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

Abstract

SummaryBackgroundThe 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.MethodsWe 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.FindingsBetween 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.InterpretationRoutine use of prophylactic radiotherapy in all patients with mesothelioma after large-bore thoracic interventions is not justified.FundingResearch for Patient Benefit Programme from the UK National Institute for Health Research.

British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma

“…The SMART trial was a randomised, multicentre, phase III trial evaluating whether prophylactic radiotherapy reduces the incidence of procedure tract metastases after surgical and large bore pleural procedures 129 . Eligible patients were recruited from 22 UK hospitals and randomised (1:1) to immediate radiotherapy (21 Gy in three fractions over three working days), or deferred radiotherapy (same dose given if a procedure tract metastasis (PTM) developed).…”

Diagnosis and management of malignant pleural effusions: state of the art in 2017

“…A recommendation from this study is to strongly consider port side radiation post procedure in patients with mesothelioma to decrease the risk of tract tumor seeding with malignant cells (48). Recent studies have shown no benefit of routine use of prophylactic radiotherapy following pleural interventions in patients with malignant mesothelioma (49,50). Figure 6 shows a modified diagnostic algorithm for patients with suspected MPE.…”

Catheter Tract Metastasis in Mesothelioma Patients with Indwelling Pleural Catheters: A Retrospective Cohort Study

“…Prior studies have reported that pain related to procedure-tract metastasis is generally mild to moderate in intensity and is responsive to treatment [21, 42, 45]. Although the incidence of CTM was higher than previously reported, we would not recommend avoidance of IPCs due to the clear symptomatic benefit.…”

“…The 2016 SMART trial by Clive et al [42], which included 25 patients (12%) with IPCs, compared immediate (prophylactic) radiotherapy to deferred radiotherapy (following diagnosis of tract metastasis). There was no difference in quality of life, chest pain, analgesia requirement, or overall development of procedure tract metastasis between groups.…”