The Level of Circulating M-MDSCs as an Indicator for the Therapeutic Outcome of BNCT in End-Stage Malignant Brain Tumor Patients

循环M-MDSC水平作为晚期恶性脑肿瘤患者BNCT治疗效果的指标

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作者:Chun-Hsiang Chang ,Ching-Fang Yu ,Fang-Hsin Chen ,Yi-Wei Chen ,Chi-Shiun Chiang

Abstract

Purpose: Boron neutron capture therapy (BNCT) is a promising treatment modality for patients diagnosed with malignant brain tumors. It is currently used for emergency and compassionate purposes to treat end-stage malignant glioma or recurrent head and neck cancer patients in Taiwan. Understanding the factors influencing treatment response is crucial for optimizing patient care. This study aimed to investigate the association between tumor response and various parameters in end-stage malignant glioma patients following BNCT. Patients and methods: Fifteen patients with end-stage malignant brain tumors underwent a single fraction of BNCT. The treatment response was evaluated using cranial magnetic resonance imaging, and the association between treatment response and BNCT parameters was analyzed. Additionally, circulating myeloid-derived suppressor cell (MDSC) levels were measured by flow cytometry and correlated with patients' survival. Results: BNCT exhibited significant therapeutic efficacy in reducing tumor volume of these end-stage glioma patients, with 3 patients achieving complete response and 10 patients achieving partial response within 1 month, resulting in an impressive objective response rate of 80%. The median overall survival is 9 (1.77, 12.47) months, and the progression-free survival is 1.34 (0.53, 9.53) months. Kaplan-Meier analysis showed that the patients with complete response and partial response displayed better survival than those with stable disease. Treatment response was not significantly associated with initial tumor size, blood boron concentration, tumor-to-normal tissue ratio, or tumor-to-blood ratio. The ROC curve revealed a cut-off value of 5% of circulating M-MDSCs with a sensitivity of 66.67% and specificity of 73.33%, respectively, for predicting the glioma patient's response to BNCT. Conclusion: This clinical study demonstrates that BNCT can reduce tumor burden, improve disease control, and prolong survival in end-stage glioma patients. Circulating M-MDSCs may serve as a predictive indicator for the treatment response of these patients following BNCT.

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