Radiotherapy and Oncology最新文献_第7页

Development and validation of A CCTA-based risk prediction model for major adverse cardiovascular events in esophageal cancer patients receiving radiotherapy 基于ccta的食管癌放疗患者主要心血管不良事件风险预测模型的建立与验证

IF 5.3 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology

Pub Date : 2026-03-01 Epub Date: 2026-01-06 DOI: 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.

背景与目的食管癌（EC）放疗患者的主要不良心血管事件（mace）仍然是一个值得关注的问题。本研究旨在开发和验证基于ccta的模型来预测该人群的mace。材料与方法将来自第一医院的322例和216例胸椎中下段EC患者随机分为训练组和内部验证组，而来自第二医院的227例患者被分配到外部验证组。冠状动脉周围脂肪组织（PCAT）放射组学特征通过最小绝对收缩和选择算子Cox回归（Lasso-Cox）和最大相关性和最小冗余（mRMR）来选择。利用7种机器学习分类器构建放射组学模型并进行比较。采用多变量Cox回归分析，建立了预测mace的nomogram。采用c指数评价模型的预测性能，采用SHapley加性解释（SHAP）分析对特征重要性进行解释。结果中位随访31个月（IQR， 25-36个月），765例患者中有139例（18.2%）出现mace。采用极限梯度增强（eXtreme gradient boost, XGBoost）构建放射组学模型。结合PCAT放射组学特征、年龄、左旋动脉（LCX）的平均剂量和LCX的脂肪衰减指数的nomogram，在训练、内部和外部验证队列中均具有中等到较强的预测能力（C-index分别为0.855、0.839和0.845）。SHAP分析显示PCAT放射组学特征是mace最重要的预测因子。结论结合临床危险因素、ccta衍生参数和PCAT放射组学特征的nomogram预测EC放疗患者的mace。

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引用次数: 0

Same risk, different scales: outcome calibration and contour provenance in a 3D deep NTCP for dysphagia? 相同的风险，不同的量表：吞咽困难的3D深度NTCP的结果校准和轮廓来源？

IF 5.3 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology

Pub Date : 2026-03-01 Epub Date: 2025-12-20 DOI: 10.1016/j.radonc.2025.111352

Xuan Liu, Xiao Liang, Ting Huang, Yaqi Luo, Rong Li

引用次数: 0

Individual patient-reported symptom items discriminate imaging-graded dysphagia in head and neck cancer patients treated with radiotherapy: secondary analysis of pooled prospective studies 个体患者报告的症状项目区分放疗治疗的头颈癌患者影像学分级吞咽困难：汇总前瞻性研究的二次分析

IF 5.3 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology

Pub Date : 2026-03-01 Epub Date: 2026-01-06 DOI: 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 , on behalf of OPC-SURVIVOR Research Program

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 Dynamic Imaging Grade of Swallowing 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.

背景和目的：通过比较接受（化疗）放疗（RT）的头颈癌（HNC）患者吞咽困难影像学标志物的鉴别能力，确定MD安德森症状清单-头颈(MDASI-HN) -吞咽和窒息项目的临床可操作阈值。材料和方法：对接受RT治疗的HNC患者在RT之前、期间或之后完成MDASI-HN和改良钡吞咽（MBS）的单机构前瞻性登记进行回顾性二次分析。吞咽毒性动态成像分级（DIGEST）总体(D)、效率(E)和安全性(S)评分与优先定义的（≥6）和数据驱动的阈值进行二项回归比较。以DIGEST D、E、S ≥ 1（任何损害）和 ≥ 2（中重度）为参考标准，采用敏感性（SN）、特异性（SP）、PPV和NPV评价诊断准确性。结果:在264例患者(平均年龄62;87 %男性,47 %鼻咽癌;55 % post-RT),燕子 ≥ 6与D ≥ 1和D ≥ 2 (RRs = 1.8 - -2.6,p 结论:MDASI-Swallow和窒息与成像进行吞咽困难。虽然 ≥ 6可能标志着中重度损伤，但较低的阈值（≥1-2）提供了更好的灵敏度，支持早期发现。联合阈值可以增强筛查和指导生存护理。

