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1.
Support Care Cancer ; 32(6): 361, 2024 May 16.
Article En | MEDLINE | ID: mdl-38753165

PURPOSE: Significant proportions of patients either refuse or discontinue radiotherapy, even in the curative setting, leading to poor clinical outcomes. This study explores patient perceptions that underlie decisions to refuse/discontinue radiotherapy at a cancer care facility in northern Sri Lanka. METHODS: An exploratory descriptive qualitative study was carried out among 14 purposively selected patients with cancer who refused/discontinued radiotherapy. In-depth semi-structured interviews were transcribed in Tamil, translated into English, coded, and thematically analyzed. RESULTS: All participants referred to radiotherapy as "current" with several understanding the procedure to involve electricity, heat, or hot vapour. Many pointed to gaps in information provided by healthcare providers, who were perceived to focus on side effects without explaining the procedure. In the absence of these crucial details, patients relied on family members and acquaintances for information, often based on second or third-hand accounts of experiences with radiotherapy. Many felt pressured by family to refuse radiation, feared radiation, or felt ashamed to ask questions, while for others COVID-19 was an impediment. All but three participants regretted their decision, claiming they would recommend radiation to patients with cancer, especially when it is offered with curative intent. CONCLUSION: Patients with cancer who refused/discontinued radiation therapy have significant information needs. While human resource deficits need to be addressed in low-resource settings like northern Sri Lanka, providing better supportive cancer care could improve clinical outcomes and save healthcare resources that would otherwise be wasted on patient preparation for radiotherapy.


Neoplasms , Qualitative Research , Treatment Refusal , Humans , Sri Lanka , Neoplasms/radiotherapy , Neoplasms/psychology , Male , Female , Middle Aged , Adult , Aged , Treatment Refusal/psychology , Radiotherapy/methods , Radiotherapy/psychology , COVID-19 , Interviews as Topic
2.
Front Immunol ; 15: 1373738, 2024.
Article En | MEDLINE | ID: mdl-38779678

Introduction: While radiotherapy has long been recognized for its ability to directly ablate cancer cells through necrosis or apoptosis, radiotherapy-induced abscopal effect suggests that its impact extends beyond local tumor destruction thanks to immune response. Cellular proliferation and necrosis have been extensively studied using mathematical models that simulate tumor growth, such as Gompertz law, and the radiation effects, such as the linear-quadratic model. However, the effectiveness of radiotherapy-induced immune responses may vary among patients due to individual differences in radiation sensitivity and other factors. Methods: We present a novel macroscopic approach designed to quantitatively analyze the intricate dynamics governing the interactions among the immune system, radiotherapy, and tumor progression. Building upon previous research demonstrating the synergistic effects of radiotherapy and immunotherapy in cancer treatment, we provide a comprehensive mathematical framework for understanding the underlying mechanisms driving these interactions. Results: Our method leverages macroscopic observations and mathematical modeling to capture the overarching dynamics of this interplay, offering valuable insights for optimizing cancer treatment strategies. One shows that Gompertz law can describe therapy effects with two effective parameters. This result permits quantitative data analyses, which give useful indications for the disease progression and clinical decisions. Discussion: Through validation against diverse data sets from the literature, we demonstrate the reliability and versatility of our approach in predicting the time evolution of the disease and assessing the potential efficacy of radiotherapy-immunotherapy combinations. This further supports the promising potential of the abscopal effect, suggesting that in select cases, depending on tumor size, it may confer full efficacy to radiotherapy.


