Unusual Soft Tissue Uptake of Tc-99m MDP in Radiation-induced Sarcoma: Diagnostic Conundrum.

Tc-99m methylene diphosphonate (MDP) is a bone imaging agent used for skeletal staging, but it can also be localized in extraosseous calcifying lesions. We report a case of an 84-year-old woman with breast carcinoma who underwent surgery followed by radiotherapy 10 years ago and now presented with a right axillary mass referred for Tc-99m MDP to exclude bone metastasis. Tc-99m MDP shows intense tracer uptake in the right thoracic region corresponding to the site of calcified soft tissue mass in the right lateral chest wall. Subsequent ultrasonography revealed an ill-defined lesion containing coarse calcifications. Biopsy showed radiation-induced sarcoma. Extra osseous Tc-99m MDP uptake may provide important diagnostic information that may alter patient management.

Amide proton transfer-weighted and arterial spin labeling imaging may improve differentiation between high-grade glioma recurrence and radiation-induced brain injury.

Rationale and objectives: The management of tumor recurrence (TR) and radiation-induced brain injury (RIBI) poses significant challenges, necessitating the development of effective differentiation strategies. In this study, we investigated the potential of amide proton transfer-weighted (APTw) and arterial spin labeling (ASL) imaging for discriminating between TR and RIBI in patients with high-grade glioma (HGG). Methods: A total of 64 HGG patients receiving standard treatment were enrolled in this study. The patients were categorized based on secondary pathology or MRI follow-up results, and the demographic characteristics of each group were presented. The APTw, rAPTw, cerebral blood flow (CBF) and rCBF values were quantified. The differences in various parameters between TR and RIBI were assessed using the independent-samples t-test. The discriminative performance of these MRI parameters in distinguishing between the two conditions was assessed using receiver operating characteristic (ROC) curve analysis. Additionally, the Delong test was employed to further evaluate their discriminatory ability. Results: The APTw and CBF values of TR were significantly higher compared to RIBI (P < 0.05). APTw MRI demonstrated superior diagnostic efficiency in distinguishing TR from RIBI (area under the curve [AUC]: 0.864; sensitivity: 75.0 %; specificity: 81.8 %) when compared to ASL imaging. The combined utilization of APTw and CBF value further enhanced the AUC to 0.922. The Delong test demonstrated that the combination of APTw and ASL exhibited superior performance in the identification of TR and RIBI, compared to ASL alone (P = 0.048). Conclusion: APTw exhibited superior diagnostic efficacy compared to ASL in the evaluation of TR and RIBI. Furthermore, the combination of APTw and ASL exhibits greater discriminatory capability and diagnostic performance.

Prospective assessment of peripapillary microvasculature using optical coherence tomography angiography in para-optic intracranial and sinonasal tumors treated with proton therapy.

PURPOSE: Radiation-induced optic neuropathy (RION) is rare but may lead to blindness. The mechanisms by which this occurs include endothelial and neuronal damage, but RION has been assessed very little in the case of extraocular tumors treated with high-energy proton therapy, the use of which is expanding worldwide. We assessed peripapillary microvascular changes by optical coherence tomography angiography (OCT-A) in patients undergoing high-energy proton therapy for para-optic intracranial or head and neck tumors. MATERIALS AND METHODS: In this prospective institutional review board approved study, patients receiving>40Gy_RBE maximal PBT dose to their optic nerve between 2018 and 2020 underwent quantitative OCT-A analyses. ImageJ software was used to assess changes in the peripapillary superficial vascular complex (SVC) using vascular area density (VAD), vessel length density (VLD) and fractal dimension (FDsk). Uni- and multivariate analyses were performed. RESULTS: Of 47 patients (78 eyes) with 29±6 months of follow-up (range 18-42), 29 patients (61.7%) had previously undergone surgery and 18 (32.1%) had microvascular abnormalities prior to proton therapy. Total radiotherapy dose was the most relevant factor in decreased peripapillary microvasculature. Duration of follow-up was associated with lower VAD (P=0.005) and mean retinal nerve fiber layer (RNFLm) thickness also decreased. There was no significant correlation between OCT-A changes and mean visual defect. CONCLUSION: Peripapillary microvasculature changes may occur from tumor compression or surgery and proton therapy for extraocular tumors. OCT-A may provide quantitative and mechanistic insights into RION before the occurrence of clinical symptoms.

CL429 enhances the renewal of intestinal stem cells by upregulating TLR2-YAP1.

Intestinal stem cells (ISCs) play a crucial role in maintaining the equilibrium and regenerative potential of intestinal tissue, thereby ensuring tissue homeostasis and promoting effective tissue regeneration following injury. It has been proven that targeting Toll-like receptors (TLRs) can help prevent radiation-induced damage to the intestine. In this study, we established an intestinal injury model using IR and evaluated the effects of CL429 on ISC regeneration both in vivo and in vitro. Following radiation exposure, mice treated with CL429 showed a significant increase in survival rates (100% survival in the treated group compared to 54.54% in the control group). CL429 also showed remarkable efficacy in inhibiting radiation-induced intestinal damage and promoting ISC proliferation and regeneration. In addition, CL429 protected intestinal organoids against IR-induced injury. Mechanistically, RNA sequencing and Western blot analysis revealed the activation of the Wnt and Hippo signaling pathways by CL429. Specifically, we observed a significant upregulation of YAP1, a key transcription factor in the Hippo pathway, upon CL429 stimulation. Furthermore, knockdown of YAP1 significantly attenuated the radioprotective effect of CL429 on intestinal organoids, indicating that CL429-mediated intestinal radioprotection is dependent on YAP1. In addition, we investigated the relationship between TLR2 and YAP1 using TLR2 knockout mice, and our results showed that TLR2 knockout abolished the activation of CL429 on YAP1. Taken together, our study provides evidence supporting the role of CL429 in promoting ISC regeneration through activation of TLR2-YAP1. And further investigation of the interaction between TLRs and other signaling pathways may enhance our understanding of ISC regeneration after injury.

Angiosarcoma: a 10-year retrospective study from a high-volume UK regional referral centre.

PURPOSE: Angiosarcoma (AS) is a rare malignancy with considerable heterogeneity seen in its aetiology, anatomical location, and clinicopathological behaviour. Diagnosis is often delayed and prognosis poor. The purpose of this study was to perform a retrospective review of all cases of AS over 10 years at a high-volume regional UK referral centre. METHODS/PATIENTS: We reviewed all cases of AS discussed at the sarcoma multidisciplinary meetings of University Hospitals Birmingham NHS Foundation Trust from September 2013 to August 2023. Demographic and clinicopathologic features at diagnosis, approaches to treatment, and outcomes were compared between four AS subtypes. RESULTS: A total of 130 cases were identified. The median age at diagnosis was 71 years, with the majority being female (78%). The most common AS subtype was radiation-induced AS (RIAS) (n = 72; 55%), followed by primary cutaneous (n = 28; 22%), primary non-cutaneous (n = 25; 19%), and AS secondary to lymphoedema (n = 5; 4%). Metastases were present at diagnosis in 18% of patients. Treatment was with surgery in the majority of patients (71%). The median survival for the cohort was 30 months (95% CI 20-40), although this differed significantly by AS subtype (p < 0.001), ranging from 5 months in primary non-cutaneous AS to 76 months in RIAS. CONCLUSION: RIAS is the most common AS subtype, with surgery the only potentially curative treatment modality. Overall prognosis varies significantly by subtype. An international consensus on classification of AS subtypes is required to allow meaningful comparisons across studies and/or a prospective multi-centre registry.

Effect of male parental gamma irradiation on host suitability of its F1 progeny of a lepidopteran tropical pest, Spodoptera litura (Fabr.) towards development and virulence of entomopathogenic nematodes, Steinernema thermophilum.

