Objectives: To describe the utilization trend of radiation-based and surgery-based treatment in patients with resectable IIIC1 cervical adenocarcinoma and explore the optimal treatment strategy for these patients.
Methods: Patients with resectable IIIC1 cervical adenocarcinoma in 2005-2022 from Surveillance, Epidemiology, and End Results program (SEER) were analyzed. Trends over time in the utilization of radiation- and surgery-based treatment were plotted and estimated using Mantel-Haenszel test. Logistic regression analysis was performed to identify factors associated with the utilization of treatment. Survival outcomes were assessed and compared using Kaplan-Meire method and log-rank test, respectively. Inverse probability of treatment weighting (IPTW) was performed for adjustment of baseline characteristics. Sensitivity analysis was conducted using a cohort of cervical adenocarcinoma patients from our institution.
Results: The utilization of radiation-based treatment has grown steadily from 2005 to 2022 while the trend for surgery-based treatment showed opposite way (P = 0.002). Age, year of diagnosed, tumor size and T stage impacted the utilization of radiation-based treatment (All P < 0.05). Surgery-based treatment demonstrated superior overall survival (HR = 0.55, 95%CI:0.44-0.69; P < 0.001) and cancer specific survival (HR = 0.58, 95%CI:0.45-0.75; P < 0.001) to radiation-based treatment before adjustment of IPTW. However, no significant differences were observed in overall survival (HR = 0.77, 95%CI:0.56-1.05; P = 0.1) and cancer specific survival (HR = 0.86, 95%CI:0.60-1.23; P = 0.4) after baseline characteristics were balanced. Besides, the cohort from our institution further verified that similar survival outcomes were observed between two treatment strategies.
Conclusions: The utilization of radiation-based treatment has increased over time and showed non-inferior efficacy for patients with resectable IIIC1 cervical adenocarcinoma when compared to surgery-based treatment.
{"title":"Radiation- versus surgery-based treatment for patients with resectable IIIC1 cervical adenocarcinoma.","authors":"Xi-Lin Yang, Jia-Wei Zhu, Chen Wang, Yun-Can Zhou, Zheng Miao, Hui Guan, Zhi-Wei Yang, Qiu Guan, Jun-Fang Yan, Ke Hu, Fu-Quan Zhang","doi":"10.1016/j.radonc.2026.111370","DOIUrl":"https://doi.org/10.1016/j.radonc.2026.111370","url":null,"abstract":"<p><strong>Objectives: </strong>To describe the utilization trend of radiation-based and surgery-based treatment in patients with resectable IIIC1 cervical adenocarcinoma and explore the optimal treatment strategy for these patients.</p><p><strong>Methods: </strong>Patients with resectable IIIC1 cervical adenocarcinoma in 2005-2022 from Surveillance, Epidemiology, and End Results program (SEER) were analyzed. Trends over time in the utilization of radiation- and surgery-based treatment were plotted and estimated using Mantel-Haenszel test. Logistic regression analysis was performed to identify factors associated with the utilization of treatment. Survival outcomes were assessed and compared using Kaplan-Meire method and log-rank test, respectively. Inverse probability of treatment weighting (IPTW) was performed for adjustment of baseline characteristics. Sensitivity analysis was conducted using a cohort of cervical adenocarcinoma patients from our institution.</p><p><strong>Results: </strong>The utilization of radiation-based treatment has grown steadily from 2005 to 2022 while the trend for surgery-based treatment showed opposite way (P = 0.002). Age, year of diagnosed, tumor size and T stage impacted the utilization of radiation-based treatment (All P < 0.05). Surgery-based treatment demonstrated superior overall survival (HR = 0.55, 95%CI:0.44-0.69; P < 0.001) and cancer specific survival (HR = 0.58, 95%CI:0.45-0.75; P < 0.001) to radiation-based treatment before adjustment of IPTW. However, no significant differences were observed in overall survival (HR = 0.77, 95%CI:0.56-1.05; P = 0.1) and cancer specific survival (HR = 0.86, 95%CI:0.60-1.23; P = 0.4) after baseline characteristics were balanced. Besides, the cohort from our institution further verified that similar survival outcomes were observed between two treatment strategies.</p><p><strong>Conclusions: </strong>The utilization of radiation-based treatment has increased over time and showed non-inferior efficacy for patients with resectable IIIC1 cervical adenocarcinoma when compared to surgery-based treatment.</p>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":" ","pages":"111370"},"PeriodicalIF":5.3,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In external beam radiotherapy for prostate cancer, inclusion of the seminal vesicles (SV) in the clinical target volume (CTV) is often complicated by considerable SV motion and deformation. This study aimed to investigate the feasibility of predicting patient-specific SV motion using anatomical features surrounding the prostate on planning CT (pCT) images.
