1/13/2014 6 british journal of cancer (2010) 103, 324 –331 british journal of cancer (2010) 103,...
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Ries et al (eds). At: http://seer.cancer.gov/csr/1975_2002
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Coldwell et al, General Selection Criteria of Patients for Radioembolization of Liver Tumors AJCO 2010
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Am J Clin Oncol. 2010 Oct 8
Am J Clin Oncol. 2010 Oct 8
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Am J Clin Oncol. 2010 Oct 8
Am J Clin Oncol. 2010 Oct 8
Am J Clin Oncol. 2010 Oct 8
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British Journal of Cancer (2010) 103, 324 – 331
British Journal of Cancer (2010) 103, 324 – 331
Am J Clin Oncol. 2010 Oct 8
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Eur J Radiol. 2010 Apr;74(1):199-205.
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Answer:
Survival Advantage and Quality of
Life!
Fatigue (100%) Anorexia (75%) Fever (50%)
Gastritis (25%) Liver Dysfunction (Minimal) Pain (Rare)
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Challenges of Sirspheres and Dealing with Complications
Charles Nutting, DO, FSIR SkyRidge Medical Center
Lone Tree, CO
VuMedi Y90 Webinar 2014
Disclosures
• Proctor- Sirtex Medical
• Consultant- Surefire Medical
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Challenges of Sirspheres
• Setting up the infrastructure of a radioembolization program – Multidisciplinary team
– FDA approved
– AU status
• Single dose 3 Gbq
– vial allows flexibility • Lobar, segmental, split dose (single session whole liver)
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Complications
• Early (within 30 days) – Inadvertent deposition of radioactive
microspheres
• Late – Toxicity related
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Complications
PRS- 20-50%
Gastrointestinal ulcer -5%
Cholecystitis – 1%
Hepatic Infection-rare
RILD-rare
General selection criteria of patients for radioembolization of liver tumors
International Working Group
Coldwell et al. AJCO 2010
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Minimize side effects medications
• Preprocedure – decadron, ondansetron, hydration
– 100 ug octreotide subQ or IV for NE disease
• Post procedure
– medrol dose pack
– proton pump inhibitor
– narcotic, antiemetic
Potential Complications
• Cystic artery – Cholecystitis, GB rupture
• Violated ampulla – hepatic absecess
• Chemotherapeutic/Biologic agents – Toxicity/decreased dose to tumor
• REILD – hepatic failure
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Cystic Artery- Embolize or Not
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Cystic Artery
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Cystic Artery
Prophylactic embolization of the cystic artery before radioembolization: feasibility, safety,
and outcomes
• 46 pts proximal cystic artery embolization
– 35 gelfoam pledgets
– 11 coils
• 100% technical success
• 2/46 developed significant RUQ pain
• 1/46 required cholecystectomy
12 McWilliams et al. Cardiovasc Intervent Radiol. 2011 Aug;34(4):786-92
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Risk of Hepatic Abscess from Radioembolization
• Traditionally patients with biliary-enteric anastamoses have been excluded from hepatic embolization procedures due to the high risk of cholangitis and abscess
• Documented complication rates due to infection range from 12-50% with CE
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Violated Ampulla
Results
• Retrospective multi-institutional review
• 27 patients underwent 35 infusions
• Follow ups is between 3 weeks – 60 months
• The mean number of radioembolization
treatments was 1.5 (range 1-2)
– The median length of outpatient stay was 2.5
(2-4) hours
GEST 2008
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Complications
• No 30 day mortality
• 3 infusions of 16 developed transient low grade fever and chills
• 2 patients developed hepatic abscesses requiring drainge (7.4%)
• 1 patient died of sepsis 6 weeks after radioembolization treatment (3.7%)
GEST 2008
Violated Ampulla
• Relative Contraindication
• Whipple, ampullotomy, metallic or plastic stent
• We medicated with levaquin and metronidazole – 500mg iv levaquin, 500 iv flagyl day of procedure
• Followed by 500 levaquin po QD x 5 days.
500 mg flagyl 500 po TID x 5 days.
Minimize Catheter Related Complications
• Non-target delivery
• Reflux
• Adverse events
• Limit dose
• Pre-treatment coils
• Distal treatment
• Anti-reflux catheter
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Lopez-Benitez, R., et al., Analysis of nontarget embolization mechanisms during embolization and chemoembolizat ion
procedures. Cardiovasc Inter vent Radiol, 2009. 32(4): p. 615-22.
