Randomized double-blind placebo-controlled trial of the effects of oral trehalose in spinocerebellar ataxia type 3: An interim analysis.

INTRODUCTION: Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease characterized by increasingly worsening ataxia and non-ataxia features, negatively impacting patients' quality of life. This study was designed to test formally evaluate whether oral trehalose was effective in SCA3 patients. METHODS: In this double-blind, randomized controlled trial, SCA3 patients received either 100 g oral trehalose or 30 g maltose to improve ataxia severity over six months. We also measured other clinical (non-ataxia), patient-reported (quality of life, motivations), and safety endpoints. An unscheduled interim analysis was conducted using two-way ANOVAs to analyze the interaction between time (baseline, 3-months, 6-months) and intervention (Trehalose vs. Placebo). RESULTS: Fifteen participants (Trehalose = 7 vs. Placebo = 8) completed the study at the time of interim analysis. There was no interaction effect on the ataxia severity, and available data suggested an estimated sample size of 132 (66 per arm) SCA3 patients required to demonstrate changes in a 6-month trial. There were significant interaction effects for executive function (ƞ2 = 0.28-0.43). Safety data indicated that 100 g oral trehalose was well-tolerated. CONCLUSION: We performed an unplanned interim analysis due to a slow recruitment rate. The new estimated sample size was deemed unfeasible, leading to premature termination of the clinical trial. In this small, current sample of SCA3 patients, 100 g oral trehalose did not differentially impact on ataxia severity compared to placebo. Interestingly, our findings may suggest an improvement in executive function. Future efforts will require a large multi-country, multi-center study to investigate the potential effect of trehalose.

Hybrid Treatment Planning for Chest Wall Irradiation Utilizing Three-Dimensional Conformal Radiotherapy (3DCRT), Intensity-Modulated Radiation Therapy (IMRT), and Volumetric Modulated Arc Therapy (VMAT): A Systematic Review.

Novel hybrid approaches for chest wall irradiation show promising outcomes regarding target coverage and sparing organs at risk (OARs). In this systematic review, we compared hybrid volumetric modulated arc therapy (H-VMAT) or hybrid intensity-modulated radiotherapy (H-IMRT) techniques with non-hybrid techniques, such as three-dimensional conformal radiation therapy (3DCRT), field-in-field (FIF), intensity-modulated arc therapy (IMRT), and volumetric modulated arc therapy (VMAT), for breast cancer patients with mastectomy. Our focus was the plan quality and dose distribution to the OARs. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, we performed a systematic review and quality appraisal of primary studies evaluating hybrid therapy to the chest wall and the OARs. An extensive online search of PubMed and Scopus databases was conducted using appropriate keywords. The dose to the OARs (lung, heart, and contralateral breast), planning target volume (PTV), homogeneity index (HI), and conformity index (CI) were extracted. The data were then tabulated and compared for the outcomes between modalities among the studies. Nine studies that met the search criteria were selected to evaluate the PTV coverage and dosimetric results of hybrid and non-hybrid techniques. In terms of 95% PTV coverage, among nine reviewed studies, the largest difference between the two techniques was between VMAT (47.6 Gy) and H-VMAT (48.4 Gy); for the conformity index, the largest difference was noted between 3DCRT (0.58) and H-VMAT (0.79). In both cases, differences were statistically significant (P < 0.005). Two studies showed dose homogeneity improvement within the treatment target in H-VMAT (0.15 and 0.07) compared with 3DCRT (0.41 and 0.12), with a P value of <0.001. Two studies did not report on the homogeneity index, and three others observed no statistical difference. Regarding OARs, in the comparison of H-VMAT and VMAT, the largest significant change was in the volume receiving 5 Gy (V5Gy) of the ipsilateral lung and the V10Gy of the contralateral lung. For the ipsilateral lung, V5Gy was 90.7% with VMAT versus 51.45% with H-VMAT. For the contralateral lung, V10Gy was 54.9% with VMAT versus 50.5% with H-VMAT. In six studies, the mean dose of the contralateral breast was lower in hybrid techniques than in single modalities: VMAT (4.2%, 6.0%, 1.9%, 7.1%, 4.57%) versus H-VMAT (1.4%, 3.4%, 1.8%, 3.5%, 2.34%) and IMRT (9.1%) versus H-IMRT (4.69%). Although most studies did not report on monitor units and treatment time, those that included them showed that hybrids had lower monitor units and shorter treatment times. Hybrid techniques in radiotherapy, such as combining two modalities, can indeed facilitate lower doses to OARs for patients with a high risk of toxicities. Prospective clinical studies are needed to determine the outcomes of breast cancer treated with hybrid techniques.

