Low-Dose Radiation Therapy for Neurological Disorders: A Double-Edged Sword.

Radiation therapy targeting the central nervous system is widely utilized for the management of various brain tumors, significantly prolonging patient survival. Presently, investigations are assessing both clinical and preclinical applications of low-dose radiation (LDR) for the treatment of neuropathological conditions beyond tumor therapy. Special focus is given to refractory neurodegenerative diseases linked to neuroinflammation, such as Alzheimer's and Parkinson's diseases, where LDR has shown promising results. This comprehensive review examines the existing experimental data regarding the utilization of LDR in neurological disorders. It covers potential advantages in reducing neurodegenerative alterations and inflammation, as well as possible adverse effects, including neurological impairments. The review underscores the importance of the exposure protocol and the age at which LDR is administered in the context of the nervous system's pathological and physiological states, as these elements are crucial in determining LDR's therapeutic and toxic outcomes. The article concludes with a discussion on the future directions and challenges in optimizing LDR use, aiming to reduce toxicity while effectively managing neurological disorders.

[Éditorial. La radiothérapie dix ans après]. / Éditorial. La radiothérapie dix ans après.

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[Radiotherapy for non-tumoral disorders : a brief history and indications in 2024]. / La radiothérapie des pathologies non tumorales : un bref historique et possibilités en 2024.

Radiotherapy for non-tumoral disorders has a long history. Lack of high-level evidence, therapeutic alternatives and fear of side effects (particularly radiation-induced cancer) reduced some indications to a trickle during the second half of the 20th century. Others were logically abandoned. There are two exceptions to this trend. On the one hand, some Central European countries (Germany in particular) still use radiotherapy regularly for diseases such as osteoarthritis, plantar fasciitis, chronic tendinopathies, Dupuytren's disease, etc. On the other hand, the development of stereotactic ablative radiotherapy has opened up new indications, whether cerebral (arteriovenous malformations, trigeminal neuralgia, obsessive-compulsive disorders) or cardiac (ventricular tachycardia). In this article, we present a non-exhaustive list of some indications (or rather possibilities) for radiotherapy in non-tumoral disorders in 2024.

La radiothérapie des pathologies non tumorales possède une longue histoire. L'absence de preuves d'un niveau élevé, les alternatives thérapeutiques et la peur d'effets secondaires (en particulier le cancer radio-induit) ont réduit certaines indications à peau de chagrin durant la seconde moitié du 20ème siècle. D'autres ont logiquement été abandonnées. Deux exceptions existent concernant cette diminution. D'une part, certains pays d'Europe centrale (l'Allemagne en particulier) continuent d'utiliser régulièrement la radiothérapie dans des pathologies telles que l'arthrose, la fasciite plantaire, les tendinopathies chroniques, la maladie de Dupuytren ... D'autre part, le développement de la radiothérapie stéréotaxique ablative a permis d'envisager de nouvelles indications qu'elles soient cérébrales (malformations artério-veineuses, névralgie du trijumeau, troubles obsessionnels compulsifs) ou cardiaques (tachycardie ventriculaire). Nous présentons, de façon non exhaustive, quelques indications (ou plutôt possibilités) de radiothérapie dans les pathologies non tumorales utilisées en 2024.

[The quality and safety approach in radiotherapy : an added value for the patient]. / La démarche qualité et sécurité en radiothérapie : une plus-value pour le patient.

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.

[Prevention of radiotherapy-related cardiotoxicity : benefits of a specialized cardio-oncologic assessment and follow-up]. / Prévention de la cardio-toxicité de la radiothérapie : apport de la prise en charge cardio-oncologique.

