Guide Treatment Decisions Research Articles

Computational fluid dynamics and shape analysis enhance aneurysm rupture risk stratification.

Accurately quantifying the rupture risk of unruptured intracranial aneurysms (UIAs) is crucial for guiding treatment decisions and remains an unmet clinical challenge. Computational Flow Dynamics and morphological measurements have been shown to differ between ruptured and unruptured aneurysms. It is not clear if these provide any additional information above routinely available clinical observations or not. Therefore, this study investigates whether incorporating image-derived features into the established PHASES score can improve the classification of aneurysm rupture status. A cross-sectional dataset of 170 patients (78 with ruptured aneurysm) was used. Computational fluid dynamics (CFD) and shape analysis were performed on patients' images to extract additional features. These derived features were combined with PHASES variables to develop five ridge constrained logistic regression models for classifying the aneurysm rupture status. Correlation analysis and principal component analysis were employed for image-derived feature reduction. The dataset was split into training and validation subsets, and a ten-fold cross validation strategy with grid search optimisation and bootstrap resampling was adopted for determining the models' coefficients. Models' performances were evaluated using the area under the receiver operating characteristic curve (AUC). The logistic regression model based solely on PHASES achieved AUC of 0.63. All models incorporating derived features from CFD and shape analysis demonstrated improved performance, reaching an AUC of 0.71. Non-sphericity index (shape variable) and maximum oscillatory shear index (CFD variable) were the strongest predictors of a ruptured status. This study demonstrates the benefits of integrating image-based fluid dynamics and shape analysis with clinical data for improving the classification accuracy of aneurysm rupture status. Further evaluation using longitudinal data is needed to assess the potential for clinical integration.

Abstract B010: Improving pancreatic cancer image classification with transfer learning: CD45 vs. PANCK

Abstract Pancreatic ductal adenocarcinoma (PDAC) is known for its high aggressiveness and is the fourth most common cause of death of cancer-related death in the United States. It is highly malignant and often goes undiagnosed until advanced stages due to its late-onset symptoms, resulting in poor prognosis. Using quantitative analyses of histological features, such as the expression of prognostic biomarker, can provide valuable insight to guide treatment decisions, monitor disease progression and predict outcomes. Previous researchers have found that CD45 and PANCK play a huge role in characterizing the tumor microenvironment of PDAC. One study using single-cell RNA sequencing compared the microenvironments of healthy pancreata and pancreatic tumors, revealing differences in cellular composition. Tumor samples showed a higher proportion of immune cells, including CD45+ cells, compared to heathy samples and utilized PANCK to differentiate between epithelial and non-epithelial cells. This study aims to enhance the accuracy of classifying pancreatic cancer pathological images based on prognostic markers using transfer learning techniques. We curated and pre-processed a dataset of pancreatic cancer pathological images with different prognostic markers. Using the pre-trained convolutional neural network (CNN) model VGG16, we fine-tuned it with our dataset to better differentiate between two prognostic markers, CD45 and PANCK. The model's performance was evaluated using a similarity matrix to illustrate distinctions among the two prognostic markers. Our results demonstrate that the transfer learning approach significantly improves classification accuracy, achieving confusion matrix validation results of 90% between CD45 and PANCK prognostic markers. SSIM values were relatively low, highlighting the ability of our model to differentiate between the two prognostic markers. The low SSIM value also shows variability within the two prognostic markers, indicating heterogeneity in structural changes due to pancreatic cancer. These findings indicate that transfer learning can be a powerful tool for improving the classification of pathological images and that there is notable variability in the structural features associated with different prognostic markers in pancreatic cancer. Citation Format: Miracle Thomas. Improving pancreatic cancer image classification with transfer learning: CD45 vs. PANCK [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B010.

The histological grading of fibrosis in Budd-Chiari syndrome: A chronic liver disease, different from others.

Budd-Chiari syndrome (BCS) is an uncommon disease caused by hepatic venous outflow obstruction. They can result in centrilobular fibrosis, nodular regenerative hyperplasia and cirrhosis. Assessing liver fibrosis is crucial for determining the stage of BCS, predicting disease progression and guiding treatment decisions. Although this pathology has been known for decades, no useful grading system was assigned. This study aims to introduce a histologic fibrosis grading system for BCS patients. All patients from 2017 to 2022 (Sanjay Gandhi Postgraduate Institute of Medical Sciences [SGPGIMS]), Lucknow diagnosed with BCS for whom liver biopsy was performed were included in the study. The Budd-Chiari syndrome-Hepatic Fibrosis system (BCS-HFS) was implemented to grade fibrosis. The fibrosis grade was compared with the fibrosis percentage area and a correlation was found with the hemodynamic variables (hepatic venous pressure gradient[HVPG])and the prognostic scores. There were 56 patients with BCS. The median age was 27years, with a male-female ratio of 1.8:1. There was a significant difference in the fibrosis percentage, hemorrhage percentage and model for end-stage liver disease (MELD) score among the BCS-HFS grades (p < 0.05). There was a significant correlation between BCS-HFS and HVPG (ρ = 0.699, p < 0.001) and the MELD prognostic score (ρ = 0.474, p < 0.001). BCS-HFS is applicable for grading fibrosis in BCS. It can help in uniform histopathology reporting and for further prospective and comparative studies.

