Could a low-dose definitive radiation therapy be the optimal treatment for choroidal hemangioma?

PURPOSE: To determine the efficacy of low-dose intensity-modulated radiation therapy (IMRT)/volumetric intensity-modulated arc therapy (VMAT) in the treatment of symptomatic choroidal hemangioma (CH). MATERIALS AND METHODS: Fifty-three consecutive patients with CH were retrospectively reviewed. All the patients underwent IMRT/VMAT as a unique treatment. Resolution of subretinal fluid (SRF), improvement of best-corrected visual acuity (BCVA), and reduction in tumor thickness were compared before and after radiotherapy. RESULTS: After definitive radiotherapy, 100 % of SRF and 76.7 % of exudative retinal detachment were resolved. 56.6 % of BCVA improvement in more than two lines was observed. The mean best-corrected visual acuity was 20/280 (range, 20/1200-20/40) at diagnosis and 20/100 (range, 20/1200-20/20) after treatment. The mean tumor thickness decreased significantly from 3.8 mm initially to 1.2 mm after treatment (p < 0.01). 66.0 % of patients were delivered with 21.6 Gy (range, 21.6-42 Gy), 84.9 % of fractional dose was 1.8 Gy (range, 1.8-2 Gy). No radiation-induced keratitis, retinopathy, or optic neuropathy were observed. Initial vision (p = 0.042), duration time of vision (p = 0.004), and tumor thickness (p = 0.049) were prognostic factors for vision recovery. CONCLUSION: Low-dose IMRT/VMAT could effectively induce involution of the CH, with reduction of subretinal fluid and relief of damage to the neurosensory retina, which is an effective treatment mode for CH.

Personalized treatment for patients with lacrimal sac squamous cell carcinoma.

OBJECTIVE: Lacrimal sac squamous cell carcinoma (LSSCC) is a rare and poor prognosis malignancy. We aimed to investigate the predictive factors for prognosis and to discuss the optimal treatment mode. METHODS: This retrospective study comprised 84 patients with LSSCC who accepted multidisciplinary treatment. We analyzed the potential prognostic factors and the efficiency of different treatment modes in univariate and multivariate analyses. RESULTS: The 5-year overall survival (OS), progression-free survival (PFS), regional failure-free survival (RFS), and distant metastasis-free survival (DMFS) rates for the entire cohort were 83.7%, 76.3%, 77.2%, and 83.7%, respectively. On univariate analysis, orbital bone erosion, lymph node metastasis, and advanced clinical stage were poor prognostic factors. Multivariate Cox regression analysis showed that orbital bone erosion was a uniquely poor predictor for OS; orbital bone erosion, positive cervical lymph nodes, and old age were poor predictors for PFS. Chemotherapy significantly improved the 5-year OS (90.4% vs. 69.6%, p = 0.03), PFS (82.1% vs. 63.6%, p = 0.036), and DMFS (90.4% vs. 69.6%, p = 0.013), except for RFS (82.5% vs. 65.6%, p = 0.15). Surgery did not improve the 5-year OS (85.6% vs. 79.3%, p = 0.062), PFS (76.0% vs. 76.2%, p = 0.41), RFS (76.1% vs. 79.5%, p = 0.54), and DMFS (85.6% vs. 79.5%, p = 0.096). However, the pre-operative radiotherapy conferred a slightly better OS (p = 0.13) and DMFS (p = 0.16) than post-operative radiotherapy and definitive radiotherapy, but without statistical significance. CONCLUSIONS: Orbital bone erosion and lymph node metastasis were poor prognostic factors in LSSCC. Chemoradiotherapy was vital and effective. Although surgery did not improve survival, multidisciplinary treatment, including surgery, was recommended for LSSCC.

The treatment efficacy of radiotherapy for optic nerve sheath meningioma.

