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1.
Front Cell Infect Microbiol ; 14: 1477143, 2024.
Article in English | MEDLINE | ID: mdl-39359935

ABSTRACT

Oral mucositis is a common and debilitating oral complication in head and neck cancer patients undergoing radiotherapy, resulting in diminished quality of life and potential treatment disruptions. Oral microbiota has long been recognized as a contributing factor in the initiation and progression of radiation-induced oral mucositis (RIOM). Numerous studies have indicated that the radiation-induced oral microbial dysbiosis promotes the occurrence and severity of oral mucositis. Therefore, approaches that modulate oral microbial ecology are promising for the management of RIOM. Probiotics as a relatively predicable and safe measure that modulates microecology have garnered significant interest. In this review, we discussed the correlation between RIOM and oral microbiota, with a particular focus on the efficacy of probiotics in the control of RIOM, in order to provide novel paradigm for the management of this disease.


Subject(s)
Dysbiosis , Probiotics , Radiation Injuries , Stomatitis , Probiotics/therapeutic use , Humans , Stomatitis/etiology , Stomatitis/microbiology , Stomatitis/therapy , Stomatitis/prevention & control , Radiation Injuries/therapy , Microbiota , Head and Neck Neoplasms/radiotherapy , Radiotherapy/adverse effects , Mouth/microbiology , Quality of Life
2.
Mol Biomed ; 5(1): 46, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39388072

ABSTRACT

Radiotherapy is a pivotal intervention for cancer patients, significantly impacting their treatment outcomes and survival prospects. Nevertheless, in the course of treating those with abdominal, pelvic, or retroperitoneal malignant tumors, the procedure inadvertently exposes adjacent intestinal tissues to radiation, posing risks of radiation-induced enteropathy upon reaching threshold doses. Stem cells within the intestinal crypts, through their controlled proliferation and differentiation, support the critical functions of the intestinal epithelium, ensuring efficient nutrient absorption while upholding its protective barrier properties. Intestinal stem cells (ISCs) regulation is intricately orchestrated by diverse signaling pathways, among which are the WNT, BMP, NOTCH, EGF, Hippo, Hedgehog and NF-κB, each contributing to the complex control of these cells' behavior. Complementing these pathways are additional regulators such as nutrient metabolic states, and the intestinal microbiota, all of which contribute to the fine-tuning of ISCs behavior in the intestinal crypts. It is the harmonious interplay among these signaling cascades and modulating elements that preserves the homeostasis of intestinal epithelial cells (IECs), thereby ensuring the gut's overall health and function. This review delves into the molecular underpinnings of how stem cells respond in the context of radiation enteropathy, aiming to illuminate potential biological targets for therapeutic intervention. Furthermore, we have compiled a summary of several current treatment methodologies. By unraveling these mechanisms and treatment methods, we aspire to furnish a roadmap for the development of novel therapeutics, advancing our capabilities in mitigating radiation-induced intestinal damage.


Subject(s)
Radiation Injuries , Signal Transduction , Stem Cells , Humans , Stem Cells/radiation effects , Stem Cells/metabolism , Animals , Radiation Injuries/therapy , Radiation Injuries/pathology , Signal Transduction/radiation effects , Intestinal Mucosa/radiation effects , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Intestinal Diseases/pathology , Intestines/radiation effects , Intestines/pathology
3.
Theranostics ; 14(14): 5492-5511, 2024.
Article in English | MEDLINE | ID: mdl-39310097