Guidance for Canadian Breast Cancer Practice: National Consensus Recommendations for Clinical Staging of Patients Newly Diagnosed with Breast Cancer

The accurate staging of breast cancer is fundamental for guiding treatment decisions and predicting patient outcomes. However, there can be considerable variation in routine clinical practice based on individual interpretation of guidelines and depending on the healthcare provider initially involved in working up patients newly diagnosed with breast cancer, ranging from primary care providers, triage nurses, surgeons, and/or oncologists. The optimal approach for clinical staging, particularly in asymptomatic patients presenting with intermediate-risk disease, remains a topic of dialogue among clinicians. Given this area of uncertainty, the Research Excellence, Active Leadership (REAL) Canadian Breast Cancer Alliance conducted a modified Delphi process to assess the level of agreement among Canadian expert clinicians on various staging recommendations. In total, 20 items were drafted covering staging based on biological status, the utilization of localization clips, both for the axilla during diagnosis and primary surgical site for margins and radiation therapy planning, and the use of advanced imaging for the investigation of distant metastases. Overall, the consensus threshold among all participants (i.e., ≥75% agreement) was reached in 20/20 items. Differences in clinical practice and recent findings from the literature are provided in the discussion. These consensus recommendations are meant to help standardize breast cancer staging practices in Canada, ensuring accurate diagnosis and optimal treatment planning.

Unipolar Voltage Mapping to Predict Recovery of Left Ventricular Ejection Fraction in Patients With Recent-Onset Nonischemic Cardiomyopathy.

The ability to predict recovery of left ventricular ejection fraction (LVEF) in response to guideline-directed therapy among patients with nonischemic cardiomyopathy is desired. We sought to determine whether left ventricular endocardial unipolar voltage measured during invasive electroanatomic mapping could be used to predict LVEF recovery among those with recent-onset nonischemic cardiomyopathy. We analyzed the left ventricular voltage maps of patients included in the eMAP trial (Electrogram-Guided Myocardial Advanced Phenotyping; NCT03293381), a prospective, nonrandomized, interventional trial conducted at 2 institutions between 2017 and 2020. Patients had recent-onset nonischemic cardiomyopathy defined by LVEF ≤45% and development of symptoms or signs of heart failure within the past 6 months. Detailed voltage maps of the left ventricular endocardium were generated using the CARTO electroanatomic mapping system. Abnormal unipolar amplitude was defined as <8.27 mV. The primary end point was recovery of LVEF (Recovery) defined by a 1-year LVEF ≥50% or ≥45% with ≥10% increase from baseline. Of the 29 enrolled patients (median age, 49 years [25th percentile, 39; 75th percentile, 59], 8 females [27.6%]), LVEF recovered in 13 (44.8%) by 1-year follow-up. The percentage of total endocardial surface area with unipolar voltage abnormality (AUA) was significantly lower among Recovery patients than No Recovery patients (18.2% [6.4, 22.4] versus 80.0% [29.5, 90.9]; P=0.004). Percent AUA was associated with lower likelihood of Recovery (odds ratio, 0.64 per 10% increase in AUA; 95% CI, 0.47-0.88; P=0.006). A 28% cutoff value for percent AUA was 92% sensitive and 75% specific with an area under the receiver operating characteristic curve of 0.81 (95% CI, 0.63-0.99; P=0.001) for predicting recovery versus no recovery. The majority of patients (12 of 13; 92.3%) with a percent AUA >28% did not recover. Left ventricular unipolar voltage abnormality is a potent predictor of LVEF recovery among patients recently diagnosed with nonischemic cardiomyopathy. Detailed left ventricular unipolar voltage mapping could therefore be used as a valuable prognostic tool in guiding treatment decisions.

A predictive and prognostic model for metastasis risk and prognostic factors in gastrointestinal signet ring cell carcinoma.

This study aimed to predict metastasis risk and identify prognostic factors of gastrointestinal signet ring cell carcinoma (SRCC) using data from the SEER database, the largest cancer dataset in North America. Data were obtained from the SEER database, covering 17 cancer registries from 2004 to 2020. Demographic and clinical data included sex, age, race, tumor location, size, pathological grade, stage, overall survival time, and treatment modalities. Statistical analyses were conducted using SPSS and R software. Propensity Score Matching (PSM) ensured comparable baseline characteristics between gastric cancer (GC) and colorectal cancer (CRC) groups. LASSO regression analysis identified predictors of metastasis, leading to the construction of predictive models using the lrm function in R. Nomograms were visualized with the "rms" package and assessed via ROC curves, calibration curves, and decision curve analysis (DCA). Cox regression analyses identified prognostic indicators for overall survival (OS), and Kaplan-Meier curves compared OS between high-risk and low-risk groups. From 2004 to 2020, 7680 SRCC patients were identified, including 4980 GC and 2700 CRC patients. CRC patients were older and had larger tumors, higher staging, and worse differentiation. Nomograms demonstrated good discriminative ability, with AUCs of 0.704 and 0.694 for GC, and 0.694 and 0.701 for CRC in training and validation cohorts, respectively. The DCA curve indicates that this predictive model has a high gain in predicting metastasis and OS. The nomograms effectively predicted metastasis risk and OS in metastatic SRCC patients, offering clinical utility in stratifying patients and guiding treatment decisions, thereby enhancing personalized treatment approaches.

