Monitoring Treatment Response Research Articles

Effects of Positive Airway Pressure on Cardiorespiratory Fitness in Patients with Concomitant Obstructive Sleep Apnea and Cardiovascular Disease

Background and Objectives: Obstructive sleep apnea (OSA) is common in cardiovascular disease (CVD), although positive airway pressure (PAP) treatment has not been demonstrated to improve the cardiovascular outcome. The objective of this study is to investigate the impact of adherence to PAP therapy on cardiopulmonary exercise testing (CPET) performance in patients with concomitant OSA and CVD. Materials and Methods: This preliminary study involved symptomatic OSA patients requiring PAP treatment who had CVD. All subjects underwent polysomnography, echocardiography, and CPET at baseline. After 6 to 12 months of PAP treatment, CPET performance was re-assessed. The changes in CPET parameters before and after PAP treatment were compared between patients who were adherent to PAP and patients who were not adherent to PAP. Results: A total of 16 OSA patients with an apnea–hypopnea index of 32.0 ± 23.4 were enrolled. Patients were classified into the adherent (n = 9) and non-adherent (n = 7) groups with regard to PAP adherence. After 6 to 12 months of PAP treatment, the PAP-adherent group showed a greater increase in peak VO2 than the PAP-non-adherent group, but the difference between the two groups was not significant (p = 0.581). The decrease in ventilatory equivalent for the carbon dioxide slope (VE/VCO2) was significantly greater in the PAP-adherent group compared to the PAP-non-adherent group (p = 0.030). Conclusions: Adherence to PAP therapy for OSA is associated with an improvement in the VE/VCO2 slope, as an index of the ventilatory response to exercise, in patients with CVD. Screening for sleep apnea in CVD patients may be warranted, and strategies to optimize adherence to PAP in these patients are beneficial. Further evidence is needed to elucidate whether CPET could be routinely used to monitor treatment responses of OSA to PAP therapy in patients with CVD.

Reproducibility and repeatability of quantitative T2 and T2* mapping of osteosarcomas in a mouse model

BackgroundNew immunotherapies activate tumor-associated macrophages (TAMs) in the osteosarcoma microenvironment. Iron oxide nanoparticles (IONPs) are phagocytosed by TAMs and, therefore, enable TAM detection on T2*- and T2-weighted magnetic resonance images. We assessed the repeatability and reproducibility of T2*- and T2-mapping of osteosarcomas in a mouse model.MethodsFifteen BALB/c mice bearing-murine osteosarcomas underwent magnetic resonance imaging (MRI) on 3-T and 7-T scanners before and after intravenous IONP infusion, using T2*-weighted multi-gradient-echo, T2-weighted fast spin-echo, and T2-weighted multi-echo sequences. Each sequence was repeated twice. Tumor T2 and T2* relaxation times were measured twice by two independent investigators. Repeatability and reproducibility of measurements were assessed.ResultsWe found excellent agreement between duplicate acquisitions for both T2* and T2 measurements at either magnetic field strength, by the same individual (repeatability), and between individuals (reproducibility). The repeatability concordance correlation coefficient (CCC) for T2* values were 0.99 (coefficients of variation (CoV) 4.43%) for reader 1 and 0.98 (CoV 5.82%) for reader 2. The reproducibility of T2* values between the two readers was 0.99 (CoV 3.32%) for the first acquisitions and 0.99 (CoV 6.30%) for the second acquisitions. Regarding T2 values, the repeatability of CCC was similar for both readers, 0.98 (CoV 3.64% for reader 1 and 4.45% for reader 2). The CCC of the reproducibility of T2 was 0.99 (CoV 3.1%) for the first acquisition and 0.98 (CoV 4.38%) for the second acquisition.ConclusionsOur results demonstrated high repeatability and reproducibility of quantitative T2* and T2 mapping for monitoring the presence of TAMs in osteosarcomas.Relevance statementT2* and T2 measurements of osteosarcomas on IONP-enhanced MRI could allow identifying patients who may benefit from TAM-modulating immunotherapies and for monitoring treatment response. The technique described here could be also applied across a wide range of other solid tumors.Key points• Optimal integration of TAM-modulating immunotherapies with conventional chemotherapy remains poorly elucidated.• We found high repeatability of T2* and T2 measurements of osteosarcomas in a mouse model, both with and without IONPs contrast, at 3-T and 7-T MRI field strengths.• T2 and T2* mapping may be used to determine response to macrophage-modulating cancer immunotherapies.Graphical

European Society for Organ Transplantation (ESOT) Consensus Statement on the Use of Non-invasive Biomarkers for Cardiothoracic Transplant Rejection Surveillance.

