Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study
Radical hemithoracic radiotherapy (RHR), after lung-sparing surgery, has recently become a concrete therapeutic option for malignant pleural mesothelioma (MPM), an asbestos-related, highly aggressive tumor with increasing incidence and poor prognosis. Although the toxicity associated to this treatme...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.784081/full |
| _version_ | 1819320275711295488 |
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| author | Sergio Crovella Alberto Revelant Elena Muraro Ronald Rodrigues Moura Lucas Brandão Marco Trovò Agostino Steffan Paola Zacchi Giuliano Zabucchi Emilio Minatel Violetta Borelli |
| author_facet | Sergio Crovella Alberto Revelant Elena Muraro Ronald Rodrigues Moura Lucas Brandão Marco Trovò Agostino Steffan Paola Zacchi Giuliano Zabucchi Emilio Minatel Violetta Borelli |
| author_sort | Sergio Crovella |
| collection | DOAJ |
| description | Radical hemithoracic radiotherapy (RHR), after lung-sparing surgery, has recently become a concrete therapeutic option for malignant pleural mesothelioma (MPM), an asbestos-related, highly aggressive tumor with increasing incidence and poor prognosis. Although the toxicity associated to this treatment has been reduced, it is still not negligible and must be considered when treating patients. Genetic factors appear to play a role determining radiotherapy toxicity. The aim of this study is the identification of biological pathways, retrieved through whole exome sequencing (WES), possibly associated to the development of lung adverse effects in MPM patients treated with RHR. The study included individuals with MPM, treated with lung-sparing surgery and chemotherapy, followed by RHR with curative intent, and followed up prospectively for development of pulmonary toxicity. Due to the strong impact of grade 3 pulmonary toxicities on the quality of life, compared with less serious adverse events, for genetic analyses, patients were divided into a none or tolerable pulmonary toxicity (NoSTox) group (grade ≤2) and a severe pulmonary toxicity (STox) group (grade = 3). Variant enrichment analysis allowed us to identify different pathway signatures characterizing NoSTox and Stox patients, allowing to formulate hypotheses on the protection from side effects derived from radiotherapy as well as factors predisposing to a worst response to the treatment. Our findings, being aware of the small number of patients analyzed, could be considered a starting point for the definition of a panel of pathways, possibly helpful in the management of MPM patients. |
| first_indexed | 2024-12-24T11:17:00Z |
| format | Article |
| id | doaj.art-c6683ddaea214031a152834007c7ea97 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-24T11:17:00Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-c6683ddaea214031a152834007c7ea972022-12-21T16:58:21ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-12-011110.3389/fonc.2021.784081784081Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary StudySergio Crovella0Alberto Revelant1Elena Muraro2Ronald Rodrigues Moura3Lucas Brandão4Marco Trovò5Agostino Steffan6Paola Zacchi7Giuliano Zabucchi8Emilio Minatel9Violetta Borelli10Department of Biological and Environmental Sciences, College of Arts and Sciences, University of Qatar, Doha, QatarDepartment of Radiation Oncology, Centro di Riferimento Oncologico di Aviano (CRO) Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, ItalyImmunopathology and Biomarker Unit, Department of Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) Istituti di Ricovero e Cura a Carattere Scientifico, Aviano, ItalyDepartment of Advanced Diagnostics, Institute for Maternal and Child Health – Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) “Burlo Garofolo”, Trieste, ItalyDepartment of Advanced Diagnostics, Institute for Maternal and Child Health – Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) “Burlo Garofolo”, Trieste, ItalyRadiation Oncology Department, Udine Academic Hospital, Udine, ItalyImmunopathology and Biomarker Unit, Department of Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) Istituti di Ricovero e Cura a Carattere Scientifico, Aviano, ItalyDepartment of Life Sciences, University of Trieste, Trieste, ItalyDepartment of Life Sciences, University of Trieste, Trieste, ItalyDepartment of Radiation Oncology, Centro di Riferimento Oncologico di Aviano (CRO) Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, ItalyDepartment of Life Sciences, University of Trieste, Trieste, ItalyRadical hemithoracic radiotherapy (RHR), after lung-sparing surgery, has recently become a concrete therapeutic option for malignant pleural mesothelioma (MPM), an asbestos-related, highly aggressive tumor with increasing incidence and poor prognosis. Although the toxicity associated to this treatment has been reduced, it is still not negligible and must be considered when treating patients. Genetic factors appear to play a role determining radiotherapy toxicity. The aim of this study is the identification of biological pathways, retrieved through whole exome sequencing (WES), possibly associated to the development of lung adverse effects in MPM patients treated with RHR. The study included individuals with MPM, treated with lung-sparing surgery and chemotherapy, followed by RHR with curative intent, and followed up prospectively for development of pulmonary toxicity. Due to the strong impact of grade 3 pulmonary toxicities on the quality of life, compared with less serious adverse events, for genetic analyses, patients were divided into a none or tolerable pulmonary toxicity (NoSTox) group (grade ≤2) and a severe pulmonary toxicity (STox) group (grade = 3). Variant enrichment analysis allowed us to identify different pathway signatures characterizing NoSTox and Stox patients, allowing to formulate hypotheses on the protection from side effects derived from radiotherapy as well as factors predisposing to a worst response to the treatment. Our findings, being aware of the small number of patients analyzed, could be considered a starting point for the definition of a panel of pathways, possibly helpful in the management of MPM patients.https://www.frontiersin.org/articles/10.3389/fonc.2021.784081/fullmesotheliomaradical hemithoracic radiotherapypulmonary toxicitieswhole exomethromboembolism |
| spellingShingle | Sergio Crovella Alberto Revelant Elena Muraro Ronald Rodrigues Moura Lucas Brandão Marco Trovò Agostino Steffan Paola Zacchi Giuliano Zabucchi Emilio Minatel Violetta Borelli Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study Frontiers in Oncology mesothelioma radical hemithoracic radiotherapy pulmonary toxicities whole exome thromboembolism |
| title | Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study |
| title_full | Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study |
| title_fullStr | Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study |
| title_full_unstemmed | Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study |
| title_short | Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study |
| title_sort | biological pathways associated with the development of pulmonary toxicities in mesothelioma patients treated with radical hemithoracic radiation therapy a preliminary study |
| topic | mesothelioma radical hemithoracic radiotherapy pulmonary toxicities whole exome thromboembolism |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.784081/full |
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