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A novel lineage-tracing tool reveals that hypoxic tumor cells drive tumor relapse after radiotherapy 一种新型细胞系追踪工具揭示了缺氧性肿瘤细胞导致放疗后肿瘤复发的原因。
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-18 DOI: 10.1016/j.radonc.2024.110592
Apostolos Menegakis , Claire Vennin , Jonathan Ient , Arjan J. Groot , Lenno Krenning , Rob Klompmaker , Anoek Friskes , Mila Ilic , Ala Yaromina , Rolf Harkes , Bram van den Broek , Jan Jakob Sonke , Monique De Jong , Jolanda Piepers , Jacco van Rheenen , Marc A. Vooijs , René H. Medema

Purpose

Tumor hypoxia imposes a main obstacle to the efficacy of anti-cancer therapy. Understanding the cellular dynamics of individual hypoxic cells before, during and post-treatment has been hampered by the technical inability to identify and trace these cells over time.

Methods and materials

Here, we present a novel lineage-tracing reporter for hypoxic cells based on the conditional expression of a HIF1a-CreERT2-UnaG biosensor that can visualize hypoxic cells in a time-dependent manner and trace the fate of hypoxic cells over time. We combine this system with multiphoton microscopy, flow cytometry, and immunofluorescence to characterize the role of hypoxic cells in tumor relapse after irradiation in H1299 tumor spheroids and in vivo xenografts.

Results

We validate the reporter in monolayer cultures and we show that tagged cells colocalize in spheroids and human tumor xenografts with the hypoxic marker pimonidazole. We found that irradiation of H1299-HIFcreUnaG spheroids leads to preferential outgrowth of cells from the hypoxic core. Similarly, in xenografts tumors, although initially UnaG-positive-cells coincide with pimonidazole-positive tumor areas and they are merely quiescent, upon irradiation UnaG-positive cells enrich in regrowing tumors and are mainly proliferative.

Conclusions

Collectively, our data provide clear evidence that the hypoxic cells drive tumor relapse after irradiation.
目的:肿瘤缺氧是抗癌疗法疗效的主要障碍。由于在技术上无法识别和追踪这些细胞,因此在治疗前、治疗中和治疗后了解单个缺氧细胞的动态一直受到阻碍:在这里,我们展示了一种新型的缺氧细胞系追踪报告物,它基于 HIF1a-CreERT2-UnaG 生物传感器的条件表达,能以时间依赖的方式观察缺氧细胞,并随时间追踪缺氧细胞的命运。我们将这一系统与多光子显微镜、流式细胞术和免疫荧光相结合,研究了缺氧细胞在 H1299 肿瘤球体和体内异种移植物照射后肿瘤复发中的作用:我们在单层培养物中验证了报告基因,并表明在球形细胞和人类肿瘤异种移植物中,标记的细胞与缺氧标记物pimonidazole共定位。我们发现,辐照 H1299-HIFcreUnaG 球体会导致细胞从缺氧核心优先生长出来。同样,在异种移植的肿瘤中,尽管最初UnaG阳性细胞与pimonidazole阳性肿瘤区域重合,但它们只是静止的,而在辐照后,UnaG阳性细胞在重新生长的肿瘤中富集,并且主要是增殖性的:总之,我们的数据提供了明确的证据,证明缺氧细胞是辐照后肿瘤复发的驱动因素。
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引用次数: 0
Patient reported fatigue after proton therapy for malignant brain tumours – Is there a relation between radiation dose and brain structures? 质子治疗恶性脑肿瘤后患者报告的疲劳--辐射剂量与脑结构有关系吗?
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-18 DOI: 10.1016/j.radonc.2024.110582
Ingrid Kristensen , Ulrica Langegård , Thomas Björk-Eriksson , Malin Blomstrand , Patrik Brodin , Per Fransson , Per Munck af Rosenschöld , Fredrik Nordström , Emma Olsson-Nevo , Katarina Sjövall , Karin Ahlberg

Background

Fatigue may significantly effect everyday- and working life for radiotherapy patients. Some studies indicate a correlation between radiation dose and irradiated volume of the brain and the presence of fatigue. Our hypothesis was that patient reported outcome measures (PROMs) can improve our understanding of the patients’ symptoms following proton beam therapy (PBT) and optimize PBT for future patients.

