Predicting Early Death in Head and Neck Cancer—A Pilot Study

Cancers, Год журнала: 2025, Номер 17(2), С. 302 - 302

Опубликована: Янв. 17, 2025

Background: The aim of this study was to evaluate biomarkers and biological characteristics tumor biopsies from patients with head neck cancer (HNC) assess the risk early death. Furthermore, we analyzed whether any combination markers could be used for prognostication death within six months after diagnosis. Materials Methods: Patients diagnosed HNC, receiving curative treatment decision at a multidisciplinary board meeting, who died diagnosis were included in study. Nine identified matched according site stage seventeen survived least two years. Results: expression compared between early-death survivors. There significantly higher Ki-67 than those surviving years, mean difference 21% (p = 0.038). A significant cytoplasmic survivin noted where had increased survivors 0.021). intensity staining differed groups 0.006). Conclusions: results pilot indicate that Ki67 potential prognostic HNC possibly panel value making.

Язык: Английский

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Immediate postoperative minimal residual disease detection with MAESTRO predicts recurrence and survival in head and neck cancer patients treated with surgery

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

Abstract Purpose While circulating tumor DNA (ctDNA) is a promising biomarker for minimal residual disease (MRD) detection in head and neck squamous cell carcinoma (HNSCC), more sensitive assays are needed accurate MRD at clinically-relevant timepoints. Ultrasensitive immediately after surgery could guide adjuvant therapy decisions, but early ctDNA dynamics poorly understood. Experimental Design We applied MAESTRO, whole-genome, tumor-informed, mutation-enrichment sequencing assay, pooled testing format called MAESTRO-Pool, to plasma samples from HNSCC patients collected during surveillance. evaluated whether predict outcomes. Results Among 24 predominantly HPV-independent (95.8%) patients, rapid clearance occurred by the first postoperative sample (1-3 days postoperatively) 9 without an event (recurrence or death). 13/15 with were MRD+ (PPV = 92.9%; NPV 80%) median fraction (TFx) of 54 ppm (range 6-1,177 ppm). In last immediate window, 8/13 10/13 had TFx below 100 ppm, respectively, limit leading commercial assays. Early correlated worse overall survival (HR 8.3; 95% CI: 1.1-66.1; P 0.02) event-free 27.4; 3.5-214.5; < 0.0001) independent high-risk pathology. Conclusions Immediate MAESTRO was predictive recurrence death. Given ultralow TFxs observed, ultrasensitive will be essential reliable timepoints enable personalized decision-making HNSCC.

Язык: Английский

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State of the Art Therapy for Recurrent or Advanced Head and Neck Cancer

Advances in Oncology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Molecular counting enables accurate and precise quantification of methylated ctDNA for tumor-naive cancer therapy response monitoring

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 18, 2025

Personalized cancer treatment can significantly extend survival and improve quality of life for many patients, but accurate real-time therapy response monitoring remains challenging. To overcome logistical technical challenges associated with via imaging scans or assays that track the variant allele fraction (VAF) somatic mutations in circulating tumor DNA (ctDNA), we developed a tumor-naive liquid biopsy assay leverages Quantitative Counting Template (QCT) technology to accurately precisely quantify methylated ctDNA (Northstar Response™). The achieves < 10% coefficient variation at 1% fraction, which is 2 × lower than tumor-naive, targeted-panel approaches using VAF. distinguishes 0.25% absolute changes contrived (AUC > 0.94) performs well 12 solid types. Finally, small cohort patients lung, colorectal, pancreatic cancer, detected methylation correlate clinical outcomes. With its precise quantification methylation, Northstar Response novel tool potential inform decision making treatment.

Язык: Английский

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Current Progress and Future Directions of Immunotherapy in Head and Neck Squamous Cell Carcinoma

JAMA Otolaryngology–Head & Neck Surgery, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

For decades, the 3 therapeutic pillars for head and neck squamous cell carcinoma (HNSCC) have been radiation therapy, chemotherapy, surgery. In recent years, a fourth pillar, immunotherapy, has shifted existing paradigm of oncologic care by improving survival outcomes. This narrative review highlights key completed ongoing clinical trials that led to new approaches are aiming further alter current standard care. Immunotherapy in HNSCC first saw success phase with immune checkpoint inhibitors (ICIs) programmed death 1 protein patients recurrent or metastatic (R/M) disease. However, only approximately 15% 20% R/M achieve durable responses. Subsequent aimed broaden ICIs definitive curative setting, combination established chemoradiation modalities. These studies yielded disappointing results, raising concerns concurrent administration ICI chemoradiation- radiation-induced attenuation responses may contribute lack efficacy. Therefore, attempted introduce sequentially, either prior surgery neoadjuvant setting following treatment adjuvant maintenance setting. demonstrated mixed results but promising initial from early demonstrating signals response. Further currently underway various combinatorial settings assess response rates survival. The introduction brought dramatic shift landscape HNSCC. Completed provided hope patients, failures several suggest based on biologic understanding required expand immunotherapeutic approaches.

