Y-90 Why Not?!? 1/5/2017. Disclosures Relating to Topic. By The End off This Talk You Should Be Able To:

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1 1/5/2017 Y-90 Why Not?!? GEEKING OUT ON GLASS AND REELING IN RESIN TECHNICAL CONSIDERATIONS David Liu MD FRCPC ABR(D) CAQ(IR) FSIR Clinical Associate Professor University Of British Columbia Faculty of Medicine Department of Radiology Interventional Radiology Section Vancouver General Hospital Vancouver British Columbia Canada Disclosures Relating to Topic Consultant: Sirtex Medical Investigator: BTG Medical (Therasphere STOP-HCC) Research Support: Sirtex Medical, BTG Medical, Siemens Medical Grant Recipient: Sirtex Medical, BTG Medical (Therasphere) Speaker/Moderator: Sirtex Medical, BTG Medical (Therasphere) Independent Director: Merit Medical By The End off This Talk You Should Be Able To: Understand the differences in physical properties Review the delivery methods Discuss the relationship between dose and activity Identify common pitfalls 1

2 1/5/2017 So lets get started! Manufacture Method Glass Melt composites in a crucible Smash them to pieces Spheriodize Sort Activate with neutrons Resin Polymer microsphere Coated with resin that has strong ionic bonding capacity to Y90 Activation via generator How To Make It Radioactive Therasphere:Bombard the matrix with radiation (Glass) Sirsphere: Coat inert particle and facilitate a bond (Resin) 2

3 1/5/2017 SIR-Spheres Delivered as a vial containing 5 ml water and 20+ million microspheres with total activity* of ~3.7 GBq (81 mci) 90 yttrium (Y90) Resin microspheres microns in diameter Single mother dose needs to be drawn at time of administration Theraspheres Delivered as a fixed vial containing 0.05 ml water and million microspheres with (original) activity of 3-20 GBq ( mci) Glass microspheres are microns in diameter Multiple administrations require multiple vials 3

4 1/5/2017 Y-90 Microspheres Compared: Actual Calculated Patient Dose Activity Parameter Glass Therasphere Resin SirSphere Size µm µm Isotope Y90 in glass matrix Y90 on resin surface Dose activity MIRD Body Surface Model Partition Manufacture Reactor (neutron flux) Generator (Sr-90) Specific Gravity 3.6g/dL 1.6g/dL Activity/Sphere Bq * Bq Right Liver Dose 3.0 GBq 1.2GBq Infusate Normal Saline D5W* # of Spheres/Dose Million Million Kritzinger Clin Rad 2013 Key consideration for administration kit: suspension of spheres Vial Delivery and Titration Glass (Therasphere) 3, 5, 7, 10, 15, 20GBq vials that are decayed to admin time Minimal handling: locked & loaded administration must be between a window May require multiple vials Resin (SirSphere) Single Mother vial delivered at 3.7GBq ( day before ) Activity drawn and loaded on site, may require multiple draws Draw to coincide with administration time Multiple draws from single vial 4

5 1/5/2017 Administration kits compared Glass (Therasphere) Higher specific gravity requires pressurized bolus Smaller number of particles No capacity to check reflux with contrast Precalibrated vials may require multiple administrations at same point Higher amount of overall radioactivity Resin (SirSphere) Lower specific activity allows implantation based on physiologic flow Larger number of particles* Ability to check flow with intermittent contrast bolus Single dose arrives and can be titrated on site (not multiple vials) Lower amount of overall radioactivity (BSA) D5W (for resin): A Sweet Deal Koran et al. Biomed Reports : In conclusion, resin microsphere infusion utilizing D5W has a significantly lower rate of stasis than H2O and results in more complete dose delivery. D5W is preferable to H2O for resin microsphere infusion. Ahmadzadehfar et al. EANM 2015 P846 Replacing sterile water with D5W favorably impacts on the safety of SIRT, eliminates and/or minimizes flow reductions/reflux during administration of 90Y-resin microspheres and improves percentage activity delivered and ease of delivery So what about EX dose? Administration of glass at 1+ week post production (Tues-Wed-Thurs) 9-11 days post = h Half life of Y h: 9 days = 3.35 half lives 11 days = 4.11 half lives 2500Bg/sphere at 4.11 t½ = <150Bq/sphere 5

