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A multi-institutional study to investigate the sparing effect after whole brain electron FLASH in mice: Reproducibility and temporal evolution of functional, electrophysiological, and neurogenic endpoints 一项多机构研究,调查小鼠全脑电子闪烁术后的疏松效应:功能、电生理和神经源终点的可重复性和时间演变。
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-16 DOI: 10.1016/j.radonc.2024.110534

Background and Purpose

Ultra-high dose-rate radiotherapy (FLASH) has been shown to mitigate normal tissue toxicities associated with conventional dose rate radiotherapy (CONV) without compromising tumor killing in preclinical models. A prominent challenge in preclinical radiation research, including FLASH, is validating both the physical dosimetry and the biological effects across multiple institutions.

Materials and Methods

We previously demonstrated dosimetric reproducibility of two different electron FLASH devices at separate institutions using standardized phantoms and dosimeters. In this study, tumor-free adult female mice were given 10 Gy whole brain FLASH and CONV irradiation at both institutions and evaluated for the reproducibility and temporal evolution of multiple neurobiological endpoints.

Results

FLASH sparing of behavioral performance on novel object recognition (4 months post-irradiation) and of electrophysiologic long-term potentiation (LTP, 5 months post-irradiation) was reproduced between institutions. Differences between FLASH and CONV on the endpoints of hippocampal neurogenesis (Sox2, doublecortin), neuroinflammation (microglial activation), and electrophysiology (LTP) were not observed at early times (48 h to 2 weeks), but recovery of immature neurons by 3 weeks was greater with FLASH.

Conclusion

In summary, we demonstrated reproducible FLASH sparing effects on the brain between two different beams at two different institutions with validated dosimetry. FLASH sparing effects on the endpoints evaluated manifested at later but not the earliest time points.
背景和目的:超高剂量率放疗(FLASH)已被证明可减轻与常规剂量率放疗(CONV)相关的正常组织毒性,同时不影响临床前模型中的肿瘤杀伤效果。临床前放射研究(包括 FLASH)的一个突出挑战是在多个机构间验证物理剂量测定和生物效应:我们曾在不同的机构使用标准化的模型和剂量计证明了两种不同的电子 FLASH 设备的剂量测定可重复性。在本研究中,两家机构都对无肿瘤的成年雌性小鼠进行了 10 Gy 全脑 FLASH 和 CONV 照射,并对多个神经生物学终点的可重复性和时间演变进行了评估:结果:FLASH对新物体识别(辐照后 4 个月)和电生理长期潜能(LTP,辐照后 5 个月)行为表现的影响在两家机构之间是相同的。FLASH和CONV在海马神经发生(Sox2、双皮质素)、神经炎症(小胶质细胞活化)和电生理学(LTP)终点方面的差异在早期(48小时至2周)没有观察到,但FLASH在3周前对未成熟神经元的恢复更大:总之,我们在两个不同的机构,通过有效的剂量测定,证明了两种不同光束对大脑的FLASH疏导效果具有可重复性。FLASH对评估终点的疏导作用在较晚的时间点而不是最早的时间点表现出来。
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引用次数: 0
Automated dose evaluation on daily cone-beam computed tomography for breast cancer patients 对乳腺癌患者每日锥形束计算机断层扫描的剂量进行自动评估
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-15 DOI: 10.1016/j.radonc.2024.110541

Background and purpose

Our goal was to develop a workflow to automatically evaluate delivered dose on daily cone beam computed tomography (CBCT) in all breast cancer patients to assess dosimetric impact of anatomical changes and guide decision-making for offline plan adaptation.

Materials and methods

The workflow automatically processes the daily CBCTs of all breast cancer patients receiving local and locoregional radiotherapy. The planning-CT is registered to the CBCT to create a synthetic CT and propagate contours. A forward dose calculation is performed, and DVH parameters are extracted and printed in a report. We evaluated the workflow on a group level and in a subset of 30 patients on a patient-specific level, including comparison to clinical evaluation on additional planning-CT in 10 patients.

Results

7454 fractions in 647 patients were analyzed over a period of seven months. Median breast clinical target volume V95% was ≥ 95 % for 97 % of the patients. The workflow would have provided useful additional insights for decision-making for the requirement of plan adaptation, based on debatable disagreement with the clinical decision in half of the cases with an additional planning-CT. The workflow also identified cases with suboptimal coverage not identified in the clinical procedure.

