Title: A study to determine the feasibility and acceptability of conducting a phase III randomised controlled trial comparing Stereotactic Ablative Radiotherapy (SABR) with surgery in patients with peripheral stage I non-small cell lung cancer (NSCLC) considered higher risk of complications from surgical resection.
Funder: Department of Health (England)

Abstract: Background: Stage I non-small cell lung cancer (NSCLC) is diagnosed in >2000 UK patients annually. Surgical resection is the standard of care but resection rates vary. Surgical resection, either an open operation or Video-Assisted Thoracscopic Surgery (VATS), ideally involves a lobectomy plus lymph sampling/dissection. In higher risk patients, a more limited anatomical sub-lobar resection or wedge excision may be performed. SABR, using small number of high dose radiotherapy treatments, delivers high local control rates for peripheral stage I NSCLC tumours. SABR is recommended in national/international guidelines for medically-inoperable peripheral stage I NSCLC tumours and is increasingly used in the UK. In case series and cohort comparisons, SABR appears to be equivalent to surgery in higher operative risk patients5-7. Surgery is associated with a significant morbidity and mortality risk, with higher rates in patients with co-morbidity1. Although SABR has very low morbidity8,9 and mortality rates it is unclear whether it results in equivalent long term survival. A trial comparing the two approaches is important and needed to establish the best treatment for higher-risk curable stage I NSCLC patients in terms of post treatment quality and quantity of life. Aims: To undertake a study to determine the feasibility and acceptability of performing a definitive phase III randomised-controlled trial to compare surgery with SABR in patients with stage I NSCLC at higher risk from surgical resection. The primary aim is to demonstrate an average recruitment rate of 3 patients/month over a consecutive 15 month period. In addition we will; quantitatively assess screening and eligibility rates quantitatively assess participant uptake of allocated treatment arm qualitatively explore patient acceptability of the trial (reasons for non-participation and participant refusal of allocated treatment uptake) from semi-structured interviews explore participant recruitment pathways at four treatment sites and two referral sites investigate the utility of available methods and a prediction tool to identify higher risk patients monitor OS at 90/180 days and at end of study Design: A multi-centre, two-group individually randomised controlled feasibility study. Population: Patients with peripheral stage 1 NSCLC at higher risk from surgery. Intervention: Patients randomised (1:1) to either surgery or SABR (stratified by site) Setting: Four treatment sites and two referral sites (UK). Follow-up: OS data, toxicities and withdrawals will be collected at the 3 and 6 month post-treatment follow-up visits. Unexpected serious adverse reactions will be collected in real-time throughout the trial duration. OS data will be collated again at the end of the study from a review of participant notes. Sample size: 54 patients from four treatment sites and two referral sites Duration: 6 month set-up, 21 month recruitment and 6 month follow-up period followed by 3 months statistical analysis and report writing (total 36 months). Analysis: This will be descriptive rather than formal hypothesis testing. Quantitative evaluation of screening, average recruitment, allocated intervention uptake and 90/180 day mortality rates will be summarised. Qualitative evaluation of participant interviews assessing acceptability of trial and intervention will be performed. Participant recruitment pathways and utility of risk assessment tools will be descriptively summarised. Future: If the feasibility study meets the primary end point/objective, this would support our application to the HTA to fund a definitive large-scale non-inferiority phase III trial, with an additional 15 treatment sites plus their associated referral sites with co-primary endpoints of 3-year OS and averaged QALY. Benefits: The result of a phase III trial will provide the highest level of evidence to determine the optimal management of patients with high-risk stage I NSCLC. If SABR is non-inferior to surgery then the potential savings to the NHS (≅£2 million/year) are high and should improve rates of curative treatment in the UK.


Research activity codes: 6.4 SURGERY;6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS