Radiation Therapy For Malignant Pleural Mesothelioma Research Articles

Survival benefit after radiotherapy for patients with malignant pleural mesothelioma: A propensity score-matched study.

Survival benefit after radiotherapy for patients with malignant pleural mesothelioma: A propensity score-matched study.

Initial clinical experience treating patients with palliative radiotherapy for malignant pleural mesothelioma on the HalcyonTM linear accelerator.

Radiation therapy (RT) can provide effective symptomatic palliation in patients with malignant pleural mesothelioma (MPM). Advances in RT technology, including intensity-modulated RT (IMRT) and volumetric-modulated arc therapy (VMAT), have improved treatment conformality, potentially improving the therapeutic ratio of RT. A novel 6-MV flattening-filter-free O-ring linear accelerator, HalcyonTM (Varian Medical Systems, Palo Alto, CA, USA), was built to provide such advanced therapies, while possibly reducing treatment time. Here, we report the initial clinical experience using HalcyonTM to deliver palliative RT for patients with MPM. We retrospectively assessed consecutive patients with MPM who received thoracic RT on HalcyonTM. Their electronic medical records were reviewed for clinical, RT planning, treatment timing, and image-guidance RT (IGRT) data. Four patients with metastatic MPM received palliative RT on HalcyonTM between 1/2017-1/2020 for severe pain (50%), dysphagia (25%), or dyspnea (25%). Targets included a combination of pleura, chest wall, lung, hilum, and mediastinum, with patient-specific dose and fractionation regimens ranging from 20-45 Gy in 5-15 fractions, and 75% of patients receiving concurrent systemic therapy. Pre-specified target and organ-at-risk constraints were met for nearly all plans. At a median follow-up of 2.2 months (range, 1.6-7.1 months), all patients experienced either improved (75%) or stable (25%) tumor-related symptoms following palliative RT. The mean 3D vector couch correction was 0.67±0.15 cm. The mean beam-on, treatment (beam-on plus cone-beam computed tomography times), and approximated total room usage times were 1.6±0.2, 1.8±0.2, and 9.8±0.2 min, respectively. Grade 2 fatigue and cough occurred in 25% and 25% of patients, and no patients experienced Grade ≥3 toxicity. In this initial clinical experience treating patients with palliative RT for MPM on HalcyonTM, treatment provided symptom palliation and local control across multiple palliative scenarios, with minimal toxicity, acceptable dosimetry, and setup corrections and treatment times that compared favorably with other published experiences of MPM RT. Palliative RT on HalcyonTM can provide patients with MPM quick and safe tumor-related symptom relief, even in a frail, elderly population.

Complex Target Volume Delineation and Treatment Planning in Radiotherapy for Malignant Pleural Mesothelioma (MPM)

Introduction: Radiotherapy alone or combined with surgery and/or chemotherapy is being investigated in the treatment of malignant pleural mesothelioma (MPM). This study aimed to simulate a Volumetric Modulated Arc Therapy (VMAT) treatment of a patient with MPM. Materials and Methods: CT images from a patient with intact lungs were imported via DICOM into the Pinnacle3 treatment planning (TP) system (TPS) and used as a model for MPM to delineate organs at risk (OAR) and both clinical and planning target volumes (CTV and PTV) with a margin of 5 mm. Elekta Synergy with 6 MV photons and 80 leafs MLCi2 was employed. VMAT plans were generated using two coplanar arcs with gantry rotation angles of 178&deg - 182&deg, the collimator angles of each arc were set to 90&deg, Octavius® 4D 729 was employed for quality assurance while the calculated and measured doses were compared using VeriSoft. Results: A TP was achieved. The Gamma volume analysis with criteria of 3 mm distance to agreement and 3% dose difference yielded the gamma passing rate = 99.9%. The reference isodose was 42.75 Gy with the coverage constraints for the PTV D95 and V95 = 95.0% of 45 Gy. The remaining dosimetric parameters met the recommendations from the clinically acceptable guidelines for the radiotherapy of MPM. Conclusion: Using well-defined TV and VMAT, a consistent TP compared to similar ones from publications was achieved. We obtained a high agreement between the 3D dose reconstructed and the dose calculated.

