title: A phase 2 cooperative group adjuvant trial using a biomarker-based decision algorithm in patients with stage I non-small cell lung cancer (SWOG-0720, NCT00792701).
abstract: BACKGROUND
  This cooperative group adjuvant phase 2 trial in patients with completely resected stage I non-small cell lung cancer with tumor diameters measuring ≥ 2 cm was designed to assess the feasibility and preliminary efficacy of assigning patients to therapy or observation using a molecularly based decision algorithm.
  
  
  METHODS
  At least a lobectomy and sampling of recommended mediastinal lymph node stations, good Zubrod performance status, adequate organ function, and a formalin-fixed and paraffin-embedded tumor specimen were required. Excision repair cross-complementing group 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) were analyzed using immunofluorescence-based in situ automated quantitative image analysis and categorized as high or low using prespecified cutoff values. Patients with high ERCC1 and RRM1 were assigned to observation and all others to 4 cycles of cisplatin and gemcitabine. Feasibility was defined as treatment assignment within 84 days from surgery in > 85% of patients. Secondary objectives were to estimate the 2-year survival.
  
  
  RESULTS
  Treatment assignment met the feasibility criteria in 88% of eligible patients (71 of 81 patients). The collective 2-year disease-free and overall survival rates were 80% and 96%, respectively. Protein levels for RRM1 fell within the previously established range, ERCC1 levels were slightly lower than expected, and they were significantly correlated (correlation coefficient, 0.4). The rates of assignment of patients to observation (22%) and chemotherapy (78%) were as expected.
  
  
  CONCLUSIONS
  Gene expression analysis for treatment assignment is feasible. Survival results are encouraging and require future validation. Real-time performance of quantitative in situ ERCC1 and RRM1 analysis requires further development.
authors.affiliation: Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Gerold
authors.initials: G
authors.lastname: Bepler
authors.forename: Ralph G
authors.initials: RG
authors.lastname: Zinner
authors.forename: James
authors.initials: J
authors.lastname: Moon
authors.forename: Royce
authors.initials: R
authors.lastname: Calhoun
authors.forename: Kemp
authors.initials: K
authors.lastname: Kernstine
authors.forename: Charles C
authors.initials: CC
authors.lastname: Williams
authors.forename: Philip C
authors.initials: PC
authors.lastname: Mack
authors.forename: Vasco
authors.initials: V
authors.lastname: Oliveira
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zheng
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stella
authors.forename: Mary W
authors.initials: MW
authors.lastname: Redman
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003657:Decision Making; D018572:Disease-Free Survival; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D057285:Precision Medicine; D012262:Ribonucleoside Diphosphate Reductase; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; C071447:ERCC1 protein, human; D004720:Endonucleases
keywords: ERCC1 (excision repair cross-complementing group 1); RRM1 (ribonucleotide reductase M1); adjuvant therapy; lung cancer; personalized medicine
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