Cancer Radiotherapie最新文献

英文中文

Differential plasma cytokine variation following X-ray or proton brain irradiation using machine-learning approaches 利用机器学习方法研究 X 射线或质子脑辐照后血浆细胞因子的差异变化。

IF 1.5 4区医学 Q4 ONCOLOGY

Cancer Radiotherapie

Pub Date : 2024-10-01 DOI: 10.1016/j.canrad.2024.08.001

Purpose

X-ray and proton irradiation have been reported to induce distinct modifications in cytokine expression in vitro and in vivo, suggesting a dissimilar inflammatory response between X-rays and protons. We aimed to investigate the differences in cytokine profiles early following fractionated brain irradiation with X-rays or protons and their relationship with leukocyte subpopulations in rodents.

Materials and methods

Our study utilized data from 80 tumor-free mice subjected to X-ray or proton brain irradiation in four fractions of 2.5 Gy. Sixteen non-irradiated mice were used as the controls. Blood was collected 12 h postirradiation to examine the profile of 13 cytokines. Correlation analysis, principal component analysis (PCA), and tree-based modeling were used to investigate the relationship between cytokine levels and leukocyte subpopulation variations following irradiation in the blood.

Results

Regardless of the irradiation type, brain irradiation resulted in a notable elevation in the plasma levels of IFN-γ and MCP-1. The use of either X-ray or proton beam had differential effect on plasma cytokine levels following brain irradiation. Specifically, X-ray irradiation was associated with significantly increased plasma levels of IFN-β, IL-12p70, and IL-23, along with a decreased level of IL-1α, in comparison to proton irradiation. Correlation analysis revealed distinct cytokine regulatory patterns between X-ray and proton brain irradiation. PCA highlighted the association of MCP-1, IL-6, TNF-α, IL-17A, and IFN-γ with neutrophils, monocytes, and naïve T-cells following X-ray irradiation. TNF-α and IL-23 levels correlated with naïve CD4+-cells following proton irradiation. Tree-based models demonstrated that high TNF-α level resulted in an increase in naïve T-cells, neutrophils, and monocytes, whereas low IL-6 level was associated with decreases in these cell counts.

Conclusion

Our findings revealed distinct inflammatory responses induced by X-ray irradiation in contrast to proton brain irradiation, as demonstrated by the differential regulation of cytokines in the bloodstream. Moreover, the study highlighted the association between specific cytokine levels and various leukocyte subpopulations. Further investigation is essential to accurately determine the impact of proton and X-ray brain irradiation on the inflammatory response and the efficacy of radiotherapy treatment.

目的：据报道，X 射线和质子辐照会引起体外和体内细胞因子表达的不同改变，这表明 X 射线和质子之间存在不同的炎症反应。我们的目的是研究啮齿类动物在接受 X 射线或质子分次脑照射后早期细胞因子谱的差异及其与白细胞亚群的关系：我们的研究利用了 80 只无肿瘤小鼠的数据，这些小鼠接受了 X 射线或质子脑辐照，辐照剂量为 2.5Gy 的四次分段辐照。16 只未接受辐照的小鼠作为对照组。辐照后 12 小时采集血液，检测 13 种细胞因子的分布情况。采用相关分析、主成分分析（PCA）和基于树的模型来研究血液中细胞因子水平与辐照后白细胞亚群变化之间的关系：结果：无论采用哪种辐照类型，脑辐照都会导致血浆中 IFN-γ 和 MCP-1 水平显著升高。X射线或质子束对脑部照射后血浆细胞因子水平的影响各不相同。具体来说，与质子照射相比，X射线照射与血浆中IFN-β、IL-12p70和IL-23水平的显著升高有关，而与IL-1α水平的降低有关。相关性分析表明，X射线和质子脑照射的细胞因子调控模式截然不同。PCA 强调了 X 射线照射后 MCP-1、IL-6、TNF-α、IL-17A 和 IFN-γ 与中性粒细胞、单核细胞和幼稚 T 细胞的关联。质子辐照后，TNF-α和IL-23水平与幼稚CD4+细胞相关。基于树的模型显示，TNF-α水平高会导致幼稚T细胞、中性粒细胞和单核细胞增加，而IL-6水平低则会导致这些细胞数量减少：我们的研究结果表明，X 射线辐照与质子脑辐照诱发的炎症反应截然不同，血液中细胞因子的不同调节也证明了这一点。此外，该研究还强调了特定细胞因子水平与各种白细胞亚群之间的关联。要准确确定质子和 X 射线脑照射对炎症反应和放疗疗效的影响，必须开展进一步的研究。

