title: Surgical management of patients with progressing metastatic gastrointestinal stromal tumors receiving sunitinib treatment: A prospective cohort study.
abstract: BACKGROUND
  For selected patients with metastatic gastrointestinal stromal tumor (GIST) who have received first-line imatinib (IM) and are undergoing cytoreductive surgery, response to IM at time of surgery correlates with resection completeness as well as favorable progression-free survival (PFS) and overall survival (OS). However, surgical impact in GIST patients receiving second-line sunitinib (SU) is still not well clarified.
  
  
  METHODS
  Between 2001 and 2014, 86 of 311 metastatic GIST patients received SU. Among them, 69 patients eventually experienced progression. Twenty-six patients who experienced local progression (LP) and underwent surgeries were investigated. Each tumor was assessed for genetic alterations before and after surgery.
  
  
  RESULTS
  Twenty-six GIST patients receiving SU who experienced LP underwent surgery after a median of 6.2 months of SU use. Nineteen patients (73.1%) had undergone prior surgery on IM. The complication rate was 15.3%, and no additional operation was required for GIST patients receiving SU and experiencing LP who underwent surgery. The median PFS and OS times after surgery and start of SU were 5.2 and 18.9 months, respectively, and 16.4 and 26.0 months, respectively (median follow-up of 15.2 months). GIST patients receiving SU with LP (N = 26) may gain a significant PFS and OS benefit with surgery when compared with those not undergoing surgery (N = 43) (p = 0.003 and p = 0.02, respectively). Secondary exon 17 mutation occurred commonly and might explain SU resistance (8/23; 34.8%).
  
  
  CONCLUSIONS
  Surgery is feasible in highly selected patients with metastatic GIST who are receiving SU and experiencing LP. Those patients may also have significantly prolonged PFS and OS after surgery. Secondary exon 17 mutation might explain SU resistance.
authors.affiliation: GIST Team, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, Taiwan. Electronic address: yehchunnan@gmail.com.
authors.forename: Chun-Nan
authors.initials: CN
authors.lastname: Yeh
authors.affiliation: GIST Team, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, Taiwan.
authors.forename: Shang-Yu
authors.initials: SY
authors.lastname: Wang
authors.affiliation: GIST Team, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, Taiwan.
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Taiwan.
authors.forename: Yen-Yang
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Cancer Prevention and Education Foundation, Taiwan.
authors.forename: Ching-Ting
authors.initials: CT
authors.lastname: Liu
authors.affiliation: General Surgery Department, Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Kun-Chun
authors.initials: KC
authors.lastname: Chiang
authors.affiliation: GIST Team, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, Taiwan.
authors.forename: Tsung-Wen
authors.initials: TW
authors.lastname: Chen
authors.affiliation: GIST Team, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, Taiwan.
authors.forename: Yu-Yin
authors.initials: YY
authors.lastname: Liu
authors.affiliation: GIST Team, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, Taiwan.
authors.forename: Ta-Sen
authors.initials: TS
authors.lastname: Yeh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D065426:Cytoreduction Surgical Procedures / Q000379:methods*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D011183:Postoperative Complications / Q000453:epidemiology / Q000209:etiology; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: GIST; Glivec; Metastatic gastrointestinal stromal tumors; Sunitinib