Conclusion

We developed a fully automated workflow for dose evaluation on daily CBCT for local and locoregional breast radiotherapy. We have demonstrated its potential for aiding decision-making for plan adaptation in patients with changing anatomy and its capability to highlight patients that may receive suboptimal treatment and require closer clinical evaluation of treatment quality.

背景和目的我们的目标是开发一个工作流程,自动评估所有乳腺癌患者每日锥形束计算机断层扫描(CBCT)的投放剂量,以评估解剖变化对剂量学的影响,并指导离线计划调整的决策。将计划 CT 注册到 CBCT 上,以创建合成 CT 和传播轮廓。进行前向剂量计算,提取 DVH 参数并打印成报告。我们对该工作流程进行了分组评估,并对 30 名患者的子集进行了患者特异性评估,包括与 10 名患者的额外规划 CT 临床评估进行比较。在 97% 的患者中,乳腺临床目标体积 V95% 的中位数≥ 95%。在半数病例中,额外的计划 CT 与临床决定存在值得商榷的分歧,因此工作流程本可为决定是否需要调整计划提供更多有用的见解。工作流程还发现了临床程序中未识别出的次优覆盖病例。我们已经证明了该工作流程的潜力,它可以帮助对解剖结构不断变化的患者进行计划调整决策,还可以突出显示可能接受次优治疗的患者,并需要对治疗质量进行更密切的临床评估。
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引用次数: 0
GEC-ESTRO recommendations for head & neck cancer brachytherapy (interventional radiotherapy): 2nd update with focus on HDR and PDR GEC-ESTRO 头颈癌近距离放射治疗(介入放射治疗)建议:第二次更新,重点关注 HDR 和 PDR。
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-14 DOI: 10.1016/j.radonc.2024.110533
Modern brachytherapy (BT) is playing an important role in the multidisciplinary treatment of Head and Neck (H&N) cancer, as an organ- and function-preserving therapy. Low-dose-rate (LDR) technology has been replaced by modern remote afterloading and stepping source equipment using pulsed dose rate (PDR) or high dose rate (HDR) sources, improved image guidance and 3D treatment planning systems. This is an update of the previous GEC-ESTRO recommendations for H&N tumors, mainly applied to squamous carcinomas. Indications, results and recommended doses for different tumor sites are presented according to the published studies.
现代近距离放射治疗(BT)作为一种保留器官和功能的疗法,在头颈部(H&N)癌症的多学科治疗中发挥着重要作用。低剂量率(LDR)技术已被使用脉冲剂量率(PDR)或高剂量率(HDR)源、改进的图像引导和三维治疗计划系统的现代远程后装和步进源设备所取代。这是 GEC-ESTRO 先前对 H&N 肿瘤建议的更新,主要适用于鳞状癌。根据已发表的研究,介绍了不同肿瘤部位的适应症、结果和推荐剂量。
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引用次数: 0
Intra-prostatic recurrences after radiotherapy with focal boost: Location and dose mapping in the FLAME trial 焦点增强放疗后的膀胱内复发:FLAME 试验中的位置和剂量图。
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-13 DOI: 10.1016/j.radonc.2024.110535

Introduction

The FLAME trial demonstrated that the dose to the gross tumor volume (GTV) is associated with tumour control in prostate cancer patients. This raises the question if dose de-escalation to the remaining prostate gland can be considered. Therefore, we investigated if intraprostatic recurrences occur at the location of the GTV and which dose was delivered at that location.

Materials and methods

For FLAME trial patients with an intra-prostatic recurrence, we collected pre-treatment images, GTV delineations, dose distributions and post-recurrence images. Pre-treatment images were registered to the post-recurrence images (PSMA-PET CT). An overlap between GTV and PSMA-PET activity was considered an intra-prostatic recurrence at the location of the primary tumor.

Results

Twenty eight out of 535 patients in the FLAME trial had an intra-prostatic recurrence. Its location could be determined for 24 patients. One patient recurred in the prostate gland outside the GTV. The median near-minimum dose to the GTV (D98%) was 76.5 Gy (range: 73.3–86.5 Gy). Only one patient with a recurrence in the GTV received a substantial focal boost of 86.5 Gy. The D98% of all remaining patients was < 81 Gy.

