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.

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.

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.

Diffusion tensor imaging indices as biomarkers for cognitive changes following paediatric radiotherapy: a systematic review and meta-analysis.

Diffusion tensor imaging (DTI) can detect subtle manifestations of white matter (WM) injury following paediatric radiotherapy, which may be a potential biomarker for cognitive changes. This study aimed to synthesise the relationships between DTI indices and cognitive changes following paediatric radiotherapy through systematic review and meta-analysis. PubMed and Scopus electronic databases were used to identify eligible studies. Quality assessment was performed using the National Institute of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Information on demographics, DTI changes, and associations to cognitive outcomes were extracted. Meta-analyses were performed on DTI changes in specific anatomical locations. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in the preparation of this report. Eighteen studies were included (median study size: 21; range 18-146). 17/18 studies showed significant cognitive decline following irradiation. Meta-analyses found significant cognitive changes within patient's group of acute lymphoblastic leukaemia (ALL; standard mean differences [SMD] = -0.075, P = 0.01) and brain tumours (BT; SMD = -1.037, P ≤ 0.001) compared to control/baseline. Both groups also had significantly lower fractional anisotropy (FA) scores in the corpus callosum (ALL: SMD = -0.979, P = 0.002; BT: SMD = -1.025, P < 0.001). Decreased FA was consistently associated with cognitive decline. Correlation on WMFA integrity to cognitive domains was statistically significant (Z = 9.86, P < 0.001) with a large effect size (r = 0.52). White matter tract integrity of the corpus callosum measured with FA has the potential to be a biomarker for radiotherapy-related cognitive decline. Inclusion of DTI in follow-up imaging should be 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.

Neurocognitive impairment following proton therapy for paediatric brain tumour: a systematic review of post-therapy assessments.

BACKGROUND: Proton therapy (PT), frequently utilised to treat paediatric brain tumour (PBT) patients, eliminates exit dose and minimises dose to healthy tissues that theoretically can mitigate treatment-related effects including cognitive deficits. As clinical outcome data are emerging, we aimed to systematically review current evidence of cognitive changes following PT of PBT. MATERIALS AND METHODS: We searched PubMed and Scopus electronic databases to identify eligible reports on cognitive changes following PT of PBT according to PRISMA guidelines. Reports were extracted for information on demographics and cognitive outcomes. Then, they were systematically reviewed based on three themes: (1) comparison with photon therapy, (2) comparison with baseline cognitive measures, to population normative mean or radiotherapy-naïve PBT patients and (3) effects of dose distribution to cognition. RESULTS: Thirteen reports (median size (range): 70 (12-144)) were included. Four reports compared the cognitive outcome between PBT patients treated with proton to photon therapy and nine compared with baseline/normative mean/radiotherapy naïve from which two reported the effects of dose distribution. Reports found significantly poorer cognitive outcome among patients treated with photon therapy compared with proton therapy especially in general cognition and working memory. Craniospinal irradiation (CSI) was consistently associated with poorer cognitive outcome while focal therapy was associated with minor cognitive change/difference. In limited reports available, higher doses to the hippocampus and temporal lobes were implicated to larger cognitive change. CONCLUSION: Available evidence suggests that PT causes less cognitive deficits compared with photon therapy. Children who underwent focal therapy with proton were consistently shown to have low risk of cognitive deficit suggesting the need for future studies to separate them from CSI. Evidence on the effect of dose distribution to cognition in PT is yet to mature.

Diffusion tensor imaging indices to predict cognitive changes following adult radiotherapy.

BACKGROUND: Diffusion tensor imaging (DTI) can detect changes to white matter tracts following assaults including high dose radiation. This study aimed to systematically evaluate DTI indices to predict cognitive changes following adult radiotherapy. MATERIALS AND METHODS: We searched PubMed and Scopus electronic databases to identify eligible studies according to PRISMA guidelines. Studies were extracted for information on demographics, DTI changes and associations to cognitive outcomes. RESULTS: Six studies were selected for inclusion with 110 patients (median study size: 20). 5/6 studies found significant cognitive decline and analysed relationships to DTI changes. Decreased fractional anisotropy (FA) was consistently associated with cognitive decline. Associations clustered at specific regions of cingulum and corpus callosum. Only one study conducted multivariable analysis. CONCLUSION: Fractional anisotropy is a clinically meaningful biomarker for radiotherapy-related cognitive decline. Studies accruing larger patient cohorts are needed to guide therapeutic changes that can abate the decline.

The utilisation of resting-state fMRI as a pre-operative mapping tool in patients with brain tumours in comparison to task-based fMRI and intraoperative mapping: A systematic review.

PURPOSE: Resting-state functional Magnetic Resonance Imaging (rs-fMRI) is suggested to be a viable option for pre-operative mapping for patients with brain tumours. However, it remains an open issue whether the tool is useful in the clinical setting compared to task-based fMRI (T-fMRI) and intraoperative mapping. Thus, a systematic review was conducted to investigate the usefulness of this technique. METHODS: A systematic literature search of rs-fMRI methods applied as a pre-operative mapping tool was conducted using the PubMed/MEDLINE and Cochrane Library electronic databases following PRISMA guidelines. RESULTS: Results demonstrated that 50% (six out of twelve) of the studies comparing rs-fMRI and T-fMRI showed good concordance for both language and sensorimotor networks. In comparison to intraoperative mapping, 86% (six out of seven) studies found a good agreement to rs-fMRI. Finally, 87% (twenty out of twenty-three) studies agreed that rs-fMRI is a suitable and useful pre-operative mapping tool. CONCLUSIONS: rs-fMRI is a promising technique for pre-operative mapping in assessing the functional brain areas. However, the agreement between rs-fMRI with other techniques, including T-fMRI and intraoperative maps, is not yet optimal. Studies to ascertain and improve the sophistication in pre-processing of rs-fMRI imaging data are needed.

