Prognostic Score of Long-Term Survival After Surgery for Malignant Pleural Mesothelioma: A Multicenter Analysis

Leuzzi, Giovanni; Rea, Federico; Spaggiari, Lorenzo; Marulli, Giuseppe; Sperduti, Isabella; Alessandrini, Gabriele; Casiraghi, Monica; Bovolato, P; Pariscenti, Gianluca; Alloisio, Marco; Infante, Maurizio; Pagan, V.; Fontana, Paolo; Oliaro, A; Ruffini, Enrico; Ratto, G. B.; Leoncini, Giacomo; Sacco, Rodolfo; Mucilli, Felice; Facciolo, Francesco

doi:10.1016/j.athoracsur.2015.04.087

Cited by 21 publications

(23 citation statements)

References 27 publications

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“…It has been reported that TNM staging is related to MPM prognosis; however, we found no significant association between OS and TNM staging. Similarly, Meyerhoff et al observed no survival difference between different clinical stages within the epithelioid histotype .…”

Section: Discussioncontrasting

confidence: 95%

Survival analysis via nomogram of surgical patients with malignant pleural mesothelioma in the Surveillance, Epidemiology, and End Results database

et al. 2019

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Background Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor that originates from the pleura and has a poor prognosis. Eligible patients can benefit from surgery, but their survival is affected by many factors. Therefore, we created a graphic model that could predict the prognosis of surgically treated patients. Methods We retrospectively analyzed data from the Surveillance, Epidemiology, and End Results database from 2004 to 2014 to identify the key factors affecting the prognosis of surgically treated MPM patients. On this basis we built a nomogram to predict survival. We then evaluated the performance of the nomogram in a validation cohort. Results In a training cohort of 828 cases, independent prognostic factors, including age, gender, histological type, differentiation, N stage, chemotherapy, type of surgery, and lymph node dissection, were identified. We then developed a nomogram to evaluate individual patient survival. In Kaplan–Meier analysis, a higher score in the nomogram was associated with a worse prognosis. We also used a validation cohort consisting of 312 patients to evaluate the performance of the nomogram, which was well calibrated and had good discrimination ability, with concordance indices of 0.715 and 0.656 for the training and validation cohorts, respectively. Conclusion This study has improved our understanding of resected MPM and shown that key factors, including age and histological type, are associated with overall survival. The nomogram is a reliable tool that can help clinicians turn individualized prediction into reality and maximize patient benefit by identifying the most beneficial treatment approach.

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Section: Discussioncontrasting

confidence: 95%

Survival analysis via nomogram of surgical patients with malignant pleural mesothelioma in the Surveillance, Epidemiology, and End Results database

et al. 2019

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“…In many series, age (in different series from under 70 to under 50), epithelioid histology, performance status, stage and in particular absence of nodal metastasis are considered good prognostic factors [8,[42][43][44][45]. An analysis of a large multi-institutional database [46] reported that in addition, the extent of surgery (radical versus palliative) and multimodality treatment have a positive impact on prognosis.…”

Section: Prognostic Factors For Radical Surgerymentioning

confidence: 97%

The role of thoracic surgery in the management of mesothelioma: an expert opinion on the limited evidence

Bertoglio

Waller

2016

Expert Review of Respiratory Medicine

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Surgery has a key role at different points in the management of Malignant Pleural Mesothelioma. Diagnosis with video assisted thoracoscopy offers excellent sensitivity and specificity and a direct view of the pleural cavity to verify the extent of the tumor. Nodal involvement can be assessed by mediastinoscopy and either talc pleurodesis or partial pleurectomy can be used for symptom control in advanced stage disease. Extra Pleural Pneumonectomy (EPP) and Extended Pleurectomy Decortication (EPD) are used to prolong survival although the benefit of radical surgery has not has been fully clarified; EPP failed to show its benefit in the MARS trial and EPD is currently under investigation in the MARS2 trial. More randomized prospective trial data are needed to fully understand the role of radical surgery in the treatment of pleural mesothelioma.

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“…Presently, in the United States the incidence of MPM is approximately 3000 cases annually {Henley, 2013 3213 /id}. Median overall survival of MPM patients undergoing aggressive multimodality therapy ranges from 14-22 months, depending on tumor stage and histology, extent of surgical resection, and response to chemotherapy {Leuzzi, 2015 3216 /id;Opitz, 2015 3217 /id;Shersher, 2013 2615 /id}.…”

Section: Introductionmentioning

confidence: 99%

Mithramycin Depletes Specificity Protein 1 and Activates p53 to Mediate Senescence and Apoptosis of Malignant Pleural Mesothelioma Cells

Rao

Atay

Shukla

et al. 2016

Clinical Cancer Research

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Purpose Specificity protein 1 (SP1) is an oncogenic transcription factor over-expressed in various human malignancies. This study sought to examine SP1 expression in malignant pleural mesotheliomas (MPM), and ascertain the potential efficacy of targeting SP1 in these neoplasms. Experimental Design qRT-PCR, immunoblot and immunohistochemistry techniques were used to evaluate SP1 expression in cultured MPM cells and MPM specimens and normal mesothelial cells/pleura. MTS, chemotaxis, soft agar, ß-galactosidase and Apo-BrdU techniques were used to assess proliferation, migration, clonogenicity, senescence and apoptosis in MPM cells following SP1 knockdown, p53 over-expression, or mithramycin treatment. Murine subcutaneous and intraperitoneal (IP) xenograft models were used to examine effects of mithramycin on MPM growth in vivo. Microarray, qRT-PCR, immunoblot and chromatin immunoprecipitation techniques were used to examine gene expression profiles mediated by mithramycin and combined SP1 knockdown/p53 over-expression, and correlate these changes with SP1 and p53 levels within target gene promoters. Results MPM cells and tumors exhibited higher SP1 mRNA and protein levels relative to control cells/tissues. SP1 knockdown significantly inhibited proliferation, migration and clonogenicity of MPM cells. Mithramycin depleted SP1 and activated p53, dramatically inhibiting proliferation and clonogenicity of MPM cells. IP mithramycin significantly inhibited growth of subcutaneous MPM xenografts, and completely eradicated mesothelioma carcinomatosis in 75% of mice. Mithramycin modulated genes mediating oncogene signaling, cell cycle regulation, senescence and apoptosis in-vitro and in-vivo. The growth inhibitory effects of mithramycin in MPM cells were recapitulated by combined SP1 knockdown/p53 overexpression. Conclusions These findings provide preclinical rationale for phase II evaluation of mithramycin in mesothelioma patients.

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Prognostic Score of Long-Term Survival After Surgery for Malignant Pleural Mesothelioma: A Multicenter Analysis

Abstract: Our prognostic model facilitates the prediction of LTS after surgery for malignant pleural mesothelioma and can help to stratify the outcome and, eventually, tailor postoperative treatment.

Cited by 21 publications

References 27 publications

Survival analysis via nomogram of surgical patients with malignant pleural mesothelioma in the Surveillance, Epidemiology, and End Results database

Survival analysis via nomogram of surgical patients with malignant pleural mesothelioma in the Surveillance, Epidemiology, and End Results database

The role of thoracic surgery in the management of mesothelioma: an expert opinion on the limited evidence

Mithramycin Depletes Specificity Protein 1 and Activates p53 to Mediate Senescence and Apoptosis of Malignant Pleural Mesothelioma Cells

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