ReviewProphylactic radiotherapy to intervention sites in mesothelioma: A systematic review and survey of UK practice
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?
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.
References (43)
- et al.
Continuing increase in mesothelioma mortality in Britain
Lancet
(1995) - et al.
Factors predictive of survival among 337 patients with mesothelioma treated between 1984 and 1994 by the Cancer and Leukemia Group B
Chest
(1998) - et al.
Prevention of malignant seeding after invasive diagnostic procedures in patients with pleural mesothelioma. A randomized trial of local radiotherapy
Chest
(1995) - et al.
Malignant pleural mesothelioma: radiotherapy for the prevention of seeding nodules
Rev Mal Respir
(2004) - et al.
Local recurrence of tumor at sites of intervention in malignant pleural mesothelioma
Lung Cancer
(2008) - et al.
A randomised controlled trial of intervention site radiotherapy in malignant pleural mesothelioma
Radiother Oncol
(2007) - et al.
Cytoreductive surgery and intraoperative hyperthermic intrathoracic chemotherapy in patients with malignant pleural mesothelioma or pleural metastases of thymoma
Chest
(2002) - et al.
Preventive irradiation after invasive diagnostic and therapeutic procedures in malignant pleural mesothelioma
Chest
(1996) - et al.
Prevention of tumour seeding following thoracoscopy in mesothelioma by prophylactic radiotherapy
Clin Oncol (Roy Coll Radiol)
(1995) - et al.
Needle-track metastases and prophylactic radiotherapy for mesothelioma
Respir Med
(2006)
Catheter-tract metastases associated with chronic indwelling pleural catheters
Chest
The role of radiation therapy in malignant pleural mesothelioma: a systematic review
Radiother Oncol
The role of radiotherapy in the treatment of malignant pleural mesothelioma
Clin Oncol (Roy Coll Radiol)
French Speaking Society for Chest Medicine (SPLF) Experts Group. Guidelines of the French Speaking Society for Chest Medicine for management of malignant pleural mesothelioma
Respir Med
Malignant pleural mesothelioma: ESMO clinical recommendations for diagnosis, treatment and follow-up
Ann Oncol
Radiation therapy in the management of patients with mesothelioma
Int J Radiat Oncol Biol Phys
Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial
Lancet
The European mesothelioma epidemic
Br J Cancer
Malignant pleural mesothelioma—an update
Int J Occup Environ Health
Prognostic factors in patients with pleural mesothelioma: the European Organization for Research and Treatment of Cancer experience
J Clin Oncol
Prognostic factors and survival in malignant pleural mesothelioma
Eur Respir J
Cited by (51)
A Narrative Review—Management of Malignant Pleural Effusion Related to Malignant Pleural Mesothelioma
2023, Heart Lung and CirculationProphylactic irradiation of tracts in patients with malignant pleural mesothelioma: A systematic review and meta-analysis of randomized trials
2021, Critical Reviews in Oncology/HematologyCitation Excerpt :in vitro studies showed that mesothelioma cell lines are radiosensitive (Carmichael et al., 1989; Hakkinen et al., 1996). Over past two decades, prophylactic irradiation of tracts (PIT) has been historically advocated to reduce the risk of tumor cell seeding at the site of a diagnostic or therapeutic intervention (Lee et al., 2009; De Ruysscher and Slotman, 2003). The efficacy basis was from a French trial published in 1995 (Boutin et al., 1995).
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
2016, The Lancet OncologyCitation Excerpt :Prophylactic radiotherapy to pleural intervention sites can be given with minimal side-effects; however, results from three small randomised controlled trials5–7 assessing its efficacy in reducing PTMs are conflicting and showed substantial variation in PTM incidence. Three meta-analyses8–10 of these data concluded that there was insufficient evidence to recommend the use of prophylactic radiotherapy. Specifically, there is a paucity of data regarding the incidence of clinically relevant, symptomatic nodules.