Treatment Monitoring Research Articles

Reproducibility of intravoxel incoherent motion quantification in the liver across field strengths and gradient hardware.

To evaluate reproducibility and interlobar agreement of intravoxel incoherent motion (IVIM) quantification in the liver across field strengths and MR scanners with different gradient hardware. Cramer-Rao lower bound optimization was performed to determine optimized monopolar and motion-robust 2D (b-value and first-order motion moment [M1]) IVIM-DWI acquisitions. Eleven healthy volunteers underwent diffusion MRI of the liver, where each optimized acquisition was obtained five times across three MRI scanners. For each data set, IVIM estimates (diffusion coefficient (D), pseudo-diffusion coefficients ( and ), blood velocity SDs (Vb1 and Vb2), and perfusion fractions [f1 and f2]) were obtained in the right and left liver lobes using two signal models (pseudo-diffusion and M1-dependent physical) with and without T2 correction (fc1 and fc2) and three fitting techniques (tri-exponential region of interest-based full and segmented fitting and blood velocity SD distribution fitting). Reproducibility and interlobar agreement were compared across methods using within-subject and pairwise coefficients of variation (CVw and CVp), paired sample t-tests, and Bland-Altman analysis. Using a combination of motion-robust 2D (b-M1) data acquisition, M1-dependent physical signal modeling with T2 correction, and blood velocity SD distribution fitting, multiscanner reproducibility with median CVw = 5.09%, 11.3%, 9.20%, 14.2%, and 12.6% for D, Vb1, Vb2, fc1, and fc2, respectively, and interlobar agreement with CVp = 8.14%, 11.9%, 8.50%, 49.9%, and 42.0%, respectively, was achieved. Recently proposed advanced IVIM acquisition, signal modeling, and fitting techniques may facilitate reproducible IVIM quantification in the liver, as needed for establishment of IVIM-based quantitative biomarkers for detection, staging, and treatment monitoring of diseases.

Evaluation of a Multimodal Confocal Therapeutic Focused Ultrasound Apparatus: Bridging Cavitation, Thermal Ablation, and Histotripsy in Preclinical Treatments

ObjectivesThe development of versatile and user-friendly preclinical platforms is vital for therapeutic ultrasound research. We introduce a flexible ultrasound-guided focused ultrasound (FUS) platform with two confocal therapeutic transducers, allowing thermal and mechanical modalities, and present its design and, features, with validation of potential applications in preclinical studies. MethodsThe probe's acoustic properties, energy delivery efficiency, and thermal and mechanical modalities are characterized. A computational model predicts thermal effects while optimizing treatment parameters. Ex vivo tissue samples are used to validate system performance, safety, and usability. In vivo experiments on mice with MC38 tumors are presented with immunohistochemistry (IHC) to validate treatment outcomes. ResultsElectroacoustic conversion efficiency levels were 80% and 40% for 1.1 MHz and 3.3 MHz, respectively. Confocal therapy transducers at 1.1 MHz and 3.3 MHz successfully demonstrated cavitation histotripsy and thermal treatments. At 1.1 MHz, for histotripsy, −20 MPa negative peak pressure is achieved, while at 3.3 MHz used for thermal ablation a maximum of 35 MPa is reached for positive peak pressure. Numerical analysis provides thermal treatment planning, aligning with in vitro and in vivo experiments for lesion prediction. Real-time in vivo cavitation monitoring was consistent with in vitro chemical dosimetry, ensuring treatment uniformity. ConclusionThe ultrasound platform induces thermal or mechanical lesions with precise spatial resolution, validated by IHC tissue characterization. Integrated cavitation monitoring enables real-time treatment monitoring. Coupling with thermal simulations provides optimization of thermal treatment parameters. This versatile “all-in-one” therapeutic platform supports multiple treatment modalities including cavitation, thermal ablation, and histotripsy, facilitating direct comparisons to assess their efficacy in diverse therapeutic settings.

