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Cancers Apr 2024to evaluate an SRT approach in patients with at least 10 lesions at the time of BM initial diagnosis.
PURPOSE
to evaluate an SRT approach in patients with at least 10 lesions at the time of BM initial diagnosis.
METHODS
This is a monocentric prospective cohort of patients treated by SRT, followed by a brain MRI every two months. Subsequent SRT could be delivered in cases of new BMs during follow-up. The main endpoints were local control rate (LCR), overall survival (OS), and strategy success rate (SSR). Acute and late toxicity were evaluated.
RESULTS
Seventy patients were included from October 2014 to January 2019, and the most frequent primary diagnosis was non-small-cell lung cancer (N = 36, 51.4%). A total of 1174 BMs were treated at first treatment, corresponding to a median number of 14 BMs per patient. Most of the patients (N = 51, 72.6%) received a single fraction of 20-24 Gy. At 1 year, OS was 62.3%, with a median OS of 19.2 months, and SSR was 77.8%. A cumulative number of 1537 BM were treated over time, corresponding to a median cumulative number of 16 BM per patient. At 1-year, the LCR was 97.3%, with a cumulative incidence of radio-necrosis of 2.1% per lesion. Three patients (4.3%) presented Grade 2 toxicity, and there was no Grade ≥ 3 toxicity. The number of treated BMs and the treatment volume did not influence OS or SSR ( > 0.05).
CONCLUSIONS
SRT was highly efficient in controlling the BM, with minimal side effects. In this setting, an SRT treatment should be proposed even in patients with ≥10 BMs at diagnosis.
PubMed: 38730695
DOI: 10.3390/cancers16091742 -
International Journal of Cancer May 2024Brainstem metastases (BSM) present a significant neuro-oncological challenge, resulting in profound neurological deficits and poor survival outcomes. Stereotactic...
Brainstem metastases (BSM) present a significant neuro-oncological challenge, resulting in profound neurological deficits and poor survival outcomes. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) offer promising therapeutic avenues for BSM despite their precarious location. This international multicenter study investigates the efficacy and safety of SRS and FSRT in 136 patients with 144 BSM treated at nine institutions from 2005 to 2022. The median radiographic and clinical follow-up periods were 6.8 and 9.4 months, respectively. Predominantly, patients with BSM were managed with SRS (69.4%). The median prescription dose and isodose line for SRS were 18 Gy and 65%, respectively, while for FSRT, the median prescription dose was 21 Gy with a median isodose line of 70%. The 12-, 24-, and 36-month local control (LC) rates were 82.9%, 71.4%, and 61.2%, respectively. Corresponding overall survival rates at these time points were 61.1%, 34.7%, and 19.3%. In the multivariable Cox regression analysis for LC, only the minimum biologically effective dose was significantly associated with LC, favoring higher doses for improved control (in Gy, hazard ratio [HR]: 0.86, p < .01). Regarding overall survival, good performance status (Karnofsky performance status, ≥90%; HR: 0.43, p < .01) and prior whole brain radiotherapy (HR: 2.52, p < .01) emerged as associated factors. In 14 BSM (9.7%), treatment-related adverse events were noted, with a total of five (3.4%) radiation necrosis. SRS and FSRT for BSM exhibit efficacy and safety, making them suitable treatment options for affected patients.
PubMed: 38720427
DOI: 10.1002/ijc.34980 -
International Journal of Dentistry 2024Medication-related osteonecrosis of the jaw (MRONJ) is a rare, serious, and debilitating disease of unknown cause that can be associated with significant health-related...
BACKGROUND
Medication-related osteonecrosis of the jaw (MRONJ) is a rare, serious, and debilitating disease of unknown cause that can be associated with significant health-related quality of life (HRQOL) impairment. Hematological disease is characterized by a nonhealing exposed jawbone in patients with a history of antiresorptive or antiangiogenic agent use without radiation exposure to the head or neck. . This prospective study over the period from May 2020 to December 2021 included a representative sample consisting of 27 patients with at least stage 2 MRONJ lesions who underwent surgical rehabilitation via oral and maxillofacial surgery at the University Medical Center Göttingen, Germany. Quality of life data were collected over a 6-month postoperative period using the Health-Related QOL (SF-12) and Oral Health-Related QOL (OHIP-14) questionnaires.
RESULTS
A total of 27 patients considered in the study had a total of 42 MRONJ lesions, corresponding to a mean of 1.56 necroses per patient. MRONJ lesions were downstaged in 85% of the patients. HRQOL was evaluated with the SF-12 questionnaire. Significant improvements were found in six of the eight categories (General Health ( < 0.001), Bodily Pain ( < 0.001), Mental Health ( < 0.001), Vitality ( < 0.001), Role-Emotional (=0.028), and Social Functioning (=0.031)). The OHRQOL score also improved significantly after surgical intervention ( < 0.001).
