Evaluation Of Treatment Efficacy Research Articles

Responsiveness of the condition-specific OVAMA questionnaire to measure symptoms and appearance in patients with vascular malformations.

Evidence-based guidelines for the treatment of vascular malformations are not readily available, possibly due to the diversity in methods used to evaluate treatment efficacy in clinical research, complicating the aggregation and comparison of study results. The OVAMA (Outcome Measures for VAscular Malformations) questionnaire was developed to uniformly measure symptoms and appearance, i.e., condition-specific core outcome domains, in patients with vascular malformations. However, the OVAMA questionnaire needs to be responsive to changes in these constructs in order to assess whether the disease status has altered since treatment. To assess the responsiveness of the OVAMA questionnaire in patients with vascular malformations. In a prospective longitudinal study, patients completed the OVAMA questionnaire at baseline and eight weeks follow-up since treatment or watchful waiting policy. Additionally, patients completed the Global rating of change (GRC) scales at follow-up. Responsiveness was evaluated following the criterion approach of testing predefined hypotheses about expected relationships between the OVAMA questionnaire and GRC scales, measuring the same constructs. The OVAMA questionnaire was considered responsive if ≥ 75% of the hypotheses were confirmed. Between July 2020 and September 2022, 89 patients were recruited in a vascular anomaly centre in the Netherlands, of which 63 patients completed the questionnaires at baseline and follow-up. In total, fifteen constructs of the OVAMA questionnaire were assessed for five hypotheses. Of these 75 hypotheses, 63 (84%) hypotheses were confirmed and thereby providing evidence that the OVAMA questionnaire is responsive to change. Our study found convincing evidence that the OVAMA questionnaire is responsive to changes in symptoms and appearance in patients with vascular malformations. In addition to determining a baseline of symptoms and appearance, the OVAMA questionnaire can now be used to evaluate the effect of treatment from the patient's perspective. The responsive OVAMA questionnaire allows for uniform evaluation and comparison of the effects of treatment on the condition-specific core outcome domains, tackling heterogeneity in outcome measurement and improving the clinical research of vascular malformations.

Integrating Imaging and Circulating Tumor DNA Features for Predicting Patient Outcomes.

Biomarkers for evaluating tumor response to therapy and estimating the risk of disease relapse represent tremendous areas of clinical need. To evaluate treatment efficacy, tumor response is routinely assessed using different imaging modalities like positron emission tomography/computed tomography or magnetic resonance imaging. More recently, the development of circulating tumor DNA detection assays has provided a minimally invasive approach to evaluate tumor response and prognosis through a blood test (liquid biopsy). Integrating imaging- and circulating tumor DNA-based biomarkers may lead to improvements in the prediction of patient outcomes. For this mini-review, we searched the scientific literature to find original articles that combined quantitative imaging and circulating tumor DNA biomarkers to build prediction models. Seven studies reported building prognostic models to predict distant recurrence-free, progression-free, or overall survival. Three discussed building models to predict treatment response using tumor volume, pathologic complete response, or objective response as endpoints. The limited number of articles and the modest cohort sizes reported in these studies attest to the infancy of this field of study. Nonetheless, these studies demonstrate the feasibility of developing multivariable response-predictive and prognostic models using regression and machine learning approaches. Larger studies are warranted to facilitate the building of highly accurate response-predictive and prognostic models that are generalizable to other datasets and clinical settings.

Baseline trait mindfulness moderates the efficacy of mindfulness interventions and active controls: A meta‐analysis of 177 randomised controlled trials

AbstractPrevious evidence suggests that benefits of mindfulness‐based interventions (MBIs) may depend on individuals' baseline trait mindfulness (BTM) levels. This meta‐analysis investigated moderating effects of BTM on changes in mental health outcomes and trait mindfulness in randomised controlled trials (RCTs) of MBIs. A total of 177 primary studies (total N = 13,486), comparing the treatment effects of MBIs against active, treatment‐as‐usual (TAU) and waitlist control groups, were synthesised via three‐level meta‐analysis. Lower BTM was associated with larger changes in mental health outcomes (B = −0.14, 95% CI [−0.21, −0.06], p < .001) and trait mindfulness (B = −0.09 [−0.16, −0.02], p = .009) in MBIs and active controls combined. These associations were significantly larger than from those in TAU and waitlist controls. Moderating effects were less tangible for changes in trait mindfulness in MBIs and active controls individually and less tangible in various sensitivity analyses which, however, were confounded by client type across the RCTs. Individuals low in BTM may, by a small effect size, benefit more from MBIs and active control interventions. BTM may thus affect the evaluation of treatment efficacy. MBIs and active interventions could be offered specifically to persons low in BTM.

