Malignant Pleural Mesothelioma in Young People

Background: malignant pleural mesothelioma (MPM) is characterized by long latency period between exposure to asbestos and development of the disease so we hypothesize that MPM in the young has different characteristics. Patients and Methods: This is a retrospective study including all eligible patients with malignant pleural mesothelioma presenting to National Cancer Institute, Cairo University during the period from 2008 to 2013. Patients were divided into two groups: Group 1: patients aged ≤45 years. Group 2: Patients aged >45 years. Both groups were assessed regarding different clinicpathological features. Primary Objectives: comparison of different epidemiological features of both groups. Secondary Objectives: assessment of clinical response (CR), progression free survival (PFS) and overall survival (OS) in both groups. Results: 102 Patients were included with median follow up of 14.4 months. Group (1) included 35 patients with mean age 40 ± 3.65 years (31 to 45 years). Group (2) included 67 patients with mean age of 58.6 ± 8.5 years (46 to 87 years). 68% of group (1) came from endemic areas which is significantly higher than group (2): (35.8%), p = 0.02. History of Asbestos exposure was highly significantly different between the 2 groups, 77.1% in group (1) versus 38.8% in group (2), p < 0.001. Other factors showed no significant differences between the two groups. Overall clinical response (CR + PR) was 20% in group (1) versus 17.9% in group (2). P = 0.7. There was a trend towards longer median PFS in young patients, (19.8 ± 8.4 versus 6.9 ± 1.4 months). p = 0.09. The median OS of young patients is significantly longer (20.6 ± 6.3 months) than older patients (11.4 ± 3.6). p = 0.05. Conclusions: Mesothelioma in the young is more sensitive to asbestos exposure, has better OS and likely a different disease entity which needs further studies to understand its underlying biological features. How to cite this paper: El Bastawisy, A., Yahia, M., Rahouma, M., Aboelazm, O. and Ahmed, J. (2017) Malignant Pleural Mesothelioma in Young People. Journal of Cancer Therapy, 8, 443-451. https://doi.org/10.4236/jct.2017.85038 Received: March 4, 2017 Accepted: May 21, 2017 Published: May 26, 2017 Copyright © 2017 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Open Access A. El Bastawisy et al.


Keywords
Malignant Pleural Mesothelioma-Young

Introduction
Mesothelioma is a rare cancer that is estimated to occur in approximately 2500 people is US every year [1].
Malignant pleural mesothelioma is the most common type, however, it can also occur in lining of other sites e.g. peritoneum, pericardium, tunica vaginalis testis.
Malignant pleural mesothelioma is the most common type, however, it can also occur in lining of other sites e.g. peritoneum, pericardium, tunica vaginalis testis. [2].
Repeated episodes of inflammation and healing, oxygen free radical production from inflammatory cells and the iron moiety within asbestos as well as di- Malignant pleural mesothelioma occurs mainly in older men (median age is 72 years) who have exposed to asbestos although it occurs decades after exposure (20 to 40 years later) [3] [4] [5] [6].
Considering the long latency period from exposure to asbestos to disease development it is hypothesized that malignant pleural mesothelioma in young age is less likely to be caused by asbestos exposure and that other factors may attribute to the disease process such as genetic predisposition or exposure to other environmental carcinogens.
So it is important to understand the clinico-pathological features of malignant pleural mesothelioma in this particular age group.

Aim of Work
Primary objectives: Assessment of different epidemiological features of malignant pleural mesothelioma in patients aged less than or equal 45 years as compared to those more than 45 years. Secondary objectives: Assessment of the clinical outcome including clinical response, progression free survival and overall survival in patients aged less than or equal 45 years compared to those more than 45 years.

Methods
This is a retrospective population study including all patients with histologically proven malignant pleural mesothelioma presenting to the National Cancer Institute Cairo University during the period from 2008 to 2013.
Patients were divided to two groups: Clinical outcome including complete response, progression free survival and overall survival.

