title: Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials.
abstract: BACKGROUND
  The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials.
  
  
  METHODS
  Eligible patients in the STARS and ROSEL studies were those with clinical T1-2a (<4 cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling. We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint. Both trials are registered with ClinicalTrials.gov (STARS: NCT00840749; ROSEL: NCT00687986).
  
  
  RESULTS
  58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40·2 months (IQR 23·0-47·3) for the SABR group and 35·4 months (18·9-40·7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85-100) in the SABR group compared with 79% (64-97) in the surgery group (hazard ratio [HR] 0·14 [95% CI 0·017-1·190], log-rank p=0·037). Recurrence-free survival at 3 years was 86% (95% CI 74-100) in the SABR group and 80% (65-97) in the surgery group (HR 0·69 [95% CI 0·21-2·29], log-rank p=0·54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three [10%] chest wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib fracture). No patients given SABR had grade 4 events or treatment-related death. In the surgery group, one (4%) patient died of surgical complications and 12 (44%) patients had grade 3-4 treatment-related adverse events. Grade 3 events occurring in more than one patient in the surgery group were dyspnoea (four [15%] patients), chest pain (four [15%] patients), and lung infections (two [7%]).
  
  
  CONCLUSIONS
  SABR could be an option for treating operable stage I NSCLC. Because of the small patient sample size and short follow-up, additional randomised studies comparing SABR with surgery in operable patients are warranted.
  
  
  BACKGROUND
  Accuray Inc, Netherlands Organisation for Health Research and Development, NCI Cancer Center Support, NCI Clinical and Translational Science Award.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: jychang@mdanderson.org.
authors.forename: Joe Y
authors.initials: JY
authors.lastname: Chang
authors.affiliation: Department of Radiation Oncology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Suresh
authors.initials: S
authors.lastname: Senan
authors.affiliation: Department of Cardiothoracic Surgery, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Marinus A
authors.initials: MA
authors.lastname: Paul
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Reza J
authors.initials: RJ
authors.lastname: Mehran
authors.affiliation: Department of Radiation Oncology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Louie
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Balter
authors.affiliation: Department of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen
authors.affiliation: Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: McRae
authors.affiliation: Department of Radiation Oncology, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Joachim
authors.initials: J
authors.lastname: Widder
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Pulmonary Diseases, Catharina Hospital, Eindhoven, Netherlands.
authors.forename: Ben E E M
authors.initials: BE
authors.lastname: van den Borne
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Munsell
authors.affiliation: Department of Radiation Oncology, Catharina Hospital, Eindhoven, Netherlands.
authors.forename: Coen
authors.initials: C
authors.lastname: Hurkmans
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Berry
authors.affiliation: Department of Biometrics, Netherlands Cancer Institute, Amsterdam, Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: van Werkhoven
authors.affiliation: Phoenix CyberKnife and Radiation Oncology Center, Phoenix, AZ, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Kresl
authors.affiliation: Department of Pulmonary Diseases, Maastricht University Medical Center, Netherlands.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Dingemans
authors.affiliation: Kona Medical, Bellevue, WA, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Dawood
authors.affiliation: Department of Radiation Oncology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Haasbeek
authors.affiliation: Department of Radiation Oncology, CHI St Luke's Health, Houston, TX, USA.
authors.forename: Larry S
authors.initials: LS
authors.lastname: Carpenter
authors.affiliation: Department of Radiation Oncology, Catharina Hospital, Eindhoven, Netherlands.
authors.forename: Katrien
authors.initials: K
authors.lastname: De Jaeger
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.affiliation: Department of Radiation Oncology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Slotman
authors.affiliation: Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D038481:Anterior Temporal Lobectomy; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D009367:Neoplasm Staging; D009426:Netherlands; D016634:Radiosurgery; D016896:Treatment Outcome