6 D O S E 1/5/2017 Conceptualizing Dose: The Dosimi-Tree Activity (GBq) Mass/Volume (g/cc) Tissue (Liver) Particle Distribution (#) D O S E ACTIVITY DISTRIBUTION VOLUME TISSUE So do physical properties effect penetration? Deeper Penetration (cm) Jernigan et al JVIR 2015: Summary 6

7 1/5/2017 Y90 Microspheres Are Not The Same. Different Physical Properties Different Behavior Different Delivery Mechanism Different Approach to Dosimi-Tree Remember: GOALS OF THERAPY Common Pitfalls Cross pollinating literature The products are the same when I want them to be and different when I don t want them to be Confusing Activity Calculators for Dosimetry Confusing Partition Model with MIRD single compartment Not accounting for Parenchymal reserve/health Tumor biology Vascular capacity/distribution 7

8 1/5/2017 Y-90 Why Not?!? GEEKING OUT ON GLASS AND REELING IN RESIN TECHNICAL CONSIDERATIONS David Liu MD FRCPC ABR(D) CAQ(IR) FSIR Clinical Associate Professor University Of British Columbia Faculty of Medicine Department of Radiology Interventional Radiology Section Vancouver General Hospital Vancouver British Columbia Canada 8

9 Principles of Y90 Dosimetry Ripal T. Gandhi, M.D. Miami Cardiac & Vascular Institute Miami Cancer Institute Associate Clinical Professor, FIU Herbert Wertheim College of Medicine Asst Clinical Professor, USF School of Medicine DAVYR Application available for iphone & ipad Objectives Common Terminology Dose vs Activity: Why Care? Interpretation and Application Practical Approach to Dosimetry 1

10 Stop the insanity!!! Hotter vs colder Glass vs Resin Too embolic vs not embolic MIRD, BSA, or Partition? terminology TERMINOLOGY: WHAT IS DOSE? Dose: Radiation dose refers to the amount of energy deposited in matter and/or biological effects of radiation (gray, Gy), and should not be confused with the unit of radioactive activity (becquerel, Bq) of the source of radiation, or the strength of the radiation field. -Wikipedia Activity: decays per unit time independent of distribution or volume (mci, GBq) 2

11 D O S E 1/4/2017 Dosimi-Tree Activity (GBq or mci) Mass/Volume (g/cc) D O S E Tissue (Liver) - radiation weighting factor of tissue (tissue vulnerability) Particle Distribution (#) ACTIVITY DISTRIBUTION TISSUE VOLUME The take home IS Dose Activity How To Determine Activity? [It is] a riddle, wrapped inside a mystery, inside an enigma -Winston Churchill 3

12 BSA or MIRD? Glass Microspheres (Therasphere) MIRD Based on Treated Volume Resin Microspheres (Sirsphere) BSA Model Based on body surface area, and tumor infiltration BSA Model Activity (GBq) = (BSA 0.2) + TI BSA (m 2 )= x height x weight TI = Tumor volume / Total Liver Volume Standard method for resin Based on clinical data and utilized in all Phase III clinical trials with validation in Phase II trials Takes into account degree of tumor infiltration and BSA It does not take into account actual liver volume Drawbacks: obese patients, large tumor burden resulting in hepatomegaly BSA Model BSA Model Depends on: 1.Size of the patient as per BSA 2.Amount of tumor infiltration 4