ABSTRACT

Background: Radiation-induced intestinal injuries are common in patients with pelvic or abdominal cancer. However, these injuries are currently not managed effectively. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been extensively used in regenerative medicine. However, the results of MSC-EVs in the repair of radiation-induced intestinal damage have been unsatisfactory. We here investigated the nanotherapeutic functions of MSC-EVs in radiation-induced intestinal injury. Methods: We visualized the biodistribution and trend of MSC-EVs through in vivo imaging. A radiation-induced intestinal injury model was constructed, and the therapeutic effect of MSC-EVs was explored through in vivo and in vitro experiments. Immunofluorescence and qRT-PCR assays were conducted to explore the underlying mechanisms. Results: MSC-EVs exhibited a dose-dependent tendency to target radiation-injured intestines while providing spatiotemporal information for the early diagnosis of the injury by quantifying the amount of MSC-EVs in the injured intestines through molecular imaging. Meanwhile, MSC-EVs displayed superior nanotherapeutic functions by alleviating apoptosis, improving angiogenesis, and ameliorating the intestinal inflammatory environment. Moreover, MSC-EVs-derived miRNA-455-5p negatively regulated SOCS3 expression, and the activated downstream Stat3 signaling pathway was involved in the therapeutic efficacy of MSC-EVs in radiation-induced intestinal injuries. Conclusion: MSC-EVs can dose-dependently target radiation-injured intestinal tissues, allow a spatiotemporal diagnosis in different degrees of damage to help guide personalized therapy, offer data for designing EV-based theranostic strategies for promoting recovery from radiation-induced intestinal injury, and provide cell-free treatment for radiation therapy.


Subject(s)
Extracellular Vesicles , Intestines , Mesenchymal Stem Cells , Extracellular Vesicles/metabolism , Animals , Mesenchymal Stem Cells/metabolism , Mice , MicroRNAs/metabolism , MicroRNAs/genetics , Apoptosis/radiation effects , Humans , Radiation Injuries/therapy , Radiation Injuries/metabolism , Mice, Inbred C57BL , Male , Signal Transduction , STAT3 Transcription Factor/metabolism
4.
Curr Urol Rep ; 26(1): 1, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39287708

ABSTRACT

PURPOSE OF REVIEW: This manuscript aims to provide a comprehensive overview of the pathophysiology, risk factors, prevention strategies, and management options for radiation cystitis. RECENT FINDINGS: Recent studies have shed light on the pathophysiology of radiation cystitis, highlighting the role of inflammation, fibrosis, and vascular damage. Emerging preventive measures like stem cell therapy offer promise, alongside novel treatments such as amniotic bladder therapy and hyperbaric oxygen therapy. This review outlines the latest research on radiation cystitis, covering its pathophysiology, risk factors, prevention, and management. Major findings include insights into the mechanisms of RC development, promising preventive and therapeutic approaches, and the importance of standardized treatment pathways. Future research should focus on identifying genetic risk factors, improving treatment efficacy, and enhancing patient outcomes. This review offers valuable insights for clinicians and researchers, guiding future investigations into radiation cystitis management.


Subject(s)
Cystitis , Radiation Injuries , Humans , Cystitis/therapy , Cystitis/etiology , Radiation Injuries/therapy , Risk Factors , Radiotherapy/adverse effects , Hyperbaric Oxygenation/methods
5.
Crit Rev Oncol Hematol ; 202: 104461, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39103129

ABSTRACT

The treatment of thoracic tumors with ionizing radiation can cause radiation-induced lung injury (RILI), which includes radiation pneumonitis and radiation-induced pulmonary fibrosis. Preventing RILI is crucial for controlling tumor growth and improving quality of life. However, the serious adverse effects of traditional RILI treatment methods remain a major obstacle, necessitating the development of novel treatment options that are both safe and effective. This review summarizes the molecular mechanisms of RILI and explores novel treatment options, including natural compounds, gene therapy, nanomaterials, and mesenchymal stem cells. These recent experimental approaches show potential as effective prevention and treatment options for RILI in clinical practice.


Subject(s)
Lung Injury , Radiation Injuries , Humans , Lung Injury/etiology , Lung Injury/therapy , Radiation Injuries/therapy , Radiation Injuries/etiology , Radiation Pneumonitis/etiology , Radiation Pneumonitis/therapy , Animals , Genetic Therapy/methods
6.
Rev Med Suisse ; 20(883): 1418-1421, 2024 Aug 21.
Article in French | MEDLINE | ID: mdl-39175292

ABSTRACT

Incidents involving ionizing radiation pose a risk of immediate and long-term clinical consequences for both victims and responders in the event of secondary contamination. Rapid identification of the problem and a coordinated response are crucial. This article summarizes the key challenges related to the emergency management of a single patient or multiple victims, addressing the importance of recognizing such a case, radioprotection measures, decontamination, and available treatments.


