Phase III randomised trial
A randomised controlled trial of intervention site radiotherapy in malignant pleural mesothelioma

https://doi.org/10.1016/j.radonc.2007.05.022Get rights and content

Abstract

Background and purpose

To assess the effectiveness of radiotherapy in preventing tumour seeding after chest drain or pleural biopsy in patients with malignant mesothelioma and to determine, if tract metastases appear, whether they are tender or troublesome to patients.

Patients and methods

Patients with a histological diagnosis of pleural mesothelioma and an invasive procedure within the preceding 21 days were stratified by age, performance status and treatment centre. Randomisation was performed between immediate drain site radiotherapy 21 Gy in three fractions (XRT arm) or best supportive care (BSC) with follow-up to 12 months. Patients were asked to complete questionnaires on treatment toxicity and on symptoms from any tract metastases detected.

Results

Sixty-one patients were recruited from two centres between 1998 and 2004; 56 men, 5 women, median age 70. 31 were allocated to drain site radiotherapy. Seven patients developed tract metastases associated with the drain site (four XRT arm, three BSC) and four developed metastases associated with subsequent procedures at other sites (three XRT, one BSC). Two patients each developed two tract metastases. Of the 12 metastases, nine overlay the previous drain site but three were adjacent to the site. No statistically significant difference was found in the risk of tract metastasis associated with the drain site between the arms (p = 0.748).

Conclusions

Prophylactic drain site radiotherapy in malignant pleural mesothelioma does not reduce the incidence of tumour seeding by the margin indicated by previous studies.

Section snippets

Patients and methods

Patients with a histological diagnosis of malignant pleural mesothelioma and an intervention site to the pleura within the preceding 21 days were considered for entry into the study. Exclusion criteria were expected survival less than 3 months and prior systemic chemotherapy or local radiotherapy for their disease. Patients were allocated to treatment using the minimization technique to ensure the two arms were well balanced. Facilities for central telephone registration/randomisation were

Statistical analysis

On the basis of the previous Boutin study this trial was designed to detect a difference in the incidence of patients developing tract metastasis from 40% (no radiotherapy) to 5% (with radiotherapy). Based on a comparison of proportions using Pearson’s chi-square test (80% power, 5% two-sided level of statistical significance) this required 22 patients to be recruited to each treatment arm.

In view of the high attrition rate on study due to patient deaths this calculation was subsequently

Pre-treatment

All randomised patients are included in the analysis (by intention-to-treat). Sixty-one patients were recruited between February 1998 and August 2004. There were 56 men and five women, age range 47–84 years, median age 70. Fifty-three patients were entered from Glasgow and eight from Newcastle. ECOG Performance status (PS) was 0 in 21 patients (34%), PS 1 in 27 patients (44%), PS 2 in 10 patients (16%) and PS 3 in 3 patients (5%). Age, performance status and centre were very balanced between

Discussion

Prophylactic radiotherapy to intervention sites in malignant pleural mesothelioma has been widely adopted around the world following publication of two small studies ten years ago. It is recognised that mesothelioma patients are at risk of developing subcutaneous tumour deposits following intervention and it seemed that local radiotherapy in short fractionated courses to superficial depth was effective in preventing this complication.

Our local experience in Glasgow on adopting this treatment

Conclusion

Radiotherapy to the drain site in mesothelioma patients does not reduce the incidence of seeding of tumour subcutaneously. Tract metastases, when they do occur, may be small and asymptomatic. We do not recommend routine prophylactic irradiation of drain sites.

Acknowledgements

The authors acknowledge the support of Cancer Research UK, for statistical input to design and analysis of the trial, and to the data collection staff in Glasgow and Newcastle, as well as the respiratory physicians who referred their patients for consideration of treatment.

References (4)

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