title: External beam radiation therapy for locally advanced and metastatic gastrointestinal stromal tumors.
abstract: BACKGROUND
  The role of radiation therapy (RT) in the management of gastrointestinal stromal tumors (GIST) is not well described. Here we report our institutional experience for patients with locally advanced or metastatic GIST treated with RT.
  
  
  METHODS
  Between 1997 and 2012, 15 patients with 22 GISTs were treated with RT at our center. The median age was 68 (range, 41-86). Fourteen patients had stage IV disease and 1 patient had stage IIIB disease, per the American Joint Committee on Cancer (AJCC), 7th Edition staging. Tumors were in a variety of locations, and were most commonly referred for palliative treatment. Eighteen of 22 tumors were symptomatic. Prior to RT, 14 of 15 patients received systemic therapy in the form of tyrosine kinase inhibitors (TKIs) (n = 11), chemotherapy (n = 4), or both (n = 1). TKIs were used concurrently for nine tumors (40.9%). No tumors were treated with concurrent chemotherapy. Several fractionation schemes were used, most commonly 3 Gy × 10 (n = 8). Local progression-free survival and overall survival were estimated using the Kaplan-Meier method. Acute toxicity was graded per Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
  
  
  RESULTS
  The median follow-up was 5.1 months (range, 1.3-28.3). At the time of analysis, 12 patients have died (80%). The estimated 6-month local progression-free survival and overall survival were 57.0% and 57.8%, respectively. Among the 18 symptomatic tumors, at least partial palliation was achieved in 17 (94.4%), and symptoms were completely palliated in eight (44.4%). Treatment was well tolerated, with no Grade 4 or 5 toxicities. There was no Grade ≥3 toxicity associated with concurrent TKI use.
  
  
  CONCLUSIONS
  In this largest series to date of GISTs treated with RT, a high rate of palliation was achieved for symptomatic tumors in a cohort of advanced stage, heavily pretreated patients. Treatment was well tolerated, and concurrent use of tyrosine kinase inhibitor therapy was not associated with additional toxicity. While follow-up was short, durable control is possible for some patients, providing evidence that GIST is not universally radioresistant and that RT can provide an important benefit in patients with progressive or metastatic disease.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. wua@mskcc.org.
authors.forename: John J
authors.initials: JJ
authors.lastname: Cuaron
authors.forename: Karyn A
authors.initials: KA
authors.lastname: Goodman
authors.forename: Nancy
authors.initials: N
authors.lastname: Lee
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D046152:Gastrointestinal Stromal Tumors / Q000473:pathology* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010166:Palliative Care / Q000379:methods; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011878:Radiotherapy / Q000379:methods*; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D011505:Protein-Tyrosine Kinases