Les incidents impliquant des rayonnements ionisants représentent un risque aux conséquences cliniques immédiates et à long terme, tant pour les victimes que pour les intervenants en cas de contamination secondaire. L'identification rapide de la problématique et une réponse coordonnée sont cruciales. Cet article résume les principaux enjeux liés à la prise en charge en urgence d'un patient unique ou de plusieurs victimes, en abordant l'importance de la reconnaissance d'un tel cas, des mesures de radioprotection, de la décontamination et des traitements disponibles.


Subject(s)
Radiation Injuries , Radioactive Hazard Release , Humans , Radiation Injuries/diagnosis , Radiation Injuries/therapy , Radiation Injuries/etiology , Radiation Injuries/prevention & control , Emergency Medical Services/methods , Decontamination/methods , Radiation Protection/methods
8.
J Cancer Res Ther ; 20(3): 776-781, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-39023582

ABSTRACT

BACKGROUND: Despite the availability of a wide range of agents, no single treatment exists for the management of radiation-induced oral mucositis, in patients, with head and neck malignancies, on radical chemoradiation; a debilitating and limiting sequela. Human placental extract is one option that has been proposed. AIMS AND OBJECTIVES: This study aimed at evaluating the therapeutic benefits of human placental extract (Placentrex) in the management of radiation-induced oral mucositis in patients on curative intent treatment for head and neck cancers with concurrent chemoradiation, and to compare the observations with other conventional approaches. MATERIAL AND METHODS: Patients presenting to the Department of Radiation Oncology, of a tertiary cancer care center, with biopsy-proven carcinoma of the oral cavity, oropharynx, and hypopharynx, planned for definitive, curative intent chemoradiation, between January 2020 and June 2021, were recruited for this study. The interventional group received a deep intramuscular injection of 2 ml of Placentrex to the deltoid muscle, once-a-day from the 11th fraction of radiation till completion, on treatment and non-treatment days. The control group received supportive, symptomatic, conventional treatments for mucositis. The response was assessed every week during treatment and at the third and sixth months of follow-up and was compared. RESULTS: The study comprised 26 patients, 15 in the interventional group and 11 in the control group. On completion of treatment, 40% in the interventional arm and 81.82% in the control arm had progressed to grade 2 and 3 mucositis (P < 0.05). Treatment interruption was seen in 13% in the interventional arm and 55% in the control arm (P < 0.001). CONCLUSIONS: Results from this study show that human placental extract, injection Placentrex, had a significant effect in decreasing the severity of radiation-induced mucositis and thereby reducing any interruption or delay in treatment when compared to other conventional methods.


Subject(s)
Chemoradiotherapy , Head and Neck Neoplasms , Placental Extracts , Radiation Injuries , Stomatitis , Humans , Female , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Stomatitis/etiology , Stomatitis/drug therapy , Stomatitis/therapy , Stomatitis/pathology , Placental Extracts/therapeutic use , Placental Extracts/administration & dosage , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/therapy , Middle Aged , Injections, Intramuscular , Radiation Injuries/etiology , Radiation Injuries/therapy , Radiation Injuries/drug therapy , Male , Adult , Aged , Treatment Outcome
9.
Mol Med ; 30(1): 105, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030525