While allograft rejection (AR) continues to threaten the success of cardiothoracic transplantation, lack of accurate and repeatable surveillance tools to diagnose AR is a major unmet need in the clinical management of cardiothoracic transplant recipients. Endomyocardial biopsy (EMB) and transbronchial biopsy (TBBx) have been the cornerstone of rejection monitoring since the field's incipience, but both suffer from significant limitations, including poor concordance of biopsy interpretation among pathologists. In recent years, novel molecular tools for AR monitoring have emerged and their performance characteristics have been evaluated in multiple studies. An international working group convened by ESOT has reviewed the existing literature and provides a series of recommendations to guide the use of these biomarkers in clinical practice. While acknowledging some caveats, the group recognized that Gene-expression profiling and donor-derived cell-free DNA (dd-cfDNA) may be used to rule out rejection in heart transplant recipients, but they are not recommended for cardiac allograft vasculopathy screening. Other traditional biomarkers (NT-proBNP, BNP or troponin) do not have sufficient evidence to support their use to diagnose AR. Regarding lung transplant, dd-cfDNA could be used to rule out clinical rejection and infection, but its use to monitor treatment response is not recommended.

Endocrinology application of molecular imaging: current role of PET/CT.

In recent years, nuclear medicine imaging methods have proven to be of paramount importance in a wide variety of diseases, particularly in oncology, where they are crucial for assessing the extent of disease when conventional methods fall short. Moreover, nuclear imaging modalities are able to better characterize lesions using target agents related to specific pathways (e.g. glucose metabolism, cellular proliferation, amino acid transport, lipid metabolism, specific receptor ligands). The clinical presentation of endocrine diseases encompasses a broad spectrum of sign and symptoms. Moreover, endocrine tumors show varying degrees of aggressiveness from well differentiated and indolent to highly aggressive cancers, respectively. With the application of new medicinal radio-compounds and increasingly advanced tomographic imaging technology, the utility of Positron Emission Tomography/Computed Tomography (PET/CT) in the field of endocrine diseases is expanding. This review aims to analyze and summarize the primary indications of PET/CT, providing a practical approach for clinicians. A comprehensive literature search on PubMed was conducted to provide an updated overview of the available evidence regarding the use of PET/CT in endocrinology. Within this review, we will discuss the applications of PET/CT, compare different radiopharmaceuticals and highlight the uptake mechanism, excluding neuroendocrine carcinomas from discussion. PET/CT is a valuable tool in diagnosing and managing endocrine disorders due to its capacity to furnish both functional and anatomical information, facilitate early lesion detection, guide treatment decisions, and monitor treatment response. Its non-invasive nature and precision make it an integral component of modern endocrine healthcare. This review aims to provide physicians with a clear perspective on the role of PET/CT imaging, discussing its emerging opportunities and appropriateness of use in endocrinological diseases.

PET-MRI Applications and Future Prospects in Psychiatry.

This article reviews the synergistic application of positron emission tomography-magnetic resonance imaging (PET-MRI) in neuroscience with relevance for psychiatry, particularly examining neurotransmission, epigenetics, and dynamic imaging methodologies. We begin by discussing the complementary insights that PET and MRI modalities provide into neuroreceptor systems, with a focus on dopamine, opioids, and serotonin receptors, and their implications for understanding and treating psychiatric disorders. We further highlight recent PET-MRI studies using a radioligand that enables the quantification of epigenetic enzymes, specifically histone deacetylases, in the brain in vivo. Imaging epigenetics is used to exemplify the impact the quantification of novel molecular targets may have, including new treatment approaches for psychiatric disorders. Finally, we discuss innovative designs involving functional PET using [18F]FDG (fPET-FDG), which provides detailed information regarding dynamic changes in glucose metabolism. Concurrent acquisitions of fPET-FDG and functional MRI provide a time-resolved approach to studying brain function, yielding simultaneous metabolic and hemodynamic information and thereby opening new avenues for psychiatric research. Collectively, the review underscores the potential of a multimodal PET-MRI approach to advance our understanding of brain structure and function in health and disease, which could improve clinical care based on objective neurobiological features and treatment response monitoring. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Magnetic Resonance Spectroscopy for Cervical Cancer: Review and Potential Prognostic Applications.

