Detection Of Relapse Research Articles

The accuracy of whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the detection of ovarian cancer relapse in patients with rising cancer antigen 125 (CA-125) levels

Background18F-fluorodeoxyglucose (FDG) PET/CT is a noninvasive imaging tool that has been used successfully for the diagnosis, staging, restaging, therapy monitoring, and prognostic prediction of ovarian cancer. For ovarian cancer surveillance, rising CA-125 levels raise the suspicion of recurrence despite its reported low specificity; being elevated in other benign and inflammatory conditions, and thus, confirmation is required. This work aimed to evaluate the role of 18F-FDG PET/CT in suspected ovarian cancer recurrence in patients presenting with elevated CA-125 levels.ResultsFifty female patients with suspected ovarian cancer recurrence owing to elevated CA-125 levels were included in this study. Recurrence was confirmed in 46/50 cases whether by histopathological confirmation or by serial follow-up imaging and clinical follow-up. Positive PET/CT findings were reported in 45/50 cases with 2 false-negative cases and 1 false-positive case. PET/CT examination was found to be superior to contrast-enhanced CT in the detection of peritoneal metastatic nodules and metastatic lymph nodes. According to this study, the estimated sensitivity, specificity, and overall diagnostic accuracy of PET/CT in the detection of recurrent ovarian cancer were 95.6%, 75%, and 94%, respectively.ConclusionsIn ovarian cancer surveillance, 18F-FDG PET/CT was found to be a sensitive and accurate noninvasive imaging tool that can be used in the detection of recurrent ovarian cancer in patients with elevated CA-125 levels, thus interfering with the management plan. The advantage of whole-body imaging in PET/CT allows for the detection and precise localization of recurrent or metastatic foci in abdominal and extra-abdominal sites as well.

Assessment of treatment outcomes of visceral leishmaniasis (VL) treated cases and impact of COVID-19 on VL management and control services in Bangladesh

BackgroundCOVID-19 has largely impacted the management of Visceral leishmaniasis (VL), like several other Neglected Tropical Diseases. The impact was particularly evident in Lower and Middle-Income countries where the already inadequate healthcare resources were diverted to managing the COVID-19 pandemic. Bangladesh achieved the elimination target for VL in 2016. To sustain this success, early diagnosis and treatment, effective vector control, and periodic surveillance are paramount. However, the specific control measures for VL in Bangladesh that were hampered during COVID-19 and their extent are unknown. MethodsThis study aimed at identifying the gaps and challenges in the follow-up of treated VL patients by interviewing both the treated VL cases and their health service providers. We followed VL cases treated between 2019 and 2020 in five VL endemic subdistricts (upazilas) both retrospectively and prospectively to monitor clinical improvement, relapse, or other consequences. Moreover, interviews were conducted with the health service providers to assess the impact of COVID-19 on VL case detection, treatment, reporting, vector control operations, and logistic supply chain management. ResultsThere was no added delay for VL diagnosis; however, VL treatment initiation and reporting time increased almost two-fold due to COVID-19. Indoor Residual Spraying activity was significantly hampered due to a shortage of insecticides. Out of 44 enrolled and treated VL patients, two relapsed (4.5 %), two developed Para Kala-Azar Dermal Leishmaniasis (4.5 %), and three (6.8 %) Post Kala-Azar Dermal Leishmaniasis (PKDL). The health service providers highlighted patients` unwillingness to visit the hospital, financial constraints, and distance from the hospitals as the main reasons for missed follow-up visits (20.5 %). Building good communication in the community, awareness schemes, and incentive-based approaches were suggested as possible solutions to mitigate these problems. ConclusionLong-term follow-up is required for the early detection and management of VL relapse and PKDL cases. Effective vector control measures, capacity development, and identification of new VL hotspots are pivotal in the VL endemic regions to sustain the elimination goal.