MA05.02 Log Odds of Positive Lymph Nodes Predicts Overall Survival and the Benefit of Postoperative Radiotherapy in Malignant Pleural Mesothelioma

Nodal categories of malignant pleural mesothelioma (MPM) are mostly adopted from lung cancer staging criteria and the N descriptors in the eighth edition of TNM staging system have not been fully verified. We aimed to evaluate the effectiveness of the current N descriptors and a novel prognosticator—the log odds of positive lymph nodes (LODDS)—in predicting overall survival (OS) and postoperative radiotherapy (PORT) benefit in MPM. Patients in the Surveillance, Epidemiology, and End Results (SEER) database with MPM undergoing surgery and lymph nodes examination were extracted and restaged according to the 8th edition TNM staging system. LODDS was calculated as loge[(positive nodes count+0.5)/(negative nodes count+0.5)]. X-tile software determined the optimal cut-point for LODDS. Log-rank tests along with Cox regression analyses were adopted for survival analyses. Harrell's C-index statistic measured discriminatory ability and prognostic performance. A total of 534 patients were enrolled in this study. N descriptors were unevenly distributed. Most cases were staged as N0 (51.9%) and N1 (47.0%), with only 1.1% staged as N2. The eighth edition N descriptors failed to clarify the survival difference between adjacent categories and were incapable of predicting PORT benefit. The cut-points for LODDS were classified as follows: LODDS1 (≤-2.61), LODDS2 (-2.56≤LODDS≤0.62), and LODDS3 (≥0.87). The median survival of LODDS1 was 23.1 months compared with 17.9 months (HR=1.397, P=0.005) and 13.0 months (HR=2.317, P<0.001) for LODDS2 and LODDS3, respectively. The survival curves stratified by LODDS separated nicely without overlapping and the benefit of PORT was limited to cases with LODDS3 (≥0.87). LODDS also provided better C-index than the conventional N descriptors. LODDS performs better than N descriptors for predicting survival and benefits of PORT in resected MPM, and it could be considered as a potential parameter to compensate for defects in the 8th AJCC TNM staging for MPM.

Invited letter to the editor on the editorials on “High dose irradiation after pleurectomy/decortication or biopsy for pleural mesothelioma treatment”

It is with great interest that we read the two editorials, “Non-ablative hypofractionated hemithoracic radiation—a new standard of care in mesothelioma?” by de Perrot and Cho (1) and “Lung-sparing intensity-modulated radiotherapy in malignant pleural mesothelioma: palliative or potentially radical?” by Botticella and De Ruysscher (2), both addressed to our previous publication on hypofractionation and pleural mesothelioma (3). We thank the physicians for their comments and take the opportunity of responding in this Letter to the Editor.

OC-0620: Dose constraints for hypofractionated, dose escalated radiotherapy in malignant pleural mesothelioma

OC-0620: Dose constraints for hypofractionated, dose escalated radiotherapy in malignant pleural mesothelioma

Single-institution experience of intensity-modulated radiotherapy for malignant pleural mesothelioma at University of Catania.

The multimodal approach to malignant pleural mesothelioma is gradually becoming the standard of care for this disease in patients with good performance status. Materials &methods: We report our experience concerning eight cases treated with the use of static step-and-shoot intensity-modulated radiotherapy to the whole pleural cavity, in patients already undergoing surgical and/or antiblastic therapy. Results &conclusion: Results at a median follow-up of 16months showed a median survival from the initial treatment of 29months, with lung toxicity of grade II reported only in two patients.

SYSTEMS-2: A randomised phase II study of radiotherapy dose escalation for pain control in malignant pleural mesothelioma

SYSTEMS-2 is a randomised study of radiotherapy dose escalation for pain control in 112 patients with malignant pleural mesothelioma (MPM). Standard palliative (20 Gy/5#) or dose escalated treatment (36 Gy/6#) will be delivered using advanced radiotherapy techniques and pain responses will be compared at week 5. Data will guide optimal palliative radiotherapy in MPM.

