title: Association of Delayed Adjuvant Chemotherapy With Survival After Lung Cancer Surgery.
abstract: OBJECTIVE
  Adjuvant chemotherapy offers a survival benefit to a number of staging scenarios in non-small-cell lung cancer. Variable recovery from lung cancer surgery may delay a patient's ability to tolerate adjuvant chemotherapy, yet the urgency of chemotherapy initiation is unclear.
  
  
  OBJECTIVE
  To assess differences in survival according to the time interval between non-small-cell lung cancer resection and the initiation of postoperative chemotherapy to determine the association between adjuvant treatment timing and efficacy.
  
  
  METHODS
  This retrospective observational study examined treatment-naive patients with completely resected non-small-cell lung cancer who received postoperative multiagent chemotherapy between 18 and 127 days after resection between January 2004 and December 2012. The study population was limited to patients with lymph node metastases, tumors 4 cm or larger, or local extension. Patients were identified from the National Cancer Database, a hospital-based tumor registry that captures more than 70% of incident lung cancer cases in the United States. The association between time to initiation of adjuvant chemotherapy and survival was evaluated using Cox models with restricted cubic splines.
  
  
  METHODS
  Adjuvant chemotherapy administered at different time points after surgery.
  
  
  METHODS
  Effectiveness of adjuvant chemotherapy according to time to initiation after surgery.
  
  
  RESULTS
  A total of 12 473 patients (median [interquartile range] age, 64 [57-70] years) were identified: 3073 patients (25%) with stage I disease; 5981 patients (48%), stage II; and 3419 patients (27%), stage III. A Cox model with restricted cubic splines identified the lowest mortality risk when chemotherapy was started 50 days postoperatively (95% CI, 39-56 days). Initiation of chemotherapy after this interval (57-127 days; ie, the later cohort) did not increase mortality (hazard ratio [HR], 1.037; 95% CI, 0.972-1.105; P = .27). Furthermore, in a Cox model of 3976 propensity-matched pairs, patients who received chemotherapy during the later interval had a lower mortality risk than those treated with surgery only (HR, 0.664; 95% CI, 0.623-0.707; P < .001).
  
  
  CONCLUSIONS
  In the National Cancer Database, adjuvant chemotherapy remained efficacious when started 7 to 18 weeks after non-small-cell lung cancer resection. Patients who recover slowly from non-small-cell lung cancer surgery may still benefit from delayed adjuvant chemotherapy started up to 4 months after surgery.
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Salazar
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Rosen
authors.affiliation: Yale School of Public Health, New Haven, Connecticut.
authors.forename: Zuoheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Brian N
authors.initials: BN
authors.lastname: Arnold
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Thomas
authors.affiliation: Medical Oncology, Yale School of Medicine and Yale Cancer Center, New Haven, Connecticut.
authors.forename: Roy S
authors.initials: RS
authors.lastname: Herbst
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Kim
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Detterbeck
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Blasberg
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Boffa
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant / Q000379:methods; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011013:Pneumonectomy / Q000379:methods; D011184:Postoperative Period; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology