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

Amelia O Clive, Hazel Taylor, Lee Dobson, Paula Wilson, Emma de Winton, Niki Panakis, Justin C T Pepperell, Timothy Howell, Samuel A Stewart, Erika Penz, Nikki Jordan, Anna J Morley, Natalie Zahan-Evans, Sarah Smith, Timothy J P Batchelor, Adrian Marchbank, Lesley Bishop, Alina A Ionescu, Mike Bayne, Samantha CooperAnthony L Kerry, Peter Jenkins, Elizabeth Toy, Vallipuram Vigneswaran, James Gildersleve, Merina Ahmed, Fiona McDonald, Mick Button, Conrad Lewanski, Charles Comins, Muthukumar Dakshinamoorthy, Y C Gary Lee, Najib M Rahman, Nick A Maskell

Research output: Contribution to journalArticle (Academic Journal)peer-review

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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.
Original languageEnglish
Pages (from-to)1094-1104
Number of pages11
JournalLancet Oncology
Volume17
Issue number8
Early online date23 Jun 2016
DOIs
Publication statusPublished - 1 Aug 2016

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