Predicting prolonged postoperative ileus in gastric cancer patients based on bowel sounds using intelligent auscultation and machine learning

BACKGROUND Prolonged postoperative ileus (PPOI) delays the postoperative recovery of gastrointestinal function in patients with gastric cancer (GC), leading to longer hospitalization and higher healthcare expenditure. However, effective monitoring of gastrointestinal recovery in patients with GC remains challenging because of the lack of noninvasive methods. AIM To explore the risk factors for delayed postoperative bowel function recovery and evaluate bowel sound indicators collected via an intelligent auscultation system to guide clinical practice. METHODS This study included data from 120 patients diagnosed with GC who had undergone surgical treatment and postoperative bowel sound monitoring in the Department of General Surgery II at Shaanxi Provincial People's Hospital between January 2019 and January 2021. Among them, PPOI was reported in 33 cases. The patients were randomly divided into the training and validation cohorts. Significant variables from the training cohort were identified using univariate and multivariable analyses and were included in the model. RESULTS The analysis identified six potential variables associated with PPOI among the included participants. The incidence rate of PPOI was 27.5%. Age ≥ 70 years, cTNM stage (I and IV), preoperative hypoproteinemia, recovery time of bowel sounds (RTBS), number of bowel sounds (NBS), and frequency of bowel sounds (FBS) were independent risk factors for PPOI. The Bayesian model demonstrated good performance with internal validation: Training cohort [area under the curve (AUC) = 0.880, accuracy = 0.823, Brier score = 0.139] and validation cohort (AUC = 0.747, accuracy = 0.690, Brier score = 0.215). The model showed a good fit and calibration in the decision curve analysis, indicating a significant net benefit. CONCLUSION PPOI is a common complication following gastrectomy in patients with GC and is associated with age, cTNM stage, preoperative hypoproteinemia, and specific bowel sound-related indices (RTBS, NBS, and FBS). To facilitate early intervention and improve patient outcomes, clinicians should consider these factors, optimize preoperative nutritional status, and implement routine postoperative bowel sound monitoring. This study introduces an accessible machine learning model for predicting PPOI in patients with GC.

Genetically Engineered Bacteria as A Living Bioreactor for Monitoring and Elevating Hypoxia-Activated Prodrug Tumor Therapy.

Tirapazamine (TPZ), an antitumor prodrug, can be activated in hypoxic environment. It specifically targets the hypoxic microenvironment of tumors and produces toxic free radicals. However, due to the tumor is not completely hypoxic, TPZ often fails to effectively treat the entire tumor tissue, resulting in suboptimal therapeutic outcomes. Herein, a low pathogenic Escherichia coli TOP10 is utilized to selectively colonize tumor tissues, disrupt blood vessels, and induce thrombus formation, leading to the expansion of hypoxic region and improving the therapeutic effect of TPZ. Additionally, a thermosensitive hydrogel is constructed by Pluronic F-127 (F127), which undergoes gelation in situ at the tumor site, resulting in sustained release of TPZ. To monitor the therapeutic process, it is genetically modified TOP10 by integrating the bioluminescent system luxCDABE (TOP10-Lux). The bioluminescent signal is associated with tumor hypoxia enhancement and thrombus formation, which is beneficial for therapeutic monitoring with bioluminescence imaging. In the murine colon cancer model, the TOP10-Lux combined with TPZ-loaded F127 hydrogel effectively suppressed tumor growth, and the treatment process is efficiently monitored. Together, this work employs genetically modified TOP10-Lux to enhance the therapeutic efficacy of TPZ and monitor the treatment process, providing an effective strategy for bacteria-based tumor-targeted chemotherapy and treatment monitoring.

Trace Element Composition of Surface Water in Almaty City and Human Health Risk Assessment

This investigation meticulously examined the elemental composition of 64 water samples collected during the seasons of spring, summer, autumn, and winter of the year 2023. The average seasonal concentrations of arsenic (As), beryllium (Be), cobalt (Co), cadmium (Cd), copper (Cu), lithium (Li), molybdenum (Mo), nickel (Ni), lead (Pb), selenium (Se), uranium (U), mercury (Hg), aluminum (Al), barium (Ba), chromium (Cr), iron (Fe), manganese (Mn), strontium (Sr), vanadium (V), zinc (Zn), calcium (Ca), potassium (K), magnesium (Mg), sodium (Na), and chlorine (Cl) as well as SO4 and dry residue were computed at 16 strategically selected sites along the Bolshaya and Malaya Almatinka, Esentai, and Kargalinka rivers situated in Almaty. The sampling locations were categorized into three distinct sectors: upper (adjacent to mountainous regions), middle (urban zone), and lower (exceeding city limits), thereby facilitating the examination of discrepancies in water quality and elemental concentrations. The results reveal that surface water resources in Almaty, particularly concerning As, Ni, Cr, U, and Pb, may present a considerable carcinogenic risk if utilized for consumption purposes. This is especially alarming given that these rivers constitute a vital source of drinking water for the inhabitants of the city. Specifically, at two sampling locations along the Bolshaya and Malaya Almatinka rivers in proximity to significant urban thoroughfares, untreated river water displayed an elevated carcinogenic risk (CR ~ 10−2). These results highlight the urgent necessity for enhanced water treatment and ongoing monitoring to safeguard public health.

