Trimodality Treatment in Malignant Pleural Mesothelioma: An Ordeal or The Real Deal?

BACKGROUND: Malignant Pleural Mesothelioma is an uncommon and aggressive disease associated with asbestos exposure. Management of MPM is complex and controversial as there is paucity of good quality evidence. Multimodality treatment with surgery, systemic therapy and radiation therapy is an option in non-metastatic MPM. We intend to analyze toxicity and outcomes in patients who received trimodality treatment for non-metastatic MPM at our institution. METHODS and MATERIALS: We reviewed the electronic medical records of surgically managed MPM patients at our institution in the last decade. Patient details, disease characteristics and treatment information were retrieved from the institutional electronic medical record and radiation oncology information system. Dosimetric parameters of target volume and organs at risk were documented from Eclipse workstation (v13.6, Varian medical systems). SPSS was used for statistical analysis. RESULTS: Between January 2008 and October 2018, 21 patients (17 male and 4 female) underwent surgery for MPM, all but 2 patients underwent extra-pleural pneumonectomy (EPP). Primary was located in the right and left in 11 and 10 patients respectively. Epithelioid MPM was the commonest histology (17 patients: 81%). Resection was R0 in 18 patients and R2 in 2 patients. Four patients had minor complications like wound erythema, wound seroma with cellulitis and hypotension and 8 Patients had major complications like pneumonia, rib fracture, pulmonary hypertension and pulmonary stump thrombus. All patients received neoadjuvant Pemetrexed/platinum doublet chemotherapy, except for 2. Fourteen patients received adjuvant hemithoracic RT; of these, 2 underwent treatment elsewhere and 2 were treated with conventional technique. Ten patients treated with conformal technique at our institute and dosimetric data was available for analysis. Average time to start RT after surgery was 51 days (range 32 to 82 days). All patients were treated with conformal technique using IMRT/VMAT to a dose of 45Gy in 25 fractions; one patient received a further boost of 5.4Gy. Mean overall RT duration was 35 days (range 30 to 42 days). Acute toxicity was uncommon; Grade I/II Pneumonitis was seen in 4 patients. One patient developed grade III acute lung toxicity unrelated to RT. At a median follow up of 25 months, 8 patients developed progressive disease. Eight patients had died, of whom six died due to disease and two died in immediate post op period. Two-year DFS and OS were 58% and 73% respectively. CONCLUSION: In spite of the extensive surgery and complex hemithoracic RT, we demonstrated excellent dosimetric, toxicity profile and favorable outcomes in non-metastatic MPM.

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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.

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Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment

European Respiratory Review ◽

10.1183/16000617.0063-2016 ◽

2016 ◽

Vol 25 (142) ◽

pp. 472-486 ◽

Cited By ~ 72

Author(s):

Anna C. Bibby ◽

Selina Tsim ◽

Nikolaos Kanellakis ◽

Hannah Ball ◽

Denis C. Talbot ◽

...

Keyword(s):

Malignant Pleural Mesothelioma ◽

Imaging Techniques ◽

Asbestos Exposure ◽

Treatment Options ◽

Incidence Rates ◽

Pleural Mesothelioma ◽

Global Epidemic ◽

Pleural Surface ◽

New Treatment ◽

Trimodality Treatment

Malignant pleural mesothelioma is an aggressive malignancy of the pleural surface, predominantly caused by prior asbestos exposure. There is a global epidemic of malignant pleural mesothelioma underway, and incidence rates are predicted to peak in the next few years.This article summarises the epidemiology and pathogenesis of malignant pleural mesothelioma, before describing some key factors in the patient experience and outlining common symptoms. Diagnostic approaches are reviewed, including imaging techniques and the role of various biomarkers. Treatment options are summarised, including the importance of palliative care and methods of controlling pleural effusions. The evidence for chemotherapy, radiotherapy and surgery is reviewed, both in the palliative setting and in the context of trimodality treatment. An algorithm for managing malignant pleural effusion in malignant pleural mesothelioma patients is presented. Finally new treatment developments and novel therapeutic approaches are summarised.

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Dosimetric Comparison of Lung-Sparing Radiation Therapy between Volumetric Arc Therapy and Helical Tomotherapy for Unresectable Malignant Pleural Mesothelioma

BioMed Research International ◽

10.1155/2019/4568958 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7

Author(s):

Berrin Pehlivan ◽

Kansu Sengul ◽

Abdullah Yesil ◽

Nilgul Nalbant ◽

Osman Ozturk ◽

...

Keyword(s):

Radiation Therapy ◽

Malignant Pleural Mesothelioma ◽

Helical Tomotherapy ◽

Organs At Risk ◽

Target Volume ◽

Pleural Mesothelioma ◽

Dosimetric Comparison ◽

Volumetric Arc Therapy ◽

Arc Therapy ◽

Target Volumes

Objective. To compare volumetric arc therapy (VMAT) and helical tomotherapy (HT) plans in terms of dosimetric parameters in positron emission tomography- (PET-) computerized tomography- (CT-) based radiation therapy planning in unresectable malignant pleural mesothelioma (MPM). Methods. CT and coregistered PET-CT data from seven patients with histologically-proven MPM were utilized for VMAT and HT plans. Target volumes and organs at risk (OARs) were delineated. The prescription doses for planning target volume 1 (PTV1) and PTV2 were 45.0 Gy and 54 Gy in 1.8 Gy/fr, respectively. Each technique was evaluated in terms of target volume coverage and OAR doses. Findings. Although the maximum (p=0.001) and mean (p<0.001) doses of PTV1, and PTV2 (p<0.001 for maximum and p=0.001 for mean doses) favored the HT technique over VMAT, both techniques efficiently covered the target volumes. Additionally, HT also provided more homogeneous dose distribution (p<0.001) and numerically lower doses received by most OARs, but again both rotational techniques were successful in keeping the OAR doses below the universally accepted limits. The major disadvantage of the HT technique was the requirement for longer treatment times (7.4 versus 2.5 minutes/fr; p<0.001) to accomplish the intended treatment. Conclusion. Results of this dosimetric comparison clearly demonstrated the possibility of safe hemithoracic irradiation of medically/technically unresectable MPM patients with either of the two rotational RT techniques, namely the VMAT and HT. Clinically, considering their poor prognosis, these promising findings may open a potential new window for curative treatment of unresectable MPM patients, if further confirmed by future clinical studies.

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Identification of Redox-Sensitive Transcription Factors as Markers of Malignant Pleural Mesothelioma

Cancers ◽

10.3390/cancers13051138 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1138

Author(s):

Martina Schiavello ◽

Elena Gazzano ◽

Loredana Bergandi ◽

Francesca Silvagno ◽

Roberta Libener ◽

...

Keyword(s):

Oxidative Stress ◽

Transcription Factors ◽

Malignant Pleural Mesothelioma ◽

Antioxidant Defense ◽

Asbestos Exposure ◽

Predictive Biomarkers ◽

Antioxidant Systems ◽

Pleural Mesothelioma ◽

Related Factor ◽

Aggressive Cancer

Although asbestos has been banned in most countries around the world, malignant pleural mesothelioma (MPM) is a current problem. MPM is an aggressive tumor with a poor prognosis, so it is crucial to identify new markers in the preventive field. Asbestos exposure induces oxidative stress and its carcinogenesis has been linked to a strong oxidative damage, event counteracted by antioxidant systems at the pulmonary level. The present study has been focused on some redox-sensitive transcription factors that regulate cellular antioxidant defense and are overexpressed in many tumors, such as Nrf2 (Nuclear factor erythroid 2-related factor 2), Ref-1 (Redox effector factor 1), and FOXM1 (Forkhead box protein M1). The research was performed in human mesothelial and MPM cells. Our results have clearly demonstrated an overexpression of Nrf2, Ref-1, and FOXM1 in mesothelioma towards mesothelium, and a consequent activation of downstream genes controlled by these factors, which in turn regulates antioxidant defense. This event is mediated by oxidative free radicals produced when mesothelial cells are exposed to asbestos fibers. We observed an increased expression of Nrf2, Ref-1, and FOXM1 towards untreated cells, confirming asbestos as the mediator of oxidative stress evoked at the mesothelium level. These factors can therefore be considered predictive biomarkers of MPM and potential pharmacological targets in the treatment of this aggressive cancer.

