Kevin N Franks1,2,3, Lucy McParland4,3, Joanne Webster4, David R Baldwin5, David Sebag-Montefiore6,2,4, Matthew Evison7, Richard Booton7, Corinne Faivre-Finn8, Babu Naidu9, Jonathan Ferguson10, Clive Peedell10, Matthew E J Callister11, Martyn Kennedy11, Jenny Hewison12, Janine Bestall12, Walter M Gregory4, Peter Hall13, Fiona Collinson4, Catherine Olivier4, Rachel Naylor4, Sue Bell4, Peter Allen14, Andrew Sloss14, Michael Snee6. 1. Leeds Cancer Centre, St James's University Hospital, Leeds, UK kevin.franks@nhs.net. 2. Leeds Institute of Medical Research, University of Leeds, Leeds, UK. 3. Joint first authors. 4. Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK. 5. Nottingham University Hospitals, Nottingham, UK. 6. Leeds Cancer Centre, St James's University Hospital, Leeds, UK. 7. Manchester University Hospitals NHS Foundation Trust and University of Manchester, Manchester, UK. 8. University of Manchester and The Christie NHS Foundation Trust, Manchester, UK. 9. Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. 10. The James Cook University Hospital, Middlesbrough, UK. 11. Dept of Respiratory Medicine, Leeds Teaching Hospitals, Leeds, UK. 12. Leeds Institute of Health Sciences, University of Leeds, Leeds, UK. 13. Western General Hospital, University of Edinburgh, Edinburgh, UK. 14. Patient and Public Involvement Representative, Leeds, UK.
Abstract
OBJECTIVES: Stereotactic ablative radiotherapy (SABR) is a well-established treatment for medically inoperable peripheral stage I nonsmall cell lung cancer (NSCLC). Previous nonrandomised evidence supports SABR as an alternative to surgery, but high-quality randomised controlled trial (RCT) evidence is lacking. The SABRTooth study aimed to establish whether a UK phase III RCT was feasible. DESIGN AND METHODS: SABRTooth was a UK multicentre randomised controlled feasibility study targeting patients with peripheral stage I NSCLC considered to be at higher risk of surgical complications. 54 patients were planned to be randomised 1:1 to SABR or surgery. The primary outcome was monthly average recruitment rates. RESULTS: Between July 2015 and January 2017, 318 patients were considered for the study and 205 (64.5%) were deemed ineligible. Out of 106 (33.3%) assessed as eligible, 24 (22.6%) patients were randomised to SABR (n=14) or surgery (n=10). A key theme for nonparticipation was treatment preference, with 43 (41%) preferring nonsurgical treatment and 19 (18%) preferring surgery. The average monthly recruitment rate was 1.7 patients against a target of three. 15 patients underwent their allocated treatment: SABR n=12, surgery n=3. CONCLUSIONS: We conclude that a phase III RCT randomising higher risk patients between SABR and surgery is not feasible in the National Health Service. Patients have pre-existing treatment preferences, which was a barrier to recruitment. A significant proportion of patients randomised to the surgical group declined and chose SABR. SABR remains an alternative to surgery and novel study approaches are needed to define which patients benefit from a nonsurgical approach.
OBJECTIVES: Stereotactic ablative radiotherapy (SABR) is a well-established treatment for medically inoperable peripheral stage I nonsmall cell lung cancer (NSCLC). Previous nonrandomised evidence supports SABR as an alternative to surgery, but high-quality randomised controlled trial (RCT) evidence is lacking. The SABRTooth study aimed to establish whether a UK phase III RCT was feasible. DESIGN AND METHODS: SABRTooth was a UK multicentre randomised controlled feasibility study targeting patients with peripheral stage I NSCLC considered to be at higher risk of surgical complications. 54 patients were planned to be randomised 1:1 to SABR or surgery. The primary outcome was monthly average recruitment rates. RESULTS: Between July 2015 and January 2017, 318 patients were considered for the study and 205 (64.5%) were deemed ineligible. Out of 106 (33.3%) assessed as eligible, 24 (22.6%) patients were randomised to SABR (n=14) or surgery (n=10). A key theme for nonparticipation was treatment preference, with 43 (41%) preferring nonsurgical treatment and 19 (18%) preferring surgery. The average monthly recruitment rate was 1.7 patients against a target of three. 15 patients underwent their allocated treatment: SABR n=12, surgery n=3. CONCLUSIONS: We conclude that a phase III RCT randomising higher risk patients between SABR and surgery is not feasible in the National Health Service. Patients have pre-existing treatment preferences, which was a barrier to recruitment. A significant proportion of patients randomised to the surgical group declined and chose SABR. SABR remains an alternative to surgery and novel study approaches are needed to define which patients benefit from a nonsurgical approach.
Authors: Henry S Park; Frank C Detterbeck; David C Madoff; Brett C Bade; Ulas Kumbasar; Vincent J Mase; Andrew X Li; Justin D Blasberg; Gavitt A Woodard; Whitney S Brandt; Roy H Decker Journal: J Thorac Dis Date: 2022-06 Impact factor: 3.005