Relationship between carotid intima-media thickness and white matter hyperintensities in non-stroke adults: a systematic review.

Introduction: Literature suggests a common pathophysiological ground between carotid atherosclerosis (CAS) and white matter alterations in the brain. However, the association between carotid intima-media thickness (CIMT) and white matter hyperintensities (WMH) has not been conclusively reported. The current systematic review explores and reports the relationship between CIMT and WMH among asymptomatic/non-stroke adults. Methods: A recent literature search on PubMed, SCOPUS, and Web of Science databases was conducted in compliance with the PRISMA protocol. The pre-defined Population-Intervention-Comparison-Outcome-Study (PICOS) criteria included observational studies investigating the CIMT-WMH association among non-stroke adults undergoing magnetic resonance imaging and carotid ultrasound. Results: Out of 255 potential results, 32 studies were critically assessed for selection, and finally, 10 articles were included, comprising 5,116 patients (females = 60.2%; males = 39.8%) aged between 36-71 years. The included studies earned high quality ratings (6-9) based on the Newcastle-Ottawa-Scale criteria. Qualitative synthesis showed a significantly parallel relationship between increased CIMT and greater WMH burden in 50% of the studies. In addition, significant risk factors related to the CIMT-WMH association included older age, hypertension, depression, migraine, Hispanic ethnicity, and apolipoprotein E (ɛ4) in postmenopausal women. Conclusion: Overall, the cumulative evidence showed a consistent CIMT-WMH association in asymptomatic middle-aged and older non-stroke adults, indicating that CAS may contribute to the progression of pathologically hyperintense white matter in the brain. However, further research is warranted to infer the plausible relationship between CIMT and WMH in the absence of stroke.

Fatigue following head and neck cancer radiotherapy: a systematic review of dose correlates.

INTRODUCTIONS: Radical radiotherapy (RT) is the cornerstone of Head and Neck (H&N) cancer treatment, but it often leads to fatigue due to irradiation of brain structures, impacting patient quality of life. OBJECTIVE: This study aimed to systematically investigate the dose correlates of fatigue after H&N RT in brain structures. METHODS: The systematic review included studies that examined the correlation between fatigue outcomes in H&N cancer patients undergoing RT at different time intervals and brain structures. PubMed, Scopus, and WOS databases were used in the systematic review. A methodological quality assessment of the included studies was conducted following the PRISMA guidelines. After RT, the cohort of H&N cancer patients was analyzed for dose correlations with brain structures and substructures, such as the posterior fossa, brainstem, cerebellum, pituitary gland, medulla, and basal ganglia. RESULT: Thirteen studies meeting the inclusion criteria were identified in the search. These studies evaluated the correlation between fatigue and RT dose following H&N RT. The RT dose ranged from 40 Gy to 70 Gy. Most of the studies indicated a correlation between the trajectory of fatigue and the dose effect, with higher levels of fatigue associated with increasing doses. Furthermore, five studies found that acute and late fatigue was associated with dose volume in specific brain structures, such as the brain stem, posterior fossa, cerebellum, pituitary gland, hippocampus, and basal ganglia. CONCLUSION: Fatigue in H&N RT patients is related to the radiation dose received in specific brain areas, particularly in the posterior fossa, brain stem, cerebellum, pituitary gland, medulla, and basal ganglia. Dose reduction in these areas may help alleviate fatigue. Monitoring fatigue in high-risk patients after radiation therapy could be beneficial, especially for those experiencing late fatigue.

Investigating functional connectivity related to stroke recovery: A systematic review.

