ctDNA detection in cerebrospinal fluid and plasma and mutational concordance with the primary tumor in a multicenter prospective study of patients with glioma

Annals of Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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ESMO Recommendations on clinical reporting of genomic test results for solid cancers

Annals of Oncology, Journal Year: 2024, Volume and Issue: 35(11), P. 954 - 967

Published: July 9, 2024

•These Recommendations cover the preparation of genomic reports to inform clinical decisions for patients with solid cancers.•Recommendations are based on consensus from a multidisciplinary group experts after reviewing available evidence.•The manuscript provides guidance structuring reports, and optimal presentation content each section.•These recommendations relevant most next-generation sequencing assays utilised in practice research.•Recommendations categorised into priority levels (A, B) adapt diverse laboratory contexts. BackgroundGenomic tumour profiling has crucial role management cancers, as it helps selecting prioritising therapeutic interventions prognostic predictive biomarkers, well identifying markers hereditary cancers. Harmonised approaches interpret results testing needed support physicians their decision making, prevent inequalities precision medicine maximise patient benefit cancer options.MethodsThe European Society Medical Oncology (ESMO) Translational Research Precision Medicine Working Group assembled international propose preparing These aim foster best practices integrating within settings. After review evidence, several rounds surveys focused discussions were conducted reach recommendation statements. Only reported. Recommendation statements graded two tiers importance: level A (required maintain common standards reporting) B (optional but necessary achieve ideal practice).ResultsGenomics should present key information front page(s) followed by supplementary one or more appendices. Reports be structured sections: (i) sample details; (ii) assay data analysis characteristics; (iii) sample-specific performance quality control; (iv) alterations functional annotation; (v) actionability assessment matching potential therapy indications; (vi) summary main findings. Specific prepare these sections made.ConclusionsWe set aimed at genomics enhance physician comprehension Communication between ordering professionals reporting is minimise uncertainties optimise impact tests care. Genomic options. The practice). Genomics made. We

Language: Английский

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Plasma Cell-Free Tumor Methylome as a Biomarker in Solid Tumors: Biology and Applications

Current Oncology, Journal Year: 2024, Volume and Issue: 31(1), P. 482 - 500

Published: Jan. 13, 2024

DNA methylation is a fundamental mechanism of epigenetic control in cells and its dysregulation strongly implicated cancer development. Cancers possess an extensively hypomethylated genome with focal regions hypermethylation at CPG islands. Due to the highly conserved nature cancer-specific methylation, detection cell-free plasma using liquid biopsies constitutes area interest biomarker research. The advent next-generation sequencing newer computational technologies have allowed for development diagnostic prognostic biomarkers that utilize profiling diagnose disease stratify risk. Methylome-based predictive can determine response anti-cancer therapy. An additional emerging application these minimal residual monitoring. Several key challenges need be addressed before cfDNA-based become fully integrated into practice. first relates biology stability cfDNA. second concerns clinical validity generalizability methylation-based assays, many which are type-specific. third involves their practicability, stumbling block translating from bench clinic. Future work on developing pan-cancer assays respective validities confirmed well-designed, prospective trials crucial pushing greater use tools oncology.

Language: Английский

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Next-generation sequencing impact on cancer care: applications, challenges, and future directions

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 15

Published: July 9, 2024

Fundamentally precision oncology illustrates the path in which molecular profiling of tumors can illuminate their biological behavior, diversity, and likely outcomes by identifying distinct genetic mutations, protein levels, other biomarkers that underpin cancer progression. Next-generation sequencing became an indispensable diagnostic tool for diagnosis treatment guidance current clinical practice. Nowadays, tissue analysis benefits from further support through methods like comprehensive genomic liquid biopsies. However, medicine field presents specific hurdles, such as cost-benefit balance widespread accessibility, particularly countries with low- middle-income. A key issue is how to effectively extend next-generation all patients, thus empowering decision-making. Concerns also quality preservation samples, well evaluation health technologies. Moreover, technology advances, novel assessments are being developed, including study Fragmentomics. Therefore, our objective was delineate primary uses sequencing, discussing its’ applications, limitations, prospective paths forward Oncology.

Language: Английский

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The evolving landscape of metastatic HER2-positive, hormone receptor-positive Breast Cancer

Cancer Treatment Reviews, Journal Year: 2024, Volume and Issue: 128, P. 102761 - 102761

Published: May 16, 2024

Language: Английский

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The expansion of liquid biopsies to vascular care: an overview of existing principles, techniques and potential applications to vascular malformation diagnostics

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 18, 2024

Vascular malformations are congenital lesions that occur due to mutations in major cellular signalling pathways which govern angiogenesis, cell proliferation, motility, and death. These have been widely studied oncology substrates for various small molecule inhibitors. Given their common molecular biology, there is now a potential repurpose these cancer drugs vascular malformation care; however, diagnosis required order tailour specific the individual patient’s mutational profile. Liquid biopsies (LBs), emerging as transformative tool field of oncology, hold significant promise this feat. This paper explores principles technologies underlying LBs evaluates revolutionize management malformations. The review begins by delineating fundamental LBs, focusing on detection analysis circulating biomarkers such cell-free DNA, tumor cells, extracellular vesicles. Subsequently, an in-depth technological advancements driving LB platforms presented. Lastly, highlights current state research applying malformations, uses aforementioned techniques conceptualize liquid biopsy framework unique clinical care.