This review article investigates the utilization of MRS in the setting of cervical cancer. A variety of different techniques have been used in this space including single-voxel techniques such as point-resolved spectroscopy (PRESS) and stimulated echo acquisition mode spectroscopy (STEAM). Furthermore, the experimental parameters for these acquisitions including field strength, repetition times (TR), and echo times (TE) vary greatly. This study critically examines eleven MRS studies that focus on cervical cancer. Out of the eleven studies, ten studies utilized PRESS acquisition, while the remaining study used STEAM acquisition. These studies generally showed that the choline signal is altered in cervical cancer (4/11 studies), the lipid signal is generally increased in cervical cancer or the lipid distribution is changed (5/11 studies), and that diffusion-weighted imaging (DWI) can quantitatively detect lower apparent diffusion coefficient (ADC) values in cervical cancer (2/11 studies). Two studies also investigated the role of MRS for monitoring treatment response and demonstrated mixed results regarding choline signal, and one of these studies showed increased lipid signal for non-responders. There are several new MRS technologies that have yet to be implemented for cervical cancer including advanced spectroscopic imaging and artificial intelligence, and those technologies are also discussed in the article.

In vivo Metabolic Sensing of Hyperpolarized [1‐13C]Pyruvate in Mice Using a Recyclable Perfluorinated Iridium Signal Amplification by Reversible Exchange Catalyst

Real‐time visualization of metabolic processes in vivo provides crucial insights into conditions like cancer and metabolic disorders. Metabolic magnetic resonance imaging (MRI), by amplifying the signal of pyruvate molecules through hyperpolarization, enables non‐invasive monitoring of metabolic fluxes, aiding in understanding disease progression and treatment response. Signal Amplification By Reversible Exchange (SABRE) presents a simpler, cost‐effective alternative to dissolution dynamic nuclear polarization, eliminating the need for expensive equipment and complex procedures. We present the first in vivo demonstration of metabolic sensing in a human pancreatic cancer xenograft model compared to healthy mice. A novel perfluorinated Iridium SABRE catalyst in a fluorinated solvent and methanol blend facilitated this breakthrough with a 2.2‐fold increase in [1‐13C]pyruvate SABRE hyperpolarization. The perfluorinated moiety allowed easy separation of the heavy‐metal‐containing catalyst from the hyperpolarized [1‐13C]pyruvate target. The perfluorinated catalyst exhibited recyclability, maintaining SABRE‐SHEATH activity through subsequent hyperpolarization cycles with minimal activity loss after the initial two cycles. Remarkably, the catalyst retained activity for at least 10 cycles, with a 3.3‐fold decrease in hyperpolarization potency. This proof‐of‐concept study encourages wider adoption of SABRE hyperpolarized [1‐13C]pyruvate MR for studying in vivo metabolism, aiding in diagnosing stages and monitoring treatment responses in cancer and other diseases.

In vivo Metabolic Sensing of Hyperpolarized [1-13 C]Pyruvate in Mice Using a Recyclable Perfluorinated Iridium Signal Amplification by Reversible Exchange Catalyst.

Real-time visualization of metabolic processes in vivo provides crucial insights into conditions like cancer and metabolic disorders. Metabolic magnetic resonance imaging (MRI), by amplifying the signal of pyruvate molecules through hyperpolarization, enables non-invasive monitoring of metabolic fluxes, aiding in understanding disease progression and treatment response. Signal Amplification By Reversible Exchange (SABRE) presents a simpler, cost-effective alternative to dissolution dynamic nuclear polarization, eliminating the need for expensive equipment and complex procedures. We present the first in vivo demonstration of metabolic sensing in a human pancreatic cancer xenograft model compared to healthy mice. A novel perfluorinated Iridium SABRE catalyst in a fluorinated solvent and methanol blend facilitated this breakthrough with a 2.2-fold increase in [1-13C]pyruvate SABRE hyperpolarization. The perfluorinated moiety allowed easy separation of the heavy-metal-containing catalyst from the hyperpolarized [1-13C]pyruvate target. The perfluorinated catalyst exhibited recyclability, maintaining SABRE-SHEATH activity through subsequent hyperpolarization cycles with minimal activity loss after the initial two cycles. Remarkably, the catalyst retained activity for at least 10 cycles, with a 3.3-fold decrease in hyperpolarization potency. This proof-of-concept study encourages wider adoption of SABRE hyperpolarized [1-13C]pyruvate MR for studying in vivo metabolism, aiding in diagnosing stages and monitoring treatment responses in cancer and other diseases.

Associations of ctDNA clearance and pathological response after neoadjuvant treatment in patients with locally advanced oral cancer.

