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BMJ Open Sep 2020Mesothelioma remains a lethal cancer. To date, systemic therapy with pemetrexed and a platinum drug remains the only licensed standard of care. As the median survival...
Mesothelioma and Radical Surgery 2 (MARS 2): protocol for a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma.
INTRODUCTION
Mesothelioma remains a lethal cancer. To date, systemic therapy with pemetrexed and a platinum drug remains the only licensed standard of care. As the median survival for patients with mesothelioma is 12.1 months, surgery is an important consideration to improve survival and/or quality of life. Currently, only two surgical trials have been performed which found that neither extensive (extra-pleural pneumonectomy) or limited (partial pleurectomy) surgery improved survival (although there was some evidence of improved quality of life). Therefore, clinicians are now looking to evaluate pleurectomy decortication, the only radical treatment option left.
METHODS AND ANALYSIS
The MARS 2 study is a UK multicentre open parallel group randomised controlled trial comparing the effectiveness and cost-effectiveness of surgery-(extended) pleurectomy decortication-versus no surgery for the treatment of pleural mesothelioma. The study will test the hypothesis that surgery and chemotherapy is superior to chemotherapy alone with respect to overall survival. Secondary outcomes include health-related quality of life, progression-free survival, measures of safety (adverse events) and resource use to 2 years. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment.
ETHICS AND DISSEMINATION
Research ethics approval was granted by London - Camberwell St. Giles Research Ethics Committee (reference 13/LO/1481) on 7 November 2013. We will submit the results for publication in a peer-reviewed journal.
TRIAL REGISTRATION NUMBERS
ISRCTN-ISRCTN44351742 and ClinicalTrials.gov-NCT02040272.
Topics: Humans; London; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Multicenter Studies as Topic; Pleural Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32873681
DOI: 10.1136/bmjopen-2020-038892 -
Annals of the Royal College of Surgeons... Apr 2022Thoracic endometriosis syndrome is an under-recognised manifestation of endometriosis and includes catamenial pneumothorax, catamenial haemothorax, catamenial...
Thoracic endometriosis syndrome is an under-recognised manifestation of endometriosis and includes catamenial pneumothorax, catamenial haemothorax, catamenial haemoptysis and pulmonary nodules. Catamenial pneumothorax presents as recurrent spontaneous pneumothorax with a temporal relationship to the onset of menses, affecting mostly the right lung. A 48-year-old woman presented with an eight-year history of right-sided catamenial pneumothorax, during which time she had three episodes of pneumothorax. Serial chest imaging revealed an enlarging mass overlying the right hemi-diaphragm. She was referred to our trust where she underwent video-assisted thoracoscopic surgery for right pleurectomy. Intraoperatively, defects were found in the right hemidiaphragm, through which parts of the liver had herniated. We describe the presenting features and management of catamenial pneumothorax.
Topics: Diaphragm; Endometriosis; Female; Humans; Middle Aged; Pneumothorax; Thoracic Surgery, Video-Assisted
PubMed: 34825583
DOI: 10.1308/rcsann.2021.0164 -
Turk Gogus Kalp Damar Cerrahisi Dergisi Oct 2021Minimally invasive repair of pectus excavatum (Nuss) operation is the current choice of surgical treatment for pectus excavatum deformities. Technical pitfalls arise in...
Minimally invasive repair of pectus excavatum (Nuss) operation is the current choice of surgical treatment for pectus excavatum deformities. Technical pitfalls arise in patients with previous thoracic and/or cardiac surgical interventions, due to severe intrathoracic fibrous adhesions. Herein, we describe an original modification technique in a patient with bilateral apical wedge resection and total pleurectomy due to recurrent spontaneous pneumothorax episodes within the past two years. Correction was performed by opening the pleura bilaterally and retrosternal release with digital palpation via a subxiphoid incision, to help to guide the introducer and the pectus bar, without a videothoracoscopic visualization.
PubMed: 35096458
DOI: 10.5606/tgkdc.dergisi.2021.21092 -
Cancers Apr 2024Surgery plays a central role in the diagnosis, staging, and management of pleural mesothelioma. Achieving an accurate diagnosis through surgical intervention and... (Review)
Review
Surgery plays a central role in the diagnosis, staging, and management of pleural mesothelioma. Achieving an accurate diagnosis through surgical intervention and identifying the specific histologic subtype is crucial for determining the appropriate course of treatment. The histologic subtype guides decisions regarding the use of chemotherapy, immunotherapy, or multimodality treatment. The goal of surgery as part of multimodality treatment is to accomplish macroscopic complete resection with the eradication of grossly visible and palpable disease. Over the past two decades, many medical centers worldwide have shifted from performing extra-pleural pneumonectomy (EPP) to pleurectomy decortication (PD). This transition is motivated by the lower rates of short-term mortality and morbidity associated with PD and similar or even better long-term survival outcomes, compared to EPP. This review aims to outline the role of surgery in diagnosing, staging, and treating patients with pleural mesothelioma.
PubMed: 38730667
DOI: 10.3390/cancers16091719 -
BMJ Open May 2024Extrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (ePD) are surgical cytoreductive techniques aimed at achieving macroscopic resection in malignant... (Review)
Review
INTRODUCTION
Extrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (ePD) are surgical cytoreductive techniques aimed at achieving macroscopic resection in malignant pleural tumours such as pleural mesothelioma, non-mesothelioma pleural malignancies such as thymoma and sarcoma, and rarely for pleural tuberculosis, in a more limited fashion. Despite extensive studies on both surgical techniques and consequences, a significant knowledge gap remains regarding how best to approach the perioperative anaesthesia challenges for EPP and ePD.It is unknown if the risk stratification processes for such surgeries are standardised or what types of functional and dynamic cardiac and pulmonary tests are employed preoperatively to assist in the perioperative risk stratification. Further, it is unknown whether the types of anaesthesia and analgesia techniques employed, and the types of haemodynamic monitoring tools used, impact on outcomes. It is also unknown whether individualised haemodynamic protocols are used to guide the rational use of fluids, vasoactive drugs and inotropes.Finally, there is a dearth of evidence regarding how best to monitor these patients postoperatively or what the most effective enhanced recovery protocols are to best mitigate postoperative complications and accelerate hospital discharge. To increase our knowledge of the perioperative and anaesthetic treatment for patients undergoing EPP/ePD, this scoping review attempts to synthesise the literature and identify these knowledge gaps.
METHODS AND ANALYSIS
This scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Review Protocols methodology. Electronic databases, OVID Medline, EMBASE and the Cochrane Library, will be systematically searched for relevant literature corresponding to EPP or ePD and perioperative or anaesthetic management. Data will be analysed and summarised descriptively and organised according to the three perioperative stages: preoperative, intraoperative and postoperative factors in clinical care.
ETHICS AND DISSEMINATION
Ethics approval was not required. The findings will be disseminated through professional networks, conference presentations and publications in scientific journals.
Topics: Humans; Pneumonectomy; Anesthesia; Pleura; Perioperative Care; Pleural Neoplasms; Postoperative Complications
PubMed: 38760041
DOI: 10.1136/bmjopen-2023-078125 -
Thoracic Cancer Dec 2020Treatment of malignant pleural mesothelioma (MPM) represents a major challenge for oncologists. Multimodality treatment, which generally involves induction chemotherapy,...
BACKGROUND
Treatment of malignant pleural mesothelioma (MPM) represents a major challenge for oncologists. Multimodality treatment, which generally involves induction chemotherapy, surgery and radiotherapy have recently shown promising results. The aim of this study was to evaluate the locoregional control and toxicity of intensity modulated radiotherapy (IMRT) after pleurectomy and decortication (P/D) as part of trimodality therapy for patients with locally advanced MPM.
METHODS
We prospectively analyzed data from 20 patients with MPM treated at a single tertiary-care institution. Initially every patient received induction chemotherapy with platinum-based chemotherapy. After chemotherapy, patients without progression underwent P/D, and if feasible, hemi-thoracic IMRT was administered at a planned dose of 50.4-54 Gy in 28-30 fractions and treated with 9-11 noncoplanar fields.
RESULTS
A total of 15 of the 20 enrolled patients underwent P/D followed by IMRT to the hemi-thoracic cavity. The median total radiotherapy dose was 48.7 Gy (23.4-54 Gy). Radiation pneumonitis (RP) developed in nine patients (60%), and of these, two patients (13.3%) experienced G3 or G4 RP. The estimated locoregional-relapse-free survival at two years was 75.9%, and the main pattern of recurrence was distant (72.7%). For the entire cohort median follow-up was 22.7 months, median progression-free survival was 18.9 months and median overall survival 23.6 months.
CONCLUSIONS
Platinum-based chemotherapy followed by lung-sparing surgery (P/D) and IMRT is a feasible and safe treatment modality that yields acceptable locoregional control in patients with locally advanced MPM; however, these results should be corroborated in larger studies.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Mesothelioma, Malignant; Middle Aged; Pleural Neoplasms; Prospective Studies; Radiotherapy, Intensity-Modulated
PubMed: 33030313
DOI: 10.1111/1759-7714.13668 -
Turk Gogus Kalp Damar Cerrahisi Dergisi Jul 2023This study aims to evaluate overall survival, diseasefree survival, and prognostic factors in patients undergoing pleurectomy-decortication and hyperthermic...
BACKGROUND
This study aims to evaluate overall survival, diseasefree survival, and prognostic factors in patients undergoing pleurectomy-decortication and hyperthermic intrathoracic chemotherapy with the diagnosis of malignant pleural mesothelioma.
METHODS
Between January 2020 and November 2021, a total of 53 patients (27 males, 26 females; mean age: 58.1±1.3 years; range, 39 to 81 years) who underwent pleurectomy-decortication and hyperthermic intrathoracic chemotherapy with the diagnosis of malignant pleural mesothelioma were retrospectively analyzed. Data including characteristics, comorbidities, postoperative complications, recurrence and mortality status of the patients were recorded. Overall survival and disease-free survival and prognostic factors were evaluated.
RESULTS
The median disease-free survival was 11.67 months and the median overall survival was 24.60 months. The median disease-free survival was 8.80 months in men and 13.17 months in women, indicating a statistically significant difference as it showed that recurrence was detected earlier in male patients (p=0.037). The median disease-free survival and overall survival was 6.13 months and 11.70 in cases diagnosed with biphasic mesothelioma, respectively, while it was 11.67 months and 25.46 months in cases with epithelial mesothelioma, respectively. Pathological subtype was found to be an effective prognostic factor for both survival (p=0.049 and p<0.001, respectively).
CONCLUSION
Hyperthermic intrathoracic chemotherapy following cytoreductive surgery is a preferable and tolerable method in the treatment of malignant pleural mesothelioma. While evaluating surgical indications, it should be kept in mind that cases with epithelial mesothelioma may benefit more from surgical treatment.
PubMed: 37664769
DOI: 10.5606/tgkdc.dergisi.2023.24329 -
Turk Gogus Kalp Damar Cerrahisi Dergisi Oct 2021Malignant pleural effusion can be described as the presence of exudate in the pleural space, accompanied by the detection of cancer cells in pleural fluid or tissue,... (Review)
Review
Malignant pleural effusion can be described as the presence of exudate in the pleural space, accompanied by the detection of cancer cells in pleural fluid or tissue, which is the indicator of the disease in its advance stages, and survival time of these patients ranges between 3 and 12 months. Treatment options for malignant pleural effusion vary from observation in asymptomatic patients to pleurectomies or even extrapleural pneumonectomies in severe cases.
PubMed: 35096460
DOI: 10.5606/tgkdc.dergisi.2021.20580 -
The Lancet. Respiratory Medicine Jun 2024Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone.
METHODS
MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants.
FINDINGS
Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group.
INTERPRETATION
Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone.
FUNDING
National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895).
Topics: Humans; Female; Male; Pleural Neoplasms; Middle Aged; Aged; Mesothelioma; Treatment Outcome; United Kingdom; Pleura; Mesothelioma, Malignant; Combined Modality Therapy; Adult; Antineoplastic Combined Chemotherapy Protocols; Lung Neoplasms
PubMed: 38740044
DOI: 10.1016/S2213-2600(24)00119-X -
Journal of Thoracic Disease Nov 2021This observational study evaluates retrospectively the long-term outcomes after pleurectomy/decortication for pleural mesothelioma, with and without the...
BACKGROUND
This observational study evaluates retrospectively the long-term outcomes after pleurectomy/decortication for pleural mesothelioma, with and without the resection/reconstruction of diaphragm and pericardium.
METHODS
Data from 155 consecutive patients undergoing lung-sparing surgery for epithelial pleural mesothelioma were reviewed. Selection criteria for surgery were cT1-3, cN0-1, good performance status, age <80 years. Perioperative Pemetrexed-Platinum regimen was administered as induction in 101 cases (65.2%) and as adjuvant treatment in 54 cases (34.8%). Extended pleurectomy/decortication was performed in 87 cases (56.12%). In 68 patients (43.87%) standard pleurectomy/decortication was performed without resection/reconstruction of diaphragm and pericardium, when tumour infiltration was deemed absent after intraoperative frozen section. The log-rank test and Cox regression model were used to assess the factors affecting overall survival and recurrence free survival.
RESULTS
Median follow-up was 20 months. The 2- and 5-year survival rate was 60.9% and 29.2% with a median survival of 34 months. An improved survival was observed when standard pleurectomy/decortication was carried out (P=0.007). A significant impact on survival was found comparing the TNM-stages (P=0.001), pT (P=0.002) and pN variables (P=0.001). Multivariate analysis identified the pN-status (P=0.003) and standard pleurectomy/decortication (P=0.017) as predictive for longer survival. The recurrence-free survival >12 months was strongly related to the overall survival (P<0.001). The macroscopic complete resection (P=0.001), TNM-stage (P=0.003) and pT-status (P=0.001) are related to relapse.
CONCLUSIONS
Within multimodal management of pleural mesothelioma, lung-sparing surgery is a valid option even with more conservative technique. A benefit for a longer survival was observed in the early stage of disease, with pN0 and when pleurectomy/decortication is carried out, preserving diaphragm and pericardium. Recurrence is not affected by the type of surgery, and a recurrence-free interval >12 months is predictive of an increased survival when the macroscopic complete resection is achieved.
PubMed: 34992808
DOI: 10.21037/jtd-21-691