title: Clinical characteristics and treatment outcome in a large multicentre observational cohort of PDGFRA exon 18 mutated gastrointestinal stromal tumour patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Medical Oncology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Sheima
authors.initials: S
authors.lastname: Farag
authors.affiliation: The University of Texas MD Anderson Cancer Center, Department of Sarcoma Medical Oncology, 1400 Holcombe Boulevard, Unit 450, FC12.3038, Houston, TX 77030, USA.
authors.forename: Neeta
authors.initials: N
authors.lastname: Somaiah
authors.affiliation: The University of Texas MD Anderson Cancer Center, Department of Radiology, 1515 Holcombe Boulevard, Unit 085, Houston, TX 77030, USA.
authors.forename: Haesun
authors.initials: H
authors.lastname: Choi
authors.affiliation: Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Radiology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Birthe
authors.initials: B
authors.lastname: Heeres
authors.affiliation: The University of Texas MD Anderson Cancer Center, Department of Pathology, 1515 Holcombe Boulevard, Unit 085, Houston, TX 77030, USA.
authors.forename: Wei-Lien
authors.initials: WL
authors.lastname: Wang
authors.affiliation: Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Pathology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Hester
authors.initials: H
authors.lastname: van Boven
authors.affiliation: Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Pathology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Nederlof
authors.affiliation: The University of Texas MD Anderson Cancer Center, Department of Sarcoma Medical Oncology, 1400 Holcombe Boulevard, Unit 450, FC12.3038, Houston, TX 77030, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Benjamin
authors.affiliation: The Radboud University Medical Center, Department of Medical Oncology, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Winette
authors.initials: W
authors.lastname: van der Graaf
authors.affiliation: Erasmus MC - Cancer Institute, Department of Surgical Oncology, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Dirk
authors.initials: D
authors.lastname: Grunhagen
authors.affiliation: University Groningen, University Medical Center Groningen, Department of Medical Oncology, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Boonstra
authors.affiliation: University Groningen, University Medical Center Groningen, Department of Medical Oncology, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Anna K L
authors.initials: AK
authors.lastname: Reyners
authors.affiliation: Leiden University Medical Center, Department of Medical Oncology, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.affiliation: Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Medical Oncology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: n.steeghs@nki.nl.
authors.forename: Neeltje
authors.initials: N
authors.lastname: Steeghs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D013505:Digestive System Surgical Procedures; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy; D009426:Netherlands; D010166:Palliative Care; D011379:Prognosis; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D000068877:Imatinib Mesylate; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: D842V; GIST; Gastrointestinal stromal tumour; Imatinib; PDGFRA exon 18