13 Limitation of BSA OBESE PATIENT AVERAGE SIZE LIVER Large Patient with Average Size Liver BSA Model could overdose the patient MIRD Model Standard method for glass Y90 Utilizing target tissue mass as a determination of theoretical absorbed dose Assumes uniform distribution of particles in entire compartment including tumor and liver Target dose Gy (usually 120 Gy) Drawback: there is no distinction between tumor and normal liver parenchyma in the treated volume Limitation of MIRD 1000 cc right hepatic lobe volume Desired dose 120 Gy, 2% lung shunt Does not take into account tumor volume For both of the these patients, same activity for right lobe Y90 5

14 So what about EX dose? Administration of glass at 1+ week post production (Tues-Wed-Thurs) Half life of Y h: 9 days = 3.35 half lives 11 days = 4.11 half lives Glass microspheres are modified by allowing the particles to decay by approximately 1 week which allows for greater number of particles with lower specific activity for better distribution at a set absorbed dose of 120 Gray Even though MIRD dosimetry model is independent of tumor burden (for a given dose), increased number of radiomicrospheres can be administered via EX dose to account for larger tumor size Tumor Vasculature Tumors are not uniform and distribution is not uniform Angiogenesis creates non uniform flow and irregular hierarchy of blood vessels An irregular hierarchy of vessels Irregular neovascularity creates eddys, vascular sumps, and pooling disproportion deposition of targeted therapy Jain Nature Medicine

15 Resection Liver with mcrc Undergoing SIRT: Microclustering Uneven distribution results in uneven radiation One sphere is not enough! Cumulative crossfire effect necessary to create isodose cloud Distribution just as important as the activity of the particle Variances in dosimetry may be due to the physical principles of the particles Sharma RA et al. J Clin Oncol 2007; 25: One is not enough - It takes more than one microsphere to kill the tumor tissue it comes in contact with. Radiation Kill Zone Tumor Microcluster These microclusters also have to overlap enough so that they achieve crossfire between the microclusters 7

16 Activity determination models & compartmental dose Factors that determine activity..and estimate dose Height/Weight Liver Fraction Tumor Fraction Lung Shunt MIRD BSA Partition Target Volume Dose Target Volume Target Volume Tumor Fraction Dose to Tumor T:N Ratio Activity Calculations and Presumed Radiation/Particle Distribution/Dose MIRD assumes uniform distribution BSA assumes uniform distribution based on theoretical liver + tumor Partition assumes weighted distribution of particles based on volume and T:N 8

17 Compartmental Dosimetry: Basic principles Protect the lungs (>25-30 Gray) Protect the liver Optimize dose to tumor The PIVOTAL dose escalation response publication A Phase I/II (n=18) Sirsphere study in 1994 using partition model! When we use MIRD with glass, we target about Gy to the tumor 205Gy required in tumor. SN and SP of 100% and 90% with TcMAA Garin Eur J Med Mol Im 2013 Tumor response significantly correlated with absorbed dose in target lesions (r , 95% CI, , P < 0.001) and a threshold of 500 Gy predicted response (area under the curve, 0.78) -Mazzafero J Hep

18 Glass: Toxicity increases at 70Gy Exposure for CP5 Chiesa QJ Mol Im 2012 Resin: Normal livers <70Gy Compromised<40-50Gy -Lau et al. Int J Radiat Oncol Biol Phys 2012; 82:401 Parenchymal Threshold is still around 70 Gy for both A comprehensive approach to resin (expert consensus panel) Lau et al. Int J Radiat Oncol Biol Phys 2012; 82:401 A practical approach (with resin) 10

19 easiest approach The Easiest Approach for glass and resin Real time calculations for all methods in all compartments Does not take into account distribution Graphical representation of relationships of T:N, tumor fraction, and LSF Avail for Free in App Store: ipad and Iphone Summary Protect the Lung and Liver Lung: <25Gy single treatment Liver: <70Gy if normal <40Gy if compromised Optimize, NOT maximize dose to tumor Higher than needed dose results in collateral Glass: >200Gy to tumor Resin: >100Gy to Tumor Glass and Resin Gray are not the same Think of the Dosimi-Tree Physical principles of the particles and distribution is key to understanding the differences 11