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引用次数: 0

Prediction of radiotherapy toxicity: 20 years of COPERNIC radiosensitivity diagnosis procedure 放疗毒性预测：COPERNIC 辐射敏感性诊断程序 20 年。

IF 1.5 4区医学 Q4 ONCOLOGY

Cancer Radiotherapie

Pub Date : 2024-10-01 DOI: 10.1016/j.canrad.2024.05.002

Purpose

Since 2004, in the frame of the care pathway, our Research Unit has replied to the demand of expertise of radiation oncologists about the individual radiosensitivity of some of their patients. This procedure, called COPERNIC, is based on a skin biopsy and the radiation-induced nucleoshuttling of the ATM protein (the RIANS model), a major actor of DNA break repair and signaling. In 2016, with the first 117 COPERNIC fibroblast lines, we obtained a significant correlation between the maximum number of the nuclear ATM foci, pATM_max, and the CTCAE severity grade of the post-radiotherapy tissue reactions. In this study, we propose to verify the validity of our previous findings with a new COPERNIC data subset obtained in the 2014–2024 period.

Materials and methods

We applied a standard immunofluorescence technique to quiescent COPERNIC fibroblasts to assess, after 2 Gy, the level of micronuclei, γH2AX and pATM foci. The 117 COPERNIC data published in 2016 were considered as the reference data subset. A new COPERNIC data subset composed of 133 fibroblast cell lines was considered as the validating data subset.

Results

Our data showed that spontaneous or residual micronuclei levels, and residual γH2AX foci levels cannot predict CTCAE grades. Conversely, the linear formula linking the maximal number of pATM foci and the corresponding CTCAE grade and obtained in 2016 from the reference data subset fitted well the validating data.

Conclusions

The maximal number of pATM foci appears to be one of the most reliable biomarkers for predicting post-radiotherapy radiotoxicity.

目的：自 2004 年以来，我们的研究小组在治疗路径的框架内，满足了放射肿瘤专家对部分患者的个体放射敏感性的专业知识需求。这一程序被称为 "COPERNIC"，基于皮肤活检和辐射诱导的ATM蛋白核分裂（RIANS模型），ATM蛋白是DNA断裂修复和信号转导的主要参与者。2016 年，通过第一批 117COPERNIC 成纤维细胞系，我们发现核 ATM 病灶的最大数量 pATMmax 与放疗后组织反应的 CTCAE 严重程度分级之间存在显著相关性。在本研究中，我们建议用 2014-2024 年间获得的新 COPERNIC 数据子集来验证我们之前发现的有效性：我们对静止的 COPERNIC 成纤维细胞采用标准免疫荧光技术，评估 2Gy 后微核、γH2AX 和 pATM 病灶的水平。2016年公布的117个COPERNIC数据被视为参考数据子集。由 133 个成纤维细胞系组成的新 COPERNIC 数据子集被视为验证数据子集：我们的数据显示，自发或残留微核水平以及残留γH2AX病灶水平不能预测CTCAE分级。相反，2016年从参考数据子集中获得的连接pATM病灶最大数量和相应CTCAE分级的线性公式与验证数据非常吻合：pATM病灶的最大数量似乎是预测放疗后放射性毒性最可靠的生物标志物之一。

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引用次数: 0

Issue Contents 议题内容

IF 1.5 4区医学 Q4 ONCOLOGY

Cancer Radiotherapie

Pub Date : 2024-10-01 DOI: 10.1016/S1278-3218(24)00162-8

引用次数: 0

Overcoming the limits of pediatric brain tumor radiotherapy: The use of preclinical 3D models 克服小儿脑肿瘤放射治疗的局限性：使用临床前三维模型。

IF 1.5 4区医学 Q4 ONCOLOGY

Cancer Radiotherapie

Pub Date : 2024-10-01 DOI: 10.1016/j.canrad.2024.06.003

Radiotherapy (RT) is an integral part of managing pediatric brain tumors, yet many patients develop tumor radioresistance, leading to recurrence and poor clinical outcomes. In addition, neurocognitive impairment is a common long-term side effect of RT, significantly impairing quality of life. Indeed, increasing evidence suggests that the developing child's brain is particularly vulnerable to the neurotoxic effects of ionizing radiation. Consequently, developing novel preclinical models is crucial for studying radiation's impact on normal brain tissue and predicting patient-specific responses to RT, enabling the development of personalized therapies combined with RT. However, this area remains underexplored, primarily due to the transfer of results gathered from in vitro tumor models from adults to pediatric entities while the location and molecular characteristics of the brain tumor differ. Recent years have seen the emergence of patient-specific 3D in vitro models, which have been established for entities including glioblastoma and medulloblastoma. These models better mimic primary parenteral tumors more closely in their histological, transcriptional, and mutational characteristics, thus approximating their intratumoral heterogeneity more accurately than conventional 2D-models. In this review, we presented the main limits of pediatric brain tumor radiotherapy, including mechanisms of radioresistance, associated tumor relapse, and the side effects of irradiation on the central nervous system. We also conducted an exhaustive review to identify studies utilizing basic or advanced 3D models of pediatric brain tumors combined with irradiation and discussed how these models can overcome the limitations of RT.

放疗（RT）是治疗小儿脑肿瘤不可或缺的一部分，但许多患者会产生肿瘤放射抵抗，导致复发和不良的临床疗效。此外，神经认知障碍是 RT 常见的长期副作用，严重影响生活质量。事实上，越来越多的证据表明，发育中的儿童大脑特别容易受到电离辐射的神经毒性影响。因此，开发新的临床前模型对于研究辐射对正常脑组织的影响和预测患者对 RT 的特异性反应至关重要，这样才能开发出结合 RT 的个性化疗法。然而，这一领域仍未得到充分探索，主要原因是将从成人体外肿瘤模型收集到的结果转移到儿童实体，而脑肿瘤的位置和分子特征各不相同。近年来出现了患者特异性三维体外模型，已建立的实体包括胶质母细胞瘤和髓母细胞瘤。与传统的二维模型相比，这些模型在组织学、转录和突变特征方面更接近于原发性实体瘤，从而更准确地接近瘤内异质性。在这篇综述中，我们介绍了小儿脑肿瘤放射治疗的主要局限性，包括放射耐药机制、相关肿瘤复发以及照射对中枢神经系统的副作用。我们还进行了详尽的综述，以确定利用小儿脑肿瘤的基本或高级三维模型结合照射的研究，并讨论了这些模型如何克服 RT 的局限性。

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引用次数: 0

Tumor reirradiation: Issues, challenges and perspectives for radiobiology 肿瘤再照射：放射生物学的问题、挑战和前景。

IF 1.5 4区医学 Q4 ONCOLOGY

Cancer Radiotherapie

Pub Date : 2024-10-01 DOI: 10.1016/j.canrad.2024.08.002

The radiobiology of tumor reirradiation is poorly understood. It pertains to tumors and their sensitivity at the time of relapse, encompassing primary tumors, metastases, or secondary cancers developed in or proximal to previously irradiated tissues. The ability to control the pathology depends, in part, on understanding this sensitivity. To date, literature data remains limited regarding changes in the radiosensitivity of tissues after initial irradiation, and most proposals are based on conjecture. The response of healthy tissues at the site of irradiation raises concerns about radio-induced complications. Cumulative dose is likely a major factor in this risk, thus using equivalent dose calculations might help reduce the risk of complications. However, the correlation between mathematical equivalence formulas and clinical effects of radiobiological origin is weak, and the lack of knowledge of the alpha/beta (α/β) ratio of healthy tissues remains an obstacle to the extensive use of these formulas. However, tissues exposed to recovery dose may have a tolerance to irradiation much higher than assumed, thus further biological work remains to be developed. Also, the functionality of previously irradiated tissues could be useful in selecting the most suitable irradiation beams. Finally, research on the genomics of irradiated healthy tissues could improve the prediction of side effects and personalize radiotherapy.