Detection of recurrent high-grade glioma using microstructure characteristics of distinct metabolic compartments in a multimodal and integrative 18F-FET PET/fast-DKI approach

ObjectivesDifferentiation between high-grade glioma (HGG) and post-treatment-related effects (PTRE) is challenging, but advanced imaging techniques were shown to provide benefit. We aim to investigate microstructure characteristics of metabolic compartments identified from amino acid PET and to evaluate the diagnostic potential of this multimodal and integrative O-(2-18F-fluoroethyl)-l-tyrosine-(FET)-PET and fast diffusion kurtosis imaging (DKI) approach for the detection of recurrence and IDH genotyping.MethodsFifty-nine participants with neuropathologically confirmed recurrent HGG (n = 39) or PTRE (n = 20) were investigated using static 18F-FET PET and a fast-DKI variant. PET and advanced diffusion metrics of metabolically defined (80–100% and 60–75% areas of 18F-FET uptake) compartments were assessed. Comparative analysis was performed using Mann–Whitney U tests with Holm-Šídák multiple-comparison test and Wilcoxon signed-rank test. Receiver operating characteristic (ROC) curves, regression, and Spearman’s correlation analysis were used for statistical evaluations.ResultsCompared to PTRE, recurrent HGG presented increased 18F-FET uptake and diffusivity (MD60), but lower (relative) mean kurtosis tensor (rMKT60) and fractional anisotropy (FA60) (respectively p < .05). Diffusion metrics determined from the metabolic periphery showed improved diagnostic performance — most pronounced for FA60 (AUC = 0.86, p < .001), which presented similar benefit to 18F-FET PET (AUC = 0.86, p < .001) and was negatively correlated with amino acid uptake (rs = − 0.46, p < .001). When PET and DKI metrics were evaluated in a multimodal biparametric approach, TBRmax + FA60 showed highest diagnostic accuracy (AUC = 0.93, p < .001), which improved the detection of relapse compared to PET alone (difference in AUC = 0.069, p = .04). FA60 and MD60 distinguished the IDH genotype in the post-treatment setting.ConclusionDetection of glioma recurrence benefits from a multimodal and integrative PET/DKI approach, which presented significant diagnostic advantage to the assessment based on PET alone.Clinical relevance statementA multimodal and integrative 18F-FET PET/fast-DKI approach for the non-invasive microstructural characterization of metabolic compartments provided improved diagnostic capability for differentiation between recurrent glioma and post-treatment-related changes, suggesting a role for the diagnostic workup of patients in post-treatment settings.Key Points• Multimodal PET/MRI with integrative analysis of 18F-FET PET and fast-DKI presents clinical benefit for the assessment of CNS cancer, particularly for the detection of recurrent high-grade glioma.• Microstructure markers of the metabolic periphery yielded biologically pertinent estimates characterising the tumour microenvironment, and, thereby, presented improved diagnostic accuracy with similar accuracy to amino acid PET.• Combined 18F-FET PET/fast-DKI achieved the best diagnostic performance for detection of high-grade glioma relapse with significant benefit to the assessment based on PET alone.

An Overview of Circulating Biomarkers in Neuroendocrine Neoplasms: A Clinical Guide.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of diseases that are characterized by different behavior and clinical manifestations. The diagnosis and management of this group of tumors are challenging due to tumor complexity and lack of precise and widely validated biomarkers. Indeed, the current circulating mono-analyte biomarkers (such as chromogranin A) are ineffective in describing such complex tumors due to their poor sensitivity and specificity. In contrast, multi-analytical circulating biomarkers (including NETest) are emerging as more effective tools to determine the real-time profile of the disease, both in terms of accurate diagnosis and effective treatment. In this review, we will analyze the capabilities and limitations of different circulating biomarkers focusing on three relevant questions: (1) accurate and early diagnosis; (2) monitoring of disease progression and response to therapy; and (3) detection of early relapse.

Whole Blood and Plasma-Based Lipid Profiling Reveals Distinctive Metabolic Changes in Systemic Lupus Erythematosus and Systemic Sclerosis.

