Phys Med Biol. 2026 Mar 13. doi: 10.1088/1361-6560/ae5209. Online ahead of print.

ABSTRACT

ObjectiveThis study aims to develop a functional-based multi-omics model for early prediction of radiation pneumonitis (RP) by extracting radiomic and dosiomic features from functionally defined lung regions, using generated perfusion (Q) and ventilation (V) from pre-radiotherapy planning computed tomography (CT).
ApproachWe retrospectively analyzed data from 121 patients with locally advanced non-small cell lung cancer (NSCLC) treated with curative-intent IMRT between 2015 and 2019, including pre-treatment CT and dose maps. Q and V maps were generated from CT with deep learning-based and supervoxel-based approaches, respectively. Regions of interest (ROIs) combined the planning target volume (PTV) with each of three functional lung regions-high functional lung (HFL), low functional lung (LFL), and whole lung (WL)-defined by thresholds on Q and V maps. Radiomic and dosiomic features were extracted from CT and dose distributions within each ROI. For each ROI, For each ROI, three methods-radiomics (R), dosiomics (D), and dual-omics (RD)-were constructed. 13 machine learning algorithms were trained and evaluated using 10-fold cross-validation, and model performance was assessed by the average area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score. RP was defined as CTCAE grade ≥ 2.
Main resultsOf the 35 selected features, 20 were from HFL. In dual-omics models, using HFL features improved predictive performance for RP (AUC 0.879±0.105) compared to WL (AUC 0.778 ± 0.100). In HFL, the RD method outperformed both R (AUC 0.786± 0.076) and D (AUC 0.791 ± 0.107) methods. Decision curve analysis showed the dual-omics model based on HFL provided the highest net benefit across threshold probabilities.
SignificanceThis study is the first to systematically demonstrate that features extracted from CT-derived HFL capture important functional differences and provide strong predictive value for RP. Compared to conventional methods, integrating radiomics, dosiomics, and CT-based functional information further improves predictive performance.&#xD.

PMID:41825133 | DOI:10.1088/1361-6560/ae5209

Gastric Cancer. 2026 Mar 13. doi: 10.1007/s10120-026-01718-x. Online ahead of print.

ABSTRACT

BACKGROUND: 5-Fluorouracil (5-FU) remains a cornerstone of first-line chemotherapy for gastric cancer, yet the emergence of resistance severely compromises its clinical efficacy. Although ferroptosis suppression has been recognized as a pivotal mechanism of chemoresistance, the mitochondrial regulatory processes involved remain poorly understood.

METHODS: We integrated clinical specimen analysis, in vitro and in vivo functional assays, multi-omics profiling, and molecular docking to delineate the role of the mitochondrial oxidoreductase OXNAD1 in mediating 5-FU resistance in gastric cancer, and to assess the therapeutic potential of the natural polyphenol resveratrol as a chemosensitizing agent.

RESULTS: OXNAD1 was found to be significantly overexpressed in gastric cancer tissues and cell lines, correlating with unfavorable prognosis and enhanced 5-FU resistance. Mechanistically, OXNAD1 directly bound to and suppressed the ferroptosis driver PTGS2, thereby attenuating lipid peroxidation and mitochondrial damage, ultimately restraining ferroptosis and promoting drug resistance. Notably, resveratrol disrupted the OXNAD1-PTGS2 interaction by directly binding OXNAD1, reinstating ferroptotic activity, markedly enhancing the cytotoxic effect of 5-FU in resistant cells, and potentiating the antitumor efficacy of 5-FU in xenograft models.

CONCLUSION: The OXNAD1-PTGS2 axis constitutes a critical metabolic-cell death cross-regulatory pathway underlying 5-FU resistance in gastric cancer. Targeting this axis with resveratrol provides a promising combinatorial strategy to overcome chemoresistance.

PMID:41824193 | DOI:10.1007/s10120-026-01718-x

Phys Med Biol. 2026 Mar 13. doi: 10.1088/1361-6560/ae5209. Online ahead of print.

ABSTRACT

ObjectiveThis study aims to develop a functional-based multi-omics model for early prediction of radiation pneumonitis (RP) by extracting radiomic and dosiomic features from functionally defined lung regions, using generated perfusion (Q) and ventilation (V) from pre-radiotherapy planning computed tomography (CT).
ApproachWe retrospectively analyzed data from 121 patients with locally advanced non-small cell lung cancer (NSCLC) treated with curative-intent IMRT between 2015 and 2019, including pre-treatment CT and dose maps. Q and V maps were generated from CT with deep learning-based and supervoxel-based approaches, respectively. Regions of interest (ROIs) combined the planning target volume (PTV) with each of three functional lung regions-high functional lung (HFL), low functional lung (LFL), and whole lung (WL)-defined by thresholds on Q and V maps. Radiomic and dosiomic features were extracted from CT and dose distributions within each ROI. For each ROI, For each ROI, three methods-radiomics (R), dosiomics (D), and dual-omics (RD)-were constructed. 13 machine learning algorithms were trained and evaluated using 10-fold cross-validation, and model performance was assessed by the average area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score. RP was defined as CTCAE grade ≥ 2.
Main resultsOf the 35 selected features, 20 were from HFL. In dual-omics models, using HFL features improved predictive performance for RP (AUC 0.879±0.105) compared to WL (AUC 0.778 ± 0.100). In HFL, the RD method outperformed both R (AUC 0.786± 0.076) and D (AUC 0.791 ± 0.107) methods. Decision curve analysis showed the dual-omics model based on HFL provided the highest net benefit across threshold probabilities.
SignificanceThis study is the first to systematically demonstrate that features extracted from CT-derived HFL capture important functional differences and provide strong predictive value for RP. Compared to conventional methods, integrating radiomics, dosiomics, and CT-based functional information further improves predictive performance.&#xD.

PMID:41825133 | DOI:10.1088/1361-6560/ae5209