6043 Background: Neoadjuvant treatment (NAT) has improved clinical outcomes in some patients with locally advanced oral squamous cell carcinoma (LAOSCC). Effective biomarkers assessing the treatment response is still lacking. Previous studies have posed the potential of circulating tumor DNA (ctDNA) in monitoring treatment response, but the underlying mechanisms behind non-shedding in tumors remain unclear. Methods: 29 LAOSCC patients received NAT followed by surgery were enrolled. Seven (24.1%), 9 (31%), and 13 (44.8%) patients received NAT of apatinib+camrelizumab, TPF chemoagents, and toripalimab+paclitaxel+cisplatin, respectively. Tumor tissues before NAT underwent whole exome sequencing and whole transcriptome resequencing. Blood samples at pre-NAT (T0), mid-NAT (T1), before surgery (T2) and after surgery (T3) were analyzed using a tumor-informed, personalized NGS assay. Multi-omics analysis, including ctDNA status, was performed with patients' clinical features and outcomes. Results: Among the 29 patients received NAT, the MPR rate was 55.2% (16/29), and the pCR rate was 27.6% (8/29). At baseline(T0), ctDNA was detectable in 25/29 (86.2%) patients, which decreased over time (T1: 77.8%; T2: 51.7%; T3: 6.9%). Persistent ctDNA at T2 indicates a higher rate of residual disease after NAT (100% non-pCR) compared to ctDNA-negative patients (42.8% non-pCR; p = 0.0047). All patients achieving pCR at T2 were ctDNA-negative (n=8, 100%) including 2 non-shedders. The PPV and NPV for predicting pCR by ctDNA clearance at T2 were 57.1% (8/14) and 100% (15/15), respectively. ARSF, CFAP47, or HAUS8 mutations at baseline were associated with significantly higher pCR rates (p<0.05). Four non-shedders with undetectable ctDNA at T0 were significantly enriched in patients with negative lymph nodes, lower clinical T stage, and high CPS score. The non-shedders had significantly lower tumor mutational burden (TMB), higher stromal score and cancer-associated fibroblast (CAF) (p<0.05). Spatial transcriptome analysis further supports that MHC-II pathway-related genes were significantly up-regulated in the non-shedders. The enhancing communication intensity between CAFs, endothelial cells and T cells might provide an anti-cancer immune microenvironment for non-shedders. Conclusions: Our results indicate that the clearance of ctDNA clearance at T2 was associated with an improved pCR rate. Furthermore, our findings shed light on the factors that prevent ctDNA release from oral squamous cell carcinoma.[Table: see text]

Cost-effectiveness of a circulating tumor fraction molecular biomarker for treatment response monitoring.

11082 Background: Clinical validation studies have demonstrated that molecular biomarkers quantifying ctDNA changes in circulating tumor fraction (TF) predict survival outcomes and may be used for treatment response monitoring (TRM). While clinical utility studies to determine the impact on outcomes of molecular biomarker-driven treatment decisions versus standard of care imaging are ongoing, cost-effectiveness has not been evaluated. Here we evaluate the cost-effectiveness of a molecular biomarker, Tempus xM, used for TRM. Methods: xM quantifies changes in TF from baseline and on-treatment liquid biopsies. We use a patient-level Markov simulation to compare xM-guided treatment (intervention) to diagnostic imaging-guided treatment (control) over 24 weeks of therapy. In both arms xM and imaging is assessed at 12 weeks and treatment decisions are made based on xM (intervention) or diagnostic imaging (control). Imaging and xM concordance (Table) was based on a retrospective, real-world (RW) study of 51 patients tested with xM that received rw-imaging that evaluated the association of xM with rw-outcomes in advanced pan-cancer patients treated with immune checkpoint inhibitors (ICIs) +/- chemotherapy (CT). We assume non-responders discontinue ICIs and switch to CT and responders remain on ICIs. Appropriate (inappropriate) therapy was defined as treatment decisions concordant (discordant) with xM results. Costs were calculated from Medicare’s perspective in 2023 USD. Control patients do not accrue the cost of xM. Sensitivity analyses were conducted. Results: Intervention patients saved $4,400 ($63,424 vs. $67,824 in controls) by preventing use of ineffective therapy (4.3 weeks avoided vs 0.2 weeks in controls), a savings of $1076 per week of ineffective therapy avoided. In all sensitivity analyses, xM-guided therapy remained cost effective (Table). The timing of therapy intervention and the cost of therapy had the largest impact on savings. Conclusions: This model demonstrates that xM-guided treatment is cost-saving compared to imaging alone during 24 weeks of treatment. Future work will incorporate variable clinical uptake and long-term outcomes by expanding the time horizon and including treatment discontinuation due to toxicities and mortality. [Table: see text]

Circulating tumor DNA as a predictor of treatment response to neoadjuvant chemotherapy in stage 2/3 rectal cancer without high risks: Subset analysis from the COPEC trial.