Autoimmune diseases (AID), such as systemic lupus erythematosus (SLE) and systemic sclerosis (SS), are complex conditions involving immune system dysregulation. Diagnosis is challenging, requiring biomarkers for improved detection and prediction of relapses. Lipids have emerged as potential biomarkers due to their role in inflammation and immune response. This study uses an untargeted C18 RP-LC-MS lipidomics approach to comprehensively assess changes in lipid profiles in patients with SLE and SS. By analyzing whole blood and plasma, the study aims to simplify the lipidomic analysis, explore cellular-level lipids, and compare lipid signatures of SLE and SS with healthy controls. Our findings showed variations in the lipid profile of SLE and SS. Sphingomyelin and ceramide molecular species showed significant increases in plasma samples from SS patients, suggesting an atherosclerotic profile and potentially serving as lipid biomarkers. Phosphatidylserine species in whole blood from SLE patients exhibited elevated levels supporting previously reported dysregulated processes of cell death and defective clearance of dying cells in this AID. Moreover, decreased phospholipids bearing PUFA were observed, potentially attributed to the degradation of these species through lipid peroxidation processes. Further studies are needed to better understand the role of lipids in the pathological mechanisms underlying SLE and SS.

Circulating H3K27 Methylated Nucleosome Plasma Concentration: Synergistic Information with Circulating Tumor DNA Molecular Profiling.

The molecular profiling of circulating tumor DNA (ctDNA) is a helpful tool not only in cancer treatment, but also in the early detection of relapse. However, the clinical interpretation of a ctDNA negative result remains challenging. The characterization of circulating nucleosomes (carrying cell-free DNA) and associated epigenetic modifications (playing a key role in the tumorigenesis of different cancers) may provide useful information for patient management, by supporting the contributive value of ctDNA molecular profiling. Significantly elevated concentrations of H3K27Me3 nucleosomes were found in plasmas at the diagnosis, and during the follow-up, of NSCLC patients, compared to healthy donors (p-value < 0.0001). By combining the H3K27Me3 level and the ctDNA molecular profile, we found that 25.5% of the patients had H3K27Me3 levels above the cut off, and no somatic alteration was detected at diagnosis. This strongly supports the presence of non-mutated ctDNA in the corresponding plasma. During the patient follow-up, a high H3K27Me3-nucleosome level was found in 15.1% of the sample, despite no somatic mutations being detected, allowing the identification of disease progression from 43.1% to 58.2% over molecular profiling alone. Measuring H3K27Me3-nucleosome levels in combination with ctDNA molecular profiling may improve confidence in the negative molecular result for cfDNA in lung cancer at diagnosis, and may also be a promising biomarker for molecular residual disease (MRD) monitoring, during and/or after treatment.

Screening of Proteinuria by Urinary Specific Gravity in Nephrotic Syndrome

Background: Nephrotic syndrome is the commonest glomerular disease in children and is often characterized by multiple relapses. Twenty-four hours urinary protein estimation is the accepted method used in the quantification of proteinuria, but it’s a time-consuming, inconvenient and cumbersome and difficult in very young children. This study emphasized screening of proteinuria by urinary specific gravity in nephrotic syndrome. Material &amp; Methods: This cross-sectional study was conducted in the Department of Pediatric Nephrology (NIKDU), Dhaka, Bangladesh from October 2019 to June 2021. A total of 153 patients with nephrotic syndrome were enrolled as the study subjects after taking written consent. Urine samples were collected for both 24 hours and spot for estimation of urinary protein, urinary creatinine (Ucr) and specific gravity by dipstick method. Spot and 24-hour urinary protein creatinine ratio (PCR) were also estimated. From urinary specific gravity, estimated urinary creatinine (estUcr) and estimated urinary protein creatinine ratio (est PCR) were measured. A descriptive method was used and data were processed by using SPSS version 22.0. Results: Among 153 study subjects, the maximum (44.4%) were from the 2-5 years age group followed by 58 (37.9%) from 5-10 years and 27 (17.6%) from &gt;10 years age groups. Boys (61.4%) were more predominant than girls (38.6%) in number. Spot and 24-hour urinary specific gravity have a significant positive correlation with urinary creatinine. Urinary creatinine was estimated by using the equation (Ucr = 1.25×1000 Usg – 1.24×1000). Both spot and 24-hour estimated urinary PCR (est PCR) measured by using urinary specific gravity have a significant positive correlation with corresponding urinary PCR. Conclusion: This study concluded that spot urinary specific gravity has a significant positive correlation with spot urinary protein and spot urinary creatinine. PCR can be estimated from dipstick urinary specific gravity instead of urinary creatinine in the cumbersome laboratory. Therefore, the study may establish an easy, rapid, inexpensive and alternative method for the detection of proteinuria in nephrotic syndrome so that it will help for early detection of relapse and prevent further complications related to nephrotic syndrome.