Methods

This study included 167 adult patients (>18 years) who received PBT for malignant brain tumours. Data on dose metrics to intra-cranial structures was obtained from PBT treatment plans. To explore fatigue and health related quality of life (HRQoL); Multidimensional Fatigue Inventory (MFI-20) and EORTC QLQ-C30 was used at 6-, 12-, 24- and 36 months post PBT. The correlation between fatigue and dosimetry was explored using Spearman’s signed rank test.

Results

No severe fatigue was recorded during the 36 months follow-up. Correlations between higher radiation dose and worsened fatigue scores were generally weak (rho < 0.3). At 12 months post PBT, higher mean dose to the brain, brainstem, hippocampi and pituitary was correlated to worsened MFI Physical Fatigue. Further, Reduced Motivation according to MFI was correlated to higher radiation dose to the brainstem and the pituitary gland. At 36 months follow-up post-PBT, both Reduced Activity and Reduced motivation according to MFI were correlated to higher radiation dose to the brain, brainstem and hippocampi.

Conclusion

Proton beam therapy are well tolerated, with similar degree of fatigue pre- and post PBT. Achieving further reduction in mean brain dose appears beneficial.
背景:疲劳会严重影响放疗患者的日常生活和工作。一些研究表明,放射剂量和脑部照射量与疲劳的存在存在相关性。我们的假设是,患者报告的结果测量(PROMs)可以提高我们对质子束治疗(PBT)后患者症状的了解,并优化未来患者的质子束治疗:这项研究包括167名接受质子束疗法治疗恶性脑肿瘤的成年患者(18岁以上)。颅内结构的剂量指标数据来自 PBT 治疗计划。为了探究疲劳和健康相关生活质量(HRQoL),使用了多维疲劳量表(MFI-20)和 EORTC QLQ-C30,时间分别为 PBT 术后 6 个月、12-24 个月和 36 个月。采用斯皮尔曼符号秩检验探讨了疲劳与剂量测定之间的相关性:结果:在 36 个月的随访期间,没有发现严重的疲劳现象。结果:在 36 个月的随访期间,没有出现严重疲劳的记录,辐射剂量增加与疲劳评分恶化之间的相关性普遍较弱(rho 结论:质子束治疗的耐受性良好:质子束治疗的耐受性良好,PBT前后的疲劳程度相似。进一步降低平均脑剂量似乎是有益的。
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引用次数: 0
Effects of photobiomodulation therapy for acute radiation dermatitis in patients with cancer: A systematic review and meta‑analysis of real-world evidence 光生物调节疗法治疗癌症患者急性放射性皮炎的效果:对真实世界证据的系统回顾和荟萃分析。
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-18 DOI: 10.1016/j.radonc.2024.110589
Ying-Tong Lin , Kuang-Mou Tung , Jeng-Fong Chiou , Yen-Chao Chen , Wen-Hsuan Hou

Purpose

To examine the effectiveness of photobiomodulation therapy (PBMT) for acute radiation dermatitis (ARD) in patients with cancer.

Materials and methods

PubMed, Embase, Cochrane Library, and CINAHL were searched for articles published between database inception until July 2024. Randomized controlled trials (RCTs) and non-RCTs examining the effects of PBMT against ARD in patients with cancer were included for analysis. A random-effects model was used to conduct meta-analyses and sensitivity analyses. Subgroup analyses were conducted for cancer types and PBMT goals (prevention or treatment of ARD) with stratification for different grades of ARD.

Results

Eight studies (five RCTs and three non-RCTs) were included in this meta-analysis. Compared with the control group, the PBMT group exhibited significantly lower ARD incidence at grades 2 and 3 (risk difference =  − 0.36, 95 % confidence interval =  − 0.53 to − 0.19, I2 = 85 %, P = < 0.00001). Subgroup analyses revealed that, compared with the control group, PBMT had a significant effect on both breast cancer and head and neck cancer. In addition, PBMT significantly reduced grades 2 and 3 ARD incidence in the PBMT group for both prevention and treatment subgroups.

