Radioembolization with Yttrium 90


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I have uploaded the presentation on Yttrium 90 & its application in treatment of Liver Cancer. Presentation elaborates on characteristics of Y-90, how treatment is planned, workup done & aspects on radiation safety & post treatment care. I would be glad to answer queries on this new emerging exciting area of treating Inoperable Liver Cancers.

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Radioembolization with Yttrium 90

  1. 1. Radioembolization with microspheres ®
  2. 2. SIR-Spheres microspheres were developed in the 1980s in Australia. Since then the product and the procedure have been refined in collaboration with SIRTEX Medical Limited (SIRTEX). Meanwhile more than 7,500 patients have been treated all over the world, especially in the US, Australia, New Zealand, Hong Kong, and Europe with experience rapidly growing in other countries. 
  3. 3. Rationale for SIRT <ul><li>Liver is sensitive to radiation </li></ul><ul><li>Hepatic circulation is uniquely organized with dual supply to the liver </li></ul><ul><li>Almost exclusive arterial supply to the metastatic tumour </li></ul>
  4. 4. Properties <ul><li>Resin microspheres which are loaded with the radionuclide Yttrium-90 </li></ul><ul><li>Between 20μm and 60μm in diameter </li></ul><ul><li>Biocompatible, not biodegradable </li></ul><ul><li>SIR-Spheres microspheres are classified by </li></ul><ul><li>regulators as a brachytherapy medical device </li></ul>
  5. 5. Properties <ul><li>The shipping-vial always contains 3GBq ± 10% </li></ul><ul><li>3GBq represent between 40 and 80 million microspheres </li></ul><ul><li>The amount of delivered microspheres can </li></ul><ul><li>cause embolic effects in the arteries </li></ul>
  6. 6. Yttrium-90 <ul><li>Yttrium-90 is a high energy pure beta emitting isotope </li></ul><ul><li>Y-90 has a half-life of 64.1 hours (2.67 days) </li></ul><ul><li>94% of radiation is delivered within 11 days </li></ul><ul><li>Mean energy is 0.9367 MeV </li></ul><ul><li>Average radiation range in tissue is 2.5 mm with </li></ul><ul><li>a maximum of 11 mm </li></ul>
  7. 7. SIRT – Treatment Algorithm 1-2 weeks 1-2 weeks Patient Selection *optional Tumour Mapping Bremsstrahlung Scan* Vessel Embolisation Labs Labs SIR-Spheres Delivery Treatment Plan Dosimetry Ordering Post Treatment Care CT/Hepatic Angiogram* Vessel Mapping Review Breakthrough Scan Follow Up
  8. 8. SIRT - A Multidisciplinary Team Approach <ul><li>Interventional Radiology </li></ul><ul><li>Radiation Oncology </li></ul><ul><li>Nuclear Medicine </li></ul><ul><li>Medical Physics </li></ul><ul><li>Hepatology </li></ul><ul><li>Surgical Oncology </li></ul><ul><li>Medical Oncology </li></ul><ul><li>Radiation Safety </li></ul>
  9. 9. 1-2 weeks 1-2 weeks Patient Selection Tumour Mapping Vessel Mapping Review SIR-Spheres Delivery Bremsstrahlung Scan* Vessel Embolisation Labs Labs Treatment Plan Dosimetry Ordering Post Treatment Care Follow Up CT/Hepatic Angiogram* *optional Breakthrough Scan
  10. 10. Indication <ul><li>Patients with liver cancer who are not suitable for resection with curative intend </li></ul>Contraindications <ul><li>Prior radiation therapy to the liver </li></ul><ul><li>Prior treatment with capecitabine within the last two months </li></ul><ul><li>or any time in future </li></ul><ul><li>Generalised ascites or any other sign of clinical liver failure </li></ul><ul><li>Albumin less than 15% below normal </li></ul><ul><li>AST and ALT more than 5 x normal </li></ul><ul><li>Elevated bilirubin above 35 µmol/L (2mg/dL) </li></ul><ul><li>Untreated bile duct obstruction </li></ul><ul><li>Main portal vein thrombosis </li></ul>