20 Thank You! Principles of Y90 Dosimetry Ripal T. Gandhi, M.D. Miami Cardiac & Vascular Institute Miami Cancer Institute Associate Clinical Professor, FIU Herbert Wertheim College of Medicine Asst Clinical Professor, USF School of Medicine 12

21 Dose Calculators 1. SMAC Calculator for Resin Radiomicrospheres from Sirtex (SIR Spheres) 2. idoc Interactive Dose Ordering Calculator from BTG (Theraspheres) 3. DAVYR Application (Dose and Activity Visalizer for Yttrium-90 Radioembolization App) Application for iphone/ipad which is a dynamic, interactive tool which provides the user with plots and calculations relative to activity and dosimetry For both glass and resin radiomicrospheres 4. Simplicit90Y dosimetry software (BTG and Mirada Medical) Not available in the US; CE mark in Europe and Canada Allows for digital processing and review of imaging with options for data display, quality control, image manipulation, quantification analysis, dosimetry planning, and post-treatment validation. Allows for personalized dosimetry The Easiest Approach for glass and resin Real time calculations for all methods in all compartments Does not take into account distribution Graphical representation of relationships of T:N, tumor fraction, and LSF Avail for Free in App Store: ipad and Iphone So Why is the App Useful? Calculates out the dose to the liver, lung and tumor using MIRD, BSA, and Partition Methods Real time recalculation of activity and dose while changing parameters Visualization of the relationships between MIRD, BSA, and Partition to improve conceptual understanding 13

22 practical considerations 14

23 How do we address Increase Activity The difference in activity administration (MIRD is usually about 2x more) Hepatomegaly Large tumor burden Cachectic, thin patient with normal liver volume Radiation Lobectomy Radiation Segmentectomy High Lung Shunt (in certain cases) How do we address Decrease Activity High lung shunt (in certain cases to keep <25-30 Gy during single administration) Chemotherapy associated steatohepatitis Small tumor burden Cirrhosis Obese patients Surgical resection Prior SBRT, external beam radiation, prior Y90 Multiple lines of chemo, radiosensitizers (i.e. gemcitabine) Partition Model for Dosimetry Partition Modeling allows for Personalized Dosimetry Trend to decreasing activity and exposure to liver parenchyma but really personalized, optimized dose to the specific patient and tumor on the basis: 1. tumor volume 2. liver volumes 3. lung shunt 4. T:N ratio (tumor to normal liver ratio) More scientifically sound, but less historical clinical data compared to BSA and MIRD Greater physician control over radiation dose (Gy) to the lung, liver, and tumor compartments Assumption: uniform distribution in each compartment Limitations: true T:N ratio difficult to calculate, difficulty in calculating volumes in miliary disease Tower of Babel 15

24 Review of Dosimetry Protect the Lung and Liver Lung: <25-30 Gy single treatment Liver: <70Gy if normal <40-50 Gy if compromised Optimize, NOT maximize dose to tumor Higher than needed dose results in collateral Glass: >200Gy to tumor Resin: >100Gy to Tumor Glass and Resin Gray are not the same Think of the Dosimi-Tree Physical principles of the particles and distribution is key to understanding the differences OBESE PATIENT WITH BORDERLINE LIVER FUNCTION If Treating with Resin Microspheres For Resin Microspheres: Tumoricidial dose > Gy Liver threshold dose < 70 Gy normal liver < Gy compromised liver Lung threshold dose < 25 Gy If Treating with Resin Microspheres OBESE PATIENT WITH BORDERLINE LIVER FUNCTION SMAC Calculator 16