Application of MR images in radiotherapy planning for brain tumor based on deep learning

Purpose Explore the function and dose calculation accuracy of MRI images in radiotherapy planning through deep learning methods. Methods 131 brain tumor patients undergoing radiotherapy with previous MR and CT images were recruited for this study. A new series of MRI from the aligned MR was firstly registered to CT images strictly using MIM software and then resampled. A deep learning method (U-NET) was used to establish a MRI-to-CT conversion model, for which 105 patient images were used as the training set and 26 patient images were used as the tuning set. Data from additional 8 patients were collected as the test set, and the accuracy of the model was evaluated from a dosimetric standpoint. Results Comparing the synthetic CT images with the original CT images, the difference in dosimetric parameters D98, D95, D2 and Dmean of PTV in 8 patients was less than 0.5%. The gamma passed rates of PTV and whole body volume were: 1%/1 mm: 93.96%±6.75%, 2%/2 mm: 99.87%±0.30%, 3%/3 mm: 100.00%±0.00%; and 1%/1 mm: 99.14%±0.80%, 2%/2 mm: 99.92%±0.08%, 3%/3 mm: 99.99%±0.01%. Conclusion MR images can be used both in delineation and treatment efficacy evaluation and in dose calculation. Using the deep learning way to convert MR image to CT image is a viable method and can be further used in dose calculation.

Deep learning ensembles for detecting brain metastases in longitudinal multi-modal MRI studies

Metastatic brain cancer is a condition characterized by the migration of cancer cells to the brain from extracranial sites. Notably, metastatic brain tumors surpass primary brain tumors in prevalence by a significant factor, they exhibit an aggressive growth potential and have the capacity to spread across diverse cerebral locations simultaneously. Magnetic resonance imaging (MRI) scans of individuals afflicted with metastatic brain tumors unveil a wide spectrum of characteristics. These lesions vary in size and quantity, spanning from tiny nodules to substantial masses captured within MRI. Patients may present with a limited number of lesions or an extensive burden of hundreds of them. Moreover, longitudinal studies may depict surgical resection cavities, as well as areas of necrosis or edema. Thus, the manual analysis of such MRI scans is difficult, user-dependent and cost-inefficient, and—importantly—it lacks reproducibility. We address these challenges and propose a pipeline for detecting and analyzing brain metastases in longitudinal studies, which benefits from an ensemble of various deep learning architectures originally designed for different downstream tasks (detection and segmentation). The experiments, performed over 275 multi-modal MRI scans of 87 patients acquired in 53 sites, coupled with rigorously validated manual annotations, revealed that our pipeline, built upon open-source tools to ensure its reproducibility, offers high-quality detection, and allows for precisely tracking the disease progression. To objectively quantify the generalizability of models, we introduce a new data stratification approach that accommodates the heterogeneity of the dataset and is used to elaborate training-test splits in a data-robust manner, alongside a new set of quality metrics to objectively assess algorithms. Our system provides a fully automatic and quantitative approach that may support physicians in a laborious process of disease progression tracking and evaluation of treatment efficacy.

Acupuncture for cognitive impairment after stroke: A systematic review and meta-analysis

ObjectiveAcupuncture as an alternative therapy for post-stroke cognitive impairment (PSCI) has emerged as a research focus. The inclusion of additional external treatments in many previous studies prevents a clear, direct assessment of acupuncture's impact on PSCI. In order to prevent patients from developing hypersensitivity to other treatments and misinterpreting acupuncture's true therapeutic value, this study establish stricter intervention criteria and exclude therapies beyond acupuncture. The review aimed to offering a clearer evaluation of acupuncture's efficacy and safety in PSCI treatment. MethodsThis research involved a comprehensive search for randomized controlled trials (RCTs) across eight databases, adhering to the Cochrane Systematic Reviewer's Handbook 5.1.0 for risk-of-bias and quality assessments. A meta-analysis was conducted using RevMan 5.3 software. ResultsThe inclusion of 18 publications, totaling 1361 patients, was achieved. The meta-analysis demonstrated a significantly higher overall efficacy of acupuncture for PSCI compared to controls (OR = 4.06, 95 % CI 2.86–5.76, Z = 7.82). Notable statistical differences were observed in the Montreal Cognitive Assessment scores (MD = 2.32, 95 % CI 1.68–2.97, Z = 7.10) and the Mini-Mental State Examination scores (MD = 2.02, 95 % CI 1.06–2.98, Z = 4.13) between the groups. Improvements in the Barthel Index scores were noted for the experimental group (MD = 5.70, 95 % CI 4.68–6.72, Z = 10.92). ConclusionIntegrating acupuncture with Western medications offers significant benefits for treating PSCI over Western medications alone. However, the long-term efficacy of acupuncture in PSCI treatment and its potential in reducing recurrence rates remain undetermined. Further high-standard RCTs are essential to explore acupuncture's effectiveness in PSCI treatment more thoroughly.