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引用次数: 0

Development and external validation of an MRI radiomics-based machine learning model to predict tumour recurrence in brain metastases treated with Gamma Knife radiosurgery 基于MRI放射组学的机器学习模型的开发和外部验证，以预测伽玛刀放射治疗的脑转移瘤复发。

IF 5.3 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology

Pub Date : 2026-03-01 Epub Date: 2025-12-25 DOI: 10.1016/j.radonc.2025.111362

Abdulrahman Umaru , Hanani Abdul Manan , Ramesh Kumar Athi Kumar , Siti Khadijah Hamsan , Daryl Tan , Noorazrul Yahya

Background

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.

背景：预测伽玛刀放射手术（GKRS）后的复发在临床上具有重要意义，因为它可以为抢救治疗和患者管理提供信息。基于mri的放射组学结合机器学习（ML）为预测脑转移肿瘤复发提供了希望，但大多数研究缺乏外部验证，限制了临床转化。该研究开发并外部验证了基于放射组学的模型，用于预测GKRS治疗脑转移瘤的复发。方法：主要数据集包括来自我们机构的103例转移（23例复发）和来自癌症影像档案（TCIA）的125例病变，其中20例复发)进行外部验证。使用64 bin灰度离散和平均相对ROI ± 3 SD强度重新缩放，在有和没有LOG滤波的情况下，从对比度增强的t1加权MRI中提取符合ibsi的放射组学特征。特征选择结合相关分析和LASSO回归。逻辑回归分类器在80% %的数据上进行训练，在20% %的数据上进行测试，然后进行外部验证。开发了5种模型：仅MRI、log -filter MRI、MRI +临床、log -filter MRI +临床和临床 + 剂量测定。特征归因采用SHAP分析，方法严谨性采用放射组学质量评分（RQS）进行评估。结果：表现最好的模型（log -filter MRI + 临床特征）在内部测试中达到81 %的准确率和0.93的AUC，在外部验证中达到79 %的准确率和0.78的AUC，显示出很强的稳健性和通用性。与仅使用mri的模型相比，添加临床特征显著提高了性能。SHAP分析显示，肿瘤形状复杂性（Compactness2 [IBSI: BQWJ]）和体素强度异质性（IntensityRange[IBSI: 2OJQ]）是重要的预测因素，最大剂量、性别和原发肿瘤部位也是重要的临床因素。结论：基于MRI的放射组学模型将日志过滤的MRI特征与临床变量相结合，获得了较高的外部验证性能。与许多优先考虑准确性和有限可解释性的黑箱模型不同，该方法将预测强度与透明特征归因相结合，增强了生物学可解释性并支持临床翻译。有必要进行前瞻性多中心研究以证实其临床应用。

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引用次数: 0

Development of the first prediction model for radiation-induced contrast enhancement after proton therapy for posterior fossa tumours in paediatric patients 小儿后窝肿瘤质子治疗后放射诱导造影剂增强第一个预测模型的建立。

IF 5.3 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology

Pub Date : 2026-03-01 Epub Date: 2025-12-20 DOI: 10.1016/j.radonc.2025.111360

Abel Bregman , Jikke J. Rutgers , Truls Andersen , Arjen van der Schaaf , Charlotte L. Brouwer , Geert O. Janssens , Eelco W. Hoving , Maarten H. Lequin , Rutger A.J. Nievelstein , Stefan Both , Johannes A. Langendijk , Hiska L. van der Weide , John H. Maduro , Dirk Wagenaar

Background/purpose

Radiation-induced contrast enhancement (RICE) has been identified as a metric of subclinical toxicity. The aim of this study was to develop a normal tissue complication probability (NTCP) model for RICE after proton therapy in paediatric patients with posterior fossa tumours.