e15623 Background: Circulating tumor DNA (ctDNA) serves as a valuable tool for minimal residual disease (MRD) assessment. It has been reported as a promising noninvasive biomarker for the dynamic monitoring of treatment response of metastatic colorectal cancers to chemotherapy and locally advanced rectal cancers (LARC) to neoadjuvant chemoradiotherapy. However, the potential role of ctDNA in neoadjuvant chemotherapy (NCT) in LARC remains unexplored. The present study aims to investigate the value of ctDNA in NCT based on a prospective, multicentered, non-inferior, randomized, controlled trial (ClinicalTrials.gov ID, NCT04922853). The COPEC trial enrolls stage 2/3 LARC with low or intermediate and is designed to determine the optimal time (after 2 or 4 cycles of CAPOX) to evaluate treatment response based on pathological regression grades. Methods: Colonoscopy biopsy was taken before neoadjuvant therapy. Peripheral blood samples were collected before neoadjuvant (baseline, BL), one cycle (C1) and two cycles (4-cycle group, C2) after NCT, before surgery (BS), and within one month after surgery (postoperative, OP). All tissue biopsy and plasma specimens were analyzed by NGS assays using the MinerVA platform (Genecast Biotechnology Co., Ltd). MRI tumor regression grade (mrTRG) was assessed after 2 and 4 cycles (4-cycle group) of NCT. The primary outcome was the accuracy of ctDNA in the prediction of pathological tumor regression grade (pTRG). Results: A total of 151 LARC patients were enrolled, including 82 in the 2-cycle group and 69 in the 4-cycle group. The ctDNA was detectable in 87.4% (132/151), 39.6% (55/139), 29.0% (18/62), 38.4% (58/151), and 4.4% (6/138) at BL, C1, C2, BS and OP, respectively. The ctDNApositivity rates were significantly lower in good responders determined by mrTRG (mrTRG 1-3) compared to mrTRG 4-5 group at C1 (29% vs. 63.89%, p < 0.001), C2 (20% vs.56.25%, p = 0.011), and BS time points (23.85% vs. 74.36%, p < 0.001). Furthermore, the ctDNA-positivity rates at C1 in the good response group determined by TRG (pTRG 0-1) were 6.25%, significantly lower than that in the pTRG 2-3 group (49.53%). At neither C2 nor BS time point, patients in the pTRG 0-1 subgroup were detected as ctDNA positive while the ctDNA positivity rates for patients in pTRG 2-3 subgroup were 39.13% and 50%, respectively. Additionally, the mean of hGE/ml was 0.045 in pTRG 0-1 group at C1, significantly lower comparing to 1.337 in pTRG 2-3 group (p < 0.001). Conclusions: We find that dynamic monitoring of ctDNA status was a useful tool in early predicting the effect of (treatment response to) NCT in LARC patients with low/intermediate risks. The monitoring of ctDNA status can supplement MRI in determining the NCT response and could potentially help identify poor responders to discontinue the treatment with inadequate efficacy. Clinical trial information: NCT04922853 .

Circulating tumor DNA (ctDNA) to predict response to neoadjuvant chemotherapy (NAC) and prognosis in patients (pts) with early breast cancer (BC).

