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Incorporating patient-specific prior clinical knowledge to improve clinical target volume auto-segmentation generalisability for online adaptive radiotherapy of rectal cancer: A multicenter validation 在直肠癌在线自适应放疗中纳入患者特定的先验临床知识以提高临床靶区自动分割的通用性：多中心验证。
IF 4.9 1区 医学 Q1 ONCOLOGY
Radiotherapy and Oncology
Pub Date : 2025-02-01 DOI: 10.1016/j.radonc.2024.110667
Nicole Ferreira Silvério , Wouter van den Wollenberg , Anja Betgen , Lisa Wiersema , Corrie A.M. Marijnen , Femke Peters , Uulke A. van der Heide , Rita Simões , Martijn P.W. Intven , Erik van der Bijl , Tomas Janssen

Background & purpose

Deep learning (DL) based auto-segmentation has shown to be beneficial for online adaptive radiotherapy (OART). However, auto-segmentation of clinical target volumes (CTV) is complex, as clinical interpretations are crucial in their definition. The resulting variation between clinicians and institutes hampers the generalizability of DL networks. In OART the CTV is delineated during treatment preparation which makes the clinician intent explicitly available during treatment. We studied whether multicenter generalisability improves when using this prior clinical knowledge, the pre-treatment delineation, as a patient-specific prior for DL models for online auto-segmentation of the mesorectal CTV.

Material & methods

We included intermediate risk or locally advanced rectal cancer patients from three centers. Patient-specific weight maps were created by combining the patient-specific CTV delineation on the pre-treatment scan with population-based variation of likely inter-fraction mesorectal CTV deformations. We trained two models to auto-segment the mesorectal CTV on in-house data, one with (MRI + prior) and one without (MRI-only) priors. Both models were applied to two external datasets. An external baseline model was trained without priors from scratch for one external center. Performance was evaluated on the DSC, surface Dice, 95HD and MSD.

Results

For both external centers, the MRI + prior model outperformed the MRI-only model significantly on the segmentation metrics (p-values < 0.01). There was no significant difference between the external baseline model and the MRI + prior model.

Conclusion

Adding patient-specific weight maps makes the CTV segmentation model more robust to institutional preferences. Performance was comparable to a model trained locally from scratch. This makes this approach suitable for generalization to multiple centers.
背景与目的：基于深度学习（DL）的自动分割已被证明对在线自适应放疗（OART）有益。然而，临床靶体积（CTV）的自动分割是复杂的，因为临床解释在其定义中至关重要。由此产生的临床医生和研究所之间的差异阻碍了深度学习网络的推广。在OART中，CTV是在治疗准备期间划定的，这使得临床医生的意图在治疗期间明确可用。我们研究了当使用这种先前的临床知识，即治疗前描绘作为DL模型用于直肠系膜CTV在线自动分割的患者特异性先验时，多中心泛化性是否得到改善。材料与方法：我们纳入了来自三个中心的中度或局部晚期直肠癌患者。通过将治疗前扫描的患者特异性CTV描绘与可能的肠系膜间CTV变形的基于人群的变化相结合，创建了患者特异性体重图。我们训练了两个模型来根据内部数据自动分割直肠系膜CTV，一个有（MRI + 先验），一个没有（仅MRI）先验。这两种模型都应用于两个外部数据集。对一个外部中心从头开始无先验地训练外部基线模型。在DSC， surface Dice， 95HD和MSD上评估性能。结果：对于两个外部中心，MRI + 先验模型在分割指标（p值 ）上明显优于仅MRI模型。结论：添加患者特异性权重图使CTV分割模型对机构偏好更具鲁棒性。其性能堪比本地从零开始训练的模型。这使得该方法适合推广到多个中心。
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引用次数: 0
Aiming for patient safety indicators in radiation oncology – Results from a systematic literature review as part of the PaSaGeRO study 瞄准放射肿瘤学患者安全指标- PaSaGeRO研究的一部分系统文献综述的结果。
IF 4.9 1区 医学 Q1 ONCOLOGY
Radiotherapy and Oncology
Pub Date : 2025-02-01 DOI: 10.1016/j.radonc.2024.110657
Andrea Baehr , Maximilian Grohmann , Eva Christalle , Felicitas Schwenzer , Isabelle Scholl

Background

Patient Safety Indicators (PSIs) allow the evaluation of safety levels in healthcare settings. Despite their use in various medical fields, a specific and comprehensive PSI catalogue for radiation oncology (RO) is lacking. The Patient Safety in German Radiation Oncology (PaSaGeRO) study aims for the development of a specific PSI catalogue in radiation oncology.

Objectives

The primary objective of this systematic literature review as part of the PaSaGeRO study is to identify, formulate, and categorize PSIs specific to RO to bridge existing gaps in comprehensive patient safety evaluation.

Methods

An electronic search in PubMed included studies from 1989 onwards, in English or German, focusing on safety and quality indicators in RO, patient safety measures, or risk analyses. Exclusions were non-transferable, country-specific measures, techniques exclusive to specific departments, and legally mandated procedures. Additional sources were identified through reference tracking and professional society websites. Two experts independently extracted PSIs from the included references.