Conclusion

Intra-prostatic recurrences of intermediate- and high-risk prostate cancer patients treated with radiotherapy appeared predominantly at the location of the primary tumor. All but one patient did not receive a high dose to the GTV. Intra-prostatic failure is likely a consequence of the undertreatment of the primary tumor rather than the undertreatment of the remaining prostate gland.
简介FLAME 试验表明,前列腺癌患者肿瘤总体积(GTV)的剂量与肿瘤控制有关。这就提出了一个问题,即是否可以考虑对剩余前列腺进行剂量递减。因此,我们研究了前列腺内复发是否发生在GTV位置,以及在该位置投放的剂量:对于前列腺内复发的 FLAME 试验患者,我们收集了治疗前图像、GTV 划线、剂量分布和复发后图像。治疗前图像与复发后图像(PSMA-PET CT)进行了对比。GTV与PSMA-PET活动重叠被认为是原发肿瘤位置的膀胱内复发:结果:在FLAME试验的535名患者中,有28名患者出现了睾丸内复发。其中 24 名患者的复发位置可以确定。一名患者在GTV以外的前列腺内复发。GTV的D98%中位数为76.5 Gy(范围:73.3-86.5 Gy)。只有一名在 GTV 内复发的患者接受了 86.5 Gy 的大量病灶增强治疗。其余所有患者的 D98% 均为结论:接受放疗的中危和高危前列腺癌患者的膀胱内复发主要出现在原发肿瘤的位置。除一名患者外,其他患者的GTV均未接受高剂量治疗。前列腺内复发可能是原发肿瘤治疗不足的结果,而不是剩余前列腺治疗不足的结果。
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引用次数: 0
Fructose 1,6-bisphosphate aldolase: A promising prognostic marker for oral cancer and its role in radiotherapy response 果糖 1,6-二磷酸醛缩酶:口腔癌有希望的预后标志物及其在放疗反应中的作用
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-13 DOI: 10.1016/j.radonc.2024.110537

Oral cancer remains a significant global health concern and its early detection plays a crucial role in improving patient outcomes. Identifying reliable prognostic markers is essential to guide treatment decisions and enhance survival rates. Fructose 1,6-bisphosphate aldolase (FBA), a glycolytic enzyme, has emerged as a promising candidate for prognostic assessment of oral cancer. This review highlights the role of FBA in tumorigenesis, its potential utility in predicting disease progression and patient survival, and its influence on response to radiotherapy. Recent studies have suggested that dysregulated metabolic pathways involving FBA may contribute to radiation resistance in oral cancer, emphasizing the need for further exploration of FBA-targeted therapeutic strategies. Understanding the role of FBA in oral cancer pathogenesis could pave the way for the development of personalized treatment strategies, including combined radiotherapy.

口腔癌仍然是全球关注的重大健康问题,其早期检测在改善患者预后方面发挥着至关重要的作用。确定可靠的预后标志物对于指导治疗决策和提高生存率至关重要。1,6-二磷酸果糖醛缩酶(FBA)是一种糖酵解酶,已成为口腔癌预后评估的有望候选指标。本综述将重点介绍 FBA 在肿瘤发生过程中的作用、其在预测疾病进展和患者生存方面的潜在用途,以及其对放疗反应的影响。最近的研究表明,涉及 FBA 的代谢途径失调可能会导致口腔癌的放射耐受性,这强调了进一步探索 FBA 靶向治疗策略的必要性。了解 FBA 在口腔癌发病机制中的作用可为开发包括联合放疗在内的个性化治疗策略铺平道路。
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引用次数: 0
Prognostic factors in post-prostatectomy salvage radiotherapy setting with and without hormonotherapy: An individual patient data analysis of randomized trials from ICECaP database 前列腺切除术后接受或不接受激素治疗的挽救性放疗的预后因素:来自ICECaP数据库的随机试验的个体患者数据分析
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-13 DOI: 10.1016/j.radonc.2024.110532

Background

Early salvage radiotherapy (SRT) is the standard of care for biochemical recurrence post-prostatectomy but outcomes are heterogeneous.

Objective

To develop a risk scoring system based on relevant standard-of-care clinico-pathological prognostic factors for patients treated with SRT with and without hormonal therapy (HT).

Design, setting, and participants

The Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) database included three randomized trials (Individual patients’ data from 1647 subjects) assessing SRT (GETUG-AFU-16; NRG/RTOG-9601, and a subset of EORTC-22911).

