Elsevier

Lung Cancer

Volume 74, Issue 3, December 2011, Pages 486-491
Lung Cancer

Mesothelioma at era of helical tomotherapy: Results of two institutions in combining chemotherapy, surgery and radiotherapy

https://doi.org/10.1016/j.lungcan.2011.05.012Get rights and content

Abstract

Purpose

There is a scarce clinical experience about adjuvant helical tomotherapy (HT) in patients affected by malignant pleural mesothelioma (MPM) even though it appears as a useful technique to treat complex volume as the pleural cavity, and seems to have better dose distribution than the “classic” intensity modulated radiotherapy (IMRT).

Methods and materials

Twenty-four patients received adjuvant radiotherapy (RT) by HT from August 1st, 2007 to December 1st, 2009 at Curie Institute (Paris) and René Gauducheau Cancer Center (Nantes). Thirteen patients had neoadjuvant chemotherapy. Extrapleural pleuropneumonectomy (EPP) was done in 23 patients. Median dose to PTV was 50 Gy [48.7–55.9 Gy] (2 Gy/fraction). Acute and long term toxicities, disease free survival (DFS), overall survival (OS) and relapses are presented.

Results

Average follow up after RT was 7 months. The disease was staged mostly as T2–T3, N1–N2. Nineteen patients had epithelial type histology. Most patients tolerated radiotherapy with grade 1–2 side effects: redness of the skin, light cough or dyspnea, fatigue, nausea and odynophagia, mild increase of the post-operative thoracic pain. Grade 3 pneumonitis was suspected in 2 patients. Two grade 5 pneumonitis were also suspected. Eleven patients had a follow up of more than 6 months and no long term side effects related with HT were noted. At 24 months, 51.8% of patients were free of disease. Thirty percent of patients relapsed, with 2 patients presenting local relapses. Two patients died from recurrence.

Conclusion

With limited follow up, HT has comparable toxicity to those observed with traditional IMRT. Higher radiation dose and good coverage results in excellent local control.

Introduction

Malignant pleural mesothelioma (MPM) is a rare disease with poor prognosis. Its incidence is about 18 cases per million in Europe, and will increase to attain its peak in 2015 or 2020, more precisely between 18.5–22.3 and 5–6.8 per million in the French male and female population respectively [1], [2], [3]. It originates from the pleura and has a strong propensity to propagate. The surgery usually performed is an extrapleural pneumonectomy (EPP) but even with this extensive procedure, rates of local relapse (LR) remain 30–60% without adjuvant treatment [4], [5]. In attempts to reduce those numbers, radiotherapy was evaluated in number of phase II and retrospective studies. Relapse rates seem to lower to 5–35% with radiation, mostly with doses >50 Gy and modern techniques [6]. This decrease in local relapse highlights the importance of distant control. Chemotherapy also plays a role in neoadjuvant or adjuvant setting. The popularized combination of pemetrexed and cisplatin gained a wide acceptance but other regimens are also being experimented (gemcitabine, liposomized doxorubicin, raltitrexed) [7], [8], [9], [10].

Intensity modulated radiotherapy (IMRT) appears as a useful technique to treat the complex volume of the pulmonary cavity, mediastinum and the area of positive margins even though major issues were raised concerning associated pulmonary toxicities [11], [12], [13], [14]. As new IMRT techniques like helical tomotherapy (HT) or dynamic arc therapy seem to have better dose distribution, we propose to evaluate retrospectively the clinical outcomes of 24 patients treated by HT from two cancer centers in France [15]. This article presents acute toxicity results, overall survival (OS) and disease free survival (DFS) with an average follow up of 7 months after radiotherapy.

Section snippets

Patients

Included in our present study are 24 consecutive patients, who were evaluated to receive adjuvant radiotherapy from August 1st, 2007 to December 1st, 2009 at the following centers: Curie Institute of Paris and René Gauducheau Cancer Center of Nantes. HT was used in all these patients as the modality of delivery of radiotherapy. No patient was treated by classic 3D radiotherapy during this period. All patients underwent a complete staging with a head, thorax, upper abdomen CT-scan and a PET

Patients and treatments

Twenty-four patients received radiotherapy by HT following their surgery. From initial diagnosis, patients had a median follow up of 11.3 months. From radiotherapy ending, patients had an average follow up of 7 months, with 8 patients having more than a year of follow up (1–24 months). Their characteristics are presented in Table 1. They were mostly men of 60 years old. Half of them had a documented history of asbestos exposure. One woman of 34 years old had a previous thoracic irradiation for

Discussion

We present the most important series of MPM patients treated by HT as an adjuvant treatment to EPP to date. Our patients were staged, diagnosed and treated in a relatively homogeneous way. The radiotherapy was regulated by a published national consensus, even though there were slight disparities between the two centers. The implementation of this new technology was also part of a national project of access to new technology in radiotherapy. Other articles presented comparison between regular

Conclusion

As experience grows with HT, toxicities will be further decreased. As the dosimetric study of traditional IMRT by Allen et al. has shown us, new technology needs new knowledge and skills [12], [13]. Prospective studies and longer follow up are needed to confirm the results presented in this current study. The balance between the toxicities and the beneficial outcome expected will hopefully confer an advantage to patients with MPM. Concerns about integral dose will be further addressed and the

Conflicts of interest statement

None declared.

Ethical approval for research

Yes.

Source of funding

None.

Name of principal investigator

Philippe Giraud.

Acknowledgements

The authors would like to thank all physicians, physicists and therapists who helped in the success of this project. We also would like to thank the French National Institute of Cancer (INCa) for their support and the Royal College of Physicians and Surgeons of Canada for the Professional Development Grant.

References (25)

Cited by (14)

  • High dose irradiation after pleurectomy/decortication or biopsy for pleural mesothelioma treatment

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    After EPP, adjuvant hemithorax radiotherapy to the chest cavity has been shown to improve local control and survival [9]. Intensity-modulated radiation therapy, in particular, intensity modulated arc therapy would appear to be the most effective adjuvant treatment [10–13]. Recently, the practice of extrapleural pneumonectomy has waned, mainly because it is burdened by higher morbidity and mortality than pleurectomy/decortication [14–17].

  • The role of radical radiotherapy in the management of malignant pleural mesothelioma: A systematic review

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    Rates of local control at one year were reported to be significantly worse in patients with non-epithelioid histology compared to their epithelioid counterparts (non-epithelioid: 0% (95% CI 0%); epithelioid: 83.3% (95% CI 53.5–100%); P = 0.0011). Clinical outcomes following adjuvant HT post-EPP were reported by 2 French institutions in 2011 [43]. A cohort of 24 patients received adjuvant radiotherapy at a dose of 50 Gy to the surgical cavity and 57 Gy to areas of clinical concern as identified by FDG-PET.

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