Conclusion

PBMT may have beneficial effects on the prevention and treatment of higher-grade ARD in patients with breast cancer and head and neck cancer. Nevertheless, the studies included in this meta-analysis exhibited high heterogeneity. Therefore, the results must be interpreted with caution.
目的:研究光生物调节疗法(PBMT)对癌症患者急性放射性皮炎(ARD)的疗效:在 PubMed、Embase、Cochrane Library 和 CINAHL 中检索了自数据库建立至 2024 年 7 月期间发表的文章。纳入了研究PBMT对癌症患者ARD影响的随机对照试验(RCT)和非RCT进行分析。采用随机效应模型进行荟萃分析和敏感性分析。根据癌症类型和PBMT目标(预防或治疗ARD)进行了分组分析,并对不同等级的ARD进行了分层:本次荟萃分析共纳入八项研究(五项研究性试验和三项非研究性试验)。与对照组相比,PBMT 组的 2 级和 3 级 ARD 发生率明显降低(风险差异 = - 0.36,95 % 置信区间 = - 0.53 至 - 0.19,I2 = 85 %,P = < 0.00001)。分组分析显示,与对照组相比,PBMT 对乳腺癌和头颈部癌症都有显著效果。此外,在预防和治疗亚组中,PBMT 组的 2 级和 3 级 ARD 发生率均明显降低:结论:PBMT 可能对预防和治疗乳腺癌和头颈部癌症患者的高级别 ARD 有益。尽管如此,这项荟萃分析所纳入的研究显示出高度的异质性。因此,必须谨慎解读研究结果。
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引用次数: 0
Perfect is the enemy of good: Reply to Struikmans et al. 完美是美好的敌人:对 Struikmans 等人的答复
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-17 DOI: 10.1016/j.radonc.2024.110585
Marianne C Aznar, Jutta Bergler-Klein, Giuseppe Boriani, David J Cutter, Coen Hurkmans, Mario Levis, Teresa López-Fernández, Alexander R Lyon, Maja V Maraldo
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引用次数: 0
Consistency in reirradiation scenarios: Terminology, tissue recovery in calculations, units and reporting 再辐射方案的一致性:术语、计算中的组织恢复、单位和报告。
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-17 DOI: 10.1016/j.radonc.2024.110587
Nick West , Elizabeth Covington , Eliana Vasquez Osorio , Joep Stroom , Michael Duchateau , Madalyne Day , Nick Hardcastle , Myriam Ayadi , Andrew Jackson , Heidi S. Rønde , Chuck Mayo , Ane Appelt
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引用次数: 0
Achieving accurate prostate auto-segmentation on CT in the absence of MR imaging 在没有磁共振成像的情况下,通过 CT 实现准确的前列腺自动分区。
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-16 DOI: 10.1016/j.radonc.2024.110588
Jingwei Duan , Riley C. Tegtmeier , Carlos E. Vargas , Nathan Y. Yu , Brady S. Laughlin , Jean-Claude M. Rwigema , Justin D. Anderson , Libing Zhu , Quan Chen , Yi Rong

Background

Magnetic resonance imaging (MRI) is considered the gold standard for prostate segmentation. Computed tomography (CT)-based segmentation is prone to observer bias, potentially overestimating the prostate volume by ∼ 30 % compared to MRI. However, MRI accessibility is challenging for patients with contraindications or in rural areas globally with limited clinical resources.

Purpose

This study investigates the possibility of achieving MRI-level prostate auto-segmentation accuracy using CT-only input via a deep learning (DL) model trained with CT-MRI registered segmentation.

Methods and Materials

A cohort of 111 definitive prostate radiotherapy patients with both CT and MRI images was retrospectively grouped into training (n = 37) and validation (n = 20) (where reference contours were derived from CT-MRI registration), and testing (n = 54) sets. Two commercial DL models were benchmarked against the reference contours in the training and validation sets. A custom DL model was incrementally retrained using the training dataset, quantitatively evaluated on the validation dataset, and qualitatively assessed by two different physician groups on the validation and testing datasets. A contour quality assurance (QA) model, established from the proposed model on the validation dataset, was applied to the test group to identify potential errors, confirmed by human visual inspection.

Results

Two commercial models exhibited large deviations in the prostate apex with CT-only input (median: 0.77/0.78 for Dice similarity coefficient (DSC), and 0.80 cm/0.83 cm for 95 % directed Hausdorff Distance (HD95), respectively). The proposed model demonstrated superior geometric similarity compared to commercial models, particularly in the apex region, with improvements of 0.05/0.17 cm and 0.06/0.25 cm in median DSC/HD95, respectively. Physician evaluation on MRI-CT registration data rated 69 %-78 % of the proposed model’s contours as clinically acceptable without modifications. Additionally, 73 % of cases flagged by the contour quality assurance (QA) model were confirmed via visual inspection.

