Relapse Patterns and Tailored Treatment Strategies for Malignant Pleural Mesothelioma Recurrence after Multimodality Therapy

To date, there have been no established therapies for recurrent malignant pleural mesothelioma (MPM) after multimodality treatment. Aims of this retrospective study are to analyze the recurrence pattern, its treatment and to identify the predictors of best oncological outcomes for relapsed MPM, comparing extrapleural pneumonectomy (EPP) vs. pleurectomy/decortication (PD). Study population: 94 patients with recurrence of MPM after multimodality treatment underwent macroscopic complete resection (52.1% with EPP and 47.9% with PD) between July 1994 and February 2020. Distant spread was the most frequent pattern of recurrence (71.3%), mostly in the EPP group, while the PD group showed a higher local-only failure rate. Post-recurrence treatment was administered in 86.2%, whereas best supportive care was administered in 13.8%. Median post-recurrence survival (PRS) was 12 months (EPP 14 vs. PD 8 months, p = 0.4338). At multivariate analysis, predictors of best PRS were epithelial histology (p = 0.026, HR 0.491, IC95% 0.263–0.916), local failure (p = 0.027, HR 0.707, IC95% 0.521–0.961), DFS ≥ 12 months (p = 0.006, HR 0.298, IC95% 0.137–0.812) and post-recurrence medical treatment (p = 0.046, HR 0.101, IC95% 0.897–0.936). The type of surgical intervention seems not to influence the PRS if patients are fit enough to face post-recurrence treatments. In patients with a prolonged disease-free interval, in the case of recurrence the most appropriate treatment seems to be the systemic medical therapy, even in the case of local-only relapse.

Download Full-text

Multimodality treatment of malignant pleural mesothelioma

F1000Research ◽

10.12688/f1000research.15796.1 ◽

2018 ◽

Vol 7 ◽

pp. 1681 ◽

Cited By ~ 6

Author(s):

Lawek Berzenji ◽

Paul Van Schil

Keyword(s):

Malignant Pleural Mesothelioma ◽

Asbestos Exposure ◽

Multimodality Treatment ◽

Treatment Modalities ◽

Surgical Approaches ◽

Extrapleural Pneumonectomy ◽

Pleural Mesothelioma ◽

Treatment Approaches ◽

Definitive Answer ◽

Platinum Based Chemotherapy

Malignant pleural mesothelioma (MPM) is a rare disease of the pleura and is largely related to asbestos exposure. Despite recent advancements in technologies and a greater understanding of the disease, the prognosis of MPM remains poor; the median overall survival rate is about 6 to 9 months in untreated patients. The main therapeutic strategies for MPM are surgery, chemotherapy, and radiation therapy (RT). The two main surgical approaches for MPM are extrapleural pneumonectomy (EPP), in which the lung is removed en bloc, and pleurectomy/decortication, in which the lung stays in situ. Chemotherapy usually consists of a platinum-based chemotherapy, such as cisplatin, often combined with a folate antimetabolite, such as pemetrexed. More recently, immunotherapy has emerged as a possible therapeutic strategy for MPM. Evidence suggests that single-modality treatments are not an effective therapeutic approach for MPM. Therefore, researchers have started to explore different multimodality treatment approaches, in which often combinations of surgery, chemotherapy, immunotherapy, and RT are investigated. There is still no definitive answer to the question of which multimodality treatment combinations are most effective in improving the poor prognosis of MPM. Research into the effects of trimodality treatment approaches have found that radical approaches such as EPP and hemithoracic RT post-EPP are less effective than was previously assumed. In general, there are still a great number of unanswered questions and unknown factors regarding the ideal treatment approach for MPM. Hopefully, more research into multimodality therapy will provide insight into which combination of treatment modalities is most effective.

Download Full-text

Surgical Techniques for Multimodality Treatment of Malignant Pleural Mesothelioma: Extrapleural Pneumonectomy and Pleurectomy/Decortication

Seminars in Thoracic and Cardiovascular Surgery ◽

10.1053/j.semtcvs.2009.07.007 ◽

2009 ◽

Vol 21 (2) ◽

pp. 132-148 ◽

Cited By ~ 56

Author(s):

Andrea S. Wolf ◽

Jonathan Daniel ◽

David J. Sugarbaker

Keyword(s):

Malignant Pleural Mesothelioma ◽

Surgical Techniques ◽

Multimodality Treatment ◽

Extrapleural Pneumonectomy ◽

Pleural Mesothelioma

Download Full-text

Prognostic factors in malignant pleural mesothelioma (MPM): A mono-institutional evaluation of Bologna Malignant Pleural Mesothelioma Group.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e18509 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e18509-e18509

Author(s):

Daniela Adua ◽

Francesca Sperandi ◽

Paolo Castellucci ◽

Barbara Melotti ◽

Stefania Giaquinta ◽

...

