Malignant pleural mesothelioma (MPM) is a tumour that originates from the pleural layers (visceral and parietal) that envelop the lungs and the inner wall of the thoracic cage.
In other tumour contexts, numerous studies have demonstrated a synergistic effect between RT and Immune Checkpoint Inhibitors (ICIs), mainly due to immunogenic effects attributed to high doses of RT and ICIs-mediated activation of anti-tumour T lymphocytes.
Both treatments, RT and immunotherapy, have demonstrated a survival advantage in MPM, but are associated with non-negligible pulmonary toxicity. Therefore, the combination of these 2 therapeutic approaches requires a careful assessment of risk factors for the occurrence of toxicity. The identification of circulating biomarkers capable of predicting the onset of severe toxicity induced by radical radiation treatment is an important clinical need in MPM.
This study aims to monitor circulating biomarkers, such as molecules involved in inflammation and oxidative stress and cellular effectors modulated by radiation treatment and potentially associated with the development of toxicity and/or markers of an immunogenic effect of radiotherapy in the peripheral blood of subjects with malignant pleural mesothelioma for treatment with radical hemithoracic radiotherapy.
Over 18 years of age;
Ability to understand, accept and sign consent informed;
Histological diagnosis of malignant pleural mesothelioma;
Previous administration of chemotherapy;
Disease not histologically established
Progression pattern not amenable to radiation treatment (ipsilateral or metastatic intrathoracic extensive disease);
Metastatic patient at diagnosis.
Patients diagnosed with non-metastatic MPM previously treated with chemotherapy, undergoing a non-radical long-sparing surgical approach and treated with RT with radical intent (retrospective cohort) or eligible for RT with radical intent (prospective cohort)
Cohort
Prospective
Not listed
Association between biomarker levels measured at the end of radiation treatment and pulmonary toxicity of grade ≥2 associated with RT developed as an acute (within 6 months) or late (after 6 months) event
Differences in fold change of selected biomarkers, between subjects experiencing or not experiencing acute or late toxicity
Relation between the severity of radio-induced toxicity and trend of biomarkers associated with it
Evaluation of linear trend of biomarkers fold change in relation with toxicity severity
Identifying biomarkers associated with lung toxicity potentially predictive of pulmonary fibrosis
Difference in frequencies of selected biomarkers between subgroups of patients with or without pulmonary fibrosis
Identifying signs of radio-induced immunomodulation among significant changes induced by hemithoracic radical radiotherapy in analysed biomarkers
difference in median values of selected biomarkers before and after treatment
Association between the levels of biomarkers measured at the end of treatment radiation and overall survival (OS) at 24 months
Relation between overall survival and levels of biomarkers fold change using Cox regression. OS will be defined as time from beginning of the therapy until death from any cause or end of follow-up, whichever comes first.
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