Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA.
Inova Mather Proton Centre, Inova Schar Cancer Institute, VA.
Am J Clin Oncol. 2024 Aug 1;47(8):373-382. doi: 10.1097/COC.0000000000001108. Epub 2024 May 20.
The aim of this study was to evaluate the incidence of radiotherapy (RT)-related lymphopenia, its predictors, and association with survival in unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated-RT (HF-RT).
Retrospective analysis of 96 patients with unresectable ICC who underwent HF-RT (median 58.05 Gy in 15 fractions) between 2009 and 2022 was performed. Absolute lymphocyte count (ALC) nadir within 12 weeks of RT was analyzed. Primary variable of interest was severe lymphopenia, defined as Grade 3+ (ALC <0.5 k/μL) per CTCAE v5.0. Primary outcome of interest was overall survival (OS) from RT.
Median follow-up was 16 months. Fifty-two percent of patients had chemotherapy pre-RT, 23% during RT, and 40% post-RT. Pre-RT, median ALC was 1.1 k/μL and 5% had severe lymphopenia. Post-RT, 68% developed RT-related severe lymphopenia. Patients who developed severe lymphopenia had a significantly lower pre-RT ALC (median 1.1 vs. 1.5 k/μL, P =0.01) and larger target tumor volume (median 125 vs. 62 cm 3 , P =0.02). In our multivariable Cox model, severe lymphopenia was associated with a 1.7-fold increased risk of death ( P =0.04); 1-year OS rates were 63% vs 77% ( P =0.03). Receipt of photon versus proton-based RT (OR=3.50, P =0.02), higher mean liver dose (OR=1.19, P <0.01), and longer RT duration (OR=1.49, P =0.02) predicted severe lymphopenia.
HF-RT-related lymphopenia is an independent prognostic factor for survival in patients with unresectable ICC. Patients with lower baseline ALC and larger tumor volume may be at increased risk, and use of proton therapy, minimizing mean liver dose, and avoiding treatment breaks may reduce RT-related lymphopenia.
本研究旨在评估不可切除的肝内胆管癌（ICC）患者接受分割放疗（HF-RT）后放疗相关性淋巴细胞减少症的发生率、预测因素及其与生存的关系。
回顾性分析了 2009 年至 2022 年间 96 例接受 HF-RT（中位剂量 58.05Gy，15 次分割）的不可切除 ICC 患者的资料。分析了放疗后 12 周内的绝对淋巴细胞计数（ALC）最低值。主要观察变量为 CTCAE v5.0 分级 3+（ALC<0.5k/μL）的重度淋巴细胞减少症。主要研究终点为从放疗开始的总生存（OS）。
中位随访时间为 16 个月。52%的患者在放疗前、23%在放疗期间和 40%在放疗后接受了化疗。放疗前，中位 ALC 为 1.1k/μL，5%的患者出现重度淋巴细胞减少症。放疗后，68%的患者发生了放疗相关性重度淋巴细胞减少症。发生重度淋巴细胞减少症的患者放疗前的 ALC 明显更低（中位值 1.1 与 1.5k/μL，P=0.01），肿瘤靶区体积也更大（中位值 125 与 62cm3，P=0.02）。在多变量 Cox 模型中，重度淋巴细胞减少症与死亡风险增加 1.7 倍相关（P=0.04）；1 年 OS 率分别为 63%与 77%（P=0.03）。光子放疗与质子放疗（OR=3.50，P=0.02）、平均肝剂量较高（OR=1.19，P<0.01）和放疗时间较长（OR=1.49，P=0.02）与重度淋巴细胞减少症相关。
HF-RT 相关性淋巴细胞减少症是不可切除 ICC 患者生存的独立预后因素。基线 ALC 较低和肿瘤体积较大的患者发生风险可能增加，质子治疗、最小化平均肝剂量和避免治疗中断可能会减少放疗相关性淋巴细胞减少症。