Conclusions

The proposed incremental learning strategy based on CT-MRI registration information enhances prostate segmentation accuracy when MRI availability is limited clinically.
背景:磁共振成像(MRI)被认为是前列腺分割的黄金标准。基于计算机断层扫描(CT)的分割容易出现观察者偏差,与核磁共振成像相比,可能会高估前列腺体积 30%。然而,对于有禁忌症的患者或全球临床资源有限的农村地区来说,MRI的可及性具有挑战性。目的:本研究通过使用CT-MRI注册分割训练的深度学习(DL)模型,研究使用纯CT输入达到MRI水平的前列腺自动分割准确性的可能性:回顾性地将111名同时具有CT和MRI图像的确诊前列腺放疗患者分为训练组(n = 37)、验证组(n = 20)(其中参考轮廓来自CT-MRI登记)和测试组(n = 54)。根据训练集和验证集中的参考轮廓,对两个商业 DL 模型进行了基准测试。使用训练数据集对自定义 DL 模型进行增量再训练,在验证数据集上进行定量评估,并由两个不同的医生小组在验证和测试数据集上进行定性评估。根据验证数据集上的建议模型建立的轮廓质量保证(QA)模型被应用于测试组,以识别潜在的错误,并通过人工目测进行确认:结果:两个商用模型在前列腺顶点与纯 CT 输入值的偏差较大(中位数为 0.77/0.78,D 值为 0.77/0.78):狄斯相似系数(DSC)为 0.77/0.78,95%定向豪斯多夫距离(HD95)为 0.80 厘米/0.83 厘米)。与商用模型相比,所提出的模型具有更高的几何相似性,尤其是在顶点区域,DSC/HD95 中值分别提高了 0.05/0.17 厘米和 0.06/0.25 厘米。医生对核磁共振-计算机断层扫描(MRI-CT)登记数据进行评估后,认为 69%-78% 的拟议模型轮廓在不做修改的情况下临床上可以接受。此外,轮廓质量保证(QA)模型标记的病例中有 73% 通过目测得到了确认:结论:基于 CT-MRI 注册信息的增量学习策略提高了前列腺分割的准确性,而磁共振成像在临床上的可用性是有限的。
{"title":"Achieving accurate prostate auto-segmentation on CT in the absence of MR imaging","authors":"Jingwei Duan ,&nbsp;Riley C. Tegtmeier ,&nbsp;Carlos E. Vargas ,&nbsp;Nathan Y. Yu ,&nbsp;Brady S. Laughlin ,&nbsp;Jean-Claude M. Rwigema ,&nbsp;Justin D. Anderson ,&nbsp;Libing Zhu ,&nbsp;Quan Chen ,&nbsp;Yi Rong","doi":"10.1016/j.radonc.2024.110588","DOIUrl":"10.1016/j.radonc.2024.110588","url":null,"abstract":"<div><h3>Background</h3><div>Magnetic resonance imaging (MRI) is considered the gold standard for prostate segmentation. Computed tomography (CT)-based segmentation is prone to observer bias, potentially overestimating the prostate volume by ∼ 30 % compared to MRI. However, MRI accessibility is challenging for patients with contraindications or in rural areas globally with limited clinical resources.</div></div><div><h3>Purpose</h3><div>This study investigates the possibility of achieving MRI-level prostate auto-segmentation accuracy using CT-only input via a deep learning (DL) model trained with CT-MRI registered segmentation.</div></div><div><h3>Methods and Materials</h3><div>A cohort of 111 definitive prostate radiotherapy patients with both CT and MRI images was retrospectively grouped into training (n = 37) and validation (n = 20) (where reference contours were derived from CT-MRI registration), and testing (n = 54) sets. Two commercial DL models were benchmarked against the reference contours in the training and validation sets. A custom DL model was incrementally retrained using the training dataset, quantitatively evaluated on the validation dataset, and qualitatively assessed by two different physician groups on the validation and testing datasets. A contour quality assurance (QA) model, established from the proposed model on the validation dataset, was applied to the test group to identify potential errors, confirmed by human visual inspection.</div></div><div><h3>Results</h3><div>Two commercial models exhibited large deviations in the prostate apex with CT-only input (median: 0.77/0.78 for Dice similarity coefficient (DSC), and 0.80 cm/0.83 cm for 95 % directed Hausdorff Distance (HD95), respectively). The proposed model demonstrated superior geometric similarity compared to commercial models, particularly in the apex region, with improvements of 0.05/0.17 cm and 0.06/0.25 cm in median DSC/HD95, respectively. Physician evaluation on MRI-CT registration data rated 69 %-78 % of the proposed model’s contours as clinically acceptable without modifications. Additionally, 73 % of cases flagged by the contour quality assurance (QA) model were confirmed via visual inspection.</div></div><div><h3>Conclusions</h3><div>The proposed incremental learning strategy based on CT-MRI registration information enhances prostate segmentation accuracy when MRI availability is limited clinically.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110588"},"PeriodicalIF":4.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473418","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