ABSTRACT

Radiotherapy is a widely used cancer treatment that utilizes powerful radiation to destroy cancer cells and shrink tumors. While radiation can be beneficial, it can also harm the healthy tissues surrounding the tumor. Recent research indicates that the microbiota, the collection of microorganisms in our body, may play a role in influencing the effectiveness and side effects of radiation therapy. Studies have shown that specific species of bacteria living in the stomach can influence the immune system's response to radiation, potentially increasing the effectiveness of treatment. Additionally, the microbiota may contribute to adverse effects like radiation-induced diarrhea. A potential strategy to enhance radiotherapy outcomes and capitalize on the microbiome involves using probiotics. Probiotics are living microorganisms that offer health benefits when consumed in sufficient quantities. Several studies have indicated that probiotics have the potential to alter the composition of the gut microbiota, resulting in an enhanced immune response to radiation therapy and consequently improving the efficacy of the treatment. It is important to note that radiation can disrupt the natural balance of gut bacteria, resulting in increased intestinal permeability and inflammatory conditions. These disruptions can lead to adverse effects such as diarrhea and damage to the intestinal lining. The emerging field of radiotherapy microbiome research offers a promising avenue for optimizing cancer treatment outcomes. This paper aims to provide an overview of the human microbiome and its role in augmenting radiation effectiveness while minimizing damage.


Subject(s)
Gastrointestinal Microbiome , Neoplasms , Probiotics , Radiotherapy , Humans , Gastrointestinal Microbiome/radiation effects , Neoplasms/radiotherapy , Neoplasms/microbiology , Neoplasms/immunology , Neoplasms/therapy , Probiotics/therapeutic use , Radiotherapy/adverse effects , Radiotherapy/methods , Animals , Microbiota/radiation effects , Radiation Injuries/microbiology , Radiation Injuries/therapy , Radiation Injuries/etiology , Treatment Outcome
10.
Life Sci ; 353: 122921, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39032692

ABSTRACT

Pelvic irradiation, a crucial treatment for pelvic malignancies, is associated with the risk of gastrointestinal (GI) damage due to the high proliferation rate of epithelial cells. The radiosensitive gastrointestinal tract acts as a dose-limiting organ. High doses of ionizing radiation can cause inflammation and rupture of mucosal barriers and can also lead to intestinal fibrosis. Intestinal damage can cause acute to chronic complications, reducing patients' quality of life. The gut microbiota plays a vital role in maintaining gut health, and any changes in the gut microbial composition can worsen damage, emphasizing the importance of therapies that target and sustain the gut microbiota during radiotherapy. One potential strategy to prevent radiation-induced GI damage is to use bacterial supplements. Research suggests that probiotic supplementation may alleviate radiation-induced gastrointestinal damage, maintaining intestinal morphology and decreasing epithelial injury in cancer patients. The observed protective effects occur through various mechanisms, including antioxidant activities, modulation of the immune response, and preservation of gut barrier function. To optimize probiotic therapies, it is imperative to elucidate these mechanisms. The efficiency of probiotics as radioprotectors is highly dependent on the time and dose of administration, and their interaction with the host immune system is a key facet of their therapeutic potential. This review explores the potential benefits of bacterial supplementation in mitigating radiation-induced GI damage and the underlying mechanism. This highlights the need for further research to establish standardized protocols and refine probiotic supplementation strategies, underscoring the potential for enhancing therapeutic outcomes in patients undergoing pelvic radiotherapy.


Subject(s)
Dietary Supplements , Gastrointestinal Microbiome , Probiotics , Radiation Injuries , Humans , Probiotics/therapeutic use , Radiation Injuries/therapy , Radiation Injuries/prevention & control , Animals , Gastrointestinal Tract/radiation effects , Gastrointestinal Tract/microbiology , Gastrointestinal Diseases/etiology , Gastrointestinal Diseases/prevention & control
11.
Undersea Hyperb Med ; 51(2): 145-157, 2024.
Article in English | MEDLINE | ID: mdl-38985151