INTRODUCTION: Stroke recovery is a complex process influenced by various factors, including specific neural reorganization. The objective of this systematic review was to identify important functional connectivity (FC) changes in resting-state fMRI data that were often correlated with motor, emotional, and cognitive outcome improvement. METHOD: A systematic search using PubMed and SCOPUS databases was conducted to identify relevant studies published between 2010 and 2023. RESULTS: A total of 766 studies were identified, of which 20 studies (602 S individuals) met the inclusion criteria. Fourteen studies focussed on motor recovery while six on cognitive recovery. All studies reported interhemispheric FC to be strongly associated with motor and cognitive recovery. The preservation and changes of M1-M1 (eight incidences) and M1-SMA (nine incidences) FC were found to be strongly correlated with motor function improvement. For cognitive recovery, restoration and preservation of FC with and between default mode network (DMN)-related regions were important for the process. CONCLUSIONS: This review identified specific patterns of FC that were consistently reported with recovery of motor and cognitive function. The findings may serve in refining future management strategies to enhance patient outcomes.

Systematic review of cardiovascular magnetic resonance imaging T1 and T2 mapping in patients with Takotsubo syndrome.

Background: Current imaging advancements quantify the use of cardiovascular magnetic resonance (CMR) derived T1 and T2 tissue characterization as robust indicators for cardiomyopathies, but limited literature exists on its clinical application in Takotsubo syndrome (TTS). This systematic review evaluated the T1 and T2 parametric mapping to delineate the current diagnostic and prognostic CMR imaging outcomes in TTS. Methods: A comprehensive literature search until October 2023 was performed on ScienceDirect, PubMed, Web of Science, and Cochrane Library by two independent reviewers adhering to the PRISMA framework. The Newcastle-Ottawa Scale (NOS) was used to evaluate the methodological quality of studies. Results: Out of 198 results, 8 studies were included in this qualitative synthesis, accounting for a total population of 399 subjects (TTS = 201, controls = 175, acute myocarditis = 14, and acute regional myocardial oedema without infarction = 9). Approximately 50.4 % were TTS patients aged between 61 and 73 years, whereof, females (n = 181, 90.0 %) and apical variants (n = 180, 89.6 %) were significantly higher, and emotional stressor (n = 42; 20.9 %) was more prevalent than physical (n = 27; 13.4 %). The NOS identified 62.5 % of studies as moderate and 37.5 % as high quality. Parametric tissue mapping revealed significantly prolonged T1 and T2 relaxation times at 1.5T and 3T respectively in TTS (1053-1164 msec, 1292-1438 msec; and 56-67 msec, 60-90 msec) with higher extracellular volume (ECV) fraction (29-36 %), compared to healthy subjects (944-1211 msec, 1189-1251 msec; and 46-54 msec, 32-68 msec; 23-29 %) and myocarditis (1058 msec, 60 msec). Other significant myocardial abnormalities included increased left ventricular (LV) end-systolic and diastolic volume and reduced global longitudinal strain. Overall, myocardial oedema, altered LV mass and strain, and worse LV systolic function, with higher native T1, T2, and ECV values were consistent. Conclusions: Future research with substantially larger clinical trials is vital to explore the CMR imaging findings in diverse TTS patient cohorts and correlate the T1 and T2 mapping outcomes with demographic/clinical covariates. CMR is a valuable imaging tool for TTS diagnosis and prognostication. T1 and T2 parametric mapping facilitates the quantification of oedema, inflammation, and myocardial injury in Takotsubo.

Toxicity profile of patients treated with proton and carbon-ion therapy for primary nasopharyngeal carcinoma: A systematic review and meta-analysis.

BACKGROUND: Proton and carbon-ion therapy may spare normal tissues in regions with many critical structures surrounding the target volume. As toxicity outcome data are emerging, we aimed to synthesize the published data for the toxicity outcomes of proton or carbon-ion therapy (together known as particle beam therapy [PBT]) for primary nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We searched PubMed and Scopus electronic databases to identify original studies reporting toxicity outcomes following PBT of primary NPC. Quality assessment was performed using NIH's Quality Assessment Tool. Reports were extracted for information on demographics, main results, and clinical and dose factors correlates. Meta-analysis was performed using the random-effects model. RESULTS: Twelve studies were selected (six using mixed particle-photon beams, five performed comparisons to photon-based therapy). The pooled event rates for acute grade ≥2 toxicities mucositis, dermatitis, xerostomia weight loss are 46% (95% confidence interval [95% CI]-29%-64%, I2 = 87%), 47% (95% CI-28%-67%, I2 = 87%), 16% (95% CI-9%-29%, I2 = 76%), and 36% (95% CI-27%-47%, I2 = 45%), respectively. Only one late endpoint (xerostomia grade ≥2) has sufficient data for analysis with pooled event rate of 9% (95% CI-3%-29%, I2 = 77%), lower than intensity-modulated radiotherapy 27% (95% CI-10%-54%, I2 = 95%). For most endpoints with significant differences between the PBT and photon-based therapies, PBT resulted in better outcomes. In two studies where dose distribution was studied, doses to the organs at risk were independent risk factors for toxicities. CONCLUSION: PBT may reduce the risk of acute toxicities for patients treated for primary NPC, likely due to dose reduction to critical structures. The pooled event rate for toxicities derived in this study can be a guide for patient counseling.

