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| Document name | Authors | DOI | Date | ||
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| Association of Cardiac and Pulmonary CT Imaging Features with Respiratory Side Effects After Whole-Breast Radiotherapy. | Fois M., Belardo A., Fodor A., Perna L., Giannini L, Mangili P., Palazzo G., Pasetti M., Torrisi M., Tummineri R., Ubeira-Gabellini M.G., Del Vecchio A., Di Muzio N.G., Rancati T., Fiorino C. | doi: 10.3390/cancers18111727 | May 2026 | Download Full Article |
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.
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| Mathematical modeling and sensitivity analysis of hypoxia-activated drugs. | Coclite A, Montanelli Sccher R, Possenti L, Vitullo P, Zunino P. | doi: 10.3934/math.20251130 | November 2025 | Download Full Article |
Hypoxia-activated prodrugs offer a promising strategy for targeting oxygen-deficient regions in solid tumors, which are often resistant to conventional therapies. However, modelling their behaviour is challenging because of the complex interplay between oxygen availability, drug activation, and cell survival.
In this work, we developed a multi-scale and mixed-dimensional model that coupled spatially resolved drug and oxygen transport with pharmacokinetics and pharmacodynamics to simulate the cellular response. The model integrated blood flow, oxygen diffusion, and consumption, drug delivery, and metabolism. To reduce computational cost, we mitigated the global nonlinearity by coupling the multi-scale and mixed-dimensional models one-way with a reduced 0D model for drug metabolization. The global sensitivity analysis was then used to identify key parameters influencing drug activation and therapeutic outcome.
This approach enabled efficient simulation and supports the design of optimized therapies targeting hypoxia.
| Document name | Authors | DOI | Date | ||
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| Density and volume of cardiac calcifications detected on planning CT predicts cardiotoxicity after hypo-fractionated whole breast Radiotherapy. | Belardo A, Dimayuga KB, Perna L, Fodor A, Giannini L, Mangili O, Palazzo G, Pasetti M, Tummineri R, Vecchio AD, Di Muzio NG, Fiorino C. | doi: 10.1016/j.radonc.2025.111098 | August 2025 | Download Full Article |
Cardiac calcifications (CAC) are emerging as predictors of cardiac toxicity after breast cancer Radiotherapy. Main purposes of this study were:1) to test the association between CAC scores and cardiac events in a cohort treated with moderate hypo-fractionation; b) to assess interaction between CAC and dosimetry/clinical predictors.
Materials and methods: Data of 1172 consecutive patients treated at our hospital with 3DCRT whole breast irradiation (40 Gy/15fr) were available. Heart was automatically segmented and the mean heart dose (MHD) was assessed. The Agatson score (AS), the CAC_volume and the max HU value in the heart (Max_HU) were assessed using an in-house script. Their association with cardiac events was tested by logistic regression, including the combined impact of MHD and relevant clinical parameters (including chemotherapy, age and smoking). CAC_volumes/Max_HU values were compared against the values obtained from our clinical planning system for 75 patients with calcifications.
Results: Twenty-nine patients experienced cardiac events (median follow-up:6.5y). AS/CAC_volume/Max_HU were highly significant predictors (p < 0.005). MHD (mean ± SD: 0.8 ± 0.1/2.4 ± 0.7 Gy for right/left) was predictive only if encoded according to the optimal cut-off based on Youden index (MHD > 1 Gy). The resulting multivariate model combined MHD > 1 Gy, age and CAC scores, with similar performances for the three different scores (AUC = 0.77/0.755, p < 0.0001, R2 = 0.99), with the three different scores always being the major predictor. TPS gave consistent values for Max_HU while CAC_volume showed larger differences, although highly correlated.
Conclusion: CAC are the most important predictors of cardiotoxicity. Max_HU is promising for fast assessment of patients at risk. The greatest clinical benefit of further heart sparing is expected in left breast cancer patients with moderate-severe CAC scores (Max_HU > 250).