Study Assessment
Evaluation was done according to the Modified RECIST (Response Evaluation Criteria in Solid Tumors) [8].

Statistical Analysis
Data was analyzed using SPSS win statistical package version 21 (SPSS Inc., Chicago, IL). Numerical data were expressed as mean and standard deviation or median and range as appropriate. Qualitative data were expressed as frequency and percentage.
Chi-square test (Fisher's exact test) was used to examine the relation between qualitative variables. For quantitative data, comparison between two groups was done using either student t-test or Mann-Whitney test (non-parametric t-test) as appropriate. A p-value < 0.05 was considered significant.
Kaplan-Meier method calculated all survival estimates. Other predictor and prognostic variables were related to survival using log rank test. P value was set significant at 0.05 level (Kleinbaum, 2005).

Results
102 Patients were included with median follow up of 14.4 months. Table 1 shows patients characteristics. 68% of group (1) came from endemic areas which is significantly higher than group (2): (35.8%), p = 0.02. History of Asbestos exposure was highly significantly different between the 2 groups, 77.1% in group (1) versus 38.8% in group (2), p < 0.001. Other factors including sex, diabetes mellitus, Hypertension, smoking, PS, pathological type and laterality showed no significant differences between the two groups.

Discussion
There are several studies that report different clinico-pathological data and prognostic factors in either elderly or young patients but this study represents one of   Leukemia Group B (CALGB) treated patients reported young age to be a good prognostic factor for survival, however he assigned the cutoff value between young and elderly to be 75 years which lies near the upper age limit among our cohort. [10] Based upon that, we sought to divide our cohort around the median of 45 years old. The most prevalent histological subtype was epithelial MPM, with male predominance among both cohorts, young and elderly, reflecting higher occupational exposure among men that are in concordance with many previously reported series [11] [12] [13].
It is well known that advanced stage is associated with poor PFS and overall survival in different thoracic malignancies; however, among our cohorts we couldn't find statistically significant stage differences among both cohorts [11] [12].
Effect of asbestos exposure and asbestosis is a cumulative one, hence several studies report higher incidence of asbestosis among elderly (76% vs. nearly 40% in the current study). Although this is the usual due to the cumulative effect of asbestos exposure making those elderly group more vulnerable to MPM development, however among our cohort, we found that those young cohort might be heavily exposed to asbestos, evident by the higher percentage of endemic areas residents, that proved to be as important as long term low asbestos dose exposure [11] [12] [13] Again young patients maybe more sensitive to asbestos exposure whether occupationally or residentially which makes young patients more liable to develop mesothelioma regardless of the length of exposure, this may be attributed to unique biological factors characterizing this group of patients.
Advanced age is a well-known factor that is associated with poor overall survival in mesothelioma, whether pleural or peritoneal [11] and in other thoracic malignancy as lung cancer. Our median OS of 11.4 months in elderly is identical to that of the Italian multicenter study reported by Ceresoli et al. [11] On the other side, several studies reported better survival in younger patients with MPM and many of them attribute this to better performance status and absence of comorbidities and low level of reactive oxygen species implicated in aging process that are abundant among elderly population [11]  Based upon our results, MPM is represents a serious health problem in cohorts, young and elderly, so an integrated national and international commitment is required to eliminate it and other asbestos-related diseases.
Further studies are needed to identify a biological cut off point for definition of MPM in young patients.
The drawbacks of this study included small sample size, absence of a biologi-cal rational to the choice of age of young patients, being retrospective. Further studies are needed to identify a biological cut off point for definition of MPM in young patients and to better understand the biological background of this disease entity including correlation with BAP1 and others.

Conclusion
Young mesothelioma patients are more significantly exposed to asbestos and coming more from endemic areas suggesting that mesothelioma in the young is more sensitive to asbestos exposure, again has better OS and likely a different disease entity which needs further studies to understand its underlying biological features.