BACKGROUND Appropriate patient stratification is of paramount importance in patients with primary central nervous system lymphomas (PCNSL) in order to improve therapeutic choices and to reduce treatment-related neurotoxicity. Age and performance status, two widely used prognostic indicators, may not be the most appropriate parameters for an optimal patient stratification, as age seldom reveals the true biological frailty of a patient and performance status scores are subject to inter-rater variability. Quantitative muscle biomarkers such as the skeletal-muscle-index at the third lumbar vertebra (L3-SMI) and temporal muscle thickness (TMT) are associated with worse prognosis in several oncological diseases. We aim to evaluate the role of these biomarkers in predicting survival in patients with PCNSL undergoing high-dose methotrexate-based chemotherapy. MATERIAL AND METHODS L3-SMI and TMT were calculated on abdominal CT and brain high-resolution 3D-T1-weighted-MR images, respectively, using predefined validated methods. Standardized sex-specific cut-offs were used to divide patients in different risk categories. Kaplan-Meier plots were calculated, and survival analysis was performed using log-rank tests, univariate, and multivariable Cox-regression models, calculating hazard ratios (HR) and 95% confidence intervals (CI), also adjusting for potential confounders (age, sex, and performance status). RESULTS Forty-three patients were included in this study. Median follow-up was 23 months (interquartile range 12–40); at median follow-up, rates of progression-free and overall survival for the cohort were 46% and 57%, respectively. Thirteen (30%) and 11 (26%) patients showed L3-SMI or TMT values below the predefined cut-offs. Subgroup analyses showed a significant association between quantitative muscle mass biomarkers and progression-free and overall survival. One-year progression free and overall survival rates were 8% and 21% for the 13 patients with L3-SMI below the standard cut-off value, respectively, compared to 66% and 68% for the 30 patients with L3-SMI above the cut-off values. Likewise, one-year progression free and overall survival rates were 10% and 15% for the 11 patients with low TMT, respectively, compared to 61% and 70% for the 32 patients with high TMT. In Cox-regression multivariable analysis patients with low L3-SMI or TMT showed significantly worse progression-free (HR 4.40, 95%CI 1.66–11.61, p = 0.003; HR 4.40, 95%CI 1.68–11.49, p=0.003, respectively) and overall survival (HR 3.16, 95%CI 1.09–9.11, p = 0.034; HR 4.93, 95%CI 1.78–13.65, p=0.002, respectively) compared to patients with high L3-SMI or TMT. CONCLUSION Quantitative muscle mass evaluation assessed by both L3-SMI and TMT is a promising tool to identify PCNSL patients at high risk of negative outcome. Confirmatory studies on larger independent series are warranted.

中文翻译：

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P14.55 定量肌肉质量生物标志物是原发性中枢神经系统淋巴瘤的独立预后因素：L3 骨骼肌指数和颞肌厚度的作用

背景 适当的患者分层对于原发性中枢神经系统淋巴瘤 (PCNSL) 患者至关重要，以改善治疗选择并减少治疗相关的神经毒性。年龄和体能状态是两个广泛使用的预后指标，可能不是最佳患者分层的最合适参数，因为年龄很少揭示患者真正的生物学脆弱性，体能状态评分受评分者间变异性的影响。定量肌肉生物标志物，如第三腰椎骨骼肌肉指数 (L3-SMI) 和颞肌厚度 (TMT) 与几种肿瘤疾病的预后较差有关。我们旨在评估这些生物标志物在预测接受大剂量甲氨蝶呤化疗的 PCNSL 患者的生存率中的作用。材料和方法 L3-SMI 和 TMT 分别使用预定义的验证方法在腹部 CT 和脑部高分辨率 3D-T1 加权 MR 图像上计算。标准化的性别特异性截止值用于将患者划分为不同的风险类别。计算 Kaplan-Meier 图，并使用对数秩检验、单变量和多变量 Cox 回归模型进行生存分析，计算风险比 (HR) 和 95% 置信区间 (CI)，同时调整潜在的混杂因素（年龄、性别和表现状态）。结果 43 名患者被纳入本研究。中位随访时间为 23 个月（四分位距 12-40）；在中位随访时，该队列的无进展生存率和总生存率分别为 46% 和 57%。13 名 (30%) 和 11 名 (26%) 患者的 L3-SMI 或 TMT 值低于预定义的临界值。亚组分析显示定量肌肉质量生物标志物与无进展生存期和总生存期之间存在显着关联。13 名 L3-SMI 低于标准临界值的患者的一年无进展生存率和总生存率分别为 8% 和 21%，而 30 名 L3-SMI 高于标准临界值的患者的一年无进展生存率和总生存率分别为 66% 和 68%截止值。同样，11 名 TMT 低的患者的一年无进展生存率和总生存率分别为 10% 和 15%，而 32 名 TMT 高的患者为 61% 和 70%。在 Cox 回归多变量分析中，L3-SMI 或 TMT 低的患者无进展情况显着更差（HR 4.40, 95%CI 1.66–11.61, p = 0.003; HR 4.40, 95%CI 1.68–11.49, p=0.003，分别) 和总生存期 (HR 3.16, 95%CI 1.09–9.11, p = 0.034; HR 4.93, 95%CI 1.78–13.65, p=0.002) 与高 L3-SMI 或 TMT 患者相比。结论 通过 L3-SMI 和 TMT 评估的定量肌肉质量评估是一种有前途的工具，可用于识别具有高阴性结果风险的 PCNSL 患者。有必要对更大的独立系列进行验证性研究。结论 通过 L3-SMI 和 TMT 评估的定量肌肉质量评估是一种有前途的工具，可用于识别具有高阴性结果风险的 PCNSL 患者。有必要对更大的独立系列进行验证性研究。结论 通过 L3-SMI 和 TMT 评估的定量肌肉质量评估是一种有前途的工具，可用于识别具有高阴性结果风险的 PCNSL 患者。有必要对更大的独立系列进行验证性研究。