Evaluation of the GATIS score for predicting prognosis in rectal neuroendocrine neoplasms

The GATIS score, developed by Zeng et al , represents a significant advancement in predicting the prognosis of patients with rectal neuroendocrine neoplasms (R-NENs). This study, which included 1408 patients from 17 major medical centres in China over 12 years, introduces a novel prognostic model based on the tumour grade, T stage, tumour size, age, and the prognostic nutritional index. Compared with traditional methods such as the World Health Organization classification and TNM staging systems, the GATIS score has superior predictive power for overall survival and progression-free survival. With a C-index of 0.915 in the training set and 0.812 in the external validation set, the GATIS score’s robustness and reliability are evident. The study’s use of a large, multi-centre cohort and rigorous validation processes underscore its significance. The GATIS score offers clinicians a powerful tool to accurately predict patient outcomes, guide treatment decisions, and improve follow-up strategies. This development represents a crucial step forwards in the management of R-NENs, addressing the complexity and variability of these tumours and setting a new benchmark for future research and clinical practice.

Abstract B010: Prognostic value of circulating tumor cells in stage III and IV melanoma: A systematic review and meta-analysis

Abstract Introduction: Previous studies have demonstrated a role for assessing circulating tumor cells (CTC) in melanoma, but significant heterogeneity among studies has limited application in the clinical setting. We sought to evaluate the prognostic value of CTCs in advanced stage melanoma using a standardized CTC enumeration platform. Methods: A PubMed literature search was conducted up to March 2024. All studies evaluating CTC enumeration using CellSearchTM with outcomes data were included. Student's t-test was used to compare differences between groups. Hazard ratios (HR) were pooled using random effects model to assess the association of CTCs with overall survival (OS). I 2 statistic and Cochran’s Q test, sensitivity analyses, and Egger’s test of asymmetry were used to assess study heterogeneity, differential impact of individual studies, and publication bias, respectively. Results: Of the 12 studies identified, nine met inclusion criteria. A total of 678 patients were included, of which 337 (49.6%) were stage III and 342 (50.4%) were stage IV. The majority of studies reported CTC rates using a cut-off of ≥ 1 (6 studies, 66.7%), while three studies used ≥ 2 and five studies used both. Median follow-up time was available for six studies and ranged from 5.9-48 months (median 13.4). Average CTC detection rate (≥ 1 or 2) was 41% (SD 14.0) and was significantly higher using a cut-off of ≥ 1 (45.4%, SD 12.6) compared to ≥ 2 (26.1%, SD 2.7, p = 0.02). Pooled analysis of two studies demonstrated significantly worse OS with CTC ≥ 1 (HR 1.6, 95% CI: 1.0-2.6, p = 0.04). Similarly, pooled analysis of five studies with available HRs demonstrated significantly worse OS with CTC ≥ 2 (HR 2.1, 95% CI: 1.4-3.1, p = 0.0003). Among these five studies, moderate heterogeneity was observed (I2 = 43.4%), although this was not statistically significant (Q statistic p = 0.13). Sensitivity analyses confirmed the prognostic value of CTC ≥ 2, with pooled HRs ranging from 1.9-2.4 after consecutive omission of each study from the overall analysis. Conclusion: Regardless of the CTC cutoff used (≥ 1 or 2), presence of any CTCs was a strong prognostic marker in patients with advanced stage melanoma. Incorporation of CTC assessments in clinical practice may help risk stratify patients and guide treatment decisions. Further studies are needed to determine the optimal cut-off point for CTC status in assessing prognosis. Citation Format: Jennifer H. Chen, Hyunsoo Hwang, Bamboo Dong, Vanessa N. Sarli, Joshua R. Upshaw, Salyna Meas, Anthony Lucci. Prognostic value of circulating tumor cells in stage III and IV melanoma: A systematic review and meta-analysis [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B010.