ABSTRACT

Introduction: Increasing cancer survivorship, in part due to new radiation treatments, has created a larger population at risk for delayed complications of treatment. Radiation cystitis continues to occur despite targeted radiation techniques. Materials and Methods: To investigate value-based care applying hyperbaric oxygen (HBO2) to treat delayed radiation cystitis, we reviewed public-access Medicare data from 3,309 patients from Oct 1, 2014, through Dec 31, 2019. Using novel statistical modeling, we compared cost and clinical effectiveness in a hyperbaric oxygen group to a control group receiving conventional therapies. Results: Treatment in the hyperbaric group provided a 36% reduction in urinary bleeding, a 78% reduced frequency of blood transfusion for hematuria, a 31% reduction in endoscopic procedures, and fewer hospitalizations when study patients were compared to control. There was a 53% reduction in mortality and reduced unadjusted Medicare costs of $5,059 per patient within the first year after completion of HBO2 treatment per patient. When at least 40 treatments were provided, cost savings per patient increased to $11,548 for the HBO2 study group compared to the control group. This represents a 37% reduction in Medicare spending for the HBO2-treated group. We also validate a dose-response curve effect with a complete course of 40 or more HBO2 treatments having better clinical outcomes than those treated with fewer treatments. Conclusion: These data support previous studies that demonstrate clinical benefits now with cost- effectiveness when adjunctive HBO2 treatments are added to routine interventions. The methodology provides a comparative group selected without bias. It also provides validation of statistical modeling techniques that may be valuable in future analysis, complementary to more traditional methods.


Subject(s)
Cost-Benefit Analysis , Cystitis , Hyperbaric Oxygenation , Medicare , Radiation Injuries , Hyperbaric Oxygenation/economics , Hyperbaric Oxygenation/methods , Humans , Cystitis/therapy , Cystitis/economics , Medicare/economics , United States , Radiation Injuries/therapy , Radiation Injuries/economics , Female , Male , Aged , Cost Savings , Hematuria/etiology , Hematuria/therapy , Hematuria/economics , Hospitalization/economics , Blood Transfusion/economics , Blood Transfusion/statistics & numerical data , Centers for Medicare and Medicaid Services, U.S. , Aged, 80 and over
13.
Adv Skin Wound Care ; 37(7): 1-4, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38899827

ABSTRACT

ABSTRACT: Radiation therapy is often accompanied by skin toxicity in the irradiated area and radiation-induced DNA damage to skin tissue cells in the surrounding pigmented area. This case report describes a patient with radiation-induced skin injury who received wound treatment and psychological intervention with satisfactory results. A 60-year-old woman was admitted to the authors' hospital on January 18, 2021, with radiation-induced skin injury caused by carbon ion radiotherapy for tonsillar carcinoma. The patient underwent wound repair combined with psychological intervention (30 minutes per dressing change). Over a period of 1 month, the wound area was reduced from 11 × 12 cm2 to 1 × 1 cm2, and wound symptoms (exudate, blood odor, wound infection, wound edge dehydration and curling, periwound skin peeling, dryness, and hyperkeratosis) improved. The patient's anxiety factor scores decreased from 18 to 1, and her depression factor scores decreased from 16 to 3. When the patient was discharged from the hospital after 1 month of treatment, she had a satisfactory self-image and normal social activities.


Subject(s)
Tonsillar Neoplasms , Humans , Female , Middle Aged , Tonsillar Neoplasms/radiotherapy , Neck , Radiation Injuries/etiology , Radiation Injuries/therapy
14.
CNS Neurosci Ther ; 30(6): e14794, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38867379

