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*Institute of Clinical Radiology and Nuclear Medicine

Selective Internal Radiation Therapy (SIRT) for GIST liver metastases resistant to tyrosine kinase inhibitors. P. Hohenberger^, N. Rathmann*, A. Peschel*, J. Schuetteº D.Pink Δ , S.O. Schoenberg*, D. Dinter*, S. Diehl*. *Institute of Clinical Radiology and Nuclear Medicine

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*Institute of Clinical Radiology and Nuclear Medicine

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  1. Selective Internal Radiation Therapy (SIRT) for GIST liver metastases resistant to tyrosine kinase inhibitors P. Hohenberger^, N. Rathmann*, A. Peschel*, J. Schuetteº D.PinkΔ, S.O. Schoenberg*, D. Dinter*, S. Diehl* *Institute of Clinical Radiology and Nuclear Medicine ^Div. of Surgical Oncology & Thoracic Surgery ΔSarcoma Center Berlin-Brandenburg, HELIOS Klinikum Bad Saarow Medical Faculty Mannheim, University of HeidelbergºHämatologische Schwerpunktpraxis Düsseldorf

  2. Metastatic sites of GIST • Liver • Peritoneum • Omentum • Liver mets affect 15.9% of all GIST patients* • different to handle from colorectal cancer DeMatteo, Ann Surg 2000: 231, 51; *Ye, Eur J Surg Oncol 2009: 35, 787

  3. Re - discovered technique : Ariel IM. 1965 Aug; Ann Surg 162: 267 - 278

  4. Radioactive particles (microspheres) carrying 90Yttrium are administered to the liver arteries lead to accumulation in the metastases GIST mets are hypervascular Predominant arterial supply

  5. Courtesy of A. Kennedy, MD

  6. Option for SIRT • In contrary to percutaneous radiation • SIRT allows the application of radiation doses of up to 200 Gray to the area treated. • steep dose gradient: within 4 mm of radiation spares toxicity to large parts of the normal liver tissue • No significant hepatitis > 8mm of the tumor area. • SIRT has been proved successfully in the treatment of colorectal or breast cancer liver metastases

  7. Eligibility • Histologically confirmed gastrointestinal stromal tumor with hepatic metastases • Standard TKI therapy unable to control hepatic progression • No further drug treatment avaiulable or thought indicated for mutational status • Hepatic disease not amenable to surgery or RFA • Extrahepatic disease controlled by drug treatment • Bilirubin < 2mg/dl, SGOT/GPT < 5fold UL, INR > 50%

  8. Patients and indication

  9. Technique and Methods • Transfemoral angiography to rule out relevant hepato-pulmonary shunting to avoid radiogenic pneumonitis. • 99mTc-labelled macroaggregated albumin (MAA) to the right and/or left liver lobe. • Distribution of the radionuclide in the lungs and in the liver measured with conventional scintigraphy. • In case of normal shunt-volume SIRT was performed within one week. • In case of a hepato-pulmonary shunt-volume of 10 to 20% dose adjustments of the therapeutic radioactivity was made. • A value above 20 % was regarded as contraindication to the procedure • 1 / 9 patients excluded • Calculation of the dosage of 90Ywas done via BSA and taking into consideration the percentage of tumor of the liver tissue

  10. Side effects of SIRT • Transient elevation of liver enzymes (NCIC grade 3) • Drop in cholinesterase (NCIC grade 2) • No radiation-induced liver disease (RILD) • One patient required surgery for persistent stomach ulcer 6 months after SIRT

  11. a b a b Patient #7 PET CT a) pre SIRT, b) Partial Response 3 months post SIRT with reduced SUV of the lesions.

  12. a b c Patient #5 complete devascularisation and cystic transformation of the metastases: a & b) GIST lesion in segment 8/5 Pre SIRT native & CE T1 VIBE FS; c & d) 5 months post SIRT native & CE T1 VIBE FS lesion is nearly completely devascularized; a) small hyperintense rim around the lesion representing inflammation d

  13. b a c d

  14. Summary of treatment results • CR in PET and Gd-MRI : n = 3lasting 8, 9, 24 months • PR / SD acc RECIST+PET 3 / 2 pts • No ‚non-responder‘ • Median follow-up 19 mos. (8 – 52) • Mean PFS of hepatic disease: 9.6 months

  15. Hepatic-Progression free survival

  16. Post- SIRT therapy

  17. Indications from location and size yes no

  18. Indications from biology • Wildtype GIST • NF- 1 associated • 2ndary mutations not responsive to any TKI (activation loop D820A, ATP- binding Y823D) • 2nd/3rd line drugs: median PFS regorafenib 4.8 months sunitinib 7 months nilotinib 6 months masitinib 3.8 months sorafenib 5 months

  19. Conclusion • SIRT may be a safe and effective option in patients suffering from liver metastases of GIST as the dominant site of tumor progression. • Patients need to be selected very carefully • Extrahepatic disease must be under control of drug therapy • Devascularisation of the gallbladder and the stomach may pose patients at risk of ischemic ulcerations

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