Registry of an Integrated Longitudinal Multimodal Biospecimen Biobank for Primary CNS Lymphoma in China

Condition(s) studied

Investigational drug(s) / intervention(s)

High-dose methotrexate-based therapy: Standard-of-care treatment containing high-dose methotrexate as the backbone regimen, administered alone or in combination with other anticancer agents according to the treating physician's judgment and institutional practice. Treatment selection, dose, schedule, combination regimen, and duration are not assigned by the study protocol. Clinical response, recurrence, survival, adverse events, imaging findings, and longitudinal molecular biomarkers will be recorded prospectively.

Bruton tyrosine kinase inhibitor-based therapy: Standard-of-care treatment containing a Bruton tyrosine kinase inhibitor as a principal therapeutic component, administered alone or in combination with other anticancer agents according to the treating physician's judgment and institutional practice. The specific BTK inhibitor, dose, schedule, combination regimen, and duration are not assigned by the study protocol. Clinical response, recurrence, survival, adverse events, imaging findings, and longitudinal molecular biomarkers will be recorded prospectively.

Study summary

This project aims to establish and prospectively register a longitudinal, multimodal biobank for primary central nervous system lymphoma (PCNSL). The study will primarily enroll patients undergoing needle biopsy or surgical resection of lesions involving the brain, spinal cord, or meninges, with a pathological diagnosis of central nervous system lymphoma. To ensure population homogeneity, patients with PCNSL will constitute the core analysis cohort. Patients with imaging findings suggestive of PCNSL but a final pathological diagnosis other than PCNSL will serve as disease controls, and matched healthy volunteers will be recruited as baseline controls.

At baseline, biopsy tissue, cerebrospinal fluid (CSF), peripheral blood, urine, saliva, and stool samples will be collected. Follow-up visits will be scheduled at 1 month after biopsy and every 3-6 months thereafter, with contrast-enhanced brain magnetic resonance imaging (MRI) and serial collection of CSF and peripheral blood. After the requirements of routine pathological diagnosis have been met, biopsy specimens will undergo tiered multi-omics profiling according to sample availability and freshness, including whole-exome sequencing, bulk RNA sequencing, single-cell RNA sequencing, metabolomics, spatial transcriptomics, and spatial metabolomics. Analyses of CSF and blood samples will focus on circulating tumor DNA and cell-free RNA (ctDNA/cfRNA), supplemented by conventional cytology, flow cytometry, and other clinical data for longitudinal disease monitoring.

The project will develop an integrated database incorporating clinical, imaging, pathological, molecular, and biospecimen data. It will characterize the relationships of baseline tissue multi-omics features and longitudinal changes in CSF- and blood-derived ctDNA/cfRNA with treatment response, recurrence prediction, and prognosis. The study will also develop diagnostic and risk-stratification models applicable to patients at our institution, across the region, and potentially throughout mainland China, while establishing standardized operating procedures for biospecimen collection and processing. This work is expected to provide high-quality evidence and a sustainable translational research platform for elucidating the biological heterogeneity of PCNSL, validating liquid-biopsy biomarkers, and optimizing precision follow-up strategies.

Eligibility

Primary outcome measure(s)

• Baseline data completeness rate — At baseline, from enrollment through completion of baseline assessments（up to 30 months）
  Percentage of enrolled participants with complete required baseline clinical, imaging, pathological, treatment, and biospecimen information in the electronic case report form. The numerator is the number of participants with all protocol-required baseline data; the denominator is the total number of enrolled participants.
• Paired tumor tissue and cerebrospinal fluid sample acquisition rate — within 1 month after biopsy or surgery (up to 30 months)
  Percentage of eligible participants from whom both evaluable tumor tissue and cerebrospinal fluid samples are successfully collected and stored according to the study standard operating procedures.
• Participant follow-up completion rate — from enrollment to follow-up at Month 3, 6, 12, 24 and 36 (up to 36 months)
  Percentage of enrolled participants who complete the protocol-required clinical and imaging follow-up assessments at Month 12 and Month 24. Completion rates will be calculated separately for each time point.
• Adherence to longitudinal cerebrospinal fluid sampling — Postoperative Month 1 and every 3-6 months thereafter (up to 36 months)
  Percentage of scheduled cerebrospinal fluid collection visits completed among participants enrolled in the longitudinal cerebrospinal fluid/peripheral blood subcohort.
• Association between cerebrospinal fluid ctDNA clearance and MRI response — 3-6 months after pathological comfirmation (up to 36 months)
  Cerebrospinal fluid circulating tumor DNA status will be classified as cleared or not cleared at postoperative Month 3 and compared with concurrent MRI response categories-complete response, partial response, stable disease, or progressive disease. The association or agreement will be assessed using contingency-table analysis, kappa statistics, and/or receiver operating characteristic analysis, as applicable.
• Association of baseline and longitudinal ctDNA/cfRNA status with progression-free survival — From the prespecified index date through Month 3, 6, 12, 24 and 36 (up to 36 months)
  Progression-free survival will be evaluated according to baseline and longitudinal cerebrospinal fluid or peripheral blood ctDNA/cfRNA status. Progression-free survival is the time from the prespecified index date to radiographic or clinical disease progression or death from any cause, whichever occurs first.

Trial sites (3)

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