OBJECTIVES: Optic nerve sheath meningioma (ONSM) is a rare benign tumour that accounts for approximately 2% of all orbital tumours. Radiotherapy has gradually become an important treatment for ONSM because of its good effect in preserving or improving vision. We aimed to explore the effect of radiotherapy on tumour control and vision preservation/improvement in patients with ONSM. METHODS: Forty-three patients with primary ONSM treated in our institution from 2015 to 2021 were enrolled. The irradiation dose was from 50.4 to 54 Gy with 28-30 fractions. We evaluated the tumour volume on MRI or CT, and visual acuity before and after the radiotherapy. RESULTS: Thirty-four patients (79%) experienced a vision decrease at diagnosis. The mean duration of follow-up was 54.1 months (ranges: 18-93, median: 56). Among 25 patients who had tumour evaluation using MRI, 16 patients (37.2%) showed stable tumours, 7 patients (16.3%) had tumour shrinkage, but 2 patients (4.7%) experienced tumour progression. Among the 39 patients performing vision acuity evaluation, 16 patients (37.2%) had vision improvement or recovery. 16 of the 23 patients without vision improvement demonstrated severe visual loss at diagnosis. Two patients had evidence of tumour progression during the follow-up. Additionally, 4 (10.2%) patients had dry eyes, 7 (17.9%) patients experienced watery eyes, and 3 (7.7%) patients had eye swelling. Patients with vision loss for more than 12 months had a lower possibility of vision recovery than those with vision loss for less than 12 months. CONCLUSIONS: Radiotherapy such as IMRT, VMAT, and 3D-CRT plays an important role in the treatment of ONSM. The probability of vision recovery is lower in patients with severe vision loss at diagnosis or the duration of vision loss is more than 12 months.

MicroRNAs in Tumor Endothelial Cells: Regulation, Function and Therapeutic Applications.

Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating evidence has shown that small single-stranded non-coding microRNAs (miRNAs) act as powerful endogenous regulators of TEC function and blood vessel formation. This systematic review provides an up-to-date overview of these endothelial miRNAs. Their expression is mainly regulated by hypoxia, pro-angiogenic factors, gap junctions and extracellular vesicles, as well as long non-coding RNAs and circular RNAs. In preclinical studies, they have been shown to modulate diverse fundamental angiogenesis-related signaling pathways and proteins, including the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway; the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; the phosphoinositide 3-kinase (PI3K)/AKT pathway; and the transforming growth factor (TGF)-ß/TGF-ß receptor (TGFBR) pathway, as well as krüppel-like factors (KLFs), suppressor of cytokine signaling (SOCS) and metalloproteinases (MMPs). Accordingly, endothelial miRNAs represent promising targets for future anti-angiogenic cancer therapy. To achieve this, it will be necessary to further unravel the regulatory and functional networks of endothelial miRNAs and to develop safe and efficient TEC-specific miRNA delivery technologies.

Immunohistochemical p16 expression in the prognosis of patients with sinonasal squamous cell carcinoma.

In sinonasal squamous cell carcinoma (SNSCC), the prognostic relevance of p16INK4a (p16) expression has been reported rarely. This study aims to examine the immunohistochemical expression of p16 and investigate the possibility of p16 as a prognostic factor for SNSCC. The medical records of 173 individuals with SNSCC between 2010 and 2022 were retrospectively reviewed. The researchers examined patients' demographics, p16 status, staging, tumor histological subtypes, treatment details, recurrence, metastasis, and survival outcomes. p16 was found in 22.0% (38/173) of SNSCC patients, and there was no difference between inverted papilloma-SNSCC (19.6%) and de novo SNSCC (23.0%). p16 status did not correlate with all the cases' age, gender, clinical stage, or therapy features. p16-positive patients had a considerably superior 5-year overall survival (OS) rate (80.7% vs. 57.5%, p=0.039) and a slight tendency in progression-free survival (PFS) rate (68.1% vs. 52.0%, p=0.15), except in stage T4b cases. In maxillary sinus lesions, p16-positive SNSCC had a better 5-year OS (87.4% vs. 49.2%, p=0.03) rate and PFS (79.1% vs. 40.7%, p=0.01) rate than p16-negative SNSCC. Among patients without skull base involvement (82.9% vs. 57.7%, p=0.037) or orbital invasion (86.9% vs. 57.3%, p=0.02), p16-positive SNSCC confers benefits in OS rates more than p16-negative SNSCC. Immunohistochemical p16 expression may be a predictive predictor in individuals with maxillary sinus SCC, non-T4b stage, without skull base involvement, and without orbital invasion.

Metal artifacts reduction in kV-CT images with polymetallic dentures and complex metals based on MV-CBCT images in radiotherapy.

