Selective internal radiation with Y-90 resin microspheres (SIRT) for liver metastases of gastro-intestinal stromal tumors (GIST) resistant to tyrosine kinase inhibitor (TKI) therapy

Br J Cancer. 2025 May;132(8):716-724. doi: 10.1038/s41416-025-02952-3. Epub 2025 Mar 5.

Abstract

Background: Hepatic metastases of GIST might be the dominant site of progression and resistant to available tyrosine kinase inhibitors (TKIs). Selective internal radiation therapy (SIRT) offers treatment by intratumoral radiation up to 200 Gy. We analyzed the hepatic progression-free survival (H-PFS) in a consecutive patient cohort.

Methods: Twenty-six patients (median age 57.6 years) with biopsy proven liver metastases of GIST were treated by SIRT. All had RECIST documented tumor progression, and 24/26 patients had up to four lines of pretreatment. Mutational status was 'quadruple wildtype' (q-wt, n = 5), KIT exon 11/9/13 in n = 15/4/1 cases and PDGFRα (n = 1). Median follow-up of this retrospective analysis of a prospectively kept database is 33.6 months.

Results: Median H-PFS was 16 months (range, 4-54+ months, 95% CI 6.5-25.4 months) and OS after SIRT was 28 months (95% CI 17.2-28.7 months). Best H-PFS was observed in patients with 'q-wt' at 25 months (range, 6+-54 months, 95% CI 16.2-33.8 months). The worst outcome was for KIT exon 11 mutations plus secondary mutations with 7 months (range, 4-33 months, 95% CI, 4.2-9.8 months).

Conclusions: 90Y-SIRT is a potent treatment for patients with liver metastases of GIST resistant to TKI therapy. In patients with 'q-wt' GIST, SIRT is an option for first-line use.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brachytherapy* / methods
  • Drug Resistance, Neoplasm
  • Female
  • Gastrointestinal Stromal Tumors* / drug therapy
  • Gastrointestinal Stromal Tumors* / genetics
  • Gastrointestinal Stromal Tumors* / pathology
  • Gastrointestinal Stromal Tumors* / radiotherapy
  • Humans
  • Liver Neoplasms* / radiotherapy
  • Liver Neoplasms* / secondary
  • Male
  • Microspheres
  • Middle Aged
  • Mutation
  • Progression-Free Survival
  • Protein Kinase Inhibitors* / therapeutic use
  • Retrospective Studies
  • Tyrosine Kinase Inhibitors
  • Yttrium Radioisotopes* / administration & dosage
  • Yttrium Radioisotopes* / therapeutic use

Substances

  • Yttrium Radioisotopes
  • Protein Kinase Inhibitors
  • Yttrium-90
  • Tyrosine Kinase Inhibitors