Prognostic factors in the treatment of malignant pleural mesothelioma at a large tertiary referral center.
ABSTRACT 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.
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ABSTRACT: Objective This study aims to report on patients (pts) with potentially resectable pleural mesothelioma treated with induction chemotherapy (CT) followed by extrapleural pneumonectomy (EPP) and adjuvant intensity-modulated radiation therapy (IMRT). Methods From 2002 to 2008 a retrospective review found 16 consecutive mesothelioma pts planned for trimodality care. CT involved a platinum-based doublet. EPP was carried out after pt restaging. IMRT to a dose of 54 Gy was given at least 4 weeks after EPP. Study endpoints included toxicity, dosimetric parameters, time to recurrence, and survival. Results Two pts progressed during CT and did not undergo EPP. One pt died after surgery. Thirteen pts (81 %) completed all treatments. Concerning IMRT, the mean of mean lung doses (MLDs) was 9.28 Gy. The mean percent of lung volume receiving 5 Gy (V5) and 20 Gy (V20) was 81.3 and 5.0 %, respectively. Acute radiation pulmonary toxicities included two grade 3 events. V30 was significantly associated with ≥grade 2 pulmonary toxicity (p = 0.041). There were no pulmonary-related deaths. Mean follow-up from CT start for 16 pts was 17.7 months (range, 1.3 to 66.3). Median survival (MS) was 20.2 months for pts completing therapy. Actuarial overall survival at 3 years was 31.6 %. Pathologic nodal stage did not correlate with overall or recurrence-free survival. Median time to local and/or distant recurrence from CT start was 15.3 months for pts completing therapy. All pts with local and regional failures also had distant failure. Two pts failed distantly only. Conclusion IMRT resulted in minimal pulmonary toxicity. Local control and survival remain challenging despite trimodality care.Journal of Radiation Oncology. 06/2014; 3(2):159-166.
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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.Methods: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).Results: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.Conclusions: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 advance online publication, 10 February 2015; doi:10.1038/bjc.2015.27 www.bjcancer.com.British journal of cancer. 02/2015;
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ABSTRACT: Background:Although the prognosis of most patients presenting with malignant pleural mesothelioma (MPM) is poor, a small proportion survives long term. We investigated factors associated with survival in a large patient series.Methods:All patients registered with the NSW Dust Diseases Board (2002-2009) were included in an analysis of prognostic factors using Kaplan-Meier and Cox regression analysis. On the basis of these analyses, we developed a risk score (Prognostic Index (PI)).Results:We identified 910 patients: 90% male; histology (epithelioid 60%; biphasic 13%; sarcomatoid 17%); stage (Tx-I-II 48%; III-IV 52%); and calretinin expression (91%). Treatment: chemotherapy(CT) 44%, and extrapleural-pneumonectomy (EPP) 6%. Median overall survival (OS) was 10.0 months. Longer OS was associated with: age <70 (13.5 vs 8.5 months; P<0.001); female gender (12.0 vs 9.9 months; P<0.001); epithelioid subtype (13.3 vs 6.2 months; P<0.001); ECOG status 0 (27.4 vs 9.7 months; P=0.015), calretinin expression (10.9 vs 5.5 months; P<0.001); neutrophil-lymphocyte ratio (NLR) <5 (11.9 vs 7.5 months; P<0.001); platelet count <400 (11.5 vs 7.2 months; P<0.001); and normal haemoglobin (16.4 vs 8.8 months; P<0.001). On time-dependent analysis, patients receiving pemetrexed-based chemotherapy (HR=0.83; P=0.048) or EPP (HR=0.41; P<0.001) had improved survival. Age, gender, histology, calretinin and haematological factors remained significant on multivariate analysis. In all, 24% of patients survived >20 months: 16% of these receiving EPP, and 66% CT. The PI offered improved prognostic discrimination over one of the existing prognostic models (EORTC).Conclusions:We identified calretinin expression, age, gender, histological subtype, platelet count and haemoglobin level as independent prognostic factors. Patients undergoing EPP or pemetrexed-based chemotherapy demonstrated better survival, but 84% and 34% of long survivors, respectively, did not receive radical surgery or chemotherapy.British Journal of Cancer advance online publication, 4 September 2014; doi:10.1038/bjc.2014.478 www.bjcancer.com.British Journal of Cancer 09/2014; · 4.82 Impact Factor