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Diagnosis of Leptomeningeal Disease in Diffuse Midline Gliomas by Detection of H3F3A K27M Mutation in Circulating Tumor DNA of Cerebrospinal Fluid.

INTRODUCTION: Leptomeningeal disease (LMD) in diffuse midline gliomas (DMGs) can lead to devastating symptoms such as severe pain, urinary incontinence, and tetraparesis, with limited treatment options. We determined whether detecting H3F3A K27M-mutant droplets in cerebrospinal fluid (CSF) circulating tumor deoxyribonucleic acid (ctDNA) could be a biomarker for detecting LMD in DMGs. METHODS: Twenty-five CSF samples were obtained from 22 DMG patients. Histological confirmation of H3F3A K27M mutation was obtained in 10 (45.5%) cases. ctDNA was extracted from CSF, and H3F3A K27M-mutant and wild

Early Dynamics of Circulating Tumor HPV-DNA with Neoadjuvant Chemotherapy and Response-Adapted De-escalation in Human Papillomavirus-Associated Oropharyngeal Cancer.

PURPOSE: Human papillomavirus-associated (HPV+) oropharyngeal carcinoma is associated with excellent survival, yet treatment drives substantial toxicity. Improved biomarkers are needed to select patients for de-escalated treatment. Circulating tumor HPV DNA (ctHPV-DNA) represents a promising noninvasive biomarker to gauge treatment response and surveil for disease recurrence. PATIENTS AND METHODS: A prospective biomarker clinical trial of response-stratified de-escalation was conducted. Eligible patients with non-metastatic HPV+ oropharyngeal carcinoma received neoadjuvant chemotherapy, follo

HPV circulating tumor DNA to monitor response to pembrolizumab and vorinostat combination in patients with advanced HPV-related squamous-cell carcinomas.

BACKGROUND: Limited data are available on the role of human papillomavirus circulating tumor DNA (HPV-ctDNA) as a pharmacodynamic marker to monitor the response to treatment in the recurrent/metastatic (R/M) setting. Our study aimed to investigate the sensitivity and pharmacodynamic value of HPV-ctDNA levels during treatment in patients with R/M HPV-related squamous cell carcinoma (SCC) treated with pembrolizumab in combination with vorinostat (PEVO trial, NCT04357873). MATERIALS AND METHODS: Plasma samples were prospectively collected from 57 patients with HPV-related SCC before treatment in…

Genomic correlates of response and resistance to the irreversible FGFR1-4 inhibitor futibatinib based on biopsy and circulating tumor DNA profiling.

BACKGROUND: Futibatinib is the only covalent inhibitor of FGFR1-4 to gain regulatory approval in oncology. In this article, we present genomic analyses of tissue biopsies and circulating tumor DNA (ctDNA) from patients with 1 of nearly 20 tumor types treated with futibatinib in the phase I/II FOENIX study. PATIENTS AND METHODS: Eligible patients included those with ctDNA samples collected per protocol at baseline and/or progression on futibatinib in the phase Ib portion of the study for FGF/FGFR-altered advanced solid tumors or the phase II portion of the study for FGFR2 fusion/rearrangement-…

Increased circulating tumor DNA as a noninvasive biomarker of early treatment response in patients with metastatic ovarian carcinoma: A pilot study.

Detection of circulating tumor DNA is a new noninvasive technique with potential roles in diagnostic, follow-up, and prognostic evaluation of patients with many types of solid tumors. We aimed to evaluate the role of circulating tumor DNA in the setting of metastatic ovarian carcinoma. A prospective cohort of patients with metastatic ovarian cancer who were referred to systemic therapy was enrolled. Blood samples were collected before the start of treatment and monthly thereafter for 6 months. Circulating tumor DNA was quantified by real-time quantitative reverse transcription polymerase chain…

Added value of tumor-stroma ratio to postsurgery circulating tumor DNA and pTN stage in risk stratification of patients with stage III colon cancer treated with adjuvant chemotherapy.

BACKGROUND: Patients with stage III colon cancer (CC) are routinely treated with resection followed by adjuvant chemotherapy (ACT). Half of patients are cured by surgery alone and overtreated with ACT, yet another ∼30% experience disease recurrence. Upfront risk stratification requires biomarkers beyond the conventional pathological stage (pTN). Detection of postsurgery circulating tumor DNA (ctDNA) is indicative of minimal residual disease and prognostic of recurrence. However, its negative predictive value is insufficient to guide treatment de-escalation. This study aimed to investigate whet…

Role of Tumor-informed Personalized Circulating Tumor DNA Assay in Informing Recurrence in Patients With Peritoneal Metastases From Colorectal and High-grade Appendix Cancer Undergoing Curative-intent Surgery.