To accept the toxic side effects of any treatment, whether medical, surgical or radiotherapeutic, cannot be avoided but implies to evaluate them taking into account the severity and prognosis of the disease that is concerned. Screening, preventing and treatment of these side effects are an integral aspect of the treatment of cancers. We will here review the contribution of the cardio-oncology, a recently emerged medical specialty. Cardiac irradiation cannot be avoided when treating several cancers, most frequently left sided breast cancer. As soon as radiotherapy is considered, it is of prime importance to evaluate each patient's risk factors and to handle them. If technical progresses have led to the complete disappearance of acute side effects of radiotherapy, this is not true for the delayed ones that may occur many years after the irradiation. Hence the need for «red flags¼ and for a systematic follow-up. Cardiac complications of left breast irradiation concern all aspects of cardiology: diseases of cardiac rhythm, valvulopathies, heart failure, coronary and pericardial disorders.

Admettre les effets secondaires d'un traitement, qu'il soit médical, chirurgical ou radiothérapique, est inévitable, mais impose de les évaluer en intégrant la gravité de l'affection pour laquelle ils sont prescrits. Leur dépistage, leur prévention et leur prise en charge font partie intégrante du traitement d'un cancer. Dans cette revue, nous ferons la synthèse de l'apport à cette démarche d'une discipline récente, la cardio-oncologie. L'irradiation cardiaque est incontournable lors du traitement de plusieurs cancers au premier rang desquels le cancer du sein gauche. Dès qu'elle est envisagée, il est essentiel d'évaluer les facteurs de risque de chaque patient et d'organiser leur prise en charge éventuelle. En effet, si les progrès techniques ont permis la disparition des complications cardiaques aiguës de la radiothérapie, ce n'est encore pas le cas des complications différées qui peuvent survenir de nombreuses années après l'irradiation. D'où la nécessité de «drapeaux rouges¼ et d'un suivi régulier systématique. Ces complications, rarement isolées, concernent tous les aspects de la cardiologie : troubles du rythme, valvulopathies, insuffisance cardiaque, maladies coronaires et atteintes péricardiques.

Clinical efficacy and applicability of natural products in the treatment and prevention of radiotherapy-induced oral mucositis: A systematic review.

The aim of this systematic review was to describe the efficacy and acceptability of natural products in the management of oral mucositis caused by radiation. From the day it started to August 7, 2023, a thorough search for randomized controlled trials (RCTs) was carried out among seven databases: the Web of Science, PubMed, Embase, OVID, Scopus, the Cochrane Library and the CINAHL database. Only English-language articles were identified during the search. Using the revised Cochrane risk-of-bias tool, version 2, two researchers screened the articles, collected information on study characteristics, and appraised risks of bias. The data were analyzed and descriptively presented with a narrative synthesis methodology involving the Synthesis Without Meta-Analysis (SWiM) reporting element applied in detail. The PROSPERO registration number of this study is CRD42023476932. Thirty-six clinical trials were included in the study; the included studies included a variety of 20 types of natural products. Honey and Curcuma longa were the most commonly assessed natural products. A total of 2,400 participants reported taking part in therapy with natural products for oral mucositis. Natural products demonstrated substantial efficacy in terms of influencing intensity, incidence, pain score, quality of life, and symptoms such as xerostomia and dysphagia. Except for manuka honey, most natural products were well accepted. Regarding the clinical trials' risk of bias, 2 clinical trials (5.56%) had a high risk of bias, 17 studies (47.2%) had a low risk of bias, and 17 studies (47.2%) were rated with "some concern." Natural remedies work well as alternate treatments for managing oral mucositis caused by radiation therapy. However, additional clinical trials are still needed. The safety of these conventional medications as well as their effectiveness and safety when used in combination with other conventional or naturopathic therapies should be fully examined.

Imaging Assessment of Radiation Therapy-Related Normal Tissue Injury in Children: A PENTEC Visionary Statement.