The role and impact of new technologies on healthcare systems

AbstractThe integration of new technologies into healthcare systems is revolutionizing the industry by significantly enhancing the capabilities of healthcare providers, improving patient outcomes, and optimizing administrative operations. This comprehensive examination critically assesses the impact of these technologies on various stakeholders within the healthcare ecosystem, highlighting both the benefits and challenges. Emerging technologies such as artificial intelligence (AI), which refers to the simulation of human intelligence by machines, the Internet of Things (IoT), which involves interconnected devices that collect and exchange health-related data in real time, Blockchain, which is a decentralized and tamper-proof ledger technology used to securely manage patient data, and wearable devices are explored for their potential applications in diagnostics, treatment, and patient monitoring. Despite their transformative potential, these technologies also bring forth a range of limitations and challenges, including ethical concerns regarding patient privacy, legal implications of data security, and technical hurdles related to interoperability and implementation. By addressing these issues, the healthcare industry can better navigate the complexities of technological advancement, ensuring that innovation contributes positively to patient care and operational efficiency.

EyeMatics-Multicenter data evaluation of real-world data with interoperable medical informatics

The evaluation of real-world data (RWD) enables insights to be gained from awide range of patient data collected in routine clinical practice. In addition, multicenter analyses represent abroad and representative patient population and have the potential to capture the actual treatment situation. As abasis for this, the definition of datasets and an infrastructure for data exchange is necessary. Data integration centers (DIC) have already been established at (university) hospitals throughout Germany in order to extract RWD for scientific analyses from the various source systems and integrate them into research-compatible data infrastructures. The project described here aims to demonstrate the added value of this data integration using a case of application in ophthalmology, defining acore dataset as an ophthalmology extension module and establishing across-site data exchange infrastructure. As afirst step, the treatment success of eye diseases treated with intravitreal injection (IVI) should be improved. To achieve this goal adashboard for clinical data is provided that clearly visualizes the merged data. Furthermore, algorithms will be developed to identify new imaging biomarkers that can be used for treatment monitoring and predict treatment outcomes.

Abstract B047: Monitoring treatment response and toxicity in BRAF V600-mutant metastatic melanoma with circulating cell-free DNA

Abstract Background: The DREAMseq trial (EA6134, NCT02224781) was a national multi-center randomized phase III trial coordinated by ECOG-ACRIN that found that immune checkpoint inhibitor (IO) treatment achieves improved survival outcomes compared to targeted therapy (TT) in patients with BRAF V600-mutant metastatic melanoma. Still, approximately 40% of patients do not respond to IO, and existing biomarkers fail to distinguish this subset of patients who do not benefit from IO therapy. Additionally, as many as 80% of patients may experience immune- related adverse events (irAEs), which range from mild dermatological symptoms to life- threatening myocarditis. Here, we explore the use of the methylation status of cell-free DNA (cfDNA) in serially collected blood samples to measure response and toxicity in the context of IO- and TT-treated metastatic melanoma. Methods: Serial serum samples were collected from patients with BRAF V600-mutant metastatic melanoma treated with ipilimumab/nivolumab (IO) or dabrafenib/trametinib (TT). Circulating cfDNA was isolated from serially collected serum samples, enriched for regions of interest by hybridization capture and sequenced using enzymatic methyl-seq. Cell-type deconvolution was performed to determine the abundance of cell type- specific methylation patterns of cfDNA molecules in patient serum at different time points of treatment. The BRAF V600 mutation abundance in total cfDNA was also assessed. Results: We identified melanocyte lineage-specific DNA methylation regions and demonstrate that the methylation status of these regions remains conserved in malignant melanoma. We characterized the changes in abundance of the melanocyte-lineage cfDNA over the course of treatment and show that these changes distinguish responders from non-responders to either IO or TT. Furthermore, we track the abundance of cell type-specific DNA from normal tissues to identify markers indicative of adverse effects or disease progression. Conclusions: We established melanocyte-lineage methylation markers and evaluated the use of cell-type specific DNA methylation to monitor treatment effects of immune checkpoint or BRAF/MEK inhibitors in metastatic melanoma using serially collected blood samples. Citation Format: Sidharth S Jain, A. Patrick IV McDeed, Megan E McNamara, Amber R Alley, Dori S Rosenstrauch, Harry Sun, Natalie Thompson, John M Kirkwood, Geoffrey T Gibney, Michael B Atkins, Anton Wellstein. Monitoring treatment response and toxicity in BRAF V600-mutant metastatic melanoma with circulating cell-free DNA [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 B047.