Quality of Life for Head and Neck Cancer Patients: A 10-Year Bibliographic Analysis.

Head and neck cancers (HNCs) have a profound impact on patients, affecting not only their physical appearance but also fundamental aspects of their daily lives. This bibliometric study examines the landscape of scientific research pertaining to the quality of life (QoL) among head and neck cancer (HNC) patients. By employing data and bibliometric analysis derived from the Web of Science Core Collection (WOS-CC) and employing R-package and VOSviewer for visualization, the study assesses the current status of and prominent areas of focus within the literature over the past decade. The analysis reveals noteworthy countries, journals, and institutions that have exhibited notable productivity in this research domain between 2013 and 2022. Notably, the United States, the Supportive Care in Cancer journal, and the University of Pittsburgh emerged as the leading contributors. Moreover, there was a discernible shift, with an increasing focus on the significance of QoL within the survivorship context, exemplified by the emergence and subsequent peak of related keywords in 2020 and the subsequent year, respectively. The temporal analysis additionally reveals a transition towards specific QoL indices, such as dysphagia and oral mucositis. Therefore, the increasing relevance of survivorship further underscores the need for studies that address the associated concerns and challenges faced by patients.

The Applications of High-Intensity Focused Ultrasound (HIFU) Ablative Therapy in the Treatment of Primary Breast Cancer: A Systematic Review.

BACKGROUND: This study evaluates the role of high-intensity focused ultrasound (HIFU) ablative therapy in treating primary breast cancer. METHODS: PubMed and Scopus databases were searched according to the PRISMA guidelines to identify studies from 2002 to November 2022. Eligible studies were selected based on criteria such as experimental study type, the use of HIFU therapy as a treatment for localised breast cancer with objective clinical evaluation, i.e., clinical, radiological, and pathological outcomes. Nine studies were included in this study. RESULTS: Two randomised controlled trials and seven non-randomised clinical trials fulfilled the inclusion criteria. The percentage of patients who achieved complete (100%) coagulation necrosis varied from 17% to 100% across all studies. Eight of the nine studies followed the treat-and-resect protocol in which HIFU-ablated tumours were surgically resected for pathological evaluation. Most breast cancers were single, solitary, and palpable breast tumours. Haematoxylin and eosin stains used for histopathological evaluation showed evidence of coagulation necrosis. Radiological evaluation by MRI showed an absence of contrast enhancement in the HIFU-treated tumour and 1.5 to 2 cm of normal breast tissue, with a thin peripheral rim of enhancement indicative of coagulation necrosis. All studies did not report severe complications, i.e., haemorrhage and infection. Common complications related to HIFU ablation were local mammary oedema, pain, tenderness, and mild to moderate burns. Only one third-degree burn was reported. Generally, the cosmetic outcome was good. The five-year disease-free survival rate was 95%, as reported in two RCTs. CONCLUSIONS: HIFU ablation can induce tumour coagulation necrosis in localised breast cancer, with a favourable safety profile and cosmetic outcome. However, there is variable evidence of complete coagulation necrosis in the HIFU-treated tumour. Histopathological evidence of coagulation necrosis has been inconsistent, and there is no reliable radiological modality to assess coagulation necrosis confidently. Further exploration is needed to establish the accurate ablation margin with a reliable radiological modality for treatment and follow-up. HIFU therapy is currently limited to single, palpable breast tumours. More extensive and randomised clinical trials are needed to evaluate HIFU therapy for breast cancer, especially where the tumour is left in situ.

Characterizing Employees with Primary and Secondary Caregiving Responsibilities: Informal Care Provision in Malaysia.

