Pierre Bischoff , Jolie Bou-Gharios , Georges Noël , Hélène Burckel
{"title":"Role of autophagy in modulating tumor cell radiosensitivity: Exploring pharmacological interventions for glioblastoma multiforme treatment","authors":"Pierre Bischoff , Jolie Bou-Gharios , Georges Noël , Hélène Burckel","doi":"10.1016/j.canrad.2024.06.001","DOIUrl":"10.1016/j.canrad.2024.06.001","url":null,"abstract":"<div><div>Autophagy is an innate cellular process characterized by self-digestion, wherein cells degrade or recycle aged proteins, misfolded proteins, and damaged organelles via lysosomal pathways. Its crucial role in maintaining cellular homeostasis, ensuring development and survival is well established. In the context of cancer therapy, autophagy's importance is firmly recognized, given its critical impact on treatment efficacy. Following radiotherapy, several factors can modulate autophagy including parameters related to radiation type and delivery methods. The concomitant use of chemotherapy with radiotherapy further influences autophagy, potentially either enhancing radiosensitivity or promoting radioresistance. This review article discusses some pharmacological agents and drugs capable of modulating autophagy levels in conjunction with radiation in tumor cells, with a focus on those identified as potential radiosensitizers in glioblastoma multiforme treatment.</div></div>","PeriodicalId":9504,"journal":{"name":"Cancer Radiotherapie","volume":"28 5","pages":"Pages 416-423"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of kV-cone beam computed tomography dose on DNA repair mechanisms: A pilot study","authors":"Christian Popotte , Élise Berthel , Romain Letellier , Tiziana Rancati , Ester Orlandi , Mélodie Munier , Paul Retif , Sandrine Pereira","doi":"10.1016/j.canrad.2024.05.001","DOIUrl":"10.1016/j.canrad.2024.05.001","url":null,"abstract":"<div><h3>Purpose</h3><div>In head and neck squamous cell carcinoma (HNSCC), early complications of the radiotherapy (RT) are observed from the beginning of the treatment to a few months after its end. During external radiotherapy treatment, several patient-dependent parameters can cause a modification of the dose distribution compared to the planned distribution due to variation in patient positioning, anatomy, or intra-fractional movements for example. To verify these parameters during treatment sessions, one of the most commonly used solutions is the cone-beam computed tomography (CBCT). Nowadays, the use of CBCT may constitutes a significant part of the total dose at the end of treatment (up to 10 cGy per session) and more often the volume irradiated by imaging is larger than the one irradiated by the treatment, leading to unintentional irradiation of nearby organs.</div><div>In this study, we asked whether the imaging low dose added to a following fraction dose (2<!--> <!-->Gy) may affect the biological response in terms of DNA repair.</div></div><div><h3>Material and methods</h3><div>Using an IVInomad dosimeter and scintillating fiber probes specially designed for this exploratory study, we exposed fibroblasts cells from head and neck cancer (HNC) patients to a CBCT dose followed by a radiotherapy fraction dose. DNA double strand breaks and DNA repair were assessed by immunofluorescence using the biomarkers gamma H2AX (γH2AX) and pATM.</div></div><div><h3>Results</h3><div>The median dose of CBCT was measured between 17 to 21 mGy per session. The kinetics of both biomarkers were found to be strongly dependent on the individual factor in radiosensitive patients. For HNC patients, a prior CBCT dose applied few minutes before the 2<!--> <!-->Gy dose may have a sublinear effect on the DNA repair mechanisms and potentially on observed health tissue toxicity.</div></div><div><h3>Conclusion</h3><div>The preliminary results obtained highlight the importance of individual and tissue factors for recognizing and repairing DSB during a treatment by radiotherapy using CBCT.</div></div>","PeriodicalId":9504,"journal":{"name":"Cancer Radiotherapie","volume":"28 5","pages":"Pages 449-452"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Combination of radiotherapy and immunotherapy in duality with the protumoral action of radiation","authors":"Benoît Paquette, Ayman Oweida","doi":"10.1016/j.canrad.2024.07.002","DOIUrl":"10.1016/j.canrad.2024.07.002","url":null,"abstract":"<div><div>Radiotherapy is widely used to treat various cancers. Its combination with immune checkpoint inhibitors is intensively studied preclinically and clinically. Although the first results were very encouraging, the number of patients who respond positively remains low, and the therapeutic benefit is often temporary. This review summarizes how radiation can stimulate an antitumor immune response and its combination with immunotherapy based on inhibiting immune checkpoints. We will provide an overview of radiotherapy parameters that should be better controlled to avoid downregulating the antitumor immune response. The low response rate of combining radiotherapy and immunotherapy could, at least in part, be caused by the stimulation of cancer cell invasion and metastasis development that occur at similar doses and number of radiation fractions. To end on a positive note, we explore how a targeted inhibition of the inflammatory cytokines induced by radiation with a cyclooxygenase-2 inhibitor could both support an antitumor immune response and block radiation-induced metastasis formation.