Cerebrospinal fluid protein biomarkers are associated with response to multiagent intraventricular chemotherapy in patients with CNS lymphoma
Bibliographic record
Abstract
Background: Central nervous system lymphoma (CNSL), is a rare subtype of non-Hodgkin lymphoma, primarily affecting the brain and spinal cord. Most therapeutic systemic agents have limited penetration of the blood-brain and blood-cerebrospinal fluid (CSF) barrier, with the latter potentially promoting a treatment "sanctuary" for cancer cells. Evaluation of occult disease, particularly in the CSF, is challenging. In limited clinical experience, the addition of multiagent intraventricular chemotherapy (MAIVC), delivered through intracranially implanted CSF reservoirs, to systemic therapy has demonstrated encouraging outcomes, enhancing both progression-free survival and overall survival. However, given the potential morbidity associated with MAIVC, identification of minimally invasive biomarkers for guiding patient selection and management is necessary. Leveraging the longitudinal, large volume of CSF, the objective of this study was to identify CSF-based proteomic biomarkers that can serve as reliable indicators of CSF clearance in response to MAIVC and CNSL treatment outcome. Methods: One hundred fifteen CSF samples from 59 CNSL patients receiving MAIVC were profiled using a high-throughput protocol coupled with mass-spectrometry that only requires 30 μL of CSF. Results: More than 2000 unique proteins were detected using shotgun proteomics. Cerebrospinal fluid proteomics revealed key proteins (SGCE, LCP1, AGRN, OLFML3, and HRSP12) distinguishing early from never responders to MAIVC, with area under the receiver operating characteristic (AUROC) 0.86 (95% CI: 0.696-1). By integrating tumor volume from brain MRI scans with proteomic data, we identified potential intraventricular tumor burden markers for CNSL management, in particular LCP1. Conclusions: The study identified CSF-based proteomic biomarkers, particularly LCP1, that can classify MAIVC response and indicate tumor burden in CNSL patients.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".