There is a need to determine the extent to which Malaysian employees reconcile both paid employment and informal care provision. We examined data from the Malaysia's Healthiest Workplace via AIA Vitality Online Survey 2019 (N = 17,286). A multivariate multinomial regression was conducted to examine characteristics for the following groups: primary caregiver of a child or disabled child, primary caregiver of a disabled adult or elderly individual, primary caregiver for both children and elderly, as well as secondary caregivers. Respondent mean age ± SD was 34.76 ± 9.31, with 49.6% (n = 8573), identifying as either a primary or secondary caregiver to at least one child under 18 years, an elderly individual, or both. Males (n = 6957; 40.2%) had higher odds of being primary caregivers to children (OR 2.06; 95% CI 1.85-2.30), elderly (OR 1.24; 95% CI 1.09-1.41) and both children and elderly (OR 1.87; 95% CI 1.57-2.22). However, males were less likely to be secondary caregivers than females (OR 0.61; 95% CI 0.53-0.71). Our results highlight the differences in characteristics of employees engaged in informal care provision, and to a lesser degree, the extent to which mid-life individual employees are sandwiched into caring for children and/or the elderly.

The Assessment of White Matter Integrity Alteration Pattern in Patients with Brain Tumor Utilizing Diffusion Tensor Imaging: A Systematic Review.

Alteration in the surrounding brain tissue may occur in the presence of a brain tumor. The present study aims to assess the characteristics and criteria of the pattern of white matter tract microstructure integrity alteration in brain tumor patients. The Scopus, PubMed/Medline, and Web of Science electronic databases were searched for related articles based on the guidelines established by PRISMA. Twenty-five studies were selected on the morphological changes of white matter tract integrity based on the differential classification of white matter tract (WMT) patterns in brain tumor patients through diffusion tensor imaging (DTI). The characterization was based on two criteria: the visualization of the tract-its orientation and position-and the DTI parameters, which were the fractional anisotropy and apparent diffusion coefficient. Individual evaluations revealed no absolute, mutually exclusive type of tumor in relation to morphological WMT microstructure integrity changes. In most cases, different types and grades of tumors have shown displacement or infiltration. Characterizing morphological changes in the integrity of the white matter tract microstructures is vital in the diagnostic and prognostic evaluation of the tumor's progression and could be a potential assessment for the early detection of possible neurological defects that may affect the patient, as well as aiding in surgery decision-making.

Role of resting-state functional MRI in detecting brain functional changes following radiotherapy for head and neck cancer: a systematic review and meta-analysis.

PURPOSE: Increasing evidence implicates changes in brain function following radiotherapy for head and neck cancer as precursors for brain dysfunction. These changes may thus be used as biomarkers for early detection. This review aimed to determine the role of resting-state functional magnetic resonance imaging (rs-fMRI) in detecting brain functional changes. METHODS: A systematic search was performed in the PubMed, Scopus, and Web of Science (WoS) databases in June 2022. Patients with head and neck cancer treated with radiotherapy and periodic rs-fMRI assessments were included. A meta-analysis was performed to determine the potential of rs-fMRI for detecting brain changes. RESULTS: Ten studies with a total of 513 subjects (head and neck cancer patients, n = 437; healthy controls, n = 76) were included. A significance of rs-fMRI for detecting brain changes in the temporal and frontal lobes, cingulate cortex, and cuneus was demonstrated in most studies. These changes were reported to be associated with dose (6/10 studies) and latency (4/10 studies). A strong effect size (r = 0.71, p < 0.001) between rs-fMRI and brain changes was also reported, suggesting rs-fMRI's capability for monitoring brain alterations. CONCLUSION: Resting-state functional MRI is a promising tool for detecting brain functional changes following head and neck radiotherapy. These changes are correlated with latency and prescription dose.

Delta-radiomics-based models for toxicity prediction in radiotherapy: A systematic review and meta-analysis.

INTRODUCTION: Delta-radiomics models are potentially able to improve the treatment assessment than single-time point features. The purpose of this study is to systematically synthesize the performance of delta-radiomics-based models for radiotherapy (RT)-induced toxicity. METHODS: A literature search was performed following the PRISMA guidelines. Systematic searches were performed in PubMed, Scopus, Cochrane and Embase databases in October 2022. Retrospective and prospective studies on the delta-radiomics model for RT-induced toxicity were included based on predefined PICOS criteria. A random-effect meta-analysis of AUC was performed on the performance of delta-radiomics models, and a comparison with non-delta radiomics models was included. RESULTS: Of the 563 articles retrieved, 13 selected studies of RT-treated patients on different types of cancer (HNC = 571, NPC = 186, NSCLC = 165, oesophagus = 106, prostate = 33, OPC = 21) were eligible for inclusion in the systematic review. Included studies show that morphological and dosimetric features may improve the predictive model performance for the selected toxicity. Four studies that reported both delta and non-delta radiomics features with AUC were included in the meta-analysis. The AUC random effects estimate for delta and non-delta radiomics models were 0.80 and 0.78 with heterogeneity, I2 of 73% and 27% respectively. CONCLUSION: Delta-radiomics-based models were found to be promising predictors of predefined end points. Future studies should consider using standardized methods and radiomics features and external validation to the reviewed delta-radiomics model.

Quality of Life and Patient-Reported Outcomes Following Proton Therapy for Oropharyngeal Carcinoma: A Systematic Review.

BACKGROUND: Complex anatomy surrounding the oropharynx makes proton therapy (PT), especially intensity-modulated PT (IMPT), a potentially attractive option due to its ability to reduce the volume of irradiated healthy tissues. Dosimetric improvement may not translate to clinically relevant benefits. As outcome data are emerging, we aimed to evaluate the evidence of the quality of life (QOL) and patient-reported outcomes (PROs) following PT for oropharyngeal carcinoma (OC). MATERIALS AND METHODS: We searched PubMed and Scopus electronic databases (date: 15 February 2023) to identify original studies on QOL and PROs following PT for OC. We employed a fluid strategy in the search strategy by tracking citations of the initially selected studies. Reports were extracted for information on demographics, main results, and clinical and dose factor correlates. Quality assessment was performed using the NIH's Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The PRISMA guidelines were followed in the preparation of this report. RESULTS: Seven reports were selected, including one from a recently published paper captured from citation tracking. Five compared PT and photon-based therapy, although none were randomized controlled trials. Most endpoints with significant differences favored PT, including xerostomia, cough, need for nutritional supplements, dysgeusia, food taste, appetite, and general symptoms. However, some endpoints favored photon-based therapy (sexual symptoms) or showed no significant difference (e.g., fatigue, pain, sleep, mouth sores). The PROs and QOL improve following PT but do not appear to return to baseline. CONCLUSION: Evidence suggests that PT causes less QOL and PRO deterioration than photon-based therapy. Biases due to the non-randomized study design remain obstacles to a firm conclusion. Whether or not PT is cost-effective should be the subject of further investigation.

Functional Alteration in the Brain Due to Tumour Invasion in Paediatric Patients: A Systematic Review.

Working memory, language and speech abilities, motor skills, and visual abilities are often impaired in children with brain tumours. This is because tumours can invade the brain's functional areas and cause alterations to the neuronal networks. However, it is unclear what the mechanism of tumour invasion is and how various treatments can cause cognitive impairment. Therefore, this study aims to systematically evaluate the effects of tumour invasion on the cognitive, language, motor, and visual abilities of paediatric patients, as well as discuss the alterations and modifications in neuronal networks and anatomy. The electronic database, PubMed, was used to find relevant studies. The studies were systematically reviewed based on the type and location of brain tumours, cognitive assessment, and pre- and post-operative deficits experienced by patients. Sixteen studies were selected based on the inclusion and exclusion criteria following the guidelines from PRISMA. Most studies agree that tumour invasion in the brain causes cognitive dysfunction and alteration in patients. The effects of a tumour on cognition, language, motor, and visual abilities depend on the type of tumour and its location in the brain. The alteration to the neuronal networks is also dependent on the type and location of the tumour. However, the default mode network (DMN) is the most affected network, regardless of the tumour type and location.Furthermore, our findings suggest that different treatment types can also contribute to patients' cognitive function to improve or deteriorate. Deficits that persisted or were acquired after surgery could result from surgical manipulation or the progression of the tumour's growth. Meanwhile, recovery from the deficits indicated that the brain has the ability to recover and reorganise itself.

Remote assessment of cognition and quality of life following radiotherapy for nasopharyngeal carcinoma: deep-learning-based predictive models and MRI correlates.