CONCLUSION
With completed surgical therapy, improvements in HRQOL and OHRQOL are measurable.
PubMed: 38715871
DOI: 10.1155/2024/4435791 -
PeerJ 2024To study the efficacy of PAD Plus-based photoactivated disinfection (PAD) for treating denture stomatitis (DS) in diabetic rats by establishing a diabetic rat DS model.
OBJECTIVE
To study the efficacy of PAD Plus-based photoactivated disinfection (PAD) for treating denture stomatitis (DS) in diabetic rats by establishing a diabetic rat DS model.
METHODS
The diabetic rat DS model was developed by randomly selecting 2-month-old male Sprague-Dawley rats and dividing them into four groups. The palate and denture surfaces of rats in the PAD groups were incubated with 1 mg/mL toluidine blue O for 1 min each, followed by a 1-min exposure to 750-mW light-emitting diode light. The PAD-1 group received one radiation treatment, and the PAD-2 group received three radiation treatments over 5 days with a 1-day interval. The nystatin (NYS) group received treatment for 5 days with a suspension of NYS of 100,000 IU. The infection group did not receive any treatment. In each group, assessments included an inflammation score of the palate, tests for fungal load, histological evaluation, and immunohistochemical detection of interleukin-17 (IL-17) and tumor necrosis factor (TNF-α) conducted 1 and 7 days following the conclusion of treatment.
RESULTS
One day after treatment, the fungal load on the palate and dentures, as well as the mean optical density values of IL-17 and TNF-α, were found to be greater in the infection group than in the other three treatment groups ( < 0.05). On the 7th day after treatment, these values were significantly higher in the infection group than in the PAD-2 and NYS groups ( < 0.05). Importantly, there were no differences between the infection and PAD-1 groups nor between the PAD-2 and NYS groups ( 0.05).
CONCLUSIONS
PAD effectively reduced the fungal load and the expressions of IL-17 and TNF-α in the palate and denture of diabetic DS rats. The efficacy of multiple-light treatments was superior to that of single-light treatments and similar to that of NYS.
Topics: Animals; Male; Rats, Sprague-Dawley; Rats; Stomatitis, Denture; Disinfection; Diabetes Mellitus, Experimental; Tolonium Chloride; Tumor Necrosis Factor-alpha; Interleukin-17; Disease Models, Animal
PubMed: 38708351
DOI: 10.7717/peerj.17268 -
Environmental Pollution (Barking, Essex... Jun 2024Although the negative effects of inorganic UV filters have been documented on several marine organisms, sunscreen products containing such filters are available in the...
Although the negative effects of inorganic UV filters have been documented on several marine organisms, sunscreen products containing such filters are available in the market and proposed as eco-friendly substitutes for harmful, and already banned, organic UV filters (e.g. octinoxate and oxybenzone). In the present study, we investigated the effects of four sunscreen products, labelled by cosmetic companies as "eco-friendly", on the early developmental stages of the sea urchin Paracentrotus lividus, a keystone species occurring in vulnerable coastal habitats. Among sunscreens tested, those containing ZnO and TiO or their mix caused severe impacts on sea urchin embryos. We show that inorganic UV filters were incorporated by larvae during their development and, despite the activation of defence strategies (e.g. phagocytosis by coelomocytes), generated anomalies such as skeletal malformations and tissue necrosis. Conversely, the sunscreen product containing only new-generation organic UV filters (e.g. methylene bis-benzotriazolyl tetramethyl, ethylhexyl triazone, butylphenol diethylamino hydroxybenzoyl hexyl benzoate) did not affect sea urchins, thus resulting actually eco-compatible. Our findings expand information on the impact of inorganic UV filters on marine life, corroborate the need to improve the eco-friendliness assessment of sunscreen products and warn of the risk of bioaccumulation and potential biomagnification of inorganic UV filters along the marine food chain.
Topics: Sunscreening Agents; Animals; Sea Urchins; Ultraviolet Rays; Titanium; Water Pollutants, Chemical; Paracentrotus; Larva; Zinc Oxide
PubMed: 38703981
DOI: 10.1016/j.envpol.2024.124093 -
Medicine May 2024Purpose of our research is to demonstrate efficacy of narrow interval dual phase [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT)...