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Increased Standardised Incidence Ratio of Malignant Pleural Mesothelioma in Taiwanese Asbestos Workers: A 29-Year Retrospective Cohort Study

BioMed Research International ◽

10.1155/2015/678598 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Cheng-Kuan Lin ◽

Yu-Ying Chang ◽

Jung-Der Wang ◽

Lukas Jyuhn-Hsiarn Lee

Keyword(s):

Cohort Study ◽

General Population ◽

Incidence Rate ◽

Malignant Pleural Mesothelioma ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Asbestos Exposure ◽

Pleural Mesothelioma ◽

Calendar Period ◽

Incident Cases

Objective. This paper aimed to determine the standardised incidence ratio (SIR) of malignant pleural mesothelioma (MPM) in workers exposed to asbestos in Taiwan.Methods. All workers employed in asbestos-related factories and registered by the Bureau of Labour Insurance between 1 March, 1950, and 31 December, 1989, were included in the study and were followed from 1 January, 1980, through 31 December, 2009. Incident cases of all cancers, including MPM (ICD-9 code: 163), were obtained from the Taiwan Cancer Registry. SIRs were calculated based on comparison with the incidence rate of the general population of Taiwan and adjusted for age, calendar period, sex, and duration of employment.Results. The highest SIR of MPM was found for male workers first employed before 1979, with a time since first employment more than 30 years (SIR 4.52, 95% CI: 2.25–8.09). After consideration of duration of employment, the SIR for male MPM was 5.78 (95% CI: 1.19–16.89) for the workers employed for more than 20 years in asbestos-related factories.Conclusions. This study corroborates the association between occupational asbestos exposure and MPM. The highest risk of MPM was found among male asbestos workers employed before 1979 and working for more than 20 years in asbestos-related factories.

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Pleural Plaques and Malignant Pleural Mesothelioma in a Patient With Previous Asbestos Exposure

Pleural Diseases ◽

10.1016/b978-0-323-79541-8.00002-3 ◽

2022 ◽

pp. 15-22

Author(s):

Marchetti Giampietro ◽

Sorino Claudio ◽

Feller-Kopman David

Keyword(s):

Malignant Pleural Mesothelioma ◽

Asbestos Exposure ◽

Pleural Mesothelioma ◽

Pleural Plaques

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Case 13.8

Mayo Clinic Body MRI Case Review ◽

10.1093/med/9780199915705.003.0332 ◽

2014 ◽

pp. 628-629

Author(s):

Christine U. Lee ◽

James F. Glockner

Keyword(s):

Malignant Pleural Mesothelioma ◽

Asbestos Exposure ◽

The United States ◽

Extrapleural Pneumonectomy ◽

Parietal Pleura ◽

Pleural Mesothelioma ◽

Pleural Plaques ◽

Abnormal Chest ◽

Left Pleura ◽

Histologic Subtypes

62-year-old man with shortness of breath and an abnormal chest CT Axial 3D SPGR postgadolinium images (Figure 13.8.1) demonstrate diffuse thickening and enhancement of the left pleura, with a few minimally enhancing, focal right-sided pleural plaques. Malignant pleural mesothelioma Malignant pleural mesothelioma is a rare neoplasm that originates from the mesothelial cells lining the visceral and parietal pleura. The incidence of malignant pleural mesothelioma in the United States is 15 cases per million; there is a strong correlation with asbestos exposure. Malignant pleural mesothelioma is divided into 3 histologic subtypes: epithelial (55%-65%), sarcomatoid (10%-15%), and mixed (20%-35%). Patients with epithelial malignant pleural mesothelioma have the best prognosis, and among those with limited disease who undergo extrapleural pneumonectomy (removal of the pleura, lung, hemidiaphragm, and part of the pericardium), survival is longer (5-year survival, 39%) than among all patients (median survival, 8-18 months after diagnosis)....

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Treatment of malignant pleural mesothelioma: current status and future directions

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2010.302 ◽

2016 ◽

Vol 73 (2) ◽

Author(s):

X. Dhalluin ◽

A. Scherpereel

Keyword(s):

Malignant Pleural Mesothelioma ◽

European Society ◽

Poor Prognosis ◽

Asbestos Exposure ◽

Therapeutic Strategies ◽

Current Status ◽

Pleural Mesothelioma ◽

European Respiratory Society ◽

Future Directions ◽

Cell Therapies

Previously considered to be rare, malignant pleural mesothelioma (MPM) is a highly aggressive tumour that has become a very important issue over recent years due to its poor prognosis and its increasing incidence mostly linked to previous asbestos exposure. An optimal treatment for MPM is not established yet; new therapies and predictive tools are still needed in the management of this cancer. Thus the aim of this review is to provide clinicians clear and up-to-dated data on the latest therapeutic strategies for MPM patients in 2010. The guidelines recently proposed by the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS) taskforce are summarized here. The authors also briefly reviewed the future directions in MPM treatment including targeted therapies, gene or cell therapies.

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