MS 06.05 The Use of Adjuvant IMRT after Pleurectomy/Decortication

MS 06.05 The Use of Adjuvant IMRT after Pleurectomy/Decortication

Low-dose photon irradiation induces invasiveness through the SDF-1α/CXCR4 pathway in malignant mesothelioma cells

BackgroundLow-dose photon irradiation has repeatedly been suspected to increase a risk of promoting local recurrence of disease or even systemic dissemination. The purpose of this study was to investigate the motility of malignant pleural mesothelioma (MPM) cell lines after low-doses of photon irradiation and to elucidate the mechanism of the detected phenotype.MethodsH28 and H226 MPM cells were examined in clonogenic survival experiments and migration assays with and without various doses of photon and carbon ion irradiation. C-X-C chemokine receptor type 4 (CXCR4), SDF-1α, β1 integrin, α3 integrin, and α5 integrin expressions were analyzed by quantitative FACS analysis, ELISA and western blots. Apoptosis was assessed via Annexin-V-staining.ResultsThe migration of MPM cells was stimulated by both fetal bovine serum and by stromal cell-derived factor 1α (SDF-1α). Low doses of photon irradiation (1 Gy and 2 Gy) suppressed clonogenicity, but promoted migration of both H28 and H226 cells through the SDF-1α/CXCR4 pathway. Hypermigration was inhibited by the administration of CXCR4 antagonist, AMD3100. In contrast, corresponding doses of carbon ion irradiation (0.3 Gy and 1 Gy) suppressed clonogenicity, but did not promote MPM cell migration.ConclusionOur findings suggest that the co-administration of photon irradiation and the CXCR4-antagonist AMD3100 or the use of carbon ions instead of photons may be possible solutions to reduce the risk of locoregional tumor recurrence after radiotherapy for MPM.

Does selective pleural irradiation of malignant pleural mesothelioma allow radiation dose escalation? : A planning study.

After lung-sparing radiotherapy for malignant pleural mesothelioma (MPM), local failure at sites of previous gross disease represents the dominant form of failure. Our aim is to investigate if selective irradiation of the gross pleural disease only can allow dose escalation. In all, 12consecutive stage I-IV MPM patients (6left-sided and 6right-sided) were retrospectively identified and included. Amagnetic resonance imaging-based pleural gross tumor volume (GTV) was contoured. Two sets of planning target volumes (PTV) were generated for each patient: (1)a"selective" PTV (S-PTV), originating from a5-mm isotropic expansion from the GTV and (2)an "elective" PTV (E-PTV), originating from a5-mm isotropic expansion from the whole ipsilateral pleural space. Two sets of volumetric modulated arc therapy (VMAT) treatment plans were generated: a"selective" pleural irradiation plan (SPI plan) and an "elective" pleural irradiation plan (EPI plan, planned with asimultaneous integrated boost technique [SIB]). In the SPI plans, the average median dose to the S‑PTV was 53.6 Gy (range 41-63.6 Gy). In 4 of 12patients, it was possible to escalate the dose to the S‑PTV to >58 Gy. In the EPI plans, the average median doses to the E‑PTV and to the S‑PTV were 48.6 Gy (range 38.5-58.7) and 49 Gy (range 38.6-59.5 Gy), respectively. No significant dose escalation was achievable. The omission of the elective irradiation of the whole ipsilateral pleural space allowed dose escalation from 49 Gy to more than 58 Gy in 4 of 12chemonaive MPM patients. This strategy may form the basis for nonsurgical radical combined modality treatment of MPM.

Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial

Postoperative hemithoracic radiotherapy has been used to treat malignant pleural mesothelioma, but it has not been assessed in a randomised trial. We assessed high-dose hemithoracic radiotherapy after neoadjuvant chemotherapy and extrapleural pneumonectomy in patients with malignant pleural mesothelioma. We did this phase 2 trial in two parts at 14 hospitals in Switzerland, Belgium, and Germany. We enrolled patients with pathologically confirmed malignant pleural mesothelioma; resectable TNM stages T1-3 N0-2, M0; WHO performance status 0-1; age 18-70 years. In part 1, patients were given three cycles of neoadjuvant chemotherapy (cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 given every 3 weeks) and extrapleural pneumonectomy; the primary endpoint was complete macroscopic resection (R0-1). In part 2, participants with complete macroscopic resection were randomly assigned (1:1) to receive high-dose radiotherapy or not. The target volume for radiotherapy encompassed the entire hemithorax, the thoracotomy channel, and mediastinal nodal stations if affected by the disease or violated surgically. A boost was given to areas at high risk for locoregional relapse. The allocation was stratified by centre, histology (sarcomatoid vs epithelioid or mixed), mediastinal lymph node involvement (N0-1 vs N2), and T stage (T1-2 vs T3). The primary endpoint of part 1 was the proportion of patients achieving complete macroscopic resection (R0 and R1). The primary endpoint in part 2 was locoregional relapse-free survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00334594. We enrolled patients between Dec 7, 2005, and Oct 17, 2012. Overall, we analysed 151 patients receiving neoadjuvant chemotherapy, of whom 113 (75%) had extrapleural pneumonectomy. Median follow-up was 54·2 months (IQR 32-66). 52 (34%) of 151 patients achieved an objective response. The most common grade 3 or 4 toxic effects were neutropenia (21 [14%] of 151 patients), anaemia (11 [7%]), and nausea or vomiting (eight [5%]). 113 patients had extrapleural pneumonectomy, with complete macroscopic resection achieved in 96 (64%) of 151 patients. We enrolled 54 patients in part 2; 27 in each group. The main reasons for exclusion were patient refusal (n=20) and ineligibility (n=10). 25 of 27 patients completed radiotherapy. Median total radiotherapy dose was 55·9 Gy (IQR 46·8-56·0). Median locoregional relapse-free survival from surgery, was 7·6 months (95% CI 4·5-10·7) in the no radiotherapy group and 9·4 months (6·5-11·9) in the radiotherapy group. The most common grade 3 or higher toxic effects related to radiotherapy were nausea or vomiting (three [11%] of 27 patients), oesophagitis (two [7%]), and pneumonitis (two [7%]). One patient died of pneumonitis. We recorded no toxic effects data for the control group. Our findings do not support the routine use of hemithoracic radiotherapy for malignant pleural mesothelioma after neoadjuvant chemotherapy and extrapleural pneumonectomy. Swiss Group for Clinical Cancer Research, Swiss State Secretariat for Education, Research and Innovation, Eli Lilly.

Optimal Definition of Target Volumes in Lung-Sparing Pleural Radiotherapy for Malignant Pleural Mesothelioma (Mpm)

ABSTRACT Aim: High dose lung-sparing pleural radiotherapy for malignant mesothelioma is difficult. Accurate target delineation is critical. The optimal imaging modality to define radiotherapy target volumes has not been studied in depth. This is the aim of the present study. Methods: Twelve consecutive patients with a histopathological diagnosis of stage I-III MPM (6 left-sided and 6 right-sided) were included. CT scans with iv contrast, 18FDG-CT/PET scans and MRI scans were obtained. CT scans were rigidly co-registered with 18FDG-CT-PET and with MRI scans. Four sets of pleural GTVs were defined: based on CT, on CT/PET, on CT/MRI and on CT/PET/MRI. The pleural tumour was contoured; mediastinal nodes were excluded. “Quantitative” evaluation of the volumesincluded the coefficient of variation [COV, defined as the ratio between the standard deviation and the mean]) and pairwise comparison of the overlap index with the Jaccard index (JI, defined as the ratio of the intersection between two volumes and their union). “Qualitative” (visual) assessment of the different volumes was also performed, in order to evaluate the “geographical miss”. Results: Pairwise comparison with the Jaccard Index PAIRWISE COMPARISON JI CT vs. CT+CT-PET 0.97 CT vs. CT+MRI 0.91 CT vs. CT+PET+MRI 0.91 CT+CT-PET vs. CT+MRI 0.91 CT+CT-PET vs. CT+PET+MRI 0.91 CT+MRI vs. CT+PET+MRI 0.99 Mean GTV CT was the smallest volume (655.9+322.1 cc): when compared with CT/PET-based, CT/MRI-based and CT/PET/MRI-based volumes, they were respectively 1.26%, 5.33% and 5.9% larger. COV was lower in MRI-based contours (0.43 vs 0.48-0.49), indicating a lower dispersion of the values. Mean JI ranges from 0.91 and 0.99: a lower concordance was registered between CT/MRI-based contours versus all the others. “Geographical miss” was identified in 11/12 patients in CT/MRI-based contours and in 4/12 patients in CT/PET-based volumes. Conclusions: To the best of our knowledge, this is the first study showing that the integration of MRI into the target volume definition in hemithoracic radiotherapy in MPM may allow to improve the accuracy of target delineation and reduce the likelihood of geographical misses. Disclosure: All authors have declared no conflicts of interest.

Radical pleurectomy/decortication followed by high dose of radiation therapy for malignant pleural mesothelioma. Final results with long-term follow-up

PurposeWe have previously shown the feasibility of delivering high doses of radiotherapy in malignant pleural mesothelioma (MPM) patients who underwent radical pleurectomy/decortication (P/D) or surgical biopsy. In this report, we present the long-term results of MPM patients treated with radical P/D followed by high doses of radiotherapy. Methods and materialsTwenty consecutive MPM patients were enrolled in this prospective study and underwent radical P/D followed by high dose radiotherapy. The clinical target volume was defined as the entire hemithorax excluding the intact lung. The dose prescribed was 50Gy in 25 fractions. Any FDG-avid areas or regions of particular concern for residual disease were given a simultaneous boost to 60Gy. Nineteen patients received cisplatin/pemetrexed chemotherapy. Kaplan–Meier analysis was used to calculate rates of overall survival (OS), progression-free survival (PFS), and loco-regional control (LRC). ResultsThe median follow-up was of 27 months. The median OS and PFS were 33 and 29 months, respectively. The median LRC was not reached. The Kaplan–Meier estimates of OS at 2 and 3 years were 70% and 49%, respectively. The estimates of PFS at 2 and 3 years were 65% and 46%, respectively. The estimates of LRC at 2 and 3 years were 68% and 59%, respectively. The predominant pattern of failure was distant: 7 patients developed distant metastases as the first site of relapse, whereas only 3 patients experienced an isolated loco-regional recurrence. No fatal toxicity was reported. Five Grades 2–3 pneumonitis were documented. ConclusionsHigh dose radiation therapy following radical P/D led to excellent loco-regional control and survival results in MPM patients. A median OS of 33 months and a 3-year OS rate of 49% are among the best observed in recent studies, supporting the idea that this approach represents a concrete therapeutic option for malignant pleural mesothelioma.

Radiotherapy applications of patients with malignant mesothelioma: A single center experience

BackgroundIn the management of malignant pleural mesothelioma, radiotherapy has been used for the purpose of prophylaxis to reduce the incidence of recurrence at surgical insertion sites or palliate the symptoms. AimThe purpose of the study was to evaluate the techniques and effectiveness of radiotherapy in malignant pleural mesothelioma. Materials and methodsForty-four (18 female, 26 male) patients diagnosed with malignant pleural mesothelioma were retrospectively evaluated. All patients had surgery or thoracoscopic biopsy for diagnosis, staging or treatment and all received palliative or prophylactic radiotherapy. Fifty-seven percent of the patients received chemotherapy. ResultsProphylactic radiation was applied to 27 patients with 4–15MeV electron energies. The median radiotherapy dose was 30Gy with 3Gy daily fraction dose. During treatment, 12 patients had grade 1 erythema according to the RTOG scale. In 3 (12%) patients, a local failure at treatment field was observed. Palliative radiotherapy was applied to 17 patients for pain palliation. The median radiation dose was 40Gy with 2Gy daily fraction dose by using 6–18MV photon and/or 4–12MeV electron energies. Two patients had grade 1 erythema and one patient had grade 2 odynophagy according to the RTOG scale. For 10 (59%) patients, palliation of chest pain was delivered. No late toxicity was observed for all cases. ConclusionOur experience showed that prophylactic and palliative radiotherapy are effective and safe therapy modalities in malignant pleural mesothelioma in preventing seeding metastasis at intervention sites or relieving pain. Prospective randomized studies are still needed to determine the benefits of radiotherapy application and to indicate optimum dose schemes.

Intrathoracic latissimus dorsi muscle transposition: a reliable technique for prevention of bronchopleural fistula developing after extrapleural pneumonectomy and external beam radiotherapy in malignant pleural mesothelioma

Objective Bronchopleural fistula (BPF) is a life threatening complication after pneumonectomy. Extra thoracic skeletal muscle transposition especially latissimus dorsi muscle flap (LDMF) had been used to prevent this complication. The aim of this study was to assess the effectiveness of LDMF in preventing BPF developing after extrapleural pneumonectomy (EPP) and external radiation therapy in malignant pleural mesothelioma (MPM).

Induction chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy for malignant pleural mesothelioma: experience of Guy’s and St Thomas’ hospitals

The treatment of malignant pleural mesothelioma (MPM) remains controversial. We present a prospective study of patients treated at our institution with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP), and radical radiotherapy. Patients with MPM who were eligible for EPP and multimodality therapy were included in this study. Staging was through computed tomography and positron emission tomography and computed tomography (PET/CT) scanning, video-assisted thoracoscopic surgery (VATS), and mediastinoscopy. Our protocol involved three cycles of cisplatin-based neoadjuvant chemotherapy followed by extrapleural pneumonectomy and adjuvant radiotherapy (54 Gy). All patients were followed up every 3-6 months until death. From March 2004 through October 2008, 25 patients were referred for EPP following neoadjuvant chemotherapy. EPP was performed in all but three patients, who were found to have T4 disease at surgery. Surgical complications included arrhythmias (28%), bronchopleural fistulas (12 %), reoperations for bleeding (8%), acute respiratory distress syndrome (4%), pneumonia (4%), septicemia (4%), vocal cord palsy (4%), and Horner's syndrome (4%). The 30-day mortality was 4%. Adjuvant radiotherapy was administered to 81% of patients after EPP. Radiotherapy toxicities included thrombocytopenia, radiation pneumonitis, pulmonary embolus, radiation hepatitis, herpes zoster, transverse myelitis, and late constrictive pericarditis. Median survival from diagnosis was 12.8 months (95% confidence interval 7.8-17.7 months). One-year survival was 54.5%; 2-year survival was 18.2%. Disease progression occurred in 77.3% of patients. Nodal status (N0 disease versus N1-N2) or histology (epithelioid versus biphasic) had no significant impact on survival. Despite recent advances in chemotherapy, surgery, and radiotherapy, survival rates remain low for patients with MPM completing multimodality therapy including EPP.

What Is the Role of Radiotherapy in Malignant Pleural Mesothelioma?

A review of the evidence supporting the use of radiotherapy in patients with mesothelioma was performed. Relevant publications were searched for on Medline. In a Medline search on radiotherapy and mesothelioma, 611 hits were obtained. A limited number of prospective phase II trials of radiotherapy as part of trimodality protocols for early disease and in the palliation of pain were found, along with three small randomized controlled trials of port-site prophylaxis. No randomized data exist to support the use of radiotherapy after radical surgery, although there are a large number of publications describing its use as an integral part of therapy, including seven phase II studies. One ongoing trial is randomizing patients to radiotherapy or not after extrapleural pneumonectomy. None of these studies provided any assessment of radiotherapy independent of the other modalities investigated, nor did any formally assess intensity-modulated radiotherapy. There have been several reports of excessive toxicity with this technique, and its use should be limited to phase I studies until the basis of this toxicity is better understood. Three trials have looked at port-site prophylaxis, one supporting its use and two showing no evidence of benefit. Two studies addressed pain control prospectively, one showing definite but short-lived benefits. Implications. Radiotherapy is widely used in treating mesothelioma with little supporting evidence. More randomized trials are required to justify this use in all three common settings for its use.

Phase II trial of extrapleural pneumonectomy followed by adjuvant radiotherapy in malignant pleural mesothelioma

7579 Background: This phase II clinical study was conducted to evaluate the effectiveness of the association of extrapleural pneumonectomy followed by radiation therapy in patients with potentially resectable malignant pleural mesothelioma (MPM). Methods: Eligible patients had histologically proven epithelial or mixed MPM with clinical stage T1–3, N0–2, M0 disease considered to be completely resectable and a WHO performance status of 0 or 1. Surgery had to consist of a complete extrapleural pneumonectomy including resection of pericardium and diaphragm. Postoperative radiotherapy (40 Gy) was delivered through anterior and posterior fields, with a 10 to 20 Gy boost dose if necessary. Results: Thirty seven patients were included in this study. Extrapleural pneumonectomy was completed in 35 patients. Overall hospital mortality was 5,7 %. Major post operative complications were: 3 acute lung injury, 1 bronchopleural fistula, 1 stroke, 1 chylothorax and one diaphragmatic patch dehiscence. IMIG post-operative staging was: stage II = 5 patients; stage III = 25 patients; stage IV = 5 patients. Adjuvant radiation was administered to 29 patients. Survival for the 35 patients with complete resection was 47 ± 8 % at 2 years. Median overall survival time was 22 months. Survival without recurrence was 37 ± 8 % at 2 years. Median time to progression was 15 months. Locoregional recurrence is the most common form of relapse. Conclusions: In the era of surgical neoadjuvant therapy in MPM treatment, extrapleural pneumonectomy followed by radiation therapy in patients with resectable epithelial or mixed MPM can achieve acceptable results. No significant financial relationships to disclose.

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

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.