Correlation between Hounsfield unit derived from head, thorax, abdomen, spine and pelvis CT and t-scores from DXA.

OBJECTIVES: CT examination can potentially be utilised for early detection of bone density changes with no additional procedure and radiation dose. We hypothesise that the Hounsfield unit (HU) measured from CT images is correlated to the t-scores derived from dual energy X-ray absorptiometry (DXA) in multiple anatomic regions. MATERIALS & METHODS: Data were obtained retrospectively from all patients who underwent both CT examinations - brain (frontal bone), thorax (T7), abdomen (L3), spine (T7 & L3) or pelvis (left hip) - and DXA between 2014 and 2018 in our centre. To ensure comparability, the period between CT and DXA studies must not exceed one year. Correlations between HU values and t-scores were calculated using Pearson's correlation. Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC) was used to determine threshold HU values for predicting osteoporosis. RESULTS: The inclusion criteria were met by 1043 CT examinations (136 head, 537 thorax, 159 lumbar and 151 left hip). The left hip consistently provided the most robust correlations (r = 0.664-0.708, p < 0.001) and the best AUC (0.875-0.893). Meanwhile, thorax T7 and lumbar L3 showed average correlations (range of r values is 0.497-0.679, p < 0.001, AUC range = 0.680-0.783, 95% CI 0.561-0.922, all p < 0.02) and moderate AUC (0.680-0.783). Frontal bone shows low correlation and weak AUC with r < 0.5, AUC = 0.538-0.655, all p > 0.05. CONCLUSION: HU values derived from the hip, T7 and L3 provided a good to moderate correlation to t-scores with a good prediction for osteoporosis. The suggested optimal thresholds may be used in clinical settings after external validations are performed.

Utilization of functional MRI language paradigms for pre-operative mapping: a systematic review.

PURPOSE: Functional MRI (fMRI) can be employed to non-invasively localize brain regions involved in functional areas of language in patients with brain tumour, for applications including pre-operative mapping. The present systematic review was conducted to explore prevalence of different language paradigms utilised in conjunction with fMRI approaches for pre-operative mapping, with the aim of assessing their effectiveness and suitability. METHODS: A systematic literature search of brain tumours in the context of fMRI methods applied to pre-operative mapping for language functional areas was conducted using PubMed/MEDLINE and Scopus electronic database following PRISMA guidelines. The article search was conducted between the earliest record and March 1, 2019. References and citations were checked in Google Scholar database. RESULTS: Twenty-nine independent studies were identified, comprising 1031 adult participants with 976 patients characterised with different types and sizes of brain tumours, and the remaining 55 being healthy controls. These studies evaluated functional language areas in patients with brain tumours prior to surgical interventions using language-based fMRI. Results demonstrated that 86% of the studies used a Word Generation Task (WGT) to evoke functional language areas during pre-operative mapping. Fifty-seven percent of the studies that used language-based paradigms in conjunction with fMRI as a pre-operative mapping tool were in agreement with intra-operative results of language localization. CONCLUSIONS: WGT was most commonly utilised and is proposed as a suitable and useful technique for a language-based paradigm fMRI for pre-operative mapping. However, based on available evidence, WGT alone is not sufficient. We propose a combination and convergence paradigms for a more sensitive and specific map of language function for pre-operative mapping. A standard guideline for clinical applications should be established.

Inclusion of dosimetric data as covariates in toxicity-related radiogenomic studies : A systematic review.

PURPOSE: This systematic review evaluates the completeness of dosimetric features and their inclusion as covariates in genetic-toxicity association studies. MATERIALS AND METHODS: Original research studies associating genetic features and normal tissue complications following radiotherapy were identified from PubMed. The use of dosimetric data was determined by mining the statement of prescription dose, dose fractionation, target volume selection or arrangement and dose distribution. The consideration of the dosimetric data as covariates was based on the statement mentioned in the statistical analysis section. The significance of these covariates was extracted from the results section. Descriptive analyses were performed to determine their completeness and inclusion as covariates. RESULTS: A total of 174 studies were found to satisfy the inclusion criteria. Studies published ≥2010 showed increased use of dose distribution information (p = 0.07). 33% of studies did not include any dose features in the analysis of gene-toxicity associations. Only 29% included dose distribution features as covariates and reported the results. 59% of studies which included dose distribution features found significant associations to toxicity. CONCLUSION: A large proportion of studies on the correlation of genetic markers with radiotherapy-related side effects considered no dosimetric parameters. Significance of dose distribution features was found in more than half of the studies including these features, emphasizing their importance. Completeness of radiation-specific clinical data may have increased in recent years which may improve gene-toxicity association studies.

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.

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.

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.

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.

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.

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.

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.

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.