Materials and methods
Interfractional SV motion was quantified using five pretreatment cone-beam CT (CBCT) scans per patient from a cohort of 191 prostate cancer patients. Patients whose SV was not fully covered by a 3-mm margin were assigned to the High SV Motion Group, which served as the target for prediction. A total of 42 anatomical features were extracted from the contours of the prostate, SV, bladder, and rectum on the pCT. Feature selection was performed using Random-Forest Recursive Feature Elimination, and a machine learning model was developed and evaluated using both internal and external patient cohorts.
Results
Four anatomical features were selected, including those based on the anatomical relationship between the prostate and the SV. Using these features, the best-performing light gradient boosting machine model achieved an area under the receiver operating characteristic curve of 0.724 in the internal test and 0.632 in the external test for identifying patients in the High SV Motion Group.
Conclusion
This study suggests an association between anatomical features derived from pCT and patient-specific SV motion. Although the current predictive performance is moderate, this approach may help support radiotherapy strategies when the SV is included in the CTV.
{"title":"Machine learning model for predicting interfraction motion of the seminal vesicles in prostate cancer radiotherapy","authors":"Mitsuaki Terabe , Takeshi Kamomae , Yuki Taniguchi , Takayuki Miyachi , Hajime Ichikawa , Risei Miyauchi , Junji Ito , Mariko Kawamura , Shunichi Ishihara , Shinji Naganawa","doi":"10.1016/j.radonc.2026.111368","DOIUrl":"10.1016/j.radonc.2026.111368","url":null,"abstract":"<div><h3>Background and purpose</h3><div>In external beam radiotherapy for prostate cancer, inclusion of the seminal vesicles (SV) in the clinical target volume (CTV) is often complicated by considerable SV motion and deformation. This study aimed to investigate the feasibility of predicting patient-specific SV motion using anatomical features surrounding the prostate on planning CT (pCT) images.</div></div><div><h3>Materials and methods</h3><div>Interfractional SV motion was quantified using five pretreatment cone-beam CT (CBCT) scans per patient from a cohort of 191 prostate cancer patients. Patients whose SV was not fully covered by a 3-mm margin were assigned to the High SV Motion Group, which served as the target for prediction. A total of 42 anatomical features were extracted from the contours of the prostate, SV, bladder, and rectum on the pCT. Feature selection was performed using Random-Forest Recursive Feature Elimination, and a machine learning model was developed and evaluated using both internal and external patient cohorts.</div></div><div><h3>Results</h3><div>Four anatomical features were selected, including those based on the anatomical relationship between the prostate and the SV. Using these features, the best-performing light gradient boosting machine model achieved an area under the receiver operating characteristic curve of 0.724 in the internal test and 0.632 in the external test for identifying patients in the High SV Motion Group.</div></div><div><h3>Conclusion</h3><div>This study suggests an association between anatomical features derived from pCT and patient-specific SV motion. Although the current predictive performance is moderate, this approach may help support radiotherapy strategies when the SV is included in the CTV.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"216 ","pages":"Article 111368"},"PeriodicalIF":5.3,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1016/j.radonc.2026.111364
Qian Xu , Hesong Shen , Liting Wen , Chunrong Tu , Wei Deng , Renwei Liu , Fandong Zhang , Dechun Zheng , Jiuquan Zhang
Background and purpose
Major adverse cardiovascular events (MACEs) remain a significant concern in esophageal cancer (EC) patients receiving radiotherapy (RT). This study aimed to develop and validate a CCTA-based model for predicting MACEs in this population.
Materials and methods
322 and 216 patients with EC at thoracic middle or lower segment from hospital 1 were randomly divided into the training and internal validation cohorts, while 227 patients from hospital 2 were assigned to the external validation cohort. Pericoronary adipose tissue (PCAT) radiomics features were selected by the least absolute shrinkage and selection operator Cox regression (Lasso-Cox) and Max-Relevance and Min-Redundancy (mRMR). Radiomics model was constructed and compared using seven machine-learning classifiers. A nomogram for predicting MACEs was developed with multivariable Cox regression analysis. Predictive performance of models was evaluated by C-index, and feature importance was interpreted using SHapley Additive exPlanations (SHAP) analysis.
Results
The median follow-up was 31 months (IQR, 25–36 months), during which 139 of 765 (18.2 %) patients experienced MACEs. The eXtreme gradient boosting (XGBoost) was used to construct radiomics model. A nomogram incorporating the PCAT radiomics signature, age, mean dose of left circumflex artery (LCX), and fat attenuation index of LCX achieved a moderate to strong predictive capacity across the training, internal, and external validation cohorts (C-index = 0.855, 0.839, and 0.845, respectively). SHAP analysis revealed that the PCAT radiomics signature was the most important predictor of MACEs.
Conclusion
A nomogram combining clinical risk factors, CCTA-derived parameters, and PCAT radiomics signature can predict MACEs in patients with EC receiving radiotherapy.
