title: Clinical impact of mutation fraction in epidermal growth factor receptor mutation positive NSCLC patients.
abstract: BACKGROUND
  We examined clinical outcomes in a population-based cohort of EGFR mutant advanced NSCLC patients, exploring the potential role of factors including tumour EGFR mutation fraction and cellularity in predicting outcomes.
  
  
  METHODS
  A cohort of patients with EGFR mutant advanced NSCLC was identified (N =2 93); clinical outcomes, pathologic and treatment details were collected. Tumour response was determined from radiology and clinical notes. Association between demographic and pathologic variables EGFR TKI response, time to treatment failure (TTF) and overall survival (OS) was examined using logistic regression and proportional hazards regression. EGFR TKI response rates were summarised by percent mutation fraction to explore their association.
  
  
  RESULTS
  Higher mutation fraction was associated with greater EGFR TKI response rate (odds ratio 1.58, 95% CI = 1.21-2.07, P = 0.0008), longer TTF (hazard ratio 0.80, 95% CI = 0.68-0.92, P = 0.003) and better OS (hazard ratio 0.81, 95% CI = 0.67-0.99, P = 0.04). However, even in patients with ⩽ 5% mutation fraction, response rate was 34%. Females had longer TTF (P = 0.02).
  
  
  CONCLUSIONS
  EGFR mutation fraction in tumour samples was significantly associated with response, TTF and OS. Despite this, no lower level of mutation fraction was detected for which EGFR TKI should be withheld in those with activating EGFR mutations.
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre/University Health Network, 5-105 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: Petra
authors.initials: P
authors.lastname: Martin
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre/University Health Network, 5-105 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Shiau
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre/University Health Network, 5-105 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: Maria
authors.initials: M
authors.lastname: Pasic
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre/University Health Network, 5-105 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: Ming
authors.initials: M
authors.lastname: Tsao
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre/University Health Network, 5-105 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre/University Health Network, 5-105 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lin
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre/University Health Network, 5-105 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: Roxana
authors.initials: R
authors.lastname: Tudor
authors.affiliation: Odette Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Susanna
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Credit Valley Hospital, Mississauga, Ontario, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Higgins
authors.affiliation: Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Ronald
authors.initials: R
authors.lastname: Burkes
authors.affiliation: Mackenzie Health Centre, Richmond Hill, Ontario, Canada.
authors.forename: Matilda
authors.initials: M
authors.lastname: Ng
authors.affiliation: Mississauga Hospital, Toronto, Ontario, Canada.
authors.forename: Saroosh
authors.initials: S
authors.lastname: Arif
authors.affiliation: Juravinski Cancer Centre, Hamilton, Ontario, Canada.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Ellis
authors.affiliation: Grand River Regional Cancer Centre, Kitchener, Ontario, Canada.
authors.forename: Stacy
authors.initials: S
authors.lastname: Hubay
authors.affiliation: London Regional Cancer Centre, London, Ontario, Canada.
authors.forename: Sara
authors.initials: S
authors.lastname: Kuruvilla
authors.affiliation: The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Laurie
authors.affiliation: Toronto East General Hospital, Toronto, Ontario, Canada.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Toronto General Hospital, Toronto, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Hwang
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre/University Health Network, 5-105 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: Anthea
authors.initials: A
authors.lastname: Lau
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre/University Health Network, 5-105 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre/University Health Network, 5-105 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Le
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre/University Health Network, 5-105 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Leighl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors