A Prospective Study Measuring Resident and Faculty Contour Concordance: A Potential Tool for Quantitative Assessment of Residents' Performance in Contouring and Target Delineation in Radiation Oncology Residency.

PURPOSE/OBJECTIVE(S): Accurate target delineation (ie, contouring) is essential for radiation treatment planning and radiotherapy efficacy. As a result, improving the quality of target delineation is an important goal in the education of radiation oncology residents. The purpose of this study was to track the concordance of radiation oncology residents' contours with those of faculty physicians over the course of 1 year to assess for patterns. MATERIALS/METHODS: Residents in postgraduate year (PGY) levels 2 to 4 were asked to contour target volumes that were then compared to the finalized, faculty physician-approved contours. Concordance between resident and faculty physician contours was determined by calculating the Jaccard concordance index (JCI), ranging from 0, meaning no agreement, to 1, meaning complete agreement. Multivariate mixed-effect models were used to assess the association of JCI to the fixed effect of PGY level and its interactions with cancer type and other baseline characteristics. Post hoc means of JCI were compared between PGY levels after accounting for multiple comparisons using Tukey's method. RESULTS: In total, 958 structures from 314 patients collected during the 2020-2021 academic year were studied. The mean JCI was 0.77, 0.75, and 0.61 for the PGY-4, PGY-3, and PGY-2 levels, respectively. The JCI score for PGY-2 was found to be lower than those for PGY-3 and PGY-4, respectively (all P < .001). No statistically significant difference of JCI score was found between the PGY-3 and PGY-4 levels. The average JCI score was lowest (0.51) for primary head and/or neck cancers, and it was highest (0.80) for gynecologic cancers. CONCLUSIONS: Tracking and comparing the concordance of resident contours with faculty physician contours is an intriguing method of assessing resident performance in contouring and target delineation and could potentially serve as a quantitative metric, which is lacking currently, in radiation oncology resident evaluation. However, additional study is necessary before this technique can be incorporated into residency assessments.

Minimally Invasive Hypoglossal Nerve Stimulator Enabled by ECG Sensor and WPT to Manage Obstructive Sleep Apnea.

A hypoglossal nerve stimulator (HGNS) is an invasive device that is used to treat obstructive sleep apnea (OSA) through electrical stimulation. The conventional implantable HGNS device consists of a stimuli generator, a breathing sensor, and electrodes connected to the hypoglossal nerve via leads. However, this implant is bulky and causes significant trauma. In this paper, we propose a minimally invasive HGNS based on an electrocardiogram (ECG) sensor and wireless power transfer (WPT), consisting of a wearable breathing monitor and an implantable stimulator. The breathing external monitor utilizes an ECG sensor to identify abnormal breathing patterns associated with OSA with 88.68% accuracy, achieved through the utilization of a convolutional neural network (CNN) algorithm. With a skin thickness of 5 mm and a receiving coil diameter of 9 mm, the power conversion efficiency was measured as 31.8%. The implantable device, on the other hand, is composed of a front-end CMOS power management module (PMM), a binary-phase-shift-keying (BPSK)-based data demodulator, and a bipolar biphasic current stimuli generator. The PMM, with a silicon area of 0.06 mm2 (excluding PADs), demonstrated a power conversion efficiency of 77.5% when operating at a receiving frequency of 2 MHz. Furthermore, it offers three-voltage options (1.2 V, 1.8 V, and 3.1 V). Within the data receiver component, a low-power BPSK demodulator was ingeniously incorporated, consuming only 42 µW when supplied with a voltage of 0.7 V. The performance was achieved through the implementation of the self-biased phase-locked-loop (PLL) technique. The stimuli generator delivers biphasic constant currents, providing a 5 bit programmable range spanning from 0 to 2.4 mA. The functionality of the proposed ECG- and WPT-based HGNS was validated, representing a highly promising solution for the effective management of OSA, all while minimizing the trauma and space requirements.

A water-soluble fluorescent organic nano-photosensitizer for the ratiometric detection of mitochondrial G-quadruplexes with photodynamic therapy potential.

We report a water-soluble AIEgen (TPAL) that can self-assemble into fluorescent organic nanoparticles for the ratiometric detection of mitochondrial DNA (mtDNA) parallel G-quadruplexes (G4s) with high selectivity, a low detection limit and photodynamic therapy (PDT) potential.

A Closed-Loop Approach to Fight Coronavirus: Early Detection and Subsequent Treatment.

The recent COVID-19 pandemic has caused tremendous damage to the social economy and people's health. Some major issues fighting COVID-19 include early and accurate diagnosis and the shortage of ventilator machines for critical patients. In this manuscript, we describe a novel solution to deal with COVID-19: portable biosensing and wearable photoacoustic imaging for early and accurate diagnosis of infection and magnetic neuromodulation or minimally invasive electrical stimulation to replace traditional ventilation. The solution is a closed-loop system in that the three modules are integrated together and form a loop to cover all-phase strategies for fighting COVID-19. The proposed technique can guarantee ubiquitous and onsite detection, and an electrical hypoglossal stimulator can be more effective in helping severe patients and reducing complications caused by ventilators.

The effect of anticonvulsants on survival among patients with GBM brain tumors undergoing radiation: A SEER-Medicare analysis.

BACKGROUND: Patients with glioblastoma multiforme (GBM) who undergo radiation often require anticonvulsants during treatment. The aim of this study was to determine the effects of anticonvulsants on GBM clinical outcomes. METHODS: A retrospective analysis was performed using the SEER-Medicare database. All patients with GBM who were treated with radiation and concurrently taking an anticonvulsant were included in final analysis. Each class of medication was further subdivided by mechanism of action. Descriptive statistics were performed for all variables. Kaplan Meier survival curves were generated for each class of medication and Cox regression analysis was performed to assess the effect of each individual variable on survival. RESULTS: There were 1561 patients available for final analysis. On multivariate Cox regression analysis, GBM patients taking sodium/calcium (Na/Ca) channel blocker anticonvulsants during radiation therapy demonstrated both improved overall survival (OS) (HR, 0.799; 95% CI [0.716, 0.891]; P < 0.001) and cancer specific survival (CSS) (HR, 0.814; 95% CI [0.727, 0.911]; P < 0.001). CONCLUSION: OS was significantly better in patients taking NA/Ca channel blockers among patients with GBM who were concurrently undergoing radiation therapy.

An Analysis of Risk Factors for Radiation Necrosis Following Cranial Radiation.

Introduction Radiation necrosis in the brain is a frequent complication of brain radiation therapy (RT) and is characterized by various neurological symptoms including cognitive dysfunction, headaches, weakness, apraxia, aphasia, and numbness. These symptoms may be progressive and treatment-resistant. Currently, risk factors for radiation necrosis are not well characterized. The goal of this study is to identify risk factors for cerebral radiation necrosis in order to improve clinicians' ability to appropriately weigh the risks and benefits of brain RT. Methods A retrospective chart review was performed on patients who were diagnosed with brain tumors and received RT (3D conformal therapy, volumetric modulated arc therapy, stereotactic radiosurgery, or stereotactic radiotherapy) at the University of Arkansas for Medical Sciences from July 1, 2017, to July 1, 2019. Data regarding demographics, characteristics of cancer, chemotherapy status and class, comorbidities, and additional medications of patients were collected via EPIC. Total RT dose, fraction size, volume of brain receiving 12 Gy (V12), and retreatment of locally recurrent tumors were recorded from Eclipse. The diagnosis of radiation necrosis was based on MRI reports that were examined for a time period of 24 months following the completion of radiation treatment and confirmed, when possible, by biopsy. Cases that did not have an MRI available at least two months after the completion of RT were excluded. Statistical association analyses were used to identify candidate risk factors to radiation necrosis. These candidate risk factors were further used to assess their associations to demographics and other characteristics of cancer and treatments. Finally, adjusted and unadjusted logistic regression models were used to predict radiation necrosis using a single risk factor or multiple risk factors. ROC curves were used to evaluate the performance of prediction or discrimination of the logistic regression models. Results A total of 139 patients were studied. The mean ± standard deviation (SD) for age was 60.4 ± 13.6 years, female:male ratio was 71:68, and White:African American:other race ratio was 112:24:3. A total of 43 (30.9%) patients were diagnosed with radiation necrosis. Radiation adjuvant to surgery, concurrent systemic therapy status, total dose, and V12 were found to be significantly associated with radiation necrosis and considered candidate risk factors of radiation necrosis in the study. Predictive models showed adjusted odds ratios ([aORs] 95% confidence intervals or CIs) of 3.70 (1.01-13.56) and 8.19 (1.78-37.78) with radiation adjuvant to surgery and concurrent systemic therapy, respectively. For every one unit (log-transformed) increase of total dose and V12, the aORs (95% CI's) were 27.35 (3.74-200.16) and 1.63 (1.15-2.32), respectively. Conclusion Our study suggested a positive correlation of concurrent systemic therapy status and post-surgical adjuvant RT with the incidence of radiation necrosis. It further demonstrated that greater total RT dose and V12 were related to the risk of developing radiation necrosis following brain RT. Given the findings of this study, the aforementioned factors should be considered when weighing the risk of radiation necrosis with the benefits of treatment.

Design and assembly of AIE-active fluorescent organic nanoparticles for anti-counterfeiting fluorescent hydrogels and inks.

Two kinds of AIE-active fluorescent organic nanoparticles were designed and constructed as anti-counterfeiting photoresponsive materials. One is fluorescent organic nanoparticles (TPELs) based on a self-assembly strategy, which were self-assembled from novel amphiphilic tetraphenylethylene (TPE) molecules decorated with a lactose moiety and different photoresponsive tags. The other is polymeric fluorescent organic nanoparticles (F-TPEs) derived from the nanoprecipitation strategy, which utilized pluronic copolymer F127 to encapsulate hydrophobic TPEs without lactosyl modifications. Upon UV light irradiation, these AIE-active materials exhibit different photooxidation behaviors in an aqueous solution to give cyan, orange and green fluorescence emissions, and they were successfully used as an anti-counterfeiting fluorescent hydrogel and ink.

Dual functional amphiphilic sugar-coated AIE-active fluorescent organic nanoparticles for the monitoring and inhibition of insulin amyloid fibrillation based on carbohydrate-protein interactions.

Amyloid-related diseases, such as Alzheimer's disease, are all considered to be related to the deposition of amyloid fibrils in the body. Insulin is a protein hormone that easily undergoes aggregation and fibrillation to form more toxic amyloid-like fibrils. So far, it is still challenging to develop a new protocol to study the ex situ detection and in situ inhibition of amyloid fibrillation. Here, we reported a modular synthetic strategy to construct nine amphiphilic sugar-coated AIE-active fluorescent organic nanoparticles (FONs, TPE2/3/4X, X = G, M or S) with glucosamine (G), mannose (M) or sialic acid (S) as a hydrophilic moiety and tetraphenylethylene (TPE) as a hydrophobic AIE core. The carbohydrate-protein interactions between insulin and TPE2/3/4X were investigated by fluorescence spectroscopy, circular dichroism spectroscopy and transmission electron microscopy. Among the nine FON AIEgens, TPE2G was screened out as the best dual functional FON for the ex situ detection and in situ inhibition of the insulin fibrillation process, indicating that the glycosyl moiety exhibited a crucial effect on the detection/inhibition of insulin fibrillation. The molecular dynamics simulation results showed that the binding mechanism between TPE2G and native insulin was through weak interactions dominated by van der Waals interactions and supplemented by hydrogen bonding interactions to stabilize an α-helix of the insulin A chain, thereby inhibiting the insulin fibrillation process. This work provides a powerful protocol for the further research of amyloid-related diseases based on carbohydrate-protein interactions.

A phantom-based study and clinical implementation of brainlab's treatment planning system for radiosurgical treatments of arteriovenous malformations.

PURPOSE: Development of a simple, phantom-based methodology allowing for pilot applications for the Elements TPS cranio-vascular module and clinical implementation prior to AVM treatments. METHODS: A customized phantom was developed to be visible in MRI and CT images. High resolution digital subtraction angiograms (DSAs) and CT images of the phantom were acquired and imported into the Brainlab Elements treatment planning system. A clinical treatment plan with 5 arcs was generated in cranial vascular planning module and delivered to the phantom using a Varian TrueBeam STx Linac equipped with HD-MLCs and Brainlab ExacTrac imaging system for non-coplanar setup verification. The delivered dose was verified using a calibrated ionization chamber placed in the phantom. Upon verification of the TPS workflow, three patients with AVM who have been treated to date at our center using the Brainlab's cranial vascular module for AVM are presented here for retrospective review. RESULTS: The difference between the planed and measured dose by the ionization chamber was found to be less than 1%. Following a successful dose verification study, a clinical workflow was created. Currently, three AVM patients have been treated successfully. Clinical aspects of imaging and treatment planning consideration are presented in retrospective setting. CONCLUSIONS: Dose verification of the Brainlab Elements cranial vascular planning module for intracranial SRS treatments of AVM on Varian TrueBeam was successfully implemented using a custom-made phantom with <1% discrepancy. The Brainlab Elements' cranial vascular module was successfully implemented in clinical workflow to treat patients with AVM. This manuscript provides a guideline for clinical implementation of frameless Linac-based AVM treatment using the Brainlab Elements TPS.

Nicotinamide riboside alleviates cisplatin-induced peripheral neuropathy via SIRT2 activation.

Background: Chemotherapy-induced peripheral neuropathy represents a major impairment to the quality of life of cancer patients and is one of the most common dose-limiting adverse effects of cancer treatment. Despite its prevalence, no effective treatment or prevention strategy exists. We have previously provided genetic evidence that the NAD+-dependent deacetylase, SIRT2, protects against cisplatin-induced peripheral neuronal cell death and neuropathy by enhancing nucleotide excision repair. In this study, we aimed to examine whether pharmacologic activation of SIRT2 would provide effective prevention and treatment of cisplatin-induced peripheral neuropathy (CIPN) without compromising tumor cell cytotoxic response to cisplatin. Methods: Using von Frey and dynamic hot plate tests, we studied the use of nicotinamide riboside (NR) to prevent and treat CIPN in a mouse model. We also performed cell survival assays to investigate the effect of NAD+ supplementation on cisplatin toxicity in neuronal and cancer cells. Lewis lung carcinoma model was utilized to examine the effect of NR treatment on in vivo cisplatin tumor control. Results: We show that NR, an NAD+ precursor and pharmacologic activator of SIRT2, effectively prevents and alleviates CIPN in mice. We present in vitro and in vivo genetic evidence to illustrate the specific dependence on SIRT2 of NR-mediated CIPN mitigation. Importantly, we demonstrate that NAD+ mediates SIRT2-dependent neuroprotection without inhibiting cisplatin cytotoxic activity against cancer cells. NAD+ may, in fact, further sensitize certain cancer cell types to cisplatin. Conclusions: Together, our results identify SIRT2-targeted activity of NR as a potential therapy to alleviate CIPN, the debilitating and potentially permanent toxicity.

Water-soluble AIE-active fluorescent organic nanoparticles for ratiometric detection of SO2 in the mitochondria of living cells.

We report a water-soluble AIEgen (TYDL) to be self-assembled into fluorescent organic nanoparticles (TYDLs) for specific sensing of SO2 in living hepatoma cells. It is demonstrated that the TYDLs were suitable for ratiometrically detecting endogenous and exogenous SO2 in mitochondria with good selectivity, low detection limit (75 nM) and excellent photostability (>30 min). These findings imply the great potential applications of TYDLs for the diagnosis of SO2-related diseases in cell biology.

#Brachytherapy: Physicians As Influencers on Instagram.

Purpose We aimed to evaluate brachytherapy-related posts on Instagram by identifying patient concerns, the content of related posts, and user outreach. Methods and materials A list of top posts from searching #brachytherapy on May 7, 2021, were generated on a mobile device and all data are representative as of May 7, 2021. Searching for #brachytherapy resulted in 1010 posts which were analyzed using Instagram. The content was categorized by source (physician, patient, hospital, or not otherwise specified), type (education or experiences), disease site (cervical, endometrial, other), and user influence (number of posts, number of followers). Patient posts were specifically analyzed and all captions and hashtags were reviewed. Results The distribution of users with brachytherapy-related posts was as follows: 23% patients, 15% physicians, 9% hospitals, 53% not otherwise specified. Physicians only made up 11% of posts analyzed while the majority, 79%, were from patients and other Instagram users. From the accounts linked to patients, 99% of them were experience-based and 1% were educational. Posts made by physicians were educational in content 66% of the time, with 34% of posts being experiences. The median number of followers from least to greatest were not otherwise specified (NOS) 450.5, patients (501), hospital-affiliated (527), and physicians (608). In gynecological cancer patients, the reported side effects were as follows: fatigue 31%, gastrointestinal (GI) 16%, genitourinary (GU) 16%, pain 28%, and anxiety 50%. Conclusion: This study shows the influential power physicians have on social media and the need for increased brachytherapy awareness on platforms such as Instagram. Patients have voiced apprehension to pursue radiation due to lack of information provided and fear of the unknown. With this concern in mind, physicians are responsible to increase the availability of knowledge to patients in a more relaxed environment than the clinic. With increased physician social media presence, patients will have another avenue for support and reliable source of treatment information.

A dosimetric comparative analysis of Brainlab elements and Eclipse RapidArc for spine SBRT treatment planning.

Purpose. This is a dosimetric study comparing stereotactic body radiotherapy (SBRT) plans of spine tumors using Brainlab Elements Spine planning module against Eclipse RapidArc plans. Dose conformity, dose gradient, dose fall-off, and patient-specific quality assurance (QA) metrics were evaluated. Methods:Twenty patients were immobilized in supine position using half Vac-Lok. A prescription dose of 16 Gy in a single fraction was planned for Varian TrueBeam. Conformal arc plans were generated with Pencil beam (PB), MonteCarlo (MC) in Elements, and RapidArc with Acuros XB algorithm in Eclipse using identical treatment geometry.Results. Eclipse, Elements PB, and Elements MC generated dosimetrically conformal plans having Inverse Paddick Conformity Index (IPCI) <1.3. All plans satisfied the dose constraints to target and OARs. Elements PB had a sharper gradient than Elements MC with average GI of 3.67(95% CI: 3.52-3.82) and 4.06 (95% CI: 3.93-4.20) respectively. Eclipse plans were more homogeneous with mean HI = 1.22 (95% CI: 1.20-1.23) that is lower than others. Average maximum clinical target volume (CTV) doses were higher in Elements MC with 22.31 Gy (95% CI: 21.87-22.74), while PB plans have 21.15 Gy (95% CI: 20.36-21.96), respectively. Elements MC and PB plans had lower average dose to 0.35 c.c. of spinal cord (D0.35cc) of 7.60 Gy (95% CI: 7.18-8.02) and 8.42 Gy (95% CI: 7.83-9.01). All plans had >95% points passing the gamma QA criteria at 3%/2 mm.Conclusion. All treatment plans achieved clinically acceptable target coverage >95% and meet spinal cord dose limits. Smart optimization in Brainlab Elements spine module produced dosimetrically superior plans by better spinal cord sparing.

Improving the adversarial transferability with relational graphs ensemble adversarial attack.

In transferable black-box attacks, adversarial samples remain adversarial across multiple models and are more likely to attack unknown models. From this view, acquiring and exploiting multiple models is the key to improving transferability. For exploiting multiple models, existing approaches concentrate on differences among models but ignore the underlying complex dependencies. This exacerbates the issue of unbalanced and inadequate attacks on multiple models. To this problem, this paper proposes a novel approach, called Relational Graph Ensemble Attack (RGEA), to exploit the dependencies among multiple models. Specifically, we redefine the multi-model ensemble attack as a multi-objective optimization and create a sub-optimization problem to compute the optimal attack direction, but there are serious time-consuming problems. For this time-consuming problem, we define the vector representation of the model, extract the dependency matrix, and then equivalently simplify the sub-optimization problem by utilizing the dependency matrix. Finaly, we theoretically extend to investigate the connection between RGEA and the traditional multiple gradient descent algorithm (MGDA). Notably, combining RGEA further enhances the transferability of existing gradient-based attacks. The experiments using ten normal training models and ten defensive models on the labeled face in the wild (LFW) dataset demonstrate that RGEA improves the success rate of white-box attacks and further boosts the transferability of black-box attacks.

Essential oil from Saussurea costus inhibits proliferation and migration of Eca109 cells via mitochondrial apoptosis and STAT3 signaling

Objective: To investigate the effect and its underlying molecular mechanisms of essential oil from Saussurea costus in esophageal cancer cell line Eca109. Methods: The chemical composition of essential oil from Saussurea costus was investigated by gas chromatography-mass spectrometry (GC-MS). The anti-proliferative, anti-migrative, and apoptotic effects of essential oil from Saussurea costus against Eca109 cells were analyzed. Moreover, the expression of proteins associated with cell cycle, metastasis, and apoptosis was determined. Results: GC-MS analysis showed that essential oil from Saussurea costus was predominantly comprised of sesquiterpenes. Saussurea costus essential oil inhibited the viability of Eca109 cells in a dose-and time-dependent manner with IC 50 values of (24.29±1.49), (19.16±2.27) and (6.97±0.86) μg/mL at 12, 24, and 48 h, respectively. The expression levels of target proteins in the cell cycle (phase G 1 /S), including cyclin D1, p21, and p53, were affected by Saussurea costus essential oil. The essential oil also downregulated the expression of metastasis-related proteins MMP-9 and MMP-2. Moreover, it induced apoptosis of Eca109 cells through the mitochondrial pathway, as well as inhibition of STAT3 phosphorylation. Conclusions: The essential oil from Saussurea costus exhibited anti-proliferative, anti-migrative, and apoptotic effects on Eca109 cells, and could be further explored as a potential anti-esophageal cancer agent.

Essential oil from Saussurea costus inhibits proliferation and migration of Eca109 cells via mitochondrial apoptosis and STAT3 signaling

Objective: To investigate the effect and its underlying molecular mechanisms of essential oil from Saussurea costus in esophageal cancer cell line Eca109. Methods: The chemical composition of essential oil from Saussurea costus was investigated by gas chromatography-mass spectrometry (GC-MS). The anti-proliferative, anti-migrative, and apoptotic effects of essential oil from Saussurea costus against Eca109 cells were analyzed. Moreover, the expression of proteins associated with cell cycle, metastasis, and apoptosis was determined. Results: GC-MS analysis showed that essential oil from Saussurea costus was predominantly comprised of sesquiterpenes. Saussurea costus essential oil inhibited the viability of Eca109 cells in a dose-and time-dependent manner with IC 50 values of (24.29±1.49), (19.16±2.27) and (6.97±0.86) μg/mL at 12, 24, and 48 h, respectively. The expression levels of target proteins in the cell cycle (phase G 1 /S), including cyclin D1, p21, and p53, were affected by Saussurea costus essential oil. The essential oil also downregulated the expression of metastasis-related proteins MMP-9 and MMP-2. Moreover, it induced apoptosis of Eca109 cells through the mitochondrial pathway, as well as inhibition of STAT3 phosphorylation. Conclusions: The essential oil from Saussurea costus exhibited anti-proliferative, anti-migrative, and apoptotic effects on Eca109 cells, and could be further explored as a potential anti-esophageal cancer agent.

Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment.

Platinum-based chemotherapies, such as cisplatin, play a large role in cancer treatment. The development of resistance and treatment toxicity creates substantial barriers to disease control, yet. To enhance the therapeutic index of cisplatin-based chemotherapy, it is imperative to circumvent resistance and toxicity while optimizing tumor sensitization. One of the primary mechanisms by which cancer cells develop resistance to cisplatin is through upregulation of DNA repair pathways. In this review, we discuss the DNA damage response in the context of cisplatin-induced DNA damage. We describe the proteins involved in the pathways and their roles in resistance development. Common biomarkers for cisplatin resistance and their utilization to improve patient risk stratification and treatment personalization are addressed. Finally, we discuss some of the current treatments and future strategies to circumvent the development of cisplatin resistance.

Photoacoustic imaging for monitoring of stroke diseases: A review.

Stroke is the leading cause of death and disability after ischemic heart disease. However, there is lacking a non-invasive long-time monitoring technique for stroke diagnosis and therapy. The photoacoustic imaging approach reconstructs images of an object based on the energy excitation by optical absorption and its conversion to acoustic waves, due to corresponding thermoelastic expansion, which has optical resolution and acoustic propagation. This emerging functional imaging method is a non-invasive technique. Due to its precision, this method is particularly attractive for stroke monitoring purpose. In this paper, we review the achievements of this technology and its applications on stroke, as well as the development status in both animal and human applications. Also, various photoacoustic systems and multi-modality photoacoustic imaging are introduced as for potential clinical applications. Finally, the challenges of photoacoustic imaging for monitoring stroke are discussed.

Pulsed reduced dose-rate radiotherapy for previously irradiated tumors in the brain and spine.

BACKGROUND: Patients with unresectable locoregional cancer recurrences have limited management options. Reirradiation increases the risk of toxicity, particularly when perilesional dose-volume constraints are exceeded. We present and discuss two cases of previously irradiated tumors in the central nervous system (CNS) that was reirradiated using the pulsed reduced dose-rate radiotherapy (PRDR) technique. CASE DESCRIPTION: A 58-year-old female with a history of metastatic small cell lung cancer to the brain status post multiple rounds of radiation and chemotherapy presented with increasing weakness in her right arm and leg. Magnetic resonance imaging (MRI) revealed a growly peripherally enhancing 1.2 cm mass in the left precentral gyrus that had previously received prophylactic cranial irradiation and stereotactic radiosurgery. The patient was re-irradiated with 35 Gy in 100 fractions over 3 weeks, using PRDR with improved motor function at 3-month follow-up. A 41-year-old male with recurrent glioblastoma of the thoracic spinal cord presented with worsening neurological symptoms, including inability to ambulate due to bilateral leg weakness, causing wheelchair use. MRI thoracic spine revealed a recurrent thoracic lesion 2.2 × 1 × 0.8 cm. In addition to chronic chemotherapy, the patient was retreated palliatively in the same area at 50 Gy in 250 fractions, over 6 weeks, using PRDR. The treated lesion was stable on follow-up imaging, and the patient was able to walk with the assistance of a walker. CONCLUSION: In our two cases, PRDR proved effective in the treatment of recurrent malignant CNS tumors that were previously irradiated. Prospective studies are needed to delineate the efficacy and toxicity of PRDR.

SIRT2 promotes murine melanoma progression through natural killer cell inhibition.

SIRT2, an NAD+-dependent histone deacetylase, has been shown to play a pivotal role in various physiological processes, however, its role in cancer is currently controversial. In recent years, SIRT2 has been described as both a tumor suppressor and oncogene with divergent expression and function in various malignancies. Using murine allograft melanoma models, our results suggest increased systemic expression of SIRT2 promotes tumor progression. In this study, SIRT2-overexpressing mice exhibited enhanced tumor growth and larger tumor volumes compared to their wild-type littermates. Mechanistically, systemic overexpression of SIRT2 reduces the number of tumor-infiltrating natural killer (NK) cells and suppresses NK cell function and proliferation within the tumor microenvironment (TME). Furthermore, despite the enhancing effect of NK cell depletion on tumor volume and growth rate in wild-type littermate mice, this effect was diminished in SIRT2-overexpressing mice. Lastly, pharmacological inhibition of SIRT2 increases NK cell tumor infiltration and suppresses allograft melanoma tumor growth. The findings of this study identify a dynamic functional interaction between systemic SIRT2 and NK cell activity, which controls melanoma tumor progression. Given the recent renewed interest in NK-cell-mediated immunotherapy response, SIRT2 could present a new opportunity to mediate immunotherapy response and resistance.