PURPOSE: Irradiation of the brain regions from nasopharyngeal carcinoma (NPC) radiotherapy (RT) is frequently unavoidable, which may result in radiation-induced cognitive deficit. Using deep learning (DL), the study aims to develop prediction models in predicting compromised cognition in patients following NPC RT using remote assessments and determine their relation to the quality of life (QoL) and MRI changes. METHODS: Seventy patients (20-76 aged) with MRI imaging (pre- and post-RT (6 months-1 year)) and complete cognitive assessments were recruited. Hippocampus, temporal lobes (TLs), and cerebellum were delineated and dosimetry parameters were extracted. Assessments were given post-RT via telephone (Telephone Interview Cognitive Status (TICS), Telephone Montreal Cognitive Assessment (T-MoCA), Telephone Mini Addenbrooke's Cognitive Examination (Tele-MACE), and QLQ-H&N 43). Regression and deep neural network (DNN) models were used to predict post-RT cognition using anatomical and treatment dose features. RESULTS: Remote cognitive assessments were inter-correlated (r > 0.9). TLs showed significance in pre- and post-RT volume differences and cognitive deficits, that are correlated with RT-associated volume atrophy and dose distribution. Good classification accuracy based on DNN area under receiver operating curve (AUROC) for cognitive prediction (T-MoCA AUROC = 0.878, TICS AUROC = 0.89, Tele-MACE AUROC = 0.919). CONCLUSION: DL-based prediction models assessed using remote assessments can assist in predicting cognitive deficit following NPC RT. Comparable results of remote assessments in assessing cognition suggest its possibility in replacing standard assessments. IMPLICATIONS FOR CANCER SURVIVORS: Application of prediction models in individual patient enables tailored interventions to be provided in managing cognitive changes following NPC RT.

Remote assessment of cognition and quality of life following radiotherapy for glioma: deep-learning-based predictive models and MRI correlates.

BACKGROUND: Glioma irradiation often unavoidably damages the brain volume and affects cognition. This study aims to evaluate the relationship of remote cognitive assessments in determining cognitive impairment of irradiated glioma patients in relation to the quality of life and MRI changes. METHODS: Thirty patients (16-76 aged) with two imaging (pre- and post-RT) and completed cognitive assessments were recruited. Cerebellum, right and left temporal lobes, corpus callosum, amygdala and spinal cord were delineated and their dosimetry parameters were collected. Cognitive assessments were given post-RT via telephone (Telephone Interview Cognitive Status (TICS), Telephone Montreal Cognitive Assessment (T-MoCA), Telephone Mini Addenbrooke's Cognitive Examination (Tele-MACE)). Regression models and deep neural network (DNN) were used to evaluate the relationship between brain volume, cognition and treatment dose in patients. RESULTS: Cognitive assessments were highly inter-correlated (r > 0.9) and impairment was shown between pre- and post-RT findings. Brain volume atrophy was shown post-RT, and cognitive impairments were correlated with radiotherapy-associated volume atrophy and dose-dependent in the left temporal lobe, corpus callosum, cerebellum and amygdala. DNN showed a good area under the curve for cognitive prediction; TICS (0.952), T-MoCA (0.909) and Tele-MACE (0.822). CONCLUSIONS: Cognition can be evaluated remotely in which radiotherapy-related brain injury is dose-dependent and volume-dependent. Prediction models can assist in the early identification of patients at risk for neurocognitive decline following RT for glioma, thus facilitating potential treatment interventions.

Evaluation of Therapeutic Efficacy and Imaging Capabilities of 153Sm2O3-Loaded Polystyrene Microspheres for Intra-Tumoural Radionuclide Therapy of Liver Cancer Using Sprague-Dawley Rat Model.