The Pediatric Normal Tissue Effects in the Clinic (PENTEC) consortium has made significant contributions to understanding and mitigating the adverse effects of childhood cancer therapy. This review addresses the role of diagnostic imaging in detecting, screening, and comprehending radiation therapy-related late effects in children, drawing insights from individual organ-specific PENTEC reports. We further explore how the development of imaging biomarkers for key organ systems, alongside technical advancements and translational imaging approaches, may enhance the systematic application of imaging evaluations in childhood cancer survivors. Moreover, the review critically examines knowledge gaps and identifies technical and practical limitations of existing imaging modalities in the pediatric population. Addressing these challenges may expand access to, minimize the risk of, and optimize the real-world application of, new imaging techniques. The PENTEC team envisions this document as a roadmap for the future development of imaging strategies in childhood cancer survivors, with the overarching goal of improving long-term health outcomes and quality of life for this vulnerable population.

Reporting Standards for Complication Studies of Radiation Therapy for Pediatric Cancer: Lessons From PENTEC.

The major aim of Pediatric Normal Tissue Effects in the Clinic (PENTEC) was to synthesize quantitative published dose/-volume/toxicity data in pediatric radiation therapy. Such systematic reviews are often challenging because of the lack of standardization and difficulty of reporting outcomes, clinical factors, and treatment details in journal articles. This has clinical consequences: optimization of treatment plans must balance between the risks of toxicity and local failure; counseling patients and their parents requires knowledge of the excess risks encountered after a specific treatment. Studies addressing outcomes after pediatric radiation therapy are particularly challenging because: (a) survivors may live for decades after treatment, and the latency time to toxicity can be very long; (b) children's maturation can be affected by radiation, depending on the developmental status of the organs involved at time of treatment; and (c) treatment regimens frequently involve chemotherapies, possibly modifying and adding to the toxicity of radiation. Here we discuss: basic reporting strategies to account for the actuarial nature of the complications; the reporting of modeling of abnormal development; and the need for standardized, comprehensively reported data sets and multivariate models (ie, accounting for the simultaneous effects of radiation dose, age, developmental status at time of treatment, and chemotherapy dose). We encourage the use of tools that facilitate comprehensive reporting, for example, electronic supplements for journal articles. Finally, we stress the need for clinicians to be able to trust artificial intelligence models of outcome of radiation therapy, which requires transparency, rigor, reproducibility, and comprehensive reporting. Adopting the reporting methods discussed here and in the individual PENTEC articles will increase the clinical and scientific usefulness of individual reports and associated pooled analyses.

Risk and prognosis of secondary lung cancer after radiation therapy for thoracic malignancies.

OBJECTIVE: Radiation therapy (RT) may increase the risk of second cancer. This study aimed to determine the association between exposure to radiotherapy for the treatment of thoracic cancer (TC) and subsequent secondary lung cancer (SLC). MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for TC. Univariate Cox regression analyses and multiple primary standardized incidence ratios (SIRs) were used to assess the risk of SLC. Subgroup analyses of patients stratified by latency time since TC diagnosis, age at TC diagnosis, and calendar year of TC diagnosis stage were also performed. Overall survival and SLC-related death were compared among the RT and no radiation therapy (NRT) groups by using Kaplan-Meier analysis and competitive risk analysis. RESULTS: In a total of 329 129 observations, 147 847 of whom had been treated with RT. And 6799 patients developed SLC. Receiving radiotherapy was related to a higher risk of developing SLC for TC patients (adjusted HR, 1.25; 95% CI, 1.19-1.32; P < 0.001). The cumulative incidence of developing SLC in TC patients with RT (3.8%) was higher than the cumulative incidence (2.9%) in TC patients with NRT(P). The incidence risk of SLC in TC patients who received radiotherapy was significantly higher than the US general population (SIR, 1.19; 95% CI, 1.14-1.23; P < 0.050). CONCLUSIONS: Radiotherapy for TC was associated with higher risks of developing SLC compared with patients unexposed to radiotherapy.

Nutritional Prognosis of Patients Submitted to Radiotherapy and Its Implications in Treatment.