The suitability of F1 progeny insect larvae of the irradiated male parent, Spodoptera litura (Fabr.) for infective juveniles (IJs) of entomopathogenic nematodes (EPN), Steinernema thermophilum was assessed to comprehend the feasibility of combining EPNs with nuclear pest control tactic. As compared to the control, the IJs induced faster host mortality with reduced proliferation in F1 host larvae. IJs derived from F1 host larvae exhibited almost similar proliferation capacity on normal hosts as in control. Further, the molecular basis of EPNs induced mortality in F1 host larvae was evaluated. Dual stress of EPN infection and irradiation induced downregulation of the relative mRNA expression of antimicrobial genes and upregulated expression of antioxidative genes. A pronounced effect of EPNs in association with irradiation stress was apparent on host mortality. Radiation induced sterile F1 insect larvae of S. litura acted as a reasonably suitable host for EPNs and also provided the environment for developing viable EPNs for their potential use as biocontrol agents.

Serum Vascular Endothelial Growth Factor and Endostatin as an adjunct to clinical decision making in managing radiation induced changes post Gamma Knife Radiosurgery in Spetzler Martin Grade 3 Arterio-venous Malformations patients: A pilot Study.

BACKGROUND: Radiation induced changes (RIC) are the most common complications observed post GKRS and may be observed within 6-18months post procedure. It has been observed that almost one third of RICs are symptomatic and half of them are persistent. There is no way to predict which patients will develop these changes and to what extent. This was a prospective analytical pilot study with the aim of understanding the role of Serum Vascular Endothelial Growth Factor and Endostatin as a predictive factor for clinically symptomatic RIC in intracranial AVMs Spetzler Martin (SM) grade 3 being managed with primary Gamma Knife radiosurgery. Total of 15 patients were analysed. 60% of them had a history of bleed. The median volume of AVM Nidus was 4.36 cc. One third of the patients had no imaging changes suggestive of RIC at 1 year follow up and 2 of the patients had symptomatic RIC needing intervention. Before Gamma Knife, the median values of serum concentration of Endostatin and VEGF are 34.98 ng/mL and 168.37 pg/mL respectively . The serum values of VEGF at 1 month post GKRS was much less than the pre GKRS values but not found to be predictive of RIC. No correlation could be observed with the levels of serum endostatin and RIC. Some patients may develop resistant oedema and necrosis post GKRS for intracranial AVMs which may warrant medical and surgical intervention. Serum biomarkers like VEGF and Endostatin may vary in post GKRS period fpo can be used to identify at risk cases, however more studies are needed to decide on appropriate time of sampling and identify clinically relevant predictive factors.

Comparative analysis of the yields of dicentrics and chromosomal translocations.

PURPOSE: Chromosomal dicentrics and translocations are commonly employed as biomarkers to estimate radiation doses. The main goal of this article is to perform a comparative analysis of yields of both types of aberrations. The objective is to determine if there are relevant distinctions between both yields, allowing for a comprehensive assessment of their respective suitability and accuracy in the estimation of radiation doses. MATERIALS AND METHODS: The analysis involved data from a partial-radiation simulation study with the calibration data obtained through two scoring methods: conventional and PAINT modified. Subsequently, a Bayesian bivariate zero-inflated Poisson model was employed to compare the posterior marginal density of the mean of dicentrics and translocations and assess the differences between them. RESULTS: When employing the conventional method of scoring, the findings indicate that there is no notable disparity between the yield of observed translocations and dicentrics. However, when utilizing the PAINT modified method, a notable discrepancy is observed for higher doses, indicating a relevant difference in the mean number of the two types of aberrations. CONCLUSIONS: The choice of scoring method significantly influences the analysis of radiation-induced aberrations, especially when distinguishing between complex and simple chromosomal formations. Further research and analysis are necessary to gain a deeper understanding of the factors and mechanisms impacting the formation of dicentrics and translocations.

Nintedanib Mitigates Radiation-Induced Pulmonary Fibrosis by Suppressing Epithelial Cell Inflammatory Response and Inhibiting Fibroblast-to-Myofibroblast Transition.

