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Hypofractionated stereotactic body radiation therapy for metastatic epidural spinal cord Compression: A case series study 低分割立体定向放射治疗转移性硬膜外脊髓压迫:一个病例系列研究。
IF 5.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-08 DOI: 10.1016/j.radonc.2025.111320
Siming Zheng , Ting Liu , Jiaxiong Zhou, Ting Wang, Zhen Li, Jianrong Yu, Lei Wen, Minying Li

Background and purpose

To describe the clinical outcomes of patients with metastatic epidural spinal cord compression (MESCC) treated with hypofractionated stereotactic body radiation therapy (SBRT).

Materials and Methods

The outcomes of MESCC patients who underwent SBRT at our institution from January 2021 to September 2023 were retrospectively reviewed. The prescribed dose was 30–35 Gy delivered in five fractions over 7 days. Differences between complete pain relief, local control (LC), overall survival (OS), and adverse reaction rates between the groups were evaluated at different time points.

Results

The study cohort included 63 patients (91 lesions) with a median follow-up of 12 months. Complete pain relief rates at post-treatment months 1, 3, and 6 were 28.6 %, 44.4 %, and 45.3 %, respectively, with no significant difference between patients with low-grade vs. high-grade MESCC. The 1-year LC rate was 91.4 % (32/35) and the 1- and 2-year OS rates were 83.1 % and 46.1 %, respectively, with no significant difference between the low-grade and high-grade MESCC groups. Furthermore, 87.5 % (14/16) of patients with high-grade MESCC exhibited a decrease in Bilsky score at 3 months post-treatment, and the majority remained stabilized at 6 months. However, nine (14.3 %) patients developed new or worsening vertebral compression fractures.

Conclusion

Hypofractionated SBRT presents a feasible option for MESCC. For patients with high-grade MESCC who are unsuitable for surgery or refuse surgical intervention, SBRT can effectively relieve spinal cord compression.
背景和目的:描述转移性硬膜外脊髓压迫(MESCC)患者接受低分割立体定向放射治疗(SBRT)的临床结果。材料和方法:回顾性分析2021年1月至2023年9月在我院接受SBRT治疗的MESCC患者的预后。处方剂量为30-35 Gy,分五次在7 天内给药。评估两组患者在不同时间点的完全疼痛缓解、局部控制(LC)、总生存期(OS)和不良反应发生率的差异。结果:研究队列包括63例患者(91个病变),中位随访时间为12 个月。治疗后1、3和6个月的完全疼痛缓解率分别为28.6 %、44.4 %和45.3 %,低级别与高级别MESCC患者之间无显著差异。1年LC率为91.4 %(32/35),1年和2年OS率分别为83.1 %和46.1 %,低分级和高分级MESCC组之间无显著差异。此外,87.5% %(14/16)的高级别MESCC患者在治疗后3 个月时Bilsky评分下降,大多数患者在6 个月时保持稳定。然而,9例(14.3 %)患者出现新的或恶化的椎体压缩性骨折。结论:切开SBRT是MESCC的可行选择。对于不适合手术或拒绝手术干预的高级别MESCC患者,SBRT可有效缓解脊髓压迫。
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引用次数: 0
A universal medical imaging modality translation model in brain and head-and-neck radiotherapy 脑及头颈部放射治疗的通用医学影像模态转换模型。
IF 5.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-07 DOI: 10.1016/j.radonc.2025.111321
Yunxiang Li, Xiao Liang, Jiacheng Xie, Jie Deng, Weiguo Lu, You Zhang

Purpose

We developed a universal image translation model—Translate Any Modality (TAM) model to synthesize MRI sequences and CT for brain and head-and-neck radiotherapy, facilitating downstream clinical tasks including multimodal registration and treatment dose calculation.

Methods and materials

We retrospectively curated multi-modal imaging from 90 patients (43 brain, and 47 head-and-neck), each with up to eight MRI sequences and a paired CT. TAM uses a two-stage translation strategy: a 3D U-Net to firstly segment soft tissues and bones to serve as anatomical anchors; and a conditional diffusion model, guided by these masks, to synthesize the target modality from any available input modalities. We evaluated 46 MRI-to-MRI and MRI-to-CT translation tasks against two comparison methods, CycleGAN and UNIT, using Frechet Inception Distance (FID), peak signal-to-noise-ratio (PSNR), structural similarity index (SSIM), and Hounsfield unit (HU)-based mean absolute error (MAE). Clinical relevance was tested via multi-modality registration with simulated B-spline deformations and dose calculation using clinical plans with Gamma criteria 1 %/1 mm and 2 %/2 mm.

Results

TAM improved image quality (PSNR 30.0 ± 3.7; SSIM 0.973 ± 0.024) versus UNIT (27.0 ± 3.2; 0.958 ± 0.026) and CycleGAN (25.4 ± 4.1; 0.949 ± 0.037). For synthesized CT, TAM-based CT achieved average Gamma indices of 99.1 ± 1.7 % (2 %/2 mm) and 94.1 ± 6.4 % (1 %/1 mm) versus CycleGAN 93.1 ± 7.5 %/84.0 ± 9.5 % and UNIT 93.8 ± 7.0 %/86.3 ± 9.4 %, with dose-volume histograms closely matching real-CT plans.

Conclusion

TAM is a novel any-to-any medical image modality translation model. It provides flexible, anatomically faithful translation among MRI sequences and CT, which subsequently improves the accuracy of downstream tasks, including registration and dose calculation.
目的:建立一种通用的图像翻译模型——TAM (translate Any Modality)模型,用于脑及头颈部放射治疗的MRI序列和CT合成,方便多模态配准和治疗剂量计算等下游临床工作。方法和材料:我们回顾性地收集了90例患者(43例脑部,47例头颈部)的多模态成像,每个患者最多有8个MRI序列和一对CT。TAM采用两阶段翻译策略:首先使用3D U-Net分割软组织和骨骼作为解剖锚;以及一个条件扩散模型,在这些掩模的指导下,从任何可用的输入模态合成目标模态。我们使用Frechet Inception Distance (FID)、峰值信噪比(PSNR)、结构相似指数(SSIM)和基于Hounsfield单位(HU)的平均绝对误差(MAE),对46个MRI-to-MRI和MRI-to-CT翻译任务进行了评估,对比两种比较方法CycleGAN和UNIT。通过多模注册临床相关性测试与模拟b样条变形和使用临床计划和γ剂量计算标准1 % / 1毫米和2 % / 2 mm.Results: TAM改善图像质量(PSNR 30.0 ± 3.7;0.973 SSIM ±0.024 )和单位(27.0 ± 3.2;0.958 ±0.026 )和CycleGAN(25.4 ± 4.1;0.949 ±0.037 )。合成CT,基于tam CT实现平均伽马指数99.1 ±1.7  %(2 % / 2毫米)和94.1 ±6.4  %(1 % / 1毫米)和CycleGAN 93.1±7.5  % / 84.0 ±9.5  %和单元 93.8±7.0  % / 86.3 ±9.4  %,密切与dose-volume直方图匹配real-CT计划。结论:TAM是一种新的任意对任意医学图像模态翻译模型。它在MRI序列和CT之间提供灵活的、解剖学上忠实的转换,从而提高下游任务的准确性,包括注册和剂量计算。
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引用次数: 0
Image-guided intensity-modulated radiotherapy with reduced margins in patients with prostate cancer: Results of the RCMIGI randomized phase II trial 影像引导下调强放疗在前列腺癌患者中的应用:RCMIGI随机II期试验的结果
IF 5.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-07 DOI: 10.1016/j.radonc.2025.111322
Olivier Riou , Pascal Fenoglietto , Marta Jarlier , Jessica Prunaretty , Norbert Aillères , Grégoire Poinas , Pierre Debuire , Sophie Gourgou , Laetitia Meignant , Bruno Segui , Carmen Llacer Moscardo , Marie Charissoux , David Azria

