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. 2025 Mar;16(5):e70024.
doi: 10.1111/1759-7714.70024.

Impact of Neoadjuvant and Adjuvant Pleural Intensity-Modulated Radiotherapy in Multimodality Treatment for Malignant Pleural Mesothelioma

Berta Mosleh  1 , Stefan Schwarz  1 , Anna Cho  2 , Katharina Sinn  1 , Ariane Steindl  3 , Sabine Zöchbauer-Müller  3 , Wolfgang J Köstler  3 , Karin Dieckmann  4 , Martin Heilmann  4 , Joachim Widder  4 , Daniela Gompelmann  5 , Clemens Aigner  1 , Thomas Klikovits  1 , Mir Alireza Hoda  1
Affiliations

Impact of Neoadjuvant and Adjuvant Pleural Intensity-Modulated Radiotherapy in Multimodality Treatment for Malignant Pleural Mesothelioma

Berta Mosleh et al. Thorac Cancer. 2025 Mar.

Abstract

Background: Few malignancies provoke as many controversies about treatment as pleural mesothelioma. There is limited experience with novel radiotherapy techniques worldwide in adjuvant and particularly in neoadjuvant settings within multimodality treatment. The objective of the current study was to investigate the long-term outcome of neoadjuvant and adjuvant pleural intensity-modulated radiotherapy (IMRT) combined with macroscopic complete resection with or without chemotherapy.

Methods: We retrospectively analyzed a consecutive cohort of 59 patients who were diagnosed with pleural mesothelioma and underwent multimodality treatment including macroscopic complete resection and neoadjuvant or adjuvant IMRT between 2005 and 2019 at the Department of Thoracic Surgery, Medical University of Vienna, Austria.

Results: In total, 59 patients (median age 59 years; IQR 54-66, male, n = 48; 81%) were included. Forty-seven patients underwent trimodality treatment consisting of induction chemotherapy, extrapleural pneumonectomy, and adjuvant IMRT. Novel neoadjuvant IMRT with (n = 9) or without (n = 3) chemotherapy followed by extrapleural pneumonectomy was performed in 12 patients. Median overall survival (OS) of all patients was 23.2 months (95% CI; 18.1-28.2) and 3- and 5-year survival rates were 33% and 28%, respectively. Survival was comparable between therapies including neoadjuvant versus adjuvant IMRT (median OS 17.5 vs. 24.0 months, p = 0.39).

Conclusions: Neoadjuvant pleural IMRT has been investigated as a novel treatment option for highly selected cases in pleural mesothelioma. Neoadjuvant IMRT was effective and safe in patients treated in a high-volume institution but showed no relevant survival benefit compared to adjuvant IMRT within multimodality treatment.

Keywords: intensity‐modulated radiotherapy (IMRT); macroscopic complete resection; multimodality treatment; pleural mesothelioma.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram showing the selection of patients throughout the analysis.
FIGURE 2
FIGURE 2
Consort flowchart of the “Vienna Neoadjuvant IMRT Protocol.”
FIGURE 3
FIGURE 3
Considerations for planning neoadjuvant hemithoracic IMRT to be delivered before extrapleural pneumonectomy for patients with resectable malignant pleural mesothelioma according to the “Vienna Neoadjuvant IMRT Protocol.”
FIGURE 4
FIGURE 4
Kaplan–Meier curve demonstrating overall survival for the entire cohort (A) and between treatment groups (B). No significant survival difference between patients receiving neoadjuvant versus adjuvant IMRT was observed (OS for the entire cohort 23.2 months; OS 24.0 vs. 17.5 months in the adjuvant vs. neoadjuvant IMRT group, p = 0.39). AIMRT: adjuvant intensity‐modulated radiotherapy; NIMRT: neoadjuvant intensity‐modulated radiotherapy.
FIGURE 5
FIGURE 5
Kaplan–Meier curve demonstrating disease‐free survival (13.2 months, 95% CI; 7.7–18.9) for the entire cohort (A) and between treatment groups (B). No significant differences in disease‐free survival between neoadjuvant and adjuvant IMRT treatment groups were found (7.9 vs. 13.7 months, p = 0.37). AIMRT: adjuvant intensity‐modulated radiotherapy; NIMRT: neoadjuvant intensity‐modulated radiotherapy.
FIGURE 6
FIGURE 6
(A) Kaplan–Meier curve demonstrating overall survival according to histology. Overall survival was 23.2 months in patients with epithelioid subtype compared to 20.9 months in patients with non‐epithelioid histology (p = 0.91). (B) Among patients with epithelioid histology, the disease‐free survival reached 13.6 months compared to 5.6 months in patients with non‐epithelioid mesothelioma (p = 0.21).
FIGURE 7
FIGURE 7
Kaplan–Meier curve demonstrating overall survival for all patients (A) and between treatment groups (B) after propensity score matching. Median overall survival for the matched study cohort was 23.2 months (95% CI; 17.6–28.7). No significant survival difference between patients receiving neoadjuvant versus adjuvant IMRT was observed (OS 17.5 vs. 24.2 months in the neoadjuvant vs. adjuvant IMRT group, p = 0.40). AIMRT: adjuvant intensity‐modulated radiotherapy; NIMRT: neoadjuvant intensity‐modulated radiotherapy.
FIGURE 8
FIGURE 8
Kaplan–Meier curve demonstrating disease‐free survival after propensity score matching; (A) for all patients (13.6 months, 95% CI; 6.3–21.0) and between treatment groups (B). No significant differences in disease‐free survival between neoadjuvant and adjuvant IMRT treatment groups were found (6.5 vs. 15.8 months, p = 0.34). AIMRT: adjuvant intensity‐modulated radiotherapy; NIMRT: neoadjuvant intensity‐modulated radiotherapy.
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