Outcome measurements and statistical analysis

Outcomes were clinical progression (CP). metastasis free-survival (MFS) and overall survival (OS). Clinico-pathological factors, including pathological Gleason Score (GS), PSA at SRT start, margin status, persistent PSA post-RP and time from RP to SRT were evaluated by multivariable models stratified by type of treatment.

Results and limitations

On multivariable analysis PSA ≥ 0.5 ng/mL at SRT start, GS ≥ 8 and negative margin status were the three strongest prognostic factors. Three prognostic groups defined by number of these risk features (high risk: 2 or 3; intermediate risk: 1 and low risk: 0) were strongly associated with OS, MFS and CP outcomes with SRT alone or with HT. This prognostic group definition was also relevant for patients with persistent PSA post RP and for patients treated < 1 year from RP to SRT and with and without HT.

Conclusion

A risk score for patients receiving SRT with or without HT, using three standard-of-care clinico-pathological risk factors provides refined prognostic information for individual patient counselling.

Patient summary

By using a composite score of pathology grading (Gleason Score), PSA at start of salvage radiation and margin status data, physicians can provide patients with more refined information on the risk of a second relapse after receiving radiation to the prostate bed after a prostatectomy for a rising or persistent PSA, both with and without hormonal therapy.

背景早期挽救性放射治疗(SRT)是治疗前列腺切除术后生化复发的标准方法,但疗效却不尽相同。目的根据相关的临床病理标准预后因素,为接受SRT治疗和未接受激素治疗(HT)的患者建立风险评分系统。结果测量和统计分析结果为临床进展(CP)、无转移生存期(MFS)和总生存期(OS)。临床病理因素包括病理格里森评分(GS)、SRT开始时的PSA、边缘状态、RP后持续PSA以及从RP到SRT的时间,这些因素通过多变量模型进行评估,并按治疗类型进行分层。根据这些风险特征的数量定义的三个预后组(高风险:2或3;中度风险:1;低风险:0)与单纯SRT或HT的OS、MFS和CP结果密切相关。这一预后分组定义也适用于 RP 后 PSA 持续存在的患者,以及从 RP 到 SRT 治疗 < 1 年的患者,也适用于使用或不使用 HT 的患者。患者总结 通过使用病理分级(Gleason 评分)、开始挽救性放射治疗时的 PSA 和边缘状态数据的综合评分,医生可以为患者提供更精细的信息,帮助他们了解因 PSA 升高或持续存在而接受前列腺切除术后接受前列腺床放射治疗后再次复发的风险,无论是否接受激素治疗。
{"title":"Prognostic factors in post-prostatectomy salvage radiotherapy setting with and without hormonotherapy: An individual patient data analysis of randomized trials from ICECaP database","authors":"","doi":"10.1016/j.radonc.2024.110532","DOIUrl":"10.1016/j.radonc.2024.110532","url":null,"abstract":"<div><h3>Background</h3><p>Early salvage radiotherapy (SRT) is the standard of care for biochemical recurrence post-prostatectomy but outcomes are heterogeneous.</p></div><div><h3>Objective</h3><p>To develop a risk scoring system based on relevant standard-of-care clinico-pathological prognostic factors for patients treated with SRT with and without hormonal therapy (HT).</p></div><div><h3>Design, setting, and participants</h3><p>The Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) database included three randomized trials (Individual patients’ data from 1647 subjects) assessing SRT (GETUG-AFU-16; NRG/RTOG-9601, and a subset of EORTC-22911).</p></div><div><h3>Outcome measurements and statistical analysis</h3><p>Outcomes were clinical progression (CP). metastasis free-survival (MFS) and overall survival (OS). Clinico-pathological factors, including pathological Gleason Score (GS), PSA at SRT start, margin status, persistent PSA post-RP and time from RP to SRT were evaluated by multivariable models stratified by type of treatment.</p></div><div><h3>Results and limitations</h3><p>On multivariable analysis PSA ≥ 0.5 ng/mL at SRT start, GS ≥ 8 and negative margin status were the three strongest prognostic factors. Three prognostic groups defined by number of these risk features (high risk: 2 or 3; intermediate risk: 1 and low risk: 0) were strongly associated with OS, MFS and CP outcomes with SRT alone or with HT. This prognostic group definition was also relevant for patients with persistent PSA post RP and for patients treated &lt; 1 year from RP to SRT and with and without HT.</p></div><div><h3>Conclusion</h3><p>A risk score for patients receiving SRT with or without HT, using three standard-of-care clinico-pathological risk factors provides refined prognostic information for individual patient counselling.</p></div><div><h3>Patient summary</h3><p>By using a composite score of pathology grading (Gleason Score), PSA at start of salvage radiation and margin status data, physicians can provide patients with more refined information on the risk of a second relapse after receiving radiation to the prostate bed after a prostatectomy for a rising or persistent PSA, both with and without hormonal therapy.</p></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0167814024035102/pdfft?md5=7cda79fcf2d454970bd27af483cccf5b&pid=1-s2.0-S0167814024035102-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhanced radiosensitivity of pancreatic cancer achieved through inhibition of Cyclin-dependent kinase 1 通过抑制细胞周期蛋白依赖性激酶 1 提高胰腺癌的放射敏感性
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-11 DOI: 10.1016/j.radonc.2024.110531

