Sheima Farag1, Neeta Somaiah2, Haesun Choi3, Birthe Heeres4, Wei-Lien Wang5, Hester van Boven6, Petra Nederlof6, Robert Benjamin2, Winette van der Graaf7, Dirk Grunhagen8, Pieter A Boonstra9, Anna K L Reyners9, Hans Gelderblom10, Neeltje Steeghs11. 1. Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Medical Oncology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. 2. The University of Texas MD Anderson Cancer Center, Department of Sarcoma Medical Oncology, 1400 Holcombe Boulevard, Unit 450, FC12.3038, Houston, TX 77030, USA. 3. The University of Texas MD Anderson Cancer Center, Department of Radiology, 1515 Holcombe Boulevard, Unit 085, Houston, TX 77030, USA. 4. Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Radiology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. 5. The University of Texas MD Anderson Cancer Center, Department of Pathology, 1515 Holcombe Boulevard, Unit 085, Houston, TX 77030, USA. 6. Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Pathology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. 7. The Radboud University Medical Center, Department of Medical Oncology, PO Box 9101, 6500 HB Nijmegen, The Netherlands. 8. Erasmus MC - Cancer Institute, Department of Surgical Oncology, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. 9. University Groningen, University Medical Center Groningen, Department of Medical Oncology, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. 10. Leiden University Medical Center, Department of Medical Oncology, P.O. Box 9600, 2300 RC Leiden, The Netherlands. 11. Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Medical Oncology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: n.steeghs@nki.nl.
Abstract
PURPOSE: Patients, platelet-derived growth factor receptor alpha (PDGFRA) D842V-mutated gastrointestinal stromal tumours (GISTs) are known for their insensitivity to imatinib. However, in clinical practice responses have been observed in some patients. We describe the natural history and treatment outcomes in a cohort of PDGFRA exon 18 mutated GIST patients. PATIENTS AND METHODS: A retrospective cohort study was conducted in PDGFRA exon 18 mutation GIST patients treated in six expert centres in the Netherlands and the United States. Two independent radiologists assessed radiological response to imatinib according to Choi's criteria in all patients with measurable disease treated with imatinib in neo-adjuvant or palliative intent. RESULTS: Seventy-one patients with PDGFRA exon 18 mutation were identified of whom 48 patients (69%) had a D842V mutation. Twenty-two (45.8%) D842V-mutated GIST patients received imatinib treatment, 16 had measurable disease. Fourteen out of the 23 (60.9%) patients with non-D842V mutations received imatinib treatment, eight had measurable disease. Two out of 16 (12.5%) D842V-mutated GIST patients had partial response, 3 patients (18.8%) had stable disease and 9 patients (56.3%) had progressive disease as best response. Two patients did not have follow-up computed tomography scans to assess response. Six out of 8 (75%) patients with non-D842V exon 18 mutations had partial response and two (25%) had stable disease as best response. CONCLUSION: Patients with D842V-mutated GISTs can occasionally respond to imatinib. In the absence of better therapeutic options, imatinib should therefore not be universally withheld in patients with this mutation.
PURPOSE:Patients, platelet-derived growth factor receptor alpha (PDGFRA) D842V-mutated gastrointestinal stromal tumours (GISTs) are known for their insensitivity to imatinib. However, in clinical practice responses have been observed in some patients. We describe the natural history and treatment outcomes in a cohort of PDGFRA exon 18 mutated GISTpatients. PATIENTS AND METHODS: A retrospective cohort study was conducted in PDGFRA exon 18 mutation GISTpatients treated in six expert centres in the Netherlands and the United States. Two independent radiologists assessed radiological response to imatinib according to Choi's criteria in all patients with measurable disease treated with imatinib in neo-adjuvant or palliative intent. RESULTS: Seventy-one patients with PDGFRA exon 18 mutation were identified of whom 48 patients (69%) had a D842V mutation. Twenty-two (45.8%) D842V-mutated GISTpatients received imatinib treatment, 16 had measurable disease. Fourteen out of the 23 (60.9%) patients with non-D842V mutations received imatinib treatment, eight had measurable disease. Two out of 16 (12.5%) D842V-mutated GISTpatients had partial response, 3 patients (18.8%) had stable disease and 9 patients (56.3%) had progressive disease as best response. Two patients did not have follow-up computed tomography scans to assess response. Six out of 8 (75%) patients with non-D842V exon 18 mutations had partial response and two (25%) had stable disease as best response. CONCLUSION:Patients with D842V-mutated GISTs can occasionally respond to imatinib. In the absence of better therapeutic options, imatinib should therefore not be universally withheld in patients with this mutation.
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