Materials and methods

Paediatric patients (n = 75) treated with proton radiotherapy (49.6–59.4 Gy (RBE)), focally or in combination with craniospinal axis irradiation, were included. Follow-up magnetic resonance imaging scans were evaluated for RICE. Dose (D), dose multiplied by dose-averaged linear energy transfer (D⋅LETd), organ at risk association, RICE association and age data were extracted to construct a multivariable logistic regression model to predict RICE in voxels. NTCP was calculated using univariable logistic regression with RICE status as the dependent variable and the expected number of RICE voxels as the independent variable.

Results

A total of 60 RICE lesions were identified in 23 patients (30.7 %), of which 36 (60 %) were located in the brainstem, primarily the pons. We observed an increased density of RICE voxels in regions with a combination of high D (38.32–55.94 Gy) and medium-to-high LETd (1.89–6.00 keV/µm) values. In addition, younger age and the anatomical location in the pons were identified as independent risk factors for RICE. The NTCP model’s optimism corrected area under the receiver operating characteristic curve (AUC) was 0.79, and the Brier score was 0.16.

Conclusion

We developed models to predict RICE in paediatric patients. The RICE probability at the voxel- and patient-level increased with D and D⋅LETd, younger age and within the brainstem pons.

背景/目的：辐射诱导的对比增强（RICE）已被确定为亚临床毒性的度量标准。本研究的目的是建立小儿后窝肿瘤患者质子治疗后RICE的正常组织并发症概率（NTCP）模型。材料和方法：纳入接受质子放射治疗（49.6-59.4 Gy (RBE)），局部或联合颅脊髓轴放射治疗的儿科患者（n = 75）。随访核磁共振成像扫描评估RICE。提取剂量(D)、剂量乘以剂量平均线性能量传递（D⋅LETd）、器官危险关联、RICE关联和年龄数据，构建多变量logistic回归模型，以体素为单位预测RICE。NTCP以RICE状态为因变量，期望RICE体素数为自变量，采用单变量logistic回归计算。结果：23例患者共发现60例RICE病变（30.7 %），其中36例（60 %）位于脑干，主要是脑桥。我们观察到高D（38.32-55.94 Gy）和中高LETd（1.89-6.00 keV/µm）值区域的RICE体素密度增加。此外，年龄较小和脑桥的解剖位置被认为是RICE的独立危险因素。NTCP模型的乐观修正面积（AUC）为0.79，Brier评分为0.16。结论：我们建立了预测儿童RICE的模型。体素和患者水平上的RICE概率随D和D·LETd、年龄的增加和脑干桥内的增加而增加。

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引用次数: 0

Deliverable proton conformal FLASH radiotherapy treatment planning for head and neck re-irradiation patients 头颈部再照射患者可输送质子适形FLASH放疗治疗方案。

IF 5.3 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology

Pub Date : 2026-03-01 Epub Date: 2025-12-19 DOI: 10.1016/j.radonc.2025.111349

Wei Zou , Lei Dong , Arnaud Pin , Rasmus Nilsson , Michele Kim , Ontida Apinorasethkul , Julia Pakela , Andrew Friberg , Brandon Koger , Rudi Labarbe , Carolina Llina Fuentes , Keith Cengel , Erik Traneus , Swati Girdhani , Costas Koumenis , Francois Vander Stappen , Eric Diffenderfer , Jeffrey Bradley , Boon-Keng Kevin Teo , Alexander Lin

Purpose

Clinical translation of ultra-high dose rate (UHDR) delivery to harness potential FLASH effect requires a treatment planning system (TPS) to optimize and calculate dose and dose rate in patients. Proton conformal FLASH treatment aims to deliver pencil beam scanning (PBS) Bragg Peaks to the tumor region with UHDR. In this work, we conducted a treatment planning study for head and neck (H&N) re-irradiation patients using a research-version of a commercial TPS paired with conformal FLASH hardware integrated into a nozzle of a clinical cyclotron-based system.