Presence of Circulating Tumor Cells Predates Imaging Detection of Relapse in Patients with Stage III Melanoma.

Stage III melanoma includes nodal metastasis or in-transit disease. Five-year survival rates vary between 32% and 93%. The identification of high-risk patients is important for clinical decision making. We demonstrated previously that ≥1 circulating tumor cells (CTCs) at baseline was associated with recurrence. In this study, we investigated how frequently CTCs were identified prior to radiologically detected recurrence. Stage III patients (n = 325) had imaging at baseline and q 3 months. Baseline and q 6-12 months blood draws (7.5 mL) were performed to identify CTCs up to 3.5 years from diagnosis. CTC assessment was performed using the immunomagnetic capture of CD146-positive cells and anti-MEL-PE. The presence of one or more CTCs was considered positive. We analyzed the cohort of patients with relapse confirmed by radiologic imaging. CTC collection dates were assessed to determine the lead time for CTC detection. CTC-negative patients were significantly less likely to relapse compared to patients positive for CTCs (p-value < 0.001). Within the 325-patient cohort, 143 patients (44%) had recurrence, with a median follow-up of 52 months from diagnosis. The cohort (n = 143) with positive imaging and CTC results revealed 76% of patients (108/143) had CTC+ results before the radiological identification of relapse. The median time between positive CTC and positive imaging was 9 months. CTCs were positive in >75% of patients prior to relapse at a median of 9 months before radiologic detection.

Intracranial Relapse in Pediatric Sarcoma.

Advances in local control techniques, chemotherapy regimens, and imaging modalities have led to improvements in both morbidity and mortality in pediatric sarcoma patients. However, approximately one-third of patients develop disease relapse and intracranial metastasis was considered rare. The incidence of sarcoma brain metastasis is thought to have increased and is associated with grim outcomes. This was a retrospective study of 3 deidentified patient charts illustrating the possibility of the central nervous system as a potential site for pediatric sarcoma relapse and investigate the patterns of such relapses. We note this is the first report of infantile fibrosarcoma brain metastasis and a rare report of sarcoma lymph node metastasis. In addition, each patient was treated with targeted therapies, including entrectinib, Ruxolitnib, and pazopanib. Caregivers in cases 2 and 3 reported new-onset neurological manifestations before identification of new brain metastasis, indicating a lag in detection of new intracranial relapse in asymptomatic sarcoma patients. We suggest implementing a brief review of systems screening tool focused on concerning neurological manifestations to screen for new brain metastasis.

Children's Oncology Group's 2023 blueprint for research: Germ cell tumors.

Extracranial germ cell tumors (GCT) are a biologically diverse group of tumors occurring in children, adolescents, and young adults. The majority of patients have excellent outcomes, but treatment-related toxicities impact their quality of survivorship. A subset of patients succumbs to the disease. Current unmet needs include clarifying which patients can be safely observed after initial surgical resection, refinement of risk stratification to reduce chemotherapy burden in patients with standard-risk disease, and intensify therapy for patients with poor-risk disease. Furthermore, enhancing strategies for detection of minimal residual disease and early detection of relapse, particularly in serum tumor marker-negative histologies, is critical. Improving the understanding of the developmental and molecular origins of GCTs may facilitate discovery of novel targets. Future efforts should be directed toward assessing novel therapies in a biology-driven, biomarker-defined, histology-specific, risk-stratified patient population. Fragmentation of care between subspecialists restricts the unified study of these rare tumors. It is imperative that trials be conducted in collaboration with national and international cooperative groups, with harmonized data and biospecimen collection. Key priorities for the Children's Oncology Group (COG) GCT Committee include (a) better understanding the biology of GCTs, with a focus on molecular targets and mechanisms of treatment resistance; (b) strategic development of pediatric and young adult clinical trials; (c) understanding late effects of therapy and identifying individuals most at risk; and (d) prioritizing diversity, equity, and inclusion to reduce cancer health disparities and studying the impacts of social determinants of health on outcomes.