OBJECTIVE: To investigate the role of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay in informing recurrence in patients with peritoneal metastases (PM) from colorectal (CRC) and high-grade appendix (HGA) cancer after curative cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). BACKGROUND: Over 50% of patients with CRC/HGA-PM recur after optimal CRS-HIPEC. The limited sensitivity of axial imaging and diagnostic biomarkers is a significant cause of delay in the detection of recurrence and initiation of further therapies. Plasma ctDNA has a prom…

Impact of Circulating Tumor DNA and Copy-Number Alterations on Clinical Outcome in Relapsed/Refractory Germ Cell Tumors Treated With Salvage High-Dose Chemotherapy.

PURPOSE: High-dose chemotherapy (HDCT) is one of the salvage therapy options for patients with relapsed/refractory germ cell tumors (rGCT) after failure of first-line chemotherapy. We aimed to identify circulating biomarkers predicting clinical response and outcome of HDCT. METHODS: Baseline and on-treatment plasma samples from 69 HDCT-treated and 26 conventional-dose chemotherapy (CDCT)-treated GCT patients were analyzed by shallow whole-genome sequencing. Tumor fraction (TF) and copy-number alterations (CNAs) were determined using ichorCNA, compared with miR-371a-3p levels, and correlated w

Immunotherapy and circulating tumor DNA in HPV-positive oropharyngeal cancer: a systematic review and exploratory meta-analysis of survival and surveillance outcomes.

BACKGROUND: Human papillomavirus-positive oropharyngeal squamous cell carcinoma is biologically distinct, yet the effect of immune checkpoint inhibition and the performance of circulating tumor DNA (ctDNA) as a biomarker remain undefined. METHODS: We searched databases through October 2025 for prospective studies of adults with HPV-positive OPSCC that reported survival after immune checkpoint inhibition or plasma ctDNA/ctHPVDNA as a prognostic or surveillance biomarker. Two reviewers performed selection, extraction, ROBINS-I, and GRADE. Hazard ratios were pooled by inverse variance (common-ef…

KIM-1 and Circulating Tumor DNA Are Prognostic Markers for Oligometastatic Clear-cell Renal Cell Carcinoma: Development of a Multivariable Prognostic Model.

Better tools are needed for clinical decision-making in oligometastatic clear-cell renal cell carcinoma (ccRCC). Plasma KIM-1 concentrations and circulating tumor DNA (ctDNA) were measured in a clinical trial evaluating metastasis-directed therapy (MDT) for oligometastatic ccRCC (NCT03575611). Shorter systemic therapy-free survival (STFS) was associated with high KIM-1 at baseline (hazard ratio per log10 pg/ml [HR]: 2.45, 95% confidence interval [CI] 1.48-4.08; p < 0.001), the end of radiation therapy (HR 2.56, 95% CI 1.56-4.21; p < 0.001), and 3-mo follow-up (HR 3.22, 95% CI 1.91-5.43; p < 0.…

Perioperative immunocircadian recovery and its association with circulating tumor DNA-based minimal residual disease and long-term survival after colorectal cancer surgery.

BACKGROUND: Postoperative outcomes after curative colorectal cancer surgery vary widely, even among patients with comparable tumor characteristics and treatment pathways. Conventional clinicopathologic factors and circulating tumor DNA predominantly characterize tumor-related risk but provide limited information regarding the dynamic host response to surgical stress. We investigated whether distinct perioperative immunocircadian recovery trajectories could be identified and whether these trajectories were associated with postoperative circulating tumor DNA-based minimal residual disease and lo…

Прогнозирующая ценность циркулирующей ДНК опухоли для клинических результатов в пациентах, проходящих трансплантацию клеток гематополиетической системы: систематический обзор и мета-анализ.

После пересадки гематопоиетических клеток (ГХТ) гематологическая недостаточность по-прежнему является основной причиной отказа в лечении. Циркуляция ДНК опухоли (ctDNA) стала перспективным минимальным инвазивным биомаркером для оценки измеримых остаточных заболеваний (MRD) и раннего обнаружения рецидивов; однако прогнозируемое значение ctDNA в посттрансплантационных условиях не было полностью синтезировано. Мы провели систематический обзор и метаанализ в соответствии с руководящими принципами PRISMA и зарегистрировали протокол в ПРОСПЕРО (CRD420261392100). По состоянию на ноябрь были проведены

Совпадение в аннотации оригинала
Relapse remains the leading cause of treatment failure following hematopoietic cell transplantation (HCT) for hematologic malignancies. Circulating tumor DNA (ctDNA) has emerged as a promising minimally invasive biomarker for measurable residual disease (MRD) assessment and early relapse detection; however, the prognostic significance of ctDNA in the post-tr…

Noninvasive Therapeutic Monitoring of Circulating Tumor DNA in BRAF-Mutant Metastatic Colon Cancer Using Droplet Digital PCR, Next-Generation Sequencing, and Fragmentomics.