Purpose of our research is to demonstrate efficacy of narrow interval dual phase [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging in distinguishing tumor recurrence (TR) from radiation necrosis (RN) in patients treated for brain metastases. 35 consecutive patients (22 female, 13 male) with various cancer subtypes, lesion size > 1.0 cm3, and suspected recurrence on brain magnetic resonance imaging (MRI) underwent narrow interval dual phase FDG-PET/CT (30 and 90 min after tracer injection). Clinical outcome was determined via sequential MRIs or pathology reports. Maximum standard uptake value (SUVmax) of lesion (L), gray matter (GM), and white matter (WM) was measured on early (1) and delayed (2) imaging. Analyzed variables include % change, late phase, and early phase for L uptake, L/GM uptake, and L/WM uptake. Statistical analysis (P < .01), receiver operator characteristic (ROC) curve and area under curve (AUC) cutoff values were obtained. Change in L/GM ratio of > -2% was 95% sensitive, 91% specific, and 93% accurate (P < .001, AUC = 0.99) in distinguishing TR from RN. Change in SUVmax of lesion alone was the second-best indicator (P < .001, AUC = 0.94) with an ROC cutoff > 30.5% yielding 86% sensitivity, 83% specificity, and 84% accuracy. Other variables (L alone or L/GM ratios in early or late phase, all L/WM ratios) were significantly less accurate. Utilizing narrow interval dual phase FDG-PET/CT in patients with brain metastasis treated with radiation therapy provides a practical approach to distinguish TR from RN. Narrow time interval allows for better patient comfort, greater efficiency of PET/CT scanner, and lower disruption of workflow.
Topics: Humans; Positron Emission Tomography Computed Tomography; Female; Male; Fluorodeoxyglucose F18; Brain Neoplasms; Middle Aged; Radiation Injuries; Neoplasm Recurrence, Local; Aged; Radiopharmaceuticals; Adult; Diagnosis, Differential; Necrosis; Brain; Magnetic Resonance Imaging; ROC Curve
PubMed: 38701250
DOI: 10.1097/MD.0000000000037789 -
Cell Communication and Signaling : CCS May 2024Anticancer immune surveillance and immunotherapies trigger activation of cytotoxic cytokine signaling, including tumor necrosis factor-α (TNF-α) and TNF-related... (Review)
Review
Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy.
Anticancer immune surveillance and immunotherapies trigger activation of cytotoxic cytokine signaling, including tumor necrosis factor-α (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL) pathways. The pro-inflammatory cytokine TNF-α may be secreted by stromal cells, tumor-associated macrophages, and by cancer cells, indicating a prominent role in the tumor microenvironment (TME). However, tumors manage to adapt, escape immune surveillance, and ultimately develop resistance to the cytotoxic effects of TNF-α. The mechanisms by which cancer cells evade host immunity is a central topic of current cancer research. Resistance to TNF-α is mediated by diverse molecular mechanisms, such as mutation or downregulation of TNF/TRAIL receptors, as well as activation of anti-apoptotic enzymes and transcription factors. TNF-α signaling is also mediated by sphingosine kinases (SphK1 and SphK2), which are responsible for synthesis of the growth-stimulating phospholipid, sphingosine-1-phosphate (S1P). Multiple studies have demonstrated the crucial role of S1P and its transmembrane receptors (S1PR) in both the regulation of inflammatory responses and progression of cancer. Considering that the SphK/S1P/S1PR axis mediates cancer resistance, this sphingolipid signaling pathway is of mechanistic significance when considering immunotherapy-resistant malignancies. However, the exact mechanism by which sphingolipids contribute to the evasion of immune surveillance and abrogation of TNF-α-induced apoptosis remains largely unclear. This study reviews mechanisms of TNF-α-resistance in cancer cells, with emphasis on the pro-survival and immunomodulatory effects of sphingolipids. Inhibition of SphK/S1P-linked pro-survival branch may facilitate reactivation of the pro-apoptotic TNF superfamily effects, although the role of SphK/S1P inhibitors in the regulation of the TME and lymphocyte trafficking should be thoroughly assessed in future studies.
Topics: Humans; Neoplasms; Immunotherapy; Sphingolipids; Tumor Necrosis Factor-alpha; Signal Transduction; Animals; Drug Resistance, Neoplasm; Tumor Microenvironment
PubMed: 38698424
DOI: 10.1186/s12964-024-01626-6 -
Nature Communications May 2024With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority....
With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.