  11. 11. Selection Criteria <ul><li>Limited extra-hepatic disease </li></ul><ul><li>Life expectancy of at least 3 month </li></ul><ul><li>Generally well and considered fit to undertake radiation therapy </li></ul><ul><li>(ECOG performance status 0-2 or Karnofsky score >60%) </li></ul><ul><li>Enough hepatic reserve* (normal or slightly compromised liver function, tumour volume of less than 70%) </li></ul><ul><li>Sufficient vascularisation of the tumour** </li></ul><ul><li>The ideal HCC patient has less than 50% tumour burden and Okuda stage 1, Child-Pugh’s class A </li></ul>*The hepatic reserve is likely to be reduced in patients with underlying liver disease such as cirrhosis and in patients heavily pretreated (systemic chemotherapy or TACE) **This can be reduced in patients pre-treated with anti-angiogenesis agents
  12. 12. Patient Precautions <ul><li>Concurrent or sequential chemotherapy : this can be an adjunct to SIRT as many chemotherapeutics are radio-sensitisers </li></ul><ul><li>Consider reducing the dose of oxaliplatin to 60mg/m 2 for three cycles after SIRT to reduce toxicity </li></ul><ul><li>Labs the day before or the day of treatment to re-check bilirubin (must be < 35 µmol/L (2mg/dL)) and other LFTs </li></ul><ul><li>Review pre-treatment medications , Nexium 2-3 days prior to SIRT and 30 days post SIRT </li></ul><ul><li>Bowel prep recommended for patients with previous Whipple surgery and appropriate antibiotics should be started </li></ul>
  13. 13. Side Effects <ul><li>Mild post-embolization syndrome </li></ul><ul><li>(fever, pain, nausea, vomiting and diarrhea) </li></ul><ul><li>Mild to moderate abnormality in liver function </li></ul><ul><li>Fatigue </li></ul>
  14. 14. Rare Serious Side Effects <ul><li>Acute gastritis </li></ul><ul><li>Acute cholecystitis </li></ul><ul><li>Acute pancreatitis </li></ul><ul><li>Radiation pneumonitis </li></ul><ul><li>Radiation hepatitis </li></ul>A meticulous mesenteric angiography, patient work-up and treatment strategy reduces complication rates drastically!
  15. 15. 1-2 weeks 1-2 weeks Patient Selection Tumour Mapping Vessel Mapping Review SIR-Spheres Delivery Bremsstrahlung Scan* Vessel Embolisation Labs Labs Treatment Plan Dosimetry Ordering Post Treatment Care Follow Up CT/Hepatic Angiogram* *optional Breakthrough Scan
  16. 16. Patient Serum Chemical Analysis <ul><li>To evaluate hepatic function * </li></ul><ul><li>To evaluate renal function ** </li></ul><ul><li>To determine the presence and magnitude of elevation of tumour markers </li></ul>*Patients with irreversible elevations in serum bilirubin (>35 µmol/L (2mg/dL)) should excluded **In the presence of renal insufficiency, care must be taken to avoid or minimize the use of iodinated contrast material
  17. 17. 1-2 weeks 1-2 weeks Patient Selection Tumour Mapping Vessel Mapping Review SIR-Spheres Delivery Bremsstrahlung Scan* Vessel Embolisation Labs Labs Treatment Plan Dosimetry Ordering Post Treatment Care Follow Up CT/Hepatic Angiogram* *optional Breakthrough Scan
  18. 18. Meticulous Mesenteric Angiography To determine the safest and most effective treatment strategy To identify all hepatic and gastric vessels , including extremely small branches , arterial variants and collaterals R.Murthy et al: RadioGraphics 2005; 25:41-55
  19. 19. Recommended Embolisation* Strategy <ul><li>Embolisation of GDA is recommended </li></ul><ul><li>Embolisation of RGA is recommended </li></ul><ul><li>Embolisation of any artery that his feeding the stomach or duodenum </li></ul><ul><li>In general the threshold for prophylactic embolisation should be low </li></ul>Care should be taken when embolising the GDA as accessory hepatic vessels feeding the tumour may arise from this artery. *Sirtex does not recommend any specific form of embolisation
  20. 20. Recommended Embolisation* Strategy If the right gastric artery can not be identified it is advisable to either not treat the patient or to treat bi-lobar with the catheters as far into the LHA and RHA as possible. Special care should be taken to infuse the microspheres slowly. *Sirtex does not recommend any specific form of embolisation !
