Liquid Biopsy

Improving personalized cancer treatments and finding the best strategies to treat each patient relies on using new diagnostic technologies. Currently, for colorectal cancer, the methods used to decide who gets additional post-surgery treatment are suboptimal. Some patients get too much treatment, while others do not get enough. There is a new way to explore if there is any cancer left in a patient's body using circulating tumor DNA (ctDNA) detected in blood samples. This can help decide who needs more treatment after surgery. Even though many tests have been developed, it has yet to be determined which test performs best at relevant time points. The GUIDE.MRD consortium is a group of experts, including scientists, technology, and pharmaceutical companies. The consortium is working on creating a reliable standard for the ctDNA tests, validating their clinical utility, and collecting data to help decide on the best treatment for each patient. FRENCH-MRD-CRC is the French study of the european GUIDE.MRD project.

Improving personalized cancer treatments and finding the best strategies to treat each patient relies on using new diagnostic technologies. Currently, for colorectal cancer, the methods used to decide who gets additional post-surgery treatment are suboptimal. Some patients get too much treatment, while others do not get enough. There is a new way to explore if there is any cancer left in a patient's body using circulating tumor DNA (ctDNA) detected in blood samples. This can help decide who needs more treatment after surgery. Even though many tests have been developed, it has yet to be determined which test performs best at relevant time points. The GUIDE.MRD consortium is a group of experts, including scientists, technology, and pharmaceutical companies. The consortium is working on creating a reliable standard for the ctDNA tests, validating their clinical utility, and collecting data to help decide on the best treatment for each patient. FRENCH.MRD.CRLM is the French study and part of the european GUIDE.MRD project.

This study evaluates whether urinary tumor DNA (utDNA) testing, together with clinical, pathologic, and radiographic assessment, can help guide treatment discontinuation and active surveillance in patients with unresectable very-high-risk non-muscle-invasive bladder cancer (VHR NMIBC) treated with bladder-sparing systemic immunotherapy. Participants receive systemic immune checkpoint inhibitor-based therapy every 3 weeks for an initial 3 cycles. Initial response assessment is performed using transurethral resection of bladder tumor (TURBT) and chest and abdominopelvic computed tomography (CT). Participants without progression to muscle-invasive, regional nodal, or distant metastatic disease then undergo post-TURBT urine cytology and urinary tumor DNA (utDNA) testing. Participants with both negative urine cytology and negative utDNA results receive an additional 3 cycles of systemic immunotherapy. After the additional treatment, participants undergo repeat evaluation using cystoscopy with biopsy, urine cytology, utDNA testing, and chest and abdominopelvic CT. Participants with negative findings on cystoscopic biopsy, urine cytology, and utDNA testing, and without radiographic evidence of nodal or distant metastatic disease, discontinue systemic immunotherapy and enter an active surveillance phase with regular follow-up monitoring. Participants who do not meet these criteria continue further clinical management and follow-up according to institutional practice. The study aims to determine whether a shortened duration of systemic immunotherapy guided by integrated molecular, clinical, pathologic, and radiographic response assessment can maintain favorable oncologic outcomes while reducing unnecessary treatment exposure in this high-risk population.

Non-muscle-invasive bladder cancer (NMIBC) accounts for approximately 75% of newly diagnosed bladder cancers and is characterized by a high risk of recurrence and progression. Current guidelines recommend that patients with stage T1 NMIBC undergo a second transurethral resection of bladder tumor (re-TURBT) within 2-6 weeks after the initial surgery to remove residual tumor, confirm staging, and obtain additional pathological information. However, the benefits of routine re-TURBT for all high-risk patients remain controversial, as many patients may not have residual disease, while the procedure carries surgical and anesthetic risks, physical and psychological burden, and additional healthcare costs. Urine tumor DNA (utDNA) refers to DNA fragments shed by tumor cells into urine. It can be detected using molecular assays with high sensitivity and specificity, offering a non-invasive method for bladder cancer diagnosis and surveillance. Previous studies have shown that positive utDNA results after initial TURBT may be associated with residual disease and higher recurrence risk. This multicenter, randomized controlled trial aims to evaluate whether utDNA testing can accurately identify NMIBC patients who are most likely to benefit from re-TURBT, thereby guiding the decision to perform the procedure. The goal is to optimize patient selection for re-TURBT, reduce unnecessary surgeries, and improve patient quality of life while maintaining oncologic safety.