{"title":"Development and validation of A CCTA-based risk prediction model for major adverse cardiovascular events in esophageal cancer patients receiving radiotherapy","authors":"Qian Xu , Hesong Shen , Liting Wen , Chunrong Tu , Wei Deng , Renwei Liu , Fandong Zhang , Dechun Zheng , Jiuquan Zhang","doi":"10.1016/j.radonc.2026.111364","DOIUrl":"10.1016/j.radonc.2026.111364","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Major adverse cardiovascular events (MACEs) remain a significant concern in esophageal cancer (EC) patients receiving radiotherapy (RT). This study aimed to develop and validate a CCTA-based model for predicting MACEs in this population.</div></div><div><h3>Materials and methods</h3><div>322 and 216 patients with EC at thoracic middle or lower segment from hospital 1 were randomly divided into the training and internal validation cohorts, while 227 patients from hospital 2 were assigned to the external validation cohort. Pericoronary adipose tissue (PCAT) radiomics features were selected by the least absolute shrinkage and selection operator Cox regression (Lasso-Cox) and Max-Relevance and Min-Redundancy (mRMR). Radiomics model was constructed and compared using seven machine-learning classifiers. A nomogram for predicting MACEs was developed with multivariable Cox regression analysis. Predictive performance of models was evaluated by C-index, and feature importance was interpreted using SHapley Additive exPlanations (SHAP) analysis.</div></div><div><h3>Results</h3><div>The median follow-up was 31 months (IQR, 25–36 months), during which 139 of 765 (18.2 %) patients experienced MACEs. The eXtreme gradient boosting (XGBoost) was used to construct radiomics model. A nomogram incorporating the PCAT radiomics signature, age, mean dose of left circumflex artery (LCX), and fat attenuation index of LCX achieved a moderate to strong predictive capacity across the training, internal, and external validation cohorts (C-index = 0.855, 0.839, and 0.845, respectively). SHAP analysis revealed that the PCAT radiomics signature was the most important predictor of MACEs.</div></div><div><h3>Conclusion</h3><div>A nomogram combining clinical risk factors, CCTA-derived parameters, and PCAT radiomics signature can predict MACEs in patients with EC receiving radiotherapy.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"216 ","pages":"Article 111364"},"PeriodicalIF":5.3,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1016/j.radonc.2026.111365
Beatrice Manduchi, Taylor C Jefferson, Amy C Moreno, Carly E A Barbon, Meagan Whisenant, Rosemary Martino, Clifton D Fuller, Katherine A Hutcheson
Background and purpose: To determine clinically actionable thresholds for the MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) -Swallow and -Choke items by comparing discriminant capacity against imaging-based markers of dysphagia in head and neck cancer (HNC) patients undergoing (chemo)radiotherapy (RT).
Materials and methods: A retrospective secondary analysis used single-institution prospective registries of HNC patients treated with RT who completed the MDASI-HN and a modified barium swallow (MBS) before, during, or after RT. The DynamicImaging Grade ofSwallowing Toxicity(DIGEST) overall (D), efficiency (E), and safety (S) scores were compared to a priori-defined (≥6) and data-driven thresholds using binomial regression. Diagnostic accuracy was evaluated using sensitivity (SN), specificity (SP), PPV and NPV, using DIGEST D, E, S ≥ 1 (any impairment) and ≥ 2 (moderate-severe) as reference standards.
Results: Among 264 patients (mean age 62; 87 % male; 47 % nasopharyngeal cancer; 55 % post-RT), -Swallow ≥ 6 was associated with D ≥ 1 and D ≥ 2 (RRs = 1.8-2.6, p < 0.05), showing high SP (92-95 %) but low SN (23-30 %). -Choke ≥ 6 demonstrated stronger associations for D ≥ 2 (RR = 3.5, p < 0.05), and similar SN/SP tradeoffs. Data-driven thresholds improved accuracy: for D ≥ 1, a combined threshold (-Swallow or -Choke) ≥ 2 yielded SN 77 %, SP 64 %; for D ≥ 2, -Choke ≥ 1 showed SN 85 %, SP 69 %, while -Choke ≥ 2 increased SP to 84 %. For aspiration risk (S ≥ 2), -Choke ≥ 1 had SN 88 %, SP 66 %; -Choke ≥ 2 improved SP to 83 %.
Conclusion: MDASI-Swallow and -Choke correlate with imaging-based dysphagia. While ≥ 6 may flag moderate-severe impairment, lower thresholds (≥1-2) offer better sensitivity, supporting early detection. Combined thresholds may enhance screening and guide survivorship care.