Echocardiographic Features in Patient Rheumatic Mitral Stenosis

Rheumatic mitral stenosis (RMS) is a progressive valvular heart disease that can lead to significant morbidity and mortality, especially in developing countries. Echocardiography plays a crucial role in the diagnosis, assessment, and management of patients with RMS. This study aims to review the utility echocardiography feature in patient RMS. We discuss the key echocardiographic parameters used for assessment and severity of RMS, and associated valvular abnormalities. Additionally, we explore the role of multimodality imaging, such as transesophageal echocardiography in enhancing the diagnostic accuracy and therapeutic decision-making in RMS. A thorough understanding of echocardiographic findings in RMS is essential for clinicians involved in the care of these patients, as it aids in risk stratification, treatment planning, and monitoring of disease progression. Integrating echocardiography is a widely used non-invasive method for comprehensive assessment, monitoring disease progression and evaluating treatment efficacy, ensuring optimal management for patient with RMS. Keyword: Echocardiography, Rheumatic Heart Disease, Mitral Stenosis.

Modelling and simulation of anisotropic growth in brain tumours through poroelasticity: A study of ventricular compression and therapeutic protocols

AbstractMalignant brain tumours represent a significant medical challenge due to their aggressive nature and unpredictable locations. The growth of a brain tumour can result in a mass effect, causing compression and displacement of the surrounding healthy brain tissue and possibly leading to severe neurological complications. In this paper, we propose a multiphase mechanical model for brain tumour growth that quantifies deformations and solid stresses caused by the expanding tumour mass and incorporates anisotropic growth influenced by brain fibres. We employ a sharp interface model to simulate localised, non-invasive solid brain tumours, which are those responsible for substantial mechanical impact on the surrounding healthy tissue. By using patient-specific imaging data, we create realistic three-dimensional brain geometries and accurately represent ventricular shapes, to evaluate how the growing mass may compress and deform the cerebral ventricles. Another relevant feature of our model is the ability to simulate therapeutic protocols, facilitating the evaluation of treatment efficacy and guiding the development of personalized therapies for individual patients. Overall, our model allows to make a step towards a deeper analysis of the complex interactions between brain tumours and their environment, with a particular focus on the impact of a growing cancer on healthy tissue, ventricular compression, and therapeutic treatment.

Automated 3D Perioral Landmark Detection Using High-Resolution Network: Artificial Intelligence-Based Anthropometric Analysis.

3D facial stereophotogrammetry, as a convenient, non-invasive and highly reliable evaluation tool, has shown great potential in pre-operative planning and treatment efficacy evaluation of plastic surgery in recent years. However, it requires manual identification of facial landmarks by trained evaluators to obtain anthropometric data, which consumes large amount of time and effort. Automatic 3D facial landmark localization may facilitate fast data acquisition and eliminate evaluator error. In this paper, we propose a novel deep-learning method based on dimension-transformation and key-point detection for automated 3D perioral landmark annotation. The 3D facial model is transformed into 2D images on which High-Resolution Network is implemented for key point detection. The 2D coordinates of key points are then mapped back to the 3D model using mathematical methods to obtain the 3D landmark coordinates. This program was trained with 120 facial models and validated in 50 facial models. Our approach achieved satisfactory accuracy of 1.30 ± 0.68 mm error in landmark detection with an average processing time of 5.2 ± 0.21 seconds per model. And subsequent analysis based on these landmarks showed an error of 0.87 ± 1.02 mm for linear measurements and 5.62 ± 6.61° for angular measurements. This automated 3D perioral landmarking method could serve as an effective tool that enables fast and accurate anthropometric analysis of lip morphology for plastic surgery and aesthetic procedures.

E025 From risk to reward: a case of systemic antineutrophilic cytoplasmic antibody associated vasculitis

Abstract Background/Aims The background and aims of this case involve a 70-year-old female patient with a history of complex medical conditions, including bronchiectasis and dementia, who initially presented with respiratory symptoms and fever. The primary aim was to understand the underlying cause of her deteriorating condition, which did not respond to initial antibiotic treatment for suspected pneumonia. Subsequent diagnostic efforts, including extensive vasculitis workup, were undertaken to identify the source of her symptoms, which led to the discovery of positive PR3 results and elevated inflammatory markers. The key goal was to determine the most effective treatment strategy, considering the patient’s unique medical history, balancing the need for immunosuppressive therapy against the potential risks of exacerbating underlying infections. The case ultimately aimed to demonstrate the successful management of the patient’s complex clinical presentation through a multidisciplinary approach, including immunosuppressive therapy and supportive care, resulting in significant improvements in her neurological and functional status. Methods We conducted a comprehensive assessment of a 70-year-old patient with ANCA-associated vasculitis (AAV) involving the central nervous system (CNS) and cutaneous manifestations. Lab tests targeted PR3-positive ANCA, and imaging assessed disease extent. A multidisciplinary team designed a tailored treatment plan with cyclophosphamide, closely monitoring progress. Ethical considerations were adhered to, and a literature review provided context. Data analysis evaluated treatment efficacy, leading to a discussion of lessons learned in managing complex AAV cases. Results We documented the remarkable trajectory of a 70-year-old patient with ANCA-associated vasculitis (AAV) presenting with central nervous system (CNS) involvement and cutaneous manifestations. With a meticulous and tailored treatment plan involving the judicious use of cyclophosphamide, we witnessed a profound recovery marked by significant improvements in both motor and cognitive function. This case underscores the importance of balancing potent immunosuppression with the imperative to curb disease progression and mitigate treatment-associated repercussions in complex AAV presentations. The patient’s restoration to baseline functioning serves as a compelling testament to the potential of precision medicine in managing intricate clinical scenarios of AAV. Our findings emphasize the need for continued awareness and consideration of individualized treatment approaches in similar cases, offering hope and insights for improved outcomes in challenging AAV presentations. Conclusion This case offers valuable lessons on the complexities and challenges involved in diagnosing and managing a multi-faceted condition like AAV. It emphasizes the urgent need for a timely and accurate diagnosis, especially when presented with atypical cases involving the central nervous system and cutaneous manifestations. Moreover, the case enriches our understanding of AAV and contributes insights into its nuanced management. It calls for a sophisticated, patient-centered approach, informed by cutting-edge research, to optimize patient outcomes in this challenging clinical scenario. Disclosure A.J. AlZeera: None. D. Gurdeep: None.

Comparison of Scheimpflug Corneal Tomography and Anterior Segment Optical Coherence Tomography Measurements in Corneal Cystinosis: A Case Series.

To report the clinical course and compare the utility of Scheimpflug tomography (ST) and anterior segment optical coherence tomography (AS-OCT) for central corneal thickness (CCT) and corneal densitometry (CD) assessment in patients with corneal crystals owing to nephropathic cystinosis. A retrospective chart analysis of three patients with nephropathic cystinosis and the presence of corneal cystine crystals in both eyes was performed. All patients underwent clinical examination and anterior segment photography, ST, and AS-OCT scans. Corneal densitometry was exported from built-in proprietary software for ST and from custom-made validated software for AS-OCT. Anterior segment optical coherence tomography images were rescaled to grayscale units from 0 (maximum transparency) to 100 (minimum transparency) to match built-in ST densitometry readings. Furthermore, the mean pixel intensity, representative of CD, was calculated from the pixels corresponding to the segmented cornea. All three patients had pathognomonic cystine crystals deposits in the cornea and were treated with cysteamine medications that resulted in clinical improvement. The CCT measured using ST exhibited a range from 560 to 958 μm. Conversely, when assessed with AS-OCT, the CCT varied within the range of 548 to 610 μm. Both examinations could be performed, but in the more severe cases, AS-OCT showed far greater utility to estimate CD. In four of six eyes examined, ST showed disproportionate CCT values, compared with the AS-OCT, whereas reliable CD measurements were only available in AS-OCT. The AS-OCT could be considered a baseline ocular measurement in cystinosis and in the evaluation of disease progression and treatment efficacy.

