USE OF YTTRIUM90 THERASPHERE FOR DOWNSTAGING PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA

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USE OF YTTRIUM-90 (THERASPHERE) FOR DOWNSTAGING
PATIENTS WITH UNRESECTABLE HEPATOCELLULAR
CARCINOMA

• Riad Salem, M.D. , Laura Kulik, M.D. , Mary
  Mulcahy, M.D. , Russell D. Hunter, Albert A.
  Nemcek Jr, M.D. and Michael M. Abecassis, M.D.
• Divisions of Interventional Radiology, Hepatology
  and TransplantationDepartments of Radiology,
  Medicine and Surgery
• Northwestern University Feinberg School of
  MedicineChicago, Illinois

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Background

• Liver transplantation for unresectable
  hepatocellular carcinoma (HCC) offers the best
  chance for cure.
• Patients not uncommonly present with advanced HCC
  or develop progressive disease while on the
  waiting list.
• Patients outside Milan criteria are not granted a
  MELD upgrade.
• Downstaging procedures have been employed as a
  bridge to transplant

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Yttrium-90 Microspheres

• Mean diameter of 25 microns
• Pure Beta emitter
• 64.1 hour ½ life
• Average and maximal tissue penetration of 2.5 mm
  and 10 mm
• Well tolerated
• Outpatient procedure
• No post embolization syndrome

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Yttrium-90 Microspheres

• Microspheres injected into the hepatic artery
  preferentially flow to tumor
• Higher doses of radiation to smaller volumes
  allows a greater tumoricidal effect
• Minimization of damage to the remaining non-tumor
  tissue

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Yttrium-90 Microspheres

• Phase 1 and 2 trials have demonstrated a positive
  safety profile
• Trends for increased survival have been shown in
  patients receiving higher radiation dose (gt 104
  Gy)
• 1 year survival rates are comparable to RCT of
  transarterial chemoembolization (TACE) versus
  supportive care

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AIM

• To determine the safety and the ability of
  TheraSpheres to radiographically downstaging
  patients with HCC outside the Milan Criteria

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Methods

• Inclusion Criteria
• Patients diagnosed with unresectable HCC by
  biopsy and/or EASL criteria
• ECOG performance status lt 2
• Transaminases lt 5x ULN
• Serum Bilirubin lt 3.0
• lt 30 Gy shunting to the lungs
• No detectable flow to the gastrointestinal organs

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Methods

• Patients were staged according to UNOS TMN
  classification
• Imaging was used to determine the volume of liver
  to be treated
• Pretreatment visceral angiography was performed
  to identify variant anatomy and the need for
  prophylactic coil embolization.
• Technetium-99 macroaggregated ablumin (MAA) scan
  was performed to determine pulmonary shunting
• Follow up imaging was performed 30 days after
  therapy and subsequently every 90 days

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Demographics

• Mean Age - 65 (50 - 74)
• All male
• All cirrhotic
• All had normal pretreatment AFP
• Mean MELD 10 (6 13)
• Etiology
• HBV 2
• HCV 1
• Alcohol 2

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Results
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Downstaging
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Post OLT
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Results

• Most common side effects were fatigue and
  transient flu-like symptoms
• No patient experienced grade 3-4 elevations in
  their liver function tests
• None of the patients developed post-embolization
  syndrome or radiation-induced liver disease
• One patient developed an infected groin requiring
  surgical repair

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Results

• Explants
• Patient 3 -
• 3.5x3.5x3 cm completely necrotic lesion
• Untreated nodules 3 x 3 x 2.5 and 1 cm
• No vascular invasion
• Patient 5 -
• 5.3 x 4.3 x 3 cm necrotic
• No vascular invasion

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Downstaging
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Downstaging
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Downstaging
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Summary

• 5 patients with unresectable HCC were
  radiographically downstaged
• 2 patients were successfully transplanted
• 2 additional patients were radiographically
  downstaged and not listed for transplant
• 1 patient developed metastatic disease 9 months
  after therapy

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Conclusions

• TheraSpheres may be a useful therapeutic adjunct
  not only to stabilize tumor growth, but also in
  downstaging patients with HCC.
• Larger studies are needed to evaluate
• Correlation of radiographic downstaging and
  explant pathology
• HCC recurrence rate after transplant
• Progression of disease after therapy