Most studies describing the natural history and prognostic factors for malignant pleural mesothelioma antedate accurate pathologic diagnosis, staging by computed tomography, and a universal staging system. We conducted a large single-institution analysis to identify prognostic factors and assess the association of resection with outcome in a contemporary patient population.
Patients with biopsy-proven malignant pleural mesothelioma at our institution were identified and clinical data were obtained from an institutional database. Survival and prognostic factors were analyzed by the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis. A p value <0.05 was considered statistically significant.
From 1990 to 2005, 945 patients were identified: 755 men, 190 women; median age, 66 years (range, 26-93). Extrapleural pneumonectomy was performed in 208 (22%), pleurectomy/decortication in 176 (19%). Operative mortality was 4% (16/384). Multimodality therapy including surgery was associated with a median survival of 20.1 months. Significant predictors of overall survival included histology, gender, smoking, asbestos exposure, laterality, surgical resection by extrapleural pneumonectomy or pleurectomy/decortication, American Joint Committee on Cancer stage, and symptoms. A Cox model demonstrated a hazard ratio of 1.4 without surgical resection when controlling for histology, stage, gender, asbestos exposure, smoking history, symptoms, and laterality (p = 0.003).
In addition to tumor histology and pathologic stage, predictors of survival include gender, asbestos exposure, smoking, symptoms, laterality, and clinical stage. Surgical resection in a multimodality setting was associated with improved survival.
"Systemic therapy represents the primary treatment option for most patients (Treasure and Sedrakyan, 2004; Tsao et al, 2009), but standard MPM therapy is still deficient and decisions for radiotherapy, surgery or combined approaches are based on a case-by-case decision leading to a palliative treatment approach for most patients (Guyatt et al, 2006; Muers et al, 2008; Stahel et al, 2009; Astoul et al, 2012). Gender, histological subtype and haematological parameters have been identified as important prognostic parameters (Flores et al, 2007; Rusch et al, 2012). "
[Show abstract][Hide abstract] ABSTRACT: Background:
Malignant pleural mesothelioma (MPM) is a highly aggressive tumour that is first-line treated with a combination of cisplatin and pemetrexed. Until now, predictive and prognostic biomarkers are lacking, making it a non-tailored therapy regimen with unknown outcome. P53 is frequently inactivated in MPM, but mutations are extremely rare. MDM2 and P14/ARF are upstream regulators of P53 that may contribute to P53 inactivation.
A total of 72 MPM patients were investigated. MDM2 immunoexpression was assessed in 65 patients. MDM2 and P14/ARF mRNA expression was analysed in 48 patients of the overall collective. The expression results were correlated to overall survival (OS) and progression-free survival (PFS).
OS and PFS correlated highly significantly with MDM2 mRNA and protein expression, showing a dismal prognosis for patients with elevated MDM2 expression (for OS: Score (logrank) test: P⩽0.002, and for PFS: Score (logrank) test; P<0.007). MDM2 was identified as robust prognostic and predictive biomarker for MPM on the mRNA and protein level. P14/ARF mRNA expression reached no statistical significance, but Kaplan-Meier curves distinguished patients with low P14/ARF expression and hence shorter survival from patients with higher expression and prolonged survival.
MDM2 is a prognostic and predictive marker for a platin-pemetrexed therapy of patients with MPMs. Downregulation of P14/ARF expression seems to contribute to MDM2-overexpression-mediated P53 inactivation in MPM patients.
British Journal of Cancer 02/2015; 112(5). DOI:10.1038/bjc.2015.27 · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mesothelioma is a malignancy with poor prognosis, with an average 5-year survival rate being less than 9%. This type of cancer is almost exclusively caused by exposure to asbestos. A long exposure can cause mesothelioma and so can short ones, as each exposure is cumulative. We report a case of a 26-year-old male who was exposed to asbestos during his primary school years from the age of 6 to 12. Although the tumor mainly affects older men who in their youth were occupationally exposed to asbestos, malignant mesothelioma can also occur in young adults. A medical history was carefully taken and asbestos exposure was immediately mentioned by the patient. We conducted biopsy on the right supraclavicular lymph node. The patient was not a candidate for surgery, and chemotherapy treatment was initiated. While patient's chemotherapy is still ongoing, no other similar cases of students or teachers have been traced up to date from his school. The school building was demolished in January 2009.
Case Reports in Medicine 07/2011; 2011:951732. DOI:10.1155/2011/951732
"However, it should be recognized that significantly more patients in the P/D/ group had early stage tumors (35% vs. 25% (p<0.001). In addition, the institutions involved in this study performed P/D not only for patients who would not medically tolerate EPP, but also for fit patients when there was 'minimal visceral involvement' (Flores 2007) and for patients with low tumor volume (Pass, 1997). This bias towards performing P/D on patients with biologically more favorable tumors makes it difficult to draw firm conclusions from the data. "
[Show abstract][Hide abstract] ABSTRACT: Controversy remains regarding the optimal therapy for MPM. In fit patients with epithelioid tumors and negative nodes, cytoreductive surgery combined with appropriate adjuvant or neoadjuvant therapy may improve survival compared to best supportive care or chemotherapy alone, although this is unproven. An ongoing randomized trial is currently underway in the United Kingdom that will compare trimodality therapy including EPP to trimodality therapy without EPP . Complete removal of all macroscopic disease should be the goal of any potentially curative surgical procedure, whether EPP or P/D. Extrapleural pneumonectomy has been associated with lower rates of local recurrence, particularly when combined with high-dose hemithoracic radiation; however, it has also been associated with higher perioperative morbidity and mortality in comparison to P/D. Currently, there is no convincing evidence of any survival difference between the 2 procedures. Distant failure remains a significant issue that limits long-term survival in patients who have undergone EPP. However, if distant metastatic disease could be prevented in the future, then the local control of achievable with EPP might translate into improved survival.
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