Abstract B049: Validation of the PGDx elio™ plasma complete for comprehensive genomic profiling of solid tumors through liquid biopsy with Epic Sciences

Abstract Introduction: To help guide treatment decisions and enable clinical trial matching for cancer patients, tissue-based comprehensive genomic profiling (CGP) is an essential precision oncology tool. Liquid biopsy may be used as a complementary approach to assess tumor-specific DNA alterations circulating in the blood when tissue is limited or unavailable. PGDx’s elio™ plasma complete is a next-generation-sequencing (NGS), cell-free DNA (cfDNA) CGP assay that identifies clinically significant variants from the plasma of patients with advanced and metastatic solid cancers. Methods: The PGDx elio plasma complete is a hybrid-capture, DNA-based kitted solution, optimized for 25 ng of cfDNA input with a targeted panel covering coding exons for 521 genes, and is designed to detect single nucleotide variants (SNVs), small insertions and deletions (indels), copy number amplifications (CNAs), and translocations. It also evaluates blood MSI and tumor mutational burden (bTMB) to guide immunotherapy selection. This study presents the validation of the PGDx elio plasma complete assay to enable the processing of patient blood samples in Epic Sciences' CAP/CLIA-certified laboratory. In the validated configuration, patient plasma will be received and isolated at Epic Sciences and subsequently shipped to PGDx/Labcorp Oncology for cfDNA extraction, library preparation, sequencing, and bioinformatics analysis. Finally, clinical report generation will be carried out by Velsera’s CGW software. Analytical validation was assessed using 105 replicates of SeraCare® (n=21) and Horizon (n=3) reference materials to establish analytical sensitivity, accuracy, and reproducibility and repeatability. Specificity was assessed using 20 non-cancerous plasma samples that were also tested orthogonally. For clinical validation a cohort of &amp;gt;150 cancer patient plasma samples were evaluated, including lung, breast, colorectal, head and neck, pancreatic, and prostate cancers, and compared to Illumina’s TSO500 ctDNA or Labcorp Plasma Focus results. Results: Analytical sensitivity and specificity were evaluated for SNVs, indels, CNAs, fusions, MSI and bTMB. Across all variant types, sensitivity was ≥90%, and specificity was ≥95% at LoDs. The reproducibility and repeatability study resulted in ≥95% agreement for all variant types. Analytical sensitivity was calculated using vendor-verified variants in each control. SeraCare® controls and Horizon reference materials were used to assess variant concordance with an aggregate analytical performance across all control samples with ≥95% PPA and NPA for all variant types. Conclusions: The validation of the PGDx elio plasma complete liquid biopsy assay as part of the Epic Sciences' CAP/CLIA diagnostic workflow for cfDNA-based NGS demonstrates that the liquid biopsy approach is highly sensitive, specific, accurate, reproducible, and robust for comprehensive genomic profiling to complement tissue- based testing and inform clinical decision making. Citation Format: Cynthia Maddox, Kenneth C Valkenburg, Cesar Nalvarte, Amanda Harvey, Amy Greer, Ellen L Verner, Renee L Sears, Martin Blankford, Eric A Severson, Taylor J Jensen, Marcia Eisenberg, Shakti Ramkissoon. Validation of the PGDx elio™ plasma complete for comprehensive genomic profiling of solid tumors through liquid biopsy with Epic Sciences [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B049.

Non-invasive testing in metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously referred to as non-alcoholic fatty liver disease (NAFLD), is a leading cause of chronic liver disease, affecting up to 30% of the global population. MASLD is strongly associated with metabolic risk factors such as obesity and type 2 diabetes, and can progress to advanced stages including cirrhosis and hepatocellular carcinoma. Early diagnosis and accurate staging of fibrosis are critical in managing the disease and preventing complications. While liver biopsy has long been considered the gold standard for assessing fibrosis, it is invasive and carries associated risks. In response, non-invasive tests (NITs) have emerged as essential alternatives for the diagnosis and monitoring of MASLD. Key methods include blood-based biomarkers such as the Fibrosis-4 (FIB-4) score, NAFLD Fibrosis Score (NFS), and Enhanced Liver Fibrosis (ELF) test, as well as imaging modalities like vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE). These tests provide safer, more accessible methods for identifying liver fibrosis and guiding clinical management. They are integral in assessing disease severity, guiding treatment decisions, and monitoring disease progression, particularly in light of emerging therapies. NITs have become increasingly recommended by clinical guidelines as they reduce the need for invasive procedures like liver biopsy, improving patient care and outcomes. In conclusion, non-invasive testing plays a crucial role in the effective management of MASLD, offering reliable alternatives for diagnosis and monitoring while minimizing risks associated with traditional invasive methods.