Language: Английский

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Current Challenges of Methylation-Based Liquid Biopsies in Cancer Diagnostics

Cancers, Journal Year: 2024, Volume and Issue: 16(11), P. 2001 - 2001

Published: May 24, 2024

In current clinical practice, effective cancer testing and screening paradigms are limited to specific types of cancer, exhibiting varying efficiency, acceptance, adherence. Cell-free DNA (cfDNA) methylation profiling holds promise in providing information about the presence malignity regardless its type location while leveraging blood-based liquid biopsies as a method obtain analytical samples. However, technical difficulties, costs challenges resulting from biological variations, tumor heterogeneity, exogenous factors persist. This exploits mechanisms behind cfDNA release but faces issues like fragmentation, low concentrations, high background noise. review explores methylation's origins, means detection, for diagnostics. The critical evaluation currently available multi-cancer early detection methods (MCEDs) well tests targeting single genes, emphasizing their potential limits refine strategies explained. methodology limitations, workflows, comparisons clinically approved biopsy-based utilization companion diagnostics limitations epigenetics approach discussed, aiming help healthcare providers researchers orient themselves this increasingly complex evolving field

Language: Английский

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Comprehensive analysis of clinical, pathological, and molecular features in chronic myelomonocytic leukemia: frequent ASXL1 and NRAS mutations and higher mutation burden in myeloproliferative CMML compared to myelodysplastic CMML

Leukemia & lymphoma/Leukemia and lymphoma, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 10

Published: Jan. 17, 2025

Various aspects of myeloproliferative chronic myelomonocytic leukemia (MP-CMML) and myelodysplastic CMML (MD-CMML) have been reported but inconsistencies remain. This study conducted a comprehensive retrospective analysis clinical, pathological, molecular data from cohort CMML. The results revealed higher frequency ASXL1 NRAS mutations greater mutation burden in MP-CMML, characterized by more tier 1 or 2 variants dominant mutations. Significant genotype-phenotype correlations were observed, including distinct patterns within MD-CMML subgroups. Additionally, RUNX1 an abnormal karyotype associated with worse overall survival progression-free survival. These findings underscore the pathological differences between MP-CMML MD-CMML, highlighting aggressive nature need for tailored treatment strategies.

Language: Английский

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Clinical integration of germline findings from a tumor testing precision medicine program

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 30, 2025

Abstract Background Integrating germline genetic testing (GGT) recommendations from tumor into hereditary cancer clinics and precision oncology trials presents challenges that require multidisciplinary expertise infrastructure. While there have been advancements in standardizing molecular boards, the implementation of profiling for germline-focused assessments has only recently gained momentum. However, this progress remains inconsistent across institutions, largely owing to a lack systematic approaches managing these findings. This study outlines development clinical pathway identifying potential variants an institutional tumor-sequencing research program at Princess Margaret Cancer Centre. Methods Between August 2022 2023, led by Molecular Tumor Board (gMTB) was established review (TGVs) flagged as findings patients with advanced via multigene panel. Eligibility syndrome investigation (‘germline criteria’) followed Care Ontario’s Hereditary Testing Criteria judgment. Germline-focused analysis TGVs European Society Medical Oncology guidelines similar published criteria (‘tumor-only criteria’). Results Of 243 profiles, 83 (34.2%) had least one TGV laboratory potentially were therefore referred gMTB further review. Among cases, 47 (56.6%) met ‘germline criteria’ GGT, regardless assessment. A total 127 assessed which 44 (34.6%) considered relevant . Tier I TGVs, interpreted pathogenic/likely pathogenic (P/LP) found most- or standard-actionable genes high conversion rates (GCRs) any context, more likely be ( p -value < 0.05). One confirmed variant identified nine meeting solely ‘tumor-only criteria’. Overall, 27/44 underwent testing. We P/LP 9 cases entire cohort, GCR 33% (9/27). Conclusions Incorporating counselors gMTBs enhanced integration care improved detection disease-causing outside traditional criteria.

Language: Английский

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Cell-Free Circulating Tumor DNA for Non-Invasive Molecular Profiling Among Patients Undergoing Definitive Chemoradiation for Locally Advanced Lung Cancer

Advances in Radiation Oncology, Journal Year: 2025, Volume and Issue: 10(4), P. 101727 - 101727

Published: Feb. 2, 2025

We prospectively explored the utility of liquid biopsy for cell-free circulating tumor DNA (ctDNA) as a prognostic and predictive biomarker in patients with non-small cell lung cancer (NSCLC) treated definitive chemoradiation therapy. This prospective clinical cohort consisted unresectable, locally advanced NSCLC who had testing before initiation Liquid was performed using an institutional assay that included 129 genes paired white blood sequencing. Variant allele frequency defined proportion mutant alleles at particular genetic locus. A US Food Drug Administration-recognized database (OncoKB) used to classify alterations. evaluated progression-free survival from start radiation therapy log-rank test. Among 25 ctDNA levels initiation, 18 adenocarcinoma (72%), 7 squamous carcinoma (28%), 23 (92%) were former or current smokers. Twelve (48%) received adjuvant durvalumab. The median dose 60 Gy 30 fractions (range, 55-66 20-33 fractions). Seventy-six percent (n = 18) one more alterations detected (median, 3 alterations, range, 1-8), including genomic markers response patients. most common driver alteration KRAS mutation 24% 6). detection significantly associated pretreatment 18F-fluorodeoxyglucose positron emission tomography standardized uptake value metrics, association strengthened by integrating number mutations (compared variant frequency) outcome variable. baseline detectable levels, 21.3 months not reached among without level (hazard ratio, 4.54, P .04). Prospective identifies direct implications personalization.

Language: Английский

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