Язык: Английский

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Cell-Free DNA: Features and Attributes Shaping the Next Frontier in Liquid Biopsy

Molecular Diagnosis & Therapy, Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

Cell-free DNA (cfDNA) is changing the face of liquid biopsy as a minimally invasive tool for disease detection and monitoring, with its main applications in oncology prenatal testing, rising roles transplant patient monitoring. However, processes cfDNA biogenesis, fragmentation, clearance are complex require further investigation. Evidence suggests that production relates to mechanisms cell death repair, both which influence fragment size applicability biomarker. An emerging domain, fragmentomics being explored advancing field diagnostics using non-mutational signatures such ratios methylation patterns. Thus, this review examines structural diversity various sizes. In examining these subsets, we discuss their distinct biological origins potential clinical utility. Development sequencing methodologies has broadened application diagnosing cancers organ-specific pathologies, well directing personalized therapies. This been achieved by identifying uncovering different subsets biofluids biofluids. Different provide important insights regarding genomic epigenetic features, enhancing understanding gene regulation, tissue-specific functions, progression. Advancement key areas asserts increasing relevance use Continued exploration expected drive innovation integration into routine practice.

Язык: Английский

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Neoadjuvant Therapy for Mucosal Head and Neck Squamous Cell Carcinoma

JAMA Otolaryngology–Head & Neck Surgery, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Importance While neoadjuvant chemotherapy for head and neck squamous cell carcinoma dates to the earliest multidisciplinary approaches, introduction of immune checkpoint inhibitors (ICIs) has renewed enthusiasm research into its use. Although therapy remained mostly investigative through single-institutional clinical trials mucosal carcinoma, new data have emerged support Observations A narrative review was conducted by American Head Neck Society address current literature, evolving research, gaps in knowledge surrounding therapy. Neoadjuvant ICIs, most notably agents targeting anti–programmed death protein 1 (anti–PD-1), are a promising approach bolstering antitumor immunity prior ablating local structures. may allow an individualized approach, biomarkers guide patient selection limited. Potential benefits include de-escalation subsequent treatment, but curable disease also carries small real risk progression compromise curative options. Measures response pathologic, clinical, radiographic, there rapidly expanding capabilities diagnostics, such as circulating tumor DNA, with emerging potential provide objective quantification burden. Further strategies adaptive therapy, treatment selection/bioselection or modification surgery, adjuvant definitive treatment. ICI summarized this review. Optimized trial designs additional needed standardize surrogate outcomes compare survival standard Conclusions Relevance can be effective option precision oncology bolstered advent anti–PD-1 immunotherapy. However, tools predicting assessing remain evaluating strategies, combinations increase efficacy, comparisons approaches.

Язык: Английский

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Tumor-informed ctDNA assay to predict recurrence in locally advanced squamous-cell carcinoma of the head and neck (SCCHN)

ESMO Open, Год журнала: 2025, Номер 10(5), С. 104534 - 104534

Опубликована: Апрель 24, 2025

Язык: Английский

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The effect of circulating tumor DNA on the prognosis of patients with head and neck squamous cell carcinoma: a systematic review and meta-analysis

BMC Cancer, Год журнала: 2024, Номер 24(1)

Опубликована: Ноя. 21, 2024

Circulating tumour DNA (ctDNA) has emerged as a valuable liquid biopsy biomarker in the field of oncology, including head and neck squamous cell carcinomas (HNSCCs), offering potential insights into cancer diagnosis, progression, prognosis. This review aims to comprehensively evaluate utility ctDNA prognostic HNSCC. PubMed Ovid were searched part our review. Studies that investigated relationship between prognosis HNSCC patients included. Outcomes extracted included basic characteristics, details survival data. Meta-analysis was performed on eligible studies determine pooled progression-free/recurrence-free (RFS/PFS) overall (OS). Twenty-two included, involving 5062 from 11 countries. The meta-analysis demonstrated positive ctDNA/methylation detection associated with worse OS (HR = 2.00, 95% CI 1.35–2.96) PFS/RFS 3.54, 1.05–11.85). Positive ctEBV poorer 2.86, 1.84–4.45) 1.93, 1.74–2.13). ctHPV 1.38, 1.07–1.38) but not PFS/PFS 1.33, 0.96–1.85). indicates status is significantly patients, ctDNA/methylation-negative demonstrating better OS.

Язык: Английский

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Decoding the Dynamics of Circulating Tumor DNA in Liquid Biopsies

Cancers, Год журнала: 2024, Номер 16(13), С. 2432 - 2432

Опубликована: Июль 1, 2024

Circulating tumor DNA (ctDNA), a fragment of found in the bloodstream, has emerged as revolutionary tool cancer management. This review delves into biology ctDNA, examining release mechanisms, including necrosis, apoptosis, and active secretion, all which offer information about state nature tumor. Comprehensive profiling been enabled by methods such whole genome sequencing methylation analysis. The low abundance ctDNA fraction makes alternative techniques, digital PCR targeted next-generation exome sequencing, more valuable accurate for mutation detection. There are numerous clinical applications analysis, non-invasive liquid biopsies minimal residual disease monitoring to detect recurrence, personalized medicine therapy identification, early detection, real-time evaluation therapeutic response. Integrating analysis routine practice creates promising avenues successful care, from diagnosis treatment follow-up.

Язык: Английский

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