Selective Internal Radiation Therapy (SIRT) & Metastatic Liver Disease

Shannon Russell MSN, CCRN, NP-C Shannon.Russell@coxhealth.com

Objectives

o Provide brief overview of current treatment options available for metastatic liver disease

o Discuss SIRT (Selective Internal Radiation Therapy) o Y-90 isotopeo Mode of action

o Review clinical data supporting use of SIRT

o Identify patients eligible for SIRT

o Review contraindications to treatment

Facts About Metastatic Disease

Cancer Type Main Sites of MetastasisMelanoma Bone Brain Liver

Breast Bone Brain Liver

Pancreas Liver Lung Peritoneum

Colorectal Liver Lung Peritoneum

Ovary Liver Lung Peritoneum

Prostate Adrenals Bone Liver

Stomach Liver Lung Peritoneum

Thyroid Bone Liver Lung

Uterus Bone Liver Lung

Bladder Bone Liver Lung

After the lymph nodes, the liver is the most common site of metastatic disease. Most liver metastases originate from the colon, rectum, pancreas, stomach, esophagus, breast, lung, melanoma and some less common sites.

www.cancer.gov/about-cancer/what-is-cancer/metastatic -fact-sheet1http://surgery.ucsf.edu/conditions--procedures/liver-metastases-%28secondary-liver-cancer%29.aspx

Colorectal Cancer & Metastatic Liver Disease…

Liver metastases from colorectal cancers (mCRC) is very common & associated with a poor prognosis

• Colorectal cancer (CRC) is the 2nd leading cause of cancer-related deaths in the U.S.3

• American Cancer Society estimates CRC will be the cause of 49,190 deaths in 20163

• Data suggests 50% of patients with CRC will develop liver metastases; <20% of patients are candidates for surgical resection initially4,5

• Up to 90% of mCRC patients die of liver failure due to the local effects of tumors4,12

Treatment Options for Metastatic Liver Disease

Surgical Resection▪ Gold Standard of

TreatmentPortal Vein EmbolizationSystemic ChemotherapyBiologic Therapies ▪ Nexavar▪ Sutent

Hepatic arterial infusion therapy (HAC)Ablation ▪ Microwave▪ Radiofrequency Chemoembolization (TACE)Selective Internal Radiation Therapy (SIRT)

Selective Internal Radiation Therapy…Y90

Method of delivering radiation to liver tumors while preventing radiation exposure to the normal liver parenchyma

Not an entirely new technology – studies date back to the 1960s

Study by Ariel & Pack in 1967 – standard chemotherapy vs. treatment with Y90 spheres vs. combination therapy6 ▪ Concluded that addition of Y90 extended the

average duration of life▪ Chemo alone 3.9 months▪ Y90 alone 4.6 months▪ Combination therapy 5.6 months

Research continued … advances in microsphere technology, standardization of Y-90 dose, etc

Collective data from multiple studies supports the use of Y90 for hepatic malignancies

FDA approved use of Y-90 microspheres in 2002 as a brachytherapy device 7

SIRT Treatment Goals

I. Decrease tumor burden in the liver8

II. Increase the time to progression8

III. Potential downsizing to liver resection or ablation8

IV. Provide palliation of symptoms8

Y-90 Isotope

Y-90 (yttrium) is a high energy, beta-emitting isotope. This form of ionizing radiation allows for very localized delivery of high-dose radiation8

Limited tissue penetration - 2.5mm average and 11mm max4,8

Yttrium half-life 64 hrs or approx 2.7 days 4,8

▪ >97% of total dose delivered over 14 days with almost no radiation remaining after 1 month 4

