title: ALK-Rearranged Non-Small-Cell Lung Cancer Is Associated With a High Rate of Venous Thromboembolism.
abstract: Patients with lung cancer are at increased risk for venous thromboembolism (VTE), particularly those receiving chemotherapy. It is estimated that 8% to 15% of patients with advanced non-small-cell lung cancer (NSCLC) experience a VTE in the course of their disease. The incidence in patients with specific molecular subtypes of NSCLC is unknown. We undertook this review to determine the incidence of VTE in patients with ALK (anaplastic lymphoma kinase)-rearranged NSCLC.
  
  
  
  We identified all patients with ALK-rearranged NSCLC diagnosed and/or treated at the Princess Margaret Cancer Centre (PM CC) in Canada between July 2012 and January 2015. Retrospective data were extracted from electronic medical records. We then included a validation cohort comprising all consecutive patients with ALK-rearranged NSCLC treated in 2 tertiary centers in Israel.
  
  
  
  Within the PM CC cohort, of 55 patients with ALK-rearranged NSCLC, at a median follow-up of 22 months, 23 (42%) experienced VTE. Patients with VTE were more likely to be white (P = .006). The occurrence of VTE was associated with a trend toward worse prognosis (overall survival hazard ratio = 2.88, P = .059). Within the validation cohort (n = 43), the VTE rate was 28% at a median follow-up of 13 months. Combining the cohorts (n = 98), the VTE rate was 36%. Patients with VTE were younger (age 52 vs. 58 years, P = .04) and had a worse Eastern Cooperative Oncology Group performance status (P = .04). VTE was associated with shorter overall survival (hazard ratio = 5.71, P = .01).
  
  
  
  The rate of VTE in our ALK-rearranged cohort was 3- to 5-fold higher than previously reported for the general NSCLC population. This warrants confirmation in larger cohorts.
authors.affiliation: Rabin Medical Center, Petach Tikva, Israel. Electronic address: alonaz@clalit.org.il.
authors.forename: Alona
authors.initials: A
authors.lastname: Zer
authors.affiliation: Rambam Medical Center, Haifa, Israel.
authors.forename: Mor
authors.initials: M
authors.lastname: Moskovitz
authors.affiliation: Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada.
authors.forename: David M
authors.initials: DM
authors.lastname: Hwang
authors.affiliation: Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Anat
authors.initials: A
authors.lastname: Hershko-Klement
authors.affiliation: Rabin Medical Center, Petach Tikva, Israel.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Fridel
authors.affiliation: Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada.
authors.forename: Grzegorz J
authors.initials: GJ
authors.lastname: Korpanty
authors.affiliation: Rabin Medical Center, Petach Tikva, Israel.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dudnik
authors.affiliation: Rabin Medical Center, Petach Tikva, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Peled
authors.affiliation: Rabin Medical Center, Petach Tikva, Israel.
authors.forename: Tzippy
authors.initials: T
authors.lastname: Shochat
authors.affiliation: Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada.
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Leighl
authors.affiliation: Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.affiliation: Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada.
authors.forename: Ronald
authors.initials: R
authors.lastname: Feld
authors.affiliation: Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Ronald
authors.initials: R
authors.lastname: Burkes
authors.affiliation: Rambam Medical Center, Haifa, Israel.
authors.forename: Mira
authors.initials: M
authors.lastname: Wollner
authors.affiliation: Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada.
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.affiliation: Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada.
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
mesh_terms: D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000235:genetics*; D002170:Canada / Q000453:epidemiology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015995:Prevalence; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D054556:Venous Thromboembolism / Q000453:epidemiology* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: Anaplastic lymphoma kinase (ALK); NSCLC; Thrombosis; Venous thromboembolism