This paper proposes a metal artifact reduction method of using MV-CBCT images to correct metal artifacts in kV-CT images, especially for the complex metal artifacts caused by multi-metal interaction of patients with head and neck tumors. The different tissue regions are segmented in the MV-CBCT images to obtain template images and the metal region is segmented in the kV-CT images. Forward projection is performed to get sinogram of the template images, kV-CT images and metal region images. Artifact images can be reconstructed through those sonograms. Corrected images is generated by subtracting the artifact images from the original kV-CT images. After the first correction, the template images are generated again and brought into the previous step for iteration to get better correction result. CT data set of 7 patients are used in this study, compared with linear interpolation metal artifact (LIMAR) and normalized metal artifact reduction method, mean relative error of CT value is reduced by 50.5% and 63.3%, noise is reduced by 56.2% and 58.9%. The Identifiability Score of the tooth, upper/lower jaw, tongue, lips, masseter muscle and cavity in the corrected images by the proposed method have significantly improved (P < 0.05) than original images. The artifacts correction method proposed in this paper can effectively remove the metal artifacts in the images and greatly improve the CT value accuracy, especially in the case of multi-metal and complex metal implantation.

Definitive-intent (chemo)radiotherapy for sinonasal undifferentiated carcinoma.

OBJECTIVE: The current study aimed to investigate the value of definitive-intent (chemo)radiotherapy in treating sinonasal undifferentiated carcinoma (SNUC) in a single institution. METHODS: The medical records of 21 patients with SNUC treated with definitive-intent (chemo)radiotherapy between 2011 and 2021 in one single institution were retrospectively reviewed. We analyzed the treatment efficiency and long-term survivals. RESULTS: A total of 21 patients were included in this cohort, 12 patients presented with T4 stage at diagnosis, and 6 in T1/T2, 3 in T3 stage. Nine patients (42.9%, 9/21) showed cervical lymph node metastases. All the patients were scheduled to receive definitive (chemo)radiotherapy and five patients had been performed surgery for residual tumor after (chemo)radiotherapy. 66.7% (14/21) of patients had a complete response after the completion of treatment, 23.8% (5/21) of partial response, one of stable disease, and one of progressed disease. The 3-year overall survival of the entire group were 86.2%, and the 3-year progress-free survival were 66.3%, respectively. 52.4% of the patients (11/21) presented orbit invasion, compared with patients without orbit invasion, the patients who had orbit invasion were not found to have significantly poor 3-year overall survival (87.5% vs 83.3%, p = 0.38) and 3-year progression-free survival (75.0% vs 55.3%, p = 0.59). CONCLUSION: Definitive-intent (chemo)radiotherapy could be the preferred treatment for patients with advanced SNUC, and salvage surgery should be performed for the lesions showing stable disease, progressed disease, or residual tumor. ADVANCES IN KNOWLEDGE: The value of definitive chemoradiotherapy in treating sinonasal undifferentiated carcinoma.

Treatment for SMARCB1 (INI-1) deficient sinonasal tumor: a single-institution study.

Currently, less than 200 cases of SMARCB1-deficient sinus cancer (SDSC) have been documented. Little information is available about the best treatment options or prognosis for SDSC. From September 2016 to November 2022, the medical records of 22 people with SDSC were evaluated retrospectively. Patient demographics, staging, pathology findings, treatment details, recurrence, metastasis, and survival outcomes were all investigated by the researchers. The 1-, 2-, and 3-year overall survival (OS) rates for the entire cohort were 89.8%, 84.2%, and 45.1%, respectively, as were the 1-, 2-, and 3-year progression-free survival (PFS) rates of 81.8%, 63.8%, and 31.9%. After induction chemotherapy, 66.7% (10/15) of patients exhibited decreased tumor volume. Patients who accepted chemoradiotherapy had a better 2-year OS (100% vs. 72.7%, p=0.048) than those who accepted surgery as a preference. However, there is no difference in 2-year PFS between the two groups (53.0% vs. 75.8%, p=0.59). Patients with progressed or stable disease after induction chemotherapy had a higher risk of developing local recurrence (p=0.007); they also showed poor 2-year PFS (40.0% vs. 82.1%, p=0.019). SDSC had a poor 3-year OS, with a PFS of less than 50%. For locally advanced SDSC, chemoradiotherapy might be managed before surgery, especially in patients who benefit from induction chemotherapy.

Brassinin Promotes the Degradation of Tie2 and FGFR1 in Endothelial Cells and Inhibits Triple-Negative Breast Cancer Angiogenesis.