Background and purpose

Overcoming radioresistance is a critical challenge in pancreatic ductal adenocarcinoma (PDAC). Our study investigates the targeting of Cyclin-dependent kinase-1 (CDK1) through genetic and pharmaceutical inhibition to radiosensitize PDAC cells.

Materials and Methods

Mass spectrometry and phosphoproteomics were used to analyze engineered radiation-resistant PDAC cell lines (MIA PaCa-2 and PANC-1) compared to parental controls. The TCGA PDAC database was queried for clinical outcomes and patients were dichotomized based on the median CDK1 mRNA expression. We generated a microRNA-based TET-on inducible shRNA to inhibit CDK1 expression in two PDAC cell lines. We used an orthotopic model of PDAC to test the radiation sensitivity of PDAC tumors with or without doxycycline treatment. We targeted CDK1 activation with a selective CDK1 inhibitor, RO-3306, followed by in vitro experiments employing immunoblotting, immunocytochemistry, and clonogenic assays.

Results

Phosphoproteomics analysis revealed that phospho-CDK1 (Tyr15) was significantly elevated in the resistant clones. We found that high CDK1 expression was associated with worse OS in PDAC patients. Radiation exposure increased CDK1 phosphorylation. In MIA PaCa-2 and PANC-1 cells, CDK1 inhibition synergized with radiation therapy to delay tumor growth in vivo. CDK1 inhibition via. RO-3306 resulted in a significant shift of cells into the G2/M phase and disrupted DNA repair after radiation exposure. In vitro, pre-treatment with RO-3306 led to enhanced radiosensitivity of PDAC cells.

Conclusion

CDK1 plays a crucial role in PDAC radioresistance. Targeting CDK1 with radiotherapy holds promise for further investigation in PDAC treatment.

背景和目的克服放射抗性是胰腺导管腺癌(PDAC)面临的一项严峻挑战。我们的研究探讨了通过基因和药物抑制来靶向细胞周期蛋白依赖性激酶-1(CDK1),从而使 PDAC 细胞具有放射敏感性。材料与方法采用质谱和磷酸化蛋白质组学分析了与亲代对照相比具有放射抗性的 PDAC 细胞系(MIA PaCa-2 和 PANC-1)。我们查询了 TCGA PDAC 数据库的临床结果,并根据 CDK1 mRNA 表达的中位数对患者进行了二分。我们生成了一种基于微RNA的TET-on诱导型shRNA,以抑制两种PDAC细胞系中CDK1的表达。我们使用 PDAC 正位模型来测试 PDAC 肿瘤在接受或不接受强力霉素治疗时的辐射敏感性。我们使用选择性 CDK1 抑制剂 RO-3306 靶向激活 CDK1,然后使用免疫印迹、免疫细胞化学和克隆生成试验进行体外实验。结果磷蛋白组学分析表明,耐药克隆中磷酸化 CDK1(Tyr15)显著升高。我们发现,CDK1的高表达与PDAC患者较差的OS有关。辐射会增加 CDK1 磷酸化。在 MIA PaCa-2 和 PANC-1 细胞中,CDK1 抑制与放射治疗协同延缓体内肿瘤生长。通过 RO-3306 抑制 CDK1RO-3306 可使细胞明显进入 G2/M 期,并破坏辐射照射后的 DNA 修复。在体外,RO-3306 的预处理增强了 PDAC 细胞的放射敏感性。放疗靶向 CDK1 有望在 PDAC 治疗中得到进一步研究。
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引用次数: 0
Physical activity at diagnosis is associated with tumor downstaging after neoadjuvant chemoradiotherapy in patients with rectal cancer 直肠癌患者确诊时的体力活动与新辅助化放疗后肿瘤下移有关
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-10 DOI: 10.1016/j.radonc.2024.110523