e12642 Background: pCR to NAC is an important predictor of clinical recurrence. Up to 16% of patients with pCR may experience disease recurrence, 45% of patients with RD do not. Longitudinal ctDNA testing offers a minimally invasive approach for monitoring treatment response EBC patients receiving NAC. We evaluated whether ctDNA status and dynamics can predict the tumor response to NAC and the risk of recurrence in patients with EBC. Methods: We conducted an observational, retrospective, single-center study to investigate whether ctDNA can predict tumor response to NAC and prognosis in BC patients. 74 pts received standard of care NAC;g 4 patients were treated in the adjuvant setting. Blood samples were collected at diagnosis from 44 pts (baseline) and longitudinally during treatment from 34 patients. Tumor response and progression outcomes were reported. A clinically validated, tumor-informed ctDNA assay (Signatera). ctDNA status and dynamics were correlated with pathologic and radiologic outcomes. Results: 29 TNBC pts were ctDNA+ at baseline, 6 were ctDNA- Of the 29 pts, early ctDNA clearance by week 6 of NAC was observed in 10 pts, weeks 7-16 in 9 pts, clearance post-surgery in 1, 3 pts remained ctDNA+ after surgery, serial ctDNA testing is underway for the remaining 6 pts. All TNBC patients who had radiological complete response (CR) had early clearance of ctDNA . All pts with persistent ctDNA positivity levels after completion of NAC had radiological partial response (PR). Of the 9 TNBC pts with undetectable baseline ctDNA, 33% achieved CR on MRI and 43% achieved pathologic CR. Of the 19 TNBC pts with ctDNA clearance in response to NAC, 89% (17/19) remained ctDNA- and with no evidence of disease (NED) (length of follow up). 1 pt initially cleared their ctDNA on NAC, turned ctDNA+ 4 weeks prior to radiological recurrence. 1 pt with ctDNA clearance on NAC remained ctDNA post-surgery but experienced recurrence. All (n=3) TNBC pts with persistent ctDNA-positivity levels after curative treatment (NAC and surgery) had disease recurrence. The remaining 6 pts ctDNA are ongoing NAC. Of the 6 pts with undetectable baseline ctDNA, 6/6 continued to be ctDNA- regardless of their disease status. At diagnosis, 8/9 ER+ ps were ctDNA+. 3/8 (38%) ER+ pts with positive baseline ctDNA had early clearance of ctDNA after NAC. All 3 had residual disease on pathology. 2/8 (25%) remained ctDNA+ after surgery and neither achieved radiologic CR or pCR. The remaining 3 pts are ongoing NAC. Conclusions: In early TNBC, ctDNA monitoring can be used to predict tumor response to NAC and tailor therapeutic regimens. ctDNA persistence can predict early recurrence and helps identify patients in which treatment escalation or enrollment on clinical trials is necessary. In ER positive breast cancer, and despite the small number of patients, ctDNA clearance does not predict response to NAC.

Asymmetric Dimethylarginine and NT-proBNP Levels Provide SynergisticInformation in PulmonaryArterial Hypertension.

Plasma asymmetric dimethylarginine (ADMA) is elevated in pulmonary arterial hypertension (PAH) and is associated with unfavorable outcomes. The aim of this study was to assess changes in ADMA plasma levels for monitoring disease progression and outcomes during PAH-specific therapy. ADMA was measured at baseline and after at least 6months of follow-up using enzyme-linked immunosorbent assay and high-performance liquid chromatography. Changes in ADMA were analyzed in relation to changes in established PAH markers, including hemodynamic status, N-terminal pro-brain natriuretic peptide (NT-proBNP) and risk assessment scores. Impact on survival was assessed using Kaplan-Meier curves and Cox proportional hazards models. Between 2008 and 2019, ADMA samples were collected prospectively from 215 patients with PAH. Change in ADMA plasma level was a predictor of disease progression and survival. ΔADMA (median-0.03μmol/L; 95%CI:-0.145 to 0.0135) was correlated with change in mean pulmonary arterial pressure (P< 0.005; rS=0.287) but was not significantly correlated with ΔNT-proBNP (P=0.056; rS=0.135). Patients with decreased ADMA plasma levels at follow-up had better 3-year and 5-year survival rates (88% and 80%, respectively, vs 72% and 53% in those without decreases in ADMA) (P< 0.005; pulmonary hypertension-related mortality or lung transplantation). Patients with decreases in both ADMA and NT-proBNP had better survival rates compared with patients in whom only 1 parameter improved (P< 0.005). ΔADMA was a significant predictor of survival in Cox regression analysis and also when corrected for ΔNT-proBNP (HRs: 1.27 and 1.35, respectively; P< 0.005). ADMA and NT-proBNP provide synergistic prognostic information for patients with PAH. ADMA could be used as an objective and distinct biomarker for monitoring treatment response in PAH.

Applications of Artificial Intelligence for Pediatric Cancer Imaging.

Artificial intelligence (AI) is transforming medical imaging of adult patients. However, its utilization in pediatric oncology imaging remains constrained, in part due to the inherent data scarcity associated with childhood cancers. Pediatric cancers are rare, and imaging technologies are evolving rapidly, leading to insufficient data of a particular type to effectively train these algorithms. The small market size of pediatrics compared to adults could also contribute to this challenge, as market size is a driver of commercialization. This article provides an overview of the current state of AI applications for pediatric cancer imaging, including applications for medical image acquisition, processing, reconstruction, segmentation, diagnosis, staging, and treatment response monitoring. While current developments are promising, impediments due to diverse anatomies of growing children and nonstandardized imaging protocols have led to limited clinical translation thus far. Opportunities include leveraging reconstruction algorithms to achieve accelerated low-dose imaging and automating the generation of metric-based staging and treatment monitoring scores. Transfer-learning of adult-based AI models to pediatric cancers, multi-institutional data sharing, and ethical data privacy practices for pediatric patients with rare cancers will be keys to unlocking AI's full potential for clinical translation and improved outcomes for these young patients.