Brassinin, a phytoalexin derived from cruciferous vegetables, has been reported to exhibit anti-cancer activity in multiple cancer types. However, its effects on triple-negative breast cancer (TNBC) development and the underlying mechanisms have not been elucidated so far. In this study, we demonstrated in vitro that brassinin preferentially reduces the viability of endothelial cells (ECs) when compared to other cell types of the tumor microenvironment, including TNBC cells, pericytes, and fibroblasts. Moreover, brassinin at non-cytotoxic doses significantly suppressed the proliferation, migration, tube formation, and spheroid sprouting of ECs. It also efficiently inhibited angiogenesis in an ex-vivo aortic ring assay and an in-vivo Matrigel plug assay. Daily intraperitoneal injection of brassinin significantly reduced tumor size, microvessel density, as well as the perfusion of tumor microvessels in a dorsal skinfold chamber model of TNBC. Mechanistic analyses showed that brassinin selectively stimulates the degradation of Tie2 and fibroblast growth factor receptor 1 in ECs, leading to the down-regulation of the AKT and extracellular signal-regulated kinase pathways. These findings demonstrate a preferential and potent anti-angiogenic activity of brassinin, which may be the main mechanism of its anti-tumor action. Accordingly, this phytochemical represents a promising candidate for the future anti-angiogenic treatment of TNBC.

The prognostic value of S-100 protein and Ki-67 index in olfactory neuroblastoma.

OBJECTIVE: To evaluate the prognostic value of S-100 protein and Ki-67 labeling index in olfactory neuroblastomas. METHODS: A retrospective study was conducted on a cohort of 85 patients with olfactory neuroblastomas. The immunohistochemical expression of S-100 and Ki-67 was assessed, and the predictive value of S-100 and Ki-67 was further evaluated. The optimal cutoff value of Ki-67 labeling index was determined using time-dependent receiver operating characteristic curve analysis. Overall survival and progression-free survival were assessed using the Kaplan-Meier method. RESULTS: A cut-off Ki-67 labeling index value of 67.5% was determined for prognosis in patients with olfactory neuroblastomas. There was a significant correlation between Ki-67 expression and cervical lymph node metastasis (P = 0.049). Compared with S-100 (+), S-100 (-) was associated with a higher rate of lymph node metastasis and a higher level of Ki-67 (P = 0.007, < 0.001, respectively), as well as an advanced Kadish stage (P = 0.037). Survival analyses showed that patients with S-100 (+) had better 5-year overall survival than those with S-100 (-) (P = 0.028), and patients with both S-100 (+) and Ki-67 (<67.5%) had superior 5-year overall survival compared with all the other patients (P = 0.0225). CONCLUSION: Our findings suggest that S-100 combined with Ki-67 labeling index are reliable prognostic factors in patients with olfactory neuroblastomas.

Mucosa-associated lymphoid tissue of nasopharynx: A case report and literature review.

Nasopharyngeal MALT lymphoma is a rare disease, with limited cases reported in the literature. To the best of our knowledge, there is no research detailing the treatment of nasopharyngeal MALT lymphoma. In this present paper, we report an unusual case of a 70-year-old female patient with nasopharyngeal MALT lymphoma. The patient was treated with radiotherapy alone. The detailed radiation therapy of the treatment was demonstrated. The patient is free of locally recurrent or distant disease at two years. Radiotherapy alone can be a helpful treatment for MALT lymphoma confined to the nasopharyngeal cavity.

Extracellular vesicle-mediated delivery of circDYM alleviates CUS-induced depressive-like behaviours.

Major depressive disorder (MDD) is the most prevalent psychiatric disorder worldwide and severely limits psychosocial function and quality of life, but no effective medication is currently available. Circular RNAs (circRNAs) have been revealed to participate in the MDD pathological process. Targeted delivery of circRNAs without blood-brain barrier (BBB) restriction for remission of MDD represents a promising approach for antidepressant therapy. In this study, RVG-circDYM-extracellular vesicles (RVG-circDYM-EVs) were engineered to target and preferentially transfer circDYM to the brain, and the effect on the pathological process in a chronic unpredictable stress (CUS) mouse model of depression was investigated. The results showed that RVG-circDYM-EVs were successfully purified by ultracentrifugation from overexpressed circDYM HEK 293T cells, and the characterization of RVG-circDYM-EVs was successfully demonstrated in terms of size, morphology and specific markers. Beyond demonstrating proof-of-concept for an RNA drug delivery technology, we observed that systemic administration of RVG-circDYM-EVs efficiently delivered circDYM to the brain, and alleviated CUS-induced depressive-like behaviours, and we discovered that RVG-circDYM-EVs notably inhibited microglial activation, BBB leakiness and peripheral immune cells infiltration, and attenuated astrocyte disfunction induced by CUS. CircDYM can bind mechanistically to the transcription factor TAF1 (TATA-box binding protein associated factor 1), resulting in the decreased expression of its downstream target genes with consequently suppressed neuroinflammation. Taken together, our findings suggest that extracellular vesicle-mediated delivery of circDYM is effective for MDD treatment and promising for clinical applications.