Background

Patients with rectal cancer are often treated with neoadjuvant chemoradiotherapy, followed by a waiting period and surgical resection. Good or complete response to neoadjuvant chemoradiotherapy might enable organ preservation, which highlights the need to increase response rates. Pre-clinical studies suggest that physical activity during neoadjuvant chemoradiotherapy may improve tumor downstaging.

Purpose

To investigate whether physical activity and physical functioning of patients with rectal cancer at diagnosis are associated with tumor downstaging after neoadjuvant chemoradiotherapy.

Materials and methods

Patients were included if they participated in the Dutch Prospective ColoRectal Cancer Cohort, a nationwide cohort providing an infrastructure for scientific research, and received neoadjuvant chemoradiotherapy for rectal cancer. Tumor downstaging was dichotomized into good/complete or moderate/poor downstaging. Physical activity (total physical activity, moderate-to-vigorous physical activity (MVPA), and Dutch physical activity guideline adherence) and physical functioning were assessed using questionnaires. Logistic regression analyses were performed to examine associations of physical activity and physical functioning with tumor downstaging, adjusted for relevant confounders.

Results

268 patients (aged 62 ± 11 years, 33 % female) with rectal cancer were included. Patients with moderate (OR = 2.07; 95%CI = 1.07 – 4.07; p = 0.03) or high (OR = 2.05; 95%CI = 1.05 – 4.07; p = 0.04) levels of MVPA were more likely to have good/complete tumor downstaging than patients with low levels. No significant associations with tumor downstaging were found for total physical activity, Dutch physical activity guideline adherence, and physical functioning.

Conclusions

We found augmented tumor downstaging in patients with rectal cancer with moderate or high levels of self-reported MVPA before the start of neoadjuvant chemoradiotherapy compared to patients with low levels.

背景直肠癌患者通常接受新辅助化放疗,然后等待一段时间再进行手术切除。对新辅助化放疗的良好或完全反应可使器官得以保留,这就凸显了提高反应率的必要性。临床前研究表明,在新辅助化放疗期间进行体育锻炼可改善肿瘤缩小。目的 研究直肠癌患者在确诊时的体育锻炼和身体机能是否与新辅助化放疗后肿瘤缩小有关。材料和方法纳入参加荷兰前瞻性结肠直肠癌队列(荷兰前瞻性结肠直肠癌队列是一个为科学研究提供基础设施的全国性队列)并接受直肠癌新辅助化放疗的患者。肿瘤降期分为良好/完全降期或中度/差降期。体力活动(总体力活动、中强度体力活动(MVPA)和荷兰体力活动指南遵守情况)和身体机能通过问卷进行评估。在对相关混杂因素进行调整后,对体力活动和身体机能与肿瘤分期的关系进行了逻辑回归分析。中度(OR = 2.07; 95%CI = 1.07 - 4.07; p = 0.03)或高度(OR = 2.05; 95%CI = 1.05 - 4.07; p = 0.04)MVPA 水平的患者比低水平的患者更有可能获得良好/完全的肿瘤缩小。结论我们发现,与自我报告MVPA水平低的直肠癌患者相比,在新辅助化放疗开始前自我报告MVPA水平达到中度或高度的直肠癌患者的肿瘤缩小率更高。
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引用次数: 0
Brachial plexopathy following stereotactic body radiation therapy in apical lung malignancies: A dosimetric pooled analysis of individual patient data 肺尖部恶性肿瘤立体定向体放射治疗后的臂丛神经病:对单个患者数据的剂量学汇总分析
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-08 DOI: 10.1016/j.radonc.2024.110529

Background and objectives

The aim of this study is to establish dosimetric constraints for the brachial plexus at risk of developing grade ≥ 2 brachial plexopathy in the context of stereotactic body radiation therapy (SBRT).