Immunotherapy , Neoplasms , Humans , Neoplasms/therapy , Neoplasms/immunology , Neoplasms/radiotherapy , Immunotherapy/methods , Combined Modality Therapy , Models, Theoretical , Radiotherapy/methods
3.
Cells ; 13(10)2024 May 14.
Article En | MEDLINE | ID: mdl-38786057

The advent of FLASH radiotherapy (FLASH-RT) has brought forth a paradigm shift in cancer treatment, showcasing remarkable normal cell sparing effects with ultra-high dose rates (>40 Gy/s). This review delves into the multifaceted mechanisms underpinning the efficacy of FLASH effect, examining both physicochemical and biological hypotheses in cell biophysics. The physicochemical process encompasses oxygen depletion, reactive oxygen species, and free radical recombination. In parallel, the biological process explores the FLASH effect on the immune system and on blood vessels in treatment sites such as the brain, lung, gastrointestinal tract, skin, and subcutaneous tissue. This review investigated the selective targeting of cancer cells and the modulation of the tumor microenvironment through FLASH-RT. Examining these mechanisms, we explore the implications and challenges of integrating FLASH-RT into cancer treatment. The potential to spare normal cells, boost the immune response, and modify the tumor vasculature offers new therapeutic strategies. Despite progress in understanding FLASH-RT, this review highlights knowledge gaps, emphasizing the need for further research to optimize its clinical applications. The synthesis of physicochemical and biological insights serves as a comprehensive resource for cell biology, molecular biology, and biophysics researchers and clinicians navigating the evolution of FLASH-RT in cancer therapy.


Neoplasms , Humans , Neoplasms/radiotherapy , Neoplasms/pathology , Neoplasms/metabolism , Tumor Microenvironment/radiation effects , Radiotherapy/methods , Animals , Reactive Oxygen Species/metabolism
4.
Rev Med Liege ; 79(S1): 129-132, 2024 May.
Article Fr | MEDLINE | ID: mdl-38778661

In a former publication, we summarized basic principles of network science in order to understand its potential, especially within the field of oncology. This rather young science offers, for example, the opportunity to identify new systemic treatment options. However, these are not the only therapeutic options within the arsenal devoted to the battle against cancer. The two other main pillars of treatment are surgery and radiotherapy. It is our purpose to highlight some applications - rather limited nowadays - of network science in radiotherapy. Data are not so abundant compared to the field of systemic treatments.


Dans un article précédent, les préceptes de base de la science des réseaux ont été sommairement abordés, afin d'en illustrer l'intérêt en cancérologie, en général. Nous avons pu faire le point - de façon non exhaustive - sur l'utilité de cette science assez jeune, en montrant, par exemple, son apport en matière d'identification de moyens systémiques de traitement. Les traitements systémiques font partie de l'arsenal thérapeutique, tout comme d'ailleurs la chirurgie et la radiothérapie. Nous voulons décrire brièvement certaines applications de la science des réseaux quand il s'agit du domaine particulier des radiations ionisantes, même si leur nombre est somme toute plus limité par rapport à ce qui est publié dans le domaine des traitements systémiques.


Neoplasms , Humans , Neoplasms/radiotherapy , Radiotherapy/methods , Radiation Oncology
5.
Sci Rep ; 14(1): 10637, 2024 05 09.
Article En | MEDLINE | ID: mdl-38724569

Hadron therapy is an advanced radiation modality for treating cancer, which currently uses protons and carbon ions. Hadrons allow for a highly conformal dose distribution to the tumour, minimising the detrimental side-effects due to radiation received by healthy tissues. Treatment with hadrons requires sub-millimetre spatial resolution and high dosimetric accuracy. This paper discusses the design, fabrication and performance tests of a detector based on Gas Electron Multipliers (GEM) coupled to a matrix of thin-film transistors (TFT), with an active area of 60 × 80 mm2 and 200 ppi resolution. The experimental results show that this novel detector is able to detect low-energy (40 kVp X-rays), high-energy (6 MeV) photons used in conventional radiation therapy and protons and carbon ions of clinical energies used in hadron therapy. The GEM-TFT is a compact, fully scalable, radiation-hard detector that measures secondary electrons produced by the GEMs with sub-millimetre spatial resolution and a linear response for proton currents from 18 pA to 0.7 nA. Correcting known detector defects may aid in future studies on dose uniformity, LET dependence, and different gas mixture evaluation, improving the accuracy of QA in radiotherapy.


Radiometry , Radiometry/instrumentation , Radiometry/methods , Humans , Radiotherapy/methods , Radiotherapy/standards , Radiotherapy/instrumentation , Quality Assurance, Health Care , Electrons , Radiotherapy Dosage , Neoplasms/radiotherapy , Equipment Design , Proton Therapy/instrumentation , Proton Therapy/methods
6.
Rev Med Liege ; 79(S1): 16-19, 2024 May.
Article Fr | MEDLINE | ID: mdl-38778644

Radiation therapy is the use of radiation to treat cancer cells while preserving healthy tissue. More than half of cancer patients will receive radiation therapy at some point during their treatment. The implementation of a Quality Management System (QMS) in radiotherapy departments guarantees high quality care and optimal safety for patients. The QMS is a set of policies, procedures and processes aimed at ensuring effective management of the quality of treatments. It is crucial for planning, implementing, monitoring and continuously improving the care of radiotherapy patients. The benefits of the QMS for patients are multiple. It provides high quality support through specific protocols and deadlines. The security of processing is reinforced by the continuous training of personnel, the monitoring of incidents and the analysis of errors. Developing a culture of safety and continuous improvement also helps to minimize risk. In conclusion, the implementation of a QMS in radiotherapy departments guarantees quality care, secure and adapted to the individual needs of patients. This improves patient satisfaction while reducing the risk of errors.


La radiothérapie consiste à utiliser des radiations pour traiter les cellules cancéreuses, tout en préservant les tissus sains. Plus de la moitié des patients atteints de cancer recevront une radiothérapie à un moment donné de leur traitement. La mise en place d'un Système de Management Qualité (SMQ) dans les services de radiothérapie garantit des soins de haute qualité et une sécurité optimale pour les patients. Le SMQ est un ensemble de politiques, procédures et processus visant à assurer la gestion efficace de la qualité des traitements. Il est crucial pour planifier, implémenter, contrôler et améliorer continuellement la prise en charge des patients en radiothérapie. Les avantages du SMQ sont multiples. Il assure une prise en charge de haute qualité grâce à des protocoles et des délais spécifiques. La sécurité des traitements est renforcée par la formation continue du personnel, la surveillance des incidents et l'analyse des erreurs. Le développement d'une culture de sécurité et d'amélioration continue contribue également à minimiser les risques. En conclusion, la mise en place d'un SMQ dans les services de radiothérapie garantit des traitements de qualité, sécurisés et adaptés aux besoins individuels des patients. Cette approche améliore la satisfaction des patients, tout en réduisant les risques d'erreurs.


Patient Safety , Radiotherapy , Humans , Radiotherapy/standards , Radiotherapy/adverse effects , Radiotherapy/methods , Quality Assurance, Health Care , Neoplasms/radiotherapy
7.
Rev Med Liege ; 79(S1): 66-74, 2024 May.
Article Fr | MEDLINE | ID: mdl-38778653

Radiation therapy has many indications in veterinary oncology and allows a multidisciplinary approach for the treatment of canine and feline patients. Radiation therapy can be recommended as a sole therapy in case of radiosensitive tumors or can be associated to surgery and/or chemotherapy after marginal excision for example. It can also be recommended as a palliative treatment for patients with an inoperable or painful tumor or disseminated disease. Radiation therapy significantly improves the quality of life and survival time of treated animals and should be part of the therapeutic modalities in veterinary medicine. The University of Liège developed the first veterinary center of radiation therapy in Belgium and can therefore participate in improving therapeutic management of cancerous animal patients.


La radiothérapie présente de nombreuses indications en oncologie vétérinaire et permet une approche multidisciplinaire pour le traitement de nos patients cancéreux canins et félins.La radiothérapie peut être recommandée seule pour le traitement de tumeurs radiosensibles, ou associée à la chirurgie et/ou la chimiothérapie notamment lors d'exérèse marginale. Elle a également sa place dans une prise en charge palliative de certains patients présentant une tumeur inopérable ou douloureuse, ou encore une maladie disséminée. La radiothérapie permet d'améliorer significativement la qualité et l'espérance de vie des animaux traités et à ce titre, doit faire partie de l'arsenal thérapeutique vétérinaire. L'Université de Liège possède, depuis peu, l'unique centre de radiothérapie vétérinaire en Belgique et peut ainsi participer à l'amélioration de la prise en charge des animaux cancéreux.


