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Lancet Oncol. 2016 Aug;17(8):1094-1104. doi: 10.1016/S1470-2045(16)30095-X. Epub 2016 Jun 23.

Prophylactic radiotherapy for the prevention of procedure-tract metastases after surgical and large-bore pleural procedures in malignant pleural mesothelioma (SMART): a multicentre, open-label, phase 3, randomised controlled trial.

Author information

1
Respiratory 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.
2
Research Design Service South West, Bristol, UK.
3
South Devon Healthcare NHS Foundation Trust, Torbay, UK.
4
University Hospitals Bristol NHS Trust, Bristol, UK.
5
Royal United Hospital, Bath, UK.
6
Oxford University Hospitals NHS Trust, Oxford, UK.
7
Musgrove Park Hospital, Taunton, UK.
8
Plymouth Hospitals NHS Trust, Plymouth, UK.
9
Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
10
Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
11
Respiratory Research Unit, North Bristol National Health Service (NHS) Trust, Southmead Hospital, Bristol, UK.
12
Portsmouth Hospitals NHS Trust, Portsmouth, UK.
13
Royal Gwent Hospital, Aneurin Bevan University Health Board, Newport, UK.
14
Poole Hospital NHS Foundation Trust, Poole, UK; Dorset County Hospital NHS Foundation Trust, Dorchester, UK.
15
Colchester Hospital University NHS Foundation Trust, Colchester, UK.
16
Great Western Hospitals NHS Trust, Swindon, UK.
17
Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK.
18
Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
19
Singleton Hospital, Swansea, UK; Withybush Hospital, Haverfordwest, UK.
20
Royal Berkshire NHS Foundation Trust, Reading, UK.
21
The Royal Marsden NHS Foundation Trust, London, UK.
22
Nevill Hall Hospital, Abergavenny, UK.
23
Imperial College Healthcare NHS Trust, London, UK.
24
Centre for Respiratory Health, School of Medicine & Pharmacology, University of Western Australia, Perth, WA, Australia.
25
Oxford University Hospitals NHS Trust, Oxford, UK; Oxford National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford, UK.
26
Respiratory 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.

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.

PMID:
27345639
PMCID:
PMC4961873
DOI:
10.1016/S1470-2045(16)30095-X
[Indexed for MEDLINE]
Free PMC Article

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