Radiation-induced pulmonary fibrosis (RIPF) represents a serious complication observed in individuals undergoing thoracic radiation therapy. Currently, effective interventions for RIPF are unavailable. Prior research has demonstrated that nintedanib, a Food and Drug Administration (FDA)-approved anti-fibrotic agent for idiopathic pulmonary fibrosis, exerts therapeutic effects on chronic fibrosing interstitial lung disease. This research aimed to investigate the anti-fibrotic influences of nintedanib on RIPF and reveal the fundamental mechanisms. To assess its therapeutic impact, a mouse model of RIPF was established. The process involved nintedanib administration at various time points, both prior to and following thoracic radiation. In the RIPF mouse model, an assessment was conducted on survival rates, body weight, computed tomography features, histological parameters, and changes in gene expression. In vitro experiments were performed to discover the mechanism underlying the therapeutic impact of nintedanib on RIPF. Treatment with nintedanib, administered either two days prior or four weeks after thoracic radiation, significantly alleviated lung pathological changes, suppressed collagen deposition, and improved the overall health status of the mice. Additionally, nintedanib demonstrated significant mitigation of radiation-induced inflammatory responses in epithelial cells by inhibiting the PI3K/AKT and MAPK signaling pathways. Furthermore, nintedanib substantially inhibited fibroblast-to-myofibroblast transition by suppressing the TGF-ß/Smad and PI3K/AKT/mTOR signaling pathways. These findings suggest that nintedanib exerts preventive and therapeutic effects on RIPF by modulating multiple targets instead of a single anti-fibrotic pathway and encourage the further clinical trials to determine the efficacy of nintedanib in patients with RIPF.

Predictors of radiation-induced changes in arteriovenous malformation patients undergoing radiosurgery: Insights from a Malaysian linear accelerator cohort.

Background: Radiation-induced changes (RICs) post-stereotactic radiosurgery (SRS) critically influence outcomes in arteriovenous malformation (AVM) treatments. This study aimed to identify predictors of RICs, described the types and severity of RICs, and assessed their impact on patient's functional outcomes to enhance risk assessment and treatment planning for AVM patients. Methods: This retrospective study analyzed 87 AVM patients who underwent SRS at Hospital Kuala Lumpur between January 2015 and December 2020. RICs were identified through detailed magnetic resonance imaging evaluations, and predictive factors were determined using multiple logistic regression. Functional outcomes were assessed with the modified Rankin scale (mRS). Results: Among the cohort, 40.2% developed RICs, with radiological RICs in 33.3%, symptomatic RICs in 5.7%, and permanent RICs in 1.1%. Severity categorization revealed 25.3% as Grade I, 13.8% as Grade II, and 1.1% as Grade III. Notably, higher Pollock-Flickinger scores and eloquence location were significant predictors of RIC occurrence. There was a significant improvement in functional outcomes post-SRS, with a marked decrease in non-favorable mRS scores from 8.0% pre-SRS to 1.1% post-SRS (P = 0.031). Conclusion: The study identified the eloquence location and Pollock-Flickinger scores as predictors of RICs post-SRS. The significant reduction in non-favorable mRS scores post-SRS underscores the efficacy of SRS in improving patient outcomes. Their results highlighted the importance of personalized treatment planning, focusing on precise strategies to optimize patient outcomes in AVM management, reducing adverse effects while improving functional outcomes.

Sinonasal Malignancy Following Cranial Irradiation: A Scoping Review and Case Report of Sinonasal Teratocarcinosarcoma.