Abstract B023: Cell-free HPV-DNA dynamics during induction chemotherapy and response-stratified de-escalation in viral-mediated oropharyngeal cancer

Abstract Background: Cell-free HPV-DNA (cfHPV-DNA) in plasma represents a promising biomarker to grade treatment response and monitor for persistence/recurrence. We evaluated the dynamic changes of cfHPV-DNA during induction chemotherapy followed by response-stratified de-escalation in HPV associated (HPV+) oropharyngeal squamous cell cancer (OPSCC). Methods: A prospective biomarker clinical trial of response-stratified de-escalation therapy was conducted. Eligible patients had loco-regional HPV+ OPSCC and received induction chemotherapy with carboplatin and paclitaxel for three cycles followed by risk and response-stratified de-escalation with transoral robotic surgery (TORS), de-escalated radiation (RT) to 50Gy with or without cisplatin, or standard RT to 70Gy with cisplatin. Patients with deep response (>=50% tumor shrinkage per RECIST 1.1) qualified for de-escalated therapy. Cell-free HPV-DNA was measured using a CLIA-certified HPV-SEQ assay that utilizes NGS technology to detect and quantify HPV16 and HPV18 DNA in plasma at baseline, after each cycle of induction chemotherapy, during radiation, and post-treatment surveillance at 3, 6, 9, 12, 18, and 24 months following treatment. Results: Forty-six eligible patients were enrolled, with 464 cfHPV-DNA plasma samples analyzed (median 10 samples per patient). There were five recurrences (10.9%), all detected by HPV-SEQ. Baseline cfHPV-DNA was detected in 44/46 patients (96%). Patients with rapid early cfHPV-DNA clearance after one 3-week cycle of induction (>=95% clearance) predicted deep radiographic response following induction therapy (p=0.003). The detection of cfHPV-DNA at 3 months or later after treatment was associated with worse progression free survival (PFS), with 2-year PFS of 25% (95% CI 0.012-0.65) compared with patients without detectable cfHPV-DNA of 100% (95% CI 1.0-1.0); p<0.001). The longest lead-time from positive cfHPV-DNA to developing recurrent disease was 25 months. Conclusion: Rapid early clearance of cfHPV-DNA during induction has utility in predicting response to treatment. Detectable cfHPV-DNA following treatment is strongly associated with worse PFS. A subsequent trial using cfHPV-DNA to select patients for treatment de-escalation is ongoing. Clinicaltrials.gov ID: NCT04572100 Citation Format: Ari Rosenberg, Evgeny Izumchenko, John Cursio, Augustin Vannier, Aditya Juloori, Rohan Katipally, Rifat Hasina, Frederick Jones, Anna Starus, Elizabeth Blair, Daniel J. Haraf, Alexander T. Pearson, Everett E. Vokes, Nishant Agrawal. Cell-free HPV-DNA dynamics during induction chemotherapy and response-stratified de-escalation in viral-mediated oropharyngeal cancer [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 B023.

Cardiodermatology: the heart of the connection between the skin and cardiovascular disease.

The skin and cardiovascular systems are connected in unique and meaningful ways, and many diseases conventionally considered as being limited to one organ system are more closely related than previously believed. Major cardiovascular diseases and phenomena such as infective endocarditis, congestive heart failure, Kawasaki disease and thromboembolism are associated with specific skin findings, and advances in genetics, immunology and clinical epidemiology show that inflammatory dermatological diseases, such as psoriasis, have serious cardiovascular and cardiometabolic consequences. Additionally, commonly used cardiovascular therapies, such as antihypertensive medications, are associated with important cutaneous adverse effects, including photosensitivity, photocarcinogenesis and eczematous skin reactions. Moreover, systemic dermatological therapies, including retinoids, Janus kinase inhibitors and biologics, can alter the risk of cardiovascular and cardiometabolic diseases. In this Review on cardiodermatology, we provide interdisciplinary insights from dermatology and cardiology that will be of practical use to both cardiologists and generalists who manage cardiovascular and cardiometabolic diseases in patients with dermatological findings or histories. We discuss specific skin findings associated with cardiovascular diseases to aid in diagnosis; important cutaneous adverse effects of common cardiovascular therapies, for the purpose of treatment monitoring; and the effect of dermatological diseases and dermatological treatment on cardiovascular risk.