"Cardiovascular toxicities of radiotherapy: From practical issues to new perspectives radiotherapy and Oncology" Marianne C. Aznar, Jutta Bergler-Klein, Giuseppe Boriani, David, J. Cutter, Coen Hurkmans, Mario Levis, Teresa Lopez-Fernandez, Alexander R. Lyon, Maja V. Maraldo. Radiother Oncol. 2024 Aug:197:110336. https://doi.org/10.1016/j.radonc.2024.110336.Epub 2024 may 24. "放射治疗的心血管毒性:从实际问题到放射治疗和肿瘤学的新视角" Marianne C. Aznar、Jutta Bergler-Klein、Giuseppe Boriani、David、J. Cutter、Coen Hurkmans、Mario Levis、Teresa Lopez-Fernandez、Alexander R. Lyon、Maja V. Maraldo。Radiother Oncol.2024 Aug:197:110336. https://doi.org/10.1016/j.radonc.2024.110336.Epub 2024 May 24.
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-15 DOI: 10.1016/j.radonc.2024.110583
Henk Struikmans, Anna Petoukhova, Mirjam Mast
{"title":"\"Cardiovascular toxicities of radiotherapy: From practical issues to new perspectives radiotherapy and Oncology\" Marianne C. Aznar, Jutta Bergler-Klein, Giuseppe Boriani, David, J. Cutter, Coen Hurkmans, Mario Levis, Teresa Lopez-Fernandez, Alexander R. Lyon, Maja V. Maraldo. Radiother Oncol. 2024 Aug:197:110336. https://doi.org/10.1016/j.radonc.2024.110336.Epub 2024 may 24.","authors":"Henk Struikmans, Anna Petoukhova, Mirjam Mast","doi":"10.1016/j.radonc.2024.110583","DOIUrl":"https://doi.org/10.1016/j.radonc.2024.110583","url":null,"abstract":"","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":" ","pages":"110583"},"PeriodicalIF":4.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473416","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
Dose-averaged linear energy transfer within the gross tumor volume of non-small-cell lung cancer affects the local control in carbon-ion radiotherapy 非小细胞肺癌肿瘤总体积内的剂量平均线性能量传递影响碳离子放疗的局部控制。
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-14 DOI: 10.1016/j.radonc.2024.110584
Guangsheng Li , Ningyi Ma , Weiwei Wang , Jian Chen , Jingfang Mao , Guoliang Jiang , Kailiang Wu
<div><h3>Background and purpose</h3><div>High linear energy transfer (LET) radiation exhibits stronger tumor-killing effect. However, the correlation between LET and the therapeutic efficacy in Carbon-ion radiotherapy (CIRT) for locally advanced non-small-cell lung cancer (LA-NSCLC) is currently not clear. This study aimed to investigate the relationship between the dose-averaged LET (<span><math><msub><mrow><mi>LET</mi></mrow><mi>d</mi></msub></math></span>) distribution within tumor and local recurrence for LA-NSCLC treated with CIRT.</div></div><div><h3>Methods and materials</h3><div>An analysis of 62 consecutive patients with LA-NSCLC who underwent CIRT from 2018 to 2022 was conducted. The <span><math><msub><mrow><mi>LET</mi></mrow><mi>d</mi></msub></math></span> distribution was calculated based on their treated plans, and the correlation between local recurrence and <span><math><msub><mrow><mi>LET</mi></mrow><mi>d</mi></msub></math></span>, relative biological effectiveness (RBE)-weighted doses (<span><math><msub><mi>D</mi><mrow><mi>RBE</mi></mrow></msub></math></span>) and clinical factors was investigated. Receiver operating characteristic (ROC) curve, log-rank test, and Cox regression analysis were performed based on that.</div></div><div><h3>Results</h3><div>16 patients were defined as local recurrence. Overall survival (OS) and local control (LC) at 24 months were 76.9 % and 73.2 %, respectively. The mean <span><math><msub><mrow><mi>LET</mi></mrow><mi>d</mi></msub></math></span> in internal gross tumor volume (iGTV) in the local recurrence group was 48.7 keV/µm, significantly lower than the mean <span><math><msub><mrow><mi>LET</mi></mrow><mi>d</mi></msub></math></span> of 53.2 keV/µm in the local control group (p = 0.016). No significant difference was observed in <span><math><msub><mi>D</mi><mrow><mi>RBE</mi></mrow></msub></math></span> between the local recurrence and local control groups. ROC curve analysis indicated that a percentage of 88 % of volume in iGTV receiving at least 40 keV/µm (<span><math><msub><mi>V</mi><mrow><mn>40</mn><mi>k</mi><mi>e</mi><mi>V</mi><mo>/</mo><mi>μ</mi><mi>m</mi></mrow></msub></math></span>) is the optimal threshold for predicting local recurrence (Area under curve (AUC) = 0.7636). The log-rank test and Cox regression analysis revealed that the <span><math><msub><mrow><mi>LET</mi></mrow><mi>d</mi></msub></math></span> value covering 98 % volume of iGTV (<span><math><mrow><msub><mrow><mi>LET</mi></mrow><mi>d</mi></msub><mn>98</mn><mo>%</mo></mrow></math></span>) was a significant risk factor for LC (p = 0.020).</div></div><div><h3>Conclusions</h3><div>Our study revealed an association between <span><math><msub><mrow><mi>LET</mi></mrow><mi>d</mi></msub></math></span> distribution and local recurrence in patients with LA-NSCLC. These findings suggest that lower <span><math><msub><mrow><mi>LET</mi></mrow><mi>d</mi></msub></math></span> may increase the probability of local recurrence. We suggest that <span