Oncological patients show intense catabolic activity, as well as a susceptibility to higher nutritional risk and clinical complications. Thus, tools are used for monitoring prognosis. Our objective was to analyze the nutrition prognosis of patients who underwent radiotherapy, correlating it with outcomes and complications. We performed a retrospective transversal study based on secondary data from hospital records of patients who started radiotherapy between July 2022 and July 2023. We established Prognostic Scores through a combination of Prognostic Nutritional Index (PNI) and a Subjective Global Assessment (SGA), assessed at the beginning and end of treatment. Score 3 patients, with PNI ≤ 45.56 and an SGA outcome of malnutrition, initially presented a higher occurrence of odynophagia, later also being indicative of reduced diet volume, treatment interruption, and dysphagia. SGA alone showed sensitivity to altered diet volume, dysphagia, and xerostomia in the second assessment. Besides this, PNI ≤ 45.56 also indicated the use of alternative feeding routes, treatment interruption, and hospital discharge with more complications. We conclude that the scores could be used to indicate complications; however, further studies on combined biomarkers are necessary.

The Assessment of the Long-Term Impact of Radiotherapy on Biophysical Skin Properties in Patients after Head and Neck Cancer.

Background and Objectives: Chronic radiotherapy-induced skin injury (cRISI) is an irreversible and progressive condition that can significantly impact a patient's quality of life. Despite the limited literature available on the assessment of the epidermal barrier in cRISI, there is a consensus that appropriate skincare, including the use of emollients, is the primary therapeutic approach for this group of patients. The aim of this study was to evaluate the biophysical properties of the skin during the late period (at least 90 days) following radiation therapy (RT) for head and neck cancer. Materials and Methods: This was a single-center prospective non-randomized study. It involved the analysis of 16 adult patients with head and neck cancer who underwent RT at the Greater Poland Cancer Center, along with 15 healthy volunteers. The study and control groups were matched for gender and age (p = 0.51). Clinical assessment, based on the LENT-SOMA scale, was conducted for all patients. Evaluation of the skin's biophysical properties included: an analysis of transepidermal water loss (TEWL), stratum corneum hydration (SCH), and skin visualization using high-frequency ultrasonography (HF-USG). Results: A significantly higher TEWL was observed in the irradiated area compared to the control area in the study group (p = 0.004). However, there was no statistically significant difference in SCH (p = 0.073). Additionally, no significant difference was observed in the values of TEWL and SCH in the irradiated area between the group of patients with and without clinically obvious RISI (p = 0.192 and p = 0.415, respectively). The skin thickness of the irradiated area, assessed by HF-USG, did not differ significantly from the skin thickness of the control area (p = 0.638). Furthermore, no difference in skin thickness was observed in patients with clinical features of cRISI in the irradiated and control areas (p = 0.345). The mean time after RT was 6.1 years. Conclusions: This study marks the first demonstration of epidermal barrier damage in patients in the long term following RT for head and neck cancer. The impairment of the epidermal barrier was observed independently of evident cRISI features. This observation underscores the necessity to recommend appropriate skin care, including the use of emollients, for all patients following RT. We also suggest that HF-USG examination is generally inconclusive in determining the degree of skin damage in the late period after RT.

Insights into pelvic insufficiency fracture following pelvic radiotherapy for cervical cancer: a comparative review.

