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Association of Cardiac and Pulmonary CT Imaging Features with Respiratory Side Effects After Whole-Breast Radiotherapy
by
, , , , , and
Marco Fois
1,
Alfonso Belardo
1,
Andrei Fodor
2,
Lucia Perna
1,
Laura Giannini
2,
Paola Mangili
1,
Gabriele Palazzo
1,
Marcella Pasetti
2,
Miriam Torrisi
2,
Roberta Tummineri
2,
Maria Giulia Ubeira-Gabellini
1,
Antonella Del Vecchio
1,
Nadia Gisella Di Muzio
2,3,
Tiziana Rancati
4 and
Claudio Fiorino
1,*
1
Medical Physics, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milano, Italy
2
Radiation Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milano, Italy
3
Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milano, Italy
4
Data Science Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy
*
Author to whom correspondence should be addressed.
Cancers 2026, 18(11), 1727; https://doi.org/10.3390/cancers18111727 (registering DOI)
Submission received: 30 April 2026
/
Revised: 21 May 2026
/
Accepted: 23 May 2026
/
Published: 25 May 2026
(This article belongs to the Special Issue Personalized Radiotherapy in Cancer Care (2nd Edition))
Simple Summary
In a single-institute cohort of 1172 patients receiving moderately hypofractionated radiotherapy to the whole breast (WBRT), pulmonary side effects were uncommon (1.5% of the total) but clinically relevant. Lung and heart densitometry features extracted from planning CTs, such as the low-density lung volume (HU < −850) and cardiac calcification scores, resulted in strong predictors of toxicity rather than radiation dose parameters. These results suggest that, in modern cohorts, most of the respiratory events after WBRT seem to be mainly related to baseline clinical conditions captured by CT imaging instead of being caused by radiation.
Abstract
Purpose: This paper aimed to identify dosimetric, clinical, and CT-based densitometric predictors of radiation-induced pulmonary events in breast cancer patients treated with moderately hypofractionated radiotherapy. Materials and Methods: A single-institution cohort of 1172 consecutive patients treated with 3D conformal whole-breast radiotherapy (40 Gy/15 fractions) before 2017 was analyzed. Ipsilateral lung DVHs and CT densitometry metrics were extracted. Clinical variables and cardiac calcification (CAC) scores (Agatston_score, CAC_volume, Max_HU_Heart) were included. Univariable and multivariable logistic regressions were performed; collinearity was assessed via Spearman correlation and VIF. Optimal thresholds were derived using the Youden index. Internal validation used bootstrap resampling. Results: After a median follow-up of 6.5 years, 18 patients developed moderate/severe pulmonary events. The univariable analysis showed associations with lung densitometric features (median/mean HU, 10th percentile, the lung volume with HU < −850 (V850)), V37 Gy, lung volume, and CAC scores. Lower lung HU values and larger lung volumes were linked to higher risk. The best models combined V850 (or lung volume) with a CAC metric. The model including V850 > 175 cc and continuous Max_HU_Heart achieved an optimism-corrected AUC of 0.68, with good fit and calibration (Hosmer–Lemeshow p = 0.33, R2 = 0.847). Conclusions: The baseline cardiopulmonary status, captured by lung and heart densitometry, predicts pulmonary toxicity better than dosimetry. V850 > 175 cc was associated with a 4-fold higher risk, consistent with air trapping, known as a marker of emphysema.