Methods

Fifteen H&N patients were planned for re-irradiation of 40 GyRBE in 5 fractions to the area of intact tumor. The TPS was configured with validated UHDR beam measurement to generate optimized patient FLASH plans with one or two beams, delivered as single-beam-per-fraction (SBPF). Each beam consists of a deliverable mono-energetic PBS map, a 3D-printable conformal energy modulator design, a selection of aluminum range shifter plates, and a brass aperture. Python scripts with machine-specific delivery timing parameters were used for Monte Carlo dose and dose rate calculations. Clinical VMAT and IMPT plans were also generated for dosimetric comparison.

Results

All plans met the tumor target and OAR planning objectives. Conformal FLASH plans showed very similar dose distributions to the clinical IMPT plans. Compared to VMAT plans, both IMPT and FLASH plans have reduced low dose region, maximum cord dose D0.03 cc (8.37 ± 0.94 vs. 3.19 ± 3.81 and 4.32 ± 3.12 GyRBE, respectively), contra-lateral parotid mean dose (1.88 ± 0.99 vs. 0.00 ± 0.01 and 0.00 ± 0.00 GyRBE, respectively) and contra-lateral submandibular gland mean dose (2.49 ± 1.06 vs. 0.14 ± 0.13 and 0.19 ± 0.19 GyRBE, respectively). With 500 nA quasi-continuous nozzle beam current, the mean dose-averaged dose rate in CTVs of these 15 patients achieved 95.75 ± 22.78 Gy/s.

Conclusions

We report the deliverable proton conformal FLASH treatment plans for H&N re-irradiation patients using the innovative hardware configuration and measured beam data in our institution. The FLASH plans have very similar plan qualities to clinical IMPT proton plans and were deliverable with our proton machine. The machine specific 3D dose rate distribution can be calculated and displayed in the TPS.

目的：超高剂量率（UHDR）给药利用潜在的FLASH效应的临床转化需要一个治疗计划系统（TPS）来优化和计算患者的剂量和剂量率。质子适形FLASH治疗旨在通过UHDR将铅笔束扫描（PBS）布拉格峰传递到肿瘤区域。在这项工作中，我们对头颈部（H&N）再照射患者进行了一项治疗计划研究，使用了商用TPS的研究版本，并将适形FLASH硬件集成到临床回旋加速器系统的喷嘴中。方法：选取15例H&N患者，分5段对完整肿瘤区域进行40次GyRBE再照射。TPS配置了经过验证的UHDR光束测量，以一束或两束的方式生成优化的患者FLASH计划，以单束/分数（SBPF）的方式交付。每个光束由一个可交付的单能量PBS图，一个3d打印的保形能量调制器设计，一个铝制范围移位板和一个黄铜孔径组成。使用带有机器特定给药时间参数的Python脚本进行蒙特卡罗剂量和剂量率计算。临床VMAT和IMPT计划也生成用于剂量学比较。结果：所有方案均达到肿瘤目标和OAR计划目标。适形FLASH计划显示与临床IMPT计划非常相似的剂量分布。相比VMAT计划,IMPT和FLASH计划减少了低剂量,最大线剂量D0.03 cc( 8.37±0.94 vs 3.19  ±  3.81和4.32±3.12 GyRBE,分别),contra-lateral腮腺意味着剂量(1.88 ±0.99 vs 0.00  ±  0.01和0.00±0.00 GyRBE,分别)和contra-lateral颌下腺意味着剂量(2.49 ±1.06 vs 0.14  ±  0.13和0.19±0.19 GyRBE,分别)。在500nA准连续喷嘴光束电流下，15例患者ctv的平均剂量率达到95.75 ± 22.78 Gy/s。结论：我们报告了在我们机构使用创新硬件配置和测量光束数据的H&N再照射患者的可交付质子适形FLASH治疗计划。FLASH计划与临床IMPT质子计划具有非常相似的计划质量，并且可以与我们的质子机一起交付。机器特定的三维剂量率分布可以计算并显示在TPS中。

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引用次数: 0

Acute adverse events in the DESTINATION 1 trial: A prospective prostate SBRT dose de-escalation feasibility study DESTINATION 1试验中的急性不良事件：一项前瞻性前列腺SBRT剂量递减可行性研究

IF 5.3 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology

Pub Date : 2026-03-01 Epub Date: 2026-01-06 DOI: 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.

