Protocol for PIT: a phase III trial of prophylactic irradiation of tracts in patients with malignant pleural mesothelioma following invasive chest wall intervention

Our plain-English summary of Protocol for PIT: a phase III trial of prophylactic irradiation of tracts in patients with malignant pleural mesothelioma following invasive chest wall intervention, by N. Bayman, D. Ardron, L. Ashcroft, et al (BMJ Open, 2016).

The study

• Authors: N. Bayman, D. Ardron, L. Ashcroft, D.R. Baldwin, R. Booton, L. Darlison, J.G. Edwards, L. Lang-Lazdunski, J.F. Lester, M. Peake, R.C. Rintoul, M. Snee, P. Taylor, C. Lunt, C. Faivre-Finn
• Journal: BMJ Open
• Published: 2016;6(1):e010589
• Type of article: Randomized trial
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Histological diagnosis of malignant mesothelioma requires an invasive procedure such as CT-guided needle biopsy, thoracoscopy, video-assisted thorascopic surgery (VATs) or thoracotomy. These invasive procedures encourage tumour cell seeding at the intervention site and patients can develop tumour nodules within the chest wall. In an effort to prevent nodules developing, it has been widespread practice across Europe to irradiate intervention sites postprocedure--a practice known as prophylactic irradiation of tracts (PIT). To date there has not been a suitably powered randomised trial to determine whether PIT is effective at reducing the risk of chest wall nodule development.

Methods And Analysis: In this multicentre phase III randomised controlled superiority trial, 374 patients who can receive radiotherapy within 42 days of a chest wall intervention will be randomised to receive PIT or no PIT. Patients will be randomised on a 1:1 basis. Radiotherapy in the PIT arm will be 21 Gy in three fractions. Subsequent chemotherapy is given at the clinicians' discretion. A reduction in the incidence of chest wall nodules from 15% to 5% in favour of radiotherapy 6 months after randomisation would be clinically significant. All patients will be followed up for up to 2 years with monthly telephone contact and at least four outpatient visits in the first year.

Ethics And Dissemination: PIT was approved by NRES Committee North West-Greater Manchester West (REC reference 12/NW/0249) and recruitment is currently on-going, the last patient is expected to be randomised by the end of 2015. The analysis of the primary end point, incidence of chest wall nodules 6 months after randomisation, is expected to be published in 2016 in a peer reviewed journal and results will also be presented at scientific meetings and summary results published online. A follow-up analysis is expected to be published in 2018.

Trial Registration Number: ISRCTN04240319; NCT01604005; Pre-results.

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In plain English

This article was a trial protocol. It described a planned clinical trial and reported no results. The trial, called PIT, was designed as a two-arm, phase III, multicentre randomised trial in adults with malignant pleural mesothelioma who had had an invasive chest wall procedure: video-assisted thoracoscopy, open surgical biopsy, local anaesthetic thoracoscopy or a chest drain. A planned 374 patients who could start radiotherapy within 42 days of the procedure were to be assigned at random, in equal numbers, to one of two groups. One group would receive prophylactic irradiation of the procedure tract, 21 Gy given in three fractions on three consecutive days. The other group would receive no such radiotherapy. Patients who had had a thoracotomy, had an indwelling pleural catheter at the site, or were currently receiving chemotherapy were excluded. The main outcome was how often chest wall tract metastasis occurred six months after randomisation, with follow-up of up to two years. The authors' hypothesis was that the radiotherapy would reduce chest wall nodules from 15% to 5%. The authors noted that the trial will not determine the role of this radiotherapy at the site of an indwelling pleural catheter.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Protocol for a two-arm, phase III, multicentre randomised superiority trial (radiotherapy versus no radiotherapy). The primary end point is the incidence of chest wall tract metastasis 6 months from randomisation. Follow-up is up to 2 years after randomisation. No results are reported.
• Who was studied: A planned 374 patients aged 18 or over with mesothelioma diagnosed by a multidisciplinary team, at multiple centres (academic centres and community hospitals). All had had a chest wall intervention (VATS, open surgical biopsy, local anaesthetic thoracoscopy or chest drain) and were able to start radiotherapy within 42 days. Excluded were patients with a thoracotomy, an indwelling pleural catheter at the intervention site, previous radiotherapy to the site, or current chemotherapy.
• Exposure: The trial did not study asbestos exposure. The intervention is prophylactic irradiation of tracts: 21 Gy in three fractions, once daily over three consecutive days, using a single electron field. The comparison group receives no prophylactic radiotherapy.
• The authors' conclusion: No conclusions from data, because this is a protocol. The authors' stated hypothesis is that prophylactic irradiation of tracts will reduce the incidence of chest wall nodules from 15% to 5%.
• Limitations the authors state:
  • The trial will not determine the role of prophylactic radiotherapy at the site of an indwelling pleural catheter.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma, Needle Biopsy, Thoracoscopy, Video-Assisted Thoracoscopic Surgery (VATS), Thoracotomy, Chemotherapy.

Related studies

• Tumor extension along chest wall tract after diagnostic intervention in malignant pleural mesothelioma — F. Chen, A. Yoshizawa, et al. (2011)
• Protocol for the surgical and large bore procedures in malignant pleural mesothelioma and radiotherapy trial (SMART Trial): an RCT evaluating whether prophylactic radiotherapy reduces the incidence of procedure tract metastases — A.O. Clive, P. Wilson, et al. (2015)
• 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 — A.O. Clive, H. Taylor, et al. (2016)
• Prophylactic irradiation of intervention sites in malignant pleural mesothelioma — M.A. Froment, E. Fréchette, et al. (2011)
• Prophylactic irradiation of tracts in patients with malignant pleural mesothelioma: A systematic review and meta-analysis of randomized trials — C.C. Lee, Y.Y. Soon, et al. (2021)
• Should all patients who have mesothelioma diagnosed by video-assisted thoracoscopic surgery have their intervention sites irradiated? — M. Nagendran, A. Pallis, et al. (2011)

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