Abstract B030: Advancing precision management in retinoblastoma via aqueous humor liquid biopsy: A case of TP53 and MDM4 alterations

Abstract Background: Precision medicine has revolutionized cancer treatment, but its application in retinoblastoma (RB) has been limited due to the risks associated with traditional tumor biopsies, which can lead to the spread of cancer outside the eye. Blood plasma has not been effective in intraocular RB management because the blood-brain barrier (BBB) prevents tumor-derived material from entering the bloodstream, and in cases of bilateral RB—occurring in over 40% of patients—each eye may harbor distinct genomic alterations, complicating the use of blood-based biomarkers. Given these challenges, the discovery of tumor-derived genomic material in the aqueous humor (AH) offers a promising and safer alternative—a liquid biopsy that provides localized and specific insights into the tumor's genetic makeup. Although AH liquid biopsies have been valuable in identifying genomic changes in RB, they have yet to guide treatment decisions. This is primarily due to the rarity of the disease, the heterogeneity of treatment modalities, and the unclear definition of in vivo RB subtype classifications. Consequently, translating these genomic insights into actionable, personalized treatment strategies has been challenging. Now, we present the first application of AH-monitored treatment in a 35-month-old male with unilateral RB, characterized by TP53 alteration and ecDNA-MDM4 amplification, highlighting a significant advancement in the precision management of RB. Methods: AH samples were obtained via clear corneal paracentesis and analyzed for copy number alterations and somatic variants using shallow whole-genome sequencing and targeted sequencing. The patient initially received systematic CEV, followed with intravitreal melphalan (IVM) monotherapy. Due to resistance, treatment was escalated to a combination of intravitreal melphalan and topotecan (IVM+IVT), monitored by the AH liquid biopsy genomic findings. Results:The patient initially showed resistance to monotherapy with intravitreal melphalan (IVM), but dual therapy with melphalan and topotecan (IVM+IVT) significantly reduced tumor fraction (TFx) from 81.61% to 26.63% and decreased tumor size. Continued dual therapy and subsequent topotecan monotherapy resulted in complete regression of vitreous seeds and stabilization of the disease, as indicated by a final AH TFx of 0%. At our institution, Children's Hospital Los Angeles (CHLA), the majority of RB cases are treated using IAC or IVM, with dual chemotherapy regimens rarely employed. Conclusions: This case underscores the importance of tailoring treatment protocols to genetic profiles identified through AH liquid biopsy in managing aggressive RB. The successful combination of genomic profiling and personalized therapy has potential to significantly improve clinical outcomes, marking a critical step toward real precision management of RB. Further clinical collaboration is essential to validate and refine protocols for TP53-altered and ecDNA-MDM4-driven RB. Citation Format: Liya Xu, Elaine Huang, Jesse Lee Berry. Advancing precision management in retinoblastoma via aqueous humor liquid biopsy: A case of TP53 and MDM4 alterations [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B030.

Cell cycle traverse rate predicts long-term outcomes in a multi-institutional cohort of patients with triple-negative breast cancer.

Ki67 index (KI) and mitotic index (MI) are proliferation markers with established prognostic value in breast carcinomas. While KI is evaluated immunohistochemically and reported as a percentage, MI is determined visually and reflects total mitotic cells in 10 high-power fields. Our objective was to integrate KI and MI into a novel metric; the cell cycle traverse rate (CCTR). Given the lack of prognostic and predictive biomarkers in TNBC, we sought to assess the potential of CCTR as a risk-stratification tool for chemotherapy-treated TNBC patients from two independent cohorts: the Nottingham group (n = 124) and the Norway group (n = 71). We evaluated the ability of CCTR to predict survival after adjuvant chemotherapy for TNBC patients (n = 195) in two independent cohorts. Using immunohistochemistry and RNA sequencing, we determined the differences in immunohistochemical biomarkers, gene ontologies, molecular pathways and immune cell fractions based on CCTR. TNBC shows a significantly lower median CCTR compared to luminal A (p < 0.01), luminal B (p < 0.01), and HER2+ samples (p < 0.01). CCTR outperformed both KI and MI in effectively risk-stratifying TNBC patients suggesting that combining KI and MI into a single metric, namely CCTR, could serve as a superior prognostic marker for Breast Cancer Specific Survival (BCSS) (p = 0.041). CCTR-high group exhibited enriched expression of various oncogenic signatures, including angiogenesis, epithelial-to-mesenchymal transition (EMT), Hedgehog signaling, hypoxia, Notch signaling, PI3K-AKT-mTOR signaling, TGFβ signaling, p53 signaling, and TNFα signaling via NFκB. These findings suggest the potential involvement of these pathways in the aggressiveness and clinical outcomes of TNBC patients. Collectively, these findings suggest that CCTR offers superior predictive information compared to KI and MI alone with respect to long-term outcomes from adjuvant chemotherapy in patients with TNBC that may guide treatment decision making.

A Novel and Comprehensive Wellness Assessment for Lifestyle-Based Interventions.