ABSTRACT

BACKGROUND: Radiation-induced brain injury is a neurological condition resulting from radiotherapy for malignant tumors, with its underlying pathogenesis still not fully understood. Current hypotheses suggest that immune cells, particularly the excessive activation of microglia in the central nervous system and the migration of peripheral immune cells into the brain, play a critical role in initiating and progressing the injury. This review aimed to summarize the latest advances in the cellular and molecular mechanisms and the therapeutic potential of microglia in radiation-induced brain injury. METHODS: This article critically examines recent developments in understanding the role of microglia activation in radiation-induced brain injury. It elucidates associated mechanisms and explores novel research pathways and therapeutic options for managing this condition. RESULTS: Post-irradiation, activated microglia release numerous inflammatory factors, exacerbating neuroinflammation and facilitating the onset and progression of radiation-induced damage. Therefore, controlling microglial activation and suppressing the secretion of related inflammatory factors is crucial for preventing radiation-induced brain injury. While microglial activation is a primary factor in neuroinflammation, the precise mechanisms by which radiation prompts this activation remain elusive. Multiple signaling pathways likely contribute to microglial activation and the progression of radiation-induced brain injury. CONCLUSIONS: The intricate microenvironment and molecular mechanisms associated with radiation-induced brain injury underscore the crucial roles of immune cells in its onset and progression. By investigating the interplay among microglia, neurons, astrocytes, and peripheral immune cells, potential strategies emerge to mitigate microglial activation, reduce the release of inflammatory agents, and impede the entry of peripheral immune cells into the brain.


Subject(s)
Brain Injuries , Microglia , Radiation Injuries , Microglia/radiation effects , Microglia/metabolism , Animals , Humans , Radiation Injuries/metabolism , Radiation Injuries/therapy , Brain Injuries/etiology , Brain Injuries/metabolism , Neuroinflammatory Diseases/etiology
15.
Urology ; 191: 86-92, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38692496

ABSTRACT

OBJECTIVE: To determine the incidence of radiation cystitis on prostate cancer (PCa) patients undergoing pelvic radiotherapy (RT), evaluating the most used management strategies, and identifying potential risk factors associated with the development of this condition. METHODS: A retrospective analysis was conducted using the PearlDiver Mariner database, containing patient records compiled between 2011 and 2022. International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes were employed to identify population and outcomes. We evaluated patients who underwent RT for PCa and subsequently developed radiation cystitis. Primary objective was to determine the overall incidence of radiation cystitis. Furthermore, we investigated its associated risk factors and management. RESULTS: A total of 274,865 PCa patients underwent RT during the study period. Of these, 48,713 (17.7%) experienced hematuria following RT, while 7721 (2.8%) were diagnosed with radiation cystitis. After the diagnosis, 2307 patients (29.9%) received diagnostic or therapeutic endoscopic interventions. Only 59 patients (0.76%) underwent endovascular embolization, while 151 patients (1.95%) required cystectomy. Hyperbaric oxygen therapy, administered to 1287 patients (16.67%), was the only treatment that displayed a significant upward trend. Multivariate logistic regression identified obesity (OR 1.29; 95% CI 1.23-1.35), smoking (OR 1.27; 95% CI 1.22-1.33), and diabetes (OR 1.32; 95% CI 1.26-1.39), as significant risk factors for radiation cystitis (all P-values <.001). CONCLUSION: Radiation cystitis represents a rare complication after pelvic RT with significant clinical impact. Its incidence has remained stable throughout the study period. The identified risk factors corroborate the pathophysiology of radiation cystitis. Hyperbaric oxygen therapy was the only treatment to show an upward trend during the study period.


Subject(s)
Cystitis , Databases, Factual , Prostatic Neoplasms , Radiation Injuries , Humans , Male , Cystitis/etiology , Cystitis/epidemiology , Cystitis/therapy , Prostatic Neoplasms/radiotherapy , Incidence , Retrospective Studies , Radiation Injuries/epidemiology , Radiation Injuries/etiology , Radiation Injuries/therapy , Aged , Middle Aged , Risk Factors , Hyperbaric Oxygenation , United States/epidemiology , Radiotherapy/adverse effects
16.
Clin Transl Oncol ; 26(10): 2594-2600, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38704813