Background Radiation therapy is a mainstay of treatment for brain tumors, but delayed complications include secondary malignancy which may occur months to years after treatment completion. Methods We reviewed the medical records of a 41-year-old female treated with 60 Gy of radiation for a recurrent astrocytoma, who 6 years later developed a locally advanced sinonasal teratocarcinosarcoma. We searched MEDLINE, Embase, and Web of Science to conduct a scoping review of biopsy-proven sinonasal malignancy in patients who previously received cranial irradiation for a brain tumor. Results To our knowledge, this is the first report of a patient to present with a sinonasal teratocarcinosarcoma after receiving irradiation for a brain tumor. Our scoping review of 1,907 studies produced 14 similar cases of secondary sinonasal malignancy. Median age of primary cancer diagnosis was 39.5 years old (standard deviation [SD]: 21.9), and median radiation dose was 54 Gy (SD: 20.3). Median latency time between the primary cancer and secondary sinonasal cancer was 9.5 years (SD: 5.8). Olfactory neuroblastoma was the most common sinonasal cancer ( n = 4). Fifty percent of patients died from their sinonasal cancer within 1.5 years. Conclusion Patients who receive radiation exposure to the sinonasal region for treatment of a primary brain tumor, including low doses or scatter radiation, may be at risk of a secondary sinonasal malignancy later in life. Physicians who monitor at-risk patients must be vigilant of symptoms which may suggest sinonasal malignancy, and surveillance should include radiographic review with careful monitoring for a secondary malignancy throughout the entire irradiated field.

Magnetic Resonance Imaging of Radiation-Induced Brachial Plexopathy.

This report illustrates the case of a 37-year-old woman following chemoradiotherapy for invasive ductal carcinoma of the right breast. The patient underwent surgery and received a radiation dose of 50 gray to the chest wall and 45 gray to the regional lymph nodes in 25 total fractions. She developed motor and sensory weakness in the right upper limb eight years after treatment. Brachial plexus neuropathy in cancer patients may result from either trauma to the plexus during surgery, the spread of cancer, or radiation therapy, and distinguishing between them may be difficult. The case highlights the importance of recognizing the signs, symptoms, and possible differential diagnosis of radiation-induced brachial plexopathy in cancer patients post-radiation therapy. It emphasizes the role of magnetic resonance imaging in the careful assessment and diagnosis of such a case.

Impact of dose volume parameters and clinical characteristics on radiation-induced acute oral mucositis for head and neck cancer patients treated with carbon-ion radiotherapy dose volume outcome analysis.

OBJECTIVES: To assess the predictive value of different dosimetric parameters for acute radiation oral mucositis (ROM) in head and neck cancer (HNCs) patients treated with carbon-ion radiotherapy (CIRT). METHODS: 44 patients with HNCs treated with CIRT were evaluated for acute ROM which was defined as severe when the score ≥3 (acute ROM was scored prospectively using the Radiation Therapy Oncology Group (RTOG) score system). Predictive dosimetric factors were identified by using univariate and multivariate analysis. RESULTS: Male gender, weight loss >5%, and total dose/fractions were related factors to severe ROM. In multivariate analysis, grade ≥3 ROM was significantly related to the Dmax, D10, D15, and D20 (P < 0.05, respectively). As the receiver operating characteristics (ROC) curve shows, the area under the curve (AUC) for D10 was 0.77 (p = 0.003), and the cutoff value was 51.06 Gy (RBE); The AUC for D15 was 0.75 (p = 0.006), and the cutoff value was 42.82 Gy (RBE); The AUC for D20 was 0.74 (p = 0.009), and the cutoff value was 30.45 Gy (RBE); The AUC for Dmax was 0.81 (p < 0.001), and the cutoff value was 69.33 Gy (RBE). CONCLUSION: Male gender, weight loss, and total dose/fractions were significantly association with ROM. Dmax, D10, D15 and D20 were identified as the most valuable predictor and we suggest a Dmax limit of 69.33 Gy (RBE), D10 limit of 51.06 Gy (RBE), D15 limit of 42.82 Gy (RBE), and D20 limit of 30.45 Gy (RBE) and for oral mucosa.

Single-cell transcriptional analysis of irradiated skin reveals changes in fibroblast subpopulations and variability in caveolin expression.

