Whole brain radiotherapy and intrathecal injection of thiotepa, combined with systemic treatment for the primary tumor, to treat solid tumor leptomeningeal metastasis: A prospective, single center, single arm, phase II clinical study.

2027 Background: To evaluate the efficacy and toxicity of a triple therapy regimen consisting of Hippocampal-sparing whole-brain radiotherapy (HS-WBRT), intrathecal Thiotepa (ITT), and primary lesion treatment for solid tumor leptomeningeal metastasis (LM). (NCT06376292). Methods: Based on the comprehensive results of MRI and cytology evidence, patients diagnosed with LM according to the diagnostic criteria in the EANO-ESMO guidelines meet the criteria. Patient began ITT twice a week, and underwent HS-WBRT as soon as possible. Before each ITT, cerebrospinal fluid (CSF) pressure is measured and CSF is collected for testing, including protein, tumor markers, IgG, albumin levels of CSF, and albumin ratio. MRI re-examination is conducted every three months, and the RANO-LM criteria is used to evaluate the response of patients after treatment. Besides,the LM-PROG SCORE we designed can be used as an indicator to evaluate the treatment effect and adjust the medication frequency or switch the treatment line of intrathecal Pemetrexed (IP). The primary endpoint is overall survival. Results: As of December 1, 2024, a total of 57 patients have been enrolled. 40 patients were included in the statistics. Most cases are lung cancer (27, 67.5%), in addition to breast cancer(8, 20%), gastric cancer (3, 7.5%), rectal cancer (1, 2.5%) and cervical cancer (1, 2.5%). The mOS was 7.8 months (95% CI 2.06-13.54 months). The mPFS was 5.63 months (95% CI 0.76-10.51 months). The RANO-assessed ORR to treatment was 62.5% (10/16), DCR was 87.5% (14/16), with 24 patients (60%) not reaching the follow-up time. The three longest survival among alive patients are 21.3 months, 14.9 months, and 12.7 months. The most significant effect of combination therapy is the rapid relief of symptoms. 25% of patients (10/40) had already experienced unconsciousness (RASS≠0) at the time of diagnosis. After our treatment, all patients regained consciousness (RASS = 0). The long-term therapeutic effect also significantly reduces tumor markers, protein content, albumin and IgG content, pressure drop, and albumin ratio in CSF, indicating the recovery of the blood-brain barrier. 85% of patients experience varying degrees of bone marrow suppression during treatment, but most are mild and can tolerate subsequent ITT maintenance after treatment. Conclusions: Under the efficacy guidance of LM-PROG SCORE we designed, our combination therapy can greatly improve patients' overall survival, progression free survival, and quality of life. And it was found that in addition to imaging, indicators such as protein content, IgG and albumin content, Albumin Ratio and tumor markers in CSF can serve as efficacy evaluation indicators. Clinical trial information: NCT06376292 .