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 1
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 Radiation Oncology Steven Feigenberg, MD William Regine, MD Pradip Amin, MD Young Kwok, MD Michael Chuong, MD Navesh Sharma, DO, PhD Svetalana Kudryasheva- SIRspheres coordinator Pathology
SIR-Spheres microspheres Biocompatible resin 32μm average diameter Yttrium 90 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 7
Theraspheres
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 10
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) A B Archer S, Gray BN. Br J Surg. 1989;76:545-548, LIV_MOA. 11
SIRT: Delivery Procedure Minimally invasive microcatheter therapy: Transfemoral access (A) to the hepatic artery (B) B A 12
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 Neovascular 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
90 Y Microsphere Prescription 90 Y 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 90 Y therapy- functional reserve Hyper vs. hypo vascular angiogram Focal-diffuse MAA scan
Activity modification scenarios T:N < 2 T:N > 4 90 Y GBq= BSA 25% 90 Y 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 90 Y is part of a comprehensive plan Treatment intent assess risk level LFT trends prior to 90 Y Mutli-disciplinary team working together pre- and post- 90 Y Follow up with all patients
Thank You!