BACKGROUND: Radiation-induced fibrosis (RIF) is an important late complication of radiation therapy, and the resulting damaging effects of RIF can significantly impact reconstructive outcomes. There is currently a paucity of effective treatment options available, likely due to the continuing knowledge gap surrounding the cellular mechanisms involved. In this study, detailed analyses of irradiated and non-irradiated human skin samples were performed incorporating histological and single-cell transcriptional analysis to identify novel features guiding development of skin fibrosis following radiation injury. METHODS: Paired irradiated and contralateral non-irradiated skin samples were obtained from six female patients undergoing post-oncologic breast reconstruction. Skin samples underwent histological evaluation, immunohistochemistry, and biomechanical testing. Single-cell RNA sequencing was performed using the 10X single cell platform. Cells were separated into clusters using Seurat in R. The SingleR classifier was applied to ascribe cell type identities to each cluster. Differentially expressed genes characteristic to each cluster were then determined using non-parametric testing. RESULTS: Comparing irradiated and non-irradiated skin, epidermal atrophy, dermal thickening, and evidence of thick, disorganized collagen deposition within the extracellular matrix of irradiated skin were readily appreciated on histology. These histologic features were associated with stiffness that was higher in irradiated skin. Single-cell RNA sequencing revealed six predominant cell types. Focusing on fibroblasts/stromal lineage cells, five distinct transcriptional clusters (Clusters 0-4) were identified. Interestingly, while all clusters were noted to express Cav1, Cluster 2 was the only one to also express Cav2. Immunohistochemistry demonstrated increased expression of Cav2 in irradiated skin, whereas Cav1 was more readily identified in non-irradiated skin, suggesting Cav1 and Cav2 may act antagonistically to modulate fibrotic cellular responses. CONCLUSION: In response to radiation therapy, specific changes to fibroblast subpopulations and enhanced Cav2 expression may contribute to fibrosis. Altogether, this study introduces a novel pathway of caveolin involvement which may contribute to fibrotic development following radiation injury.

A pretreatment multiparametric MRI-based radiomics-clinical machine learning model for predicting radiation-induced temporal lobe injury in patients with nasopharyngeal carcinoma.

BACKGROUND: To establish and validate a machine learning model using pretreatment multiparametric magnetic resonance imaging-based radiomics data with clinical data to predict radiation-induced temporal lobe injury (RTLI) in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). METHODS: Data from 230 patients with NPC who received IMRT (130 with RTLI and 130 without) were randomly divided into the training (n = 161) and validation cohort (n = 69) with a ratio of 7:3. Radiomics features were extracted from pretreatment apparent diffusion coefficient (ADC) map, T2-weighted imaging (T2WI), and CE-T1-weighted imaging (CE-T1WI). T-test, spearman rank correlation, and least absolute shrinkage and selection operator (LASSO) algorithm were employed to identify significant radiomics features. Clinical features were selected with univariate and multivariate analyses. Radiomics and clinical models were constructed using multiple machine learning classifiers, and a clinical-radiomics nomogram that combined clinical with radiomics features was developed. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were drawn to compare and verify the predictive performances of the clinical model, radiomics model, and clinical-radiomics nomogram. RESULTS: A total of 5064 radiomics features were extracted, from which 52 radiomics features were selected to construct the radiomics signature. The AUC of the radiomics signature based on multiparametric MRI was 0.980 in the training cohort and 0.969 in the validation cohort, outperforming the radiomics signature only based on T2WI and CE-T1WI (p < 0.05), which highlighted the significance of the DWI sequence in the prediction of temporal lobe injury. The area under the curve (AUC) of the clinical model was 0.895 in the training cohort and 0.905 in the validation cohort. The nomogram, which integrated radiomics and clinical features, demonstrated an impressive AUC value of 0.984 in the validation set; however, no statistically significant difference was observed compared to the radiomics model. The calibration curve and decision curve analysis of the nomogram demonstrated excellent predictive performance and clinical feasibility. CONCLUSIONS: The clinical-radiomics nomogram, integrating clinical features with radiomics features derived from pretreatment multiparametric MRI, exhibits compelling predictive performance for RTLI in patients diagnosed with NPC.

Possible association of dose rate and the development of late visual toxicity for patients with intracranial tumours treated with pencil beam scanned proton therapy.

