SIRT Dosimetry: Sometimes Less Is More

Navesh K. Sharma, DO, PhD Assistant Professor, Departments of Radiation Oncology, Diagnostic Radiology and

Nuclear Medicine Medical Director, Radiation Oncology, Kaufman Cancer Center

University of Maryland Medical Center Baltimore, MD

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Disclosures

Sirtex Medical- Speaking Engagements

Bristol-Myers Squibb- Speaking Engagement

UMMS Liver Directed Therapy Team

Surgery Surgical Oncology Transplant

Medical Oncology

Radiology

Interventional Radiology Fred Moeslein, MD, PhD Jason Mitchell, MD Brian Swehla, MD Nabeel Akhtar, MD Nuclear Medicine

Pathology

Radiation Oncology

Steven Feigenberg, MD

William Regine, MD

Pradip Amin, MD

Young Kwok, MD

Michael Chuong, MD

Navesh Sharma, DO, PhD

Svetalana Kudryasheva- SIR-

spheres coordinator

SIR-Spheres® microspheres

Biocompatible resin

32μm average diameter

Yttrium90 permanently bound

Mean pure beta emission @ 0.93MeV

Half life 64.1 hours

Penetration – 2.5mm mean

– 11mm max

Scanning electron

micrograph

SIR-Spheres® is a registered trademark of Sirtex SIR-Spheres Pty Ltd.

Data on file, Sirtex Medical Limited

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Theraspheres

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Concept of SIRT (Selective Internal Radiation Therapy) Radioembolization “Brachytherapy”

Treatment Goals:

Selectively deliver a

tumoricidal dose of beta radiation

to the liver tumor while

maintaining a low

radiation dose to the

normal liver tissue

SIRT: Microsphere Delivery Concept

SIRT takes advantage of the hepatic dual blood supply

Normal liver parenchyma:

Majority of blood supply from portal vein (A)

Metastatic liver tumors:

Majority of blood supply from hepatic artery (B)

Archer S, Gray BN. Br J Surg. 1989;76:545-548, LIV_MOA. 11

A

B

SIRT: Delivery Procedure

Minimally invasive microcatheter therapy:

Transfemoral access (A) to the hepatic artery (B)

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A

B

Explanted liver from patient treated with SIR-Spheres. Liver donated following transplantation for HCC…

Source: Andrew S Kennedy, M.D., Wake Radiology Oncology, Cary NC

Entrapment of SIR-Spheres in Neo-vascular Bed

Scanner for H and E slides

3D position of all SIR-Spheres in 2x2x2cm block of tissue were mapped…

Source: Andrew S Kennedy, M.D., Wake Radiology Oncology, Cary NC

3D position of all SIR-Spheres in 2x2x2cm block of

tissue were mapped (cont.)

100 Gy Dose Volume 1000 Gy Dose Volume

Source: Andrew S Kennedy, M.D., Wake Radiology Oncology, Cary NC

Distribution of Y-90 resin microspheres

DISTRIBUTION OPTIMIZES CROSS-FIRE (collateral) EFFECT

90Y Microsphere Prescription

90Y Sphere Activity Prescribed in GBq

Individualized (whole vs. lobar vs. segment)

Eg 1.5 GBq to Right Lobe

Estimate absorbed energy- Dose (Gy)

Normal Liver

Lung

Tumor (target)

SI Definitions:

Dose (Gray, Gy)

Absorbed energy (Gy): 100 cGy = 100 rad = 1 Gy

1 Joule of energy absorbed/1 Kg of tissue

Activity (Becquerel, Bq)

Strength of X-ray source = Bq

Atoms decay per second (1 Bq = 2.7 X 10-11 Ci)

1903 Nobel Prize shared by Curies and Becquerel

Activity Calculation

1. Empiric (historical, not recommended)

Eg <25%, 50%, >50% tumor burden

2. Body Surface Area (BSA) - standard

3. Partition Model – Specific cases, HCC

BSA Method

Activity (90Y) GBq

= (BSA-0.2) + Vol tumor___

Vol tumor + Vol liver

Partition Method

Activity (Gy)

Dose liver ((T:N x Mass tumor ) + (Mass liver )

= ---------------------------------------------------------------

49670 (1-L/100)

Must partition 3 volumes:

1. Normal liver

2. Tumor

3. Lung

Dose (Gy) to each partition estimated based on MIRD

Maximum dose to tumor within normal liver/lung tolerance

But we need to be VERY careful

Liver disease induced by radioembolization of liver tumors

Cancer

Volume 112, Issue 7, pages 1538-1546, 7 FEB 2008 DOI: 10.1002/cncr.23339

http://onlinelibrary.wiley.com/doi/10.1002/cncr.23339/full#fig1

Hepatic Radiation Tolerance

External Beam RT

30 Gy whole liver

70 Gy partial liver

Dose-volume factors

Sinusoidal congestion

Similar to VOD

Radiation Induced Liver Disease (RILD)

Lawrence et al, 1994

Radioembolization (RE)

50 Gy whole liver, compromised (cirrhosis, chemotherapy, hepatitis etc)

70 Gy whole liver uncompromised

Radioembolization Induced Liver Disease (REILD)

Sangro et al, 2008

Sangro et al

REILD Risk Factors

Multi-Center retrospective review (US + EU)

515 patients, 680 procedures (mets + HCC)

REILD crude incidence: 4% (0.8% actual)

Significant Factors (p <0.0001)

Empiric Method (high activity)

Activity delivered

Prior chemotherapy

Prior partial hepatectomy

Kennedy et al, IJROBP, 2009

RILD vs REILD

Feature RILD REILD

Total Bilirubin Anicteric Elevated > 3 mg/dL

Ascites Present Present

Rapid Weight Gain Present Present

Presentation 2-16 weeks 4-8 weeks

AST and ALT Normal Normal

Alk phos Elevated Possibly elevated

Prior Chemo None Present

Mortality 10-20% < 10%

Reference Lawrence, IJROBP, 1995 Sangro, Cancer, 2008

Activity Calculation Algorithm

Activity Calculation Algorithm

Clinical Considerations

Prior chemotherapy- gemcitabine, oxaliplatin, irinotecan

Prior biologic agents – type, number, etc

LFT trends – 6 months

total bilirubin, albumin, Childs-Pugh score

Liver reserve after 90Y therapy- functional reserve

Hyper vs. hypo vascular angiogram

Focal-diffuse MAA scan

Activity modification scenarios

T:N < 2

90Y GBq= BSA – 25%

T:N > 4

90Y GBq= BSA

ALARA Principle

As Low as Reasonably Achievable!

Challenges

Challenges

Is number of particles administered important?

Role for stasis/true embolization

Differences between SIR-Spheres and Theraspheres

Differences in number of particles delivered within each product (activity dependent)

Conclusions

Safety first – 90Y is part of a comprehensive plan

Treatment intent – assess risk level

LFT trends prior to 90Y

Mutli-disciplinary team working together pre- and post- 90Y

Follow up with all patients

Thank You!