BACKGROUND: Radiotherapy (RT)-induced pelvic insufficiency fractures (PIF) are prevalent in patients with cervical cancer. Inconclusive studies on PIF after cervical irradiation create uncertainty. This review examined PIF after RT in cervical patients, including its pathobiology, likely locations of fractures, incidence, clinical symptoms, and predisposing factors. We further discussed study limitations and therapeutic possibilities of PIF. METHODS: The following online resources were searched for relevant articles: Google Scholar and PubMed. The keywords 'pelvic insufficiency fractures', 'cervical carcinoma' and 'cervical cancer', as well as 'chemoradiotherapy', 'chemoradiation', and 'radiotherapy', were some of the terms that were used during the search. RESULTS: Patients with PIF report pelvic pain after radiation treatment for cervical cancer; the incidence of PIF ranges from 1.7 to 45.2%. Evidence also supports that among all patients treated with pelvic radiation, those who experienced pelvic insufficiency fractures invariably had at least one sacral fracture, making it the most frequently fractured bone in the body. Menopausal status, weight, BMI, age, and treatments and diagnosis modalities can influence PIF during radiotherapy. CONCLUSIONS: In conclusion, our comparative review of the literature highlights significant heterogeneity in various aspects of PIF following radiation for patients with cervical cancer. This diversity encompasses prevalence rates, associated risk factors, symptoms, severity, diagnosis methods, preventive interventions, and follow-up periods. Such diversity underscores the complexity of PIF in this population and emphasizes the critical need for further research to elucidate optimal management strategies and improve patient outcomes.

Study on carotid artery stenosis after radiotherapy for nasopharyngeal carcinoma.

OBJECTIVE: This study investigated carotid artery stenosis (CAS) and associated risk factors in patients with nasopharyngeal carcinoma (NPC) post-radiotherapy. MATERIALS AND METHODS: The observation group comprised 86 reexamined patients with NPC, divided into Group 1 and Group 2 based on post-radiotherapy duration, alongside 34 newly diagnosed patients with NPC (Group 0). Carotid artery ultrasonography and chi-square analysis were performed. RESULTS: Moderate-to-severe vascular abnormalities were exclusively in Group 2. Considering mild vascular abnormalities as the standard, the overall vascular abnormality rates in Group 2 and Group 0 were 65.9% and 41.2%, respectively. In Group 2 and Group 0, the abnormality rates for unilateral carotid artery (UCA), common carotid artery (CCA), internal carotid artery (ICA), and external carotid artery (ECA) were 47.4% and 30.9%, 44.3% and 22.1%, 44.3% and 16.2%, and 39.8% and 5.9%, respectively. Comparing group 1 to group 0, only UCA abnormalities were statistically significant (45.4% vs. 30.9%). Considering moderate-to-severe vascular abnormalities as the standard, Group 2 had higher overall vascular, UCA, CCA, ICA, and ECA abnormality rates compared to Group 0. The age at revisit over 45 years, T stage, and N stage may influence CAS. CONCLUSION: Radiation increasing CAS incidence after 3 years. So, regular examinations are recommended to dynamically monitor CAS after 3 years of radiotherapy.

Radiation-induced lumbosacral plexopathy and pelvic insufficiency fracture: A case report of unique coexistence of complications after radiotherapy for prostate cancer.

Case reports of plexopathy after prostate cancer are usually neoplastic. Radiation-induced lumbosacral plexopathy and insufficiency fractures have clinical significance due to the need to differentiate them from tumoral invasions, metastases, and spinal pathologies. Certain nuances, including clinical presentation and screening methods, help distinguish radiation-induced plexopathy from tumoral plexopathy. This case report highlights the coexistence of these two rare clinical conditions. Herein, we present a 78-year-old male with a history of radiotherapy for prostate cancer who developed right foot drop, severe lower back and right groin pain, difficulty in standing up and walking, and tingling in both legs over the past month during remission. The diagnosis of lumbosacral plexopathy and pelvic insufficiency fracture was made based on magnetic resonance imaging, positron emission tomography, and electroneuromyography. The patient received conservative symptomatic treatment and was discharged with the use of a cane for mobility. Radiation-induced lumbosacral plexopathy following prostate cancer should be kept in mind in patients with neurological disorders of the lower limbs. Pelvic insufficiency fracture should also be considered if the pain does not correspond to the clinical findings of plexopathy. These two pathologies, which can be challenging to diagnose, may require surgical or complex management approaches. However, in this patient, conservative therapies led to an improvement in quality of life and a reduction in the burden of illness.

Acupuncture for Chronic Radiation-Induced Xerostomia in Head and Neck Cancer: A Multicenter Randomized Clinical Trial.

