title: Changes in plasma mass-spectral profile in course of treatment of non-small cell lung cancer patients with epidermal growth factor receptor tyrosine kinase inhibitors.
abstract: BACKGROUND
  Our previous study showed that pretreatment serum or plasma Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry may predict clinical outcome of non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). In this study, plasma proteomic profiles of NSCLC patients were evaluated in the course of EGFR TKIs therapy.
  
  
  METHODS
  Plasma samples were collected at baseline, in the course of gefitinib therapy and at treatment withdrawal. Samples were analyzed by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Acquired spectra were classified by the VeriStrat test into "good" and "poor" profiles. The association between VeriStrat classification and progression-free survival (PFS) and overall survival (OS), and types of clinical progression, was analyzed.
  
  
  RESULTS
  Plasma samples from 111 NSCLC patients treated with gefitinib were processed. VeriStrat "good" classification at baseline correlated with longer PFS (hazard ratio [HR], 0.54; 95% confidence interval, 0.35-0.83; p = 0.005) and OS (HR, 0.40; 95% confidence interval, 0.26-0.61; p < 0.0001), when compared with VeriStrat "poor." Multivariate analysis confirmed longer PFS (HR, 0.52; p = 0.025) and OS (HR, 0.44; p = 0.001) in patients classified as VeriStrat "good", when VeriStrat was considered as a time-dependent variable. About one-third of baseline "good" classifications had changed to "poor" at the time of treatment withdrawal; progression in these patients was associated with the development of new lesions.
  
  
  CONCLUSIONS
  Our findings support the role of VeriStrat in the assistance in treatment selection of NSCLC patients for EGFR TKI therapy and its potential utility in treatment monitoring.
authors.affiliation: Department of Oncology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Lazzari
authors.forename: Anna
authors.initials: A
authors.lastname: Spreafico
authors.forename: Angela
authors.initials: A
authors.lastname: Bachi
authors.forename: Heinrich
authors.initials: H
authors.lastname: Roder
authors.forename: Irene
authors.initials: I
authors.lastname: Floriani
authors.forename: Daniela
authors.initials: D
authors.lastname: Garavaglia
authors.forename: Angela
authors.initials: A
authors.lastname: Cattaneo
authors.forename: Julia
authors.initials: J
authors.lastname: Grigorieva
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Viganò
authors.forename: Cristina
authors.initials: C
authors.lastname: Sorlini
authors.forename: Domenico
authors.initials: D
authors.lastname: Ghio
authors.forename: Maxim
authors.initials: M
authors.lastname: Tsypin
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bulotta
authors.forename: Luca
authors.initials: L
authors.lastname: Bergamaschi
authors.forename: Vanesa
authors.initials: V
authors.lastname: Gregorc
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001798:Blood Proteins / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D004252:DNA Mutational Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D001798:Blood Proteins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib