Management Of Malignant Pleural Mesothelioma Research Articles

Current Trends in Radiologic Management of Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive pleural tumor with a complex growth pattern. Imaging plays a crucial role in diagnosis and management. Computed tomography (CT) has been the mainstay in the clinical evaluation of MPM; however it underestimates early chest wall invasion, peritoneal involvement, and has well-known limitations in nodal metastatic evaluation. Perfusion CT can evaluate the microvasculature of tumors; however its disadvantages, such as high radiation exposure and side effects from iodinated contrast, have limited its use to research settings. Magnetic resonance imaging (MRI) is superior to CT, both in the differentiation of malignant from benign pleural disease and in the assessment of chest wall and diaphragmatic involvement. Perfusion and diffusion MRI are promising new techniques for the assessment of tumor cellularity and microvasculature and can be used for quantitative and qualitative assessment of treatment response. Fluorodeoxyglucose positron emission tomography (FDG-PET) is useful for the differentiation of benign from malignant lesions, for staging, and for monitoring response to therapy. PET-CT is superior to other imaging modalities in detecting more extensive disease involvement and identifying unsuspected occult distant metastases. This review focuses on the practical aspects of the radiological assessment of MPM, highlighting the role of the radiologist in preoperative and postoperative evaluation with a multimodality approach.

Prognostic Features of Long-term Survivors After Surgical Management of Malignant Pleural Mesothelioma

The primary aim of this study was to evaluate prognostic features of long-term survivors with pleural mesothelioma. Overall survival outcome was analyzed in 456 patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy (EPP), pleurectomy/decortications, or pleurodesis/biopsy with at least 18 months of follow-up. Prospectively collected clinicopathologic and treatment data were assessed for their correlations with actual 18-month survivors in both univariate and multivariate analyses. The actual 18-month survival was 28%. Epithelial subtype was present in 185 patients (41%) and nonepithelial subtype in 183 (40%). Procedures were EPP in 59 patients (13%), pleurectomy/decortication in 250 (55%), and pleurodesis/biopsy in 147 (32%). Forty-two patients (9%) underwent positron emission tomography (PET) scanning. Forty patients (9%) received adjuvant radiotherapy and 45 (10%) received postoperative pemetrexed combination chemotherapy. In univariate analysis, age 65 years or younger (p < 0.001), malignant pleural effusion (p = 0.041), epithelial subtype (p < 0.001), EPP (p < 0.001), PET scan (p = 0.012), adjuvant radiotherapy (p = 0.042), and postoperative pemetrexed combination chemotherapy (p = 0.035) were strongly associated with 18-month survivors. In multivariate analysis, epithelial histopathologic subtype (p < 0.001) and EPP (p < 0.001) were independently associated with 18-month survivors. The actual 18-month survival was 28% in 456 pleural mesothelioma patients who underwent operation. Epithelial histologic subtype and EPP were identified as independent predictors for 18-month survivors.

Future developments in the management of malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis and an increasing incidence as a result of widespread exposure to asbestos. In the past few years, there have been several developments in the management of patients with MPM, including more accurate staging and patient selection, improvements in surgical techniques and postoperative care, novel chemotherapy regimens and new radiotherapy techniques. However, chemotherapy remains the mainstay of treatment, considering that surgery and radiotherapy have a limited role in highly selected patients, and its results are still modest, with a median survival of approximately 1 year. The principal goals of this review are to summarize the improvements in the management of MPM that have been achieved recently and to outline the therapeutic approaches in development.

Surgery for malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) remains a challenging disease from the surgical perspective. Its diffuse nature with involvement of the lung, pericardium, and diaphragm; the inability to reliably obtain negative margins; the significant morbidity and mortality associated with radical resection; and most importantly, the high recurrence rate after surgery, all contribute to the nihilistic attitude with which most clinicians view this disease. Despite major improvements in operative mortality over the last 2 decades, which is now between 2% and 8% at most centers, surgery alone is associated with high rates of local failure. For this reason, adjuvant and neoadjuvant modalities have been integrated into the surgical management of MPM. In most centers today, aggressive therapeutic approaches involve a trimodality regimen including extrapleural pneumonectomy (EPP), radiation therapy, and chemotherapy. The low incidence of MPM (2500-3000 cases per year in the United States) has contributed to the lack of reliable clinical data regarding optimal therapy for this disease. Most surgical series have been single-center retrospective studies that have spanned many years or prospective phase I and II trials that have involved small numbers of patients. To date, there has been no randomized study that has included surgery in the therapeutic regimen. Evidence for the efficacy of surgery has been largely based on comparison of highly selected patients who have undergone resection to unselected historical controls. Comparisons between retrospective studies in MPM are confounded by numerous factors including:

Carboplatin and pemetrexed in the management of malignant pleural mesothelioma: A realistic treatment option?

Background Malignant pleural mesothelioma is an aggressive cancer. Chemotherapy with cisplatin and pemetrexed can improve overall survival but has a toxic profile. Substitution of cisplatin with carboplatin may avoid some potential side-effects. Therefore, we undertook a retrospective review to assess the effectiveness and tolerability of carboplatin and pemetrexed in patients with malignant pleural mesothelioma in clinical practice. Methods Patients with malignant pleural mesothelioma who had been treated with carboplatin and pemetrexed were retrospectively identified from pharmacy databases. The endpoints were disease control rate, time to treatment failure, clinical improvement rate and overall survival. We also evaluated any significant haematological and non-haematological toxicities. Results A total of 49 patients were identified. Of 45 evaluable cases, the disease control rate was achieved in 34 patients (69%, 95% CI 55–82, intention to treat analysis). The clinical response rate was achieved in 34 out of 49 patients (69%, 95% CI 55–82). The median time to treatment failure was 4.6 months (95% CI 3.4–5.8) and median overall survival was 14 months (95% CI 9.5–18.5). Grade 3/4 haematological toxicities were observed in 7 patients (14.3%). Grade 3/4 non-haematological toxicities were seen in 12 patients (24.5%). No toxic deaths were recorded. Conclusion The combination of carboplatin and pemetrexed may be a viable option in the treatment of malignant pleural mesothelioma.

Malignant mesothelioma: current status and perspective in Japan and the world

Malignant pleural mesothelioma (MPM) is associated with a poor prognosis; and to make things worse, its incidence is increasing throughout the world. Surgical management of MPM is comprised of two aspects: diagnosis and resection. Surgical biopsy with thoracoscopy provides a higher yield but a higher rate of tumor cell seeding than blind biopsy. In some surgical cases, extended surgical staging with mediastinoscopy, laparoscopy, and contralateral thoracoscopy is required for the preoperative evaluation for resectablity. There are two types of surgical resection for MPM. Pleurectomy/decortication (P/D) involves removal of as much of the visceral, parietal, and pericardial pleura and the tumor as possible without removing the underlying lung. Because P/D is less radical but less invasive compared to extrapleural pneumonectomy (EPP), it can be tolerated by poor-risk patients. EPP comprises en bloc resection of visceral, parietal, and pericardial pleura and adjacent components such as ipsilateral lung, pericardium, and diaphragm, without opening the pleural cavity. EPP was considered a highly dangerous procedure with a surgical mortality of more than 30% decades ago, but its current operative mortality/morbidity rates are 4%-9% and 60%, respectively. As macroscopic complete resection is the primary goal of surgery for MPM because of its diffuse intrapleural growth, surgical resection alone is associated with poor survival. In this context, combination therapy with surgery plus chemotherapy and/or radiotherapy is currently considered the standard treatment for patients with respectable MPM. A national survey of EPP was conducted recently in Japan, and a few multicenter clinical trials will start soon.

Surgical Treatment in the Management of Malignant Pleural Mesothelioma: A Single Institution’s Experience

A minority of patients with malignant pleural mesothelioma (MPM) are considered for surgery. To achieve a microscopically radical resection, combination with other treatment modalities is mandatory. The most effective combination is unknown. In our institute we have retrospectively analyzed the results of two combined modality regimens containing surgery. Between January 2002 and September 2005, 15 MPM patients were treated with extrapleural pneumonectomy (EPP) and postoperative hemithoracic radiation (RT; 54 Gy). Previously, between January 1999 and December 2001, 20 patients underwent a combination of cytoreductive surgery - pleurectomy or EPP - and intraoperative hyperthermic intrathoracic chemotherapy (HITHOC), followed by radiotherapy to the thoracotomy scar and drainage tracts (24 Gy). The median operating time for EPP/RT was shorter (5.3 versus 6.9 h; P < 0.0001). Postoperative complications occurred in 8 EPP/RT patients (53%) and in 14 HITHOC patients (70%). Two HITHOC patients died postoperatively. Median overall survival was 29 months for EPP/RT patients and 11 months for HITHOC patients (P = ns). The median time to local recurrence was not reached for EPP/RT patients, and was 9 months for HITHOC patients (P = 0.003). Local control was achieved in ten EPP/RT patients (67%) with a follow-up of 5-59 months compared to four HITHOC patients (20%) with a follow-up of 4-27 months. In highly selected patients local control can be achieved with combination therapy but is accompanied by a high rate of (surgical) complications. Distant failure rates warrant further studies exploring the role of systemic chemotherapy while the use of cytoreductive surgery with intraoperative chemoperfusion for MPM is not supported.

Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: Results in 663 patients

The optimal procedure for resection of malignant pleural mesothelioma is controversial, partly because previous analyses include small numbers of patients. We performed a multi-institutional study to increase statistical power to detect significant differences in outcome between extrapleural pneumonectomy and pleurectomy/decortication. Patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy or pleurectomy/decortication at 3 institutions were identified. Survival and prognostic factors were analyzed by the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis. From 1990 to 2006, 663 consecutive patients (538 men and 125 women) underwent resection. The median age was 63 years (range, 26-93 years). The operative mortality was 7% for extrapleural pneumonectomy (n = 27/385) and 4% for pleurectomy/decortication (n = 13/278). Significant survival differences were seen for American Joint Committee on Cancer stages 1 to 4 (P < .001), epithelioid versus non-epithelioid histology (P < .001), extrapleural pneumonectomy versus pleurectomy/decortication (P < .001), multimodality therapy versus surgery alone (P < .001), and gender (P < .001). Multivariate analysis demonstrated a hazard rate of 1.4 for extrapleural pneumonectomy (P < .001) controlling for stage, histology, gender, and multimodality therapy. Patients who underwent pleurectomy/decortication had a better survival than those who underwent extrapleural pneumonectomy; however, the reasons are multifactorial and subject to selection bias. At present, the choice of resection should be tailored to the extent of disease, patient comorbidities, and type of multimodality therapy planned.

Alternative Options in the Management of Malignant Pleural Mesothelioma

Malignant pleural mesothelioma is a solid, locally aggressive tumor that has been linked to asbestos exposure. Without treatment MPM is associated with a poor median survival, ranging from 4 to 12 months. Extrapleural pneumonectomy offers better local control compared to pleurectomy/decortication. Chemotherapy combined with IL-2 and radiation provides some palliation. However, unsatisfactory results of these approaches have led clinicians to pursue novel therapeutic options. Local photodynamic therapy (PDT) has been studied with pleurectomy or extrapleural pneumonectomy. Intrapleural IFN-α radiosensitization and targeted immunotherapies may downstage tumors preoperatively. Gene therapies can sensitize tumor cells to antiviral drugs and may be used as a neoadjuvant therapy or to destroy residual tumor after resection. Inhibition of angiogenic growth factors or their receptors can slow tumor growth. Intracavitary hyperthermic chemotherapy, photodynamic therapy, vaccination, immunotherapy, and gene therapy are relatively new options with potential to be integrated into multimodality approach.

The role of video assisted thoracoscopic pleurectomy/decortication in the therapeutic management of malignant pleural mesothelioma☆

Extrapleural pneumonectomy (EPP) has high mortality and morbidity; radical pleurectomy decortication (P/D) carries less mortality but still significant morbidity. This surgery is not suitable for many patients with malignant pleural mesothelioma (MPM) for whom video assisted thoracic surgery (VATS) offers a minimally invasive alternative. We aimed to assess the role of VATS decortication for MPM. Over a 9-year period 208 patients underwent therapeutic surgery for MPM in our unit. One hundred and twelve of the patients underwent EPP, 29 had a P/D and 67 had VATS decortication. Sixty-three of the 208 patients (EPP n=13, P/D n=8 and VATS decortication n=42) were 65 years of age or older at the time of the operation (57 males and 6 females, age 70 (65-80) years). In this group we analyzed perioperative morbidity and mortality and long-term survival data using the Kaplan-Meier method. Postoperative stay and 30-day mortality was significantly lower for VATS P/D than for EPP (14.3 days vs 36.6 days, p<0.05 and mortality 7.1% vs 23%, respectively). There was no significant difference in the overall mean survival between the two groups (11.5 months for EPP and 14 months for VATS P/D, p=0.6). VATS decortication should be considered in the therapeutic strategy for MPM.

Phase II Study of Vinflunine in Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a disease of increasing incidence for which treatment options are limited. This study reports the clinical efficacy data for vinflunine, a novel microtubule inhibitor, in MPM. Patients with a histologically confirmed diagnosis of MPM were eligible for enrollment onto this multicenter phase II trial if they had not received prior chemotherapy or radiotherapy and had measurable lesions by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Vinflunine 320 mg/m2 by 10-minute intravenous infusion was administered on day 1 of 21-day cycles. Modifications of dose and schedule were made according to National Cancer Institute Common Toxicity Criteria version 2.0. Efficacy was assessed by an external, independent radiologist. The one-sample multiple testing procedure of Fleming was applied at the predetermined recruitment stages of 20 and 40 assessable patients. Sixty-seven patients were enrolled. Five patients were not assessable for tumor response. The response rate was 13.8% (95% CI, 6.5% to 24.7%). The median survival was 10.8 months (95% CI, 7.8 to 12.0 months). The most common adverse events were anemia, neutropenia, fatigue, constipation, and nausea. Of grade 3 and 4 toxicities, neutropenia and constipation were the most common (45% and 9% of patients, respectively). Vinflunine can be delivered with high-dose intensity in patients with MPM. The response rate and median survival are encouraging for a single agent. These data suggest that vinflunine should be further evaluated in the management of MPM.

Advances in diagnosis and treatment of malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive but relatively rare malignancy with median survival ranging from 8 to 14 months depending on stage and presentation of disease. New diagnostic procedures are urgently needed, selecting patients in earlier stages to evaluate therapeutic approaches which combine chemotherapy, surgery and radiotherapy. Combination chemotherapy represents the only resource available for advanced disease. The combination of cisplatin and pemetrexed is the treatment of choice. This review summarizes the latest developments in diagnostic techniques and the available therapeutic options for the management of MPM. Particular attention is given to the molecular basis of biologically targeted therapies to be used in the future.

51 The role of VATS Decortication in the therapeutic management of Malignant Pleural Mesothelioma (MPM)

51 The role of VATS Decortication in the therapeutic management of Malignant Pleural Mesothelioma (MPM)

P1-139: A survey of Canadian practice in management of malignant pleural mesothelioma (MPM)

P1-139: A survey of Canadian practice in management of malignant pleural mesothelioma (MPM)

Emerging drugs for mesothelioma

Malignant mesothelioma is an aggressive, but relatively rare, malignancy, affecting the pleura and peritoneum. The prognosis for malignant pleural mesothelioma (MPM) is poor, with median survival in the range of 8 – 14 months, depending on stage and presentation of disease. Long-term results of available treatments are disappointing not only in terms of prognosis, but also of local control of the disease. Therefore, relief of symptoms and improvement of quality of life parameters are the short-term goals of therapy. In advanced disease not amenable to any local approach, such as surgery, combination chemotherapy represents the current standard of care. At present, the regimen of cisplatin/pemetrexed is the medical treatment of choice. This review summarizes standard chemotherapy options and focusses on the molecular basis of the newest biologically targeted therapies to be implemented in the near future, in the management of MPM.

Guidelines of the French Speaking Society for Chest Medicine for management of malignant pleural mesothelioma

Previously considered as a rare tumor, malignant pleural mesothelioma (MPM) has become a very important public health issue. In fact, MPM is a tumor with a poor survival, and its incidence is expected to continue to increase for at least the next 10 years. Asbestos exposure is the main factor involved in MPM pathogenesis. The diagnosis of MPM may be difficult because of differential diagnosis such as pleural benign disease induced by asbestos exposure or pleural metastasis of adenocarcinoma. Management of patients with MPM also remains complicated because they are often referred for evaluation late in the evolution of the disease. Moreover, MPM exhibits a high resistance to radiotherapy and chemotherapy; only few patients are candidates for radical surgery. New therapeutic strategies such as gene or cell therapy are still on clinical trial. Therefore, an optimal treatment of MPM is not clearly defined yet, despite the introduction of recent drugs. Between April 2005 and January 2006, the French Speaking Society for Chest Medicine (SPLF), in collaboration with other French scientific societies, brought together experts on mesothelioma to draw up recommendations in order to provide clinicians with clear, concise, up-to-date guidelines on management of MPM, presented in this report.