Patients and Methods

Individual patient data from 349 patients with 356 apical lung malignancies who underwent SBRT were extracted from 5 articles. The anatomical brachial plexus was delineated following the guidelines provided in the atlases developed by Hall, et al. and Kong, et al.. Patient characteristics, pertinent SBRT dosimetric parameters, and brachial plexopathy grades (according to CTCAE 4.0 or 5.0) were obtained. Normal tissue complication probability (NTCP) models were used to estimate the risk of developing grade ≥ 2 brachial plexopathy through maximum likelihood parameter fitting.

Results

The prescription dose/fractionation schedules for SBRT ranged from 27 to 60 Gy in 1 to 8 fractions. During a follow-up period spanning from 6 to 113 months, 22 patients (6.3 %) developed grade ≥2 brachial plexopathy (4.3 % grade 2, 2.0 % grade 3); the median time to symptoms onset after SBRT was 8 months (ranged, 3–54 months). NTCP models estimated a 10 % risk of grade ≥2 brachial plexopathy with an anatomic brachial plexus maximum dose (Dmax) of 20.7 Gy, 34.2 Gy, and 42.7 Gy in one, three, and five fractions, respectively. Similarly, the NTCP model estimates the risks of grade ≥2 brachial plexopathy as 10 % for BED Dmax at 192.3 Gy and EQD2 Dmax at 115.4 Gy with an α/β ratio of 3, respectively. Symptom persisted after treatment in nearly half of patients diagnosed with grade ≥2 brachial plexopathy (11/22, 50 %).

Conclusions

This study establishes dosimetric constraints ranging from 20.7 to 42.7 Gy across 1–5 fractions, aimed at mitigating the risk of developing grade ≥2 brachial plexopathy following SBRT. These findings provide valuable guidance for future ablative SBRT in apical lung malignancies.

背景和目的本研究旨在为立体定向体放射治疗(SBRT)中有可能发生≥2级臂丛神经病的臂丛神经建立剂量限制。患者和方法从5篇文章中提取了349名患者的个人数据,这些患者患有356种肺部恶性肿瘤,接受了SBRT治疗。根据 Hall 等人和 Kong 等人开发的图谱中提供的指南,对解剖臂丛进行了划分。获得了患者特征、相关的 SBRT 剂量学参数和臂丛神经病变等级(根据 CTCAE 4.0 或 5.0)。通过最大似然参数拟合,使用正常组织并发症概率(NTCP)模型来估计发生≥2级臂丛神经病的风险。在 6 至 113 个月的随访期间,22 名患者(6.3%)出现了≥2 级臂丛神经病(4.3% 为 2 级,2.0% 为 3 级);SBRT 后症状出现的中位时间为 8 个月(范围为 3-54 个月)。NTCP 模型估计,解剖臂丛最大剂量(Dmax)分别为 20.7 Gy、34.2 Gy 和 42.7 Gy,分 1 次、3 次和 5 次照射时,发生≥2 级臂丛神经病的风险为 10%。同样,NTCP 模型估计,BED Dmax 为 192.3 Gy 和 EQD2 Dmax 为 115.4 Gy 时,≥2 级臂丛神经病的风险分别为 10%,α/β 比值为 3。近一半被诊断为≥2级臂丛神经病的患者(11/22,50%)在治疗后症状持续存在。结论本研究确定了1-5个分段20.7-42.7 Gy的剂量限制,旨在降低SBRT治疗后发生≥2级臂丛神经病的风险。这些研究结果为今后肺尖部恶性肿瘤的SBRT消融治疗提供了宝贵的指导。
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引用次数: 0
RSPO3 regulates the radioresistance of Non-Small cell lung cancer cells via NLRP3 Inflammasome-Mediated pyroptosis RSPO3 通过 NLRP3 炎症体介导的化脓过程调节非小细胞肺癌细胞的放射抗性。
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-07 DOI: 10.1016/j.radonc.2024.110528

Purpose

Radioresistance is a significant challenge in the radiotherapy of non-small cell lung cancer (NSCLC). This study aimed to investigate the role of R-spondin 3 (RSPO3) in regulating NSCLC radioresistance.

Methods and Materials

RNA sequencing was performed to analyze genes that are differentially expressed in radioresistant NSCLC cell lines. RSPO3 overexpression and knockdown experiments were conducted to assess its impact on radiosensitivity. The involvement of the β-catenin-NF-κB signaling pathway and the NLRP3 inflammasome in RSPO3-mediated radiosensitivity was also evaluated. In vivo experiments were conducted using a clinical-grade anti-RSPO3 antibody (OMP-131R10/rosmantuzumab) to assess its impact on radiation-induced pyroptosis and subsequent anti-tumor immunity.