Background and purpose

Intensity-modulated (IMRT) and image-guided (IGRT) radiotherapies reduce radiation-induced toxicities in localized prostate cancer. This randomized phase II trial (NCT03254420) evaluated late pelvic toxicity (LPT) and quality of life after IMRT/IGRT with standard or reduced margins in patients with low- to intermediate-risk prostate cancer.

Materials and methods

Between August 2016 and May 2022, 74 patients were randomized (1:2) to IMRT/IGRT with standard (Control, n = 30) or reduced (Experimental, n = 44) margins. Control IGRT used cone-beam computed tomography (CBCT), while experimental IGRT combined CBCT with real-time tracking (Calypso® 4D Localization System) and smaller margins. Prostate margins were 3 mm in the Experimental arm versus 1 cm (0.5 cm posteriorly) in the Control arm. The primary endpoint was grade ≥ 2 LPT (CTCAE v4.03). Toxicities were assessed by physician-scored CTCAE and patient-reported quality-of-life outcomes.

Results

Grade ≥ 2 LPT occurred in 5 patients in each arm. Over the study period, 88.6 % (95 % CI: 75.4–96.2) of patients in the Experimental arm and 80.8 % (95 % CI: 60.6–93.4) in the Control arm did not experience a grade ≥ 2 LPT. Under conventional fractionation, the Experimental arm had significantly lower rectal (V70Gy, D50%) and bladder (D50%, V70Gy, V76Gy) doses (p < 0.01), but higher rectal (D1%, V76Gy) and bladder (V80Gy) doses (p < 0.01). At two years post-radiotherapy, urinary symptom scores were significantly lower in the Experimental arm (mean 12.3 vs. 21.2, p = 0.028).

Conclusion

IMRT/IGRT with reduced margins is feasible and may improve some dosimetric outcomes. Both arms had low LPT rates, but reduced margins may improve patient-reported urinary symptoms.
背景与目的:调强(IMRT)和图像引导(IGRT)放疗可降低局限性前列腺癌的放射毒性。这项随机II期试验(NCT03254420)评估了低至中危前列腺癌患者标准或缩小切缘IMRT/IGRT后的晚期盆腔毒性(LPT)和生活质量。材料和方法:2016年8月至2022年5月,74例患者随机(1:2)接受标准(对照,n = 30)或缩小(实验,n = 44)边缘的IMRT/IGRT治疗。对照IGRT使用锥束计算机断层扫描(CBCT),而实验IGRT将CBCT与实时跟踪(Calypso®4D定位系统)和较小的边缘相结合。实验组前列腺边缘为3 mm,对照组为1 cm(后置0.5 cm)。主要终点为 ≥ 2级LPT (CTCAE v4.03)。通过医生评分的CTCAE和患者报告的生活质量结果来评估毒性。结果:分级 ≥ 2级LPT每组5例发生。在研究期间,实验组中88.6% %(95 % CI: 75.4-96.2)的患者和对照组中80.8% %(95 % CI: 60.6-93.4)的患者没有经历 ≥ 2级LPT。在常规分割下,实验组直肠(V70Gy, D50%)和膀胱(D50%, V70Gy, V76Gy)剂量(p 1%,V76Gy)和膀胱(V80Gy)剂量(p )显著降低。结论:缩小切度的IMRT/IGRT是可行的,并可能改善某些剂量学结果。两组LPT发生率均较低,但切缘减少可能改善患者报告的泌尿系统症状。
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引用次数: 0
Local therapy with hypoxia-targeting radiopharmaceutical [64Cu]Cu-ATSM in high-grade glioma patient-derived xenograft models 低氧靶向放射性药物[64Cu]Cu-ATSM在高度胶质瘤患者来源的异种移植模型中的局部治疗
IF 5.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-07 DOI: 10.1016/j.radonc.2025.111325
Yukie Yoshii , Fukiko Hihara , Hiroki Matsumoto , Chika Igarashi , Tomoko Tachibana , Mitsuhiro Shinada , Makoto Ohtake , Hisashi Suzuki , Ming-Rong Zhang , Akito Oshima , Tomohiro Kaneta , Nobuhiro Nitta , Sayaka Shibata , Hidemitsu Sato , Kimiteru Ito , Yoshitaka Narita , Daniel P. Cahill , Hiroaki Wakimoto , Ukihide Tateishi , Hiroaki Kurihara , Kensuke Tateishi

Background

World Health Organization (WHO)-defined central nervous system (CNS) grade 4 high-grade gliomas (HGGs) are aggressive brain tumors marked by hypoxia and diffuse infiltration, which leaves residual tumor cells after surgery and drives inevitable local recurrence. Here, we propose a novel local therapeutic approach with 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) ([64Cu]Cu-ATSM), a hypoxia-targeting radiopharmaceutical, using HGG-patient-derived xenograft (PDX) models.

Methods

The maximum tolerated dose (MTD) of local injection of [64Cu]Cu-ATSM into the tumor was determined in mice via biodistribution, dosimetry, and toxicity analyses. Intratumoral distribution was evaluated using PET/CT and MRI in multiple HGG-PDX models recapitulating human tumor characteristics. Therapeutic efficacy was assessed by survival analysis, along with evaluation of DNA damage and apoptosis.

Results

The MTD of [64Cu]Cu-ATSM local injection was established at 3.7 MBq. PET/CT demonstrated rapid intratumoral penetration, widespread distribution, and prolonged retention of [64Cu]Cu-ATSM in HGG-PDX tumors. Local treatment significantly extended survival and induced pronounced DNA double-strand breaks and apoptosis within tumors.

Conclusion

Local injection of [64Cu]Cu-ATSM into the tumor is a novel therapeutic strategy for HGG-PDX models, which combines hypoxia-targeted radiotherapy with PET-based treatment monitoring to address residual tumor cells and improve therapeutic outcomes.
背景:世界卫生组织(WHO)定义的中枢神经系统(CNS) 4级高级别胶质瘤(HGGs)是一种侵袭性脑肿瘤,其特征是缺氧和弥漫性浸润,术后留下残留的肿瘤细胞,不可避免地导致局部复发。在这里,我们提出了一种新的局部治疗方法,使用hgg患者来源的异种移植(PDX)模型,使用低氧靶向放射性药物64Cu-二乙酰-双(n4 -甲基硫代氨基脲)([64Cu]Cu-ATSM)。方法:通过生物分布、剂量学和毒性分析,测定小鼠肿瘤局部注射[64Cu]Cu-ATSM的最大耐受剂量。利用PET/CT和MRI对多个重现人类肿瘤特征的HGG-PDX模型进行肿瘤内分布评估。通过生存分析评估治疗效果,同时评估DNA损伤和细胞凋亡。结果:[64Cu]Cu-ATSM局部注射MTD为3.7 MBq。PET/CT显示[64Cu]Cu-ATSM在HGG-PDX肿瘤中快速渗透、广泛分布、长时间滞留。局部治疗可显著延长生存期,并诱导肿瘤内DNA双链断裂和细胞凋亡。结论:肿瘤局部注射[64Cu]Cu-ATSM是一种新的治疗HGG-PDX模型的治疗策略,它将低氧靶向放疗与基于pet的治疗监测相结合,可以清除残留的肿瘤细胞,提高治疗效果。
{"title":"Local therapy with hypoxia-targeting radiopharmaceutical [64Cu]Cu-ATSM in high-grade glioma patient-derived xenograft models","authors":"Yukie Yoshii ,&nbsp;Fukiko Hihara ,&nbsp;Hiroki Matsumoto ,&nbsp;Chika Igarashi ,&nbsp;Tomoko Tachibana ,&nbsp;Mitsuhiro Shinada ,&nbsp;Makoto Ohtake ,&nbsp;Hisashi Suzuki ,&nbsp;Ming-Rong Zhang ,&nbsp;Akito Oshima ,&nbsp;Tomohiro Kaneta ,&nbsp;Nobuhiro Nitta ,&nbsp;Sayaka Shibata ,&nbsp;Hidemitsu Sato ,&nbsp;Kimiteru Ito ,&nbsp;Yoshitaka Narita ,&nbsp;Daniel P. Cahill ,&nbsp;Hiroaki Wakimoto ,&nbsp;Ukihide Tateishi ,&nbsp;Hiroaki Kurihara ,&nbsp;Kensuke Tateishi","doi":"10.1016/j.radonc.2025.111325","DOIUrl":"10.1016/j.radonc.2025.111325","url":null,"abstract":"<div><h3>Background</h3><div>World Health Organization (WHO)-defined central nervous system (CNS) grade 4 high-grade gliomas (HGGs) are aggressive brain tumors marked by hypoxia and diffuse infiltration, which leaves residual tumor cells after surgery and drives inevitable local recurrence. Here, we propose a novel local therapeutic approach with <sup>64</sup>Cu-diacetyl-bis(N4-methylthiosemicarbazone) ([<sup>64</sup>Cu]Cu-ATSM), a hypoxia-targeting radiopharmaceutical, using HGG-patient-derived xenograft (PDX) models.</div></div><div><h3>Methods</h3><div>The maximum tolerated dose (MTD) of local injection of [<sup>64</sup>Cu]Cu-ATSM into the tumor was determined in mice via biodistribution, dosimetry, and toxicity analyses. Intratumoral distribution was evaluated using PET/CT and MRI in multiple HGG-PDX models recapitulating human tumor characteristics.<!--> <!-->Therapeutic efficacy was assessed by survival analysis, along with evaluation of DNA damage and apoptosis.</div></div><div><h3>Results</h3><div>The MTD of [<sup>64</sup>Cu]Cu-ATSM local injection was established at 3.7 MBq. PET/CT demonstrated rapid intratumoral penetration, widespread distribution, and prolonged retention of [<sup>64</sup>Cu]Cu-ATSM in HGG-PDX tumors. Local treatment significantly extended survival and induced pronounced DNA double-strand breaks and apoptosis within tumors.</div></div><div><h3>Conclusion</h3><div>Local injection of [<sup>64</sup>Cu]Cu-ATSM into the tumor is a novel therapeutic strategy for HGG-PDX models, which combines hypoxia-targeted radiotherapy with PET-based treatment monitoring to address residual tumor cells and improve therapeutic outcomes.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111325"},"PeriodicalIF":5.3,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715706","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
Systemic complement protein levels as biomarkers of chemoradiotherapy response in anal squamous cell carcinoma 全身补体蛋白水平作为肛门鳞状细胞癌放化疗反应的生物标志物。
IF 5.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-07 DOI: 10.1016/j.radonc.2025.111324
D. Majorova , R. Samuel , R. Muirhead , A. Hasson , DJ. MacLean , F. Ismail , EJ. Cheadle , C. Jacobs , D. Halliday , M. Saunders , BD. Nicholson , E. O’Neill , D. Sebag-Montefiore , A. Samson , MM. Olcina

Background

Identification of easily measurable biomarkers that are able to predict locoregional failure or disease progression following chemoradiotherapy (CRT) would enable more personalised cancer management. Anal squamous cell cancer (ASCC) is the most common type of anal cancer, accounting for approximately 90% of all cases. While CRT is the standard of care for most locally advanced anal cancers, treatment failure occurs in up to 30% of patients. However, it is currently difficult to predict which patients will fail to respond to treatment, highlighting the need for predictive biomarkers. This study aims to assess whether plasma levels of complement proteins can serve as potential biomarkers of treatment response.

Materials and Methods

Serial peripheral blood samples from ASCC patients (n = 40) were collected before, during, and after CRT, alongside 6-month clinical and radiological outcomes. Using multiplex ELISA-based technology, we assessed levels of 14 complement proteins at baseline, during CRT, and 3 months post-CRT. Additionally, the same technology was used to compare levels of complement analytes in ASCC and in age- and sex-matched patients without a cancer diagnosis.

Results

Our data indicate that CRT decreases levels of most complement analytes measured, with intact C2, intact C3, intact C5, C3a, C5a, Ba, Bb, SC5b9, Factor D, Factor H, Factor I, and Factor P decreasing 3 months after treatment specifically in those patients achieving complete responses (all p < 0.05). Moreover, the treatment failure group showed changes indicative of persistent alternative complement pathway activation, with a less pronounced decline following CRT compared to responders. Furthermore, intact C2 and intact C5 levels were significantly higher in ASCC patients compared to age- and sex-matched patients without a cancer diagnosis (both p < 0.005). In contrast, C3a and C4a were expressed at higher levels in patients without cancer diagnosis compared to ASCC patients (both p < 0.02). Importantly, patients in the treatment failure group had elevated baseline (pre-treatment) levels of intact C2 and Factor D compared to those achieving complete response (both p < 0.03).

