Abstract
Malignant pleural mesothelioma (MPM) is an aggressive malignancy, frequently diagnosed at locally-advanced/metastatic stages. Due to a very poor prognosis and limited treatment options, the need to identify new prognostic markers represents a great clinical challenge. The prognostic role of metabolic information derived from Positron Emission Tomography (PET) with 18F-Fluoro-deoxy-glucose (18F-FDG) has been investigated in different MPM settings, however with no definitive consensus. In this comprehensive review, the prognostic value of FDG-PET imaging exclusively performed at staging in MPM patients was evaluated, conducting a literature search on PubMed/MEDLINE from 2010 to 2020. From the 19 selected studies, despite heterogeneity in several aspects, staging FDG-PET imaging emerges as a valuable prognostic biomarker, with higher tumor uptake predictive of worse prognosis, and with volumetric metabolic parameters like Metabolic Tumor Volume, (MTV) and Total Lesion Glycolisis (TLG) performing better than SUVmax. However, PET uptake parameters were not always confirmed as independent prognostic factors, especially in patients previously treated with pleurodesis and with a non-epithelioid histotype. Future prospective studies in larger and clinically homogeneous populations, and using more standardized methods of PET images analysis, are needed to further validate the value of staging FDG-PET in the prognostic MPM stratification, with a potential impact on better patient-tailored treatment planning, in the perspective of personalized medicine.
Highlights
Malignant pleural mesothelioma (MPM) is the most common primary neoplasm of the pleura, arising from pleural mesothelial cells, and it is usually related to occupational or environmental asbestos exposure [1]
In MPM cells, it has been demonstrated that increased 18F-FDG uptake is associated with an over-expression of GLUT-1 and hexokinase I, both reflecting an increased glucose metabolism needed for tumor growth, and with an up-regulation of tumoral cells factors related to angiogenesis, hypoxia (hypoxia-inducible factor-1 alpha—HIF-1a—cell proliferation (Ki-67 index), and cell cycle regulation, which are well-known to be associated with a more aggressive behaviour and worse prognoses [39]
Albeit the overall prognostic value of staging 18F-FDG Positron Emission Tomography (PET) imaging that emerges from this review, it has to be considered that PET uptake parameters were not always confirmed as independent prognostic factors, and that a minority of studies did not find any relationship between tumor metabolic activity and survival, for a total of 9/19 included studies
Summary
Malignant pleural mesothelioma (MPM) is the most common primary neoplasm of the pleura, arising from pleural mesothelial cells, and it is usually related to occupational or environmental asbestos exposure [1]. At present, there being no widely accepted standard of care, treatment strategy is mainly determined by disease stage (I-II vs III-IV), histological type (epithelioid vs non-epithelioid), and patient’s performance status. Multimodality therapy (combining surgery with either neoadjuvant and/or adjuvant treatment that includes chemotherapy and radiotherapy) with curative intent is considered in selected patients judged medically operable, with limited stages and epithelioid subtype, whereas the remaining cases ( representing the majority of patients) are candidates to systemic chemotherapy with pemetrexed and platinum-based agents (+/− radiotherapy) or palliative-best supportive care [4,7,8,9]. Regardless of the therapeutic strategy, the survival benefits of the current treatment options remain unsatisfactory, even in the case of multimodality therapy that has improved survival in select patients, but with inter-individual variability in response [10,11]. The prognostic stratification of MPM patients remains a great challenge for clinicians, both in aiming for a better patient-tailored treatment strategy and in the perspectives of new therapeutic frontiers and patients’ enrolment into prospective clinical trials
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