Elsevier

Lung Cancer

Volume 66, Issue 2, November 2009, Pages 150-156
Lung Cancer

Review
Prophylactic radiotherapy to intervention sites in mesothelioma: A systematic review and survey of UK practice

https://doi.org/10.1016/j.lungcan.2009.06.014Get rights and content

Abstract

Background and purpose

Patients with malignant pleural mesothelioma (MPM), who undergo chest instrumentation, may develop seeding at the site of intervention, leading to subcutaneous tumour. This is believed to be reduced by the common practice of prophylactic irradiation to intervention tracts (PIT). However, evidence to support PIT is currently inadequate and contentious.

Materials and methods

We carried out a systematic search of published literature for articles relating to the incidence of chest wall intervention tract metastases and the use of PIT in mesothelioma. In addition, a survey of current practice was conducted in 54 UK oncology centres.

Results

Fourteen studies revealed an incidence of chest wall intervention tract metastases of 0–48% with a trend toward a higher rate of metastases for more invasive procedures. Three randomised controlled trials (RCTs), two prospective non-randomised studies and five retrospective series met the eligibility criteria to evaluate the role of PIT in MPM. Of the three RCTs, two did not support the use of PIT. None of the RCTs included patients who had received systemic chemotherapy. Of the oncology centres responding to the survey, 75% practiced PIT, and 80% would be interested in a trial to determine the efficacy of PIT.

Conclusions

No consensus has been reached to support the use of PIT. However, most centres in the UK still offer PIT. There was widespread interest in a randomised controlled trial to establish PIT efficacy in the era of effective systemic chemotherapy for malignant pleural mesothelioma.

Introduction

Malignant mesothelioma is a rare disease with approximately 1300 cases per annum in the United Kingdom, and is almost exclusively linked with 50–70-year olds who have been exposed to asbestos with a latency period of 35–45 years [1], [2]. Given the widespread historic use of asbestos it is predicted that the incidence of mesothelioma deaths will peak between 2010 and 2020 [1]. There is a male:female ratio of 3:1 [3] that may reflect the increased exposure of the male population, particularly ex-shipyard workers. Prognosis is poor with a 5-year survival rate of approximately 5% [4] and a median survival between 4 and 14 months [4], [5], [6], [7], [8].

The disease affects the pleura and more rarely the peritoneum. Diagnosis involves obtaining a pleural biopsy/aspiration either via computerised tomography (CT) guided needle biopsy, thoracoscopy, video assisted thoracic surgery (VATs), or thoracotomy. Patients often have associated pleural effusions and require chest drains/aspirations for symptomatic benefit. These invasive diagnostic procedures encourage tumour cell seeding at the site of intervention, resulting in a subcutaneous tumour at the site of intervention. The rationale is that chest wall interventions produce ‘tracts’ from the pleural cavity to the skin surface through which tumour cells can migrate and form metastatic chest wall nodules. In an effort to minimise tumour seeding and prevent nodule development, it has been widespread practice for more than 20 years to prophylactically irradiate intervention sites post-procedure—a practice known as prophylactic irradiation of tracts (PIT).

The purpose of our study was to perform a systematic review of the literature to answer the following questions regarding the role of PIT in mesothelioma:

  • (1)

    What is the risk of chest wall tract metastases following chest wall intervention without RT and is this the same for all procedures?

  • (2)

    Is PIT effective in reducing the risk of chest wall metastases?

  • (3)

    Is there a need for a further randomised controlled trial to assess the role of PIT?

We also conducted a survey of UK practitioners, to investigate current practice of PIT in the UK, and determined respondents’ opinions regarding a future randomised controlled trial (RCT) to assess the role of PIT.

Section snippets

Literature search strategy

A comprehensive computer literature search was performed to identify publications relating to the use of PIT in mesothelioma. The databases Pubmed (1950 to December 2008), Medline (1950 to December 2008), Embase (1974 to December 2008), Cinahl (1982 to December 2008), Web of science (1945 to December 2008) and Cochrane Library (1995 to December 2008) were searched with the following Medical Subject Heading (MeSH)/Excerpta Medica Tree (EMTREE) and Cinahl thesaurus keywords “mesothelioma” and

Literature search results

Fourteen original articles were identified reporting on the incidence of tract metastases following chest wall intervention in patients with mesothelioma who had not received PIT [7], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22]. Three RCTs evaluating the role of PIT reported on the incidence of tract metastases in the control arms [12], [13], [18]. Four studies included patients who had undergone palliative radiotherapy [11], [17], [19], [22]. One post-mortem

UK survey of practice

Results of the survey of 54 UK oncology centres are presented in Table 4. The overall response rate to the questionnaire was 66.6% (36 centres). Of the 27/36 (75%) respondents who offered PIT, one clarified the practice of their centre by stating that patients were only given PIT if there was a “significant scar”, i.e. after more invasive procedures such as VATS or chest drain. Similarly, another respondent commented that PIT was used for all thoracotomy sites, plus drain sites with mixed and

Discussion

The availability of image-guided needle biopsies to assist the diagnosis of malignant mesothelioma and palliative chemotherapy having become more common place may have reduced the incidence of malignant seeding from the 40% reported in the control arm of the Boutin study in 1995. A recent observational study of 212 MPM patients who had not received PIT recorded a tract metastasis rate of 13.2% [17]. Most of these patients (157) had received palliative chemotherapy. Overestimation of the

Conclusion

In 2008 the majority of centres in the UK were using PIT to prevent nodule tract metastases based on evidence from early studies and recommendations from the UK British Thoracic Society. Data from more recent studies has thrown the practice of PIT into doubt. In the UK there is interest in a nationwide prospective randomised controlled trial to address the role of PIT in mesothelioma. The incidence of mesothelioma is increasing and, as a consequence, a rise in metastatic nodule formation at

Conflicts of interest

None declared.

Acknowledgements

We thank Dr. Melanie Green for help with manuscript preparation and Helen Flight and Sally Falk for their involvement with the UK survey. With gratitude to all the UK centres that contributed time and effort to respond to the survey.

Contributors: CL, NB and CFF conducted survey and wrote paper. RS gave statistical input and helped to edit and proof the paper.

Funding: None.

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