Cat Diseases , Dog Diseases , Neoplasms , Animals , Cats , Belgium , Cat Diseases/radiotherapy , Dogs , Neoplasms/radiotherapy , Dog Diseases/radiotherapy , Radiotherapy/methods , Veterinary Medicine
8.
Rev Med Liege ; 79(S1): 100-106, 2024 May.
Article Fr | MEDLINE | ID: mdl-38778656

Because of its prevalence and high mortality rate, cancer is a major public health challenge. Radiotherapy is an important treatment option, and makes extensive use of medical imaging. Until now, this type of tool has been reserved to professionals, but it is now opening up to wider use, including by patients themselves for educational purposes. However, this type of usage has been little explored so far. An experimental feasibility study was carried out in the radiotherapy department of the University Hospital of Liège on adult patients with cancer or pulmonary metastases, assigned to two randomized groups. In addition to the usual information given by the radiotherapist, the patients of the experimental group benefited from an intervention consisting in the 3D visualization of their own medical images via the free and open-source computer software «Stone of Orthanc¼. The study results show a low refuse rate (8.2 %) for the 15 patients recruited. Although non-significant, the experimental group showed a median gain in global perception of knowledge, a decrease in anxiety scores and emotional distress. A significant reduction (p = 0.043) was observed for the depression score. The positive results of the feasibility study encourage further work and reinforce the positioning of medical imaging as a tool for therapeutic patient education.


De par sa fréquence et son taux de mortalité élevé, le cancer représente un problème de santé publique majeur. Parmi les traitements possibles, la radiothérapie tient une place importante et fait appel massivement à l'imagerie médicale. Jusqu'ici réservé aux professionnels, ce type d'outil s'ouvre à un usage plus large, y compris par le patient lui-même dans une perspective éducative. Mais cette utilisation est restée peu explorée jusqu'à présent. Une étude expérimentale de faisabilité a ainsi été menée au sein du service de Radiothérapie du CHU de Liège sur des patients adultes avec cancer ou métastases pulmonaires, répartis en deux groupes randomisés. En plus des informations habituellement données par le radiothérapeute, le groupe expérimental a bénéficié d'une intervention consistant en la visualisation en 3D de ses propres images médicales via le logiciel libre et open-source «Stone of Orthanc¼. Les résultats de l'étude indiquent un taux de refus faible (8,2 %) pour les 15 patients recrutés. Bien que non significatif, le groupe expérimental a montré, par rapport au groupe contrôle, un gain médian dans la perception globale de connaissances ainsi qu'une diminution des scores liés à l'anxiété et à la détresse émotionnelle. Une réduction significative (p = 0,043) est observée pour le score de dépression. Les résultats positifs de l'étude de faisabilité encouragent la poursuite des travaux et renforcent le positionnement de l'usage de l'imagerie médicale en tant qu'outil d'éducation thérapeutique du patient.


Feasibility Studies , Patient Education as Topic , Humans , Male , Female , Middle Aged , Aged , Neoplasms/radiotherapy , Neoplasms/diagnostic imaging , Adult , Diagnostic Imaging , Lung Neoplasms/radiotherapy , Lung Neoplasms/diagnostic imaging , Radiotherapy/methods
9.
BMC Cancer ; 24(1): 556, 2024 May 03.
Article En | MEDLINE | ID: mdl-38702617

Radiotherapy is a mainstay of cancer treatment. The clinical response to radiotherapy is heterogeneous, from a complete response to early progression. Recent studies have explored the importance of patient characteristics in response to radiotherapy. In this editorial, we invite contributions for a BMC Cancer collection of articles titled 'Advances in personalized radiotherapy' towards the improvement of treatment response.


