Should all patients who have mesothelioma diagnosed by video-assisted thoracoscopic surgery have their intervention sites irradiated?

Our plain-English summary of Should all patients who have mesothelioma diagnosed by video-assisted thoracoscopic surgery have their intervention sites irradiated?, by M. Nagendran, A. Pallis, K. Patel, et al (Interactive Cardiovascular and Thoracic Surgery, 2011).

The study

• Authors: M. Nagendran, A. Pallis, K. Patel, M. Scarci
• Journal: Interactive Cardiovascular and Thoracic Surgery
• Published: 2011;13(1):66-9
• Type of article: Systematic review
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether patients diagnosed with mesothelioma by video-assisted thoracoscopic surgery should have their intervention sites irradiated to prevent metastatic seeding. Altogether 334 papers were found using the reported search, of which nine represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. There is no general consensus in the literature. Four studies recommend prophylactic irradiation therapy (PIT), while three studies stated that PIT was unnecessary. A systematic review identified only three suitable randomized controlled trials (RCTs) from the literature. One trial found that 23% of radiotherapy (RT) patients developed tract metastases compared to 10% of control patients (P=0.748) with an estimated hazard ratio (RT to control) of 1.28 (95% CI: 0.29-5.73). Time from procedure to tract metastases was in fact shorter in patients treated with RT (2.4 months RT vs. 6.4 months control, non-significant). Another trial found that seeding of metastatic tumour to the intervention site occurred in 7% of RT sites vs. 10% of control sites (P=0.53). Freedom from tract metastasis survival was also non-significant between RT and control arms (P=0.82). However, the third trial reported a significantly greater incidence of intervention site metastases in control vs. RT patients (40% vs. 0%, respectively, P<0.001). Non-randomised studies found mixed results. One reported that median survival between patients with and without local metastases was not significantly different (P=0.64) while another article described no local metastases in PIT sites. None of the studies reported significant skin or side reactions and treatment was generally well tolerated. Based on the available evidence, we conclude that PIT is not currently justified.

In plain English

This article was a best evidence topic, a short structured review rather than new research. The authors asked whether people with malignant pleural mesothelioma diagnosed by video-assisted thoracoscopic surgery should have their surgical entry sites irradiated to stop tumour from seeding there. A Medline search found 334 papers. Nine were chosen as the best evidence, including three randomised trials. In the oldest trial (Boutin et al.), 8 of 20 control patients (40%) developed metastases at intervention sites, compared with none of the irradiated patients (P less than 0.001). In another trial (O'Rourke et al.), 7 of 31 irradiated patients and 3 of 30 patients given best supportive care developed tract metastases (P = 0.748). In a third trial (Bydder et al.), seeding occurred at 7% of irradiated sites and 10% of control sites (P = 0.53). The non-randomised studies gave mixed results. The authors said the trials were small and underpowered. Giving the most weight to the trials, they concluded that prophylactic irradiation was not currently justified, and they suggested a large trial.

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: Best evidence topic: a structured literature review of nine selected papers (three randomised controlled trials, retrospective cohort studies, and one systematic review)
• Who was studied: Published studies of patients with malignant pleural mesothelioma (MPM) diagnosed by video-assisted thoracoscopic surgery. A Medline search covering 1948 to January 2011 found 334 papers, and nine were selected. The reviewed studies came from the UK, Italy, Turkey, Australia and France.
• Exposure: Prophylactic irradiation therapy (PIT), meaning radiotherapy to the intervention sites, compared with conservative management or no irradiation. The article does not study asbestos or fiber exposure.
• Main results:
  • Boutin et al. randomised trial of 40 patients: 8 of 20 control-arm patients (40%) developed intervention site metastases, compared with none in the radiotherapy arm (P < 0.001).
  • O'Rourke et al. randomised trial of 61 patients: 7 of 31 patients given immediate radiotherapy developed tract metastases, compared with 3 of 30 patients given best supportive care (P = 0.748).
  • O'Rourke et al. trial: the estimated hazard ratio (radiotherapy to best supportive care) was 1.28 (95% CI: 0.29 to 5.73).
  • Bydder et al. randomised trial of 43 patients with 58 intervention sites, using single-dose radiotherapy: seeding occurred at 7% of irradiated sites and 10% of control sites (P = 0.53).
  • Metintas et al. retrospective cohort of 46 patients who did not receive PIT: seeding to intervention sites was found in 13% of patients who had undergone thoracoscopy. Median survival did not differ significantly between patients with and without local metastases (P=0.64).
  • Di Salvo et al. retrospective cohort of 32 patients who received PIT: no surviving patient had detectable seeding at their intervention sites at a mean follow-up of 13.6 months.
  • Di Salvo et al. cohort: the treatment was well tolerated, with temporary and mild erythema (skin reddening) in 34% of patients.
  • Low et al. retrospective analysis: none of the 19 analysed patients developed seeding at treated sites. Four patients (21%) developed tumour deposits only at additional untreated sites.
  • Across the reviewed studies, no significant skin or other side reactions were reported.
• The authors' conclusion: The authors concluded that prophylactic irradiation of intervention sites is not currently justified. They suggested that a large-scale randomised trial would be a sensible step before further guidelines are formed.
• Limitations the authors state:
  • The existing trials were small and underpowered because their sample sizes assumed a 40% rate of tract metastases in control patients, which recent data suggest may be an overestimate.
  • In the O'Rourke et al. trial, fewer than half of patients completed the planned 12-month follow-up, which reduced the study's power.
  • The Bydder et al. trial randomised intervention sites rather than patients, and multiple sites on the same patient may not have behaved independently.
  • Small sample sizes, differing study designs and lack of statistical significance weaken the conclusions that can be drawn from the reviewed papers.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Video-Assisted Thoracoscopic Surgery (VATS), Thoracic Surgery, Systematic Review, Hazard Ratio, Tract Metastasis, Median Survival.

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