{"title":"Individual patient-reported symptom items discriminate imaging-graded dysphagia in head and neck cancer patients treated with radiotherapy: secondary analysis of pooled prospective studies.","authors":"Beatrice Manduchi, Taylor C Jefferson, Amy C Moreno, Carly E A Barbon, Meagan Whisenant, Rosemary Martino, Clifton D Fuller, Katherine A Hutcheson","doi":"10.1016/j.radonc.2026.111365","DOIUrl":"10.1016/j.radonc.2026.111365","url":null,"abstract":"<p><strong>Background and purpose: </strong>To determine clinically actionable thresholds for the MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) -Swallow and -Choke items by comparing discriminant capacity against imaging-based markers of dysphagia in head and neck cancer (HNC) patients undergoing (chemo)radiotherapy (RT).</p><p><strong>Materials and methods: </strong>A retrospective secondary analysis used single-institution prospective registries of HNC patients treated with RT who completed the MDASI-HN and a modified barium swallow (MBS) before, during, or after RT. The DynamicImaging Grade ofSwallowing Toxicity(DIGEST) overall (D), efficiency (E), and safety (S) scores were compared to a priori-defined (≥6) and data-driven thresholds using binomial regression. Diagnostic accuracy was evaluated using sensitivity (SN), specificity (SP), PPV and NPV, using DIGEST D, E, S ≥ 1 (any impairment) and ≥ 2 (moderate-severe) as reference standards.</p><p><strong>Results: </strong>Among 264 patients (mean age 62; 87 % male; 47 % nasopharyngeal cancer; 55 % post-RT), -Swallow ≥ 6 was associated with D ≥ 1 and D ≥ 2 (RRs = 1.8-2.6, p < 0.05), showing high SP (92-95 %) but low SN (23-30 %). -Choke ≥ 6 demonstrated stronger associations for D ≥ 2 (RR = 3.5, p < 0.05), and similar SN/SP tradeoffs. Data-driven thresholds improved accuracy: for D ≥ 1, a combined threshold (-Swallow or -Choke) ≥ 2 yielded SN 77 %, SP 64 %; for D ≥ 2, -Choke ≥ 1 showed SN 85 %, SP 69 %, while -Choke ≥ 2 increased SP to 84 %. For aspiration risk (S ≥ 2), -Choke ≥ 1 had SN 88 %, SP 66 %; -Choke ≥ 2 improved SP to 83 %.</p><p><strong>Conclusion: </strong>MDASI-Swallow and -Choke correlate with imaging-based dysphagia. While ≥ 6 may flag moderate-severe impairment, lower thresholds (≥1-2) offer better sensitivity, supporting early detection. Combined thresholds may enhance screening and guide survivorship care.</p>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":" ","pages":"111365"},"PeriodicalIF":5.3,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1016/j.radonc.2026.111363
Sian Cooper , Sophie Alexander , Charlotte Cherry , Joan Chick , Mathijs G. Dassen , Alex Dunlop , Shermarke Hassan , Trina Herbert , Francesca Mason , Adam Mitchell , Simeon Nill , Uwe Oelfke , Floris Pos , Murtuza Saifuddin , Rosalyne Westley , Uulke A van der Heide , Danny Vesprini , Alison Tree
Background
Stereotactic body radiotherapy (SBRT) is effective for localised prostate cancer but increases genitourinary adverse events (AE). Focal boost to the dominant lesion may improve disease control. The DESTINATION study investigates whole gland dose de-escalation, with focal boost, using MR-guided adaptive radiotherapy (MRgART), to maintain cancer control whilst demonstrating acceptable AE.
Methods
DESTINATION is a prospective, phase II federated study that enrolled men with localised prostate cancer across three institutions (The Royal Marsden Hospital, Sunnybrook Health Sciences Centre, and The Netherlands Cancer Institute). Patients received MRgART with daily online replanning to deliver 30 Gy in 5 fractions to the whole prostate with no margin. The gross tumour volume (GTV) + 4 mm intra-prostatic margin received an isotoxic boost of 45 Gy. Acute AE were assessed using CTCAEv5 at baseline, end of treatment, 4 weeks, and 12 weeks post-treatment. Patient-reported outcomes were collected using IPSS, EPIC-26 and IIEF5.
Results
All 60 patients completed 12-weeks follow-up. Grade 2 genitourinary AE occurred in 55 % of patients by 12 weeks. Grade 2 gastrointestinal AE occurred in 11.7 %. Patient-reported outcomes demonstrated expected symptom flare at final fraction of treatment followed by gradual recovery. EPIC scores were consistently higher at NKI compared to RMH/SB, with sexual function decline during follow-up across all centres.
Conclusion
The DESTINATION study demonstrates that dose de-escalation 5-fraction SBRT with isotoxic focal boost produces acute AE rates similar to or above the levels seen in the PACE-B trial. The focal boost may have offset any potential decrease in AE from whole gland de-escalation.