Neoplasms , Precision Medicine , Humans , Precision Medicine/methods , Neoplasms/radiotherapy , Radiotherapy/methods , Radiotherapy/trends , Treatment Outcome
10.
J Exp Med ; 221(7)2024 Jul 01.
Article En | MEDLINE | ID: mdl-38771260

The majority of cancer patients receive radiotherapy during the course of treatment, delivered with curative intent for local tumor control or as part of a multimodality regimen aimed at eliminating distant metastasis. A major focus of research has been DNA damage; however, in the past two decades, emphasis has shifted to the important role the immune system plays in radiotherapy-induced anti-tumor effects. Radiotherapy reprograms the tumor microenvironment, triggering DNA and RNA sensing cascades that activate innate immunity and ultimately enhance adaptive immunity. In opposition, radiotherapy also induces suppression of anti-tumor immunity, including recruitment of regulatory T cells, myeloid-derived suppressor cells, and suppressive macrophages. The balance of pro- and anti-tumor immunity is regulated in part by radiotherapy-induced chemokines and cytokines. Microbiota can also influence radiotherapy outcomes and is under clinical investigation. Blockade of the PD-1/PD-L1 axis and CTLA-4 has been extensively investigated in combination with radiotherapy; we include a review of clinical trials involving inhibition of these immune checkpoints and radiotherapy.


Neoplasms , Radiotherapy , Tumor Microenvironment , Humans , Neoplasms/radiotherapy , Neoplasms/immunology , Neoplasms/therapy , Tumor Microenvironment/immunology , Tumor Microenvironment/radiation effects , Animals , Radiotherapy/methods , Immunity, Innate/radiation effects , CTLA-4 Antigen/immunology , CTLA-4 Antigen/metabolism , Immune Checkpoint Inhibitors/therapeutic use , Programmed Cell Death 1 Receptor/metabolism , Programmed Cell Death 1 Receptor/immunology , B7-H1 Antigen/metabolism , B7-H1 Antigen/immunology , Adaptive Immunity
11.
Sci Rep ; 14(1): 11120, 2024 05 15.
Article En | MEDLINE | ID: mdl-38750131

Very High Energy Electron (VHEE) beams are a promising alternative to conventional radiotherapy due to their highly penetrating nature and their applicability as a modality for FLASH (ultra-high dose-rate) radiotherapy. The dose distributions due to VHEE need to be optimised; one option is through the use of quadrupole magnets to focus the beam, reducing the dose to healthy tissue and allowing for targeted dose delivery at conventional or FLASH dose-rates. This paper presents an in depth exploration of the focusing achievable at the current CLEAR (CERN Linear Electron Accelerator for Research) facility, for beam energies >200 MeV. A shorter, more optimal quadrupole setup was also investigated using the TOPAS code in Monte Carlo simulations, with dimensions and beam parameters more appropriate to a clinical situation. This work provides insight into how a focused VHEE radiotherapy beam delivery system might be achieved.


Electrons , Monte Carlo Method , Radiotherapy Dosage , Humans , Particle Accelerators/instrumentation , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy/methods , Radiotherapy, High-Energy/methods , Radiotherapy, High-Energy/instrumentation
13.
EBioMedicine ; 103: 105089, 2024 May.
Article En | MEDLINE | ID: mdl-38579363

Advances in radiation techniques have enabled the precise delivery of higher doses of radiotherapy to tumours, while sparing surrounding healthy tissues. Consequently, the incidence of radiation toxicities has declined, and will likely continue to improve as radiotherapy further evolves. Nonetheless, ionizing radiation elicits tissue-specific toxicities that gradually develop into radiation-induced fibrosis, a common long-term side-effect of radiotherapy. Radiation fibrosis is characterized by an aberrant wound repair process, which promotes the deposition of extensive scar tissue, clinically manifesting as a loss of elasticity, tissue thickening, and organ-specific functional consequences. In addition to improving the existing technologies and guidelines directing the administration of radiotherapy, understanding the pathogenesis underlying radiation fibrosis is essential for the success of cancer treatments. This review integrates the principles for radiotherapy dosimetry to minimize off-target effects, the tissue-specific clinical manifestations, the key cellular and molecular drivers of radiation fibrosis, and emerging therapeutic opportunities for both prevention and treatment.


