Bridging and Downstaging to Surgery.
Logo

Bridging and Downstaging to Surgery

Cancer Therapies & Ablation / TheraSphere / Proven Results / Bridging and Downstaging to Surgery
 

Bridging and Downstaging to Surgery
HEPATOLOGY: Liver Transplantation Following Y-90 for HCC


15-year, 207 patient experience highlights TheraSphere™ as an effective treatment for Bridging or Downstaging

HCC to Liver Transplant therapy with a median overall survival* of 12.5 years

Liver Transplantation Following Yttrium-90 Radioembolization: 15-year Experience in 207-Patient Cohort - Ahmed Gabr, Laura Kulik, Samdeep Mouli, Ahsun Riaz, Rehan Ali, Kush Desai, RonaldA Mora, Daniel Ganger, Haripriya Maddur, Steven Flamm, Justin Boike, Christopher Moore, Bartley Thornburg, Ali Alasadi, Talia Baker, Daniel Borja-Cacho, Nitin Katariya, Daniela P Ladner, Juan Carlos Caicedo, Robert J Lewandowski, Riad Salem

Methods: A multidisciplinary team comprised of hepatology, oncology, transplant surgery, and interventional radiology retrospectively reviewed data from 207 patients with unresectable HCC who underwent liver transplant after being treated with Y-90 as part of a bridging or downstaging care pathway.

Results: Of the 207 patients included in these analyses, 38 (19%) patients were downstaged to within Milan transplant criteria and 169 (82%) bridged to transplant with TheraSphere either using lobar (18%, median dose of 124 Gy [IQR: 132-146]) or radiation segmentectomy (82%, median dose 260Gy [IQR: 235-350]) administration.

 

169 Patients were Bridged and 38 Patients were Downstaged to T2 for Liver Transplant


Median Time to LT was 7.5 Months

Median Overall Survival after Liver Transplant was 12.5 years


Survival Probability Post Transplant chart.
 

HEPATOLOGY: Liver Transplantation Following Y-90


Results & Conclusions

Three, five and ten-year Overall Survival (OS) rates were 84%, 77%, and 60% respectively. 94 (45%), 60 (29%) and 53 (26%) of patients showed complete (no viable tumor), extensive (50-99% necrosis) and partial tumor necrosis (<50% necrosis) on histopathology of which 2%, 7% and 34% had recurrence in each group, respectively. There was a trend towards better OS for patients achieving complete/extensive tumor necrosis (p=0.056). Median recurrence free survival (RFS) post transplant was 120 Months (95%CI: 69-150). There was no differences in OS or RFS for bridged versus downstaged patients.


Based on this analysis, locoregional therapy with TheraSphere Y-90 Glass Microspheres should be considered a standard treatment option for neoadjuvant bridging or downstaging to liver transplantation.

 

74% of Patients Showed Complete or Extensive Tumor Necrosis on Histopathology with an average 10 Year Recurrence-Free Survival following Liver Transplant


Histopathology and Recurrence Rate Post TheraSphere chart.

Survival and Recurrence Outcomes (N=207)

  Median 3-year 5-year 10-year
Overall Survival from Y-90 157 mo. (13.1 years) [CI: 120-157] 87% 80% 62%
Overall Survival from LT 150 mo. (12.5 years) [CI: 120-150] 84% 71% 60%
Recurrence-Free Survival from LT 120 mo. (10.0 years) [CI: 69-150] 77% 65% 43%
Disease-Specific Mortality Rate Not Reached 6% 11% 16%
Time-to-Recurrence
(Recurrence-Free Probability)
Not Reached 88% 79% 76%
Overall Survival <65 years NR at 150 mo. 88% 85% 71%
Overall Survival >65 years P=0.003 12.5 years 73% 58% 43%
Abbreviations
HCC: hepatocellular carcinoma
LT: Liver transplantation
Y90: Yttrium-90 radioembolization
MELD: Model of endstage liver disease
BCLC: Barcelona Clinic Liver Cancer
cTACE: conventional chemoembolization
LRT: locoregional therapy
OS: Overall survival
RFS: Recurrence-free survival
TTP: time-to-progression
TTR: Time-to-recurrence
DSM: Disease-specific-mortality
MRI: gadolinium-enhanced magnetic resonance imaging
CT: triphasic contrast-enhanced computerized tomography
CP: Child-Pugh
IQR: Interquartile range
KM: Kaplan-Meier analysis
CI: 95% Confidence Interval
ECOG: Eastern Cooperative Oncology Group
UNOS: United Network for Organ Sharing
AFP: Alpha fetoprotein
ETOH: Alcoholic cirrhosis
NASH: Non-alcoholic steatohepatitis
PBC: Primary biliary cirrhosis
PSC: Primary sclerosing cholangitis
HCV: Hepatitis C virus infection
HBV: Hepatitis B virus Infection

Baseline Characteristics at Y-90

Median [IQR] N (%)
Age (years) 60 [56-65]

ECOG 0 145 (70%)
  1 61 (29.5%)
  2 1 (0.5%)
Child-Pugh   A 99 (48%)
  B 91 (44%)
  C 17 (8%)
BCLC A 106 (51%)
  B 20 (10%)
  C 64 (31%)
  D 17 (8%)
UNOS TNM T1 9 (4%)
  T2 160 (77%)
  T3 22 (11%)
  T4a 12 (6%)
  T4b 4 (2%)
AFP (ng/dL) <13 (normal) 114 (55%)
  13-100 48 (23%)
  >100 45 (22%)
  Range 0.8-15735
Prior Liver therapy Surgical Resection 8 (3.5%)
  Prior HCC LRT 35 (17%)
  Treatment Naive 164 (79.5%)
Listing Prior to Y-90 117 (57%)
  After Y-90 90 (43%)
Y-90 Administration Lobar 37 (18%)
  Segmental 170 (82%)
Y-90 Dose (Gy) Lobar 124 [132-146]
  Segmental 260 [235-350]

Baseline Characteristics at Liver Transplant

Median [IQR] N (%)
Age (years) 62 [57-66]
MELD-Na Score 13 [10-17]
Wait-list time (months) 7 [4-10]
Time from Y-90 (months) 7.5 [4.4-10.3]

Etiology of HC Autoimmune hepatitis 3 (1.5%)
  Alpha 1 antitrypsin 1 (0.5%)
  Biliary Atresia 1 (0.5%)
  Cryptogenic 13 (6%)
  ETOH 30 (14%)
  HCV + ETOH 11 (5%)
  HV  102 (49%)
  HBV 22 (10%)
  NASH 13 (6%)
  PBC 7 (3%)
  Wilson’s 1 (0.5%)
  PSC  1 (0.5%)
  Hemochromatosis 2 (1%)
AFP (ng/dL) <13 (normal) 132 (64%)
  13-100 62 (30%)
  >100 13 (6%)
  Range 0.8-13774
Liver Parenchyma Cirrhosis 202 (97.5%)
  Bridging Fibrosis 5 (2.5%)
Tumor Grade Grade 1 37 (18%)
  Grade 2 69 (33%)
  Grade 3 6 (3%)
  Fibromellar 1 (0.5%)
  Mixed HCC - cholangiocarcinoma 4 (2%)
  Unable to identify due to extensive necrosis 90 (43.5%)
Tumor Necrosis Complete (100%) 94 (45%)
  Extensive (51-99%) 60 (29%)
  Partial (<50%) 53 (26%)
 

 

PI-823306-AA 

Top