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


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British Journal of Cancer (2010) 103, 324 – 331

British Journal of Cancer (2010) 103, 324 – 331


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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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1

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®

http://www.cancer.gov/

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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 University


Topics of Interest

• Ulcer

• Lung Shunt Fraction

• Non-target via the Umbilical Artery

• 2nd Week Dosing


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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Why the obsession?


Problem


Who Gets Embolized?

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Lung Shunt Fraction



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Umbilical Artery

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1/13/2014 6 british journal of cancer (2010) 103, 324 –331 british journal of cancer (2010) 103,...

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