</div></div>","PeriodicalId":9504,"journal":{"name":"Cancer Radiotherapie","volume":"28 5","pages":"Pages 484-492"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Flavia Gesualdi , Ludovic de Marzi , Marie Dutreix , Vincent Favaudon , Charles Fouillade , Sophie Heinrich
{"title":"A multidisciplinary view of flash irradiation","authors":"Flavia Gesualdi , Ludovic de Marzi , Marie Dutreix , Vincent Favaudon , Charles Fouillade , Sophie Heinrich","doi":"10.1016/j.canrad.2024.07.003","DOIUrl":"10.1016/j.canrad.2024.07.003","url":null,"abstract":"<div><div>The delivery of ultra-high dose rates of radiation, called flash irradiation or flash-RT, has emerged as a new modality of radiotherapy shaking up the paradigm of proportionality of effect and dose whatever the method of delivery of the radiation. The hallmark of flash-RT is healthy tissue sparing from the side effects of radiation without decrease of the antitumor efficiency in animal models. In this review we will define its specificities, the molecular mechanisms underlying the flash effect and the ongoing developments to bring this new modality to patient treatment.</div></div>","PeriodicalId":9504,"journal":{"name":"Cancer Radiotherapie","volume":"28 5","pages":"Pages 453-462"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Differential plasma cytokine variation following X-ray or proton brain irradiation using machine-learning approaches","authors":"Thao-Nguyen Pham , Julie Coupey , Viktoriia Ivanova , Juliette Thariat , Samuel Valable","doi":"10.1016/j.canrad.2024.08.001","DOIUrl":"10.1016/j.canrad.2024.08.001","url":null,"abstract":"<div><h3>Purpose</h3><div>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.</div></div><div><h3>Materials and methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":9504,"journal":{"name":"Cancer Radiotherapie","volume":"28 5","pages":"Pages 474-483"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laurène Sonzogni , Adeline Granzotto , Eymeric Le Reun , Joëlle Al-Choboq , Michel Bourguignon , Nicolas Foray , Larry Bodgi
{"title":"Prediction of radiotherapy toxicity: 20 years of COPERNIC radiosensitivity diagnosis procedure","authors":"Laurène Sonzogni , Adeline Granzotto , Eymeric Le Reun , Joëlle Al-Choboq , Michel Bourguignon , Nicolas Foray , Larry Bodgi","doi":"10.1016/j.canrad.2024.05.002","DOIUrl":"10.1016/j.canrad.2024.05.002","url":null,"abstract":"<div><h3>Purpose</h3><div>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<sub>max</sub>, 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.</div></div><div><h3>Materials and methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>The maximal number of pATM foci appears to be one of the most reliable biomarkers for predicting post-radiotherapy radiotoxicity.</div></div>","PeriodicalId":9504,"journal":{"name":"Cancer Radiotherapie","volume":"28 5","pages":"Pages 435-441"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Overcoming the limits of pediatric brain tumor radiotherapy: The use of preclinical 3D models","authors":"Élodie Czuba , Marlène Deschuyter , Natacha Entz-Werlé , Georges Noël , Hélène Burckel","doi":"10.1016/j.canrad.2024.06.003","DOIUrl":"10.1016/j.canrad.2024.06.003","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":9504,"journal":{"name":"Cancer Radiotherapie","volume":"28 5","pages":"Pages 424-434"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tumor reirradiation: Issues, challenges and perspectives for radiobiology","authors":"Georges Noël , Jolie Bou-Gharios , Hélène Burckel","doi":"10.1016/j.canrad.2024.08.002","DOIUrl":"10.1016/j.canrad.2024.08.002","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":9504,"journal":{"name":"Cancer Radiotherapie","volume":"28 5","pages":"Pages 493-502"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Radiobiology research: From the present to the future","authors":"Georges Noël","doi":"10.1016/j.canrad.2024.10.001","DOIUrl":"10.1016/j.canrad.2024.10.001","url":null,"abstract":"","PeriodicalId":9504,"journal":{"name":"Cancer Radiotherapie","volume":"28 5","pages":"Page 415"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}