Results

Out of 157 included publications and nine secondary sources, we identified and formulated 145 PSIs. These were categorized into patient-specific processes (82, 56%), quality and risk management (42, 28%), human resources (15, 10%), and institutional culture (13, 9%).

Conclusion

The hereby developed PSIs provides a base for professionals to systematically evaluate and improve safety practices, addressing previously unmet needs in this field. By offering clear guidance on safety assessment, the catalogue has the potential to drive significant improvements in patient care and safety outcomes in RO.
Funded by Deutsche Krebshilfe. Registered in the German Clinical Trials Register (DRKS00034690).
背景：患者安全指标（psi）允许评估医疗保健环境中的安全水平。尽管它们在各种医学领域中使用，但缺乏针对放射肿瘤学（RO）的具体和全面的PSI目录。德国放射肿瘤学中的患者安全（PaSaGeRO）研究旨在开发放射肿瘤学中特定的PSI目录。目的：作为PaSaGeRO研究的一部分，本系统文献综述的主要目的是识别、制定和分类针对RO的psi，以弥补综合患者安全性评估中的现有差距。方法：电子检索PubMed，包括1989年以来的英文或德文研究，重点是RO的安全和质量指标，患者安全措施或风险分析。排除是不可转让的、针对具体国家的措施、特定部门专有的技术和法律规定的程序。通过参考文献跟踪和专业协会网站确定了其他来源。两位专家分别从纳入的参考文献中提取了psi。结果：在纳入的157篇出版物和9个二手来源中，我们确定并制定了145个psi。这些因素被分类为患者特定流程（82,56%）、质量和风险管理（42,28%）、人力资源（15,10%）和机构文化（13.9%）。结论：本文开发的psi为专业人员系统评估和改进安全实践提供了基础，解决了该领域以前未满足的需求。通过提供关于安全评估的明确指导，该目录有可能推动RO患者护理和安全结果的重大改进。由德意志银行资助。在德国临床试验注册（DRKS00034690）中注册。
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引用次数: 0
Ninety-day mortality following curative intent radiotherapy for stage I-III lung cancer in the Netherlands 荷兰I-III期肺癌治疗意图放疗后90天死亡率。
IF 4.9 1区 医学 Q1 ONCOLOGY
Radiotherapy and Oncology
Pub Date : 2025-02-01 DOI: 10.1016/j.radonc.2024.110661
Krista C.J. van Doorn-Wink , Pieter E. Postmus , Dirk de Ruysscher , Ronald A.M. Damhuis

Background and purpose

The 90-day mortality following lung cancer treatment is a common performance indicator. The aim of this study was to investigate 90-day mortality following (chemo)radiotherapy for stage I–III lung cancer to evaluate the applicability of this outcome indicator in this patient population.

Materials and methods

The Netherlands National Cancer Registry was queried for this retrospective population-based study. Early mortality rates from the start and end of radiotherapy are reported with 95% confidence intervals (CI). The association between clinical characteristics and 90-day mortality was evaluated with multivariable logistic regression analysis.

Results

18,355 Patients treated between 2015 and 2020 were included. The 90-day mortality was 2.56% in stages I-II and 4.60% in stage III, was significantly higher in males, elderly patients and patients with a poor performance status and independent of facility volume. In stage I-II, 90-day mortality was lower after stereotactic versus conventional radiotherapy (2.0% versus 5.25%, OR 0.5 (95%CI 0.4–0.7)). In stage III, mortality decreased from 5.26% in 2015–2016 to 3.73% in 2019–2020 (OR 0.7 (95% CI 0.5–0.9)) and was lower after concurrent versus sequential chemoradiotherapy (3.4% versus 5.9%, OR 1.5 (95%CI 1.2–1.9)). Early mortality increased to 3.20% in stages I-II and 6.70% in stage III when calculated from the end of radiotherapy.

Conclusion

Short-term mortality rates following curative intent radiotherapy for lung cancer in the Netherlands are low and independent of facility volume. It was demonstrated that 90-day mortality is an arguable indicator to monitor radiotherapy quality and that standardization of definitions and relevant case-mix factors is warranted.
背景与目的：肺癌治疗后90天死亡率是一个常见的临床表现指标。本研究的目的是调查I-III期肺癌（化疗）放疗后90天死亡率，以评估这一结局指标在该患者群体中的适用性。材料和方法：我们向荷兰国家癌症登记处查询了这项基于人群的回顾性研究。放疗开始和结束时的早期死亡率报告有95%可信区间（CI）。采用多变量logistic回归分析评估临床特征与90天死亡率之间的关系。结果：纳入2015-2020年间治疗的18355例患者。I-II期和III期90天死亡率分别为2.56%和4.60%，其中男性、老年患者和表现不佳且与设施容量无关的患者死亡率较高。在I-II期，立体定向放疗后90天死亡率低于常规放疗（2.0%对5.25%,OR 0.5 (95%CI 0.4-0.7)）。在III期，死亡率从2015-2016年的5.26%下降到2019-2020年的3.73% (OR 0.7 (95%CI 0.5-0.9))，同时放化疗与顺序放化疗后死亡率更低（3.4%对5.9%,OR 1.5 (95%CI 1.2-1.9)）。从放疗结束计算，早期死亡率在I-II期增加到3.20%，在III期增加到6.70%。结论：在荷兰，肺癌治疗目的放疗后的短期死亡率较低，且与设施容量无关。研究表明，90天死亡率是监测放射治疗质量的一个有争议的指标，有必要对定义和相关病例组合因素进行标准化。
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引用次数: 0
Is the omission of the external iliac or upper pelvic lymph nodes from elective irradiation safe in selected anal canal squamous cell cancers? 对于选定的肛管鳞状细胞癌，不对髂外淋巴结或盆腔上淋巴结进行选择性照射是否安全？
IF 4.9 1区 医学 Q1 ONCOLOGY
Radiotherapy and Oncology
Pub Date : 2025-02-01 DOI: 10.1016/j.radonc.2024.110682
Karol Paciorek , Anna Zawadzka , Lucyna Pietrzak , Bartłomiej Skrzypiec , Wojciech Michalski , Joanna Socha , Krzysztof Bujko