Introduction: Neutron-activated samarium-153-oxide-loaded polystyrene ([153Sm]Sm2O3-PS) microspheres has been developed in previous study as a potential theranostic agent for hepatic radioembolization. In this study, the therapeutic efficacy and diagnostic imaging capabilities of the formulation was assessed using liver cancer Sprague-Dawley (SD) rat model. Methods: Twelve male SD rats (150-200 g) that implanted with N1-S1 hepatoma cell line orthotopically were divided into two groups (study versus control) to monitor the tumour growth along 60 days of treatment. The study group received an intra-tumoural injection of approximately 37 MBq of [153Sm]Sm2O3-PS microspheres, while control group received an intra-tumoural injection of 0.1 mL of saline solution. A clinical single photon emission computed tomography/computed tomography (SPECT/CT) system was used to scan the rats at Day 5 post-injection to investigate the diagnostic imaging capabilities of the microspheres. All rats were monitored for change in tumour volume using a portable ultrasound system throughout the study period. Histopathological examination (HPE) was performed after the rats were euthanized at Day 60. Results: At Day 60, no tumour was observed on the ultrasound images of all rats in the study group. In contrast, the tumour volumes in the control group were 24-fold larger compared to baseline. Statistically significant difference was observed in tumour volumes between the study and control groups (p < 0.05). The SPECT/CT images clearly displayed the location of [153Sm]Sm2O3-PS in the liver tumour of all rats at Day 5 post-injection. Additionally, the [153Sm]Sm2O3-PS microspheres was visible on the CT images and this has added to the benefits of 153Sm as a CT contrast agent. The HPE results showed that the [153Sm]Sm2O3-PS microspheres remained concentrated at the injection site with no tumour cells observed in the study group. Conclusions: Neutron-activated [153Sm]Sm2O3-PS microspheres demonstrated excellent therapeutic and diagnostic imaging capabilities for theranostic treatment of liver cancer in a SD rat model. Further studies with different animal and tumour models are planned to validate this finding.

Ultrasonographic Evaluation of Skin Toxicity Following Radiotherapy of Breast Cancer: A Systematic Review.

The present review aimed to systematically review skin toxicity changes following breast cancer radiotherapy (RT) using ultrasound (US). PubMed and Scopus databases were searched according to PRISMA guidelines. The characteristics of the selected studies, measured parameters, US skin findings, and their association with clinical assessments were extracted. Seventeen studies were included with a median sample size of 29 (range 11-166). There were significant US skin changes in the irradiated skin compared to the nonirradiated skin or baseline measurements. The most observed change is skin thickening secondary to radiation-induced oedema, except one study found skin thinning after pure postmastectomy RT. However, eight studies reported skin thickening predated RT attributed to axillary surgery. Four studies used US radiofrequency (RF) signals and found a decrease in the hypodermis's Pearson correlation coefficient (PCC). Three studies reported decreased dermal echogenicity and poor visibility of the dermis-subcutaneous fat boundary (statistically analysed by one report). The present review revealed significant ultrasonographic skin toxicity changes in the irradiated skin most commonly skin thickening. However, further studies with large cohorts, appropriate US protocol, and baseline evaluation are needed. Measuring other US skin parameters and statistically evaluating the degree of the association with clinical assessments are also encouraged.

Assessment of gene expressions from squamous cell carcinoma of the head and neck to predict radiochemotherapy-related xerostomia and dysphagia.

PURPOSE: We tested the hypothesis that gene expressions from biopsies of locally advanced head and neck squamous cell carcinoma (HNSCC) patients can supplement dose-volume parameters to predict dysphagia and xerostomia following primary radiochemotherapy (RCTx). MATERIAL AND METHODS: A panel of 178 genes previously related to radiochemosensitivity of HNSCC was considered for nanoString analysis based on tumour biopsies of 90 patients with locally advanced HNSCC treated by primary RCTx. Dose-volume parameters were extracted from the parotid, submandibular glands, oral cavity, larynx, buccal mucosa, and lips. Normal tissue complication probability (NTCP) models were developed for acute, late, and for the improvement of xerostomia grade ≥2 and dysphagia grade ≥3 using a cross-validation-based least absolute shrinkage and selection operator (LASSO) approach combined with stepwise logistic regression for feature selection. The final signatures were included in a logistic regression model with optimism correction. Performance was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: NTCP models for acute and late xerostomia and the improvement of dysphagia resulted in optimism-corrected AUC values of 0.84, 0.76, and 0.70, respectively. The minimum dose to the contralateral parotid was selected for both acute and late xerostomia and the minimum dose to the larynx was selected for dysphagia improvement. For the xerostomia endpoints, the following gene expressions were selected: RPA2 (cellular response to DNA damage), TCF3 (salivary gland cells development), GBE1 (glycogen storage and regulation), and MAPK3 (regulation of cellular processes). No gene expression features were selected for the prediction of dysphagia. CONCLUSION: This hypothesis-generating study showed the potential of improving NTCP models using gene expression data for HNSCC patients. The presented models require independent validation before potential application in clinical practice.