Non-muscle-invasive bladder cancer (NMIBC) is usually treated with surgery to remove the tumor (transurethral resection of bladder tumor, or TURBT), often followed by bladder-instilled medications to reduce the chance of the cancer coming back. Even with this treatment, high-grade NMIBC can return or progress, so patients need regular check-ups, usually with cystoscopy (a camera examination of the bladder) and urine cytology. Cystoscopy is effective but invasive, can cause discomfort, and carries risks such as infection and bleeding. This makes follow-up costly and sometimes burdensome for patients. This study is testing whether a urine tumor DNA (utDNA) test - a type of "liquid biopsy" that detects cancer-related DNA changes in urine - can help guide the timing of cystoscopy for people with high-risk or very high-risk NMIBC. utDNA testing is non-invasive and has shown high accuracy in detecting bladder cancer, sometimes spotting signs of recurrence earlier than standard methods. By combining utDNA testing with cystoscopy, we hope to safely reduce the number of unnecessary cystoscopies without missing cancer recurrences. The study will evaluate whether this approach can make bladder cancer follow-up more comfortable, more precise, and more efficient.

Brief Summary: This prospective, multicenter study aims to discover, develop, and validate a plasma exosomal RNA-based signature as a rule-out test for predicting bone metastasis in prostate cancer, using baseline treatment-naïve PSMA PET as the gold standard. The study is designed in four sequential phases: Phase 1 (Discovery, n=250): High-throughput sequencing of plasma exosomal RNAs to identify differentially expressed candidate RNAs. Phase 2 (Model Development, n=300): Digital droplet PCR (ddPCR) analysis of candidates in an independent cohort to construct and lock the final multi-RNA predictive signature using appropriate machine learning methods. Phase 3 (Internal Validation, n=300): Independent validation of the locked signature in a consecutive cohort reflecting natural disease prevalence. Phase 4 (External Validation, n=150): Final independent validation in a multi-center cohort enriched for bone metastasis. Primary Outcome: To evaluate the diagnostic performance of the signature as a rule-out test for PSMA PET-defined bone metastasis. The primary performance metrics are: Sensitivity, with a prespecified target of ≥95% (to ensure minimal false negatives). Specificity at the threshold that achieves the ≥95% sensitivity. A specificity of ≥30% will be considered supportive of clinical utility. A specificity of ≥30% (or a lower bound of the 95% confidence interval exceeding 20%) will be considered supportive of clinical utility. Need: Current biomarkers lack sensitivity and specificity for early detection of bone metastasis. More importantly, existing tools lack adequate negative predictive value to safely rule out bone metastasis in low-risk patients, leading to over-imaging or delayed detection. There is an urgent need for a non-invasive rule-out test to safely defer PSMA PET/CT in very-low-risk patients. Plasma exosomal RNAs offer a promising liquid biopsy approach, but prospective multicenter studies with rigorous validation are lacking. Secondary Outcomes: 1. Secondary metrics include negative predictive value (NPV), positive predictive value (PPV), area under the ROC curve (AUC), calibration, and decision curve analysis. 2. Correlation between exosomal RNA levels and number of bone metastatic lesions (PSMA PET). 3. Association with PSA, PSMA PET SUVmax, and MRI findings. 4. Tissue-plasma correlation to confirm tumor origin (exploratory). 5. Mechanistic exploration of key candidates via in vitro/in vivo assays (exploratory). 6. Subgroup analyses by hormone sensitivity, metastatic pattern, Gleason grade (exploratory). Inclusion Criteria: 1. Histologically confirmed prostate cancer scheduled for baseline PSMA PET. 2. PSMA PET performed prior to any prostate cancer-related treatment. 3. Blood samples collected prior to any treatment AND prior to prostate biopsy. 4. Willing to undergo prostate biopsy if clinically indicated (after blood collection). 5. Written informed consent. 6. Age ≥18 years. Exclusion Criteria: 1. Any prior prostate cancer treatment before baseline PSMA PET. 2. Blood samples collected after prostate biopsy. 3. Other active malignancy within past two years (excluding non-melanoma skin cancer). 4. Inadequate blood sample quality or quantity. 5. Severe comorbidities interfering with study conduct.

To learn if drawing blood directly from veins inside the brain is safe and can effectively provide the same kind of detailed information about high-grade glioma as traditional surgical biopsy.