人们对肿瘤再照射的放射生物学知之甚少。它与肿瘤及其复发时的敏感性有关，包括原发肿瘤、转移瘤或在先前接受过照射的组织内或其近端发生的继发性癌症。控制病理的能力部分取决于对这种敏感性的了解。迄今为止，有关初次照射后组织放射敏感性变化的文献数据仍然有限，大多数建议都是基于猜测。辐照部位健康组织的反应引发了对放射诱导并发症的担忧。累积剂量可能是造成这种风险的主要因素，因此使用当量剂量计算可能有助于降低并发症的风险。然而，数学当量公式与放射生物学临床效应之间的相关性很弱，而且对健康组织的α/β（α/β）比值缺乏了解仍是广泛使用这些公式的障碍。然而，受到恢复剂量照射的组织对辐照的耐受性可能比假定的要高得多，因此仍需进一步开展生物学研究。此外，以前辐照过的组织的功能也有助于选择最合适的辐照束。最后，对接受过辐照的健康组织进行基因组学研究，可以提高对副作用的预测能力，实现个性化放疗。

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引用次数: 0

Radiobiology research: From the present to the future 放射生物学研究：从现在到未来

IF 1.5 4区医学 Q4 ONCOLOGY

Cancer Radiotherapie

Pub Date : 2024-10-01 DOI: 10.1016/j.canrad.2024.10.001

引用次数: 0

Issue Contents 议题内容

IF 1.5 4区医学 Q4 ONCOLOGY

Cancer Radiotherapie

Pub Date : 2024-08-01 DOI: 10.1016/S1278-3218(24)00107-0

引用次数: 0

Nuclear protein in testis (NUT) midline carcinoma of the larynx: A rare case report of a paediatric patient and literature review 睾丸核蛋白（NUT）喉中线癌：一例罕见的儿科患者病例报告和文献综述。

IF 1.5 4区医学 Q4 ONCOLOGY

Cancer Radiotherapie

Pub Date : 2024-08-01 DOI: 10.1016/j.canrad.2024.02.004

Nuclear protein in testis (NUT) carcinoma is a rare neoplasm arising mainly from midline structures. It is an aggressive type of carcinoma associated with poor survival despite the use of multiple treatment modalities. Here, we present a case of a 17-year-old paediatric patient with NUT carcinoma of larynx, which is even rarer among all reported cases. The patient underwent surgery followed by radiotherapy and systemic treatment and he died 15 months after the diagnosis. The management of this rare disease requires further investigation.

睾丸核蛋白癌（NUT）是一种罕见的肿瘤，主要发生于中线结构。它是一种侵袭性癌，尽管采用了多种治疗方法，但患者的生存率很低。在这里，我们介绍了一例 17 岁儿童喉 NUT 癌患者的病例，这在所有报道的病例中更为罕见。患者接受了手术、放疗和全身治疗，确诊后 15 个月死亡。这种罕见疾病的治疗需要进一步研究。

引用次数: 0

Étude prospective longitudinale sur l’évolution de la mémoire autobiographique de patients irradiés pour une tumeur bénigne de la base du crâne [良性颅底肿瘤照射患者自传体记忆演变的前瞻性纵向研究]。

IF 1.5 4区医学 Q4 ONCOLOGY

Cancer Radiotherapie

Pub Date : 2024-08-01 DOI: 10.1016/j.canrad.2023.11.003

Purpose

Cranial irradiation can lead to long-term neurological complications, in particular memory disorders. The aim of this prospective study is to evaluate the impact of irradiation of benign skull base tumours located near the hippocampi on autobiographical memory.

Patients and methods

From 2016 to 2019, patients with cavernous sinus meningioma or pituitary adenoma treated with normofractionated irradiation were included. Patients underwent full neuropsychological assessment at baseline, 1 year and 2 years post-treatment. Neuropsychological tests were converted to Z-Score for comparability.

Results

Twelve of the 19 patients included had a complete neuropsychological evaluation at 2 years and were analysed. On the “TEMPau” test, no significant difference in autobiographical memory was found at 2 years, regardless of the period of autobiographical memory. The mean hippocampal dose had no impact on the variation in autobiographical memory. There was no significant cognitive impairment in the other domains assessed, such as attention, anterograde memory, working memory and executive functions. Autobiographical memory was independent of these other cognitive domains, which justifies its specific study.

Conclusion

Radiotherapy to the skull base for a benign pathology does not lead to significant cognitive impairment. Longer follow-up would be needed to confirm these results.