Keyword(s):

Prognostic Factors ◽

Prognostic Factor ◽

Malignant Pleural Mesothelioma ◽

Cox Regression ◽

Statistical Significance ◽

Multimodality Treatment ◽

Extrapleural Pneumonectomy ◽

Pleural Mesothelioma ◽

Histological Subtype ◽

The Impact

e18509 Background: The prognostic systems currently in use in MPM, such as the EORTC and CALGB score, include the clinical and histological parameters, excluding the FDG-PET (PET) evaluation and the possibility of surgery. The aim of our study was to investigate the role of PET baseline SUV-max and surgery as prognostic factors in MPM. Methods: From April 2002to December 2012, 48 pts with a certain histological diagnosis of MPM underwent staging by PET scan before peri-operative (multimodality treatment) or palliative first-line chemotherapy (CT). Surgery was performed in 22(45.8%) pts. Pt characteristics: males 44(91.7%), females 4(8.3%); median age 65 (51-77) years; ECOG PS 0-1 45(93.7 %), PS 2 3(6.3 %); IMIG stage I-II 18(37.5%), III-IV 30(62.5%); histological subtype epithelial 40(83.3%), mixed 5(10.4%), sarcomatoid 3(6.3%); extrapleural pneumonectomy 8(16.8%), pleurectomy/decortication 14(29.2%), 17 (35.4%) VATS plus pleurodesis, 19(39.6%) no surgical procedures. Platinum based CT was performed in combination with pemetrexed in 39(81.3%) pts and with gemcitabine in 9(18.7%). According to the EORTC score 30(62.5%) pts were classified in the good prognosis group and 18(37.5%) as poor prognosis. The cut-off value of PET baseline SUV-max calculated by ROC analysis was 9; SUV-max at baseline PET was ≤ 9 in 32(66.7%) pts and >9 in 16(33.3%). Median overall survival (OS) was 12 (3-60) months. Results: Upon validating the impact of individual factors on OS using the Kaplan-Meier analysis, we found statistical significance was reached by histology (p=0.0038) and surgery (p=0.0027). In a multivariate analysis using the Cox regression system, considering OS as a dependent variable, according to age, histology, stage, PET baseline SUV-max and surgery, epithelial histology (p =0.002) and surgery (p=0.012) achieved a statistical significance. SUV-max at baseline PET was not statistically significant (p = 0.290), excluding it as a possible independent prognostic factor in MPM. Conclusions: This analysis does not indicate any prognostic value for baseline PET in MPM, confirming the importance of histological subtype and introducing surgery as a possible prognostic factor.

Download Full-text

Faculty Opinions recommendation of Pleurectomy/decortication is superior to extrapleural pneumonectomy in the multimodality management of patients with malignant pleural mesothelioma.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.715898021.791402848 ◽

2012 ◽

Author(s):

Paul Van Schil

Keyword(s):

Malignant Pleural Mesothelioma ◽

Extrapleural Pneumonectomy ◽

Pleural Mesothelioma

Download Full-text

Faculty Opinions recommendation of Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725915176.793512682 ◽

2015 ◽

Author(s):

Paul Van Schil

Keyword(s):

Neoadjuvant Chemotherapy ◽

Malignant Pleural Mesothelioma ◽

Extrapleural Pneumonectomy ◽

Pleural Mesothelioma ◽

Phase 2 ◽

Multicentre Phase ◽

Phase 2 Trial

Download Full-text

Hitting the Bull’s-Eye: Mesothelin’s Role as a Biomarker and Therapeutic Target for Malignant Pleural Mesothelioma

Cancers ◽

10.3390/cancers13163932 ◽

2021 ◽

Vol 13 (16) ◽

pp. 3932

Author(s):

Dannel Yeo ◽

Laura Castelletti ◽

Nico van Zandwijk ◽

John E. J. Rasko

Keyword(s):

Malignant Pleural Mesothelioma ◽

Treatment Options ◽

Survival Rates ◽

Treatment Strategies ◽

Pleural Mesothelioma ◽

Normal Tissues ◽

Drug Conjugates ◽

Aggressive Cancer ◽

Immunotherapy Target ◽

Bull's Eye

Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited treatment options and poor prognosis. MPM originates from the mesothelial lining of the pleura. Mesothelin (MSLN) is a glycoprotein expressed at low levels in normal tissues and at high levels in MPM. Many other solid cancers overexpress MSLN, and this is associated with worse survival rates. However, this association has not been found in MPM, and the exact biological role of MSLN in MPM requires further exploration. Here, we discuss the current research on the diagnostic and prognostic value of MSLN in MPM patients. Furthermore, MSLN has become an attractive immunotherapy target in MPM, where better treatment strategies are urgently needed. Several MSLN-targeted monoclonal antibodies, antibody–drug conjugates, immunotoxins, cancer vaccines, and cellular therapies have been tested in the clinical setting. The biological rationale underpinning MSLN-targeted immunotherapies and their potential to improve MPM patient outcomes are reviewed.

Download Full-text