Response to nilotinib as a first-line treatment for metastatic gastrointestinal stromal tumors.

PURPOSE: Effective and safe treatment options are needed for patients with advanced gastrointestinal stromal tumors (GIST) who are initially unresponsive to the tyrosine kinase inhibitor (TKI) imatinib, or develop acquired secondary imatinib resistance. CASE REPORT: We report a 39-year-old woman with primary rectal GIST who underwent abdominoperineal resection in December 2004, achieving R0 margins. In August 2009, the patient was referred to our clinic, and we detected metastatic GIST of the liver, as well as peritoneal and gluteal lesions. The patient was treated with imatinib 400 mg/day for 3 weeks and subsequently switched to nilotinib (400 mg bid) after enrolling in a clinical trial. After 8 weeks of nilotinib treatment, a response was observed in the liver metastasis, and metabolic activity was no longer detected. Also, the gluteal and peritoneal lesions were no longer detected. After 16 weeks of nilotinib treatment, a cystic mass was identified in the liver metastasis. Tumor rupture was considered a strong possibility, prompting resection of the liver metastasis. Greater than 80% of the resected tumor mass was necrotic, consistent with the lack of metabolism observed 8 weeks prior. The patient resumed nilotinib treatment (400 mg bid) shortly after surgery and continues treatment while remaining disease-free for more than 9 months with normal liver function. CONCLUSION: This is the first report demonstrating the feasibility of nilotinib (400 mg bid) for the first-line treatment of metastatic GIST. Furthermore, these results underscore that responses to TKIs may be underestimated by Response Evaluation Criteria in Solid Tumors.

Perfusion patterns of metastatic gastrointestinal stromal tumor lesions under specific molecular therapy.

RATIONALE AND OBJECTIVE: The aim of this pilot study was the evaluation of CT perfusion patterns in metastatic GIST lesions under specific molecular therapy with sunitinib or imatinib both in responders and non-responders. PATIENTS AND METHODS: 24 patients with metastatic GIST under tyrosine kinase inhibition were retrospectively evaluated. A total of 46 perfusion and venous phase CT scans were acquired. Volume of distribution, blood flow, blood volume, permeability and hepatic perfusion index measurements of metastatic lesions were carried out. Lesions were classified as "good response" or "poor response" to therapy, and perfusion parameters were compared for these two types of lesions. RESULTS: 24 patients were evaluated. In the extrahepatic abdominal lesions (N = 15), good responders showed significant lower perfusion values than poor responders (volume of distribution: 3.3 ± 2.0 vs. 13.0 ± 1.8 ml/100ml, p = 0.001). The same tendency was observed in intrahepatic lesions (N = 31) (liver volume of distribution: 2.1 ± 0.3 vs. 7.1 ± 1.3 ml/100ml, p = 0.003); (hepatic perfusion index: 24.3 ± 7.9 vs. 76.1 ± 1.5%, p = 0.0001). CONCLUSION: Our data indicate that there are characteristic perfusion patterns of metastatic GIST lesions showing a good or poor response to molecular pharmacotherapy. Perfusion should be further evaluated in cross-sectional imaging studies as a possible biomarker for treatment response in targeted therapies of GIST.