Importance: Patients with head and neck cancer who undergo radiotherapy can develop chronic radiation-induced xerostomia. Prior acupuncture studies were single center and rated as having high risk of bias, making it difficult to know the benefits of acupuncture for treating radiation-induced xerostomia. Objective: To compare true acupuncture (TA), sham acupuncture (SA), and standard oral hygiene (SOH) for treating radiation-induced xerostomia. Design, Setting, and Participants: A randomized, blinded, 3-arm, placebo-controlled trial was conducted between July 29, 2013, and June 9, 2021. Data analysis was performed from March 9, 2022, through May 17, 2023. Patients reporting grade 2 or 3 radiation-induced xerostomia 12 months or more postradiotherapy for head and neck cancer were recruited from community-based cancer centers across the US that were part of the Wake Forest National Cancer Institute Community Oncology Research Program Research Base. Participants had received bilateral radiotherapy with no history of xerostomia. Interventions: Participants received SOH and were randomized to TA, SA, or SOH only. Participants in the TA and SA cohorts were treated 2 times per week for 4 weeks. Those experiencing a minor response received another 4 weeks of treatment. Main Outcomes and Measures: Patient-reported outcomes for xerostomia (Xerostomia Questionnaire, primary outcome) and quality of life (Functional Assessment of Cancer Therapy-General) were collected at baseline, 4 (primary time point), 8, 12, and 26 weeks. All analyses were intention to treat. Results: A total of 258 patients (201 men [77.9%]; mean [SD] age, 65.0 [9.16] years), participated from 33 sites across 13 states. Overall, 86 patients were assigned to each study arm. Mean (SD) years from diagnosis was 4.21 (3.74) years, 67.1% (n = 173) had stage IV disease. At week 4, Xerostomia Questionnaire scores revealed significant between-group differences, with lower Xerostomia Questionnaire scores with TA vs SOH (TA: 50.6; SOH: 57.3; difference, -6.67; 95% CI, -11.08 to -2.27; P = .003), and differences between TA and SA (TA: 50.6; SA: 55.0; difference, -4.41; 95% CI, -8.62 to -0.19; P = .04) yet did not reach statistical significance after adjustment for multiple comparisons. There was no significant difference between SA and SOH. Group differences in Functional Assessment of Cancer Therapy-General scores revealed statistically significant group differences at week 4, with higher scores with TA vs SOH (TA: 101.6; SOH: 97.7; difference, 3.91; 95% CI, 1.43-6.38; P = .002) and at week 12, with higher scores with TA vs SA (TA: 102.1; SA: 98.4; difference, 3.64; 95% CI, 1.10-6.18; P = .005) and TA vs SOH (TA: 102.1; SOH: 97.4; difference, 4.61; 95% CI, 1.99-7.23; P = .001). Conclusions and Relevance: The findings of this trial suggest that TA was more effective in treating chronic radiation-induced xerostomia 1 or more years after the end of radiotherapy than SA or SOH. Trial Registration: ClinicalTrials.gov Identifier: NCT02589938.

Long-term neurocognitive, psychosocial, and physical outcomes after prenatal exposure to radiotherapy: a multicentre cohort study of the International Network on Cancer, Infertility, and Pregnancy.