  21. 21. Recommended Embolisation* Strategy <ul><li>It is to be noted that these vessels/organs can revascularise quickly , and therefore the embolization should be performed close to the intended time of treatment, with a check arteriogram to ensure that such revascularization has not occurred </li></ul><ul><li>Small previously unseen vessels can become more prominent after embolization of the GDA and right gastric artery. If this redistribution phenomenon is not recognized at the time of treatment, complications may ensue </li></ul>*Sirtex does not recommend any specific form of embolization
  22. 22. Breakthrough Scan (MAA Lung Shunting Scan) <ul><li>MAA is similar in size to Y-90 but bio-degradable </li></ul><ul><li>Used as pre-treatment simulation to select suitable patients for SIRT </li></ul><ul><li>To determine extra-hepatic shunting to the lungs and non- target organs </li></ul><ul><li>In patients with metastatic disease, significant shunting is rare unless the tumour burden is high </li></ul><ul><li>In lobar or segmental infusion, MAA injection should be performed on the segment/lobar level as different segments/lobes might shunt to different levels </li></ul>
  23. 23. <ul><li>Injection of 150MBq (4mCi) 99m Tc-MAA </li></ul><ul><ul><li>after coil embolization is completed </li></ul></ul><ul><ul><li>with catheter tip in same position as planed treatment </li></ul></ul><ul><li>Imaging should be </li></ul><ul><ul><li>done within 1 hour after injection </li></ul></ul><ul><ul><li>at a minimum be a planar imaging (ideally SPECT) </li></ul></ul><ul><li>Scan shouldn’t be done on the day of treatment due to the large number of particles injected </li></ul><ul><li>Lung shunting scan should be repeated if original study is 4-6 weeks old </li></ul>Breakthrough Scan (MAA Lung Shunting Scan)
  24. 24. Treatment Approach <ul><li>Bi-lobar (whole liver) </li></ul><ul><ul><li>Preferred approach for bilobar disease </li></ul></ul><ul><ul><li>Microcatheter in PHA </li></ul></ul><ul><li>Bi-lobar lobar </li></ul><ul><ul><li>If GDA or RHA cannot be embolised </li></ul></ul><ul><ul><li>Use of two Microcatheter </li></ul></ul><ul><ul><li>Microcatheter in RHA and LHA respectively </li></ul></ul><ul><ul><li>Both lobes on the same day </li></ul></ul><ul><li>Lobar </li></ul><ul><ul><li>Saver approach if hepatic reserve is low </li></ul></ul><ul><ul><li>Lobes treated separately 6 weeks apart </li></ul></ul><ul><li>Super Selective </li></ul><ul><ul><li>Localised single lesion (most likely HCC) </li></ul></ul><ul><ul><li>Allows higher doses to tumour tissue </li></ul></ul>
  25. 25. Dosimetry – Methods <ul><li>Partition Model </li></ul><ul><li>Body Surface Area (BSA) Method </li></ul>There are two accepted methods for calculating the activity of SIR-Spheres microspheres to implant The initially also used Empiric Method is not recommended any more.
  26. 26. Dosimetry – BSA Method Alternatively to the Partition Model the BSA Method can be used. It is based on a whole liver approach and the patient specific dose (A Yttrium-90 ) is given by: With: V Tumour = Volume of the total tumour mass in the liver V Total Liver = Volume of the total liver (inclusive tumour) BSA [m 2 ] = 0.20247 x height[m] 0.725 x weight [kg] 0.425 A Yttrium-90 [GBq] = (BSA-0.2) + V Tumour V Total Liver
  27. 27. Dosimetry – BSA Method To stay within the safety limits for lung and normal liver, the calculated dose has to be reduced by 20% in case of: <ul><li>A lung shunting fraction of more than 10% and less than 15% </li></ul><ul><li>Patients are heavily pre-treated with chemotherapy </li></ul>by 25% in case of: <ul><li>Patients with moderately (bilirubin more than normal and less than 35 µmol/L (2mg/dL)) impaired liver function </li></ul>
  28. 28. Dosimetry – BSA Method by 30% in case of: <ul><li>Patients having a tumour involvement more than 60% </li></ul><ul><li>A lung shunting fraction of more than 15% and less than 20% </li></ul><ul><li>Patients having a tumour involvement of less than 10% </li></ul>by 40% in case of:
  29. 29. Dosimetry – BSA Method Patients with… <ul><li>A lung shunting fraction of more than 20% </li></ul><ul><li>Serum bilirubin levels of more than 35µmol/L (2mg/dL) </li></ul><ul><li>Serum albumin level reduced by more than 15% </li></ul>… should not be treated at all!