背景和目的:高线性能量转移(LET)辐射具有更强的肿瘤杀伤效果。然而,在局部晚期非小细胞肺癌(LA-NSCLC)的碳离子放射治疗(CIRT)中,LET与疗效之间的相关性目前尚不清楚。本研究旨在探讨接受 CIRT 治疗的 LA-NSCLC 肿瘤内剂量平均 LET(LETd)分布与局部复发之间的关系:对2018年至2022年连续接受CIRT治疗的62例LA-NSCLC患者进行了分析。根据其治疗方案计算LETd分布,并研究局部复发与LETd、相对生物有效性(RBE)加权剂量(DRBE)和临床因素之间的相关性。在此基础上进行了接收者操作特征曲线(ROC)、对数秩检验和 Cox 回归分析:结果:16 例患者被定义为局部复发。24个月的总生存率(OS)和局部控制率(LC)分别为76.9%和73.2%。局部复发组肿瘤内部总体积(iGTV)的平均LETd为48.7 keV/µm,明显低于局部控制组53.2 keV/µm的平均LETd(p = 0.016)。局部复发组和局部对照组的 DRBE 无明显差异。ROC 曲线分析表明,iGTV 中至少有 88% 的体积接受了 40 keV/µm(V40keV/μm),是预测局部复发的最佳阈值(曲线下面积 (AUC) = 0.7636)。对数秩检验和 Cox 回归分析显示,覆盖 iGTV 98% 体积的 LETd 值(LETd98%)是 LC 的重要风险因素(p = 0.020):我们的研究揭示了LA-NSCLC患者LETd分布与局部复发之间的关系。这些发现表明,较低的 LETd 可能会增加局部复发的概率。我们建议在肺癌 CIRT 中常规评估 iGTV 中的 LETd 分布。
{"title":"Dose-averaged linear energy transfer within the gross tumor volume of non-small-cell lung cancer affects the local control in carbon-ion radiotherapy","authors":"Guangsheng Li ,&nbsp;Ningyi Ma ,&nbsp;Weiwei Wang ,&nbsp;Jian Chen ,&nbsp;Jingfang Mao ,&nbsp;Guoliang Jiang ,&nbsp;Kailiang Wu","doi":"10.1016/j.radonc.2024.110584","DOIUrl":"10.1016/j.radonc.2024.110584","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background and purpose&lt;/h3&gt;&lt;div&gt;High linear energy transfer (LET) radiation exhibits stronger tumor-killing effect. However, the correlation between LET and the therapeutic efficacy in Carbon-ion radiotherapy (CIRT) for locally advanced non-small-cell lung cancer (LA-NSCLC) is currently not clear. This study aimed to investigate the relationship between the dose-averaged LET (&lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;LET&lt;/mi&gt;&lt;/mrow&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt;) distribution within tumor and local recurrence for LA-NSCLC treated with CIRT.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods and materials&lt;/h3&gt;&lt;div&gt;An analysis of 62 consecutive patients with LA-NSCLC who underwent CIRT from 2018 to 2022 was conducted. The &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;LET&lt;/mi&gt;&lt;/mrow&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt; distribution was calculated based on their treated plans, and the correlation between local recurrence and &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;LET&lt;/mi&gt;&lt;/mrow&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt;, relative biological effectiveness (RBE)-weighted doses (&lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;D&lt;/mi&gt;&lt;mrow&gt;&lt;mi&gt;RBE&lt;/mi&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt;) and clinical factors was investigated. Receiver operating characteristic (ROC) curve, log-rank test, and Cox regression analysis were performed based on that.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;16 patients were defined as local recurrence. Overall survival (OS) and local control (LC) at 24 months were 76.9 % and 73.2 %, respectively. The mean &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;LET&lt;/mi&gt;&lt;/mrow&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt; in internal gross tumor volume (iGTV) in the local recurrence group was 48.7 keV/µm, significantly lower than the mean &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;LET&lt;/mi&gt;&lt;/mrow&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt; of 53.2 keV/µm in the local control group (p = 0.016). No significant difference was observed in &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;D&lt;/mi&gt;&lt;mrow&gt;&lt;mi&gt;RBE&lt;/mi&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt; between the local recurrence and local control groups. ROC