SIR-Spheres Microspheres: Biocompatible polymer microspheres, average diameter 32 microns4

http://www.sirflox.com/files/user/microspheres.jpg

Y-90 … Mode of Action

Portal Vein & Hepatic Artery: • 75% of total liver blood flows

through the portal vein• Hepatic artery supplies the

remaining 25%

http://www.sirtex.com/media/47526/liver-with-highlighted-hepatic-artery.png

Delivery system capitalizes on the anatomic differences in liver perfusion

Hepatic tumors obtain 90% of their blood supply from the hepatic artery5

Y-90 … Mode of Action

Microcatheter advanced via femoral artery to right or left hepatic artery

Y-90 microspheres administered, travel to the tumor and lodge in the arterioles• Liver tumor vessel diameter 25-75 µm • End arteriole diameter 8 µm • Average diameter of microsphere 32 µm

Beta radiation is released killing tumor cells

Spheres are too large to pass through capillaries and into the venous system • No systemic exposure• Permanently implant in the tumor bed › embolic effect (cell death)

Y-90 … Mode of Action

Tumor death results from:1) Release of internal beta radiation 2) Embolic effect of microspheres

http://www.utmedicalcenter.org/lib/image/manager/Departments/CancerCenter/LiverBile_Duct/Theraspheres.png

http://toledoxray.com/Images/SiteImages/liver_tumor_w_microspheres.jpg

Clinical Studies of SIR-Spheres

Gray & van Hazel both conducted randomized controlled trials suggesting benefits greater if used earlier & in combination with systemic chemotherapy8

Gray et al was pivotal study that led to FDA approval of Y90 in U.S.

/

SIRFLOX Study

Preliminary data reveals no statistically significant improvement in overall Progression-Free Survival10

Does show a statistically significant improvement in Progression-Free Survival in the liver by 7.9 months (31% risk reduction)10

The first large phase III randomized, multicenter controlled trial to assess efficacy & safety of adding SIRT

to FOLFOX chemotherapy for first-line combination therapy10

SIRLFOX Study

The final analysis of the study will be submitted to the American Society of Clinical Oncology (ASCO) Annual Meeting, 29thMay –2nd June 2015 in Chicago, Illinois.

Safety Profile

In comparison to other treatment options (i.e. HAC, TACE, RFA),

Y-90 is associated with less adverse effects5

Most Common Reported Adverse Effects: • Fatigue (grade 1-2)4

• Fever11

• Abdominal pain4,11

• Nausea4,11

• Elevated LFTs4 • Mild gastritis/duodenitis4,11

Radiation-induced hepatic failure

»RARE OCCURRENCE

With appropriate patient selection & standardized dosing is <1% 4

Patient Eligibility

Stable labs (CBC with differential, BUN, serum creatinine, electrolytes, LFTs, albumin, LDH, PT/PTT)5,9

Imaging (CT and/or MRI) with assessment of portal vein patency 5,9

Liver involvement <60%9

Successful Arterial Mapping - arteriography and macroaggregated albumin (MAA) lung shunting study9 ▪ Assess anatomy of vessels, patency of portal vein▪ Assess gastroduodenal flow to identify collateral vessels and avoid

infusion of radioactive spheres into areas that can cause toxicity▪ Assess for lung shunt: Lung tumors can have arteriovenous

connections which create shunting from the liver to the lungs

ECOGECOG Scale

Characteristics

0 Asymptomatic and fully active1 Symptomatic; fully ambulatory; restricted in

physical strenuous activity

2 Symptomatic; ambulatory; capable of self-care; more than 50% of waking hours are spent out of bed

3 Symptomatic; limited self-care; spends more than 50% of time in bed

4 Completely disabled; no self-care; bedridden

Eastern Cooperative Oncology Group: Numerical score reflecting

functional status5

The higher the ECOG score, the more risk for morbidity with

treatment

Recommended ECOG score0-2

Contraindications

Decompensated liver function4

Elevated bilirubin (>2mg/dl)4

Poor performance status (ECOG>2) 4Greater than 20% lung shunting of the hepatic artery blood flow (determined in pre-procedure mapping)9

Abnormal vascular anatomy that would result in significant reflux of hepatic arterial blood to the stomach, pancreas or bowel9Disseminated extra-hepatic malignant disease9Portal vein thrombosis4,5,9