  30. 30. Dosimetry – BSA Method To calculate the radiation dose to only a portion of the liver (either lobe or segment), the following formula may be used: A Yttrium-90 [GBq] = (BSA-0.2) V Total Liver V Treated Portion • + V Total Liver V Tumour in Treated Portion
  31. 31. Product Ordering <ul><li>SIR-Spheres microspheres are provided on an individual order basis </li></ul><ul><li>Sir-Spheres microspheres are typically manufactured 45- 48hours before calibration to allow time for shipping </li></ul><ul><li>Sir-Spheres microspheres are intended to be used on the day of calibration (maximal 24 hours later) </li></ul><ul><li>Typically 7-10 days should be allowed between placing the order and availability of the product </li></ul><ul><li>For the US delivery can only be made to a licensed facility with an authorized user </li></ul>
  32. 32. Pre-Treatment – Liver Function Test Labs the day before or the day of treatment to re-check bilirubin and LFTs <ul><li>Bilirubin must be < 35 µmol/L (2mg/dL) </li></ul><ul><li>Albumin must not be more than 15% below normal </li></ul><ul><li>AST and ALT must not be more than 5 x normal </li></ul>
  33. 33. Pre-Treatment – Patient Medication <ul><li>Proton pump inhibitor 3 days before treatment and 30 days post treatment (or longer if needed) </li></ul><ul><li>If proton pump inhibitor is not given 3 days prior, give IV on the day of treatment </li></ul><ul><li>Have pain medications on board </li></ul><ul><li>Antiemetics should be commenced on the morning of treatment </li></ul><ul><li>No antibiotics are needed unless the patient had a Whipple procedure </li></ul>
  34. 34. Post-Treatment – Complications <ul><li>Radiation Gastritis </li></ul><ul><ul><li>can be avoided by meticulous angiographic technique, appropriate embolization and correct delivery technique </li></ul></ul><ul><li>Radiation Induced Liver Disease (RILD) </li></ul><ul><ul><li>risk can be minimized by meticulous dosimetry technique </li></ul></ul><ul><li>Radiation pneumonitis </li></ul><ul><ul><li>can be avoided by determination of lung-shunting (MAA-Scan) and appropriate dose reductions </li></ul></ul><ul><li>Radiation pancreatitis </li></ul><ul><ul><li>very rare, risk can be minimized by meticulous angiographic technique, appropriate embolization and correct delivery technique </li></ul></ul>
  35. 35.  <ul><li>may be moved into a recovery room </li></ul><ul><li>should be monitored by qualified staff for an hour </li></ul><ul><li>may then be moved to a general ward </li></ul><ul><li>can be discharged the same day </li></ul>The patient If any dressings, such as those over the chemotherapy port or the transfemoral wound need attendance, staff should wear gloves not only as a sterile barrier but also to avoid any radiation contamination. Post-Treatment – Immediate post-implant care
  36. 36.  Data from patients implanted with an average of 2.1 GBq emitted the following Bremsstrahlung radiation at approximately 5-6 hours post implantation: Dose equivalent Distance to abdomen Post-Treatment – Radiation Safety 0.25m 0.0188 mSv/hr 0.50m 0.0092 mSv/hr 1.00m 0.0015mSv/hr 2.00m 0.0004mSv/hr 4.00m <0.0001mSv/hr
  37. 37.  <ul><li>Pregnant staff should not nurse the patient </li></ul><ul><li>Pregnant women should be cautioned regarding spending a long time in close proximity to the patient </li></ul>Post-Treatment – Radiation Safety