Background

Guidelines recommend elective irradiation of the external iliac and upper pelvic lymph nodes (LNs) regardless of clinical stage, but the supporting evidence for this recommendation is limited.

Methods

We conducted a retrospective analysis of 68 consecutive patients with squamous cell carcinoma of the anal canal who underwent volumetric modulated arc therapy chemoradiation, excluding external iliac LNs from elective irradiation. In patients with negative bilateral inguinal LNs, both external iliac regions were omitted, while in those with unilateral positive inguinal LNs, only the ipsilateral external iliac region was included and the contralateral side was omitted. For patients with early-stage tumours, the cranial border of elective irradiation was located in the inferior aspect of the sacroiliac joints.

Results

The median follow-up was 4.0 years. Six patients (9 %) experienced recurrence of the primary tumour and three (4 %) developed distant metastases. No isolated nodal recurrences were seen in the LNs that were positive at baseline, or in or outside electively irradiated regions. Notably, no recurrences were seen in any of the 124 external iliac regions omitted from elective irradiation across the 68 patients, or in the upper pelvic region among the subgroup of 33 patients where the cranial irradiation border was at the bottom of the sacroiliac joint. Reducing the elective irradiation volume significantly decreased the dose–volume parameters for organs-at-risk.

Conclusions

The present findings suggest that omitting the external iliac and upper pelvic LNs from elective irradiation is safe for selected patients and allows dose reduction in organs-at-risk.
背景：指南建议，无论临床分期如何，均应选择性照射髂外淋巴结和盆腔上淋巴结（LN），但支持这一建议的证据有限：我们对68例连续接受容积调控弧形疗法化疗的肛管鳞状细胞癌患者进行了回顾性分析，其中不包括选择性照射的髂外淋巴结。在双侧腹股沟淋巴结阴性的患者中，两侧髂外淋巴结均被省略，而在单侧腹股沟淋巴结阳性的患者中，仅同侧髂外淋巴结被包括在内，对侧则被省略。对于早期肿瘤患者，选择性照射的头颅边界位于骶髂关节的下侧：中位随访时间为 4.0 年。6名患者（9%）原发肿瘤复发，3名患者（4%）出现远处转移。在基线阳性的淋巴结中，或在选择性照射区域内外，均未发现孤立的结节复发。值得注意的是，在68名患者中，有124个髂外区域未进行选择性照射，在33名患者中，头颅照射边界位于骶髂关节底部的骨盆上部区域也未见复发。减少选择性照射量可显著降低危险器官的剂量-体积参数：本研究结果表明，选择性照射时不照射髂外静脉结节和骨盆上静脉结节对选定的患者是安全的，并且可以减少风险器官的剂量。
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引用次数: 0
Revisiting hydrogen peroxide as radiosensitizer for solid tumor cells 再谈过氧化氢作为实体肿瘤细胞的放射增敏剂。
IF 4.9 1区 医学 Q1 ONCOLOGY
Radiotherapy and Oncology
Pub Date : 2025-02-01 DOI: 10.1016/j.radonc.2024.110692
F. Geirnaert , L. Kerkhove , A. Rifi , T. Everaert , J. Sanders , J. Coppens , H. Vandenplas , C. Corbet , T. Gevaert , I. Dufait , M. De Ridder

Background and purpose

Tumor hypoxia is the principal cause of clinical radioresistance. Despite its established role as radiosensitizer, hydrogen peroxide (H2O2) encounters clinical limitations due to stability and toxicity concerns. Recent advancements in drug delivery combine H2O2 with sodium hyaluronate (SH), enabling intratumoral administration of H2O2. This study investigates the radiomodulatory pathways of Kochi Oxydol-Radiation for Unresectable Carcinomas (KORTUC) (H2O2 + SH) under hypoxia.