curve analysis indicated that a percentage of 88 % of volume in iGTV receiving at least 40 keV/µm (&lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;V&lt;/mi&gt;&lt;mrow&gt;&lt;mn&gt;40&lt;/mn&gt;&lt;mi&gt;k&lt;/mi&gt;&lt;mi&gt;e&lt;/mi&gt;&lt;mi&gt;V&lt;/mi&gt;&lt;mo&gt;/&lt;/mo&gt;&lt;mi&gt;μ&lt;/mi&gt;&lt;mi&gt;m&lt;/mi&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt;) is the optimal threshold for predicting local recurrence (Area under curve (AUC) = 0.7636). The log-rank test and Cox regression analysis revealed that the &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;LET&lt;/mi&gt;&lt;/mrow&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt; value covering 98 % volume of iGTV (&lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;LET&lt;/mi&gt;&lt;/mrow&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;/msub&gt;&lt;mn&gt;98&lt;/mn&gt;&lt;mo&gt;%&lt;/mo&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;) was a significant risk factor for LC (p = 0.020).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Our study revealed an association between &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;LET&lt;/mi&gt;&lt;/mrow&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt; distribution and local recurrence in patients with LA-NSCLC. These findings suggest that lower &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;LET&lt;/mi&gt;&lt;/mrow&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt; may increase the probability of local recurrence. We suggest that &lt;span","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110584"},"PeriodicalIF":4.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473435","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
The Assisi think tank focus review on postoperative radiation for lobular breast cancer 阿西西智囊团对乳腺小叶癌术后放射治疗的重点审查。
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-11 DOI: 10.1016/j.radonc.2024.110573
O. Kaidar-Person , I Ratosa , P. Franco , V. Masiello , F. Marazzi , S. Pedretti , A. Ciabattoni , M.C. Leonardi , T. Tramm , CE Coles , I Meattini , M. Arenas , B.V. Offersen , L.J. Boersma , V. Valentini , D. Dodwell , P. Poortmans , C. Aristei
The “Assisi Think Tank Meeting” (ATTM) on Breast Cancer, endorsed by the European Society for Radiotherapy & Oncology (ESTRO) and the Italian Association of Radiotherapy and Clinical Oncology (AIRO), and conducted under the auspices of the European Society of Breast Cancer Specialists (EUSOMA), is a bi-annual meeting aiming to identify major clinical challenges in breast cancer radiation therapy (RT) and proposing clinical trials to address them. The topics discussed at the meeting are pre-selected by the steering committee. At the meeting, these topics are discussed in different working groups (WG), after preparation of the meeting by performing a systematic review of existing data and of ongoing trials. Prior to the meeting, each WG designs a survey on the topic to be discussed to reflect current clinical practice and to identify areas requiring further research. Herein, we present the work done by the Assisi WG focusing on lobular carcinoma and the RT perspectives in its treatment, including providing recommendations for locoregional therapy, mainly RT for patients with non-metastatic lobular breast cancer.
乳腺癌 "阿西西智囊团会议"(ATM)由欧洲放射治疗与肿瘤学会(ESTRO)和意大利放射治疗与临床肿瘤学会(AIRO)批准,在欧洲乳腺癌专家学会(EUSOMA)的支持下举行,是一年两次的会议,旨在确定乳腺癌放射治疗(RT)的主要临床挑战,并针对这些挑战提出临床试验建议。会议讨论的主题由指导委员会预先选定。在对现有数据和正在进行的试验进行系统回顾,为会议做准备后,这些议题将在不同的工作组(WG)中进行讨论。会前,每个工作组都会就讨论主题设计一份调查问卷,以反映当前的临床实践,并确定需要进一步研究的领域。在此,我们将介绍阿西西工作组所做的工作,重点是小叶癌及其治疗中的 RT 观点,包括为局部治疗提供建议,主要是针对非转移性小叶乳腺癌患者的 RT。
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引用次数: 0
Hybrid ultra-high and conventional dose rate treatments with electrons and photons for the clinical transfer of FLASH-RT to deep-seated targets: A treatment planning study 利用电子和光子进行超高剂量率和常规剂量率混合治疗,将FLASH-RT应用于深部靶点的临床转移:治疗规划研究
IF 4.9 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-11 DOI: 10.1016/j.radonc.2024.110576
Till Tobias Böhlen , Michele Zeverino , Jean‐François Germond , Rémy Kinj , Luis Schiappacasse , François Bochud , Fernanda Herrera , Jean Bourhis , Raphaël Moeckli