{"title":"Acute adverse events in the DESTINATION 1 trial: A prospective prostate SBRT dose de-escalation feasibility study","authors":"Sian Cooper , Sophie Alexander , Charlotte Cherry , Joan Chick , Mathijs G. Dassen , Alex Dunlop , Shermarke Hassan , Trina Herbert , Francesca Mason , Adam Mitchell , Simeon Nill , Uwe Oelfke , Floris Pos , Murtuza Saifuddin , Rosalyne Westley , Uulke A van der Heide , Danny Vesprini , Alison Tree","doi":"10.1016/j.radonc.2026.111363","DOIUrl":"10.1016/j.radonc.2026.111363","url":null,"abstract":"<div><h3>Background</h3><div>Stereotactic body radiotherapy (SBRT) is effective for localised prostate cancer but increases genitourinary adverse events (AE). Focal boost to the dominant lesion may improve disease control. The DESTINATION study investigates whole gland dose de-escalation, with focal boost, using MR-guided adaptive radiotherapy (MRgART), to maintain cancer control whilst demonstrating acceptable AE.</div></div><div><h3>Methods</h3><div>DESTINATION is a prospective, phase II federated study that enrolled men with localised prostate cancer across three institutions (The Royal Marsden Hospital, Sunnybrook Health Sciences Centre, and The Netherlands Cancer Institute). Patients received MRgART with daily online replanning to deliver 30 Gy in 5 fractions to the whole prostate with no margin. The gross tumour volume (GTV) + 4 mm intra-prostatic margin received an isotoxic boost of 45 Gy. Acute AE were assessed using CTCAEv5 at baseline, end of treatment, 4 weeks, and 12 weeks post-treatment. Patient-reported outcomes were collected using IPSS, EPIC-26 and IIEF5.</div></div><div><h3>Results</h3><div>All 60 patients completed 12-weeks follow-up. Grade 2 genitourinary AE occurred in 55 % of patients by 12 weeks. Grade 2 gastrointestinal AE occurred in 11.7 %. Patient-reported outcomes demonstrated expected symptom flare at final fraction of treatment followed by gradual recovery. EPIC scores were consistently higher at NKI compared to RMH/SB, with sexual function decline during follow-up across all centres.</div></div><div><h3>Conclusion</h3><div>The DESTINATION study demonstrates that dose de-escalation 5-fraction SBRT with isotoxic focal boost produces acute AE rates similar to or above the levels seen in the PACE-B trial. The focal boost may have offset any potential decrease in AE from whole gland de-escalation.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"216 ","pages":"Article 111363"},"PeriodicalIF":5.3,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-05DOI: 10.1016/j.radonc.2026.111369
Mihaela Ghita-Pettigrew , Kathryn H. Brown , Brianna N. Kerr , Gerard M. Walls , Ioannis I. Verginadis , Gabriel Adrian , Kristoffer Petersson , Stephen J. McMahon , Karl T. Butterworth
Introduction
Preclinical studies have demonstrated the ability of FLASH irradiation to expand the therapeutic window by sparing normal tissues. The heart is a critical organ at risk in patients receiving radiotherapy for thoracic cancers. This study aimed to quantify the cardiac sparing effects of photon FLASH delivered as single (FLASH) or FLASH split dose (FSD) exposures.
Methods
Female C57BL/6 mice were irradiated with 18.5 ± 0.6 Gy delivered to the whole heart using a FLASH-SARRP (Xstrahl Life Sciences, UK) at a dose rate of 85.6 ± 1.6 Gy/s (isocentre dose rate 75.9 ± 1.5 Gy/s). Comparative studies were undertaken using 18.6 ± 0.4 Gy delivered using two consecutive pulses (FSD) at an average dose rate of 2.8 ± 0.9 Gy/s, and with 20.1 ± 0.5 Gy using a conventional SARRP at a dose rate of 3.4 ± 0.2 Gy/min (CONV). Transthoracic echocardiography was performed at 10 and 30 weeks with supporting histology and analysis of serum biomarkers 30 weeks post irradiation.
Results
In comparison to CONV and FSD exposures, FLASH significantly reduced radiation-induced loss of cardiac function, cardiac remodelling and arrythmia 30 weeks after irradiation. These observations were supported by reduced myocardial fibrosis, cardiac injury biomarkers and inflammatory cytokines.
Conclusions
This study highlights the ability of photon FLASH to preserve cardiac function and structure from radiation damage with the level of sparing dependent on average dose rate and beam structure.