Materials and methods

CT26 and 4T1 tumor cells were exposed to H2O2, SH and KORTUC under hypoxic conditions. Toxicity levels were determined using MTT and live-cell analysis. KORTUC’s radiomodulatory properties were evaluated by colony formation assay and in spheroids. Reactive oxygen species (ROS) levels, DNA damage, apoptosis and ferroptosis were analyzed using flow cytometry. Oxygen consumption rate (OCR) and mitochondrial complex activity were assessed by Seahorse Analyzer. Oxygen levels were investigated using fiber-optic sensors. The in vitro findings were validated in CT26-bearing mice.

Results

KORTUC demonstrated less cytotoxicity than H2O2-alone. KORTUC radiosensitized hypoxic tumor cells in a dose-dependent manner with enhancement ratios of 3.1 (CT26) and 2.7 (4T1). Dose-dependent OCR reduction following KORTUC exposure correlated with complex I and II inhibition, accompanied by mitochondrial ROS elevation. KORTUC injection into a 2D hypoxic tumor model surged O2 levels. KORTUC radiosensitized CT26-tumors, delaying growth by 14 days.

Conclusions

SH in KORTUC mitigates H2O2 cytotoxicity. We demonstrate that KORTUC overcomes hypoxia-induced radioresistance through inhibition of OCR, via complex I- and II-blockade, leading to tumor reoxygenation. Understanding KORTUC’s pathways is essential for developing effective cancer combination therapies.
背景与目的：肿瘤缺氧是临床放射耐药的主要原因。尽管过氧化氢（H2O2）具有放射增敏剂的作用，但由于稳定性和毒性问题，它在临床中受到限制。最近的进展是将H2O2与透明质酸钠（SH）结合起来，使H2O2在肿瘤内给药成为可能。本研究探讨缺氧条件下高知氧dolo辐射治疗不可切除癌（KORTUC） （H2O2 + SH）的辐射调节途径。材料和方法：CT26和4 T1肿瘤细胞在缺氧条件下暴露于H2O2、SH和KORTUC。用MTT和活细胞分析测定毒性水平。KORTUC的辐射调节特性通过集落形成试验和球体来评估。流式细胞术分析各组小鼠活性氧（ROS）水平、DNA损伤、细胞凋亡及铁下垂情况。采用海马分析仪测定各组小鼠的耗氧量（OCR）和线粒体复合体活性。用光纤传感器检测氧含量。体外研究结果在ct26小鼠中得到了验证。结果：KORTUC的细胞毒性低于h2o2。KORTUC以剂量依赖的方式使缺氧肿瘤细胞放射增敏，增强比为3.1 （CT26）和2.7（4 T1）。KORTUC暴露后的剂量依赖性OCR降低与复合体I和II抑制相关，并伴有线粒体ROS升高。注射KORTUC后，二维缺氧肿瘤模型血氧水平升高。KORTUC使ct26肿瘤放射致敏，使肿瘤生长延迟14 天。结论：SH在KORTUC中减轻H2O2的细胞毒性。我们证明，KORTUC通过复合物I-和ii -阻断抑制OCR，从而克服缺氧诱导的辐射抗性，从而导致肿瘤再氧化。了解KORTUC的通路对于开发有效的癌症联合疗法至关重要。
{"title":"Revisiting hydrogen peroxide as radiosensitizer for solid tumor cells","authors":"F. Geirnaert ,&nbsp;L. Kerkhove ,&nbsp;A. Rifi ,&nbsp;T. Everaert ,&nbsp;J. Sanders ,&nbsp;J. Coppens ,&nbsp;H. Vandenplas ,&nbsp;C. Corbet ,&nbsp;T. Gevaert ,&nbsp;I. Dufait ,&nbsp;M. De Ridder","doi":"10.1016/j.radonc.2024.110692","DOIUrl":"10.1016/j.radonc.2024.110692","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Tumor hypoxia is the principal cause of clinical radioresistance. Despite its established role as radiosensitizer, hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) encounters clinical limitations due to stability and toxicity concerns. Recent advancements in drug delivery combine H<sub>2</sub>O<sub>2</sub> with sodium hyaluronate (SH), enabling intratumoral administration of H<sub>2</sub>O<sub>2</sub>. This study investigates the radiomodulatory pathways of Kochi Oxydol-Radiation for Unresectable Carcinomas (KORTUC) (H<sub>2</sub>O<sub>2</sub> + SH) under hypoxia.</div></div><div><h3>Materials and methods</h3><div>CT26 and 4T1 tumor cells were exposed to H<sub>2</sub>O<sub>2,</sub> SH and KORTUC under hypoxic conditions. Toxicity levels were determined using MTT and live-cell analysis. KORTUC’s radiomodulatory properties were evaluated by colony formation assay and in spheroids. Reactive oxygen species (ROS) levels, DNA damage, apoptosis and ferroptosis were analyzed using flow cytometry. Oxygen consumption rate (OCR) and mitochondrial complex activity were assessed by Seahorse Analyzer. Oxygen levels were investigated using fiber-optic sensors. The in vitro findings were validated in CT26-bearing mice.</div></div><div><h3>Results</h3><div>KORTUC demonstrated less cytotoxicity than H<sub>2</sub>O<sub>2</sub>-alone. KORTUC radiosensitized hypoxic tumor cells in a dose-dependent manner with enhancement ratios of 3.1 (CT26) and 2.7 (4T1). Dose-dependent OCR reduction following KORTUC exposure correlated with complex I and II inhibition, accompanied by mitochondrial ROS elevation. KORTUC injection into a 2D hypoxic tumor model surged O<sub>2</sub> levels. KORTUC radiosensitized CT26-tumors, delaying growth by 14 days.</div></div><div><h3>Conclusions</h3><div>SH in KORTUC mitigates H<sub>2</sub>O<sub>2</sub> cytotoxicity. We demonstrate that KORTUC overcomes hypoxia-induced radioresistance through inhibition of OCR, via complex I- and II-blockade, leading to tumor reoxygenation. Understanding KORTUC’s pathways is essential for developing effective cancer combination therapies.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"203 ","pages":"Article 110692"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882736","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
Comparison of definitive radiotherapy outcomes between younger and older patients with high- or very-high-risk prostate cancer
IF 4.9 1区 医学 Q1 ONCOLOGY
Radiotherapy and Oncology
Pub Date : 2025-02-01 DOI: 10.1016/j.radonc.2025.110763
Yong-Hyub Kim , Jae-Uk Jeong , Jung-Ho Yang , Taek-Keun Nam , Ju-Young Song , Mee Sun Yoon , Shinhaeng Cho , Sung-Ja Ahn