While weight status and clinical laboratory measures are important in assessing obesity-related disease severity and chronic disease risk, including a broader range of emotional, psychosocial, and behavioral factors would provide greater context of an individual's overall state of wellness and could be used to better guide treatment decisions. The purpose of this research was to develop a comprehensive Lifestyle Wellness assessment for use in lifestyle-based wellness interventions and programs. A cross-sectional exploratory factor analysis (EFA) was conducted using baseline data from N=138 adults participating in behavioral weight loss trials. An unweighted least squares extraction method with oblique rotation was used. Twenty-one putative measures spanning constructs related to metabolic health, emotional health/wellbeing, body weight and composition, diet quality, and fitness were analyzed for retention. Mean body mass index (BMI) was 38.0±6.6kg/m2, mean age was 57.3±11.1years, and 77.5% of participants were female. The EFA produced a five-factor model with 13 items that explained 80.3% of the variance. The retained factors included: (1) Psychosocial State: mindfulness, resilience, quality of life, and happiness; (2) Blood Pressure State: systolic and diastolic blood pressure; (3) Lipid State: total cholesterol and LDL-cholesterol; (4) Fitness State: grip strength, jump height, and percent body fat; and (5) Body State: BMI and waist circumference. Lifestyle Wellness is a comprehensive assessment that enables innovative wellness-related research such as metabolically healthy obese phenotypes and weight-neutral interventions. Future research should include investigations in additional populations with greater age, sex/gender, and body size diversity.

BIOM-42. RESPONSE TO DABRAFENIB/TRAMETINIB IN A PATIENT WITH WHO-CNS GRADE 3 BRAF V600E-MUTATED PLEOMORPHIC XANTHOASTROCYTOMA

Abstract BACKGROUND Pleomorphic xanthoastrocytoma (PXA) is a rare central nervous system tumor. Mutations in BRAF V600E are present in 60-80% of cases. While traditionally managed with surgical resection and adjuvant radiation, emerging evidence suggests targeted therapies may be effective, particularly in cases harboring the BRAF V600E mutation. CASE SUMMARY A 35-year-old male with no significant medical history presented in November 2023 with diplopia and headache leading to the discovery of a large left temporal/parietal tumor. A partial resection was performed. Initial histopathological diagnosis was glioblastoma (GBM); thus, the patient was treated with concurrent radiation and temozolomide for 6 weeks. Molecular pathological analysis demonstrated the presence of BRAF V600E mutation and CDKN2A/B copy number loss. Methylation-based tumor profiling was performed at the National Cancer Institute, with composite methylation profile indicating a consensus match to pleomorphic xanthoastrocytoma. Following chemoradiation, a repeat brain MRI in March 2024 showed tumor progression, prompting the initiation of dabrafenib and trametinib therapy. After 1 month of targeted treatment, a repeat brain MRI demonstrated a partial response with a decrease in tumor size and enhancement. In April 2024, he underwent a planned repeat resection. Symptomatically, the patient experienced intermittent headaches and nausea that were responsive to oral steroids with no serious adverse effects to targeted therapy. DISCUSSION This case highlights the therapeutic potential of double BRAF/MEK blockade with dabrafenib and trametinib in BRAF V600E-mutant anaplastic PXA. The observed partial response on imaging suggests the efficacy of targeted therapy in this molecular subtype. These findings underscore the importance of molecular profiling in guiding treatment decisions.

QLTI-17. COMPARATIVE ANALYSIS OF LUMBAR PUNCTURE UTILITY IN DIAGNOSIS OF PRIMARY VERSUS SECONDARY CNS LYMPHOMA: A RETROSPECTIVE STUDY

Abstract OBJECTIVES Central nervous system lymphoma (CNSL) is a subtype of non-Hodgkin lymphoma, which affects the brain, spinal cord, leptomeninges, or eyes. It includes primary (PCNSL) and secondary CNSL (SCNSL). CNSL diagnosis relies on neuroimaging, cerebrospinal fluid (CSF) analysis (cytology, flow cytometry), and/or tissue biopsy. Lumbar punctures (LP) aid in investigating leptomeningeal involvement. Positive findings confirm CNS involvement and guide treatment decisions. This study seeks to determine the effectiveness of CSF analysis via LP in diagnosing SCNSL compared to PCNSL. METHODS This retrospective study comprised patients who received treatment with HD-MTX treated at our center from July 2020 to January 2024. Data was retrospectively collected from electronic medical records (EMR). Pathology reports from tissue biopsy and enhancement of CNS visualized on imaging were utilized to diagnose and differentiate PCNSL and SCNSL. CNS cytology and flow cytometry from LP were analyzed to determine the diagnostic accuracy of LP CSF cytology results in diagnosing CNSL. Descriptive statistical and comparative analysis was conducted to analyze the results. RESULTS The sample included 70 patients, 35 each diagnosed with PCNSL and SCNSL. Of these, only 49 patients underwent LP, with a significantly higher proportion of patients in the SCNSL group, 33 (67%), compared to the PCNSL group, 16 (33%) (P&amp;lt;0.001). Among those who underwent LP, CSF cytology and/or flow cytometry were positive in 19 cases, with significantly higher detection rates among the SCNSL cases (16 of 33, 48.5%) compared to the PCNSL cases (3 of 16, 18.8%; p=0.045). CONCLUSION Our findings indicate that LPs play a crucial role in diagnosing SCNSL, with a significantly higher CSF detection rate than PCNSL. LP has a limited impact on diagnosing PCNSL, suggesting that tissue biopsy should be prioritized to avoid increased time for PCNSL diagnosis. This study underscores the importance of tailored diagnostic approaches for suspected PCNSL and SCNSL, emphasizing the utility of LP in diagnosing SCNSL and tissue biopsy for PCNSL.

