Upload
others
View
9
Download
0
Embed Size (px)
Citation preview
Selective Internal Radiation Therapy (SIRT) & Metastatic Liver Disease
Shannon Russell MSN, CCRN, NP-C [email protected]
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