Background and purpose

This study aimed to compare the oncologic outcomes of definitive intensity-modulated radiotherapy (IMRT) between younger and older high- or very-high-risk prostate cancer patients using propensity score matching (PSM) and competing risk analysis (CRA).

Materials and methods

A total of 569 patients were included in this analysis: 265 younger than 75 years (Group A) and 304 aged 75 years or above (Group B). All patients received IMRT with a daily fraction of 2.2 Gy, administered over 34 fractions, resulting in a total dose of 74.8 Gy. The primary outcomes included biochemical-failure-free survival (BCFFS), distant-metastasis-free survival (DMFS), clinical-failure-free survival (CFFS), cancer-specific survival (CSS), and overall survival (OS). PSM was used to balance the groups, employing a full matching method, while CRA distinguished between cancer-specific events and non-cancer-specific events.

Results

Before PSM, the 7-year BCFFS, DMFS, CFFS, CSS, and OS rates in Groups A and B were 83.0 % vs. 66.7 % (p = 0.011), 84.1 % vs. 68.0 % (p = 0.002), 82.1 % vs. 66.7 % (p = 0.008), 95.6 % vs. 97.3 % (p = 0.704), and 87.4 % vs. 68.6 % (p < 0.001), respectively. After PSM, the 7-year survival rates were comparable between both groups for all outcomes except OS. CRA revealed that cancer-specific events were more frequent in Group A, whereas non-cancer-specific events predominated in Group B.

Conclusions

Both PSM and CRA indicated that definitive IMRT can be safely and effectively delivered to older patients with high- or very high-risk prostate cancer, achieving oncologic outcomes comparable to those in younger patients.
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引用次数: 0
Interferon signaling is enhanced by ATR inhibition in glioblastoma cells irradiated with X-rays, protons or carbon ions 干扰素信号通过x射线、质子或碳离子照射的胶质母细胞瘤细胞ATR抑制而增强。
IF 4.9 1区 医学 Q1 ONCOLOGY
Radiotherapy and Oncology
Pub Date : 2025-02-01 DOI: 10.1016/j.radonc.2024.110669
Gro Elise Rødland , Mihaela Temelie , Adrian Eek Mariampillai , Ana Maria Serban , Nina Frederike Jeppesen Edin , Eirik Malinen , Lilian Lindbergsengen , Antoine Gilbert , François Chevalier , Diana I. Savu , Randi G. Syljuåsen

Background and purpose

Interferon (IFN) signaling plays an important role in antitumor immune responses. Inhibitors of the DNA damage response, such as ATR inhibitors, can increase IFN signaling upon conventional radiotherapy with X-rays. However, it is not known whether such inhibitors also enhance IFN signaling after irradiation with high linear energy transfer (LET) particles.

Materials and methods

Human glioblastoma U-251 and T98G cells were irradiated with X-rays, protons (LET: 4.8 and 41.9 keV/µm) and carbon ions (LET: 28 and 73 keV/µm), with and without ATR inhibitor (VE-822) or ATM inhibitor (AZD1390). DNA damage signaling and cell cycle distribution were analyzed by immunoblotting and flow cytometry, and radiosensitivity was assessed by clonogenic survival assay. IFN-β secretion was measured by ELISA, and STAT1 activation was examined by immunoblotting.

Results

High-LET protons and carbon ions caused stronger activation of the DNA damage response compared to low-LET protons and X-rays at similar radiation doses. G2 checkpoint arrest was abrogated by the ATR inhibitor and prolonged by the ATM inhibitor after all radiation types. The inhibitors increased radiosensitivity, as measured after X- and carbon ion irradiation. ATR inhibition increased IFN signaling following both low-LET and high-LET irradiation. ATM inhibition also increased IFN signaling, but to a lesser extent. Notably, both cell lines secreted significantly more IFN-β when the inhibitors were combined with high-LET compared to low-LET irradiation.

