Damen Pim J J, Peters Max, Hobbs Brian, Chen Yiqing, Titt Uwe, Nout Remi, Mohan Radhe, Lin Steven H, van Rossum Peter S N
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Radiation Oncology, Amsterdam University Medical Center, Amsterdam, The Netherlands; Department of Radiotherapy, Erasmus Medical Center Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Radiotherapy, Radiotherapiegroep, Deventer, The Netherlands.
Int J Radiat Oncol Biol Phys. 2025 May 1;122(1):31-42. doi: 10.1016/j.ijrobp.2024.12.014. Epub 2025 Jan 2.
A detrimental association between radiation-induced lymphopenia (RIL) and oncologic outcomes in patients with esophageal cancer has been established. However, an optimal metric for RIL remains undefined but is important for the application of this knowledge in clinical decision-making and trial designs. The aim of this study was to find the optimal RIL metric discerning survival.
Patients with esophageal cancer treated with concurrent chemoradiation therapy (CRT; 2004-2022) were selected. Studied metrics included absolute lymphocyte counts (ALCs) and neutrophil counts-and calculated derivatives-at baseline and during CRT. Multivariable Cox regression models for progression-free survival (PFS) and overall survival (OS) were developed for each RIL metric. The optimal RIL metric was defined as the one in the model with the highest c-statistic.
Among 1339 included patients, 68% received photon-based and 32% proton-based CRT (median follow-up, 24.9 months). In multivariable analysis, the best-performing models included "ALC in week 3 of CRT" (corrected c-statistic 0.683 for PFS and 0.662 for OS). At an optimal threshold of <0.5 × 10/μL (ie, grade ≥3 RIL), ALC in week 3 was significantly associated with PFS (adjusted hazard ratio, 1.64; 95% CI, 1.27-2.13) and OS (adjusted hazard ratio, 1.56; 95% CI, 1.15-2.08), with 5-year PFS of 29% vs 40% and OS of 38% vs 51%, respectively.
Reaching grade ≥3 RIL in week 3 of CRT for esophageal cancer is the strongest RIL metric to distinguish survival outcomes. We suggest that this metric should be the target for lymphopenia-mitigating strategies and propose this metric to be included in future trials.
食管癌患者中，辐射诱导淋巴细胞减少（RIL）与肿瘤学结局之间的有害关联已得到证实。然而，RIL的最佳衡量指标仍未明确，但对于将该知识应用于临床决策和试验设计而言至关重要。本研究的目的是找到区分生存情况的最佳RIL指标。
选取接受同步放化疗（CRT；2004 - 2022年）治疗的食管癌患者。研究的指标包括基线时以及CRT期间的绝对淋巴细胞计数（ALC）和中性粒细胞计数及其计算得出的衍生指标。针对每个RIL指标，建立了无进展生存期（PFS）和总生存期（OS）的多变量Cox回归模型。最佳RIL指标定义为模型中c统计量最高的那个指标。
在纳入的1339例患者中，68%接受基于光子的CRT，32%接受基于质子的CRT（中位随访时间为24.9个月）。在多变量分析中，表现最佳的模型包括“CRT第3周时的ALC”（PFS的校正c统计量为0.683，OS的校正c统计量为0.662）。在最佳阈值<0.5×10⁹/μL（即≥3级RIL）时，CRT第3周时的ALC与PFS（调整后风险比，1.64；95%置信区间，1.27 - 2.13）和OS（调整后风险比，1.56；95%置信区间，1.15 - 2.08）显著相关，5年PFS分别为29%和40%，5年OS分别为38%和51%。
食管癌患者在CRT第3周时达到≥3级RIL是区分生存结局的最强RIL指标。我们建议该指标应成为减轻淋巴细胞减少策略的目标，并提议将该指标纳入未来试验。