Biology and management of malignant pleural mesothelioma

Malignant mesothelioma is an aggressive tumour, with a poor prognosis and an increasing incidence as a result of widespread exposure to asbestos. The results of the treatments available are poor. Surgery and radiotherapy have a limited role in highly selected patients and systemic therapy is the only potential treatment option for the majority of patients. Despite some definite activity of the novel antifolates such as pemetrexed and raltitrexed, the results, even in combination with platinating agents, are still modest, with a median survival of approximately one year. The better understanding of the biology of mesothelioma makes the assessment of a number of targeted agents particularly interesting. Unfortunately, the targeted agents imatinib, gefitinib, erlotinib and thalidomide have been shown to be ineffective in unselected patients. Studies with anti-angiogenesis agents are ongoing. An improvement of the knowledge of major molecular pathways involved in malignant mesothelioma is needed in order to define proper targets for the systemic treatment of this disease.

The role of radiation therapy in malignant pleural mesothelioma: A systematic review

Introduction Radiation therapy may offer patients presenting with malignant pleural mesothelioma (MPM) symptom palliation and improvements in quality of life. This systematic review will address the role of radiation therapy in the management of MPM. Methods A thorough systematic search of the literature was conducted for published articles and conference proceedings for applicable abstracts. Relevant trials were selected and assessed. Results Three small randomized controlled trials compared prophylactic external beam radiation therapy to no radiation therapy for patients with thoracic tracts caused by drainage tubes or diagnostic procedures. None of those trials reported any serious adverse effects. A pooled analysis found no significant reduction in the frequency of procedure tract metastases. Four non-comparative studies have shown that hemithoracic irradiation alone resulted in significant toxicity, including radiation-induced pulmonary fibrosis, radiation pneumonitis, and bronchopleural fistula, without any survival benefit. Few of the identified studies reported on symptom control, and no studies included formal measures of quality of life. Conclusion There is limited evidence for the role of radiotherapy in the management of patients with MPM. Future studies including radiotherapy for the treatment of such patients should include formal measures of quality of life and symptom control.

Current trends in the management of malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a common primary tumor of the pleura. The overall incidence is increasing throughout the world, with 3000 new cases reported in the USA each year. Demographi...

Thoracoscopic biopsy and Surgical management of malignant pleural mesothelioma

胸膜中皮腫は, 胸部CT検査でも存在すら指摘できない非常に狭い胸腔内を進展した後に, 胸水や胸部レントゲン異常陰影 (胸膜肥厚像) として発見されるため, 早期に発見することは困難である. また, 中皮腫は, 画像上, 胸水や胸膜肥厚を伴う, 結核性胸膜炎, 肺癌, 胸壁腫瘍, 胸膜プラーク, 良性胸膜炎, びまん性胸膜肥厚との鑑別が非常に難しい. さらに, 病理組織学的にも, 他臓器の腺癌の胸膜転移, 線維肉腫, 悪性繊維性組織球症, 滑膜肉腫, 癌肉腫などとの鑑別が難しい腫瘍である. このため, 積極的な胸腔鏡下生検による胸腔内の観察と十分な組織の採取が, 早期発見, 確定診断率の向上につながると期待されている. 胸膜中皮腫の治療においては, これまでさまざまな治療法が試みられてきたが, 未だに予後不良の疾患で, 生存期間中央値は, 6-18ヵ月とされている. 放射線療法, 化学療法, 手術療法の単独治療では, 局所コントロールや生存率の改善が得られず, 近年では, これらを合わせた集学的治療が盛んに試みられている. 特に早期の症例においては, Sugarbakerらが, 胸膜肺全摘術術後に放射線化学療法を加えた集学的治療の結果, 5年生存率が40%を越えたという画期的な成績を報告した. また, 胸膜肺全摘術自体の安全性も許容範囲までに向上し, いくつかの予後因子も同定された. このような状況の中で, 胸膜中皮腫の外科治療に対する期待は急速に高まりつつある.