A nomogram model to predict recurrence of early-onset endometrial cancer after resection based on clinical parameters and immunohistochemical markers: a multi-institutional study

ObjectiveThis study aimed to investigate the prognosis value of the clinical parameters and immunohistochemical markers of patients with early-onset endometrial cancer (EC) and establish a nomogram to accurately predict recurrence-free survival (RFS) of early-onset EC after resection.MethodsA training dataset containing 458 patients and an independent testing dataset consisting of 170 patients were employed in this retrospective study. The independent risk factors related to RFS were confirmed using Cox regression models. A nomogram model was established to predict RFS at 3 and 5 years post-hysterectomy. The C-index, area under the curve (AUC) of the receiver operating characteristic (ROC) curve, and calibration curve were calculated to assess the predictive accuracy of the nomogram.ResultsIn all early-onset EC patients, more than half (368/628, 58.6%) were diagnosed in the age range of 45-49 years. Meanwhile, the recurrence rate of early-onset EC is approximately 10.8%. Multivariate Cox regression analyses showed that histological subtype, FIGO stage, myometrial invasion, lymphovascular space invasion (LVSI), P53 expression, and MMR status were independent prognostic factors related to RFS (all P &amp;lt; 0.05) and established the nomogram predicting 3- and 5-year RFS. The C-index and calibration curves of the nomogram demonstrated a close correlation between predicted and actual RFS. Patients were divided into high- and low-risk groups according to the model of RFS.ConclusionsCombining clinical parameters and immunohistochemical markers, we developed a robust nomogram to predict RFS after surgery for early-onset EC patients. This nomogram can predict prognosis well and guide treatment decisions.

The Role of Immunohistochemistry as a Surrogate Marker in Molecular Subtyping and Classification of Bladder Cancer

Background/Objectives: Bladder cancer (BC) is a highly heterogeneous disease, presenting clinical challenges, particularly in predicting patient outcomes and selecting effective treatments. Molecular subtyping has emerged as an essential tool for understanding the biological diversity of BC; however, its implementation in clinical practice remains limited due to the high costs and complexity of genomic techniques. This review examines the role of immunohistochemistry (IHC) as a surrogate marker for molecular subtyping in BC, highlighting its potential to bridge the gap between advanced molecular classifications and routine clinical application; Methods: We explore the evolution of taxonomic classification in BC, with a particular focus on cytokeratin (KRT) expression patterns in normal urothelium, which are key to identifying basal and luminal subtypes. Furthermore, we emphasise the need for consensus on IHC markers to reliably define these subtypes, facilitating wider and standardised clinical use. The review also analyses the application of IHC in both muscle-invasive (MIBC) and non-muscle-invasive bladder cancer (NMIBC), with particular attention to the less extensively studied NMIBC cases. We discuss the practical advantages of IHC for subtyping, including its cost effectiveness and feasibility in standard pathology laboratories, alongside ongoing challenges such as the requirement for standardised protocols and external validation across diverse clinical settings; Conclusions: While IHC has limitations, it offers a viable alternative for laboratories lacking access to advanced molecular techniques. Further research is required to determine the optimal combination of markers, establish a consensus diagnostic algorithm, and validate IHC through large-scale trials. This will ultimately enhance diagnostic accuracy, guide treatment decisions, and improve patient outcomes.

Ceftazidime-avibactam treatment dilemma of blaKPC−2-containing Klebsiella pneumoniae due to the development of co-existence of mixed strains carrying blaKPC−2 or blaKPC−33 in lung transplant recipients

BackgroundCarbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat to immunocompromised populations, including lung transplant recipients. This study investigates mixed CRKP strains carrying either blaKPC−2 or blaKPC−33 following ceftazidime-avibactam (CAZ/AVI) exposure, particularly in the context of lung transplantation. Mixed CRKP strains with shifting resistance phenotypes were frequently identified in patients exposed to CAZ/AVI. We aimed to elucidate the transitional state of blaKPC variants by selecting CAZ/AVI-sensitive and -resistant CRKP strains from a lung transplantation patient.MethodsThe blaKPC-variant-carrying CRKP strains were collected from lung transplant recipients exposed to CAZ/AVI in less than two years. Antibiotic susceptibility testing (AST) was conducted using microbroth dilution, and whole-genome sequencing (WGS) was used to identify genotypes and resistance mechanisms. Limiting dilution, drop-plate, and in vitro induction experiments determined blaKPC-variant changes during CAZ/AVI administration. qPCR primers/probes were designed to identify blaKPC−2 mutations.ResultsAmong 104 lung transplant recipients infected by blaKPC-harboring CRKP strains and receiving CAZ/AVI, 10 (9.6%) experienced changing resistance phenotypes. The limiting dilution method found that Patient 10’s CRKP strains carried either blaKPC−2 or blaKPC−33. The drop-plate experiment showed differing growth patterns on CAZ/AVI mediums. The in vitro induction experiment demonstrated shifting from blaKPC−2 to blaKPC−33.ConclusionsThe study identified a “transitional state” of the mixed CRKP strains carrying either blaKPC−2 or blaKPC−33 in CAZ/AVI-exposed patients. Molecular diagnostics are crucial for identifying mixed strains and the transitional state of blaKPC variants, guiding treatment decisions in this complex landscape.