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Lobar vs Whole Liver
• Whole Liver Infusions* – 53%
• Lobar infusions – 40%
• Segmental infusions – 7%
19 *Per individual based on performance status, LFT’s and prior chemotherapy
• Technique
Split Dose Single Session Whole Liver
• Allows more distal delivery of radioembolic – Stays away from extrahepatic hilar arteries that
most commonly arise from the proper hepatic and proximal left hepatic branches
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Typical Whole Liver Single Session Resin Infusion
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Typical Whole Liver Single Session Resin Infusion
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REILD
• RadioEmbolization Induced Liver Disease
– Hepatic sinusoidal obstruction syndrome (VOD) that presents clinically as jaundice and ascites in the absence of tumor progression
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Liver Tolerance - Radiation
25 Gy 35 Gy 70-90 Gy
Effective Doses:
Testicular Ca,
Lymphoma,
Myeloma
Curative Doses:
Adenocarcinoma
RILD – Radiation induced Liver Disease
Preoperative Radiation –
Rectal Ca
50 Gy
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REILD
Pre Treatment 3 months Post Treatment
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REILD – Clinical Picture
– jaundice and ascites
– 4 to 8 weeks after RE
– Increases in alk phos
– minimal change in transaminases
– Hyperammonemia
Sangro, B Liver disease induced by Radioembolization of liver tumors Cancer 2008
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REILD – Histology
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REILD
• Veno-occlusive disease is histologic hallmark
• 9 patients (20%) developed REILD
• Potential Causes – Low tumor burden
– Whole liver treaments
– polychemotherapy
Sangro, B Liver disease induced by Radioembolization of liver tumors Cancer 2008
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Treatment for REILD
• Steroids
• Diuretics
• Lactulose
• TIPS
Concurrent Chemotherapy-Challenges
• FOLFOX
– Decrease oxaliplatin
• FOLFIRI
– No need to dose reduce
• Gemcitabine
– Hold one week prior and 2 weeks post Y-90 infusion
• Bevacizumab
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Bevacizumab
• Angiogenesis inhibitor via VEGF pathway
• May be unable to deliver spheres through attenuated vessels
• Half life 20 days
Challenge-Response to Therapy
• PET imaging – 91%
• Tumor markers -70%
• CT imaging – 35%
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CEA After 90Y-Microspheres
0 2 4 6 8 10 12 14 16 180
102030405060708090
100110120
Weeks After Treatment
Per
cen
t C
ha
ng
e
Kennedy et al. Resin Y90 microsphere therapy for unresectable
colorectal liver metastasis: Modern USA Experience Int J Rad
Onc Physics June 2006
Limit Complications-Know When Not to Treat
• Poor hepatic reserve – Worsening ascites
– Increasing bilirubin levels which are uncorrectable
• Poor performance status
• Significant extrahepatic disease not responding to therapy
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Summary-Challenges and Minimizing Complications
• Multidisciplinary team, become an AU
• Resin microspheres allow customization of the dose to be delivered, the day of procedure
• Don’t be too concerned about the cystic artery
• Safer to treat an instrumented biliary tree with RE than CE
• Be aware of chemotherapy regimen and keep pt off bevacizumab 4 weeks prior
• REILD is rare but potentially fatal 34
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! Aaron Shiloh, MD
Section Chief, IR
Diagnostic Imaging, Inc.
Philadelphia
Therasphere®
Therasphere®
Disclosures:
Consultant for BTG
84 year old female with chronic autoimmune hepatitis
LFTs elevation lead to CT
PMH: Atrial Fibrillation, Hypertension, hypothyroidism
ECOG 0, CP A
T. Bili 0.8, cr 0.8, AFP 3320
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BEFORE 6 months later
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Therasphere®
Introduction – Epidemiology of HCC
Indications
Mechanism of action
Patient selection
Contraindications
Starting a program
Therasphere®
HCC one of most common forms of cancer worldwide (est. 1
million new cases annually)
In US, NCI estimate 19,160 new cases and 16,780 deaths in 20071
Incidence increasing with rise in hepatitis C-induced cirrhosis
5-10% of HCC patients are resectable2 1 National Cancer Institute www.cancer.gov (accessed December 1, 2008)
2 Llovet, JM. Current Treatment Options for Gastroenterology. 2004;7:431-441
HCC Epidemiology
Limited Treatment Options for HCC
Therapeutic Options:
Resection or transplantation
Unresectable HCC treatment options: Radiofrequency ablation
Transarterial chemoembolization (TACE or Drug Eluting Beads)
Transarterial TheraSphere, Y90 Glass Microspheres
External Beam radiation
Systemic therapy (ie. Sorafenib)
No treatment
Therasphere®
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Therasphere® Indications