Topics: Radiosurgery; Humans; Brain Neoplasms; Male; Female; Middle Aged; Aged; Magnetic Resonance Imaging; Melanoma; Adult; Treatment Outcome; Tumor Burden; Aged, 80 and over; Treatment Failure; Retrospective Studies
PubMed: 38697991
DOI: 10.1038/s41467-024-47998-8 -
Technology in Cancer Research &... 2024Laser Interstitial Thermotherapy is a minimally invasive treatment option in neurosurgery for intracranial tumors, including recurrent gliomas. The technique employs the... (Review)
Review
Laser Interstitial Thermotherapy is a minimally invasive treatment option in neurosurgery for intracranial tumors, including recurrent gliomas. The technique employs the thermal ablation of target tissue to achieve tumor control with real-time monitoring of the extent by magnetic resonance thermometry, allowing targeted thermal injury to the lesion. Laser Interstitial Thermotherapy has gained interest as a treatment option for recurrent gliomas due to its minimally invasive nature, shorter recovery times, ability to be used even in patients with numerous comorbidities, and potential to provide local tumor control. It can be used as a standalone treatment or combined with other therapies, such as chemotherapy or radiation therapy. We describe the most recent updates regarding several studies and case reports that have evaluated the efficacy and safety of Laser Interstitial Thermotherapy for recurrent gliomas. These studies have reported different outcomes, with some demonstrating promising results in terms of tumor control and patient survival, while others have shown mixed outcomes. The success of Laser Interstitial Thermotherapy depends on various factors, including tumor characteristics, patient selection, and the experience of the surgical team, but the future direction of treatment of recurrent gliomas will include a combined approach, comprising Laser Interstitial Thermotherapy, particularly in deep-seated brain regions. Well-designed prospective studies will be needed to establish with certainty the role of Laser Interstitial Thermotherapy in the treatment of recurrent glioma.
Topics: Humans; Glioblastoma; Hyperthermia, Induced; Neoplasm Recurrence, Local; Laser Therapy; Brain Neoplasms; Treatment Outcome; Combined Modality Therapy
PubMed: 38693845
DOI: 10.1177/15330338241249026 -
Frontiers in Immunology 2024Skin injuries represent a prevalent form of physical trauma, necessitating effective therapeutic strategies to expedite the wound healing process. Hesperidin, a...
INTRODUCTION
Skin injuries represent a prevalent form of physical trauma, necessitating effective therapeutic strategies to expedite the wound healing process. Hesperidin, a bioflavonoid naturally occurring in citrus fruits, exhibits a range of pharmacological attributes, including antimicrobial, antioxidant, anti-inflammatory, anticoagulant, and analgesic properties. The main objective of the study was to formulate a hydrogel with the intention of addressing skin conditions, particularly wound healing.
METHODS
This research introduces a methodology for the fabrication of a membrane composed of a Polyvinyl alcohol - Sodium Alginate (PVA/A) blend, along with the inclusion of an anti-inflammatory agent, Hesperidin (H), which exhibits promising wound healing capabilities. A uniform layer of a homogeneous solution comprising PVA/A was cast. The process of crosslinking and the enhancement of hydrogel characteristics were achieved through the application of gamma irradiation at a dosage of 30 kGy. The membrane was immersed in a Hesperidin (H) solution, facilitating the permeation and absorption of the drug. The resultant system is designed to deliver H in a controlled and sustained manner, which is crucial for promoting efficient wound healing. The obtained PVA/AH hydrogel was evaluated for cytotoxicity, antioxidant and free radical scavenging activities, anti-inflammatory and membrane stability effect. In addition, its action on oxidative stress, and inflammatory markers was evaluated on BJ-1 human normal skin cell line.
RESULTS AND DISCUSSION
We determined the effect of radical scavenging activity PVA/A (49 %) and PVA/AH (87%), the inhibition of Human red blood cell membrane hemolysis by PVA/AH (81.97 and 84.34 %), hypotonicity (83.68 and 76.48 %) and protein denaturation (83.17 and 85.8 %) as compared to 250 μg/ml diclofenac (Dic.) and aspirin (Asp.), respectively. Furthermore, gene expression analysis revealed an increased expression of genes associated with anti-oxidant and anti-inflammatory properties and downregulated TNFα, NFκB, iNOS, and COX2 by 67, 52, 58 and 60%, respectively, by PVA/AH hydrogel compared to LPS-stimulated BJ-1 cells. The advantages associated with Hesperidin can be ascribed to its antioxidant and anti-inflammatory attributes. The incorporation of Hesperidin into hydrogels offers promise for the development of a novel, secure, and efficient strategy for wound healing. This innovative approach holds potential as a solution for wound healing, capitalizing on the collaborative qualities of PVA/AH and gamma irradiation, which can be combined to establish a drug delivery platform for Hesperidin.
Topics: Hesperidin; Polyvinyl Alcohol; Humans; Alginates; NF-kappa B; Tumor Necrosis Factor-alpha; Hydrogels; Signal Transduction; Anti-Inflammatory Agents; Wound Healing; Cyclooxygenase 2; Nitric Oxide Synthase Type II; Antioxidants; Inflammation
PubMed: 38686374
DOI: 10.3389/fimmu.2024.1347420