
63 (22)
Gender
Male
223 (77)
Female
68 (23)
Ethnicity
Caucasian
208 (71)
African American
37 (13)
Asian
29 (10)
Hispanic
17 (6)

9. 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
HCV + HBV
3 (1)
PBC
1 (0.6)
Unknown
14 (5)

10. Imaging Characteristics
Distribution
Solitary
78 (27)
Multifocal
213 (73)
Tumor location
Bilobar
139 (48)
Unilobar
152 (52)
Morphology
Uninodular & <50%
73 (25)
Multinodular & <50%
180 (62)
Massive or >50%
38 (13)
Tumor Burden
0-25%
223 (76.6)
26-50%
48 (16)
51-75%
19 (7)
76-100%
1 (0.4)

11. Imaging Characteristics
PVT
None
166 (57)
Branch
58 (20)
Main
67 (23)
Metastases
245 (84) LN
29 (10)
Other
17 (6)

12. Tumor Size N Mean (Range) Size Overall 291 7 (1.2-22) < 5 cm
116 (40)
3.4
( )
5-10 cm
123 (42)
7.1
(5-10)
> 10 cm
52 (18)
14.9
( )

13. Baseline Stage N (%) Child Pugh A 131 (45) B 152 (52) C 8 (3) BCLC
3 (1) A2
22 (8) A3
8 (2) A4
6 (2)
66 (23)
178 (61) D

14. Treatment Characteristics
Location
Number of Treatments (N)
Median dose (Gy)
Mean dose (Gy) [Range]
Liver
526
103
112
( )
Lung (per treatment)
5.4
8.8
( )
Lung (cumulative)
291
9.3
15.7
( )

15. Clinical Toxicities Adverse Event No. of Patients % Fatigue 167 57
Abdominal Pain 67 23
Nausea/Vomiting 20
Anorexia 45 15
Fever/Chills 10 3
Diarrhea 7 2
Weight Loss 4 1

16. Overall Survival Median
Liver-only disease
Child’s Class
PVT
UNOS N
EASL PR
N (%)
WHO PR
TTP
Median
(95% CI)
Overall Survival Median A
Overall CP A
116 (113)
78 (69)
59 (52)
10.8 (7.4-14)
17.2 ( )
PVT Absent
Overall
81 (79)
61 (77)
42 (53)
15.5 ( )
22.1 ( )
T1/T2
27 (25)
22 (88)
13 (52)
27.1 (8, -)
20.5 ( ) T3
27 (27)
24 (89)
17 (63)
21.9 ( )
35.7 ( )
T4a
15 (56)
12 (44)
8.6 (6, -)
14.9 ( )
PVT Present
T4b
35 (34)
17 (50)
5.6 ( )
10.4 ( ) B
Overall CP B
122 (114)
44 (39)
8.4 ( )
7.7 ( )
65 (64)
43 (67)
30 (47)
13.0 ( )
14.8 ( )
22 (22)
15 (68)
8 (36)
13.0 (6.3-25)
29.1 (17.1, -)
21 (21)
18 (86)
12 (57)
17.4 ( )
38.3 ( )
22 (21)
10 (48)
8.8 ( )
11.8 (6.2-19)
57 (50)
16 (32)
14 (28)
5.9 ( )
5.6 ( )

17. 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

18. AFP 8.0
AFP 800 18

19. 6 months post treatment AFP  4.5
Pre treatment AFP  2200
6 months post treatment AFP  4.5 19

20. After 2 treatments 20

21. Pre treatment
22 months 21

22. Pre Tx: AFP 1368 36 months post Tx: AFP 9.522

23. Northwestern 5-yr Experience 291-Patient Cohort
Continues to be evolving role of Y90 in HCC
Cohort data permits
Exploratory subgroup analyses
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)

24. 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 24