Validation of Biomarkers and Patient-Reported Outcome Measures to Improve the Diagnosis and Treatment of Eustachian Tube Dysfunction

Patients who suffer from Eustachian tube dysfunction (ETD) experience a significant decline in quality of life. To enhance patient outcomes, it is crucial to establish an accurate diagnosis, assess treatment effectiveness, and evaluate the severity of the condition. Substantial progress has recently been made in identifying biomarkers (BMs) and developing ETD clinical outcome assessments (COAs). This study examines the current state of BMs and COAs in ETD, including the methods evaluated historically and their potential clinical applications. The research in this area emphasizes the importance of using objective measures, such as middle ear pressure (MEP) and patient-reported outcome measures (PROMs), for diagnosing and evaluating ETD. Further, I discuss how electronic PROMs (ePROMs) and other digital health technologies can guide the development of innovative PROMs that ETD. Despite significant advances in COAs for ETD, much work remains to validate and improve them before their implementation in clinical practice. There has been less focus on vertigo as a symptom in recent assessments of ETD, suggesting that further examination of this aspect is needed. By validating BMs and COAs for ETD, we could enhance long-term patient outcomes and quality of life through improved diagnostic accuracy and evaluation of treatment efficacy.

Evaluating treatment efficacy in hospitalized COVID-19 patients, with applications to Adaptive COVID-19 Treatment Trials.

The current endpoints for therapeutic trials of hospitalized COVID-19 patients capture only part of the clinical course of a patient and have limited statistical power and robustness. We specify proportional odds models for repeated measures of clinical status, with a common odds ratio of lower severity over time. We also specify the proportional hazards model for time to each level of improvement or deterioration of clinical status, with a common hazard ratio for overall treatment benefit. We apply these methods to Adaptive COVID-19 Treatment Trials. For remdesivir versus placebo, the common odds ratio was 1.48 (95% confidence interval (CI) = 1.23-1.79; p < 0.001), and the common hazard ratio was 1.27 (95% CI = 1.09-1.47; p = 0.002). For baricitinib plus remdesivir versus remdesivir alone, the common odds ratio was 1.32 (95% CI = 1.10-1.57; p = 0.002), and the common hazard ratio was 1.30 (95% CI = 1.13-1.49; p < 0.001). For interferon beta-1a plus remdesivir versus remdesivir alone, the common odds ratio was 0.95 (95% CI = 0.79-1.14; p = 0.56), and the common hazard ratio was 0.98 (95% CI = 0.85-1.12; p = 0.74). The proposed methods comprehensively characterize the treatment effects on the entire clinical course of a hospitalized COVID-19 patient.

Dual‐Sensing Nanoreporter for Dynamic and High‐Throughput Monitoring of Immune Checkpoint Inhibitor Responses in Tumor‐Derived Organoids

AbstractHeterogenous immune responses to checkpoint blockade therapy remain a major challenge to early prediction of treatment efficacy. Current methods of evaluating treatment efficacy in tumors are ineffective in accurately monitoring the disease status after immunotherapy early on. This study reports an immune response monitoring strategy that longitudinally reports on two crucial protease activities involved in T cell‐mediated target cell death, granzyme B (GrzB) and downstream caspase 3 (Casp3), during and after immune checkpoint antibody treatment. Specifically, activatable nanoreporters are engineered to sensitively and selectively capture the activity of GrzB and Casp3 enzymes in tumor cells triggered by cytotoxic T cells in real‐time, providing a direct readout of the tumor response to immune checkpoint inhibitors (ICIs). Furthermore, incorporating 3D tumor‐derived organoids and ex vivo cultures on microfluidic devices with nanoreporters enables high‐throughput screening of various ICIs and their combinations in immunocompetent tumor models. These findings suggest that efficient monitoring of dynamic immunological processes in the tumor microenvironment could help uncover mechanisms associated with ICI response or resistance. It is further anticipated that combining the dual‐sensing nanoreporter with tumor‐derived organoid‐on‐chip technology could lead to an early prediction of treatment outcomes with high fidelity and accelerate the development of optimal treatment in immuno‐oncology.

Results of Definitive (Chemo)radiotherapy Using Computed Tomography-based Brachytherapy for Cervical Cancer.

