title: A Novel Neoadjuvant Therapy for Operable Locally Invasive Non-Small-Cell Lung Cancer. Phase I Study of Neoadjuvant Stereotactic Body Radiotherapy. LINNEARRE I (NCT02433574).
abstract: Despite improved staging and surgical techniques, the rate of incomplete resection (R1) of non-small-cell lung cancer (NSCLC) has not significantly decreased. Patients with R1 resection have worse survival compared with those with complete resection (R0). Stereotactic body radiotherapy (SBRT) is a rapid and convenient radiotherapy treatment that delivers high-dose radiotherapy to tumors with high precision while sparing normal organs. Although its efficacy in treating small lung tumors is documented, its use as neoadjuvant therapy for locally advanced (LA) NSCLC has not been examined. We hypothesized that a short course of preoperative SBRT is feasible and can be delivered safely as a neoadjuvant therapy in patients at risk for incomplete resection.
  
  
  
  In this phase I study, 20 patients with cT3 to 4, N0 to 1, M0 NSCLC at risk for incomplete resection will be treated with neoadjuvant SBRT followed by surgery and adjuvant chemotherapy. Four groups of 5 patients will be treated with escalating doses (35, 40, 45, and 50 Gy) in 10 daily fractions. The primary outcome is feasibility (ie, the ability to complete SBRT and surgery as planned; within 7 weeks). Secondary outcomes include acute and late adverse events; R0, R1, and R2 rates; and secondary surrogates of feasibility and safety.
  
  
  
  This study is an important first step in introducing a new therapeutic modality to patients with LA NSCLC that could improve surgical outcomes in the future. If neoadjuvant SBRT is found to be feasible and safe for LA NSCLC, its effect in achieving R0 resection could be investigated in randomized trials.
authors.affiliation: Division of Radiation Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada; Department of Oncology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Nhu-Tram A
authors.initials: NA
authors.lastname: Nguyen
authors.affiliation: Division of Radiation Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada; Department of Oncology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Naghmeh
authors.initials: N
authors.lastname: Isfahanian
authors.affiliation: Department of Oncology, McMaster University, Hamilton, Ontario, Canada; Ontario Clinical Oncology Group, Hamilton, Ontario, Canada.
authors.forename: Gregory
authors.initials: G
authors.lastname: Pond
authors.affiliation: Division of Thoracic Surgery, St Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada; Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Wael
authors.initials: W
authors.lastname: Hanna
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Cutz
authors.affiliation: Division of Radiation Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada; Department of Oncology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Wright
authors.affiliation: Division of Radiation Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada; Department of Oncology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Anand
authors.initials: A
authors.lastname: Swaminath
authors.affiliation: Division of Thoracic Surgery, St Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada; Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Shargall
authors.affiliation: Medical Physics, Juravinski Cancer Centre, Hamilton, Ontario, Canada.
authors.forename: Tom
authors.initials: T
authors.lastname: Chow
authors.affiliation: Medical Physics, Juravinski Cancer Centre, Hamilton, Ontario, Canada.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wierzbicki
authors.affiliation: Division of Radiation Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada; Department of Oncology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Gordon
authors.initials: G
authors.lastname: Okawara
authors.affiliation: Division of Radiation Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada; Department of Oncology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Kimmen
authors.initials: K
authors.lastname: Quan
authors.affiliation: Department of Surgery, McMaster University, Hamilton, Ontario, Canada; Division of Medical Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Finley
authors.affiliation: Department of Oncology, McMaster University, Hamilton, Ontario, Canada; Division of Medical Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada.
authors.forename: Rosalyn
authors.initials: R
authors.lastname: Juergens
authors.affiliation: Division of Radiation Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada; Department of Oncology, McMaster University, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: theos.tsakiridis@hhsc.ca.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Tsakiridis
mesh_terms: D000328:Adult; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D003131:Combined Modality Therapy; D054796:Drug Dosage Calculations; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011013:Pneumonectomy; D016634:Radiosurgery; D016896:Treatment Outcome
keywords: Borderline resectable NSCLC; Feasibility and safety; Locally advanced non–small-cell lung cancer; Lung cancer surgery; Neoadjuvant SBRT