{"title":"Photon FLASH spares radiation-induced changes in cardiac function, remodelling and arrythmia in a preclinical model","authors":"Mihaela Ghita-Pettigrew , Kathryn H. Brown , Brianna N. Kerr , Gerard M. Walls , Ioannis I. Verginadis , Gabriel Adrian , Kristoffer Petersson , Stephen J. McMahon , Karl T. Butterworth","doi":"10.1016/j.radonc.2026.111369","DOIUrl":"10.1016/j.radonc.2026.111369","url":null,"abstract":"<div><h3>Introduction</h3><div>Preclinical studies have demonstrated the ability of FLASH irradiation to expand the therapeutic window by sparing normal tissues. The heart is a critical organ at risk in patients receiving radiotherapy for thoracic cancers. This study aimed to quantify the cardiac sparing effects of photon FLASH delivered as single (FLASH) or FLASH split dose (FSD) exposures.</div></div><div><h3>Methods</h3><div>Female C57BL/6 mice were irradiated with 18.5 ± 0.6 Gy delivered to the whole heart using a FLASH-SARRP (Xstrahl Life Sciences, UK) at a dose rate of 85.6 ± 1.6 Gy/s (isocentre dose rate 75.9 ± 1.5 Gy/s). Comparative studies were undertaken using 18.6 ± 0.4 Gy delivered using two consecutive pulses (FSD) at an average dose rate of 2.8 ± 0.9 Gy/s, and with 20.1 ± 0.5 Gy using a conventional SARRP at a dose rate of 3.4 ± 0.2 Gy/min (CONV). Transthoracic echocardiography was performed at 10 and 30 weeks with supporting histology and analysis of serum biomarkers 30 weeks post irradiation.</div></div><div><h3>Results</h3><div>In comparison to CONV and FSD exposures, FLASH significantly reduced radiation-induced loss of cardiac function, cardiac remodelling and arrythmia 30 weeks after irradiation. These observations were supported by reduced myocardial fibrosis, cardiac injury biomarkers and inflammatory cytokines.</div></div><div><h3>Conclusions</h3><div>This study highlights the ability of photon FLASH to preserve cardiac function and structure from radiation damage with the level of sparing dependent on average dose rate and beam structure.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"216 ","pages":"Article 111369"},"PeriodicalIF":5.3,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-05DOI: 10.1016/j.radonc.2026.111366
Bijuan Chen, Di Wang, Jiali Huang, Sisi Yu, Siping Fang, Chuying Chen, Jie Wang, Jianji Pan, Shaojun Lin, Qiaojuan Guo, Yun Xu, Zhouwei Zhan
Background: Circulating cell-free DNA (cfDNA) 5-hydroxymethylcytosine (5hmC) is a promising epigenetic biomarker in cancer. Its prognostic role in nasopharyngeal carcinoma (NPC), however, remains unclear.
Methods: Genome-wide 5hmC profiling was conducted using 5hmC-Seal sequencing on cfDNA from 174 newly diagnosed NPC patients. Patients were randomly assigned to training (n = 105) and test (n = 69) sets. Differential analysis was performed by survival outcome, EBV status, and tumor stage. The primary endpoint was overall survival (OS); the secondary endpoint was event-free survival (EFS). A prognostic score based on a seven-gene 5hmC signature was developed using LASSO-Cox regression in the training set and validated in the test cohort. A nomogram integrating the 5hmC score, tumor stage, and EBV status was constructed. Model performance was assessed via Kaplan-Meier survival analysis, time-dependent ROC curves, calibration plots, and decision curve analysis (DCA).
Results: Marked 5hmC differences were detected between survivors and non-survivors. The 5hmC score stratified OS with AUCs of 0.83 (3-year) and 0.87 (5-year) in the training set and 0.78 (3-year) and 0.80 (5-year) in the test set, and remained predictive across EBV and stage subgroups. The integrated nomogram demonstrated robust calibration and offered the greatest net clinical benefit in DCA, with a 5-year C-index of 0.796.
Conclusions: cfDNA 5hmC profiling enables noninvasive prognostic risk stratification in NPC. The proposed model may support personalized treatment planning and long-term management.
{"title":"A seven-gene 5-hydroxymethylcytosine signature in circulating cell-free DNA for prognostic stratification of nasopharyngeal carcinoma.","authors":"Bijuan Chen, Di Wang, Jiali Huang, Sisi Yu, Siping Fang, Chuying Chen, Jie Wang, Jianji Pan, Shaojun Lin, Qiaojuan Guo, Yun Xu, Zhouwei Zhan","doi":"10.1016/j.radonc.2026.111366","DOIUrl":"https://doi.org/10.1016/j.radonc.2026.111366","url":null,"abstract":"<p><strong>Background: </strong>Circulating cell-free DNA (cfDNA) 5-hydroxymethylcytosine (5hmC) is a promising epigenetic biomarker in cancer. Its prognostic role in nasopharyngeal carcinoma (NPC), however, remains unclear.</p><p><strong>Methods: </strong>Genome-wide 5hmC profiling was conducted using 5hmC-Seal sequencing on cfDNA from 174 newly diagnosed NPC patients. Patients were randomly assigned to training (n = 105) and test (n = 69) sets. Differential analysis was performed by survival outcome, EBV status, and tumor stage. The primary endpoint was overall survival (OS); the secondary endpoint was event-free survival (EFS). A prognostic score based on a seven-gene 5hmC signature was developed using LASSO-Cox regression in the training set and validated in the test cohort. A nomogram integrating the 5hmC score, tumor stage, and EBV status was constructed. Model performance was assessed via Kaplan-Meier survival analysis, time-dependent ROC curves, calibration plots, and decision curve analysis (DCA).</p><p><strong>Results: </strong>Marked 5hmC differences were detected between survivors and non-survivors. The 5hmC score stratified OS with AUCs of 0.83 (3-year) and 0.87 (5-year) in the training set and 0.78 (3-year) and 0.80 (5-year) in the test set, and remained predictive across EBV and stage subgroups. The integrated nomogram demonstrated robust calibration and offered the greatest net clinical benefit in DCA, with a 5-year C-index of 0.796.</p><p><strong>Conclusions: </strong>cfDNA 5hmC profiling enables noninvasive prognostic risk stratification in NPC. The proposed model may support personalized treatment planning and long-term management.</p>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":" ","pages":"111366"},"PeriodicalIF":5.3,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Predicting recurrence after gamma knife radiosurgery (GKRS) is clinically important, as it informs salvage treatment and patient management. MRI-based radiomics combined with machine learning (ML) offers promise for predicting tumour recurrence in brain metastasis, yet most studies lack external validation, limiting clinical translation. This study developed and externally validated radiomics-based models for predicting recurrence in brain metastases treated with GKRS.