BACKGROUND AND PURPOSE: Rare but severe toxicities of the optic apparatus have been observed after treatment of intracranial tumours with proton therapy. Some adverse events have occurred at unusually low dose levels and are thus difficult to understand considering dose metrics only. When transitioning from double scattering to pencil beam scanning, little consideration was given to increased dose rates observed with the latter delivery paradigm. We explored if dose rate related metrics could provide additional predicting factors for the development of late visual toxicities. MATERIALS AND METHODS: Radiation-induced intracranial visual pathway lesions were delineated on MRI for all index cases. Voxel-wise maximum dose rate (MDR) was calculated for 2 patients with observed optic nerve toxicities (CTCAE grade 3 and 4), and 6 similar control cases. Additionally, linear energy transfer (LET) related dose enhancing metrics were investigated. RESULTS: For the index cases, which developed toxicities at low dose levels (mean, 50 GyRBE), some dose was delivered at higher instantaneous dose rates. While optic structures of non-toxicity cases were exposed to dose rates of up to 1 to 3.2 GyRBE/s, the pre-chiasmatic optic nerves of the 2 toxicity cases were exposed to dose rates above 3.7 GyRBE/s. LET-related metrics were not substantially different between the index and non-toxicity cases. CONCLUSIONS: Our observations reveal large variations in instantaneous dose rates experienced by different volumes within our patient cohort, even when considering the same indications and beam arrangement. High dose rate regions are spatially overlapping with the radiation induced toxicity areas in the follow up images. At this point, it is not feasible to establish causality between exposure to high dose rates and the development of late optic apparatus toxicities due to the low incidence of injury.

Characteristics of radiation-induced brain tumors: case series and systematic review.

OBJECTIVE: Radiation therapy (RT) improves the outcome of patients with cancer but introduces the risk of radiation-induced neoplasms in cancer survivors. The most common radiation-induced brain tumors (RIBTs) are gliomas (RIGs), meningiomas (RIMs), and sarcomas (RISs). To investigate the characteristics of these RIBTs, the authors conducted a comprehensive review and analysis of their case series and relevant cases from the literature. METHODS: Sixteen patients in the case series and 941 patients from the literature who previously underwent cranial irradiation were included in this study. The age at irradiation for primary disease was recorded, and the latency period from irradiation to the development of RIBT and the median overall survival (OS) of patients with RIBTs were analyzed using the Kaplan-Meier method. Patients were stratified by age at the time of irradiation (pediatric vs nonpediatric) and the irradiation dose (higher vs lower dose), and latency and OS were compared using the log-rank test. RESULTS: Among patients with RIBTs, 23.4% underwent radiation at < 5 years of age, and 46.6% underwent RT in the 1st decade of life. The median ages at cranial irradiation were 8.4 (IQR 4.1-16) years in patients with RIMs, 9 (IQR 5-23) years in patients with RIGs, and 27.7 (IQR 13.8-40) years in patients with RISs. The median latency period from irradiation to the development of RIM was significantly longer than that to the development of RIG and RIS (RIM: 20 years, RIG: 9 years, RIS: 10 years; p < 0.0001). The latency period was shorter in the nonpediatric patient group with RIMs (p = 0.047). The OS was significantly longer in patients with RIMs than in those with RIGs and RISs (RIM: not reached, RIG: 11 months, RIS: 11 months; p < 0.0001). The OS of patients with RIMs and RIGs was significantly shorter in patients who received higher radiation doses (p = 0.0095 and p = 0.0026, respectively). CONCLUSIONS: The prognosis was poor and worse for patients with RIGs and RISs than for those with RIMs, and patients with RIBTs who underwent higher-dose irradiation for primary disease had poor prognoses. Because RIBTs develop more than a decade after cranial irradiation, long-term follow-up is crucial.

NLRP3 promotes radiation-induced brain injury by regulating microglial pyroptosis.