Liquid-Biopsy Glycan Score Biomarker Accurately Indicates and Stratifies Primary and Metastatic Prostate Cancers.

Prostate cancer (PCa) is the most commonly diagnosed cancer in males. Early PCa usually shows no clinical symptoms and its primary diagnosis is currently guided by liquid-biopsy testing of serum prostate-specific antigen (PSA). This testing suffers from high false-positive and false-negative rates. Identifying new biomarkers for precise liquid-biopsy detection of PCa is, thus, an acute clinical request. Here, by using an advanced dual-functional aptamer assay, we quantified the extent of glycosylation of PSA circulating in cancer patients' serum, linked it to cancer-related breakage of PSA complexes with serum-circulating proteins, and proved its facility for stratification of primary and metastatic PCa. PSA's "Glycan Score" 100% accurately informed about PCa status in a 30-patient cohort, while serum PSA's concentration correctly classified only 53% of PCa patients and did not inform about their PCa status. The Glycan Score liquid-biopsy test thus has a huge potential for accurate diagnosis and staging of PCa, enabling mass-screening program progress and advanced PCa treatment monitoring.

Abstract A028: Precise monitoring of osteosarcoma patients by noninvasive assessment of matrix metalloproteinases activities in plasma extracellular vesicles

Abstract Osteosarcoma (OS) is the most prevalent bone cancer in children, characterized by aggressive primary tumors and high metastatic potential. Current treatment protocols involve a combination of neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy, tailored based on histological grade and metastatic risk. Identifying metastatic lesions through routine imaging significantly impacts treatment outcomes, highlighting the need for innovative diagnostic tools for timely monitoring. Noninvasive in vitro diagnostics, analyzing circulating tumor components like tumor-derived extracellular vesicles (EVs), would offer promise for monitoring treatment responses in pediatric sarcomas. Matrix metalloproteinases (MMPs) play a crucial role in tumor progression by degradation of the extracellular matrix; thus, recent research has focused on understanding their functional roles by profiling their proteolytic activities. Tumor EVs are crucial in transporting MMPs to facilitate invasion and metastasis, making them suitable surrogate for noninvasive profiling of MMP activities. Herein, we introduce an innovative OS EV MMP Activity Assay to assess MMP activities in OS patients noninvasively. This assay evaluates six different combinations of surface markers on OS EVs and OS-associated MMPs, generating a unique profile for each patient. Using a logistic regression model, an OS EV MMP Activity Score is generated from the most effective combinations. This Score has shown excellent performance in distinguishing between metastatic and localized OS. In a longitudinal study of six OS patients undergoing treatment, the Score strongly correlated with treatment response as measured by routine imaging. The assay represents a significant advancement in harnessing tumor EVs for diagnostics, providing a noninvasive, quantitative, and reliable approach to assess MMP activities in solid tumors. Citation Format: Junseok Lee, You-Ren Ji, Hyoyong Kim, Zhao Chen, Ryan Zhang, Diego Banuet, Yusef Mathkour, Kenny Vo, Steven Jonas, Yazhen Zhu, Hsian-Rong Tseng. Precise monitoring of osteosarcoma patients by noninvasive assessment of matrix metalloproteinases activities in plasma extracellular vesicles [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 A028.

Abstract A003: CD45 positive circulating tumor cells as a prognostic marker in prostate cancer