Corneal cross-linking for treatment of keratoconus relapse in post-keratoplasty eyes.

Keratoconus relapse after penetrating keratoplasty is a rare condition that may result in severe visual deterioration and corneal graft thinning. Therefore, treatment to stabilize the cornea should be considered. The purpose of this study was to evaluate the safety and efficacy of Corneal Cross-Linking (CXL) in eyes with relapse of keratoconus after penetrating keratoplasty for keratoconus. A retrospective review of eyes that developed keratoconus relapse following a penetrating keratoplasty and treated with CXL. The main outcome measures were change in maximal keratometry (Kmax), best-corrected distance visual acuity (BCVA), thinnest corneal thickness (TCT) and central corneal thickness (CCT), and complications. We identified 10 consecutive eyes of 9 patients. Preoperative median BCVA before the CXL and 1year after the CXL procedure remained stable (p = 0.68). The median (IQR) of Kmax improved from 63.2 (24.9) D before the CXL procedure to 62.2 (27.1) D at 1year postoperatively (P = 0.028). Median TCT and CCT also remained with no significant change 1year after CXL. No complications were noted following the procedure. CXL in eyes with keratoconus relapse after keratoplasty is a safe and effective procedure enabling not only visual stabilization but also might bring keratometry improvement. Routine follow-up after keratoplasty should be performed for early detection of keratoconus relapse and CXL is timely advised when such a relapse is documented.

Identification of predictive markers in the cerebrospinal fluid of patients with glioblastoma

Introduction. Glioblastoma (GB) is not yet curable despite recent advances in the treatment of other malignant solid tumors. The management of GB is based solely on histopathological features, imaging of the tumor and its genomic analysis (somatic mutations in the isocitrate dehydrogenase genes, methylation status of the O6-methylguanine-DNA methyltransferase gene promoter). To adapt the treatment to the most recent tumor evolution, molecular information should be received regularly throughout the course of therapy. However, tumor tissue is often not available for diagnosis as the disease progresses. In this regard, the development of less invasive methods, such as analysis of the proteome of biological fluids of patients, is of particular interest. Cerebrospinal fluid (CSF) is an important source disease biomarkers to monitor the presence and progression of the disease.Aim. To identify proteomic predictive biomarkers in the CSF of patients with GB.Materials and methods. During the study, samples of patients’ CSF samples, high-resolution proteomic mass spectrometry, modern biochemical methods and bioinformatic technologies were used.Results. For the first time, the analysis of proteomes of CSF samples of patients with GB obtained before and 7 days after the removal of the primary tumor was carried out. Potential biomarkers of GB have been identified. After their validation using open databases, 11 proteomic predictive markers of GB (S100A9, S100A8, PLA2G15, PPIB, LTBP2, VIM, LAMB1, STC1, NRP1, COL6A1, HSPA5) were selected and their role in the molecular mechanisms of gliomagenesis was assessed. Conclusion. The proposed panel of proteomic predictive CSF biomarkers in GB patients can be further used in the development of test systems for assessing the effectiveness of therapy and early detection of disease relapses.

Eyes: The windows to the detection of leukemia relapse

Eyes: The windows to the detection of leukemia relapse

Biomarkers for monitoring alcohol sobriety after liver transplantation for alcoholic liver disease.