The role of 18F-FDG PET/CT in diagnosis and treatment evaluation for ocular adnexal mucosa-associated lymphoid tissue lymphoma.

OBJECTIVE: The purpose of this study is to evaluate the value of fluorine-18-fludeoxyglucose positron emission tomography (18F-FDG PET)/CT in the diagnosis and treatment evaluation of ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: 70 patients with OAML who received radiotherapy were recruited in our study. All the patients had the 18F-FDG PET/CT examination before the treatment. We retrospectively reviewed the medical records, pathological reports, laboratory results, and imaging features of all patients. The associations between 18F-FDG PET/CT parameters and Epstein-Barr virus antibodies, treatment response, MRI data, and Ki-67 expression were investigated. RESULTS: The PET/CT scan indicated that 80% (56/70) of the patients showed orbital FDG avidity. The median level of maximum standardized uptake value (SUVmax) of the lesions was 4.65 ± 3.00 (range:1.2-13.5). 92.0% (46/50) of the mass-forming lesions showed 18F-FDG avidity, while only 50.0% (10/20) of the non-massive lesions had 18F-FDG avidity (χ2 = 13.23, p=0.01). The SUVmax in orbit, conjunctiva, and lacrimal gland lymphoma were 5.6, 2.9, and 3.7, respectively. A significant difference was identified of SUVmax among the three locations' lymphoma using one-way ANOVA analysis (F = 5.039, p = 0.01). After completion of radiotherapy, the complete remission rate was achieved in 30.8% (4/13) of the patients without 18F-FDG avidity, and 70.4% (38/54) in cases with 18F-FDG avidity (χ2 = 5.43, p = 0.02). The correlation between high Ki-67 score and 18F-FDG avidity was confirmed (χ2 = 3.916, p = 0.048); however, no significant correlation was found between the SUVmax and Ki-67 score of the lesions (p = 0.971). Three patients (3/70, 4.3%) were upregulated the stage via PET/CT. CONCLUSION: 18F-FDG PET/CT had some potential values in the diagnosis and assessment of treatment response in patients with OAML. ADVANCES IN KNOWLEDGE: The value of 18F-FDG PET/CT for patients with OAML.

Extracellular Vesicle-Mediated Delivery of Circular RNA SCMH1 Promotes Functional Recovery in Rodent and Nonhuman Primate Ischemic Stroke Models.

BACKGROUND: Stroke is a leading cause of adult disability that can severely compromise the quality of life of patients, yet no effective medication currently exists to accelerate rehabilitation. A variety of circular RNA (circRNA) molecules are known to function in ischemic brain injury. Lentivirus-based expression systems have been widely used in basic studies of circRNAs, but safety issues with such delivery systems have limited exploration of the potential therapeutic roles for circRNAs. METHODS: Circular RNA SCMH1 (circSCMH1) was screened from the plasma of patients with acute ischemic stroke by using circRNA microarrays. Engineered rabies virus glycoprotein-circSCMH1-extracellular vesicles were generated to selectively deliver circSCMH1 to the brain. Nissl staining was used to examine infarct size. Behavioral tasks were performed to evaluate motor functions in both rodent and nonhuman primate ischemic stroke models. Golgi staining and immunostaining were used to examine neuroplasticity and glial activation. Proteomic assays and RNA-sequencing data combined with transcriptional profiling were used to identify downstream targets of circSCMH1. RESULTS: CircSCMH1 levels were significantly decreased in the plasma of patients with acute ischemic stroke, offering significant power in predicting stroke outcomes. The decreased levels of circSCMH1 were further confirmed in the plasma and peri-infarct cortex of photothrombotic stroke mice. Beyond demonstrating proof-of-concept for an RNA drug delivery technology, we observed that circSCMH1 treatment improved functional recovery after stroke in both mice and monkeys, and we discovered that circSCMH1 enhanced the neuronal plasticity and inhibited glial activation and peripheral immune cell infiltration. CircSCMH1 binds mechanistically to the transcription factor MeCP2 (methyl-CpG binding protein 2), thereby releasing repression of MeCP2 target gene transcription. CONCLUSIONS: Rabies virus glycoprotein-circSCMH1-extracellular vesicles afford protection by promoting functional recovery in the rodent and the nonhuman primate ischemic stroke models. Our study presents a potentially widely applicable nucleotide drug delivery technology and demonstrates the basic mechanism of how circRNAs can be therapeutically exploited to improve poststroke outcomes.