Abstract Prostate cancer is one of the most common types of cancer among male patients worldwide, making early diagnosis and effective treatment crucial for improving patient survival rates. In this regard, circulating tumor cells (CTCs) have garnered attention as an important biomarker for cancer staging and monitoring treatment response. In prostate cancer, CTCs are typically identified as keratin+/CD45- cells, with additional markers such as PSA or PSMA also being used. The conventional CTC identification way have dismissed CD45+/keratin+ double-positive cells as artifacts by nonspecific binding during the staining process. However, recent studies have reported the presence of CD45+/keratin+ CTCs in various types of cancers, highlighting metastatic potential and their ability to evade the immune system. These findings require re- examination of the role for the double positive CTCs. Therefore, this study aimed to identify the presence of CD45+ CTCs in prostate cancer and to assess their clinical significance. Blood samples were collected from 80 prostate cancer patients, followed by unbiased isolation of CTCs, which were stained using PSA, keratin, and CD45. The detected CTCs were categorized based on CD45 expression, and the clinical relevance of each group was validated using patient information. Through this study, we aimed to confirm whether the CD45+ CTCs can be a clinical indicator in prostate cancer. The results revealed that CD45+ CTCs accounted for 90% of all detected CTCs, likely due to their high immune evasion capabilities. Additionally, in 17% of the patients, only CD45+ CTCs were detected, indicating the potential to expand CTC detection even in patients where CTCs were previously undetected using conventional criteria. The number of CD45+ CTCs was significantly higher in patients with progressive disease compared to those with complete or partial response, showing greater statistical significance than analyses using CD45- CTCs. Furthermore, the number of PSA+ CTCs was closely linked to changes in plasma PSA levels, suggesting they could be used as a supporting marker to enhance the accuracy of current plasma PSA tests. These findings indicate that CD45+ CTCs in prostate cancer are not merely artifacts of nonspecific binding but are indeed meaningful cells closely related to cancer progression. This study suggests that CD45+ CTCs have the potential to be utilized as a prognostic biomarker in prostate cancer. By including CD45+ CTCs, which were previously overlooked in conventional CTC analysis methods, more sensitive and accurate cancer monitoring could be achieved. In-depth future studies on the clinical applicability of CD45+ CTCs could significantly contribute to predicting prognosis and developing personalized treatment strategies for prostate cancer patients. Citation Format: Hyeongjung Woo, Woon-Hae Kim, Hyun Young Shin, Hyerin Jung, Hyung Ho Lee, Minseok S. Kim, Jae Young Joung. CD45 positive circulating tumor cells as a prognostic marker in prostate cancer [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 A003.

Abstract B013: An mDETECT assay for monitoring treatment response in metastatic breast cancer patients

Abstract Metastatic breast cancer treatment response is currently assessed every 3-6 months and this long delay results in many patients undergoing ineffective and toxic treatments for long periods of time. We have developed the methylation DETEction of Circulating Tumour DNA (mDETECT) assay, a targeted DNA methylation-based Next Generation Sequencing liquid biopsy that detects cancer-specific patterns in all subtypes of breast cancer. The assay targets 60 differentially hypermethylated regions in breast cancer across the genome and assesses over 400 individual CpGs with an average of 8 CpGs per target amplicon. The assay has been assessed on DNA from 73 breast cancer tumour samples which on average had 40 regions hypermethylated per patient with similar rates across all subtypes. We will present results from plasma samples from locally advanced and metastatic breast cancer patients along with plasma from age-matched, healthy female controls. A prospective, multi-centre observational cohort study to monitor metastatic breast cancer patients using the mDETECT liquid biopsy as they undergo treatment is active and recruiting patients. Blood is drawn with every standard-of-care blood draw for up to 3 years. Plasma has been assessed using the mDETECT assay to determine the methylation status of the DNA at each time point. 35 patients have been enrolled to date with ongoing recruitment up to 150 patients. Patients are being monitored with the mDETECT assay for earlier detection of disease progression on a treatment. They will also be monitored through treatment changes to assess a patient’s initial response to a given treatment. Changes in mDETECT levels will be correlated with clinical response to determine if the mDETECT breast cancer assay can detect a response to treatment at an earlier timepoint. This assay could allow for improved monitoring of treatment response allowing clinicians to make informed decisions, improving outcomes and prolonging patient’s lives. Citation Format: Keira Frosst, Brooke Wilson, Katrina Cristall, Catherine Crawford-Brown, Christopher R Mueller. An mDETECT assay for monitoring treatment response in metastatic breast cancer patients [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 B013.