Results

RSPO3 expression was downregulated in radioresistant NSCLC cells. Overexpression of RSPO3 increased NSCLC radiosensitivity through the induction of pyroptosis, which was mediated by the β-catenin-NF-κB signaling pathway and the NLRP3 inflammasome. The anti-RSPO3 antibody effectively blocked radiation-induced pyroptosis and anti-tumor immunity in vivo. Conversely, upregulation of RSPO3 enhanced NSCLC tumor radiosensitivity.

Conclusions

The findings demonstrated that RSPO3 plays a crucial role in regulating NSCLC radioresistance via NLRP3 mediated pyroptosis. Targeting the RSPO3-NLRP3 inflammasome axis may offer a potential therapeutic strategy to enhance the efficacy of radiotherapy for NSCLC patients.

目的:放射抗性是非小细胞肺癌(NSCLC)放射治疗面临的一个重大挑战。本研究旨在探讨R-spondin 3(RSPO3)在调控NSCLC放射抗性中的作用:方法:采用 RNA 测序分析耐药 NSCLC 细胞系中差异表达的基因。进行了RSPO3过表达和敲除实验,以评估其对放射敏感性的影响。此外,还评估了β-catenin-NF-κB信号通路和NLRP3炎性体在RSPO3介导的放射敏感性中的参与情况。使用临床级抗RSPO3抗体(OMP-131R10/rosmantuzumab)进行了体内实验,以评估其对辐射诱导的热蛋白沉积和随后的抗肿瘤免疫的影响:结果:抗放射NSCLC细胞中RSPO3表达下调。RSPO3的过表达通过诱导热蛋白沉积增加了NSCLC的放射敏感性,而热蛋白沉积是由β-catenin-NF-κB信号通路和NLRP3炎性体介导的。抗RSPO3抗体能有效阻断辐射诱导的体内热蛋白沉积和抗肿瘤免疫。相反,RSPO3的上调增强了NSCLC肿瘤的放射敏感性:研究结果表明,RSPO3 在通过 NLRP3 介导的热蛋白沉积调节 NSCLC 放射抗性方面起着关键作用。靶向RSPO3-NLRP3炎性体轴可能是提高NSCLC患者放疗疗效的一种潜在治疗策略。
{"title":"RSPO3 regulates the radioresistance of Non-Small cell lung cancer cells via NLRP3 Inflammasome-Mediated pyroptosis","authors":"","doi":"10.1016/j.radonc.2024.110528","DOIUrl":"10.1016/j.radonc.2024.110528","url":null,"abstract":"<div><h3>Purpose</h3><p>Radioresistance is a significant challenge in the radiotherapy of non-small cell lung cancer (NSCLC). This study aimed to investigate the role of R-spondin 3 (RSPO3) in regulating NSCLC radioresistance.</p></div><div><h3>Methods and Materials</h3><p>RNA sequencing was performed to analyze genes that are differentially expressed in radioresistant NSCLC cell lines. RSPO3 overexpression and knockdown experiments were conducted to assess its impact on radiosensitivity. The involvement of the β-catenin-NF-κB signaling pathway and the NLRP3 inflammasome in RSPO3-mediated radiosensitivity was also evaluated. In vivo experiments were conducted using a clinical-grade anti-RSPO3 antibody (OMP-131R10/rosmantuzumab) to assess its impact on radiation-induced pyroptosis and subsequent anti-tumor immunity.</p></div><div><h3>Results</h3><p>RSPO3 expression was downregulated in radioresistant NSCLC cells. Overexpression of RSPO3 increased NSCLC radiosensitivity through the induction of pyroptosis, which was mediated by the β-catenin-NF-κB signaling pathway and the NLRP3 inflammasome. The anti-RSPO3 antibody effectively blocked radiation-induced pyroptosis and anti-tumor immunity in vivo. Conversely, upregulation of RSPO3 enhanced NSCLC tumor radiosensitivity.</p></div><div><h3>Conclusions</h3><p>The findings demonstrated that RSPO3 plays a crucial role in regulating NSCLC radioresistance via NLRP3 mediated pyroptosis. Targeting the RSPO3-NLRP3 inflammasome axis may offer a potential therapeutic strategy to enhance the efficacy of radiotherapy for NSCLC patients.</p></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154908","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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