Conclusions

These findings suggest that dysregulation of the complement system, particularly involving the alternative pathway, may be more prevalent in patients with a poor treatment response. Intact C2 and Factor D may represent potential markers of treatment failure.
背景:确定易于测量的生物标志物,能够预测放化疗(CRT)后的局部区域失败或疾病进展,将实现更个性化的癌症管理。肛门鳞状细胞癌(ASCC)是最常见的肛门癌类型,约占所有病例的90%。虽然CRT是大多数局部晚期肛门癌的标准治疗方法,但高达30%的患者出现治疗失败。然而,目前很难预测哪些患者对治疗没有反应,这突出了对预测性生物标志物的需求。本研究旨在评估血浆补体蛋白水平是否可以作为治疗反应的潜在生物标志物。材料和方法:收集ASCC患者(n = 40)在CRT之前,期间和之后的一系列外周血样本,以及6个月的临床和放射学结果。使用基于多重elisa的技术,我们在基线、CRT期间和CRT后3个 月评估了14种补体蛋白的水平。此外,同样的技术被用于比较ASCC和年龄和性别匹配的无癌症诊断患者的补体分析物水平。结果:我们的数据表明,CRT降低了大多数补体分析物的水平,在治疗后3 个月,特别是在那些获得完全缓解的患者中,完整的C2、完整的C3、完整的C5、C3a、C5a、Ba、Bb、SC5b9、因子D、因子H、因子I和因子P下降(所有P )。结论:这些发现表明补体系统失调,特别是涉及替代途径,可能在治疗反应较差的患者中更为普遍。完整的C2和因子D可能是治疗失败的潜在标志。
{"title":"Systemic complement protein levels as biomarkers of chemoradiotherapy response in anal squamous cell carcinoma","authors":"D. Majorova ,&nbsp;R. Samuel ,&nbsp;R. Muirhead ,&nbsp;A. Hasson ,&nbsp;DJ. MacLean ,&nbsp;F. Ismail ,&nbsp;EJ. Cheadle ,&nbsp;C. Jacobs ,&nbsp;D. Halliday ,&nbsp;M. Saunders ,&nbsp;BD. Nicholson ,&nbsp;E. O’Neill ,&nbsp;D. Sebag-Montefiore ,&nbsp;A. Samson ,&nbsp;MM. Olcina","doi":"10.1016/j.radonc.2025.111324","DOIUrl":"10.1016/j.radonc.2025.111324","url":null,"abstract":"<div><h3>Background</h3><div>Identification of easily measurable biomarkers that are able to predict locoregional failure or disease progression following chemoradiotherapy (CRT) would enable more personalised cancer management. Anal squamous cell cancer (ASCC) is the most common type of anal cancer, accounting for approximately 90% of all cases. While CRT is the standard of care for most locally advanced anal cancers, treatment failure occurs in up to 30% of patients. However, it is currently difficult to predict which patients will fail to respond to treatment, highlighting the need for predictive biomarkers. This study aims to assess whether plasma levels of complement proteins can serve as potential biomarkers of treatment response.</div></div><div><h3>Materials and Methods</h3><div>Serial peripheral blood samples from ASCC patients (n = 40) were collected before, during, and after CRT, alongside 6-month clinical and radiological outcomes. Using multiplex ELISA-based technology, we assessed levels of 14 complement proteins at baseline, during CRT, and 3 months post-CRT. Additionally, the same technology was used to compare levels of complement analytes in ASCC and in age- and sex-matched patients without a cancer diagnosis.</div></div><div><h3>Results</h3><div>Our data indicate that CRT decreases levels of most complement analytes measured, with intact C2, intact C3, intact C5, C3a, C5a, Ba, Bb, SC5b9, Factor D, Factor H, Factor I, and Factor P decreasing 3 months after treatment specifically in those patients achieving complete responses (all p &lt; 0.05). Moreover, the treatment failure group showed changes indicative of persistent alternative complement pathway activation, with a less pronounced decline following CRT compared to responders. Furthermore, intact C2 and intact C5 levels were significantly higher in ASCC patients compared to age- and sex-matched patients without a cancer diagnosis (both p &lt; 0.005). In contrast, C3a and C4a were expressed at higher levels in patients without cancer diagnosis compared to ASCC patients (both p &lt; 0.02). Importantly, patients in the treatment failure group had elevated baseline (pre-treatment) levels of intact C2 and Factor D compared to those achieving complete response (both p &lt; 0.03).</div></div><div><h3>Conclusions</h3><div>These findings suggest that dysregulation of the complement system, particularly involving the alternative pathway, may be more prevalent in patients with a poor treatment response. Intact C2 and Factor D may represent potential markers of treatment failure.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111324"},"PeriodicalIF":5.3,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715740","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
Clustering of dosimetric profiles reveals distinct local control probabilities after SABR in oligometastatic head and neck cancer: insights from the OMET phase II trial quality assurance Process 聚类剂量谱揭示了寡转移性头颈癌SABR后不同的局部控制概率:来自OMET II期试验质量保证过程的见解
IF 5.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-04 DOI: 10.1016/j.radonc.2025.111316
P. Maury , Y. Sayous , D. Vernerey , X.S. Sun , J. Bourhis , A. Falcoz , J. Thariat

Background

Stereotactic ablative radiotherapy (SABR) is increasingly used in the management of oligometastatic disease. However, variability in SABR plans raises questions about their impact on local control at SABR-treated lesions (LC). We aimed to explore whether quantitative dosimetric parameters could predict LC in head and neck squamous cell carcinoma (HNSCC) patients in the OMET (GORTEC 2014–04) trial.

Methods

OMET is a multicentre randomized phase II trial comparing SABR-alone versus chemo-SABR in patients with ≤ 3 PET-confirmed oligometastases. A post-hoc analysis of all irradiated lesions (N = 98) from 69 patients was performed. Twenty spatial and dosimetric indices, together with conventional metrics including Dmin, Dmean, Dmax, total target volume and homogeneity/conformity indices, were extracted from the DICOM files. Hierarchical clustering was used to identify phenotypes of plan quality. Kaplan–Meier analyses evaluated associations with LC.

Results

Wide inter-patient variability in dosimetric parameters and three clusters was observed, despite SABR standardization per trial protocol. The cluster of lesions (N = 13) with high intra-tumoral dose heterogeneity and non-optimal conformity was associated with significantly improved LC. In contrast, a more homogeneous and conformal phenotype was linked to inferior LC (N = 14). The largest cluster (N = 69) showed no clearly distinctive pattern and had intermediate LC.

Conclusions

In SABR for oligometastatic HNSCC, intra-tumoral dose heterogeneity may be more predictive of LC than strict conformity, particularly in high-dose per fraction regimens. A quantitative, phenotype-based machine learning approach using unsupervised clustering of composite dosimetric metrics may be explored further within SABR quality assurance frameworks beyond binary expert review alone.
背景立体定向消融放疗(SABR)越来越多地用于治疗少转移性疾病。然而,SABR计划的可变性引发了对SABR治疗病变(LC)局部控制影响的疑问。在OMET (GORTEC 2014-04)试验中,我们旨在探讨定量剂量学参数是否可以预测头颈部鳞状细胞癌(HNSCC)患者的LC。方法:somet是一项多中心随机II期试验,比较sabr单用与化疗联合sabr治疗≤3个pet证实的低转移灶患者的疗效。对69例患者的所有辐照病灶(N = 98)进行事后分析。从DICOM文件中提取20个空间和剂量学指标,以及常规指标,包括Dmin、Dmean、Dmax、总靶体积和均匀性/一致性指标。采用分层聚类方法鉴定计划质量表型。Kaplan-Meier分析评估了与LC的关联。结果尽管SABR对每个试验方案进行了标准化,但仍观察到剂量学参数和三个聚类的患者间差异。肿瘤内剂量异质性高且非最佳符合性的病变簇(N = 13)与LC显著改善相关。相比之下,更均匀和适形的表型与较差的LC有关(N = 14)。最大的星团(N = 69)没有明显的特征,具有中度LC。结论:在低转移性HNSCC的SABR中,肿瘤内剂量异质性可能比严格的一致性更能预测LC,特别是在高剂量/分数方案中。在SABR质量保证框架内,除了单独的二元专家审查之外,还可以进一步探索使用复合剂量计量的无监督聚类的定量、基于表型的机器学习方法。
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引用次数: 0
ESTRO-ISRS clinical practice recommendations for re-irradiation of spinal metastases with Stereotactic Body Radiotherapy: Delphi consensus supported by a systematic review and meta-analysis ESTRO-ISRS对脊柱转移灶立体定向放射治疗再照射的临床实践建议:系统回顾和荟萃分析支持德尔菲共识。
IF 5.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-02 DOI: 10.1016/j.radonc.2025.111304
Filippo Alongi , Francesco Cuccia , Rupesh Kotecha , Marina Campione , Alexander V. Louie , Lijun Ma , Giuseppe Minniti , Alison C. Tree , Max Dahele , Simon Lo , Per Munck af Rosenschold , John H. Suh , Maximilian Niyazi , Jason Sheehan , Matthias Guckenberger , Arjun Sahgal