Abstract PR002: The clinical relevance of circulating tumor cell size in head and neck squamous cell carcinoma patients

Abstract Circulating tumor cells (CTCs) play a critical role in the metastatic process of cancer and are widely recognized as important biomarkers that provide valuable information related to tumor characteristics. While most research to date has focused on the biological markers and molecular properties of CTCs, their physical characteristics, particularly size, have been relatively underexplored. However, recent studies suggest that smaller CTCs exhibit enhanced tumor- initiating and metastatic abilities compared to larger CTCs. This indicates that CTC size is not merely a physical trait but may directly influence the invasiveness and metastatic potential of tumors. Such findings suggest that CTC size could be an important indicator for predicting tumor malignancy and provide a new perspective on understanding cancer progression and metastasis. As such, there is a growing emphasis on research that considers the size of CTCs. In this study, it was speculated whether CTC size holds clinical significance in patients with head and neck squamous cell carcinoma (HNSCC). The study was involved with 20 HNSCC patients, analyzing the morphological characteristics of CTCs collected from blood samples before and after treatment, while exploring the potential for monitoring treatment response. Our results found that CTCs were detected 20% more frequently in oropharyngeal cancer (OPC) patients compared to non-OPC patients. This is likely due to the rich vascularity in the oropharyngeal region, which may facilitate greater entry of CTCs into the bloodstream. Additionally, the cell size (23.9 μm in average) and nuclear size (16.4 μm in average) of HPV-positive patients were 32% and 10% larger, respectively, than those of HPV-negative patients (cell size: 18.1 μm; nuclear size: 12.60 μm). This suggests that the sizes of CTC and their nuclei may be associated with HPV status, which is presumed to be due to HPV causing disruptions in the cell cycle. In addition, we could successfully cultivate the CTCs obtained from HPV-positive patients with relatively smaller CTCs for 30 days, predicting that small CTCs have affordable for CTC culture. In conclusion, this study confirms that the physical characteristics of CTCs, particularly size, are linked to HPV infection status in HNSCC patients. CTC- and nucleus- size are closely related to tumor characteristics, demonstrating the potential for developing diagnostic and prognostic tools based on these physical traits. Although more in-depth research is required, poor prognosis in HPV- positive patients may also be related to the physical characteristics of CTCs. Citation Format: Hyeongjung Woo, Hyun Young Shin, So Yeon Oh, Sun Min Lee, Minseok S. Kim. The clinical relevance of circulating tumor cell size in head and neck squamous cell carcinoma patients [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 PR002.

Diagnostic Utility of MicroRNAs in Pancreatic Cancers

Pancreatic cancer (PC) is a serious malignant tumor with a high mortality rate, mainly due to late diagnosis and a lack of effective therapeutic interventions. The possibility of recognizing this cancer with reliable biomarkers using minimally invasive methods is of great importance for improving early detection, prognostic assessment, and targeted treatment methods. In recent years, small non-coding RNAs, especially microRNAs, have emerged as promising candidates for biomarkers of pancreatic cancer. Despite the methodological and analytical limitations of microRNA determination and a lack of available automated and standardized tests, a prospective systematic assessment of this new parameter’s use in the detection of pancreatic cancer is warranted. This review provides general information on the diagnostic and prognostic utility of microRNAs, which appear to be well-established in many studies. In summary, microRNAs are promising non-invasive biomarkers of pancreatic cancer, offering potential opportunities for early detection, prognosis, and treatment monitoring. As research in this field progresses, microRNAs should become valuable tools in the fight against pancreatic cancer.

DOENÇA RENAL CRÔNICA CONCOMITANTE À ERLIQUIOSE: RELATO DE CASO

Kidney disease can range from acute kidney injury to chronic kidney disease, often caused by inflammation that impairs filtration. When kidney function is compromised, toxins accumulate, which can lead to kidney failure. In advanced cases, dialysis treatment becomes necessary. Other associated pathologies, such as ehrlichiosis, can make the condition irreversible. Ehrlichiosis triggers an inflammatory response affecting the kidneys, with the formation of immune complexes during infection. These complexes deposit in the renal capillaries, causing glomerulonephritis, an inflammation that impairs the function of the glomeruli, responsible for blood filtration. The purpose of this report is to present a case where kidney disease developed concomitantly with ehrlichiosis. In this case, an animal was referred to a veterinary hospital for dialysis treatment due to kidney disease. Laboratory tests were conducted, including a complete blood count, biochemical analysis, rapid ehrlichiosis test, and PCR, which confirmed the presence of active ehrlichiosis infection. Additionally, hemodialysis and dialysis sessions were performed, among other treatments. This case highlights the complexity and challenges of treating chronic kidney disease aggravated by ehrlichiosis, emphasizing the importance of advanced therapies and the need for ethical planning to balance available resources and the animal's quality of life. Raising awareness among pet owners about the risks, the importance of early diagnosis, correct treatment, and continuous monitoring are fundamental measures that can help in the early detection of kidney impairment and increase the chances of successful treatment.