Dollars & Cents

Most insurance companies cover the cost of the SIR-Spheres

Under the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) of 2003 , Medicare reimburses hospitals for the full cost of outpatient treatment 15

Many private payors also have provided coverage including Aetna, Anthem, Cigna, HealthNet, Humana, and United Healthcare15

SIRT available at 700 centers worldwide, 300 centers in the United States alone15

http://www.sirtex.com/media/70435/2016-sirtex-coding-sheet-updated032116-final.pdf

http://www.sirtex.com/media/70435/2016-sirtex-coding-sheet-updated032116-final.pdf

Questions …

References1. National Cancer Institute. Metastatic cancer. Retrieved from http://www.cancer.gov/about-cancer/what-is-cancer/metastatic-fact-sheet2. University of California San Fransisco. Liver metastases. Retrieved from http://surgery.ucsf.edu/conditions--procedures/liver-metastases-

%28secondary-liver-cancer%29.aspx3. American Cancer Society. Key statistics for colorectal cancer. Retrieved from http://www.cancer.org/cancer/colonandrectumcancer/

detailedguide/colorectal-cancer-key-statistics4. Fakih M. SIR-Spheres radioembolization in the management of metastatic colorectalcancer: a medical oncology perspective. Colorectal

Cancer , 2014; 3(4):331-3435. Lewandowski R, Salem, R. Yttrium-90 radioembolization of hepatocellular carcinoma and metastatic disease to the liver. Sem Interv Radiol.

2006 23(1); 64-72.6. Ariel I , Pack G. Treatment of inoperable cancer of the liver by intra-arterial radioactive isotopes and chemotherapy. Cancer. 1967;

20: 793–804. doi: 10.1002/1097-0142(1967)20:5<793::AID-CNCR2820200534>3.0.CO;2-I7. Food and Drug Administration. SIR-Spheres – P990065. Summary of Safety and Effectiveness Data. http://www.accessdata.fda.gov/

cdrh_docs/pdf/P990065b.pdf. Accessed April 2, 2016. 8. Mehta D. SIR-Spheres Microspheres: An emerging treatment for mCRC liver tumors. Clin Oncol News. 2012; 7(5):10-119. Data on file. Sirtex Medical Inc. Retreived from http://www.sirtex.com/us/clinicians/about-sir-spheres-microspheres/mode-of-action/10. Van Hazel, G, Heinemann, V, Sharma, N, et al. SIRFLOX: Randomized phase III trial comparing first-line mFOLFOX6 (plus or minus

bevacizumab) versus mFOLFOX6 (plus or minus bevacizumab) plus selective internal radiation therapy in patients with metastatic colorectal cancer. J Clin Oncol. 2016;1-11. DOI 10.1200/JCO.2015.66.1184

11. SIRFLOX. Study design. www.sirflox.com/study-design. Accessed May 18, 2016.12. Kosmider S, Tan TH, Yip, D, et al. Radioembolization in combination with systemic chemotherapy as first-line therapy for liver metastases

from colorectal cancer. J Vasc Interv Radiol. 2011; 22(6):780-786.13. Sharma RA, vanHazel GA, Morgan B, et al. Radioembolization of liver metastases from colorectal cancer using yttrium-90 microspheres

with concomitant systemic oxaliplatin, flurouracil, and leucovorin chemotherapy. J Clin Oncol. 2007;25(9):1099-1106

References

14. SirTex Medical Inc. Extending treatment options for colorectal liver metastases. Woburn, MA: Sirtex Medical Inc. 15. Espat NJ and Pishvaian M. Special Report: Addressing misconceptions about selective internal radiation therapy. Clin Oncol News.

2014.16. Sirtex Medical Inc. Coding Sheet, January 2016. Retrieved from http://www.sirtex.com/media/70435/2016-sirtex-coding-sheet-

updated032116-final.pdfSirtex coding sheet jan 2016 retrieved from