Methods
The primary dataset comprised 103 metastases from our institution (23 recurrent) and 125 lesions from the Cancer Imaging Archive (TCIA; 20 recurrent) for external validation. IBSI-compliant radiomics features were extracted from contrast-enhanced T1-weighted MRI using 64-bin grey-level discretisation and mean relative ROI ± 3 SD intensity rescaling, with and without LOG filtering. Feature selection combined correlation analysis and LASSO regression. Logistic regression classifiers were trained on 80 % of the data and tested on 20 %, followed by external validation. Five models were developed: MRI-only, LOG-filtered MRI, MRI + clinical, LOG-filtered MRI + clinical, and clinical + dosimetric. SHAP analysis was used for feature attribution, and methodological rigour was assessed using the Radiomics Quality Score (RQS).
Results
The best-performing model (LOG-filtered MRI + clinical features) achieved 81 % accuracy and an AUC of 0.93 in internal testing, and 79 % accuracy with an AUC of 0.78 on external validation, demonstrating strong robustness and generalisability. Adding clinical features significantly improved performance compared with MRI-only models. SHAP analysis revealed that tumour shape complexity (Compactness2 [IBSI: BQWJ]) and voxel intensity heterogeneity (IntensityRange[IBSI: 2OJQ]) were strong predictors, while maximum dose, gender, and primary tumour site also contributed among the clinical factors.
Conclusion
The MRI-based radiomics model integrating LOG-filtered MRI features with clinical variables achieved high external validation performance. Unlike many black-box models that prioritise accuracy with limited interpretability, this approach combines predictive strength with transparent feature attribution, enhancing biology interpretability and supporting clinical translation. Prospective multi-centre studies are warranted to confirm its clinical utility.
{"title":"Development and external validation of an MRI radiomics-based machine learning model to predict tumour recurrence in brain metastases treated with Gamma Knife radiosurgery","authors":"Abdulrahman Umaru , Hanani Abdul Manan , Ramesh Kumar Athi Kumar , Siti Khadijah Hamsan , Daryl Tan , Noorazrul Yahya","doi":"10.1016/j.radonc.2025.111362","DOIUrl":"10.1016/j.radonc.2025.111362","url":null,"abstract":"<div><h3>Background</h3><div>Predicting recurrence after gamma knife radiosurgery (GKRS) is clinically important, as it informs salvage treatment and patient management. MRI-based radiomics combined with machine learning (ML) offers promise for predicting tumour recurrence in brain metastasis, yet most studies lack external validation, limiting clinical translation. This study developed and externally validated radiomics-based models for predicting recurrence in brain metastases treated with GKRS.</div></div><div><h3>Methods</h3><div>The primary dataset comprised 103 metastases from our institution (23 recurrent) and 125 lesions from the Cancer Imaging Archive (TCIA; 20 recurrent) for external validation. IBSI-compliant radiomics features were extracted from contrast-enhanced T1-weighted MRI using 64-bin grey-level discretisation and mean relative ROI ± 3 SD intensity rescaling, with and without LOG filtering. Feature selection combined correlation analysis and LASSO regression. Logistic regression classifiers were trained on 80 % of the data and tested on 20 %, followed by external validation. Five models were developed: MRI-only, LOG-filtered MRI, MRI + clinical, LOG-filtered MRI + clinical, and clinical + dosimetric. SHAP analysis was used for feature attribution, and methodological rigour was assessed using the Radiomics Quality Score (RQS).</div></div><div><h3>Results</h3><div>The best-performing model (LOG-filtered MRI + clinical features) achieved 81 % accuracy and an AUC of 0.93 in internal testing, and 79 % accuracy with an AUC of 0.78 on external validation, demonstrating strong robustness and generalisability. Adding clinical features significantly improved performance compared with MRI-only models. SHAP analysis revealed that tumour shape complexity (Compactness2 [IBSI: BQWJ]) and voxel intensity heterogeneity (IntensityRange[IBSI: 2OJQ]) were strong predictors, while maximum dose, gender, and primary tumour site also contributed among the clinical factors.</div></div><div><h3>Conclusion</h3><div>The MRI-based radiomics model integrating LOG-filtered MRI features with clinical variables achieved high external validation performance. Unlike many black-box models that prioritise accuracy with limited interpretability, this approach combines predictive strength with transparent feature attribution, enhancing biology interpretability and supporting clinical translation. Prospective multi-centre studies are warranted to confirm its clinical utility.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"216 ","pages":"Article 111362"},"PeriodicalIF":5.3,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-22DOI: 10.1016/j.radonc.2025.111361
Rachel Allcock, Kari Tanderup, Jenny Bertholet, Amanda Webster, Robert Chuter
Background: Climate change is an escalating crisis with significant implications for public health and healthcare services. We aimed to survey radiation oncology (RO) professionals on their understanding and concerns about climate change and the role of ESTRO in addressing the crisis.