Background

Stereotactic body radiotherapy (SBRT) is an established treatment for previously unirradiated spinal metastases; however, the literature is limited with respect to SBRT as a re-irradiation salvage therapy. We performed a systematic review and meta-analysis as basis for joint ESTRO-ISRS clinical practice recommendations of salvage SBRT for spinal metastases.

Methods

A systematic review and meta-analysis were performed using PRISMA methodology, including publications from January 2006 to September 2024, reporting on the clinical outcomes of ≥ 5 patients treated with spine SBRT re-irradiation (≥5 Gy per fraction) for vertebral metastases. These data served as basis for joint ESTRO-ISRS clinical practice recommendations.

Results

After the initial article screen, 20 studies (5 prospective, 15 retrospective) met the inclusion criteria for analysis. A total of 1538 spine metastases were treated in 1284 patients. The median re-irradiation dose was 24 Gy in 2 fractions (range: 16–30 Gy in 1–5 fractions) after a median 30 Gy in 10 fractions of prior conventional radiotherapy. Vertebral compression fracture, nerve root damage, and myelopathy events were observed in a pooled proportion of 5.0 %, 5.6 %, and 1.7 %, respectively. With a median follow-up of 12 months, the pooled 1- and 2-year LC rates were 81 % (95 % CI: 77–86 %) and 70 % (95 % CI: 61–79 %), respectively. Despite the low level of evidence, a consensus was reached after the first round of voting for 11 practice recommendations, suggesting a substantial level of agreement among the experts.

Conclusions

Re-irradiation with SBRT for spine metastases following prior conventional radiation or SBRT was efficacious, safe, and is a recommended treatment option in appropriately selected patients. Joint practice recommendations are provided on behalf of ESTRO and ISRS to guide clinical practice.
背景:立体定向放射治疗(SBRT)是先前未放疗的脊柱转移的一种既定治疗方法;然而,关于SBRT作为再照射补救性治疗的文献有限。我们进行了系统回顾和荟萃分析,作为ESTRO-ISRS联合临床实践推荐的脊髓转移性SBRT的基础。方法:采用PRISMA方法进行系统回顾和荟萃分析,包括2006年1月至2024年9月的出版物,报告 ≥ 5例脊柱SBRT再照射(每分数≥5 Gy)治疗椎体转移的临床结果。这些数据作为ESTRO-ISRS联合临床实践建议的基础。结果:经过最初的文章筛选,20项研究(5项前瞻性研究,15项回顾性研究)符合纳入标准。1284例患者共治疗了1538例脊柱转移瘤。既往常规放疗10次中位再照射剂量为30 Gy,再照射剂量中位为2次24 Gy(范围:16-30 Gy, 1-5次)。椎骨压缩性骨折、神经根损伤和脊髓病事件的合并比例分别为5.0 %、5.6 %和1.7 %。中位随访时间为12 个月,1年和2年总LC率分别为81 %(95 % CI: 77-86 %)和70 %(95 % CI: 61-79 %)。尽管证据水平较低,但在第一轮投票后,对11项实践建议达成了共识,这表明专家之间达成了相当程度的一致。结论:在先前的常规放疗或SBRT之后再用SBRT治疗脊柱转移是有效、安全的,并且在适当选择的患者中是一种推荐的治疗选择。代表ESTRO和ISRS提供联合实践建议,以指导临床实践。
{"title":"ESTRO-ISRS clinical practice recommendations for re-irradiation of spinal metastases with Stereotactic Body Radiotherapy: Delphi consensus supported by a systematic review and meta-analysis","authors":"Filippo Alongi ,&nbsp;Francesco Cuccia ,&nbsp;Rupesh Kotecha ,&nbsp;Marina Campione ,&nbsp;Alexander V. Louie ,&nbsp;Lijun Ma ,&nbsp;Giuseppe Minniti ,&nbsp;Alison C. Tree ,&nbsp;Max Dahele ,&nbsp;Simon Lo ,&nbsp;Per Munck af Rosenschold ,&nbsp;John H. Suh ,&nbsp;Maximilian Niyazi ,&nbsp;Jason Sheehan ,&nbsp;Matthias Guckenberger ,&nbsp;Arjun Sahgal","doi":"10.1016/j.radonc.2025.111304","DOIUrl":"10.1016/j.radonc.2025.111304","url":null,"abstract":"<div><h3>Background</h3><div>Stereotactic body radiotherapy (SBRT) is an established treatment for previously unirradiated spinal metastases; however, the literature is limited with respect to SBRT as a re-irradiation salvage therapy. We performed a systematic review and <em>meta</em>-analysis as basis for joint ESTRO-ISRS clinical practice recommendations of salvage SBRT for spinal metastases.</div></div><div><h3>Methods</h3><div>A systematic review and <em>meta</em>-analysis were performed using PRISMA methodology, including publications from January 2006 to September 2024, reporting on the clinical outcomes of ≥ 5 patients treated with spine SBRT re-irradiation (≥5 Gy per fraction) for vertebral metastases. These data served as basis for joint ESTRO-ISRS clinical practice recommendations.</div></div><div><h3>Results</h3><div>After the initial article screen, 20 studies (5 prospective, 15 retrospective) met the inclusion criteria for analysis. A total of 1538 spine metastases were treated in 1284 patients. The median re-irradiation dose was 24 Gy in 2 fractions (range: 16–30 Gy in 1–5 fractions) after a median 30 Gy in 10 fractions of prior conventional radiotherapy. Vertebral compression fracture, nerve root damage, and myelopathy events were observed in a pooled proportion of 5.0 %, 5.6 %, and 1.7 %, respectively. With a median follow-up of 12 months, the pooled 1- and 2-year LC rates were 81 % (95 % CI: 77–86 %) and 70 % (95 % CI: 61–79 %), respectively. Despite the low level of evidence, a consensus was reached after the first round of voting for 11 practice recommendations, suggesting a substantial level of agreement among the experts.</div></div><div><h3>Conclusions</h3><div>Re-irradiation with SBRT for spine metastases following prior conventional radiation or SBRT was efficacious, safe, and is a recommended treatment option in appropriately selected patients. Joint practice recommendations are provided on behalf of ESTRO and ISRS to guide clinical practice.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111304"},"PeriodicalIF":5.3,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678629","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
Acute toxicity and quality of life after 5-fraction versus 15-fraction adjuvant radiotherapy following conventional or oncoplastic breast-conserving surgery − a real-world prospective cohort study 常规或癌性保乳手术后5分次和15分次辅助放疗的急性毒性和生活质量——一项现实世界前瞻性队列研究
IF 5.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-11-30 DOI: 10.1016/j.radonc.2025.111310
Dieuwke R. Mink van der Molen , Marilot C.T. Batenburg , Tanja van ’t Westeinde , Antonetta C. Houweling , Wies Maarse , Karolien Verhoeven , Jennifer Strijbos , Lars Murrer , Sabine Siesling , Evelyn M. Monninkhof , Helena M. Verkooijen , Liesbeth J. Boersma , Femke van der Leij , UMBRELLA study group

