Lo Yu Tung, Lim Vivian Yujing, Ng Melissa, Tan Ya Hwee, Chiang Jianbang, Chang Esther Wei Yin, Chan Jason Yongsheng, Poon Eileen Yi Ling, Somasundaram Nagavalli, Bin Harunal Rashid Mohamad Farid, Tao Miriam, Lim Soon Thye, Yang Valerie Shiwen
Department of Neurosurgery, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore.
Department of Neurosurgery, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.
Cancers (Basel). 2022 Apr 3;14(7):1818. doi: 10.3390/cancers14071818.
Background: Ratios of differential blood counts (hematological indices, HIs) had been identified as prognostic variables in various cancers. In primary central nervous system lymphomas (PCNSLs), higher baseline neutrophil-lymphocyte ratio (NLR) in particular was found to portend a worse overall survival. However, it was often observed that differential counts shift drastically following steroid administration. Moreover, steroids are an important part of the arsenal against PCNSL due to its potent lymphotoxic effects. We showed that the effect of steroids on differential blood cell counts and HIs could be an early biomarker for subsequent progression-free (PFS) and overall survival (OS). Methods: This study retrospectively identified all adult patients who received a brain biopsy from 2008 to 2019 and had histologically confirmed PCNSL, and included only those who received chemoimmunotherapy, with documented use of corticosteroids prior to treatment induction. Different blood cell counts and HIs were calculated at three time-points: baseline (pre steroid), pre chemoimmunotherapy (post steroid) and post chemoimmunotherapy. Tumor progression and survival data were collected and analyzed through Kaplan−Meier estimates and Cox regression. We then utilized selected variables found to be significant on Kaplan−Meier analysis to generate a decision-tree prognostic model, the NNI-NCCS score. Results: A total of 75 patients who received chemoimmunotherapy were included in the final analysis. For NLR, OS was longer with higher pre-chemoimmunotherapy (post-steroid) NLR (dichotomized at NLR ≥ 4.0, HR 0.42, 95% CI: 0.21−0.83, p = 0.01) only. For platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR), OS was better for lower post-chemoimmunotherapy PLR (dichotomized at PLR ≥ 241, HR 2.27, 95% CI: 1.00 to 5.18, p = 0.05) and lower pre-chemoimmunotherapy (post-steroid) LMR (dichotomized at LMR ≥25.7, HR 2.17, 95% CI: 1.10 to 4.31, p = 0.03), respectively, only. The decision-tree model using age ≤70, post-steroid NLR >4.0, and pre-steroid (baseline) NLR <2.5 and the division of patients into three risk profiles—low, medium, and high—achieved good accuracy (area-under-curve of 0.78), with good calibration (Brier score: 0.16) for predicting 2-year overall survival. Conclusion: We found that post-steroid NLR, when considered together with baseline NLR, has prognostic value, and incorporation into a prognostic model allowed for accurate and well-calibrated stratification into three risk groups.
不同血细胞计数比值（血液学指标，HIs）已被确定为多种癌症的预后变量。在原发性中枢神经系统淋巴瘤（PCNSLs）中，尤其发现较高的基线中性粒细胞与淋巴细胞比值（NLR）预示着总体生存期较差。然而，经常观察到在使用类固醇后，血细胞分类计数会发生急剧变化。此外，由于类固醇具有强大的淋巴细胞毒性作用，它是对抗PCNSL的重要药物之一。我们发现，类固醇对不同血细胞计数和HIs的影响可能是后续无进展生存期（PFS）和总生存期（OS）的早期生物标志物。方法：本研究回顾性确定了2008年至2019年期间所有接受脑活检且组织学确诊为PCNSL的成年患者，仅纳入接受化疗免疫治疗且在诱导治疗前有使用皮质类固醇记录的患者。在三个时间点计算不同的血细胞计数和HIs：基线（类固醇治疗前）、化疗免疫治疗前（类固醇治疗后）和化疗免疫治疗后。通过Kaplan-Meier估计和Cox回归收集并分析肿瘤进展和生存数据。然后，我们利用在Kaplan-Meier分析中发现具有显著意义的选定变量生成一个决策树预后模型，即NNI-NCCS评分。结果：最终分析纳入了75例接受化疗免疫治疗的患者。对于NLR，仅化疗免疫治疗前（类固醇治疗后）NLR较高（以NLR≥4.0二分法划分，HR 0.42，95%CI：0.21−0.83，p = 0.01）时，OS更长。对于血小板与淋巴细胞比值（PLR）和淋巴细胞与单核细胞比值（LMR），仅化疗免疫治疗后PLR较低（以PLR≥241二分法划分，HR 2.27，95%CI：1.00至5.18，p = 0.05）和化疗免疫治疗前（类固醇治疗后）LMR较低（以LMR≥25.7二分法划分，HR 2.17，95%CI：1.10至4.31，p = 0.03）时，OS更好。使用年龄≤70岁、类固醇治疗后NLR>4.0、类固醇治疗前（基线）NLR<2.5以及将患者分为低、中、高三个风险组的决策树模型，在预测2年总生存期方面具有良好的准确性（曲线下面积为0.78）和良好的校准度（Brier评分：0.16）。结论：我们发现，将类固醇治疗后的NLR与基线NLR一起考虑具有预后价值，将其纳入预后模型可实现准确且校准良好的分层，分为三个风险组。