Conclusion

These findings indicate that DNA damage response inhibitors can enhance IFN signaling following X-, proton and carbon ion irradiation, with a strong positive dependency on LET.
背景与目的：干扰素（IFN）信号在抗肿瘤免疫应答中起重要作用。DNA损伤反应的抑制剂，如ATR抑制剂，可增加常规x射线放射治疗后IFN信号传导。然而，尚不清楚这些抑制剂是否也能在高线性能量转移（LET）颗粒照射后增强IFN信号传导。材料和方法：用x射线、质子（LET: 4.8和41.9 keV/µm）和碳离子（LET: 28和73 keV/µm）照射人胶质母细胞瘤U-251和T98G细胞，含和不含ATR抑制剂（VE-822）或ATM抑制剂（AZD1390）。通过免疫印迹和流式细胞术分析DNA损伤信号和细胞周期分布，通过克隆生存试验评估放射敏感性。ELISA法检测IFN-β分泌，免疫印迹法检测STAT1激活情况。结果：在相同的辐射剂量下，与低let质子和x射线相比，高let质子和碳离子对DNA损伤反应的激活作用更强。ATR抑制剂消除G2检查点阻滞，ATM抑制剂延长G2检查点阻滞时间。在X离子和碳离子照射后测量，抑制剂增加了放射敏感性。ATR抑制增加了低let和高let辐照后IFN信号转导。ATM抑制也增加IFN信号，但程度较轻。值得注意的是，与低let照射相比，当抑制剂与高let照射联合使用时，两种细胞系分泌的IFN-β显著增加。结论：这些发现表明DNA损伤反应抑制剂可以增强X、质子和碳离子辐照后的IFN信号，并且与LET有很强的正依赖性。
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引用次数: 0
Risk reduction of radiation-induced aspiration by sparing specific aspiration-related-organs at risk; an in silico feasibility study 通过保留有危险的特定吸入相关器官来降低辐射诱导误吸的风险；一项计算机可行性研究。
IF 4.9 1区 医学 Q1 ONCOLOGY
Radiotherapy and Oncology
Pub Date : 2025-02-01 DOI: 10.1016/j.radonc.2024.110698
Hans Paul van der Laan , Agata Gawryszuk , Arjen van der Schaaf, Johannes A. Langendijk

Purpose

To assess the feasibility and benefit of NTCP optimized aspiration-prevention treatment planning by sparing specific aspiration related organs at risk, and to assess the impact of baseline complaints on the planning results.

Materials and Methods

This in silico planning study included 30 HNC patients who were previously treated with definitive radiotherapy. New fully automated plans, allowing for sparing specific aspiration related organs at risk, were optimised directly on normal tissue complication probability (NTCP) models for common toxicities: xerostomia and dysphagia. Optimisation was performed with and without aspiration-prevention, i.e., with and without specific sparing of recently identified aspiration-related muscles, and with and without the assumption of existing baseline complaints.

Results

All plans complied with the pre-defined treatment planning quality criteria and were successful in limiting the risk of xerostomia and dysphagia. Aspiration-prevention VMAT, optimized using the additional NTCP model for aspiration, significantly reduced the estimated risk of late aspiration (p < 0.001) in all 30 patients when compared to plans without NTCP optimisation for late aspiration. The predicted risk of late aspiration was reduced even further when baseline aspiration was assumed present during optimisation, resulting in an average risk reduction of 13.3 % versus 8.3 % in plans assuming no aspiration at baseline. Aspiration-prevention did not reduce overall plan quality and maintained NTCP values obtained for various other toxicities.

Conclusion

Sparing specific aspiration-related organs at risk has the potential to significantly reduce the risk of late RT-induced aspiration, especially in patients who experience aspiration already at baseline.
目的：评估NTCP优化误吸预防治疗方案的可行性和效益，保留特定误吸相关器官的风险，并评估基线投诉对计划结果的影响。材料和方法：本计算机计划研究包括30例既往接受明确放疗的HNC患者。新的全自动计划，允许保留特定吸入相关器官的风险，直接在正常组织并发症概率（NTCP）模型上优化常见毒性：口干和吞咽困难。优化是在有和没有吸气预防的情况下进行的，即，有和没有最近确定的吸气相关肌肉的特定保留，有和没有现有基线投诉的假设。结果：所有方案均符合预先制定的治疗计划质量标准，成功地限制了口干和吞咽困难的风险。预防误吸的VMAT，使用额外的NTCP误吸模型进行了优化，显著降低了晚期误吸的估计风险（p ）结论：保留处于危险中的特定误吸相关器官有可能显著降低晚期rt诱导误吸的风险，特别是在基线时已经经历误吸的患者中。
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引用次数: 0
Association of the time of day of chemoradiotherapy and durvalumab with tumor control in lung cancer 肺癌患者放化疗时间和杜伐单抗与肿瘤控制的关系
IF 4.9 1区 医学 Q1 ONCOLOGY
Radiotherapy and Oncology
Pub Date : 2025-02-01 DOI: 10.1016/j.radonc.2024.110658
Matthew T. McMillan , Annemarie Shepherd , Alissa J. Cooper , Adam J. Schoenfeld , Abraham J. Wu , Charles B. Simone II , Puneeth Iyengar , Daphna Y. Gelblum , Jamie E. Chaft , Daniel R. Gomez , Narek Shaverdian

Background/purpose

The circadian clock governs the expression of genes related to immunity and DNA repair. We investigated whether the time of day of radiotherapy and/or systemic therapy infusions (chemotherapy or anti-PD-L1) are associated with disease control and survival in locally advanced non-small cell lung cancer (LA-NSCLC).