25 OBESE PATIENT WITH BORDERLINE LIVER FUNCTION If Treating with Glass Microspheres For Glass Microspheres: Tumoricidial dose > 200 Gy Liver threshold dose < 70 Gy Lung threshold dose < 30 Gy OBESE PATIENT WITH BORDERLINE LIVER FUNCTION If Treating with Glass Microspheres HIGH LUNG SHUNT If Treating with Resin Microspheres For Resin Microspheres: Tumoricidial dose > Gy Liver threshold dose < 70 Gy normal liver < Gy compromised liver Lung threshold dose < 25 Gy 17

26 HIGH LUNG SHUNT If Treating with Glass Microspheres For Glass Microspheres: Tumoricidial dose > 200 Gy Liver threshold dose < 70 Gy Lung threshold dose < 30 Gy HYPERVASCULAR TUMOR (High T:N Ratio) If Treating with Resin Microspheres For Resin Microspheres: Tumoricidial dose > Gy Liver threshold dose < 70 Gy normal liver < Gy compromised liver Lung threshold dose < 25 Gy HYPERVASCULAR TUMOR (High T:N Ratio) If Treating with Glass Microspheres For Glass Microspheres: Tumoricidial dose > 200 Gy Liver threshold dose < 70 Gy Lung threshold dose < 30 Gy 18

27 Thank You! 19

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29 04/01/2017 Sos Omni Simmons Cobra Mickelson 2

30 04/01/2017 Vertebral Berenstein BENEFITS DISADVANTAGES TF ACCESS - Familiarity, operator comfort - Easier to perform DynaCT - Straightforward Y90 administration set-up - Celiac/SMA down-going - Base cather access can be tenuous - Immediate microcatheterization may be needed for super-selection TR ACCESS - Ease of visceral vessel cannulation - Base catheter can often be advanced further - Non-familiarity (patient preparation/recovery, room set-up, operator comfort, Y90 set-up) - DynaCT requires patient arm movement 3

31 04/01/2017 Braat A, Smits M, Braat M, et al. (2015) 90Y hepatic radioembolization: an update on current practice and recent developments. J Nucl Med 56:

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37 04/01/2017 Aram JL et al (2012). The road less traveled: importance of the lesser branches of the celiac axis in liver embolotherapy. RadioGraphics 32:4,

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40 Siddharth Padia, MD Associate Professor Interventional Radiology University of California, Los Angeles Disclosures Consultant: BTG Case 1 65 year old male Chronic Hepatitis C Mass on surveillance US Clin: Asymptomatic No ascites No encephalopathy ECOG 1 Labs: Platelets 145k Total bilirubin 2.1 Albumin 3.4 INR 1.1 AFP

41 Y90 mapping celiac Seg 4 left Seg 8 right Baseline Y90 Brem Baseline 1 month AFP 1876 AFP 7.5 2

42 Baseline 24 months AFP 1876 AFP <5 Y90 Superselective concept Volume of normal hepatic tissue exposed to treatment decreases with a more selective approach Doses of greater than 200 Gray can theoretically achieve complete tumor necrosis >90% of the time* Segmentectomy allows for very high doses in a superselective fashion *Garin et al. J Nuc Med patients over 5 years DEFINITION: Y90 to 2 or fewer segments ECOG 0-2 (73/25/2) BCLC A/B/C (32/30/37) Child-Pugh A/B (50/50) Riaz et al. Int. J. Radiation Oncology Biol. Phys., Vol. 79, No. 1, pp ,

43 7% of liver volume treated (range 6-11%) Dose calculated was 120 gray for the entire lobe Median dose 521 gray to segment Riaz et al. Int. J. Radiation Oncology Biol. Phys., Vol. 79, No. 1, pp , 2011 Dosimetry Glass Activity (GBq) = Desired Dose [Gy] x Liver mass [kg] 50 x [1-lung shunt fraction] Resin Activity (GBq) = BSA (tumor volume/total volume) Validated for lobar infusions (i.e. large volume) Does not take into account tumor vascularity Assumes no interaction between particles Mapping/treatment technique Similar to lobar technique Lower rates of prophylactic embolization Routine use of c-arm CT Catheter in lobar artery Identify feeding arteries Segmental infusions: small microcatheters (2.3 F distal OD) 4