背景：立体定向放射治疗（SBRT）对局部前列腺癌有效，但会增加泌尿生殖系统不良事件（AE）。对显性病变的局部强化可改善疾病控制。DESTINATION研究使用mr引导的适应性放疗（MRgART）研究了整个腺体剂量的降低，局部增强，以维持癌症控制，同时显示可接受的AE。destination是一项前瞻性II期联合研究，招募了来自三个机构（皇家马斯登医院、Sunnybrook健康科学中心和荷兰癌症研究所）的局限性前列腺癌患者。患者接受MRgART每日在线重新计划，分5次向整个前列腺无边界地输送30 Gy。总肿瘤体积(GTV) + 4mm前列腺内边缘接受45 Gy的同毒增强。在基线、治疗结束、治疗后4周和12周使用CTCAEv5评估急性AE。使用IPSS、EPIC-26和IIEF5收集患者报告的结果。结果60例患者均完成随访12周。到12周时，55%的患者发生2级泌尿生殖系统AE。2级胃肠道AE发生率为11.7%。患者报告的结果显示，预期的症状在治疗的最后阶段出现，随后逐渐恢复。与RMH/SB相比，NKI的EPIC评分始终较高，在所有中心的随访期间性功能下降。DESTINATION研究表明，剂量递减5分次SBRT加等毒性局灶增强可产生与PACE-B试验相似或高于其水平的急性AE。局部增强可能抵消了整个腺体降级引起的声发射的任何潜在下降。

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引用次数: 0

Radiation- versus surgery-based treatment for patients with resectable IIIC1 cervical adenocarcinoma 可切除IIIC1型宫颈腺癌患者的放疗与手术治疗。

IF 5.3 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology

Pub Date : 2026-03-01 Epub Date: 2026-01-08 DOI: 10.1016/j.radonc.2026.111370

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

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.

目的：了解可切除IIIC1型宫颈腺癌患者放疗与手术治疗的应用趋势，探讨该类患者的最佳治疗策略。方法：对2005-2022年监测、流行病学和最终结果项目（SEER）中可切除的IIIC1型宫颈腺癌患者进行分析。利用Mantel-Haenszel试验绘制和估计放射治疗和手术治疗随时间的趋势。进行Logistic回归分析以确定与治疗利用相关的因素。生存结果分别采用Kaplan-Meire法和log-rank检验进行评估和比较。采用治疗加权逆概率法（IPTW）调整基线特征。敏感性分析是在我们机构的子宫颈腺癌患者队列中进行的。结果：2005 - 2022年放疗使用率稳步上升，手术使用率呈相反趋势（P = 0.002）。年龄、诊断年份、肿瘤大小和T分期影响放射治疗的使用（P均为 ）结论：可切除的IIIC1型宫颈腺癌患者放射治疗的使用随着时间的推移而增加，与手术治疗相比，放射治疗的疗效并不逊色。

{"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":"10.1016/j.radonc.2026.111370","url":null,"abstract":"<div><h3>Objectives</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>The utilization of radiation-based treatment has grown steadily from 2005 to 2022 while the trend for surgery-based treatment showed opposite way (<em>P</em> = 0.002). Age, year of diagnosed, tumor size and T stage impacted the utilization of radiation-based treatment (All <em>P</em> < 0.05). Surgery-based treatment demonstrated superior overall survival (HR = 0.55, 95%CI:0.44–0.69; <em>P</em> < 0.001) and cancer specific survival (HR = 0.58, 95%CI:0.45–0.75; <em>P</em> < 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; <em>P</em> = 0.1) and cancer specific survival (HR = 0.86, 95%CI:0.60–1.23; <em>P</em> = 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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"216 ","pages":"Article 111370"},"PeriodicalIF":5.3,"publicationDate":"2026-03-01","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}

引用次数: 0

ZIP10 drives radioresistance and malignant progression in lung adenocarcinoma by inhibiting the Hippo pathway via a Zinc-LATS axis ZIP10通过锌- lats轴抑制Hippo通路，从而驱动肺腺癌的放射耐药和恶性进展。