Concurrent cisplatin-based chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer. Especially, CCRT with magnetic resonance imaging (MRI) or computed tomography-based image-guided brachytherapy (CT-based 3D-IGBT) for cervical cancer has resulted in good LC rates. However, progression-free survival (PFS) and overall survival (OS) rates for locally advanced cervical cancer are still low and could be improved. The aim of the study was to evaluate treatment efficacy and late toxicity of external beam radiotherapy (EBRT) and CT-based IGBT with or without concurrent chemotherapy in patients with squamous cell carcinoma of the uterine cervix and investigate patterns of failure. We retrospectively analyzed clinical data of cervical squamous cell carcinoma patients treated with definitive radiotherapy with or without concurrent chemotherapy at Saitama Medical University International Medical Center. Local control (LC), PFS, patterns of failure, and late toxicity were the evaluated outcomes. Overall, 290 patients were enrolled in the study. Median follow-up was 51.5 months. During follow-up, 74 patients developed recurrence: 10 patients with intra-pelvic failure only, 45 with extra-pelvic failure only, and 19 with both. The 3-year LC was 100% for T1b-T2a, 96.8% for T2b, 89.5% for T3b, and 88.5% for T4 disease. The 3-year PFS was 100% for stage IB-IIA, 89.0% for stage IIB, 70.7% for stage IIIB, 72.6% for stage IIIC1r, and 40.1% for stage IVA. The incidence of grade 3-4 gastrointestinal and genitourinary toxicities was 3.0% and 1.7%, respectively. Combination of EBRT and CT-based IGBT with or without concurrent chemotherapy produced favorable LC with acceptable rates of late toxicities. However, extra-pelvic failures frequently occurred and PFS was less satisfactory in patients with stage III-IVA disease, which indicated the need for additional treatment in these patients.

Oxidative modification products of lipids in the intraocular fluid of patients with cataracts associated with chronic non-infectious diseases

Introduction. To clarify the role of oxidative stress in the development of cataracts, it is necessary to determine the content of oxidative modification products directly in the eye tissue, but such studies are scarce, which is due to the difficulty of obtaining a sufficient amount of biomaterial for analysis and the need to use highly sensitive research methods as a result. Therefore, to assess the pathological changes in the lens, intraocular or tear fluid is used.Aim. To elucidate the role of oxidative stress in the development of cataracts by determining the content of lipid oxidation products and their comparative characteristics in intraocular fluid and in blood plasma in patients with cataracts associated with chronic non-infectious diseases.Materials and methods. The study involved 83 patients with cataracts associated with non-infectious diseases, who underwent surgical treatment. Of these, 30 patients had chronic obstructive pulmonary disease (COPD) as a comorbid condition, 45 had cardiovascular diseases (CVD), and 13 had diabetes mellitus (DM). The control group consisted of 30 practically healthy individuals without clinical signs of acute or chronic diseases. Lipid oxidation products were determined by ultraviolet spectroscopy. Absorption spectra of non-oxidized lipids (E204), diene conjugates (E233), conjugated trienes, and ketodiene (E278) were recorded. Additionally, the ratios of absorption spectra of diene conjugates to non-oxidized lipids (E233/E204), as well as conjugated dienes and ketodienes to non-oxidized lipids (E278/E204), were calculated. Tear and intraocular fluids, as well as blood plasma, served as materials for the study.Results. In the group of patients with cataracts associated with non-infectious diseases, the content of diene conjugates, conjugated trienes, and ketodienes was increased relative to similar indicators in the tear fluid of people in the control group. Moreover, more pronounced changes were observed in the group of patients with cataracts associated with COPD relative to those with CVD and DM. A comparative analysis confirmed that in the group of patients with cataracts associated with COPD, the content of oxidized lipids in intraocular fluid and in blood plasma was increased. Correlation-regression analysis showed a positive relationship between the indicators of diene conjugates in intraocular fluid and in blood plasma.Conclusions. The significant direct linear relationship between the indicators of oxidized lipids in intraocular fluid and in blood plasma in patients with cataracts and non-infectious diseases may indicate the possibility of using blood plasma for studying oxidative processes in the lens and its pathological changes for the purpose of selecting therapy and evaluating treatment efficacy. The results obtained confirm the role of oxidative stress in the development of cataracts in patients with chronic non-infectious diseases.

