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Abstract

BACKGROUND:

The use of prophylactic radiotherapy to prevent procedure-tract metastases (PTMs) in malignant pleural mesothelioma remains controversial, and clinical practice varies worldwide. We aimed to compare prophylactic radiotherapy with deferred radiotherapy (given only when a PTM developed) in a suitably powered trial.

METHODS:

We did a multicentre, open-label, phase 3, randomised controlled trial in 22 UK hospitals of patients with histocytologically proven mesothelioma who had undergone large-bore pleural interventions in the 35 days prior to recruitment. Eligible patients were randomised (1:1), using a computer-generated sequence, to receive immediate radiotherapy (21 Gy in three fractions within 42 days of the pleural intervention) or deferred radiotherapy (same dose given within 35 days of PTM diagnosis). Randomisation was minimised by histological subtype, surgical versus non-surgical procedure, and pleural procedure (indwelling pleural catheter vs other). The primary outcome was the incidence of PTM within 7 cm of the site of pleural intervention within 12 months from randomisation, assessed in the intention-to-treat population. This trial is registered with ISRCTN, number ISRCTN72767336.

FINDINGS:

Between Dec 23, 2011, and Aug 4, 2014, we randomised 203 patients to receive immediate radiotherapy (n=102) or deferred radiotherapy (n=101). The patients were well matched at baseline. No significant difference was seen in PTM incidence in the immediate and deferred radiotherapy groups (nine [9%] vs 16 [16%]; odds ratio 0·51 [95% CI 0·19-1·32]; p=0·14). The only serious adverse event related to a PTM or radiotherapy was development of a painful PTM within the radiotherapy field that required hospital admission for symptom control in one patient who received immediate radiotherapy. Common adverse events of immediate radiotherapy were skin toxicity (grade 1 in 50 [54%] and grade 2 in four [4%] of 92 patients vs grade 1 in three [60%] and grade 2 in two [40%] of five patients in the deferred radiotherapy group who received radiotherapy for a PTM) and tiredness or lethargy (36 [39%] in the immediate radiotherapy group vs two [40%] in the deferred radiotherapy group) within 3 months of receiving radiotherapy.

INTERPRETATION:

Routine use of prophylactic radiotherapy in all patients with mesothelioma after large-bore thoracic interventions is not justified.

FUNDING:

Research for Patient Benefit Programme from the UK National Institute for Health Research. 

Author information​

Clive AO1, Taylor H2, Dobson L3, Wilson P4, de Winton E5, Panakis N6, Pepperell J7, Howell T8, Stewart SA9, Penz E10, Jordan N11, Morley AJ11, Zahan-Evans N11, Smith S11, Batchelor TJ4, Marchbank A8, Bishop L12, Ionescu AA13, Bayne M14, Cooper S15, Kerry A16, Jenkins P17, Toy E18, Vigneswaran V19, Gildersleve J20, Ahmed M21, McDonald F21, Button M22, Lewanski C23, Comins C4, Dakshinamoorthy M15, Lee YC24, Rahman NM25, Maskell NA26.

1Respiratory Research Unit, North Bristol National Health Service (NHS) Trust, Southmead Hospital, Bristol, UK; Academic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol, UK.

2Research Design Service South West, Bristol, UK.

3South Devon Healthcare NHS Foundation Trust, Torbay, UK.

4University Hospitals Bristol NHS Trust, Bristol, UK.

5Royal United Hospital, Bath, UK.

6Oxford University Hospitals NHS Trust, Oxford, UK.

7Musgrove Park Hospital, Taunton, UK.

8Plymouth Hospitals NHS Trust, Plymouth, UK.

9Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.

10Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.

11Respiratory Research Unit, North Bristol National Health Service (NHS) Trust, Southmead Hospital, Bristol, UK.

12Portsmouth Hospitals NHS Trust, Portsmouth, UK.

13Royal Gwent Hospital, Aneurin Bevan University Health Board, Newport, UK.

14Poole Hospital NHS Foundation Trust, Poole, UK; Dorset County Hospital NHS Foundation Trust, Dorchester, UK.

15Colchester Hospital University NHS Foundation Trust, Colchester, UK.

16Great Western Hospitals NHS Trust, Swindon, UK.

17Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK.

18Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.

19Singleton Hospital, Swansea, UK; Withybush Hospital, Haverfordwest, UK.

20Royal Berkshire NHS Foundation Trust, Reading, UK.

21The Royal Marsden NHS Foundation Trust, London, UK.

22Nevill Hall Hospital, Abergavenny, UK.

23Imperial College Healthcare NHS Trust, London, UK.

24Centre for Respiratory Health, School of Medicine & Pharmacology, University of Western Australia, Perth, WA, Australia.

25Oxford University Hospitals NHS Trust, Oxford, UK; Oxford National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford, UK.

26Respiratory Research Unit, North Bristol National Health Service (NHS) Trust, Southmead Hospital, Bristol, UK; Academic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol, UK. Electronic address: Nick.maskell@bristol.ac.uk.