Fibrosis , Radiation Injuries , Humans , Radiation Injuries/etiology , Radiation Injuries/pathology , Animals , Radiotherapy/adverse effects , Radiotherapy/methods , Neoplasms/etiology , Neoplasms/radiotherapy , Neoplasms/pathology , Radiation, Ionizing
14.
Phys Med Biol ; 69(11)2024 May 14.
Article En | MEDLINE | ID: mdl-38657630

Objective. We provide optimal particle split numbers for speeding up TOPAS Monte Carlo simulations of linear accelerator (linac) treatment heads while maintaining accuracy. In addition, we provide a new TOPAS physics module for simulating photoneutron production and transport.Approach.TOPAS simulation of a Siemens Oncor linac was used to determine the optimal number of splits for directional bremsstrahlung splitting as a function of the field size for 6 MV and 18 MV x-ray beams. The linac simulation was validated against published data of lateral dose profiles and percentage depth-dose curves (PDD) for the largest square field (40 cm side). In separate simulations, neutron particle split and the custom TOPAS physics module was used to generate and transport photoneutrons, called 'TsPhotoNeutron'. Verification of accuracy was performed by comparing simulations with published measurements of: (1) neutron yields as a function of beam energy for thick targets of Al, Cu, Ta, W, Pb and concrete; and (2) photoneutron energy spectrum at 40 cm laterally from the isocenter of the Oncor linac from an 18 MV beam with closed jaws and MLC.Main results.The optimal number of splits obtained for directional bremsstrahlung splitting enhanced the computational efficiency by two orders of magnitude. The efficiency decreased with increasing beam energy and field size. Calculated lateral profiles in the central region agreed within 1 mm/2% from measured data, PDD curves within 1 mm/1%. For the TOPAS physics module, at a split number of 146, the efficiency of computing photoneutron yields was enhanced by a factor of 27.6, whereas it improved the accuracy over existing Geant4 physics modules.Significance.This work provides simulation parameters and a new TOPAS physics module to improve the efficiency and accuracy of TOPAS simulations that involve photonuclear processes occurring in high-Zmaterials found in linac components, patient devices, and treatment rooms, as well as to explore new therapeutic modalities such as very-high energy electron therapy.


Monte Carlo Method , Neutrons , Particle Accelerators , Photons , Photons/therapeutic use , Time Factors , Radiotherapy Dosage , Reproducibility of Results , Computer Simulation , Humans , Radiotherapy/methods
15.
Free Radic Biol Med ; 219: 88-103, 2024 Jul.
Article En | MEDLINE | ID: mdl-38631648

This review explores the convergence of clinical radiotherapy and space radiation therapeutics, focusing on ionizing radiation (IR)-generated reactive oxygen species (ROS). IR, with high-energy particles, induces precise cellular damage, particularly in cancer treatments. The paper discusses parallels between clinical and space IR, highlighting unique characteristics of high-charge and energy particles in space and potential health risks for astronauts. Emphasizing the parallel occurrence of ROS generation in both clinical and space contexts, the review identifies ROS as a crucial factor with dual roles in cellular responses and potential disease initiation. The analysis covers ROS generation mechanisms, variations, and similarities in terrestrial and extraterrestrial environments leading to innovative ROS-responsive delivery systems adaptable for both clinical and space applications. The paper concludes by discussing applications of personalized ROS-triggered therapeutic approaches and discussing the challenges and prospects of implementing these strategies in clinical radiotherapy and extraterrestrial missions. Overall, it underscores the potential of ROS-targeted delivery for advancing therapeutic strategies in terrestrial clinical settings and space exploration, contributing to human health improvement on Earth and beyond.