Abstract 3658: Longitudinal tumor-informed ctDNA monitoring with the originally developed OTS-Assay system

Abstract Background: Cancer Genome Profiling (CGP) tests are now widely available in daily practice. However, only a very small fraction of patients have the opportunity for genome-guided therapies. Somatic mutations from cancer specimens are unique to individual patients and hold utility as individual tumor markers in blood. We have developed an original circulating tumor DNA (ctDNA) monitoring system, called OTS (Off-The-Shelf)-Assay, at Iwate Medical University Hospital, Yahaba, Japan. Patients and Methods: Between April 2022 and October 2023, 79 patients who received the OTS-Assay were enrolled in the present analysis. The OTS-Assay includes three steps: (a) OTS-Scan (somatic mutation identification by either tissue or blood), (b) OTS-Select (somatic mutation selection), and (c) OTS-Monitor (periodical somatic mutation quantification as ctDNA). For the OTS-Select, we established an originally developed &amp;gt;90 stepwise selection algorithm. One of the determinants is the availability of appropriate digital PCR (dPCR) probes for individual patients. Here, we search the probes for individual patients from the dPCR probe library, OTS-1000ex, which consists of &amp;gt;1000 probes against frequently reported human somatic mutations (Quantdetect, Tokyo, Japan). Results: All 79 patients were subject to the analysis. The cancer stage of all the patients was advanced. More than 10 tumor types were enrolled, including esophagus (n=42), colorectal (n=12), breast (n=7), lung (n=4), pancreas (n=3), hematological (n=3), and others (n=8). Fifty patients received OTS-Scan, and 29 patients had received a CGP test before the OTS-Assay (i.e., OTS-Scan was not needed). Seventy-five patients received OTS-Select, meaning that four patients had somatic mutations that were designated for ctDNA monitoring. All 79 patients received at least one OTS-monitor. The number of OTS-Monitors received ranged from 1 to 11 during the 19-month period, and the average interval was 3.0 months. The average pretreatment variant allele frequency (VAF) was 4.96% and the majority of the follow-up VAF was less than 1%. More than 90% of the patients had at least one clinical validity defined by: (a) early relapse prediction, (b) treatment efficacy evaluation, or (c) no relapse corroboration. Conclusion: The OTS-Assay system provides stable longitudinal ctDNA monitoring at the range of less than 1% of VAF using the originally developed dPCR probe library. The sensitivity and affordability of the OTS-Assay system allows frequent monitoring, which leads to obtaining important clinical information in the context of advanced cancer therapy. Citation Format: Satoshi S. Nishizuka, Hayato Hiraki, Akiko Yashima-Abo, Takeshi Iwaya. Longitudinal tumor-informed ctDNA monitoring with the originally developed OTS-Assay system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3658.

Abstract 5027: Simplified selective electrochemical detection of ctDNA differentiates between cancer progression and regression

Abstract Advanced cancers therapies, including personalized ones, often fail. Rapid evaluation of treatment efficacy is therefore critical to reduce medical and financial side effects and, most importantly, facilitate the implementation of a therapy most appropriate for that individual. Current approaches for evaluating treatment are too slow and expensive to rapidly modify therapy. The previously documented selective affinity of DNA to Au surfaces, albeit cumbersome, unsuitable for point-of-care (PoC) applications and having poor discrimination ability, suggested a solution to this clinically important problem. Methods presented herein potentially solve the problem as first illustrated by a studies of plasma from those with and without cancers. Multiple improvements, most notably optimized buffer conditions dramatically changed and enhanced the difference in adsorption between ctDNA and normal cfDNA drastically improving assay performance. The enhanced sensitivity of this Therascape™ assay was not only able to better detect the difference between healthy and cancer cfDNA but demonstrated potential for the monitoring of cancer treatment efficacy. De-identified clinical samples of the few patients that the Scripps Biorepository and University of Colorado supplied had samples before and after treatment, and were known to have progressed or responded in the interim, were analyzed. This initial group included 6 lymphoma patients and two NSCLC patients (in one case the cfDNA was isolated from urine). One of the patient samples taken before initiating therapy was in the healthy range and considered ineligible for the assay. Ten before and after pairs were then evaluated in a blinded fashion. TheraScape correctly correlated with the change in cancer burden in each pair (10/10 times, p = 0.00016, paired t-test). In some cases the “after” specimen was ~1 month after therapy began. The presentation will include additional patients. The CVs of repeat electrodes were less than 10%, interoperator variability did not increase this. The novel method of detecting cfDNA using disposable electrodes presents a significant advancement in monitoring the efficacy of treatments for advanced cancers, and may be particularly critical for immunotherapy. This approach reduced expenses by 10 to 50 times compared to current reimbursement rates for sequence dependent methods, even more critical is the same day turn around would allow rapid, truly individualized, patient therapy optimization. Citation Format: Matthew Jordan Russo, Kirsten Arnold, Shannon Tunney, Suzin Wright, Floyd Taub, Charles S. Henry. Simplified selective electrochemical detection of ctDNA differentiates between cancer progression and regression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5027.

