Lee Shing Fung, Yip Pui Lam, Wong Aray, Ng Francesca, Koh Vicky, Wong Lea Choung, Luk Hollis, Ng Chuk Kwan, Lee Francis Ann Shing, Mamon Harvey J
Department of Clinical Oncology, Tuen Mun Hospital, Hospital Authority, Hong Kong.
Department of Clinical Oncology, Queen Mary Hospital, Hospital Authority, Hong Kong.
Clin Transl Radiat Oncol. 2022 Jul 21;36:83-90. doi: 10.1016/j.ctro.2022.07.007. eCollection 2022 Sep.
Adjuvant chemoradiation therapy (CRT) in gastric cancer inevitably results in an unintentional spleen radiation dose. We aimed to determine the association between the spleen radiation dose and the observed severity of lymphopenia which may affect the clinical outcomes (survival time and infection risk).
Patients who received adjuvant CRT for gastric cancer between January 2015 and December 2020 were analyzed. The splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least × Gray (Gy). Peripheral blood counts were recorded pre- and post-CRT. The development of severe (Common Terminology Criteria for Adverse Events, version 5.0, grade ≥ 3) post-CRT lymphopenia (absolute lymphocyte count [ALC] < 0.5 K/μL) was assessed by multivariable logistic regression using patient and dosimetric factors. Overall survival (OS), recurrence-free survival (RFS), and cumulative incidence of infectious events were estimated and analyzed using the Cox model or competing risk analysis.
Eighty-four patients with a median follow-up duration of 42 months were analyzed. Pre- and post-CRT median ALC values were 1.8 K/μL (0.9-3.1 K/μL) and 0.9 K/μL (0.0-4.9 K/μL), respectively ( < 0.001). MSD > 40 Gy (odds ratio [OR], 1.13; 95 % confidence interval [CI], 1.01-1.26; = 0.041), sex (OR for male to female, 0.25; 95 % CI, 0.09-0.70; = 0.008), and baseline absolute neutrophil count (OR per 1 unit increase, 1.61; 95 % CI, 1.02-2.58; = 0.040) were associated with the development of severe post-CRT lymphopenia, which was a risk factor for poorer OS (hazard ratio [HR] = 2.47; 95 % CI, 1.24-4.92; = 0.010) and RFS (HR = 2.27; 95 % CI, 1.16-4.46; = 0.017). The cumulative incidence of infections was higher among severe post-CRT lymphopenia patients (2.53, 95 % CI, 1.03-6.23, = 0.043).
High splenic radiation doses increase the odds of severe post-CRT lymphopenia, an independent predictor of lower OS and higher risks of recurrence and infections in gastric cancer patients receiving adjuvant CRT. Therefore, optimizing the splenic DVH parameters may decrease the risk of severe post-CRT lymphopenia.
胃癌辅助放化疗（CRT）不可避免地会导致脾脏受到无意的辐射剂量。我们旨在确定脾脏辐射剂量与观察到的淋巴细胞减少严重程度之间的关联，这可能会影响临床结局（生存时间和感染风险）。
分析了2015年1月至2020年12月期间接受胃癌辅助CRT的患者。脾脏剂量体积直方图（DVH）参数报告为平均脾脏剂量（MSD）和接受至少×格雷（Gy）的脾脏体积百分比。在CRT前后记录外周血细胞计数。使用患者和剂量学因素通过多变量逻辑回归评估CRT后严重（不良事件通用术语标准，第5.0版，≥3级）淋巴细胞减少（绝对淋巴细胞计数[ALC]<0.5 K/μL）的发生情况。使用Cox模型或竞争风险分析估计并分析总生存期（OS）、无复发生存期（RFS）和感染事件的累积发生率。
分析了84例患者，中位随访时间为42个月。CRT前后的中位ALC值分别为1.8 K/μL（0.9 - 3.1 K/μL）和0.9 K/μL（0.0 - 4.9 K/μL）（<0.001）。MSD>40 Gy（比值比[OR]，1.13；95%置信区间[CI]，1.01 - 1.26；=0.041）、性别（男性与女性的OR，0.25；95%CI，0.09 - 0.70；=0.008）和基线绝对中性粒细胞计数（每增加1个单位的OR，1.61；95%CI，1.02 - 2.58；=0.040）与CRT后严重淋巴细胞减少的发生相关，这是较差OS（风险比[HR]=2.47；95%CI，1.24 - 4.92；=0.010）和RFS（HR=2.27；95%CI，1.16 - 4.46；=0.017）的危险因素。CRT后严重淋巴细胞减少患者的感染累积发生率更高（2.53，95%CI，1.03 - 6.23，=0.043）。
高脾脏辐射剂量增加了CRT后严重淋巴细胞减少的几率，这是接受辅助CRT的胃癌患者OS较低以及复发和感染风险较高的独立预测因素。因此，优化脾脏DVH参数可能会降低CRT后严重淋巴细胞减少的风险。