Alcoholic liver disease (ALD) has become the most common indication for liver transplantation in Western countries, and its incidence is rapidly increasing in East Asia. Alcohol abstinence remains the standard of care for promoting liver transplantation for ALD and for preventing posttransplant graft loss. However, efficient monitoring methods are still being developed due to the limitations of traditional biomarkers, interviews, and questionnaires. The development of alcohol biomarkers has shifted from detecting alcohol and methanol to indirect byproducts, and to current mid-term and long-term direct alcohol metabolites, which provide higher accuracy and cover almost all types of alcohol relapse detection. However, in most clinical studies, biomarkers are used and validated in healthy individuals and alcohol use disorder (AUD) patients and for pretransplant evaluations. The evidence for their use in posttransplant abstinence monitoring is still lacking, but it is crucial for early detection of alcohol relapse and initiating intervention. This review aims to summarize the current evidence of the use of biomarkers for monitoring sobriety and alcohol relapse after liver transplantation, as well as to cover the diagnostic accuracy, detection window, and optimal multidisciplinary strategies.

ATRT-07. CLINICAL APPLICABILITY OF C19MC MIRNA DETECTION IN LIQUID BIOPSIES OF ETMR PATIENTS

Abstract Embryonal tumor with multilayered rosettes (ETMR) is a distinct central nervous system tumor entity which is characterized by dysregulation of oncogenic micro RNAs (miRNA). In the majority of cases (approx. 90%), tumors are characterized by amplification of the C19MC locus accompanied by a fusion of this locus to the TTYH1 gene. Beside the very young age of the patients, ETMR is a highly aggressive brain tumor with a dismal clinical outcome. About half of the patients relapse within the first 6 months despite intensive therapy. Based on these facts, a more rapid diagnosis as well as more accurate and faster detection of tumor response or tumor relapse would significantly improve the management of these severely affected young patients. Liquid biopsy has emerged as a highly promising tool to enable minimal invasive detection of molecular parameters to facilitate diagnosis and patient monitoring. Here, we developed a miRNA based liquid biopsy tool and performed a comprehensive profiling of the miRNA landscape in 11 ETMR tumor tissues and matching liquid biopsy samples of patients. The screening of the initial liquid biopsy samples (plasma or serum) taken at diagnosis revealed distinctly enriched miRNA levels. Further, we evaluated the use of the miRNA levels as a longitudinal tumor-monitoring tool. We detected decreasing levels after tumor resection and in long-term survivors and vice versa increasing levels in patients with progressive tumor disease. In conclusion, we developed a reliable and fast method with a turnaround time of only 4 hours between blood draw and analysis of the aberrant expressed miRNA in liquid biopsy samples of ETMR patients correlating with the clinical course of the individual patient.

Evaluation of the GELTAMO guidelines for surveillance in follicular lymphomas after first‐line immunochemotherapy: a real‐world prospective study

Introduction: CT scans have been traditionally recommended in the surveillance of patients (pts) with follicular lymphoma (FL) by international societies. In asymptomatic FL pts responding to first line (1L) immunochemotherapy, the Spanish GELTAMO FL guidelines recommends CT scan every 6 months for 2 years (during rituximab maintenance). The real value of surveillance with CT scans remains an open question, even more after the incorporation of PET in the response evaluation of FL. Our aim was to evaluate the detection rate of relapses by CT surveillance according to GELTAMO guidelines in FL pts with complete metabolic response (CMR) or partial metabolic response (PMR). Methods: observational prospective study in a single center between 2008 and 2020. Newly diagnosed FL who had CMR or PMR to 1L therapy were identified. Evaluation for both relapse and method of relapse detection, having special interest in the CT surveillance according to GELTAMO guidelines. Results: From 108 FL treated pts, 81 were included in the final analysis. Median age and female proportion were 59 years (range 24–83) and 49.4%. Treatment: R-CHOP/R-CHOP-like 63%, R-CVP 15% and rituximab 22%. Response: CMR 82%, PMR 18%. Median follow-up was 79.7 months (IQR 57.8–117.3). A total of 29 pts relapsed or progressed (35.8%) during the whole study period: 24 from CMR and 5 from PMR. Of these pts, 9 relapsed in the first 2-y (31.0% of all relapses and 11.1% of all patients) and were more common in pts in PMR versus CMR (60% vs. 25%, p = 0.1238). Relapse detection method in the first 2-y was: 5 (55.5%) by CT scan, 2 by physical examination and 2 by other methods. Beyond 2-y, 12 (60%) were detected by physical examination, 5 (25%) by CT scan, 2 (10%) by blood tests and 1 (5%) by ultrasound echography. Protocol adherence was 75.3%. A total of 262 CTs were performed in first 2-y with only 5 positive CT scans in this time-lapse (diagnostic yield 2%). Globally, 17.2% of all relapses were diagnosed by GELTAMO recommended surveillance CT scans. Time from first relapse to second line treatment was 4.02 months in those with relapse detected by CT in schedule versus 2.03 months in those detected by other methods (p = 0.81) (Figure 1A). In relapsed pts, OS at 3-y from relapse was 30.0 months in those with relapse detected by CT in schedule versus 66.2 months in the other patients (p = 0.077) (Figure 1B), probably because of the enrichment of POD24 cases in the first group. However, OS at 3-y from relapse in those patients in which relapse was detected by CT at any time (in or out schedule) was 43.8 months versus 66.9 months in those detecting relapse by other methods (p = 0.19). Keywords: Imaging and Early Detection, Indolent non-Hodgkin lymphoma, PET-CT No conflicts of interests pertinent to the abstract.