目的：颅骨照射可导致长期的神经系统并发症，尤其是记忆障碍。本前瞻性研究旨在评估位于海马附近的良性颅底肿瘤照射对自传体记忆的影响：从2016年至2019年，纳入了接受正常分次照射治疗的海绵窦脑膜瘤或垂体腺瘤患者。患者在基线、治疗后1年和2年接受了全面的神经心理学评估。为便于比较，神经心理测试结果被转换成Z-分数：在 19 名患者中，有 12 人在治疗后 2 年接受了完整的神经心理学评估，并对其进行了分析。在 "TEMPau "测试中，无论自传体记忆的时间长短，2 年后的自传体记忆均无明显差异。海马平均剂量对自传体记忆的变化没有影响。在其他评估领域，如注意力、前向记忆、工作记忆和执行功能等，没有发现明显的认知障碍。自传体记忆与其他认知领域无关，因此有必要对其进行专门研究：结论：针对良性病变的颅底放疗不会导致明显的认知障碍。要证实这些结果，还需要更长时间的随访。

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引用次数: 0

Automatic segmentation of high-risk clinical target volume and organs at risk in brachytherapy of cervical cancer with a convolutional neural network 利用卷积神经网络自动分割宫颈癌近距离治疗中的高危临床靶区和危险器官

IF 1.5 4区医学 Q4 ONCOLOGY

Cancer Radiotherapie

Pub Date : 2024-08-01 DOI: 10.1016/j.canrad.2024.03.002

Purpose

This study aimed to design an autodelineation model based on convolutional neural networks for generating high-risk clinical target volumes and organs at risk in image-guided adaptive brachytherapy for cervical cancer.

Materials and methods

A novel SERes-u-net was trained and tested using CT scans from 98 patients with locally advanced cervical cancer who underwent image-guided adaptive brachytherapy. The Dice similarity coefficient, 95th percentile Hausdorff distance, and clinical assessment were used for evaluation.

Results

The mean Dice similarity coefficients of our model were 80.8%, 91.9%, 85.2%, 60.4%, and 82.8% for the high-risk clinical target volumes, bladder, rectum, sigmoid, and bowel loops, respectively. The corresponding 95th percentile Hausdorff distances were 5.23 mm, 4.75 mm, 4.06 mm, 30.0 mm, and 20.5 mm. The evaluation results revealed that 99.3% of the convolutional neural networks-generated high-risk clinical target volumes slices were acceptable for oncologist A and 100% for oncologist B. Most segmentations of the organs at risk were clinically acceptable, except for the 25% sigmoid, which required significant revision in the opinion of oncologist A. There was a significant difference in the clinical evaluation of convolutional neural networks-generated high-risk clinical target volumes between the two oncologists (P < 0.001), whereas the score differences of the organs at risk were not significant between the two oncologists. In the consistency evaluation, a large discrepancy was observed between senior and junior clinicians. About 40% of SERes-u-net-generated contours were thought to be better by junior clinicians.

Conclusion

The high-risk clinical target volumes and organs at risk of cervical cancer generated by the proposed convolutional neural networks model can be used clinically, potentially improving segmentation consistency and efficiency of contouring in image-guided adaptive brachytherapy workflow.

目的：本研究旨在设计一种基于卷积神经网络的自动划线模型，用于生成宫颈癌图像引导自适应近距离治疗中的高风险临床靶体积和高风险器官：使用 98 例接受图像引导自适应近距离治疗的局部晚期宫颈癌患者的 CT 扫描结果，对新型 SERes-u-net 进行了训练和测试。使用 Dice 相似性系数、第 95 百分位数 Hausdorff 距离和临床评估进行评估：在高风险临床靶体积、膀胱、直肠、乙状结肠和肠套叠方面，我们模型的平均 Dice 相似系数分别为 80.8%、91.9%、85.2%、60.4% 和 82.8%。相应的第 95 百分位数豪斯多夫距离分别为 5.23 毫米、4.75 毫米、4.06 毫米、30.0 毫米和 20.5 毫米。评估结果显示，肿瘤学家 A 和肿瘤学家 B 分别认为卷积神经网络生成的高风险临床目标容积切片的 99.3% 和 100%是可接受的，大多数高风险器官的分割在临床上是可接受的，只有 25% 的乙状结肠在肿瘤学家 A 看来需要进行重大修改：由所提出的卷积神经网络模型生成的宫颈癌高危临床靶体积和高危器官可用于临床，有可能提高图像引导自适应近距离治疗工作流程中分割的一致性和轮廓塑造的效率。

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