Materials/methods

178 consecutive patients with inoperable LA-NSCLC who received definitive chemoradiotherapy followed by durvalumab between 5/2017–8/2022 were reviewed. Outcomes evaluated included progression-free survival (PFS), distant metastasis-free survival (DMFS), locoregional control (LRC), and overall survival (OS).

Results

At a median follow up of 48.0 mo from durvalumab initiation, median PFS and OS were 26.2 mo and 50.0 mo, respectively. Median LRC and DMFS were not reached and 41.0 mo, respectively. Receiving > 50 % (N = 23) versus ≤ 50 % (N = 155) of radiotherapy treatments within 3 h of sunset was associated with younger age; otherwise, there were no other differences between cohorts. There were no significant differences in characteristics between patients who received > 50 % (N = 23) versus ≤ 50 % (N = 155) of durvalumab infusions within 3 h of sunset. On multivariable analysis, receiving > 50 % of radiotherapy treatments within 3 h of sunset was independently associated with reduced risk for progression (HR 0.39, p = 0.017) and distant metastasis (HR 0.27, p = 0.007); conversely, receiving > 50 % of durvalumab infusions within 3 h of sunset was independently associated with increased risk for distant metastasis (HR 2.13, p = 0.025). The timing of chemotherapy was not associated with disease outcomes.

Conclusion

The time of day of radiotherapy and durvalumab infusion may be associated with disease control in LA-NSCLC, and the optimal time of treatment depends on the treatment modality.
背景/目的：生物钟控制着免疫和DNA修复相关基因的表达。我们研究了局部晚期非小细胞肺癌（LA-NSCLC）患者的放疗和/或全身治疗输注时间（化疗或抗pd - l1）是否与疾病控制和生存相关。材料/方法：在2017年5月至2022年8月期间，178例连续接受终期放化疗和杜伐单抗治疗的不能手术的LA-NSCLC患者进行了回顾性研究。评估的结果包括无进展生存期（PFS）、无远处转移生存期（DMFS）、局部区域控制（LRC）和总生存期（OS）。结果：从durvalumab开始的中位随访时间为48.0个月，中位PFS和OS分别为26.2个月和50.0个月。中位LRC和DMFS分别为未达到和41.0个月。接收 > 50 % (N = 23)与 ≤50  % (N = 155)内放疗治疗3日落与年轻有关的人力资源;除此之外，队列之间没有其他差异。没有明显的特征差异病人 > 50 % (N = 23)与 ≤50  % (N = 155)中的durvalumab注入3人力资源的日落。在多变量分析中，在日落后3小时内接受 > 50% %的放疗与降低进展风险（HR 0.39, p = 0.017）和远处转移风险（HR 0.27, p = 0.007）独立相关；相反，日落后3小时内接受 > 50% %的durvalumab输注与远处转移风险增加独立相关（HR 2.13, p = 0.025）。化疗时间与疾病结果无关。结论：放疗和杜伐单抗输注的时间可能与LA-NSCLC的疾病控制有关，最佳治疗时间取决于治疗方式。
{"title":"Association of the time of day of chemoradiotherapy and durvalumab with tumor control in lung cancer","authors":"Matthew T. McMillan ,&nbsp;Annemarie Shepherd ,&nbsp;Alissa J. Cooper ,&nbsp;Adam J. Schoenfeld ,&nbsp;Abraham J. Wu ,&nbsp;Charles B. Simone II ,&nbsp;Puneeth Iyengar ,&nbsp;Daphna Y. Gelblum ,&nbsp;Jamie E. Chaft ,&nbsp;Daniel R. Gomez ,&nbsp;Narek Shaverdian","doi":"10.1016/j.radonc.2024.110658","DOIUrl":"10.1016/j.radonc.2024.110658","url":null,"abstract":"<div><h3>Background/purpose</h3><div>The circadian clock governs the expression of genes related to immunity and DNA repair. We investigated whether the time of day of radiotherapy and/or systemic therapy infusions (chemotherapy or anti-PD-L1) are associated with disease control and survival in locally advanced non-small cell lung cancer (LA-NSCLC).</div></div><div><h3>Materials/methods</h3><div>178 consecutive patients with inoperable LA-NSCLC who received definitive chemoradiotherapy followed by durvalumab between 5/2017–8/2022 were reviewed. Outcomes evaluated included progression-free survival (PFS), distant metastasis-free survival (DMFS), locoregional control (LRC), and overall survival (OS).</div></div><div><h3>Results</h3><div>At a median follow up of 48.0 mo from durvalumab initiation, median PFS and OS were 26.2 mo and 50.0 mo, respectively. Median LRC and DMFS were not reached and 41.0 mo, respectively. Receiving &gt; 50 % (N = 23) versus ≤ 50 % (N = 155) of radiotherapy treatments within 3 h of sunset was associated with younger age; otherwise, there were no other differences between cohorts. There were no significant differences in characteristics between patients who received &gt; 50 % (N = 23) versus ≤ 50 % (N = 155) of durvalumab infusions within 3 h of sunset. On multivariable analysis, receiving &gt; 50 % of radiotherapy treatments within 3 h of sunset was independently associated with reduced risk for progression (HR 0.39, p = 0.017) and distant metastasis (HR 0.27, p = 0.007); conversely, receiving &gt; 50 % of durvalumab infusions within 3 h of sunset was independently associated with increased risk for distant metastasis (HR 2.13, p = 0.025). The timing of chemotherapy was not associated with disease outcomes.</div></div><div><h3>Conclusion</h3><div>The time of day of radiotherapy and durvalumab infusion may be associated with disease control in LA-NSCLC, and the optimal time of treatment depends on the treatment modality.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"203 ","pages":"Article 110658"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771896","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
Deglutition preservation after swallowing (SWOARs)-sparing IMRT in head and neck cancers: definitive results of a multicenter prospective study of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) 头颈部癌症患者吞咽（Swoars）后保留吞咽功能的即时放射治疗（IMRT）：意大利放射治疗和临床肿瘤学协会（Airo）多中心前瞻性研究的最终结果。
IF 4.9 1区 医学 Q1 ONCOLOGY
Radiotherapy and Oncology
Pub Date : 2025-02-01 DOI: 10.1016/j.radonc.2024.110651
Stefano Ursino , Giulia Malfatti , Francesca De Felice , Pierluigi Bonomo , Isacco Desideri , Pierfrancesco Franco , Francesca Arcadipane , Caterina Colosimo , Rosario Mazzola , Marta Maddalo , Riccardo Morganti , Giacomo Fiacchini , Salvatore Coscarelli , Maurizio Bartolucci , Marco De Vincentis , Diletta Angeletti , Franca De Biase , Elsa Juliani , Fabio Di Martino , Alessia Giuliano , Fabiola Paiar

