Study design and patient selection

Institutional Research Ethics Board approval was obtained prior to study initiation, and the study was centrally registered (NCT02136355). Eligible patients had histologically-confirmed T1 or T2a (≤5 cm) NSCLC, with no evidence of nodal or distant metastases. Additional requirements included age ≥18, informed consent, Eastern Cooperative Oncology Group (ECOG) performance status 0–2, life expectancy > 6 months and a predicted post-operative forced expiratory volume in 1 second (FEV 1 ) of ≥ 30%. Ineligibility criteria included patients with contraindication to either treatment, previous lung cancer within the past 5 years, previous thoracic radiation or a contrast allergy.

Interventions

SABR was delivered according to a risk-adapted protocol, with the dose and fractionation dependent on the size and location of the tumor (54 Gy / 3 fractions, 55 Gy/5 fractions or 60 Gy/8 fractions). Treatment was delivered every second day regardless of the dose-fractionation regimen [6, 7]. A 4-D CT simulation scan was acquired for all patients. Respiratory gating was considered in cases where motion was > 7 mm in any direction.

The gross tumor volume (GTV) was defined as the visible tumor on CT imaging ± PET, and an internal GTV encompassed the GTV from all phases of respiration. No additional margin was included for microscopic spread of disease. A planning target volume (PTV) margin of 5 mm was used. The prescription point was approximately the 80% isodose line surrounding the PTV, with the requirement that 95% of the PTV was covered by 100% of the prescription dose.

Surgical resection was planned to occur at 10 ± 2 weeks following SABR and consisted of a lobectomy or sublobar resection by either an open or video-assisted thoracoscopic approach. All patients received sampling of high risk hilar and mediastinal lymph nodes at the time of resection. All procedures were done at a high-volume tertiary surgical centre, with a case volume of >200 lung resections annually.

Patients with pathologic node-positive disease (N1, N2, or N3) were referred for adjuvant chemotherapy. For patients with N2 or N3 disease, adjuvant radiotherapy to the mediastinum was to be considered as long as there was minimal overlap with the SABR dose distribution.

The trial protocol mandated that after 10 patients have been accrued and completed surgery, a safety analysis to review treatment toxicity would be undertaken separately by the study team and the data safety monitoring committee.