BACKGROUND: The main data available on the safety of radiation during pregnancy originate from animal studies and from studies of survivors of atomic or nuclear disasters. The effect of radiotherapy to treat maternal cancer on fetal development is uncertain. This report presents a unique cohort and aims to determine the long-term neurocognitive, psychosocial and physical outcomes of offspring of mothers treated with radiotherapy during pregnancy. METHODS: In this international, multicentre, mixed retrospective-prospective cohort study, we recruited participants between Aug 5, 2006, and Aug 24, 2023, aged between 1·5 and 46 years, at three referral centres in Belgium, the Netherlands, and the USA. Participants were eligible if they were born from mothers treated with radiotherapy during pregnancy. Fetal radiation doses were obtained from medical records and participants were followed up at predefined ages (1·5, 3, 6, 9, 12, 15, and 18 years) and 5-yearly in adulthood, based on age at enrolment, using a neurocognitive test battery (measuring intelligence, attention, and memory), parent-reported executive function and psychosocial questionnaires, and a medical assessment. Results were compared with test-specific normative data. Linear regression models investigated associations between radiotherapy factors (fetal radiation dose, gestational age at the start and end of radiotherapy, and radiotherapy duration) and outcomes. FINDINGS: 68 maternal cases of radiotherapy during pregnancy were registered by the three participating centres, of which 61 resulted in a livebirth and were therefore eligible to participate in the child follow-up study. After excluding those who did not give consent, 43 participants born from 42 mothers treated with radiotherapy during pregnancy were included in the study (median age at first assessment 3 years [IQR 2-11]; median age at last assessment 12 years [9-18]; median number of assessments two [1-4]). 18 (42%) of the included participants were female and 25 (58%) male, and 37 (86%) were of White ethnicity. Mean neurocognitive outcomes of the entire cohort were within normal ranges. No associations were found with fetal radiation dose or timing of radiotherapy during pregnancy. Six (16%) of 38 participants with neurocognitive outcomes scored lower than one SD on at least one neurocognitive outcome, three (7%) reported chronic medical conditions (spasmophilia, spastic diplegia, and IgG deficiency), and three (7%) were diagnosed with attention-deficit hyperactivity disorder (of whom two scored lower on attention). Of ten (23%) participants with lower neurocognitive score(s), a chronic medical condition, or attention-deficit hyperactivity disorder, eight were born preterm. The remaining 33 (77%) participants showed no neurocognitive, psychosocial, or chronic physical problems. INTERPRETATION: We show on average normal neurocognitive, psychosocial, and physical outcomes after prenatal exposure to radiotherapy. Differences in outcomes could not be explained by exposure to radiotherapy during pregnancy. These results suggest that extra-abdomino-pelvic radiotherapy exposure during pregnancy in general does not adversely affect outcomes of liveborn children. Further research with a larger sample is necessary to confirm these findings. FUNDING: Kom Op Tegen Kanker, KWF Kankerbestrijding, Stichting Tegen Kanker, Research Foundation Flanders.

Honey in Alleviating Severe Oral Mucositis Among Head and Neck Cancer Patients Undergoing Radiation Therapy.

BACKGROUND/AIM: Aiming to resolve debates on honey's efficacy for radiotherapy-induced severe oral mucositis in head and neck cancer, we conducted a meta-analysis focused on randomized trials, primarily assessing severe mucositis incidence. Secondary outcomes included weight loss, pain management, and honey types. MATERIALS AND METHODS: A comprehensive literature search was conducted in PubMed, Embase, WOS, and the Cochrane Library up to December 2023. The analysis concentrated on randomized controlled trials that assessed the efficacy of honey, targeting the incidence of mucositis as the main outcome. Additional outcomes explored were weight loss, intolerable pain, and the specific types of honey used in interventions. Data analysis was performed using CMA software, and a funnel plot was employed to identify publication bias. RESULTS: The analysis of 176 records resulted in the inclusion of 10 studies with 599 patients receiving radiotherapy. The research showed that honey significantly reduced the occurrence of grade 3-4 mucositis (severe mucositis), provided significant pain relief, and had a positive effect on reducing weight loss. Regarding the type of honey used, no significant differences were found in their effectiveness in alleviating severe mucositis. CONCLUSION: Honey serves as an effective intervention for individuals with oral mucositis. It can be considered as an adjuvant in the management of clinical radiotherapy-associated oral mucositis, particularly for patients requiring prolonged use of anti-analgesic or antifungal medications.

The clinical manifestations and molecular pathogenesis of radiation fibrosis.

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.