44 Dosimetry - glass Non-standardized High activity per particle and low particle load First week infusion (i.e. Thurs/Fri) Activity No. of Microspheres (millions) Radiation Segmentectomy Dosimetry Retrospective dosimetry of 20 patients Segment was 16% of total hepatic volume treated Treatment area was 6.5% of total hepatic volume treated Majority received a 5 GBq ordered vial Median dose to segment = 255 Gray Median dose to treatment area = 536 Gray Calculated dose to the ipsilateral lobe = 69 Gray Activity (GBq) = Dose [Gy] x Liver mass 50 x [1-LSF] Padia et al. JVIR 2014 Segmental HCC: Y90 vs. TACE University of Washington Experience Single hospital retrospective study Curative procedure (e.g. immediate liver transplantation, surgical resection, ablation) was not possible No extrahepatic disease ECOG performance status of 0-2 Procedure in which Y90 or TACE was performed to a single hepatic Couinaud segment Padia et al. ASCO

45 Segmental HCC: Y90 vs. TACE University of Washington Experience Baseline TACE Y90 p-value # of patients # of tumors Tumor size (mm) <0.001 Infiltrative tumors 9% 23% PVT 1% 18% <0.001 ECOG 0/1/2 56/31/12 76/19/ BCLC A/B/C/D 38/14/38/10 31/19/46/ Child-Pugh A/B/C 52/39/9 65/31/ Within Milan criteria 84% 52% <0.001 Padia et al. ASCO 2016 Segmental HCC: Y90 vs. TACE University of Washington Experience Technique Y90 Glass Y90 (TheraSphere) in all cases Target dose >>> 200 gray 93% required 1 treatment, 7% required 2 treatments TACE 72% DEB, 28% oil 79% required 1 treatment, 21% required 2 treatments Padia et al. ASCO 2016 Segmental Y90 v TACE Toxicity TACE Y90 p-value (adj) Fatigue 27% 39% 0.22 Pain 1% 8% 0.03 Post-embo syndrome 9% 2% 0.08 Ascites 1% 1% Encephalopathy 1% 0 Ulcer 0 1% Death 0 0 AST 8% 3% 0.14 ALT 3% 1.5% 0.67 Albumin 3% 2% 0.59 Bilirubin 9% 3% 0.12 Padia et al. ASCO

46 Segmental Y90 v TACE Response (mrecist) TACE Y90 p-value Complete response 74% 92% Partial response 18% 5% Stable disease 5% 2% Progression 3% 1% Padia et al. ASCO 2016 Local tumor recurrence Y90 TACE 1 year 8% 30% 2 years 15% 42% Padia et al. ASCO 2016 Survival Survival determined by cancer and cirrhosis Better responses by Y90 may NOT result in better survival Padia et al. ASCO

47 Summary Y90 segmentectomy is a potential leap in liver tumor therapy Consider replacing TACE with Y90 in this setting Minimal repeat treatments Use in advanced stage (Child B/PVT) Preserved hepatic function Preserved liver vascularity More path data and surgical correlation needed Need to continue to refine the dosimetry model Potential for high doses to small volumes of tissue Thank you! spadia@gmail.com 8

48 SELECTIVE INTERNAL RADIATION THERAPY FOR LIVER TUMORS: Three Key Studies Nicholas Fidelman, MD Associate Professor UCSF Department of Radiology Outline Y90 literature direction Prospectively acquired data on HCC Prospective acquired on mcrc Ongoing trials 90 Y Glass Microspheres for HCC Mazzaferro V, et al. Hepatology 2013; 57:

49 Mazzaferro V, et al. Hepatology 2013; 57: First phase II evaluating Y90 for HCC 52 patients; BCLC B (17) or BCLC C (35), UNOS stage 3 (8), 4a (9), or 4b (35) Lobar TheraSphere; target dose 120 Gy Mazzaferro V, et al. Hepatology 2013; 57: Total BCLC B BCLC C Time to progression 11 months 13 months 7 months Overall survival 15 months 18 months 13 months EASL CR + PR 21 (40%) 9 (53%) 12 (34%) EASL CR + PR + SD 41 (79%) 15 (88%) 26 (74%) WHO CR + PR 21 (40% 8 (47%) 13 (37%) Mazzaferro V, et al. Hepatology 2013; 57: HCC: Ongoing Trials SIR-Sphere v. sorafenib (RCT, Singapore) [360 pts] SIR-Sphere v. sorafenib (RCT, France) [400 pts] TheraSphere v. sorafenib (STOP-HCC) [360 pts] TheraSphere v. sorafenib (YES-P) TheraSphere v. DEB-TACE (RCT, Ghent) [140 pts] 2

50 90 Y Resin Microspheres for mcrc Hendlisz A, et al. J Clin Oncol 2010; 28: Hendlisz A, et al. J Clin Oncol 2010; 28: First RCT evaluating radioembolization Chemorefractory, liver-limited mcrc 5-FU (225mg/m 2 ) vs. 5-FU + SIR-Sphere* *Cross-over to SIR-sphere treatment allowed upon progression in 5-FU arm Hendlisz A, et al. J Clin Oncol 2010; 28: Fluorouracil N = 23 Fluorouracil+SIR-Spheres N=21 P-value Time to liver progression Time to tumor progression 2.1 months 5.5 months months 4.5 months 0.03 Overall survival 7.3 months 10 months 0.80 Grade 3 or 4 AEs 26% 5%

51 90 Y Resin Microspheres for mcrc van Hazel GA, et al. J Clin Oncol 2016; 34: SIRFLOX: Randomized phase III trial comparing first-line mfolfox6 (+bevacizumab) versus mfolfox6 (+bevacizumab) + selective internal radiation therapy (SIRT) in patients with metastatic colorectal cancer Gibbs P et al. J Clin Oncol 2015; 33 (Suppl): Abs 3502 SIRFLOX: Endpoints Primary PFS in ITT population Secondary PFS in the liver Radiographic response Hepatic resection rate Toxicity and safety (NCI CTCAE v 3.0) Gibbs P et al. J Clin Oncol 2015; 33 (Suppl): Abs

52 SIRFLOX: ITT Population Gibbs P et al. J Clin Oncol 2015; 33 (Suppl): Abs 3502 SIRFLOX: Treatments Gibbs P et al. J Clin Oncol 2015; 33 (Suppl): Abs 3502 SIRFLOX: PFS at Any Site Gibbs P et al. J Clin Oncol 2015; 33 (Suppl): Abs

53 SIRFLOX: Hepatic PFS Gibbs P et al. J Clin Oncol 2015; 33 (Suppl): Abs 3502 SIRFLOX: ORR Gibbs P et al. J Clin Oncol 2015; 33 (Suppl): Abs 3502 SIRFLOX: Conclusions Addition of SIRT using Y-90 resin microsphere to first-line FOLFOX Did not improve overall PFS 7.9 month improvement in hepatic PFS No negative impact on duration of systemic therapy Gibbs P et al. J Clin Oncol 2015; 33 (Suppl): Abs

54 Combination Therapy: Future Directions Gibbs P et al. J Clin Oncol 2015; 33 (Suppl): Abs 3502 mcrc: Ongoing Trials With First-line FOXFIRE (UK) [364 pts] FOXFIRE Global [209 pts] With Second-line FOLFOX/FOLFIRI +/- TheraSphere (Phase III) [360 pts] Thank you Nicholas.Fidelman@ucsf.edu 7