Neoplasms , Reactive Oxygen Species , Space Flight , Reactive Oxygen Species/metabolism , Humans , Neoplasms/radiotherapy , Neoplasms/metabolism , Radiotherapy/methods , Cosmic Radiation , Radiation, Ionizing , Animals , Astronauts
16.
Chronobiol Int ; 41(4): 587-597, 2024 Apr.
Article En | MEDLINE | ID: mdl-38606920

The timing of radiotherapy (RT) delivery has been reported to affect both cancer survival and treatment toxicity. However, the association among the timing of RT delivery, survival, and toxicity in locally advanced nasopharyngeal carcinoma (LA-NPC) has not been investigated. We retrospectively reviewed patients diagnosed with LA-NPC who received definitive RT at multiple institutions. The median RT delivery daytime was categorized as morning (DAY) and night (NIGHT). Seasonal variations were classified into the darker half of the year (WINTER) and brighter half (SUMMER) according to the sunshine duration. Cohorts were balanced according to baseline characteristics using propensity score matching (PSM). Survival and toxicity outcomes were evaluated using Cox regression models. A total of 355 patients were included, with 194/161 in DAY/NIGHT and 187/168 in WINTER/SUMMER groups. RT delivered during the daytime prolonged the 5-year overall survival (OS) (90.6% vs. 80.0%, p = 0.009). However, the significance of the trend was lost after PSM (p = 0.068). After PSM analysis, the DAY cohort derived a greater benefit in 5-year progression-free survival (PFS) (85.6% vs. 73.4%, p = 0.021) and distant metastasis-free survival (DMFS) (89.2% vs. 80.8%, p = 0.051) in comparison with the NIGHT subgroup. Moreover, multivariate analysis showed that daytime RT was an independent prognostic factor for OS, PFS, and DMFS. Furthermore, daytime RT delivery was associated with an increase in the incidence of leukopenia and radiation dermatitis. RT delivery in SUMMER influenced only the OS significantly (before PSM: p = 0.051; after PSM: p = 0.034). There was no association between toxicity and the timing of RT delivery by season. In LA-NPC, the daytime of radical RT served as an independent prognostic factor. Furthermore, RT administered in the morning resulted in more severe toxic side effects than that at night, which needs to be confirmed in a future study.


Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Propensity Score , Humans , Male , Female , Nasopharyngeal Carcinoma/radiotherapy , Middle Aged , Nasopharyngeal Neoplasms/radiotherapy , Retrospective Studies , Prognosis , Adult , Aged , Treatment Outcome , Circadian Rhythm/physiology , Time Factors , Radiotherapy/adverse effects , Radiotherapy/methods , Seasons
17.
Biomed Pharmacother ; 174: 116532, 2024 May.
Article En | MEDLINE | ID: mdl-38574625

Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking immunotherapy. However, it faces formidable challenges in treating solid tumors, grappling with issues like poor trafficking, limited penetration, and insufficient persistence within the tumor microenvironment (TME). CAR-T cells are engineered to express receptors that target specific cancer antigens, enhancing their ability to recognize and eliminate cancer cells. This review paper explores the intricate interplay between CAR-T therapy and radiotherapy (RT), investigating their synergistic potential. Radiotherapy, a standard cancer treatment, involves using high doses of radiation to target and damage cancer cells, disrupting their ability to grow and divide. We highlight that RT modulates the TME, augments antigen presentation, and promotes immune cell infiltration, bolstering CAR-T cell-mediated tumor eradication. Molecular insights shed light on RT-induced alterations in tumor stroma, T cell recruitment promotion, and induction of immunogenic cell death. Noteworthy, strategies, such as combining hypofractionated radiotherapy with myeloid-derived suppressor cell blockade, underscore innovative approaches to enhance CAR-T cell therapy in solid tumors. Bridging indications for RT and CAR-T cells in hematological malignancies are discussed, emphasizing scenarios where RT strategically enhances CAR-T cell efficacy. The paper critically evaluates the RT as a bridge compared to traditional chemotherapy, highlighting timing and dosage considerations crucial for optimizing CAR-T therapy outcomes. In summary, the paper provides valuable insights into the intricate molecular mechanisms activated by RT and innovative strategies to improve CAR-T cell therapy, fostering a deeper understanding of their combined potential in cancer treatment.