Detection of bladder cancer relapse after TURBT through urinary tumor DNA analysis: A prospective real-world evidence study.

e16605 Background: Bladder cancer is a common malignancy and detection of tumor recurrence is important to improve patient outcomes. Transurethral resection of bladder tumor (TURBT) is the standard treatment for early-stage bladder cancer, but the molecular detection of disease relapse remains a challenge. Reliable and non-invasive methods for monitoring the molecular changes in urine are crucial for timely intervention and disease management. Methods: In this study, 108 patients with early-stage bladder cancer who were selected for detection of disease relapse after the 1st TURBT (median timing 4.8 months after TURBT) were prospectively enrolled. The molecular recurrence in these patients was detected from the urinary tumor DNA (utDNA) using a targeted next-generation sequencing (NGS) assay (PredicineCARE). This assay identifies somatic alterations in utDNA, including single nucleotide variations (SNVs), gene fusions and copy number variations (CNVs), and based on these variations, the tumor fraction was called to identify molecular relapse in the patients. Results: 77 out of 108 (71.3%) patients were found to be tumor positive in utDNA with a tumor fraction ≥ 0.5%. The assay identified 525 SNVs and 32 CNVs in the tumor positive patients. The most frequently mutated genes in the urine samples were TP53 (38%), TERT (32%), KMT2D (28%), ARID1A (19%), FGFR3 (19%), PIK3CA (14%) and ERBB2 (12%). Conclusions: This study demonstrates the feasibility of using urine ctDNA assay to detect molecular recurrence in early-stage bladder cancer patients treated by TURBT. This information can be used to improve patient outcomes by enabling early detection of tumor recurrence and guiding treatment decisions. The findings of this study highlight the promising potential of urine-based NGS assays for cancer detection and disease surveillance.

Approach to relapsed CLL including Richter Transformation

Approach to relapsed CLL including Richter Transformation

AGCT1531: Evaluating the utility of circulating microRNA in the management of children, adolescents, and adults with malignant germ cell tumors.

TPS5104 Background: Conventional serum tumor markers for malignant germ cell tumors (MGCTs) have limited performance characteristics, especially in non-secreting histologies such as embryonal carcinoma or seminoma. Growing evidence has shown circulating microRNAs (miRNA), particularly miR-371a-3p, to be a more sensitive biomarker, elevated across all MGCT subtypes except teratoma. However, studies to date have been retrospective or non-randomized. If confirmed in prospective clinical trials, circulating miRNA may have the potential to become a universal MGCT biomarker, aiding in diagnosis, prognostication, relapse detection, and prediction of viable disease after chemotherapy. One of the key objectives of AGCT1531 is to test the performance characteristics of circulating miRNA in children, adolescents, and young adults (AYAs) with low-risk and standard-risk MGCTs. AGCT1531 is unique among MGCT trials for including patients across all ages, genders, sites, histologies, and treatments. Methods: AGCT1531 is a prospective clinical trial sponsored by the Children’s Oncology Group (COG), co-designed with United Kingdom, Japan, and India, and supported by all NCTN groups. It has three strata for low-risk tumors, defined as stage I tumors treated with surgery followed by active surveillance: non-seminomatous tumors of any site; testis seminomas; and ovarian immature teratomas. Patients of any age are eligible. Target accruals are 432, 277, and 212 patients, respectively. Key endpoints include overall and event-free survival and longitudinal measurements of circulating miRNA. Serum is collected at intervals aligned with NCCN follow-up guidelines to minimize testing burden. For patients over 11 years old with stage I non-seminomatous tumors, serum is collected at enrollment, months 4, 8, 12, 18, and 24; and (if applicable) at relapse. The trial also has two strata for standard-risk MGCTs: SR1 for children under age 11 years and SR2 for AYAs age 11-25 years. Target accruals are 518 and 595 patients, respectively. Both strata are randomized trials of cisplatin-based versus carboplatin-based regimens, with carboplatin used at doses higher than those previously tested in adult MGCTs. Serum collection is recommended at enrollment, months 6, 12, 18, 24, and (if applicable) at relapse. AGCT1531 was activated in August 2017. The low-risk seminoma stratum was added on November 2021. The trial is currently open at 466 sites across seven countries. For adults with testicular GCTs, data from AGCT1531 can contribute to joint analyses of parallel trials evaluating circulating miR-371a-3p in this population: SWOG1823, ANZUP1906 (CLIMATE), and ANZUP P3BEP. Together, this suite of trials will help validate the utility of circulating miRNA and set the stage for future investigations where miRNA is used to influence real-time management decisions for patients with MGCTs. Clinical trial information: NCT03067181 .

Circulating tumor DNA–based detection of molecular residual disease as a biomarker for recurrence monitoring predict disease recurrence in patients with ovarian cancer.

e17542 Background: Despite recent advances in cancer diagnostics and treatments, nearly 75% ovarian cancer patients relapse within two years of primary therapy and become candidates for treatment of recurrent diseases. A novel approach to post-surgical risk stratification for molecular residual disease (MRD) detection and treatment monitoring is needed to improve patient outcomes. Methods: We analyzed a cohort of 22 stage Ⅰ-Ⅳ ovarian cancer patients which were followed up at median 6 (range,3-15) times between July 2017 and December 2020. Among the 22 patients, stage I, II, III and Ⅳ comprised 9%, 5%, 50% and 36%, respectively. Tumor tissue and blood samples of all subjects were collected at Ruijin Hospital, Shanghai Jiao Tong University.Somatic mutations were identified by whole exome sequencing and assessed from plasma collected during treatment using personalized tumor-informed MRDtect assays with a median of 25（range,17-30） amplicons/assay targeting tumor-specific variants unique to each patient, sequenced at mean 200,000X depth. Plasma samples with ≥2 variants detected were considered MRD-positive and ctDNA levels were reported in mean tumor molecules per mL (MTM/mL) of plasma. Sequencing data were analyzed using PiVAT secondary analysis software and MRD positive was concluded when at least two variants were detected in plasma. Results: CtDNA was preoperatively detectable in 18 (85.7%) patients, and the positive rate became 38.8% (7/18) after surgery. Serial ctDNA analysis during surveillance after definitive treatment of the 22 patients with longitudinal collected plasma samples identified relapse with 100% sensitivity and 100% specificity. The median lead time from ctDNA detection in plasma to relapse detection by standard-of-care computed tomography was 135 days (range,45-387days). Variants from a total of 526 genes were selected from the WES results of these 22 patients. Among these 526 genes, 96% (505 genes) were selected for only one patient, 3.4% (18 genes) were selected for two patients and 0.2% (one gene) were selected for three patients. Compared with tumor-agnostic assay, tumor-informed assay is a more accurate route that is more consistent with the heterogeneity of tumor and can maximize the ability to reflect the real situation of each patient. Conclusions: Sensitive methods for risk stratification, therapeutic efficacy monitoring, and early relapse detection may have a major impact on treatment decisions and patient management for ovarian cancer patients. MRD can be used as an effective biomarker to prompt prognosis and recurrence risk, providing powerful assistance for accurate diagnosis and treatment for patients.