ABSTRACT

PURPOSE: The aim of this systematic review was to assess the role of hyperbaric oxygen therapy  (HBOT) in patients with dysphagia after radiation therapy for head and neck cancer. METHOD: A systematic search was conducted in the electronic databases Ovid MEDLINE, Ovid Embase, and Cochrane Central Register of Controlled Trials for relevant studies until March 14, 2023. No restriction on language or publication date. The criteria for inclusion: patients with HNC who had received both radiation therapy and HBOT as 1) a preventive treatment against swallowing difficulties, 2) to preserve swallowing function, or 3) to promote swallowing difficulties. RESULTS: We identified 1396 records. After removal of 31 duplicates, 1365 records were accessible for title and abstract screening. This yielded 53 studies for full text assessment. Six studies met the eligibility criteria and were included for qualitative analysis. CONCLUSION: Evidence of HBOT benefits in patients with dysphagia after radiation therapy for head and neck cancer is inconsistent. Well-designed studies using validated outcome measures and long-term follow-up are warranted.


Subject(s)
Deglutition Disorders , Head and Neck Neoplasms , Hyperbaric Oxygenation , Radiation Injuries , Humans , Deglutition Disorders/etiology , Deglutition Disorders/therapy , Head and Neck Neoplasms/radiotherapy , Hyperbaric Oxygenation/methods , Radiation Injuries/therapy , Radiation Injuries/etiology
17.
JAMA Netw Open ; 7(5): e2410421, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38739392

ABSTRACT

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.


Subject(s)
Acupuncture Therapy , Head and Neck Neoplasms , Radiation Injuries , Xerostomia , Humans , Xerostomia/etiology , Xerostomia/therapy , Male , Head and Neck Neoplasms/radiotherapy , Female , Middle Aged , Aged , Acupuncture Therapy/methods , Radiation Injuries/therapy , Radiation Injuries/etiology , Quality of Life , Treatment Outcome , Radiotherapy/adverse effects
18.
Int J Radiat Biol ; 100(7): 969-981, 2024.
Article in English | MEDLINE | ID: mdl-38787685

ABSTRACT

PURPOSE: A U. S. and European joint effort fostering the development of medical countermeasures (MCMs) operable in case of radiological or nuclear emergencies. METHODS: Based on the joint engagement between the U.S. National Institute of Allergy and Infectious Diseases (NIAID) and the French Institut de Radioprotection et de Sûreté Nucléaire (IRSN), a Statement of Intent to Collaborate was signed in 2014 and a series of working group meeting were established. In December 2022, the NIAID and IRSN hosted a five-day, U.S./European meeting titled 'Radiation-Induced Cutaneous and Gastrointestinal Injuries: Advances in Understanding Pathologies, Assessment, and Clinically Accepted Practices' in Paris, France. The goals of the meeting were to bring together U.S. and European investigators to explore new research avenues for the medical management of skin and gastrointestinal injuries, including specific diagnostics for each organ system, animal models, and promising medical countermeasures (MCMs) to mitigate radiation damage. There was also an emphasis on exploring additional areas of medicine and response to understand best practices from other emergency scenarios, which could be leveraged to improve radiation preparedness, and the importance of accurate dosimetry in preclinical work. RESULTS: Subsequent to the workshop, seven collaborative projects, funded by both organizations, were established on topics ranging from MCMs and predictive biomarkers, and using physical methods to assess cutaneous radiation injuries, to mechanistic studies to understand radiation-induced damage in multiple organ systems. The importance of accurate dosimetry in preclinical works was highlighted and two recently published U.S./European commentaries that focus on the need for dosimetry standardization in the reported literature had their origins in this meeting. This commentary summarizes the workshop and open discussions among academic investigators, industry researchers, and U.S. and IRSN program representatives. CONCLUSIONS: Given the substantive progress made due to these interactions, both groups plan to expand out these meetings by incorporating high-level investigators from across the globe, while endeavoring to maintain the informal setting that was conducive to in-depth scientific discussion and enhanced the state of the science in radiation research.