A prospective observational role of magnetic resonance imaging and magnetic resonance spectroscopy in evaluation of choline levels in gall bladder carcinoma in tertiary care hospital in central India

Background Gall bladder carcinoma (GBC) is a challenging malignancy characterized by late-stage diagnosis and poor prognosis. Early detection and accurate staging are crucial for improving patient outcomes. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) offer non-invasive imaging modalities that may aid in the evaluation of GBC. Choline, a metabolite detected by MRS, has been implicated in tumor growth and may serve as a potential biomarker for GBC. This study aims to investigate the role of MRI and MRS in evaluating choline levels as biomarkers for GBC. Method A prospective observational study will be conducted involving patients with suspected or confirmed GBC referred to the Department of Radiology, AVBRH, Sawangi. Patients meeting inclusion criteria will undergo MRI scans and MRS examinations to assess tumor characteristics and choline levels. Data collected will include MRI images, MRS spectra, histopathological results, and clinical outcomes. Statistical analysis will be performed to examine correlations between MRI findings, choline levels, and histopathological characteristics. Expected Outcome It is anticipated that MRI and MRS will demonstrate utility in evaluating choline levels as imaging biomarkers for GBC. Correlations between choline levels, tumor characteristics, and clinical outcomes are expected to provide valuable insights into the role of choline in GBC pathogenesis and prognosis. If successful, MRI and MRS could serve as non-invasive tools for early detection, staging, and treatment response monitoring in GBC, ultimately leading to improved patient outcomes and management strategies.

Progress of circulating tumor DNA methylation for gastric cancer screening and management

Circulating tumor DNA (ctDNA) is cell-free DNA released by tumors or circulating tumor cells, containing abundant tumor-specific information that can serve as biomarkers for cancer early screening, monitoring, prognosis, and prediction of treatment response. This is particularly attractive in the field of gastric cancer, where high-quality screening, monitoring, and prediction methods are currently lacking. Gastric cancer exhibits significant tumor heterogeneity, with large differences in genetic and epigenetic characteristics among different subgroups. Methylated ctDNA has high sensitivity and specificity, which can help clarify tumor genotyping and facilitate the formulation of precise diagnostic and therapeutic strategies. Furthermore, numerous studies have confirmed the unique advantages of methylated DNA in predicting treatment response, adjuvant therapy, and drug resistance assessment, which may be used in the future to enhance the efficacy of chemotherapy regimens and improve patient chemotherapeutic response, and even treat multidrug resistance. However, there are several challenges associated with methylated ctDNA, such as low sensitivity and specificity at single-target sites, limited association between some gastric cancer subtypes and ctDNA, off-target risks, and the lack of large-scale and high-quality clinical research evidence. This review mainly summarizes current research on the methylation status of ctDNA in gastric cancer and connects these findings to early screening, recurrence monitoring, and potential treatment opportunities for gastric cancer. With advances in technology and the deepening of interdisciplinary research, ctDNA detection will reveal more disease information and become an essential foundation for gastric cancer research and precision medicine treatment.

Comparison of Outcome of Concurrent Chemoradiotherapy and Sequential Chemoradiotherapy in Locally Advanced, Inoperable Squamous Cell Carcinoma of Head and Neck Region

Background: Head and neck cancer is prevalent in Bangladesh, with a majority of patients presenting with locally advanced, inoperable disease. This study aimed to compare the effectiveness and accessibility of concurrent and sequential (CCRT with RT) chemoradiotherapy in treating this condition, addressing a debate among oncologists. Materials and Methods: A quasi-experimental study at Rajshahi Medical College Hospital (June 2019 - May 2020) involved 60 inoperable head and neck cancer patients, comparing concurrent chemoradiotherapy with Cisplatin and sequential chemoradiotherapy with Paclitaxel and Cisplatin, monitoring treatment response and toxicities. Results: The mean age was 56.1 (±9.5) years in Arm-A and 56.9 (±9.4) years in Arm-B. The primary endpoint was loco-regional control and early toxicities. In the final response, 14 weeks after the completion of treatment, the overall loco-regional control rate was 86.67% and 76.67% in Arm-A and Arm-B, respectively. Severe toxicities include grade 3 reaction only and happened 18(58%) vs 13(42%) in Arm-A and Arm-B, respectively. Among severe toxicities, mucositis and skin reaction were higher in the concurrent Arm and anemia and neutropenia were higher in the sequential Arm. However, there was no actual difference in the two treatment modalities (p=&gt;0.05). The overall treatment time was short in concurrent chemoradiotherapy (49 vs 133 days) and lower treatment cost as well, which was statistically significant (p=&lt;0.0001). Conclusion: concurrent chemoradiotherapy proves cost-effective and accessible, demonstrating outcomes similar to sequential chemoradiotherapy. It stands as a viable treatment choice for locally advanced, inoperable head and neck squamous cell carcinoma.