IF 5.3 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology

Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI: 10.1016/j.radonc.2026.111374

Lu Yang , Yaoxiong Xia , Li Chang , Hui Yu , Tao Wei , Di Zhou , Chenxi Wang , Chengshu Gong , Zhengting Chen , Wenhui Li

Background

Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality globally. Although radiotherapy is a cornerstone treatment, its efficacy is severely limited by intrinsic and acquired radioresistance. Zinc transporters, particularly ZIP10, act as critical metabolic regulators in various cancers; however, their specific roles in modulating the radiation response and oncogenic signaling in LUAD remain ill-defined.

Methods

Using a subcutaneous Lewis lung carcinoma (LLC) mouse model, we evaluated four hypofractionated radiotherapy regimens, identifying 8 Gy × 3 fractions as the optimal protocol for tumor regression. Transcriptomic profiling of these irradiated tumors identified ZIP10 as the most significantly downregulated gene. We employed functional assays (knockdown/overexpression) to assess the impact of ZIP10 on LUAD cell proliferation, metastasis, and radiosensitivity. Mechanistically, we investigated the zinc-dependent regulation of the Hippo pathway, focusing on the upstream kinase LATS1, using the zinc chelator TPEN and molecular analyses.

Results

Clinical analysis revealed that ZIP10 is significantly upregulated in LUAD tissues and correlates with advanced TNM stage and poor prognosis. In vitro, ZIP10 silencing markedly suppressed proliferation, migration, and invasion, while inducing G0/G1 cell cycle arrest and apoptosis. In vivo, ZIP10 depletion synergized with radiotherapy to potently inhibit tumor growth. Mechanistically, we demonstrate that ZIP10-mediated zinc influx directly inhibits the phosphorylation of LATS1, the core kinase of the Hippo pathway. This inactivation of LATS1 prevents the cytoplasmic phosphorylation of YAP/TAZ, thereby promoting their nuclear accumulation and transcriptional activity. Importantly, zinc chelation (TPEN) reversed these effects, confirming a ZIP10–Zinc–LATS1–YAP signaling axis.

Conclusion

Our study establishes ZIP10 as a critical metabolic driver of malignant progression and radioresistance in LUAD. By inhibiting LATS1 via intracellular zinc accumulation, ZIP10 locks the Hippo pathway in an inactive state. These findings highlight ZIP10 as a promising therapeutic target for sensitizing LUAD to radiotherapy.

背景：肺腺癌（LUAD）仍然是全球癌症相关死亡的主要原因。虽然放射治疗是一种基础治疗，但其疗效受到内在和获得性放射耐药的严重限制。锌转运蛋白，特别是ZIP10，在各种癌症中起着关键的代谢调节作用；然而，它们在LUAD中调节辐射反应和致癌信号传导中的具体作用仍不明确。方法：使用皮下Lewis肺癌（LLC）小鼠模型，我们评估了四种低分割放疗方案，确定了8种 Gy × 3分数作为肿瘤消退的最佳方案。这些辐照肿瘤的转录组学分析发现ZIP10是最显著下调的基因。我们采用功能分析（敲低/过表达）来评估ZIP10对LUAD细胞增殖、转移和放射敏感性的影响。在机制上，我们利用锌螯合剂TPEN和分子分析研究了Hippo通路的锌依赖调控，重点研究了上游激酶LATS1。结果：临床分析显示，ZIP10在LUAD组织中表达显著上调，与TNM晚期及预后不良相关。在体外，ZIP10沉默可显著抑制细胞增殖、迁移和侵袭，同时诱导G0/G1细胞周期阻滞和凋亡。在体内，ZIP10耗竭与放疗协同作用可有效抑制肿瘤生长。在机制上，我们证明了zip10介导的锌内流直接抑制了LATS1的磷酸化，LATS1是Hippo通路的核心激酶。LATS1的失活阻止了YAP/TAZ的胞质磷酸化，从而促进了它们的核积累和转录活性。重要的是，锌螯合（TPEN）逆转了这些效应，证实了ZIP10-Zinc-LATS1-YAP信号轴。结论：我们的研究表明ZIP10是LUAD恶性进展和放射耐药的关键代谢驱动因素。ZIP10通过细胞内锌积累抑制LATS1，将Hippo通路锁定在非活性状态。这些发现突出表明ZIP10是使LUAD对放射治疗增敏的有希望的治疗靶点。