Prognostic value of computed tomography-derived fractional flow reserve in patients with diabetes mellitus and unstable angina

BackgroundCoronary artery calcification is commonly found in patients with type 2 diabetes mellitus (T2DM), which may compromise the diagnostic accuracy of coronary computed tomography angiography (CTA). Computed tomography-derived fractional flow reserve (CT-FFR), which integrates coronary anatomy with functional assessment, holds the potential to become a powerful diagnostic tool for evaluating calcified lesions.ObjectiveWe aim to assess the prognostic value of CT-FFR for calcific lesions in patients with T2DM and unstable angina (UA).MethodsWe conducted a retrospective study involving 3,392 patients who were diagnosed with T2DM and UA who underwent coronary CTA, with at least one visible calcification site. Of those, 1,091 patients and 1,372 vessels were recommended by cardiovascular specialists and completed invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR) measurements. Simultaneously, those patients also underwent CT-FFR measurements and were divided into two groups based on CT-FFR values: one group with CT-FFR > 0.80 and the other with CT-FFR ≤ 0.80. Demographics, clinical data, the diagnostic performance of CT-FFR, analysis of calcified lesions on CTA, and major adverse events during follow-up were recorded.ResultsThe diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the curve (AUC) of CT-FFR were 84.8%, 84.6%, 85.1%, 84.7%, 85.0%, and 84.8%, respectively, per patient, and 82.2%, 80.3.2%, 81.8%, 79.7%, 81.1%, and 82.9% respectively, per vessel. For lesion and calcification characteristics, the degree of stenosis, lesion length, rate of bifurcation lesions, diffusive lesions, occlusion, calcium volume, and coronary artery calcification score (CACS) were significantly higher in the CT-FFR ≤ 0.8 group compared to the CT-FFR > 0.8 group. In contrast, the minimum cross-sectional area was smaller in the CT-FFR ≤ 0.8 group than in the CT-FFR > 0.8 group. Major adverse cardiovascular and cerebrovascular events (MACCE) at the 3-year follow-up was significantly higher in the CT-FFR ≤ 0.8 group compared to the CT-FFR > 0.8 group. The CT-FFR value is an independent predictor of MACCE at the 3-year follow-up.ConclusionCT-FFR demonstrated significant diagnostic performance using invasive FFR as the reference standard and proved to be an important predictive tool for assessing prognosis not only in calcified lesions but also in lesions with a CACS score of zero in patients with T2DM and UA. CT-FFR may serve as a valuable tool for guiding treatment decisions in these patients.Graphical abstract

Assessing 3D volumetric asymmetry in facial palsy patients via advanced multi-view landmarks and radial curves

The research on facial palsy, a unilateral palsy of the facial nerve, is a complex field with many different causes and symptoms. Even modern approaches to evaluate the facial palsy state rely mainly on stills and 2D videos of the face and rarely on dynamic 3D information. Many of these analysis and visualization methods require manual intervention, which is time-consuming and error-prone. Moreover, they often depend on alignment algorithms or Euclidean measurements and consider only static facial expressions. Volumetric changes by muscle movement are essential for facial palsy analysis but require manual extraction. We propose to extract an estimated unilateral volumetric description for dynamic expressions from 3D scans. Accurate landmark positioning is required for processing the unstructured facial scans. In our case, it is attained via a multi-view method compatible with any existing 2D predictors. We analyze prediction stability and robustness against head rotation during video sequences. Further, we investigate volume changes in static and dynamic facial expressions for 34 patients with unilateral facial palsy and visualize volumetric disparities on the face surface. In a case study, we observe a decrease in the volumetric difference between the face sides during happy expressions at the beginning (13.8 ± 10.0 mm3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\hbox {mm}^{3}$$\\end{document}) and end (12.8 ± 10.3 mm3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\hbox {mm}^{3}$$\\end{document}) of a ten-day biofeedback therapy. The neutral face kept a consistent volume range of 11.8-\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$-$$\\end{document}12.1 mm3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\hbox {mm}^3$$\\end{document}. The reduced volumetric difference after therapy indicates less facial asymmetry during movement, which can be used to monitor and guide treatment decisions. Our approach minimizes human intervention, simplifying the clinical routine and interaction with 3D scans to provide a more comprehensive analysis of facial palsy.