An insight to PDAC tumor heterogeneity across pancreatic subregions using computed tomography images

Pancreatic Ductal Adenocarcinoma (PDAC) is an exceptionally deadly form of pancreatic cancer with an extremely low survival rate. From diagnosis to treatment, PDAC is highly challenging to manage. Studies have demonstrated that PDAC tumors in distinct regions of the pancreas exhibit unique characteristics, influencing symptoms, treatment responses, and survival rates. Gaining insight into the heterogeneity of PDAC tumors based on their location in the pancreas can significantly enhance overall management of PDAC. Previous studies have explored PDAC tumor heterogeneity across pancreatic subregions based on their genetic and molecular profiles through biopsy-based histologic assessment. However, biopsy examinations are highly invasive and impractical for large populations. Abdominal imaging, such as Computed Tomography (CT) offers a completely non-invasive means to evaluate PDAC tumor heterogeneity across pancreatic subregions and an opportunity to correlate image feature of tumors with treatment outcome and monitoring. In this study, we explored the inter-tumor heterogeneity in PDAC tumors across three primary pancreatic subregions: the head, body, and tail. Utilizing contrast-enhanced abdominal CT scans and a thorough radiomic analysis of PDAC tumors, several morphological and textural tumor features were identified to be notably different between tumors in the head and those in the body and tail regions. To validate the significance of the identified features, a machine learning ML model was trained to automatically classify PDAC tumors into their respective regions i.e. head or body/tail subregion using their CT features. The study involved 200 CT abdominal scans, with 100 used for radiomic analysis and model training, and the remaining 100 for model testing. The ML model achieved an average classification accuracy, sensitivity, and specificity of 87%, 86%, and 88% on the testing scans respectively. Evaluating the heterogeneity of PDAC tumors across pancreatic subregions provides valuable insights into tumor composition and has the potential to enhance diagnosis and personalize treatment based on tumor characteristics and location.

Abstract 4143225: Carotid Artery Ultrasound Grayscale and Incident Dementia: The Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Vascular contributions to cognitive impairment and dementia are potentially modifiable. Early detection of reversible arterial injury may improve dementia risk stratification and provide an opportunity for treatment monitoring. We hypothesized that carotid ultrasound grayscale-median (GSM), a novel imaging biomarker of early arterial injury, would predict incident all-cause dementia in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: The MESA enrolled adults aged 45-84 years old who were free of atherosclerotic cardiovascular disease at baseline. Common carotid artery GSM (grayscale units) was measured at baseline. Incident all-cause dementia events were identified by hospital and death records. Adjusted Cox proportional hazards models with natural cubic splines allowing for non-linear effects investigated the associations of baseline GSM and incident all-cause dementia. Results: The 1,788 participants were a mean (standard deviation) 63.1 (10.3) years old (53% female). Over a median of 13.7 years, 157 all-cause dementia events occurred. Lower (worse) carotid GSM independently predicted incident all-cause dementia (Hazard Ratio [HR] 1st to 3rd tertile, 1.39 [95% Confidence Intervals, 1.08-1.80], p =0.04). In models adjusting additionally for carotid IMT there was no attenuation of the association of GSM and incident all-cause dementia (HR 1.63 [95% CI 1.13-2.35], p=0.033) (Figure 1). Conclusions: Lower GSM predicts incident all-cause dementia independent of carotid intima-media thickness, suggesting it may serve as an early marker of dementia risk.

Advancing Cancer Vaccines with Radionuclide Imaging.

Cancer vaccines are emerged as a beacon of hope in the fight against cancer. However, the lack of effective methods to directly observe their in vivo behavior and monitor therapeutic responses hinders their translation into clinical settings. Radionuclide imaging allows for non-invasive and real-time visualization of vaccine biodistribution and immunological response, offering valuable insights into the effectiveness of cancer vaccines and aiding in patient stratification. In this review, the latest advances and potential applications of radionuclide imaging in cancer vaccines are discussed, with a specific focus on strategies for visualizing the spatiotemporal distribution of vaccines in vivo and monitoring treatment efficacy. The challenges and considerations for implementing these techniques in clinical practice are also highlighted, aiming to inform and guide future research in this field.