Purpose

This study explores the dosimetric feasibility and plan quality of hybrid ultra-high dose rate (UHDR) electron and conventional dose rate (CDR) photon (HUC) radiotherapy for treating deep-seated tumours with FLASH-RT.

Methods

HUC treatment planning was conducted optimizing a broad UHDR electron beam (between 20–250 MeV) combined with a CDR VMAT for a glioblastoma, a pancreatic cancer, and a prostate cancer case. HUC plans were based on clinical prescription and fractionation schemes and compared against clinically delivered plans. Considering a HUC boost treatment for the glioblastoma consisting of a 15-Gy-single-fraction UHDR electron boost supplemented with VMAT, two scenarios for FLASH sparing were assessed using FLASH-modifying-factor-weighted doses.

Results

For all three patient cases, HUC treatment plans demonstrated comparable dosimetric quality to clinical plans, with similar PTV coverage (V95% within 0.5 %), homogeneity, and critical OAR-sparing. At the same time, HUC plans delivered a substantial portion of the dose to the PTV (Dmedian of 50–69 %) and surrounding tissues at UHDR. For the HUC boost treatment of the glioblastoma, the first FLASH sparing scenario showed a moderate FLASH sparing magnitude (10 % for D2%,PTV) for the 15-Gy UHDR electron boost, while the second scenario indicated a more substantial sparing of brain tissues inside and outside the PTV (32 % for D2%,PTV, 31 % for D2%,Brain).

Conclusions

From a planning perspective, HUC treatments represent a feasible approach for delivering dosimetrically conformal UHDR treatments, potentially mitigating technical challenges associated with delivering conformal FLASH-RT for deep-seated tumours. While further research is needed to optimize HUC fractionation and delivery schemes for specific patient cohorts, HUC treatments offer a promising avenue for the clinical transfer of FLASH-RT.
目的 本研究探讨了超高剂量率(UHDR)电子和常规剂量率(CDR)光子混合放疗(HUC)的剂量学可行性和计划质量,以FLASH-RT治疗深部肿瘤。方法 对一例胶质母细胞瘤、一例胰腺癌和一例前列腺癌病例进行了超高剂量率电子束(20-250MeV)与常规剂量率光子混合放疗计划优化。HUC计划以临床处方和分层方案为基础,并与临床实施计划进行比较。结果在所有三个病例中,HUC 治疗计划的剂量质量与临床计划相当,具有相似的 PTV 覆盖率(V95% 在 0.5 % 以内)、均匀性和临界 OAR 保留率。同时,HUC 计划在 UHDR 时向 PTV(Dmedian 为 50-69%)和周围组织投放了大量剂量。对于胶质母细胞瘤的 HUC 增量治疗,第一种 FLASH 清除方案显示,15-Gy UHDR 电子增量对 FLASH 的清除程度适中(D2%,PTV 为 10%),而第二种方案显示对 PTV 内外的脑组织的清除程度更高(D2%,PTV 为 32%,D2%,Brain 为 31%)。结论从计划的角度来看,HUC 治疗是一种可行的方法,可用于进行剂量学保形 UHDR 治疗,从而有可能减轻与对深部肿瘤进行保形 FLASH-RT 治疗相关的技术挑战。虽然还需要进一步研究来优化针对特定患者群的 HUC 分层和给药方案,但 HUC 治疗为 FLASH-RT 的临床应用提供了一条前景广阔的途径。
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Radiotherapy and Oncology
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