title: Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection.
abstract: OBJECTIVE
  Surgical resection of gastric cancer has produced suboptimal survival despite multiple randomized trials that used postoperative chemotherapy or more aggressive surgical procedures. We performed a randomized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure (LRF) following surgery. We originally reported results with 4-year median follow-up. This update, with a more than 10-year median follow-up, presents data on failure patterns and second malignancies and explores selected subset analyses.
  
  
  METHODS
  In all, 559 patients with primaries ≥ T3 and/or node-positive gastric cancer were randomly assigned to observation versus radiochemotherapy after R0 resection. Fluorouracil and leucovorin were administered before, during, and after radiotherapy. Radiotherapy was given to all LRF sites to a dose of 45 Gy.
  
  
  RESULTS
  Overall survival (OS) and relapse-free survival (RFS) data demonstrate continued strong benefit from postoperative radiochemotherapy. The hazard ratio (HR) for OS is 1.32 (95% CI, 1.10 to 1.60; P = .0046). The HR for RFS is 1.51 (95% CI, 1.25 to 1.83; P < .001). Adjuvant radiochemotherapy produced substantial reduction in both overall relapse and locoregional relapse. Second malignancies were observed in 21 patients with radiotherapy versus eight with observation (P = .21). Subset analyses show robust treatment benefit in most subsets, with the exception of patients with diffuse histology who exhibited minimal nonsignificant treatment effect.
  
  
  CONCLUSIONS
  Intergroup 0116 (INT-0116) demonstrates strong persistent benefit from adjuvant radiochemotherapy. Toxicities, including second malignancies, appear acceptable, given the magnitude of RFS and OS improvement. LRF reduction may account for the majority of overall relapse reduction. Adjuvant radiochemotherapy remains a rational standard therapy for curatively resected gastric cancer with primaries T3 or greater and/or positive nodes.
authors.affiliation: Radiation Oncology Center of Olathe, 20375 West 151st St, Suite 180, Olathe, KS 66061, USA. s_smalley@msn.com
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Smalley
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Benedetti
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Haller
authors.forename: Scott A
authors.initials: SA
authors.lastname: Hundahl
authors.forename: Norman C
authors.initials: NC
authors.lastname: Estes
authors.forename: Jaffer A
authors.initials: JA
authors.lastname: Ajani
authors.forename: Leonard L
authors.initials: LL
authors.lastname: Gunderson
authors.forename: Bryan
authors.initials: B
authors.lastname: Goldman
authors.forename: James A
authors.initials: JA
authors.lastname: Martenson
authors.forename: J Milburn
authors.initials: JM
authors.lastname: Jessup
authors.forename: Grant N
authors.initials: GN
authors.lastname: Stemmermann
authors.forename: Charles D
authors.initials: CD
authors.lastname: Blanke
authors.forename: John S
authors.initials: JS
authors.lastname: Macdonald
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D059186:Chemoradiotherapy, Adjuvant; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005743:Gastrectomy / Q000379:methods*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery* / Q000628:therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D002955:Leucovorin; D005472:Fluorouracil