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引用次数: 0

Brain irradiation drives remote liver changes via senescence-independent mechanisms 脑辐射通过与衰老无关的机制驱动远程肝脏变化。

IF 5.3 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology

Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI: 10.1016/j.radonc.2026.111373

Yuting Jiang , Daniëlle C. Voshart , Alessandro Gustinelli , Ayla C. Scholma , Eline Hageman , Luiza Reali Nazario , Uilke Brouwer , Marco Demaria , Rob P. Coppes , Lara Barazzuol

Background and purpose

Although radiotherapy is essential for treating brain tumors, it often damages surrounding healthy brain tissue, causing long-term neurocognitive dysfunction. Cellular senescence, a stable state of cell cycle arrest triggered by various stressors including radiation-induced DNA damage, has been implicated in aging- and neurodegeneration-associated cognitive decline via its pro-inflammatory secretome and has been reported to exert paracrine effects on distant organs. However, whether brain irradiation, particularly through the induction of cellular senescence, can trigger changes in peripheral tissues remains largely unknown.

Materials and methods

Adult male rats received 14 Gy X-ray irradiation to the brain. Senescence-associated markers were assessed in the brain at 6 and 12 weeks post-irradiation and in peripheral tissues, including the kidney, small intestine, skeletal muscle, and liver, at 17 weeks post-irradiation. Liver samples were further examined for proliferation and fibrosis markers, as well as for liver enzyme activity. The senolytic ABT263 was administered to eliminate senescent cells.

Results

Brain irradiation induced senescence-like features in the brain but did not trigger p21-dependent senescence in the tested peripheral tissues. However, brain-irradiated rats exhibited increased proliferation, elevated GFAP levels, and enhanced ALT and AST activity in the liver. These hepatic changes were likely independent of cellular senescence, as they were not reversed by treatment with ABT263.

Conclusion

Brain irradiation induces liver proliferation, increased GFAP levels, and altered ALT and AST activity, via mechanisms likely independent of senescence. Future investigation of blood GFAP levels is needed to determine whether the enhanced hepatic GFAP levels originate from the brain.

背景与目的：虽然放射治疗是治疗脑肿瘤的必要手段，但放射治疗往往会损害周围健康的脑组织，造成长期的神经认知功能障碍。细胞衰老是由包括辐射诱导的DNA损伤在内的各种应激源引发的细胞周期停滞的稳定状态，通过其促炎分泌组与衰老和神经退行性相关的认知能力下降有关，并已报道对远处器官产生旁分泌作用。然而，脑辐射，特别是通过诱导细胞衰老，是否能引发外周组织的变化，在很大程度上仍然未知。材料与方法：成年雄性大鼠接受14 Gy x线脑照射。在照射后6周和12周 评估大脑中衰老相关标志物，在照射后17 周评估外周组织，包括肾脏、小肠、骨骼肌和肝脏。进一步检查肝脏样本的增殖和纤维化标志物，以及肝酶活性。给予抗衰老药物ABT263以消除衰老细胞。结果：脑辐照在脑内诱导了类似衰老的特征，但在测试的外周组织中没有触发p21依赖性衰老。然而，脑辐照大鼠表现出增殖增加，GFAP水平升高，肝脏ALT和AST活性增强。这些肝脏变化可能与细胞衰老无关，因为它们不会被ABT263治疗逆转。结论：脑辐照诱导肝脏增生，GFAP水平升高，ALT和AST活性升高，其机制可能与衰老无关。需要进一步研究血液GFAP水平，以确定肝脏GFAP水平升高是否源于大脑。

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引用次数: 0