Immunotherapy, Adoptive , Neoplasms , Tumor Microenvironment , Humans , Neoplasms/radiotherapy , Neoplasms/immunology , Neoplasms/pathology , Immunotherapy, Adoptive/methods , Animals , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/metabolism , Combined Modality Therapy/methods , Radiotherapy/methods
18.
Phys Med Biol ; 69(11)2024 May 17.
Article En | MEDLINE | ID: mdl-38608644

Purpose. Radiation delivered over ultra-short timescales ('FLASH' radiotherapy) leads to a reduction in normal tissue toxicities for a range of tissues in the preclinical setting. Experiments have shown this reduction occurs for total delivery times less than a 'critical' time that varies by two orders of magnitude between brain (∼0.3 s) and skin (⪆10 s), and three orders of magnitude across different bowel experiments, from ∼0.01 to ⪆(1-10) s. Understanding the factors responsible for this broad variation may be important for translation of FLASH into the clinic and understanding the mechanisms behind FLASH.Methods.Assuming radiolytic oxygen depletion (ROD) to be the primary driver of FLASH effects, oxygen diffusion, consumption, and ROD were evaluated numerically for simulated tissues with pseudorandom vasculatures for a range of radiation delivery times, capillary densities, and oxygen consumption rates (OCR's). The resulting time-dependent oxygen partial pressure distribution histograms were used to estimate cell survival in these tissues using the linear quadratic model, modified to incorporate oxygen-enhancement ratio effects.Results. Independent of the capillary density, there was a substantial increase in predicted cell survival when the total delivery time was less than the capillary oxygen tension (mmHg) divided by the OCR (expressed in units of mmHg/s), setting the critical delivery time for FLASH in simulated tissues. Using literature OCR values for different normal tissues, the predicted range of critical delivery times agreed well with experimental values for skin and brain and, modifying our model to allow for fluctuating perfusion, bowel.Conclusions. The broad three-orders-of-magnitude variation in critical irradiation delivery times observed inin vivopreclinical experiments can be accounted for by the ROD hypothesis and differences in the OCR amongst simulated normal tissues. Characterization of these may help guide future experiments and open the door to optimized tissue-specific clinical protocols.


Oxygen , Oxygen/metabolism , Kinetics , Time Factors , Radiotherapy/methods , Humans , Models, Biological , Oxygen Consumption/radiation effects , Cell Survival/radiation effects
19.
Radiography (Lond) ; 30(3): 920-925, 2024 May.
Article En | MEDLINE | ID: mdl-38631102

INTRODUCTION: In the UK it is commonplace for patients completing radiotherapy to be invited to ring a bell as a form of celebration. The project aimed to explore the experiences of the end of treatment bell from the perspective of patients who had received treatment for cancer, and therapeutic radiographers who treat patients. The study also aimed to consider possible alternative methods of commemorating the EoT, considering the needs of patients, family members and healthcare professionals. METHODS: Online focus groups were held with patients (n = 5) and therapeutic radiographers (n = 4) in December 2020; a joint online event (n = 6) was held in March 2022. They were all facilitated by two members of the research team. Thematic analysis was used for data analysis. RESULTS: Participants' views and experiences were mixed; however, there was a consensus that alternative forms of commemoration should be available to meet patients' diverse needs. Features of a specification were considered and suggestions made for alternative practices, with a focus upon patients' transition needs after radiotherapy has ended. CONCLUSION: The results indicate that departments should consider the harms as well as the benefits conferred by the EoT bell and explore alternative ways to mark an episode of treatment. IMPLICATIONS FOR PRACTICE: A one-size-fits-all approach is not appropriate in relation to marking the end of an episode of treatment.


Focus Groups , Neoplasms , Humans , Neoplasms/radiotherapy , United Kingdom , Female , Radiotherapy/methods , Male
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