Background and purpose

The FAST-Forward trial demonstrated that 26 Gy in 5 fractions for whole breast irradiation (WBI) has similar outcomes as 40 Gy in 15 fractions. Since radiation treatment plans in the Netherlands in general deliver higher target doses, we aimed to compare acute toxicity and quality of life of the adjuvant 26 Gy and the 40 Gy schedules in a real-world setting, including after oncoplastic surgery.

Materials and methods

Eligible were women ≥50 years with breast cancer receiving WBI or partial breast irradiation (PBI) between 2018 and 2023 in two Dutch centres, with either 26 Gy/5 fractions in 1 week or 40 Gy/15 fractions in 3 weeks. Acute toxicity was assessed using CTCAE v5.0 during and ≤ 4 weeks following radiotherapy. Patient-reported outcomes were evaluated using EORTC-QLQ-C30/BR23 prior to radiotherapy, at 3 months and 1 year post-radiotherapy.

Results

In total, 832 patients received 26 Gy/5 fractions (70.2% WBI, 12.9% oncoplastic surgery) and 845 patients 40 Gy/15 fractions (81.9% WBI, 14.2% oncoplastic surgery). For WBI and PBI, grade ≥ 1 dermatitis and fatigue were less common after 26 Gy than 40 Gy: 61–67 % versus 86–91% and 42–43% versus 56% respectively (p < 0.001–0.005). After oncoplastic surgery, 26 Gy patients less often experienced grade ≥ 1 dermatitis than 40 Gy patients (77% vs 94%, p < 0.001). At 3 months and 1-year post-radiotherapy, 26 Gy and 40 Gy patients reported comparable patient-reported outcomes.

Conclusion

We confirmed the safety of the 26 Gy/5 fractions schedule in terms of acute toxicity and quality of life compared to the 40 Gy/15 fractions schedule, also when treated with higher target coverage and following oncoplastic breast-conserving surgery.
背景和目的:FAST-Forward试验表明,全乳照射(WBI)的5次剂量26 Gy与15次剂量40 Gy的效果相似。由于荷兰的放射治疗计划通常提供更高的目标剂量,我们的目的是在现实环境中,包括肿瘤整形手术后,比较26 Gy和40 Gy辅助方案的急性毒性和生活质量。材料和方法:符合条件的是在2018年至2023年期间在两个荷兰中心接受WBI或部分乳房照射(PBI)的≥50 岁乳腺癌妇女,在1 周内接受26 Gy/5分数或在3 周内接受40 Gy/15分数。放疗期间及放疗后 ≤ 4周采用CTCAE v5.0评价急性毒性。在放疗前,放疗后3 个月和1 年,使用EORTC-QLQ-C30/BR23评估患者报告的结果。结果:832例患者接受了26次 Gy/5(70.2 % WBI, 12.9 %肿瘤整形手术),845例患者接受了40次 Gy/15(81.9 % WBI, 14.2 %肿瘤整形手术)。WBI和PBI 年级≥1 皮炎和疲劳后被不太常见的26比40 Gy Gy: 86 - 91 61 - 67 %与 %和42-43 分别%和56 % (p 结论:我们确认26 Gy / 5分数的安全安排的急性毒性和生活质量相比40 Gy / 15分数时间表,也当处理更高目标覆盖率和oncoplastic后手术。
{"title":"Acute toxicity and quality of life after 5-fraction versus 15-fraction adjuvant radiotherapy following conventional or oncoplastic breast-conserving surgery − a real-world prospective cohort study","authors":"Dieuwke R. Mink van der Molen ,&nbsp;Marilot C.T. Batenburg ,&nbsp;Tanja van ’t Westeinde ,&nbsp;Antonetta C. Houweling ,&nbsp;Wies Maarse ,&nbsp;Karolien Verhoeven ,&nbsp;Jennifer Strijbos ,&nbsp;Lars Murrer ,&nbsp;Sabine Siesling ,&nbsp;Evelyn M. Monninkhof ,&nbsp;Helena M. Verkooijen ,&nbsp;Liesbeth J. Boersma ,&nbsp;Femke van der Leij ,&nbsp;UMBRELLA study group","doi":"10.1016/j.radonc.2025.111310","DOIUrl":"10.1016/j.radonc.2025.111310","url":null,"abstract":"<div><h3>Background and purpose</h3><div>The FAST-Forward trial demonstrated that 26 Gy in 5 fractions for whole breast irradiation (WBI) has similar outcomes as 40 Gy in 15 fractions. Since radiation treatment plans in the Netherlands in general deliver higher target doses, we aimed to compare acute toxicity and quality of life of the adjuvant 26 Gy and the 40 Gy schedules in a real-world setting, including after oncoplastic surgery.</div></div><div><h3>Materials and methods</h3><div>Eligible were women ≥50 years with breast cancer receiving WBI or partial breast irradiation (PBI) between 2018 and 2023 in two Dutch centres, with either 26 Gy/5 fractions in 1 week or 40 Gy/15 fractions in 3 weeks. Acute toxicity was assessed using CTCAE v5.0 during and ≤ 4 weeks following radiotherapy. Patient-reported outcomes were evaluated using EORTC-QLQ-C30/BR23 prior to radiotherapy, at 3 months and 1 year post-radiotherapy.</div></div><div><h3>Results</h3><div>In total, 832 patients received 26 Gy/5 fractions (70.2% WBI, 12.9% oncoplastic surgery) and 845 patients 40 Gy/15 fractions (81.9% WBI, 14.2% oncoplastic surgery). For WBI and PBI, grade ≥ 1 dermatitis and fatigue were less common after 26 Gy than 40 Gy: 61–67 % versus 86–91% and 42–43% versus 56% respectively (p &lt; 0.001–0.005). After oncoplastic surgery, 26 Gy patients less often experienced grade ≥ 1 dermatitis than 40 Gy patients (77% vs 94%, p &lt; 0.001). At 3 months and 1-year post-radiotherapy, 26 Gy and 40 Gy patients reported comparable patient-reported outcomes.</div></div><div><h3>Conclusion</h3><div>We confirmed the safety of the 26 Gy/5 fractions schedule in terms of acute toxicity and quality of life compared to the 40 Gy/15 fractions schedule, also when treated with higher target coverage and following oncoplastic breast-conserving surgery.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111310"},"PeriodicalIF":5.3,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661764","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
Quality of life and late toxicity after total neoadjuvant treatment for locally advanced rectal cancer – LARCT-US 局部晚期直肠癌新辅助治疗后的生活质量和晚期毒性——LARCT-US
IF 5.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-11-28 DOI: 10.1016/j.radonc.2025.111318
Israa Imam , Tanweera Khan , Per J Nilsson , Bengt Glimelius

Introduction

Total neoadjuvant therapy (TNT) is increasingly used to treat locally advanced rectal cancer (LARC) due to more complete responses and fewer systemic recurrences. However, its impact on quality-of-life (QoL) or late toxicity remains under-investigated. This study evaluates this in a large real-world Swedish cohort treated with an abbreviated RAPIDO-TNT-protocol (LARCT-US).