High-risk non-muscle-invasive bladder cancer (NMIBC) carries a substantial risk of residual disease after initial transurethral resection of bladder tumor (TURBT). Current guidelines recommend a second TURBT (re-TURBT) within 2-6 weeks for patients with stage T1 disease to remove residual tumor, confirm staging, and obtain additional pathological information. However, the actual survival benefit of routine re-TURBT for all high-risk patients remains debated, and the procedure may pose surgical risks, increase healthcare costs, and impact patient quality of life. Urine tumor DNA (utDNA) and urine tumor RNA (utRNA) are molecular biomarkers detectable through non-invasive "liquid biopsy" methods. In urothelial carcinoma, tumor-derived nucleic acids can be shed into urine, where they can be detected with high sensitivity and specificity. These biomarkers may help identify patients most likely to harbor residual disease after initial TURBT, and thus most likely to benefit from re-TURBT. This prospective, open-label, observational, single-center study aims to evaluate the clinical value of utDNA/utRNA testing in guiding re-TURBT for patients with high-risk NMIBC. The study will assess whether molecular urine testing can improve patient selection for re-TURBT, potentially reducing unnecessary procedures while maintaining oncological safety.

Application of Multi-Component Liquid Biopsy (ctDNA, utDNA, Exosomes, and Protein Biomarkers in Blood and Urine) for Auxiliary Diagnosis, Therapeutic Response Evaluation, and Recurrence Monitoring in Urothelial Carcinoma

The overall objective of this GUIDE.MRD consortium is to confirm that ctDNA detected after curative intended treatment for PDAC is a marker of residual disease and for risk-of-recurrence, and applicable in clinical practice. Primary objective To confirm that ctDNA analyses performed after PDAC treatment can identify patients with a high risk-of-recurrence. Specifically, the investigators want to determine the association between disease-free survival (DFS) and ctDNA detection status after 1. curative-intended surgery and 2. adjuvant chemotherapy. FRENCH.MRD.PDAC is the French study of the european GUIDE.MRD project

The goal of this prospective clinical trial is to identify a predictive biomarker in patients with advanced HCC (stage B and C) using a combinatorial approach of the liquid biopsy. The main questions it aims to answer are: * Is multi-omic liquid biopsy approach able to identify a strong predictive biomarker of immunotherapy efficiency? * Is there a correlation between tissue biopsy (PD-L1 tissue level of expression) and liquid biopsy (detection of CTC expressing PD-L1) in HCC patients? Participants blood will be collected at several time points.

The trial will test a paradigm-changing in vitro diagnostic device for Liquid Biopsy enabling facile simultaneous detection of protein and nucleic acid analytes with sensitivity at single-molecule level, e.g. not achievable with any alternative technology. A novel affinity-mediated transport amplification (AMT) method will be tested allowing for the multiplexed quantification of rare biomarkers circulating in blood. The Versilib AMT photonic biosensor will test two analytes: the known actionable DNA mutation BRAF p.V600E, and a melanoma-restricted protein antigen. The results will be compared to digital PCR and ELISA methods.

The current study aims to assess high-risk patients using both liquid-based cytology and cervical methylation testing. The results will be compared with the traditional hysteroscopic pathological findings to determine the sensitivity and specificity of these methods for early detection of endometrial cancer, thereby evaluating their potential application in early screening. Primary Objectives： 1. To evaluate the sensitivity, specificity, and accuracy of endometrial cytology for screening endometrial cancer. 2. To assess the sensitivity, specificity, and accuracy of methylation testing for screening endometrial cancer. 3. To perform further molecular testing on tissue samples obtained from endometrial cytology and cervical methylation tests, aiming to explore early screening-sensitive indicators. Secondary Objectives： 1. To determine the value of endometrial cytology in evaluating the efficacy of fertility-sparing treatments for endometrial cancer. 2. To assess the value of methylation testing in evaluating the efficacy of fertility-sparing treatments for endometrial cancer.

Based on the evidence summarized in the introduction, the clinician hypothesize that the detection of the presence and expression of HPV-DNA, certain miRNAs, and a certain mutational profile in the tissues and biological fluids of these patients, may have important prognostic and diagnostic value not only in HPV-related OPSCCs but also in HPV+ occult T. Accordingly, this study aims to aim to better characterize their potential as biomarkers and to detect the possibility of their their use to implement the sensitivity and specificity of radiological methodologies (PET-CT and MRI), already in use in clinical practice, for monitoring disease progression in this specific subgroup. Finally, by using the collected material to generate organoids and Patient Derived Xenograft (PDX), the study also aims to identify possible new molecular drugs, which could solve the problem of resistance to radiochemotherapy.

The Jinling Cohort is a prospective, multicenter cohort study in which 15,000 eligible individuals aged 45-75 in Nanjing China will be enrolled.

The study is perfomed with adult patients with non-small cell lung cancer treated with tyrosine kinase inhibitor. The objective is to collect repeated samples of blood from patients (starting) on a tyrosine kinase inhibitor, for liquid mutation testing, and pharmacokinetic analysis.