PURPOSE: BRAFV600E-mutated metastatic colorectal cancers (mCRCs) are associated with poorer prognosis. We present a case, in which noninvasive therapeutic monitoring was performed on a patient with BRAF-mutant mCRC, aiming to track disease progression and elucidate the mechanisms of response and resistance towards anti-BRAF therapy. METHODS: A 40-year-old man diagnosed with metastatic BRAFV600E mutant sigmoid adenocarcinoma received multiple lines of treatment, including first-line chemotherapy + bevacizumab and targeted therapy of cetuximab, encorafenib ± binimetinib. Noninvasive therapeutic

Circulating tumor DNA as a powerful tool in diagnostics and treatment outcome prediction - focus on large B-cell lymphomas and follicular lymphomas.

INTRODUCTION: Pathogenesis of large B-cell lymphomas (LBCL) and follicular lymphomas (FL) is a multistep process associated with the development of diverse DNA alterations and consequent deregulation of critical cellular processes. Detection of tumor-associated mutations within non-tumor compartments (mainly plasma) is the basis of the 'liquid biopsy' concept. Apart from tumor mutational profiling, quantitative analysis of circulating tumor DNA (ctDNA) allows longitudinal assessment of tumor burden. ctDNA-based technologies provide a new tool for tumor diagnostics and treatment personalization…

Phase I Study of Acalabrutinib Plus Danvatirsen (AZD9150) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma Including Circulating Tumor DNA Biomarker Assessment.

PURPOSE: Novel targeted and immunotherapies have improved outcomes in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but t … mbination is safe and tolerable but efficacy is limited in R/R DLBCL. Results support evaluation of circulating tumor DNA as a biomarker for clinical response.

Olaparib Efficacy in Patients with Metastatic Castration-resistant Prostate Cancer and BRCA1, BRCA2, or ATM Alterations Identified by Testing Circulating Tumor DNA.

PURPOSE: The phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control) in metastatic castration-resistant prostate cancer (mCRPC) with tumor homologous recombination repair (HRR) gene alterations. We present exploratory analyses on the use of circulating tumor DNA (ctDNA) testing as an additional method to identify patients with mCRPC with HRR gene alterations who may be eligible for olaparib treatment. PATIENTS AND METHODS: Plasma samples collected during screening in PROfound were retrospectively sequenced using the FoundationOne®Liquid CDx test …

Circulating tumor DNA dynamics and recurrence risk in patients undergoing curative intent resection of colorectal cancer liver metastases: A prospective cohort study.

BACKGROUND: In patients with resectable colorectal liver metastases (CRLM), the role of pre- and postoperative systemic therapy continues to be debated. Previous studies have shown that circulating tumor DNA (ctDNA) analysis, as a marker of minimal residual disease, is a powerful prognostic factor in patients with nonmetastatic colorectal cancer (CRC). Serial analysis of ctDNA in patients with resectable CRLM could inform the optimal use of perioperative chemotherapy. Here, we performed a validation study to confirm the prognostic impact of postoperative ctDNA in resectable CRLM observed in a …

Rapid Clearance Profile of Plasma Circulating Tumor HPV Type 16 DNA during Chemoradiotherapy Correlates with Disease Control in HPV-Associated Oropharyngeal Cancer.

PURPOSE: To identify a profile of circulating tumor human papilloma virus (HPV) DNA (ctHPVDNA) clearance kinetics that is associated with disease control after chemoradiotherapy (CRT) for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). EXPERIMENTAL DESIGN: A multi-institutional prospective biomarker trial was conducted in 103 patients with (i) p16-positive OPSCC, (ii) M0 disease, and (iii) receipt of definitive CRT. Blood specimens were collected at baseline, weekly during CRT, and at follow-up visits. Optimized multianalyte digital PCR assays were used to quantify ctHPVDNA (typ

Cell-free circulating tumor DNA supplementing tissue biopsies for identification of targetable mutations: Implications for precision medicine and considerations for reconciling results.

Cell-free circulating tumor DNA (ctDNA) next-generation sequencing (NGS) is emerging as a noninvasive technique for detecting targetable mutations. We describe two lung adenocarcinoma cases that show the clinical utility of supplementing tumor biopsy molecular interrogation with ctDNA NGS. For both cases, ctDNA NGS identified actionable mutations that were previously not reported by molecular interrogation of tissue. Explanations are provided for the observed differences between ctDNA and tumor biopsy genomic results along with considerations for reconciling findings. Case 1 consisted of a pat…

Real-world outcomes in circulating tumor DNA-detected isocitrate dehydrogenase 1-mutant cholangiocarcinoma: First-line gemcitabine and cisplatin with versus without immunotherapy.

BACKGROUND: Comprehensive genomic profiling (CGP) is recommended for advanced cholangiocarcinoma (aCCA). Circulating tumor DNA (ctDNA) testing provides a noninvasive alternative with concordance to tissue. Standard first-line (1L) therapy is gemcitabine and cisplatin (GemCis) with or without immune checkpoint inhibitors (ICIs). Data suggest that patients with isocitrate dehydrogenase 1 (IDH1) mutations may derive less benefit from ICIs. This study evaluated outcomes with 1L GemCis versus GemCis + ICI in ctDNA-identified IDH1-mutant (IDH1+) aCCA. METHODS: Real-world data were analyzed from the…