title: Short report: interim safety results for a phase II trial measuring the integration of stereotactic ablative radiotherapy (SABR) plus surgery for early stage non-small cell lung cancer (MISSILE-NSCLC).
abstract: A phase II trial was launched to evaluate if neoadjuvant stereotactic ablative radiotherapy (SABR) before surgery improves oncologic outcomes in patients with stage I non-small cell lung cancer (NSCLC). We report a mandated interim safety analysis for the first 10 patients who completed protocol treatment. Operable patients with biopsy-proven T1-2 N0 NSCLC were eligible. SABR was delivered using a risk-adapted fractionation (54Gy/3 fractions, 55/5 or 60/8). Surgical resection was planned 10 weeks later at a high-volume center (>200 lung cancer resections annually). Patients were imaged with dynamic positron emission tomography-computed tomography scans using18F-fludeoxyglucose (18F-FDG-PET CT) and dynamic contrast-enhanced CT before SABR and again before surgery. Toxicity was recorded using CTCAE version 4.0. Twelve patients were enrolled between 09/2014 and 09/2015. Two did not undergo surgery, due to patient or surgeon preference; neither patient has developed toxicity or recurrence. For the 10 patients completing both treatments, median age was 70 (range: 54-76), 60% had T1 disease, and 60% had adenocarcinoma. Median FEV1was 73% predicted (range: 54-87%). Median time to surgery post-SABR was 10.1 weeks (range: 9.3-15.6 weeks). Surgery consisted of lobectomy (n = 8) or wedge resection (n = 2). Median follow-up post-SABR was 6.3 months. After combined treatment, the rate of acute grade 3-4 toxicity was 10%. There was no post-operative mortality at 90 days. The small sample size included herein precludes any definitive conclusions regarding overall toxicity rates until larger datasets are available. However, these data may inform others who are designing or conducting similar trials.
  
  
  BACKGROUND
  NCT02136355 . Registered 8 May 2014.
authors.affiliation: Department of Radiation Oncology, London Health Sciences Centre, London, Canada. David.Palma@lhsc.on.ca.|Department of Oncology, Western University, London, Canada. David.Palma@lhsc.on.ca.
authors.forename: David A
authors.initials: DA
authors.lastname: Palma
authors.affiliation: Department of Radiation Oncology, London Health Sciences Centre, London, Canada.
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Nguyen
authors.affiliation: Department of Pathology, Western University, London, Canada.
authors.forename: Keith
authors.initials: K
authors.lastname: Kwan
authors.affiliation: Department of Oncology, Western University, London, Canada.|Department of Medical Biophysics, Western University, London, Canada.|Department of Physics and Engineering, London Health Sciences Centre, London, Canada.
authors.forename: Stewart
authors.initials: S
authors.lastname: Gaede
authors.affiliation: Department of Radiology, Western University, London, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Landis
authors.affiliation: Department of Surgery, Division of Thoracic Surgery, Western University, London, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Malthaner
authors.affiliation: Department of Surgery, Division of Thoracic Surgery, Western University, London, Canada.
authors.forename: Dalilah
authors.initials: D
authors.lastname: Fortin
authors.affiliation: Department of Radiation Oncology, London Health Sciences Centre, London, Canada.|Department of Oncology, Western University, London, Canada.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Louie
authors.affiliation: Department of Surgery, Division of Thoracic Surgery, Western University, London, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Frechette
authors.affiliation: Department of Radiation Oncology, London Health Sciences Centre, London, Canada.|Department of Oncology, Western University, London, Canada.
authors.forename: George B
authors.initials: GB
authors.lastname: Rodrigues
authors.affiliation: Department of Radiation Oncology, London Health Sciences Centre, London, Canada.|Department of Oncology, Western University, London, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Yaremko
authors.affiliation: Department of Radiation Oncology, London Health Sciences Centre, London, Canada.|Department of Oncology, Western University, London, Canada.
authors.forename: Edward
authors.initials: E
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, London Health Sciences Centre, London, Canada.|Department of Oncology, Western University, London, Canada.
authors.forename: A Rashid
authors.initials: AR
authors.lastname: Dar
authors.affiliation: Department of Medical Biophysics, Western University, London, Canada.|Imaging Program, Lawson Health Research Institute, London, Canada.
authors.forename: Ting-Yim
authors.initials: TY
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, London Health Sciences Centre, London, Canada.
authors.forename: Al
authors.initials: A
authors.lastname: Gratton
authors.affiliation: Department of Radiation Oncology, London Health Sciences Centre, London, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Warner
authors.affiliation: Department of Oncology, Western University, London, Canada.|Department of Medical Biophysics, Western University, London, Canada.
authors.forename: Aaron
authors.initials: A
authors.lastname: Ward
authors.affiliation: Department of Surgery, Division of Thoracic Surgery, Western University, London, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Inculet
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy* / Q000601:surgery*; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000532:radiotherapy* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods; D011013:Pneumonectomy / Q000009:adverse effects / Q000379:methods; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome
keywords: Lung cancer; Non-small cell; Stereotactic ablative radiotherapy; Stereotactic body radiotherapy; Surgery