Material and methods

In the prospective LARCT-US study, 273 LARC patients from 16 Swedish hospitals received short-course radiotherapy (5x5 Gy) followed by four cycles of CAPOX (or six cycles of mFOLFOX-6). An additional 189 patients who received similar treatment were included (ad modum LARCT-US, AdmL). QoL was assessed three years post-treatment using EORTC QLQ-C30, QLQ-CR29 and bowel function using the LARS-score. Physician-reported grade 3+ late toxicity was recorded at three- and five-years follow-up.

Results

Of curatively treated recurrence-free LARCT-US patients, 144/176 (82%) were included in the QoL assessment. Global health score (GHS) and all functioning scores were high (mean 73 and ∼86, respectively). Flatulence, urinary frequency, and fatigue were the most commonly reported symptoms. LARS was present in 79% of patients (n = 42/53), with 47% experiencing major LARS. Grade 3+ late toxicity occurred in 12% (n = 33/265) of LARCT-US/AdmL patients after three years and in 8% (n = 16/254) after five years. Patients with late toxicity reported worse scores for GHS, fatigue, dysuria, financial difficulties, and role and social functioning.

Conclusions

An abbreviated TNT schedule, compared with the RAPIDO-study, used in LARCT-US, achieves favourable oncological outcomes with low risk of late toxicity, and an acceptable QoL similar to other less effective neoadjuvant treatments.
全新辅助治疗(TNT)越来越多地用于局部晚期直肠癌(LARC)的治疗,因为其更完全的反应和更少的全身复发。然而,其对生活质量(QoL)或晚期毒性的影响仍未得到充分研究。本研究在一个大型现实世界瑞典队列中进行了简短的rapido - tnt协议(LARCT-US)的评估。材料和方法:在前瞻性LARCT-US研究中,来自瑞典16家医院的273名LARC患者接受了短期放疗(5x5 Gy),随后接受了4个周期的CAPOX(或6个周期的mFOLFOX-6)。另外189名接受类似治疗的患者被纳入研究(LARCT-US, AdmL)。使用EORTC QLQ-C30、QLQ-CR29评估治疗后3年的生活质量,使用lars评分评估肠道功能。医生报告的3级 + 晚期毒性在3年和5年随访中记录。结果:在治愈无复发的LARCT-US患者中,144/176(82% %)被纳入QoL评估。总体健康评分(GHS)和所有功能评分都很高(平均分别为73分和 ~ 86分)。肠胃胀气、尿频和疲劳是最常见的症状。79% %的患者出现LARS (n = 42/53),其中47% %的患者出现重度LARS。3级 + 晚期毒性发生在12 % (n = 33/265)的LARCT-US/AdmL患者中,5年后发生在8 % (n = 16/254)的患者中。晚期毒性患者报告GHS、疲劳、排尿困难、经济困难、角色和社会功能评分较差。结论:与LARCT-US中使用的rapido研究相比,缩短的TNT计划获得了良好的肿瘤学结果,晚期毒性风险低,生活质量与其他效果较差的新辅助治疗相似。
{"title":"Quality of life and late toxicity after total neoadjuvant treatment for locally advanced rectal cancer – LARCT-US","authors":"Israa Imam ,&nbsp;Tanweera Khan ,&nbsp;Per J Nilsson ,&nbsp;Bengt Glimelius","doi":"10.1016/j.radonc.2025.111318","DOIUrl":"10.1016/j.radonc.2025.111318","url":null,"abstract":"<div><h3>Introduction</h3><div>Total neoadjuvant therapy (TNT) is increasingly used to treat locally advanced rectal cancer (LARC) due to more complete responses and fewer systemic recurrences. However, its impact on quality-of-life (QoL) or late toxicity remains under-investigated. This study evaluates this in a large real-world Swedish cohort treated with an abbreviated RAPIDO-TNT-protocol (LARCT-US).</div></div><div><h3>Material and methods</h3><div>In the prospective LARCT-US study, 273 LARC patients from 16 Swedish hospitals received short-course radiotherapy (5x5 Gy) followed by four cycles of CAPOX (or six cycles of mFOLFOX-6). An additional 189 patients who received similar treatment were included (<em>ad modum</em> LARCT-US, AdmL). QoL was assessed three years post-treatment using EORTC QLQ-C30, QLQ-CR29 and bowel function using the LARS-score. Physician-reported grade 3+ late toxicity was recorded at three- and five-years follow-up.</div></div><div><h3>Results</h3><div>Of curatively treated recurrence-free LARCT-US patients, 144/176 (82%) were included in the QoL assessment. Global health score (GHS) and all functioning scores were high (mean 73 and ∼86, respectively). Flatulence, urinary frequency, and fatigue were the most commonly reported symptoms. LARS was present in 79% of patients (n = 42/53), with 47% experiencing major LARS. Grade 3+ late toxicity occurred in 12% (n = 33/265) of LARCT-US/AdmL patients after three years and in 8% (n = 16/254) after five years. Patients with late toxicity reported worse scores for GHS, fatigue, dysuria, financial difficulties, and role and social functioning.</div></div><div><h3>Conclusions</h3><div>An abbreviated TNT schedule, compared with the RAPIDO-study, used in LARCT-US, achieves favourable oncological outcomes with low risk of late toxicity, and an acceptable QoL similar to other less effective neoadjuvant treatments.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111318"},"PeriodicalIF":5.3,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649236","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
Impact of dose and dose-averaged linear energy transfer on oro-pharyngeal-mucosal toxicity in patients with non-squamous head and neck cancers treated with carbon-ion radiotherapy 剂量和剂量平均线性能量转移对接受碳离子放疗的非鳞状头颈癌患者口咽粘膜毒性的影响
IF 5.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-11-28 DOI: 10.1016/j.radonc.2025.111314
Ankita Nachankar , Joanna Gora , Mansure Schafasand , Martina Fuß , Eugen Hug , Antonio Carlino , Carola Lütgendorf-Caucig , Markus Stock , Piero Fossati

Background

In head and neck carbon-ion radiotherapy (CIRT), high dose-averaged LET (LETd) and relative biological effectiveness weighted dose (DRBE) often overlap the oro-pharyngeal-mucosa (mucosa of oral cavity, oro-pharynx, nasopharynx, pharynx) beyond the target, resulting in serious complications. We investigated clinical and dosimetric predictors for late severe mucosal-toxicity/ oro-antral fistula (OAF) post-CIRT.

