title: Canadian Phase III Randomized Trial of Stereotactic Body Radiotherapy Versus Conventionally Hypofractionated Radiotherapy for Stage I, Medically Inoperable Non-Small-Cell Lung Cancer - Rationale and Protocol Design for the Ontario Clinical Oncology Group (OCOG)-LUSTRE Trial.
abstract: We describe a Canadian phase III randomized controlled trial of stereotactic body radiotherapy (SBRT) versus conventionally hypofractionated radiotherapy (CRT) for the treatment of stage I medically inoperable non-small-cell lung cancer (OCOG-LUSTRE Trial). Eligible patients are randomized in a 2:1 fashion to either SBRT (48 Gy in 4 fractions for peripherally located lesions; 60 Gy in 8 fractions for centrally located lesions) or CRT (60 Gy in 15 fractions). The primary outcome of the study is 3-year local control, which we hypothesize will improve from 75% with CRT to 87.5% with SBRT. With 85% power to detect a difference of this magnitude (hazard ratio = 0.46), a 2-sided α = 0.05 and a 2:1 randomization, we require a sample size of 324 patients (216 SBRT, 108 CRT). Important secondary outcomes include overall survival, disease-free survival, toxicity, radiation-related treatment death, quality of life, and cost-effectiveness. A robust radiation therapy quality assurance program has been established to assure consistent and high quality SBRT and CRT delivery. Despite widespread interest and adoption of SBRT, there still remains a concern regarding long-term control and risks of toxicity (particularly in patients with centrally located lesions). The OCOG-LUSTRE study is the only randomized phase III trial testing SBRT in a medically inoperable population, and the results of this trial will attempt to prove that the benefits of SBRT outweigh the potential risks.
authors.affiliation: Department of Oncology, McMaster University, Hamilton, Ontario, Canada. Electronic address: swaminath@hhsc.ca.
authors.forename: Anand
authors.initials: A
authors.lastname: Swaminath
authors.affiliation: Department of Medical Physics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wierzbicki
authors.affiliation: Department of Oncology, McMaster University, Hamilton, Ontario, Canada; Ontario Clinical Oncology Group, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sameer
authors.initials: S
authors.lastname: Parpia
authors.affiliation: Department of Oncology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: James R
authors.initials: JR
authors.lastname: Wright
authors.affiliation: Department of Oncology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Theodoros K
authors.initials: TK
authors.lastname: Tsakiridis
authors.affiliation: Department of Oncology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Okawara
authors.affiliation: Department of Radiation Oncology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Vijayananda
authors.initials: V
authors.lastname: Kundapur
authors.affiliation: Département de Radio-oncologie Clinique-Enseignement-Recherche, Centre Hospitalier de l'Université de Montréal - Hôpital Maisonneuve-Rosemont, Montréal, Quebec, Canada.
authors.forename: Alexis
authors.initials: A
authors.lastname: Bujold
authors.affiliation: Department of Radiation Oncology, CancerCare Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Naseer
authors.initials: N
authors.lastname: Ahmed
authors.affiliation: Department of Radiation Oncology, Windsor Regional Cancer Centre, Windsor, Ontario, Canada.
authors.forename: Khalid
authors.initials: K
authors.lastname: Hirmiz
authors.affiliation: Department of Oncology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kurien
authors.affiliation: Radiation Oncology Department, Centre Hospitalier de l'Université de Montréal, Notre Dame Hospital, Montréal, Quebec, Canada.
authors.forename: Edith
authors.initials: E
authors.lastname: Filion
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Gabos
authors.affiliation: Department of Radiation Oncology, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Sergio
authors.initials: S
authors.lastname: Faria
authors.affiliation: Department of Radiation Oncology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Louie
authors.affiliation: Department of Oncology, Queen's University, Kingston, Ontario, Canada.
authors.forename: Timothy
authors.initials: T
authors.lastname: Owen
authors.affiliation: Department of Surgery, University of British Columbia, Victoria, British Columbia, Canada.
authors.forename: Elaine
authors.initials: E
authors.lastname: Wai
authors.affiliation: Department of Oncology, Northern Ontario School of Medicine, Thunder Bay, Ontario, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Ramchandar
authors.affiliation: Department of Radiation Oncology, Dalhousie University, Saint John, New Brunswick, Canada.
authors.forename: Elisa K
authors.initials: EK
authors.lastname: Chan
authors.affiliation: Department of Oncology, McMaster University, Hamilton, Ontario, Canada; Ontario Clinical Oncology Group, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jim
authors.initials: J
authors.lastname: Julian
authors.affiliation: Ontario Clinical Oncology Group, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Cline
authors.affiliation: Department of Oncology, McMaster University, Hamilton, Ontario, Canada; Ontario Clinical Oncology Group, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Whelan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011788:Quality of Life; D016634:Radiosurgery; D012107:Research Design
keywords: Local control; Quality assurance; Quality of life; Radiation; Toxicity