Background

To investigate changes of objective instrumental measures and correlate with patient reported outcomes (PROs) of radiation-induced dysphagia (RID) after swallowing organs at risk (SWOARs)-sparing IMRT.

Methods

Patients (pts) underwent Fiberoptic Endoscopic Evaluation of Swallowing (FEES), Videofluoroscopy (VFS) and M.D. Anderson Dysphagia Inventory (MDADI) questionnaire at baseline, 6 and 12 months after treatment. They were categorized in two groups: MDADI-C ≥ 80 and MDADI-C < 80. Pharyngeal residue (PR) and penetration (P) or aspiration (A) were considered as surrogate of RID.

Results

Between 2016 and 2022 we enrolled 75 pts, 40 (53 %) MDADI-C ≥ 80 and 35 (47 %) MDADI-C < 80 at baseline.
Among MDADI-C ≥ 80 the mean baseline PR score at FEES was 0,42 rising to 1,36 at 6 months (p = 0,001) and stabilizing to 1,15 at 12 months (p = 0,21); indeed, the mean baseline PR score at VFS was 0,55 rising to 1 at 6 months (p = 0,069) and slightly dropping to 0,7 at 12 months (p = 0,069). Among MDADI-C < 80 the mean baseline PR score at FEES was 0,56 rising to 1,07 at 6 months (p = 0,012) and stabilizing to 1,07 at 12 months (p = 0,99); indeed the mean baseline PR score at VFS was 0,67 rising to 1,19 at 6 months (p = 0,04) and dropping to 0,78 at 12 months (p = 0,04). No correlation was found between PROs and objective measures.

Conclusion

Our results show optimal acceptable deglutition preservation from major complications after SWOARs-sparing IMRT by means of low objective scores in both MDADI-C groups. Lack of correlation between PROs and objective measures suggest that referred RID is likely associated to persistence of SWOARs inflammation rather than to a real impairment of function.
背景：目的：研究吞咽器官风险（SWOARs）--IMRT--后放射诱发吞咽困难（RID）的客观工具测量的变化以及与患者报告结果（PROs）的相关性：患者（pts）在基线、治疗后 6 个月和 12 个月接受了纤维内窥镜吞咽评估（FEES）、视频荧光屏检查（VFS）和 M.D. Anderson 吞咽困难量表（MDADI）问卷调查。他们被分为两组：MDADI-C ≥ 80 和 MDADI-C 结果：在 2016 年至 2022 年期间，我们招募了 75 名患者，其中 40 人（53%）MDADI-C ≥ 80，35 人（47%）MDADI-C：我们的研究结果表明，在 MDADI-C 两组中，SWOARs-sparing IMRT 的客观评分均较低，因此可以最佳、可接受地保留脱落口腔，避免出现重大并发症。PROs 与客观测量之间缺乏相关性，这表明转诊的 RID 可能与 SWOARs 炎症的持续存在有关，而不是与功能的真正损害有关。
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