In the United States, TheraSphere1 is indicated for:
Radiation treatment or as a neoadjuvant to surgery or
transplantation in patients with unresectable HCC who can have placement of appropriately positioned hepatic arterial catheters
HCC patients with partial or branch portal vein thrombosis/occlusion, when clinical evaluation warrants
the treatment
Approved for use in EU, Canada, Russia, India, Saudi Arabia & S. Africa
1TheraSphere US Package Insert
Therasphere®
TheraSphere designated as Humanitarian Use
Device (HUD)
Legally marketed under Humanitarian Device Exemption (HDE)
Demonstrated safety and probable clinical benefit
HDE Requirements:
IRB oversight/approval required
Use within approved labelling does not constitute research or investigational use
What is Therasphere®
20-30 mm glass microspheres
Y-90 is an integral constituent of the glass matrix
Innovative treatment to deliver powerful, targeted radiation inside the liver
Y-90 glass microspheres comparison to human hair TheraSphere dose vial
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Administered via hepatic artery catheter
Targeted internal radiation due to tumor hypervascularity
Microspheres are trapped in the tumor arterioles and are minimally-
embolic (microembolization)
Pure beta-emitter
Average beta emission energy is
0.9367 MeV
Average penetration range in tissue
is 2.5 mm
Physical half-life is 64.2 hours and
decays to stable zirconium-90
Mechanism of Action
Therasphere®
Therasphere®
Low toxicities: well tolerated
Outpatient procedure
Minimal PES syndrome (TACE vs. TheraSphere)
Promising survival data
Bridge to transplant, downstaging
Neoadjuvant to surgery
Use in Portal Vein Thrombosis
Post-TheraSphere patients eligible for further therapeutic options due to preserved liver vascularity
Targeted Therapy:
Sparing Healthy Tissue Benefits Overview:
Patient Selection
The ideal candidate for
TheraSphere presents with:
Non-infiltrative tumor type
Elevated AFP
Child-Pugh A
Bilirubin < 2 mg/dL
AST/ALT < 5 x ULN
Tumor volume < 50% and Albumin > 3
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Contraindications
Standard contraindications to angiography
Inability to safely deploy the Therasphere® due to anatomic variants
Extremely high lung shunt fraction
Hepatic mapping
Lung Shunt study
and LSF calculation
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Liver volume assessment
Dose calculation
Administer
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Getting Started! Figure 1. TheraSphere Program Overview Flowchart
TheraSphere Introductory Presentation
Reference Manual Provided
Site Enrollment Requirements
BTG
Customer Service
IRB Submission
Customer Information
Form
Shipment of TheraSphere
Administration System
IRB Approval Letter RAML License
Center of Excellence Training –
TheraSphere University (TSU)
Patient Selection
Subsequent TheraSphere Patient Treatments
Estimated
Timeline
Week 0
Week 2
Week 8 - 10
Week 10
Week 16 TheraSphere Patient Treatment
Radioactive Materials License (RAML)
Application/Amendment
Dose Ordering
Proctoring of first 3
TheraSphere Patients
Week 12-14
TheraSphere
Introduction by BTG
Information from
Hospital (assisted
by BTG)
Information/supplies
required prior to 1st
treatment
TheraSphere Training
and 1st Three (3)
Treatments
(coordinated with
BTG)
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Vanderbilt-Ingram Cancer Center
Challenges with
Glass Microspheres
Daniel B. Brown, MD FSIR
Professor of Radiology and Radiologic Sciences
Director, Division of Interventional Oncology
Vanderbilt-Ingram Cancer Center
Vanderbilt University
Vanderbilt-Ingram Cancer Center
Topics of Interest
• Ulcer
• Lung Shunt Fraction
• Non-target via the Umbilical Artery
• 2nd Week Dosing
Vanderbilt-Ingram Cancer Center
Non-Target Therapy
• Best advice is AVOIDANCE
• ALWAYS select the lobar/segmental
artery(ies) at the level you will be infusing
– Power inject and do delayed runs to look for
anything suspicious
– Know where the RGA and GDA are
– If not sure if a problem, embolize
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Vanderbilt-Ingram Cancer Center
Why the obsession?
Vanderbilt-Ingram Cancer Center
Problem
Vanderbilt-Ingram Cancer Center
Who Gets Embolized?
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Vanderbilt-Ingram Cancer Center
Lung Shunt Fraction
Vanderbilt-Ingram Cancer Center
Vanderbilt-Ingram Cancer Center
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Vanderbilt-Ingram Cancer Center
Vanderbilt-Ingram Cancer Center
Vanderbilt-Ingram Cancer Center
Umbilical Artery
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Vanderbilt-Ingram Cancer Center
Vanderbilt-Ingram Cancer Center
Vanderbilt-Ingram Cancer Center
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Vanderbilt-Ingram Cancer Center
Vanderbilt-Ingram Cancer Center
Vanderbilt-Ingram Cancer Center
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