Open lung-sparing surgery for malignant pleural mesothelioma: the benefits of a radical approach within multimodality therapy

Department of Thoracic Surgery, Glenfield Hospital, Groby Road, Leicester LE3 9QA, United Kingdom.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery (Impact Factor: 3.3). 10/2008; 34(4):886-91. DOI: 10.1016/j.ejcts.2008.06.010
Source: PubMed


To identify the optimal debulking procedure in patients with malignant pleural mesothelioma who are not suitable for extrapleural pneumonectomy (EPP).
We reviewed 102 consecutive patients (93 male; 9 female, mean age 63 years) who were not suitable for EPP because of either advanced tumour stage or suboptimal fitness. Patients underwent either a non-radical tumour decortication to obtain lung expansion (group NR) or latterly a radical pleurectomy/decortication to obtain macroscopic tumour clearance (group R). We analysed the comparative perioperative courses and long-term survival.
The two groups were similar for age and gender distribution but epithelioid type was more predominant in group R: 78% compared to 55% epithelioid in group NR. Thirty-day mortality was similar (5.9% in group R and 9.8% in the group NR, p=0.36) but 90-day mortality was significantly higher in the group NR (29.4% vs 9.8% in group R, p=0.012). More patients in group R received adjuvant chemotherapy (65% vs 28%, p=0.000) and radiotherapy (65% vs 26%, p=0.000). Median survival for all cell types was significantly higher in group R (15.3 months vs 7.1 months, p<0.000). Group R survival rates at 1, 2, 3 and 4 years were 53, 41, 25 and 13%, respectively while for group NR they were 32, 9.6, 2 and 0%, respectively. For epithelioid cell type there was still a significant median survival advantage in group R (25.4 months vs 10.2 months, p<0.000), but there was no difference for sarcomatoid (9.3 months vs 3.2 months, p=0.16) or biphasic cell types (9.4 months vs 7 months, p=0.38).
If a patient with epithelioid MPM is fit enough to tolerate a thoracotomy then macroscopic clearance of the tumour is the preferred option as part of a multimodality regime including chemotherapy.

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Available from: Apostolos Nakas
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    • "The authors reported that radical surgery in the form of EPP within trimodal therapy offers no benefit for survival or quality of life[20]. Several studies evaluated the potential role of adjuvant RT in MPM[4,6,19]; however, to date there has been limited reported experience in the feasibility of dose escalation with IMRT for unresectable MPM[21,22]. In our study, for the first time, we demonstrated from a dosimetric/radiobiological point of view the potential of HT to selectively increase the dose to high-risk areas detected by 18 FDG-PET from 62.5 to 70 Gy using an accelerated hypofractionated regimen in 25 fractions ; with a simultaneous integrated boost (SIB) to the pleural cavity of 56 Gy without significantly increasing the toxicity risk in the surrounding normal organs. "
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    ABSTRACT: Aim: The aim of this study was to investigate whether a safe escalation of the dose to the pleural cavity and PET/CT-positive areas in patients with unresectable malignant pleural mesothelioma (MPM) is possible using helical tomotherapy (HT). Material and methods: We selected 12 patients with MPM. Three planning strategies were investigated. In the first strategy (standard treatment), treated comprised a prescribed median dose to the planning target volume (PTV) boost (PTV1) of 64.5 Gy (range: 56 Gy/28 fractions to 66 Gy/30 fractions) and 51 Gy (range: 50.4 Gy/28 fractions to 54 Gy/30 fractions) to the pleura PTV (PTV2). Thereafter, for each patient, two dose escalation plans were generated prescribing 62.5 and 70 Gy (2.5 and 2.8 Gy/fraction, respectively) to the PTV1 and 56 Gy (2.24 Gy/fraction) to the PTV2, in 25 fractions. Dose-volume histogram (DVH) constraints and normal tissue complication probability (NTCP) calculations were used to evaluate the differences between the plans. Results: For all plans, the 95 % PTVs received at least 95 % of the prescribed dose. For all patients, it was possible to perform the dose escalation in accordance with the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) constraints for organs at risk (OARs). The average contralateral lung dose was < 8 Gy. NTCP values for OARs did not increase significantly compared with the standard treatment (p > 0.05), except for the ipsilateral lung. For all plans, the lung volume ratio was strongly correlated with the V20, V30, and V40 DVHs of the lung (p < 0.0003) and with the lung mean dose (p < 0.0001). Conclusion: The results of this study suggest that by using HT it is possible to safely escalate the dose delivery to at least 62.5 Gy in PET-positive areas while treating the pleural cavity to 56 Gy in 25 fractions without significantly increasing the dose to the surrounding normal organs.
    Full-text · Article · Oct 2015 · Strahlentherapie und Onkologie
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    • "Therefore, discrepancies concerning performance practices and recommendations for P/D and EPP clearly exist. Furthermore, many MPM centers in Europe and some in North America and Japan are currently performing P/D with curative intent [20, 21, 28, 29, 33–37]. "
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    ABSTRACT: Malignant pleural mesothelioma (MPM) is associated with a very poor prognosis. Unlike other solid tumors, any type of planned surgery for MPM would be cytoreductive rather than radical. There are two types of surgery for MPM. Extrapleural pneumonectomy (EPP) involves en bloc resection of the lung, pleura, pericardium, and diaphragm. Pleurectomy/decortication (P/D) is a lung-sparing surgery that removes only parietal/visceral pleura. In comparison with EPP, P/D is theoretically less radical but is associated with less perioperative mortality/morbidity and less postoperative deterioration of cardiopulmonary function. It still remains unclear which surgical technique is superior in terms of the risk/benefit ratio. In this context, selection between EPP and P/D has been a matter to debate.
    Preview · Article · Mar 2014 · General Thoracic and Cardiovascular Surgery
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    • "Nakas et al. [26] maintained a prospectively updated database which they used to analyse patients that underwent P/D only. These were patients unfit for EPP. "
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    ABSTRACT: Introduction. Malignant pleural mesothelioma (MPM) is an aggressive cancer arising from pleural mesothelium. Surgery aims to either cure the disease or control the symptoms. Two surgical procedures exist: extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). In this systematic review we assess current evidence on safety and efficacy of surgery. Methods. Five electronic databases were reviewed from January 1990 to January 2013. Studies were selected according to a predefined protocol. Primary endpoint was overall survival. Secondary endpoints included quality of life, disease-free survival, disease recurrence, morbidity, and length of hospital stay. Results. Sixteen studies were included. Median survival ranged from 8.1 to 32 months for P/D and from 6.9 to 46.9 months for EPP. Perioperative mortality was 0%-9.8% and 3.2%-12.5%, respectively. Perioperative morbidity was 5.9%-55% for P/D and 10%-82.6% for EPP. Average length of stay was 7 days for P/D and 9 days for EPP. Conclusion. Current evidence cannot definitively answer which procedure (EPP or P/D) is more beneficial in terms of survival and operative risks. This systematic review suggests that surgery in the context of trimodality therapy offers acceptable perioperative outcomes and long-term survival. Centres specialising in MPM management have better results.
    Full-text · Article · Feb 2014
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