Abstract

Background

We investigated differences in radiation-induced grade 3+ lymphopenia (G3+L), defined as an absolute lymphocyte count (ALC) nadir of <500 cells/µL, after proton therapy (PT) or X-ray (photon) therapy (XRT) for patients with glioblastoma (GBM).

Methods

Patients enrolled in a randomized phase II trial received PT (n = 28) or XRT (n = 56) concomitantly with temozolomide. ALC was measured before, weekly during, and within 1 month after radiotherapy. Whole-brain mean dose (WBMD) and brain dose-volume indices were extracted from planned dose distributions. Univariate and multivariate logistic regression analyses were used to identify independent predictive variables. The resulting model was evaluated using receiver operating characteristic (ROC) curve analysis.

Results

Rates of G3+L were lower in men (7/47 [15%]) versus women (19/37 [51%]) (P < 0.001), and for PT (4/28 [14%]) versus XRT (22/56 [39%]) (P = 0.024). G3+L was significantly associated with baseline ALC, WBMD, and brain volumes receiving 5‒40 Gy(relative biological effectiveness [RBE]) or higher (ie, V5 through V40). Stepwise multivariate logistic regression analysis identified being female (odds ratio [OR] 6.2, 95% confidence interval [CI]: 1.95‒22.4, P = 0.003), baseline ALC (OR 0.18, 95% CI: 0.05‒0.51, P = 0.003), and whole-brain V20 (OR 1.07, 95% CI: 1.03‒1.13, P = 0.002) as the strongest predictors. ROC analysis yielded an area under the curve of 0.86 (95% CI: 0.79–0.94) for the final G3+L prediction model.

Conclusions

Sex, baseline ALC, and whole-brain V20 were the strongest predictors of G3+L for patients with GBM treated with radiation and temozolomide. PT reduced brain volumes receiving low and intermediate doses and, consequently, reduced G3+L.

中文翻译：

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质子治疗降低胶质母细胞瘤患者高级别放射诱导淋巴细胞减少的可能性：质子与光子的 II 期随机研究

摘要

背景

我们研究了质子治疗 (PT) 或 X 射线（光子）治疗 (XRT) 后辐射诱导的 3+ 级淋巴细胞减少 (G3+L) 的差异，定义为绝对淋巴细胞计数 (ALC) 最低点 <500 个细胞/μL ) 用于胶质母细胞瘤 (GBM) 患者。

方法

参加随机 II 期试验的患者同时接受 PT（n = 28）或 XRT（n = 56）和替莫唑胺。在放疗前、放疗期间和放疗后 1 个月内每周测量 ALC。从计划的剂量分布中提取全脑平均剂量 (WBMD) 和脑剂量体积指数。使用单变量和多变量逻辑回归分析来确定独立的预测变量。使用接收者操作特征 (ROC) 曲线分析评估所得模型。

结果

男性 (7/47 [15%]) 与女性 (19/37 [51%]) 相比，G3+L 的发生率较低 ( P < 0.001)，而 PT (4/28 [14%]) 与 XRT ( 22/56 [39%]) ( P = 0.024)。G3+L 与基线 ALC、WBMD 和接受 5-40 Gy（相对生物有效性 [RBE]）或更高（即 V5 至 V40）的脑容量显着相关。逐步多元逻辑回归分析确定为女性（优势比 [OR] 6.2，95% 置信区间 [CI]：1.95-22.4，P = 0.003），基线 ALC（OR 0.18，95 % CI：0.05-0.51，P = 0.003 ) 和全脑 V20（OR 1.07，95% CI：1.03-1.13，P = 0.002）作为最强的预测因子。ROC 分析得出的最终 G3+L 预测模型的曲线下面积为 0.86（95% CI：0.79–0.94）。

结论

对于接受放疗和替莫唑胺治疗的 GBM 患者，性别、基线 ALC 和全脑 V20 是 G3+L 的最强预测因子。接受低剂量和中等剂量的 PT 减少了脑容量，因此减少了 G3+L。