ESTRO 2024 - Abstract Book

S1787

Clinical - Lung

ESTRO 2024

2880

Proffered Paper

SYSTEMS-2: randomised phase II study of radiotherapy dose escalation in pleural mesothelioma

Miranda J Ashton 1 , Lucy Paterson 2 , Laura Alexander 2 , Jamie Stobo 3 , Caroline Kelly 2 , Ann Shaw 2 , Laura Divers 2 , Elspeth Banks 2 , Kevin N Franks 4 , Iain Philips 5 , Merina Ahmed 6 , Barry Laird 7 , Anthony J Chalmers 8 1 NHS Greater Glasgow & Clyde, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom. 2 University of Glasgow, Glasgow Oncology Clinical Trials Unit, Glasgow, United Kingdom. 3 University of Dundee, Molecular and Clinical Medicine, Dundee, United Kingdom. 4 Leeds Teaching Hospitals NHS Trust, Oncology, Leeds, United Kingdom. 5 Western General Hospital, Oncology, Edinburgh, United Kingdom. 6 Royal Marsden NHS Foundation Trust, Oncology, London, United Kingdom. 7 University of Edinburgh, Edinburgh Cancer Research Centre, Edinburgh, United Kingdom. 8 University of Glasgow, School of Cancer Sciences, Glasgow, United Kingdom

Purpose/Objective:

Malignant pleural mesothelioma (MPM) is an aggressive cancer in which pain is highly prevalent and analgesics often ineffective. The SYSTEMS study demonstrated that palliative radiotherapy (20 Gray in 5 fractions) achieves clinically significant pain improvement in one third of patients. We hypothesised that radiotherapy dose escalation would achieve pain relief in more patients and extend its duration, and might also improve radiological response and survival.

Material/Methods:

SYSTEMS-2 is a randomised multicentre trial comparing hypofractionated, dose escalated radiotherapy (36 Gy, 6 fractions, 2 weeks) with conventional radiotherapy (20 Gy, 5 fractions, 1 week). The trial was funded by the June Hancock Mesothelioma Research Fund and Beatson Cancer Charity Participants had a histological or multidisciplinary team agreed diagnosis of MPM, ECOG performance status 0-2, life expectancy >12 weeks and ‘worst pain score’ >4/10 after optimisation of analgesia. Radiotherapy plans compatible with dose escalation were required prior to randomisation. Exclusion criteria included anti-cancer therapy within 4 weeks of study entry, previous radiotherapy to an overlapping volume, and co- existing lung cancer. The primary endpoint was ‘worst pain score’ measured by Brief Pain Inventory (BPI) 5 weeks after start of radiotherapy. Secondary endpoints included acute toxicity, overall BPI score and quality of life (measured at weeks 5 and 9), radiological response (week 9) and overall survival (OS). 112 patients were required to detect a 20% increase in proportion of responders at week 5 on dose escalated radiotherapy with 90% power and 20% 1-sided statistical significance. Follow-up and analysis will be completed in April 2024 so preliminary results are presented here.

Results:

122 patients were consented between August 2016 and September 2022 of whom 110 were randomised across 17 sites. In the ‘Intention to Treat’ analysis of the primary endpoint (worst pain score 5 weeks post -radiotherapy),