Prophylactic radiotherapy for procedure tract metastases in mesothelioma: a review

Our plain-English summary of Prophylactic radiotherapy for procedure tract metastases in mesothelioma: a review, by D.T. Arnold, A.O. Clive (Current Opinion in Pulmonary Medicine, 2017).

The study

• Authors: D.T. Arnold, A.O. Clive
• Journal: Current Opinion in Pulmonary Medicine
• Published: 2017;23(4):357-364
• Type of article: Review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose Of Review: Malignant pleural mesothelioma is an aggressive malignancy with a very poor prognosis. The majority of patients require pleural procedures for diagnostic or fluid management purposes. Damage to the pleura during these procedures can lead to procedure tract metastases (PTMs), with increasing risk from larger interventions. Prophylactic radiotherapy to these sites is a controversial topic with conflicting results from trial data. In this review, we summarize the recent evidence.

Recent Findings: Four RCTs have been published on this topic, with another in follow-up. The earliest, from a cohort of 40 patients, strongly advocated the use of prophylactic radiotherapy. More recent trials, most notably the Surgical and large bore procedures in Malignant pleural mesothelioma And Radiotherapy Trial (SMART) (which randomized over 200 patients) did not demonstrate any benefit, especially when patient report symptoms and cost-effectiveness are considered. Certain subgroups demand further investigation, such as those not receiving systematic chemotherapy or with surgical intervention sites. The soon to be published Prophylactic Irradiation of Tracts (PIT) trial may help to further clarify best practice.

Summary: Recent studies have shown that prophylactic radiotherapy should not be routinely used to prevent PTMs in mesothelioma. Instead patients should undergo careful clinical follow-up to ensure PTMs are identified and treated promptly to minimize symptoms.

In plain English

This article was a review, not a new study. The authors summarized published research on whether radiotherapy given to the sites of pleural procedures, such as biopsies, drains and surgery, prevents tumour nodules from growing along those procedure tracts in people with malignant pleural mesothelioma. They covered four randomized trials, a fifth trial (PIT, 374 patients) still in follow-up, several case series and cohort studies, and clinical guidelines. In the earliest trial, of 40 patients, no treated patient (0 of 20) developed a tract metastasis, compared with 8 of 20 untreated patients. Two later trials found no significant difference. In SMART, a 203-patient UK trial first-authored by Clive, one of this review's authors, tract metastases occurred in 9 of 102 patients given immediate radiotherapy and 16 of 101 given deferred radiotherapy. That difference was not statistically significant. SMART also found no significant differences in symptoms or quality of life. The authors concluded that the trial evidence does not support routine prophylactic radiotherapy. They favoured careful follow-up instead and said some subgroups need further study.

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: Review of published trials, case series, cohort studies and guidelines on prophylactic radiotherapy to procedure tracts in mesothelioma
• Who was studied: Patients with malignant pleural mesothelioma who had pleural procedures, as studied in four published randomized trials (40, 43, 61 and 203 patients), one trial in follow-up (374 patients), and a set of case series and cohort studies listed in the review's table
• Exposure: Prophylactic radiotherapy to the sites of pleural interventions (in most studies 21 Gy in three fractions; one trial used a single 10 Gy dose), compared with no radiotherapy or deferred radiotherapy. The article does not study asbestos exposure.
• Main results:
  • Boutin trial (40 patients): no procedure tract metastases in the radiotherapy group (0 of 20), compared with 8 of 20 (40%) in the control group
  • Bydder trial (Australia, single 10 Gy dose): no significant difference in tract metastasis incidence between the treatment and control arms
  • O'Rourke trial (UK, 61 patients): tract metastases in 13% of the treatment arm and 10% of the control arm, so no treatment effect
  • SMART trial (203 patients), main intention-to-treat analysis: tract metastases in 9 of 102 in the immediate radiotherapy group and 16 of 101 in the deferred group, odds ratio 0.51 (95% CI 0.19 to 1.32), not statistically significant
  • SMART per-protocol analysis: odds ratio 0.33 (0.09 to 1.00), p = 0.04, described by the authors as a marginally significant difference favouring immediate radiotherapy
  • SMART found no significant differences in symptom control, pain medication use or health-related quality of life between groups over 12 months
  • SMART subgroup with epithelioid-only histology: 6 of 71 (8%) with immediate radiotherapy and 15 of 72 (21%) with deferred radiotherapy developed tract metastases, odds ratio 0.35 (0.11 to 1.04), p = 0.057. This did not reach statistical significance.
  • SMART subgroup of patients not receiving chemotherapy: 2 of 46 (4%) with immediate radiotherapy versus 8 of 37 (22%) with deferred radiotherapy developed tract metastases, p = 0.02
  • When three earlier systematic reviews pooled the earlier trial data, they found no difference between treatment and control arms
  • In SMART, prophylactic radiotherapy was not deemed cost-effective, although the full health economic assessment was still awaited
• The authors' conclusion: The authors concluded that the trial evidence does not support routine prophylactic radiotherapy to procedure tracts in mesothelioma. They recommended careful clinical follow-up so that tract metastases are found and treated promptly, and said further data are needed on subgroups such as patients with epithelioid-only histology or those not having chemotherapy.
• Limitations the authors state:
  • No published study had enough patients to answer conclusively whether specific subgroups benefit
  • Few patients with large thoracotomy (surgical) scars were included in the trials, so any benefit in this group could not be measured
  • The trials differed in design and radiotherapy regimens
  • The quality-of-life findings in the O'Rourke trial rested on small numbers

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: Mesothelioma, Pleural Mesothelioma, Prognosis, Pleura, Chemotherapy.

Related studies

• 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 radiotherapy to prevent procedure-tract metastases — G. Zalcman, S. Brosseau, et al. (2016)
• Prophylactic radiotherapy to prevent procedure-tract metastases — D. Landau, E. Lim (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)
• Pseudo-tumor mimicking indwelling pleural catheter tract metastasis in mesothelioma — R.L. Shrestha, B.A. Wood, et al. (2014)

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