ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Dynamic Mutational Landscape of Cerebrospinal Fluid Circulating Tumor DNA and Predictors of Survival after Proton Craniospinal Irradiation for Leptomeningeal Metastases.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Cerebrospinal fluid ctDNA as a prognostic and disease-activity biomarker in leptomeningeal metastases: systematic review, meta-analysis, and implications for CSF-guided care.Journal of neuro-oncology · 2026Pooled it
- Proton Craniospinal Irradiation for Patients With Leptomeningeal Metastasis: A Randomized Clinical Trial.JAMA oncology · 2025Trial
- Advances in cerebrospinal fluid biomarkers for the diagnosis, treatment and monitoring of leptomeningeal metastases (Review).Oncology letters · 2026Review
- Integration of Liquid Biopsy for Optimal Management of Non-small Cell Lung Cancer.Tuberculosis and respiratory diseases · 2025Article
- Tumor Marker Test in Cerebrospinal Fluid for Leptomeningeal Metastasis Diagnosis and Response Assessment in Non-Small-Cell Lung Cancer.European journal of neurology · 2025Article
- Article
- Leptomeningeal metastatic disease: new frontiers and future directions.Nature reviews. Clinical oncology · 2025Review
- Clinical characteristics and analysis of cerebrospinal fluid biochemical, tumor markers and cytologic indices in 209 patients with meningeal carcinomatosis: a cross-sectional study.Frontiers in oncology · 2025Article
- Leptomeningeal metastases from solid tumors: A Society for Neuro-Oncology and American Society of Clinical Oncology consensus review on clinical management and future directions.Neuro-oncology · 2024Review
- Quantification of cerebrospinal fluid tumor DNA in lung cancer patients with suspected leptomeningeal carcinomatosis.NPJ precision oncology · 2024Article
- Applications of cerebrospinal fluid circulating tumor cells and circulating tumor-derived DNA in diagnosis, prognosis, and personalized treatment of CNS metastases.Frontiers in oncology · 2024Review
- Leptomeningeal Metastases in Melanoma Patients: An Update on and Future Perspectives for Diagnosis and Treatment.International journal of molecular sciences · 2023Review
- Emerging technologies for cancer therapy using accelerated particles.Progress in particle and nuclear physics · 2023Article
- Comparative evaluation of the diagnostic and prognostic performance of CNSide™ versus standard cytology for leptomeningeal disease.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
purposeProton craniospinal irradiation (pCSI) is a promising treatment for patients with solid tumor leptomeningeal metastasis (LM). We hypothesize that genetic characteristics before and changes resulting after pCSI will reflect clinical response to pCSI. We analyzed the cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) from patients receiving pCSI for LM and explored genetic variations associated with response. EXPERIMENTAL
designWe subjected CSF from 14 patients with LM before and after pCSI to cell-free DNA sequencing using a targeted-sequencing panel. In parallel, plasma ctDNA and primary tumors were subjected to targeted sequencing. Variant allele frequency (VAF) and cancer cell fraction (CCF) were calculated; clonality of observed mutations was determined. Kaplan-Meier analysis was used to associate genomic changes with survival.
resultsThe median overall survival (OS) for the cohort was 9 months [interquartile range (IQR), 5-21 months]. We showed clonal evolution between tumor and ctDNA of the CSF and plasma with unique mutations identified by compartment. Higher CSF ctDNA mean VAF before pCSI (VAFpre) had worse OS (6 months for VAFpre ≥ 0.32 vs. 9 months for VAFpre < 0.32; P = 0.05). Similarly, increased VAF after pCSI portended worse survival (6 vs. 18 months; P = 0.008). Higher mean CCF of subclonal mutations appearing after pCSI was associated with worse OS (8 vs. 17 months; P = 0.05).
conclusionsIn patients with solid tumor LM undergoing pCSI, we found unique genomic profiles associated with pCSI through CSF ctDNA analyses. Patients with reduced genomic diversity within the leptomeningeal compartment demonstrated improved OS after pCSI suggesting that CSF ctDNA analysis may have use in predicting pCSI response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.