Levels of circulating tumor DNA correlate with tumor volume in gastro-intestinal stromal tumors: an exploratory long-term follow-up study.

Patients with gastro-intestinal stromal tumors (GISTs) undergoing tyrosine kinase inhibitor therapy are monitored with regular computed tomography (CT) scans, exposing patients to cumulative radiation. This exploratory study aimed to evaluate circulating tumor DNA (ctDNA) testing to monitor treatment response and compare changes in ctDNA levels with RECIST 1.1 and total tumor volume measurements. Between 2014 and 2021, six patients with KIT proto-oncogene, receptor tyrosine kinase (KIT) exon-11-mutated GIST from whom long-term plasma samples were collected prospectively were included in the study. ctDNA levels of relevant plasma samples were determined using the KIT exon 11 digital droplet PCR drop-off assay. Tumor volume measurements were performed using a semi-automated approach. In total, 94 of 130 clinically relevant ctDNA samples were analyzed. Upon successful treatment response, ctDNA became undetectable in all patients. At progressive disease, ctDNA was detectable in five out of six patients. Higher levels of ctDNA correlated with larger tumor volumes. Undetectable ctDNA at the time of progressive disease on imaging was consistent with lower tumor volumes compared to those with detectable ctDNA. In summary, ctDNA levels seem to correlate with total tumor volume at the time of progressive disease. Our exploratory study shows promise for including ctDNA testing in treatment follow-up.

A blood-based 3-gene signature score for therapeutic monitoring in patients with pulmonary tuberculosis

ObjectiveTo assess the validity of Xpert Tuberculosis Fingerstick score for monitoring treatment response and analyze factors influencing its performance. Methods122 adults with pulmonary tuberculosis were recruited and stratified into three cohorts: Diabetic-drug-susceptible-TB (DM-TB), Non-diabetic-drug-susceptible-TB (NDM-TB) and Non-diabetic Multidrug-resistant TB (MDR-TB). Fingerstick blood specimens were tested at treatment initiation (M0) and the end of the first (M1), second (M2), and sixth month (M6) to generate a TB-score. ResultsThe TB-score in all participants yielded an AUC of 0.707 (95% CI: 0.579–0.834) at M2 when its performance was evaluated against sputum culture conversion. In all non-diabetes patients, the AUC reached 0.88 (95% CI: 0.756–1.000) with an optimal cut-off value of 1.95 at which sensitivity was 90.0% (95% CI: 59.6–98.2%) and specificity was 81.3% (95% CI: 70.0–88.9%). The mean TB score was higher in patients with low bacterial loads (n = 31) than those with high bacterial loads (n = 91) at M0, M1, M2, and M6, and was higher in non-cavitary patients (n = 71) than those with cavitary lesions (n = 51) at M0, M1, and M2. ConclusionXpert TB-score shows promising predictive value for culture conversion in non-diabetic TB patients. Sputum bacterial load and lung cavitation status have an influence on the value of TB score.

A look inside the gut as a clue to nutritional status.

Malabsorption and malnutrition are common gastrointestinal manifestations clinicians face, requiring diagnostic workup for effective diagnosis and management of the underlying cause. This review discusses recent advances in diagnostic approaches to malabsorption and maldigestion of macronutrients - lipids, proteins, and carbohydrates. We highlight underrecognized causes, available testing modalities, and ongoing diagnostic unmet needs. Innovations in the diagnostic landscape are enhancing our understanding of malabsorption syndromes. Stool collection and handling is uncomfortable and commonly avoided. The objective quantification of stool lipids, bile acids, and gut enzymes is therefore underused in the diagnosis and management of common disorders such as exocrine pancreatic insufficiency, bile acid diarrhea, protein-losing enteropathy, and more. We review the recent advancements in spot quantification of stool fat and bile acid content, endoscopic imaging techniques such as endocytoscopy, confocal laser endomicroscopy, and optical coherence tomography and the future place in clinical practice. Malabsorption and maldigestion represent significant challenges in clinical nutrition and gastroenterology. Through the integration of advanced diagnostic techniques, clinicians will be better equipped to tailor therapy and monitor treatment response, ultimately improving patient health outcomes. This review underscores the critical role of innovative diagnostic tools in accurately detecting and effectively managing gastrointestinal disorders linked to nutritional status.