PURPOSE: Radiation-induced brain injury, one of the side effects of cranial radiotherapy in tumour patients, usually results in durable and serious cognitive disorders. Microglia are important innate immune-effector cells in the central nervous system. However, the interaction between microglia and neurons in radiation-induced brain injury remains uncharacterised. METHODS AND MATERIALS: We established a microglia-neuron indirect co-culture model to assess the interaction between them. Microglia exposed to radiation were examined for pyroptosis using lactate dehydrogenase (LDH) release, Annexin V/PI staining, SYTOX staining and western blot. The role of nucleotide-binding oligomerisation domain-like receptor family pyrin domain containing 3 (NLRP3) was investigated in microglia exposed to radiation and in mouse radiation brain injury model through siRNA or inhibitor. Mini-mental state examination and cytokines in blood were performed in 23 patients who had experienced cranial irradiation. RESULTS: Microglia exerted neurotoxic features after radiation in the co-culture model. NLRP3 was up-regulated in microglia exposed to radiation, and then caspase-1 was activated. Thus, the gasdermin D protein was cleaved, and it triggered pyroptosis in microglia, which released inflammatory cytokines. Meanwhile, treatment with siRNA NLRP3 in vitro and NLRP3 inhibitor in vivo attenuated the damaged neuron cell and cognitive impairment, respectively. What is more, we found that the patients after radiation with higher IL-6 were observed to have a decreased MMSE score. CONCLUSIONS: These findings indicate that radiation-induced pyroptosis in microglia may promote radiation-induced brain injury via the secretion of neurotoxic cytokines. NLRP3 was evaluated as an important mediator in radiation-induced pyroptosis and a promising therapeutic target for radiation-induced brain injury.

Mitigating radiation-induced brain injury via NLRP3/NLRC4/Caspase-1 pyroptosis pathway: Efficacy of memantine and hydrogen-rich water.

Radiation-induced brain injury (RIBI) is a significant challenge in radiotherapy for head and neck tumors, impacting patients' quality of life. In exploring potential treatments, this study focuses on memantine hydrochloride and hydrogen-rich water, hypothesized to mitigate RIBI through inhibiting the NLRP3/NLRC4/Caspase-1 pathway. In a controlled study involving 40 Sprague-Dawley rats, divided into five groups including a control and various treatment groups, we assessed the effects of these treatments on RIBI. Post-irradiation, all irradiated groups displayed symptoms like weight loss and salivation, with notable variations among different treatment approaches. Particularly, hydrogen-rich water showed a promising reduction in these symptoms. Histopathological analysis indicated substantial hippocampal damage in the radiation-only group, while the groups receiving memantine and/or hydrogen-rich water exhibited significant mitigation of such damage. Molecular studies, revealed a decrease in oxidative stress markers and an attenuated inflammatory response in the treatment groups. Immunohistochemistry further confirmed these molecular changes, suggesting the effectiveness of these agents. Echoing recent scientific inquiries into the protective roles of specific compounds against radiation-induced damages, our study adds to the growing body of evidence on the potential of memantine and hydrogen-rich water as novel therapeutic strategies for RIBI.

Lactobacillus rhamnosus GG alleviates radiation-induced intestinal injury by modulating intestinal immunity and remodeling gut microbiota.

Radiation injury to the intestine is one of the most common complications in patients undergoing abdominal or pelvic cavity radiotherapy. In this study, we investigated the potential protective effect of Lactobacillus rhamnosus GG (LGG) on radiation-induced intestinal injury and its underlying mechanisms. Mice were assigned to a control group, a 10 Gy total abdominal irradiation (TAI) group, or a group pretreated with 108 CFU LGG for three days before TAI. Small intestine and gut microbiota were analyzed 3.5 days post-exposure. LGG intervention improved intestinal structure, reduced jejunal DNA damage, and inhibited the inflammatory cGAS/STING pathway. Furthermore, LGG reduced M1 proinflammatory macrophage and CD8+ T cell infiltration, restoring the balance between Th17 and Treg cells in the inflamed jejunum. LGG also partially restored the gut microbiota. These findings suggest the possible therapeutic radioprotective effect of probiotics LGG in alleviating radiation-induced intestinal injury by maintaining immune homeostasis and reshaping gut microbiota.