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The Role of Dosimetric Parameters in Radiation Pneumonitis: A Functional Approach in Adjuvant Treatment of Malignant Pleural Mesothelioma
by
, , , , , , and
Luca Dominici
1,*, 
Davide Franceschini
1,
Mauro Loi
2,
Ruggero Spoto
1,
Antonio Marco Marzo
1,
Beatrice Marini
1,
Mariya Boyanova Ilieva
1,3,
Nicola Lambri
1,4,
Francesco La Fauci
1,
Ciro Franzese
1,3 and
Marta Scorsetti
1,3 1
Department of Radiotherapy and Radiosurgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
2
Department of Radiation Oncology, Azienda Universitaria Ospedaliera Careggi, 50134 Florence, Italy
3
Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090 Milan, Italy
4
Scuola di Specializzazione di Fisica Medica, Università Degli Studi di Milano, 20133 Milan, Italy
*
Author to whom correspondence should be addressed.
Cancers 2026, 18(3), 405; https://doi.org/10.3390/cancers18030405
Submission received: 29 December 2025
/
Revised: 21 January 2026
/
Accepted: 24 January 2026
/
Published: 27 January 2026
(This article belongs to the Special Issue Radiation Therapy in Lung Cancer: From a Technical Revolution to a Combination with New Systemic Approaches (2nd Edition))
Simple Summary
Malignant pleural mesothelioma (MPM) is a very aggressive cancer that is quite rare and is mostly linked to asbestos exposure. In the case of MPM patients undergoing lung-saving surgery (pleurectomy/decortication), radiation therapy forms an integral part of the treatment plan. However, its use is often limited because of the danger of lung toxicity, especially radiation pneumonitis (RP). It is of utmost importance to discover reliable predictors of radiation pneumonitis that can be utilized for personalizing the treatment plan. This retrospective study was conducted to evaluate the prognostic power of conventional dosimetric parameters—the so-called “functional” parameters which are determined by the exclusion of the emphysematous regions of the lungs—in a group of MPM patients receiving adjuvant intensity-modulated radiation therapy. The results in our hands suggest that functional parameters might offer additional value over standard parameters.
Abstract
Background: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm, the major cause of which is asbestos exposure. Adjuvant radiotherapy after pleurectomy/decortication (P/D) aims at reducing locoregional recurrence but is limited by the risk of radiation pneumonitis (RP). In this study, we attempted to evaluate the predictive value of conventional and functional dosimetric parameters in assessing RP risk. Methods: This retrospective study analyzed 68 patients with non-metastatic MPM treated with adjuvant radiotherapy after P/D. Dosimetric parameters, including V20, V5, and mean lung dose (MLD), were calculated for both total lung volume and functional lung volume (FLV), with emphysematous regions excluded based on CT imaging thresholds. Statistical analyses assessed correlations between these parameters and acute RP incidence. Results: Acute RP developed in 42% of patients, and 28% had moderate-to-severe (Grade 2–3) events. V20 and FCL_V20 were significantly associated with the risk of RP (p = 0.017 and p = 0.028, respectively). Predictive accuracy for conventional V20 (AUC = 0.668) and Functional Contralateral Lung V20 (FCL_V20) (AUC = 0.655) showed moderate efficacy, without further significant improvement in using functional parameters. A V20 threshold > 1.8% predicted severe RP with high specificity (89.8%). Conclusion: While functional lung delineation provides an alternative in dosimetry, conventional V20 is a robust predictor of RP. Optimization of dosimetric constraints, in an effort to reduce pulmonary toxicity in MPM patients, should be further combined with advanced radiotherapy techniques and biomarkers.
