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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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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
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
Re - discovered technique : Ariel IM. 1965 Aug; Ann Surg 162: 267 - 278
Radioactive particles (microspheres) carrying 90Yttrium are administered to the liver arteries lead to accumulation in the metastases GIST mets are hypervascular Predominant arterial supply
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
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%
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
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
a b a b Patient #7 PET CT a) pre SIRT, b) Partial Response 3 months post SIRT with reduced SUV of the lesions.
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
b a c d
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
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
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