Materials and methods: A 14-item survey covering environmental impact of RO activities, personal actions, and expectations of ESTRO's responses to the climate crisis was developed, validated, and disseminated to RO professionals by email and online platforms.
Results: 706 responses were received out of 9,781 ESTRO members. Concern about climate change was indicated by 90% of respondents and 94% had changed their personal lives to help combat the climate crisis. Yet 50% of respondents could not identify RO's main contributors to climate change. 39% reported positive attitudes to online conferences and 79% agreed that ESTRO should offer digital participation to reduce the carbon impact of travel. Reported barriers to digital participation were mainly related to lack of face-to-face interaction. Although additional time was the most common barrier to reducing flying for work-related trips, 47 % of respondents were willing to travel by train for ≥ 7 h to an ESTRO conference. The majority of respondents (82 %) agreed that ESTRO should 'Increase engagement with manufacturers around environmental sustainability'.
Conclusion: Our results reveal strong concern about the climate crisis among RO professionals, willingness to implement change, lack of knowledge about climate impact of RO and support for ESTRO actions to support its members and the community in these efforts.
{"title":"How can a radiation oncology society support its members and the community to help reduce the carbon footprint of radiation oncology?","authors":"Rachel Allcock, Kari Tanderup, Jenny Bertholet, Amanda Webster, Robert Chuter","doi":"10.1016/j.radonc.2025.111361","DOIUrl":"https://doi.org/10.1016/j.radonc.2025.111361","url":null,"abstract":"<p><strong>Background: </strong>Climate change is an escalating crisis with significant implications for public health and healthcare services. We aimed to survey radiation oncology (RO) professionals on their understanding and concerns about climate change and the role of ESTRO in addressing the crisis.</p><p><strong>Materials and methods: </strong>A 14-item survey covering environmental impact of RO activities, personal actions, and expectations of ESTRO's responses to the climate crisis was developed, validated, and disseminated to RO professionals by email and online platforms.</p><p><strong>Results: </strong>706 responses were received out of 9,781 ESTRO members. Concern about climate change was indicated by 90% of respondents and 94% had changed their personal lives to help combat the climate crisis. Yet 50% of respondents could not identify RO's main contributors to climate change. 39% reported positive attitudes to online conferences and 79% agreed that ESTRO should offer digital participation to reduce the carbon impact of travel. Reported barriers to digital participation were mainly related to lack of face-to-face interaction. Although additional time was the most common barrier to reducing flying for work-related trips, 47 % of respondents were willing to travel by train for ≥ 7 h to an ESTRO conference. The majority of respondents (82 %) agreed that ESTRO should 'Increase engagement with manufacturers around environmental sustainability'.</p><p><strong>Conclusion: </strong>Our results reveal strong concern about the climate crisis among RO professionals, willingness to implement change, lack of knowledge about climate impact of RO and support for ESTRO actions to support its members and the community in these efforts.</p>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":" ","pages":"111361"},"PeriodicalIF":5.3,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-20DOI: 10.1016/j.radonc.2025.111352
Xuan Liu, Xiao Liang, Ting Huang, Yaqi Luo, Rong Li
{"title":"Same risk, different scales: outcome calibration and contour provenance in a 3D deep NTCP for dysphagia?","authors":"Xuan Liu, Xiao Liang, Ting Huang, Yaqi Luo, Rong Li","doi":"10.1016/j.radonc.2025.111352","DOIUrl":"10.1016/j.radonc.2025.111352","url":null,"abstract":"","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"216 ","pages":"Article 111352"},"PeriodicalIF":5.3,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145808394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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