Tumor Marker Test in Cerebrospinal Fluid for Leptomeningeal Metastasis Diagnosis and Response Assessment in Non-Small-Cell Lung Cancer.

BACKGROUNDS: Current methods for diagnosis and disease monitoring for leptomeningeal metastasis (LM) face significant challenges, as they are relatively complex and lack the precision needed to detect subtle changes.

METHODS

We conducted a retrospective study with the primary endpoint of assessing the diagnostic effectiveness of cerebrospinal fluid (CSF) tumor markers in LM patients with non-small-cell lung cancer (NSCLC). Secondary endpoints included evaluating the concordance with EANO-ESMO response assessment, determining optimal thresholds, and comparing costs against CSF ctDNA tests.

RESULTS

We retrospectively included 368 patients (151 LM patients, 219 non-LM patients) as the training set, and another 137 patients (63 LM patients, 74 non-LM patients) on a consecutive basis as the validation set. The CSF tumor marker panel using a logistic model showed the best performance both in the training set (AUC [95% CI] = 0.992 [0.984-1.000]) and the validation set (AUC [95% CI] = 0.939 [0.891-0.986]). In the response assessment, 167 events were evaluated, with 33 classified as response, 59 as stable, and 75 as progression. We found a concordance with EANO-ESMO response assessment, and a threshold of ± 25% of the maximal CSF tumor marker level change (maxTML) yielded the optimal predictive performance. Finally, the cost of the CSF tumor marker test (0.76%, IQR (0.30%-1.67%)) was significantly lower in a single hospitalization than CSF ctDNA (62.45%, IQR (32.62%-85.81%)).

CONCLUSION

Our study demonstrated that the CSF tumor marker test was an accurate, easily interpretable, and cheap tool for both diagnosis and monitoring therapeutic response in LM patients with NSCLC.

TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) number: ChiCTR2300078556.