Subject(s)
Radiation Injuries , Animals , Humans , Europe , Gastrointestinal Diseases/etiology , Gastrointestinal Tract/radiation effects , Gastrointestinal Tract/injuries , Medical Countermeasures , Radiation Injuries/etiology , Radiation Injuries/therapy , Skin/radiation effects , Skin/injuries , United States
19.
Int J Radiat Biol ; 100(7): 996-1008, 2024.
Article in English | MEDLINE | ID: mdl-38776447

ABSTRACT

PURPOSE: Radiation injury (RI) is a common occurrence in malignant tumors patients receiving radiation therapy. While killing tumor cells, normal tissue surrounding the target area is inevitably irradiated at a certain dose, which can cause varying results of radiation injury. Currently, there are limited clinical treatments available for radiation injuries. In recent years, the negative effects of stem cell therapy have been reported more clearly and non-cellular therapies such as exosomes have become a focus of attention for researchers. As a type of vesicle-like substances secreted by mesenchymal stem cells (MSC), MSC derived exosomes (MSC-exo) carry DNA, mRNA, microRNA (miRNAs), specific proteins, lipids, and other active substances involved in intercellular information exchange. miRNAs released by MSC-exo are capable of alleviating and repairing damaged tissues through anti-apoptosis, modulating immune response, regulating inflammatory response and promoting angiogenesis, which indicates that MSC-exo miRNAs have great potential for application in the prevention and treatment of radiation injury. Therefore, it is necessary to explore the underlying therapeutic mechanisms of MSC-exo miRNAs in this process, which may shed new lights on the treatment of radiation injury. CONCLUSIONS: Increasing evidence confirms that MSC-exo has shown encouraging applications in tissue repair due to the anti-apoptotic, immunoreactive, and pro-angiogenesis effects of the miRNAs it carries as intercellular communication carriers. However, miRNA-based therapeutics are still in their infancy and many practical issues remain to be addressed for clinical applications.


Subject(s)
Exosomes , Mesenchymal Stem Cells , MicroRNAs , Radiation Injuries , Exosomes/metabolism , Mesenchymal Stem Cells/radiation effects , Mesenchymal Stem Cells/metabolism , MicroRNAs/metabolism , Humans , Radiation Injuries/therapy , Animals
20.
Urologia ; 91(3): 623-627, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38646941

ABSTRACT

PURPOSE: Chronic radiation cystitis (CRC) develops after radiation therapy and can present with symptoms like urinary frequency, urgency, pelvic pain, and nocturia. We have previously reported that amniotic bladder therapy (ABT) provides symptomatic improvement in refractory CRC patients for up to 3 months. Herein, we evaluated the durability of ABT up to 6 months. MATERIALS AND METHODS: CRC patients recalcitrant to previous treatments received ABT comprised of intra-detrusor injections of 100 mg micronized AM diluted in 10 mL 0.9% preservative-free sodium chloride. Clinical evaluation and questionnaires (Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS), Overactive Bladder (OAB) Assessment Tool, SF-12 Health Survey) were repeated at pre-op and 2, 4, 8, 12, 16, 20, 24, and 36 weeks post-injection. RESULTS: Five consecutive patients with a mean age of 64.4 ± 20.1 years with a median CRC duration of 10 years were included and followed for 6 months. After ABT, the lower urinary tract symptoms improved as early as 2 weeks and were maintained up to 20 weeks. BPIC significantly improved from 36.6 ± 1.1 at baseline to 12.6 ± 1.5 at 16 weeks and 13.8 ± 2.9 at 20 weeks. At 24 and 36 weeks, the improvement was maintained in four (80%) of the five patients (BPIC = 13.8 ± 1.0). Uroflow assessment showed voiding volume improved two-fold in four of the five patients at 24 weeks compared to baseline. CONCLUSION: Our data suggest that a significant number of CRC patients may have durable benefit after ABT. Despite this, some of them can show symptoms rebound at 24 weeks.


Subject(s)
Cystitis , Radiation Injuries , Humans , Radiation Injuries/etiology , Radiation Injuries/therapy , Female , Middle Aged , Cystitis/etiology , Cystitis/therapy , Chronic Disease , Time Factors , Male , Aged , Treatment Outcome , Urethra , Urinary Bladder/radiation effects
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