MR-guided percutaneous microwave coagulation of small breast tumors

BackgroundTo evaluate the technical success and patient safety of magnetic resonance-guided percutaneous microwave coagulation (MR-guided PMC) for breast malignancies.MethodsFrom May 2018 to December 2019, 26 patients with breast tumors measuring 2 cm or less were recruited to participate in a prospective, single-institution clinical study. The primary endpoint of this study was the evaluation of treatment efficacy for each patient. Histochemical staining with α-nicotinamide adenine dinucleotide and reduced (NADH)-diaphorase was used to determine cell viability following and efficacy of PMC. The complications and self-reported sensations from all patients during and after ablation were also assessed. The technical success of the PMC procedure was defined when the area of the NADH-diaphorase negative region fully covered the hematoxylin–eosin (H&E) staining region in the tumor.ResultsAll patients had a complete response to ablation with no residual carcinoma on histopathological specimen. The mean energy, ablation duration, and procedure duration per tumor were 36.0 ± 4.2 kJ, 252.9 ± 30.9 S, and 104.2 ± 13.5 min, respectively. During the ablation, 14 patients underwent prolonged ablation time, and 1 patient required adjusting of the antenna position. Eleven patients had feelings of subtle heat or swelling, and 3 patients experienced slight pain. After ablation, one patient took two painkillers because of moderate pain, and no patients had postoperative oozing or other complications after PMC. Induration around the ablation area appeared in 16 patients.ConclusionMR-guided PMC of small breast tumors is feasible and could be applied in clinical practice in the future.Critical relevance statementMR-guided PMC of small breast tumors is feasible and could be applied in clinical practice in the future.Key points• MR-guided PMC of small breast tumors is feasible.• PMC was successfully performed for all patients.• All patients were satisfied with the final cosmetic result.Graphical

Metabolomic Alterations in Methotrexate Treatment of Moderate-to-Severe Psoriasis.

BACKGROUND Aberrant lipid metabolism alterations in skin tissue, blood, or urine have been implicated in psoriasis. Here, we examined lipid metabolites related to psoriasis and their association with the age of disease onset. MATERIAL AND METHODS Differences in lipid metabolites before and after methotrexate (MTX) treatment were evaluated. The discovery cohort and validation cohort consisted of 50 and 46 patients, respectively, with moderate-to-severe psoriasis. After MTX treatment, the patients were divided into response (Psoriasis Area and Severity Index [PASI] 75 and above) and non-response (PASI below 75) groups, blood was collected for serum metabolomics, and multivariate statistical analysis was performed. RESULTS We detected 1546 lipid metabolites. The proportion of the top 3 metabolites was as follows: triglycerides (TG, 34.8%), phospholipids (PE, 14.5%), phosphatidylcholine (PC, 12.4%); diglycerides (DG) (16: 1/18: 1), and DG (18: 1/18: 1) showed strong positive correlations with onset age. There were marked changes in TG (16: 0/18: 0/20: 0), TG (18: 0/18: 0/22: 0), TG (14: 0/18: 0/22: 0), TG (14: 0/20: 0/20: 0), lysophosphatidylcholine (LPC) (16: 0/0: 0), LPC (18: 0/0: 0), LPC (14: 0/0: 0), and LPC (18: 1/0: 0) levels before and after 12 weeks of MTX treatment. The glycerophospholipid metabolic pathway was implicated in psoriasis development. Of the 96 recruited patients, 35% were MTX responders and 65% non-responders. PE (34: 4) and PE (38: 1) levels were significantly different between the groups. Obvious differences in lipid metabolism were found between early-onset (<40 years) and late-onset (≥40 years) psoriasis. Significant changes in serum lipid profile before and after MTX treatment were observed. CONCLUSIONS The specific lipid level changes in responders may serve as an index for MTX treatment efficacy evaluation.