Yttrium-90 resin microspheres selective internal radiation therapy (90Y-SIRT) is a potent treatment for patients with liver metastases due to gastrointestinal stromal tumors (GIST) resistant to TKI therapy, according to study findings published in British Journal of Cancer.
Furthermore, patients with quadruple wildtype mutation GIST have the option for SIRT in first-line use. This study also represents the largest reporting on the use of SIRT in patients with GIST, the study authors note.
90Y-SIRT is a local treatment delivering radiation doses up to 200 Gy to liver metastases.
“Our study documents that SIRT is a very valuable treatment in GIST patients suffering from progressive liver metastasis which cannot or no longer be controlled by TKI therapy offering a median of 16 months of hepatic progression-free survival,” wrote study author Dr. Peter Hohenberger and colleagues. “The approach is not a prefinal attempt in an otherwise desperate treatment situation.
Hohenberger works for the Division of Surgical Oncology and Thoracic Surgery, University Medical Center Mannheim, Medical Faculty Mannheim – Heidelberg University, Heidelberg, Germany.
After a median follow-up time of 25 months, the median hepatic progression-free survival — the length of time before liver tumors progress — after SIRT was 16 months. Patients with quadruple wildtype mutation had the best median hepatic progression-free survival at 25 months, while those with KIT exon 11 mutations plus secondary mutations had the worst at 7 months.
In addition, the median overall survival after SIRT was 28 months, with six patients alive between six and 78 months. Overall survival after diagnosis of the primary tumor was 102.5 months. The median progression-free interval for patients with extrahepatic disease was six months, and there was no significant correlation between the time to metastatic disease.
Side Effects and Trial Design
Three patients developed major complications following SIRT, with gastric ulcers occurring at 6, 7 and 17 months that required surgical resection. One patient needed emergency surgery for ulcer perforation grade 4 (life-threatening), while the other two underwent elective segmental gastric resection for chronic ulcers grade 3 (severe). One patient was receiving Sutent (sunitinib) and another Nexavar (sorafenib) for extrahepatic tumor progression. Another patient developed cholangitis grade 2 (moderate), which was managed conservatively.
Within three months after SIRT, blood tests showed grade 3 toxicity for bilirubin in one patient, who also had grade 2 toxicity for aspartate aminotransferase and gamma-glutamyl transferase. Five patients developed grade 2 toxicity, affecting gamma-glutamyl transferase in four patients and bilirubin in one. Sixteen patients experienced grade 1 (mild) toxicity, commonly showing elevated levels of aspartate aminotransferase (14 patients), alanine aminotransferase (12 patients), alkaline phosphatase (12 patients), gamma-glutamyl transferase (9 patients), bilirubin (12 patients) and creatinine (9 patients), often in combination. No patients showed changes in international normalized ratio between pre-SIRT and post-SIRT values. Six patients (23.1%) did not experience any side effects.
The study included 26 patients with unresectable liver metastases of gastrointestinal stromal tumors (GIST) who underwent SIRT with 90Y-SIRT resin microspheres from February 2008 to March 2022. The patients, ages 17 to 72, had liver metastases that were not amenable to surgery or radio-frequency ablation.
All patients had an ECOG score of 0 or 1 — describes patients who are either fully active (0) or restricted in physically strenuous activity but still ambulatory and able to do light work (1) — and were treated with tyrosine kinase inhibitors (TKIs) before SIRT. Standard TKIs failed to control liver tumor progression in most cases. The median number of prior treatments before SIRT was three, including imatinib, sunitinib and regorafenib. Three patients continued TKI treatment during SIRT. SIRT was not recommended for patients with extrahepatic disease progression.
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