Materials and methods

CIRT plans for 51 patients with non-squamous head and neck cancers (NSHNCs) were evaluated and correlated with clinical outcome. Prescription was DRBE of 68.8 Gy (65.6–76.8)/16 fractions optimized using Local Effect Model-I (LEM-I). After the first 21 patients a mucosa-sparing approach (MS-CIRT) was adopted, delineating healthy mucosa-to-spare within the high-dose PTV and applying DRBE constraints (DRBE|0.1cm3 < 70 Gy), maintaining target coverage. For the present analysis, DRBE was recomputed also with the modified microdosimetric kinetic model (mMKM) and LETd was calculated. Several clinical and dosimetric parameters including DLV-parameters (61 Gy ≤ DRBE ≤ 70 Gy, LETd ≥ 50 keV/µm, volume) that may be predictors of OAF were analyzed.

Results

MS-CIRT reduced mucosal doses to < 70 Gy, preserving local control (preliminary results in limited number of patients). Seven patients developed late G3 OAF after median follow-up of 23 months, including 2 with MS-CIRT. Doses to oro-pharyngeal mucosa > 70 Gy were predictive of OAF development. Even moderate-high doses correlated with OAF if they coincided with high-LETd. For instance, when more than 1 cm3 of mucosa-to-spare was exposed to DRBE|mMKM ≥ 63 Gy and LETd ≥ 75 keV/µm, 2-yr OAF-free survival probability was 38 % versus 100 % in cases where these thresholds were not exceeded (p < 0.001). Sino-nasal primary and HD–CTV ≥ 100 cm3 also influenced OAF development.

Conclusion

Besides MS-CIRT strategy, optimizing DLV-parameters for oro-pharyngeal-mucosa may be a promising strategy in preventing late G3 OAF post-CIRT.
背景:在头颈部碳离子放疗(CIRT)中,高剂量平均LET (LETd)和相对生物有效性加权剂量(DRBE)经常重叠超出靶标的口腔-咽-粘膜(口腔、口腔-咽、鼻咽、咽粘膜),导致严重并发症。我们研究了cirt后晚期严重粘膜毒性/口-心房瘘(OAF)的临床和剂量学预测因素。材料和方法:对51例非鳞状头颈癌(NSHNCs)患者的CIRT计划进行评估,并与临床结果相关联。处方DRBE为68.8 Gy(65.6-76.8)/16个分数,采用局部效应模型i (LEM-I)优化。在前21例患者后,采用粘膜保留入路(MS-CIRT),划定高剂量PTV内的健康粘膜,并应用DRBE约束(DRBE|0.1 1cm3 ),并使用改进的微剂量动力学模型(mMKM)重新计算RBE,并计算LETd。一些临床和剂量测定的参数包括DLV-parameters(61 Gy ≤ DRBE ≤ 70 Gy, LETd ≥50  keV /µm,卷),可能是畸形儿的预测进行了分析。结果:MS-CIRT将黏膜剂量降低至70  Gy可预测OAF的发展。即使是中高剂量也与OAF相关,如果它们与高led同时发生的话。例如,当超过1 立方厘米的mucosa-to-spare被暴露在DRBE | mMKM ≥63  Gy和LETd ≥ 75 keV /µm, OAF-free时颁发新加坡莱佛士学院集团与生存概率是38 %与100 %在这些阈值的情况下不超过(p 3也影响畸形儿的发展。结论:除了MS-CIRT策略外,优化口腔-咽-粘膜dlv参数可能是预防cirt后晚期G3 OAF的一种有希望的策略。
{"title":"Impact of dose and dose-averaged linear energy transfer on oro-pharyngeal-mucosal toxicity in patients with non-squamous head and neck cancers treated with carbon-ion radiotherapy","authors":"Ankita Nachankar ,&nbsp;Joanna Gora ,&nbsp;Mansure Schafasand ,&nbsp;Martina Fuß ,&nbsp;Eugen Hug ,&nbsp;Antonio Carlino ,&nbsp;Carola Lütgendorf-Caucig ,&nbsp;Markus Stock ,&nbsp;Piero Fossati","doi":"10.1016/j.radonc.2025.111314","DOIUrl":"10.1016/j.radonc.2025.111314","url":null,"abstract":"<div><h3>Background</h3><div>In head and neck carbon-ion radiotherapy (CIRT), high dose-averaged LET (LETd) and relative biological effectiveness weighted dose (D<sub>RBE</sub>) often overlap the oro-pharyngeal-mucosa (mucosa of oral cavity, oro-pharynx, nasopharynx, pharynx) beyond the target, resulting in serious complications. We investigated clinical and dosimetric predictors for late severe mucosal-toxicity/ oro-antral fistula (OAF) post-CIRT.</div></div><div><h3>Materials and methods</h3><div>CIRT plans for 51 patients with non-squamous head and neck cancers (NSHNCs) were evaluated and correlated with clinical outcome. Prescription was D<sub>RBE</sub> of 68.8 Gy (65.6–76.8)/16 fractions optimized using Local Effect Model-I (LEM-I). After the first 21 patients a mucosa-sparing approach (MS-CIRT) was adopted, delineating healthy mucosa-to-spare within the high-dose PTV and applying D<sub>RBE</sub> constraints (D<sub>RBE|0.1cm</sub><sub>3</sub> &lt; 70 Gy), maintaining target coverage. For the present analysis, D<sub>RBE</sub> was recomputed also with the modified microdosimetric kinetic model (mMKM) and LETd was calculated. Several clinical and dosimetric parameters including DLV-parameters (61 Gy ≤ D<sub>RBE</sub> ≤ 70 Gy, LETd ≥ 50 keV/µm, volume) that may be predictors of OAF were analyzed.</div></div><div><h3>Results</h3><div>MS-CIRT reduced mucosal doses to &lt; 70 Gy, preserving local control (preliminary results in limited number of patients). Seven patients developed late G3 OAF after median follow-up of 23 months, including 2 with MS-CIRT. Doses to oro-pharyngeal mucosa &gt; 70 Gy were predictive of OAF development. Even moderate-high doses correlated with OAF if they coincided with high-LETd. For instance, when more than 1 cm<sup>3</sup> of mucosa-to-spare was exposed to D<sub>RBE|mMKM</sub> ≥ 63 Gy and LETd ≥ 75 keV/µm, 2-yr OAF-free survival probability was 38 % versus 100 % in cases where these thresholds were not exceeded (<em>p</em> &lt; 0.001). Sino-nasal primary and HD–CTV ≥ 100 cm<sup>3</sup> also influenced OAF development.</div></div><div><h3>Conclusion</h3><div>Besides MS-CIRT strategy, optimizing DLV-parameters for oro-pharyngeal-mucosa may be a promising strategy in preventing late G3 OAF post-CIRT.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"214 ","pages":"Article 111314"},"PeriodicalIF":5.3,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145638168","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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Radiotherapy and Oncology
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