Li Jiaxin, Mali Rahul, Gan Gregory N, Lominska Christopher, Guida Kenny, Juloori Aditya, Chen Matthew Wen-Ruey, Li Wangyao, Setianegara Jufri, Wang Chao, Lin Yuting, Li Qiang, Chen Weiqiang, Gao Hao
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.
University of Chinese Academy of Sciences, Beijing, China.
Med Phys. 2025 Apr 14. doi: 10.1002/mp.17829.
Radiation-induced lymphopenia (RIL) is a frequent complication in head and neck cancer (HNC) patients undergoing radiotherapy (RT), and its severity is associated with poorer survival outcomes.
This work aims to develop a patient-specific modeling method to simulate lymphocyte kinetics during and after RT and evaluate the lymphocyte-sparing effects across different RT treatment regimens.
A cohort of 17 HNC patients receiving unilateral irradiation with protons or photons were included in this study. The dose to circulating lymphocytes was calculated using the HEDOS model, considering lymph nodes on the irradiated side, the esophagus, auto-segmented bilateral carotid arteries and jugular veins, skeletal muscle, fat, skin, compact bone, spongy bone, red marrow, and other skeleton. A patient-specific model was developed to simulate lymphocyte kinetics that account for radiation-induced damage to both circulating lymphocytes and lymph nodes. The weekly absolute lymphocyte counts (ALC) before, during and after RT, were assembled to estimate the patient-specific parameters. Four different RT treatment regimens-conventional fractionation, hypofractionation, stereotactic body radiotherapy (SBRT), and FLASH-were evaluated to compare their lymphocyte-sparing effects.
Patients treated with protons had 17.1% less grade 3 and 4 RIL compared to photons. The mean dose to circulating lymphocytes was 1.28 ± 0.37 Gy(RBE) for proton therapy and 3.12 ± 0.75 Gy for photon therapy. The patient-specific model captured three distinct patterns of ALC kinetics: plateau phase, normal recovery, and incomplete recovery, with a mean squared error (MSE) of 0.024 ± 0.025 (mean ± SD) between the simulated and observed ALC values. On average, 42.72% of circulating lymphocytes received more than 0.1 Gy(RBE) in proton FLASH, significantly less than the 81.94% in photon FLASH. Hypofractionated RT, SBRT, and FLASH were 6.5%, 20.2%, and 29.9%, respectively, higher than conventional RT in term of ALC levels 3 months post-RT. At 1 year post-RT, most patients achieved at least 70% recovery of baseline ALC for all treatment regimens.
A patient-specific method has been developed for modeling lymphocyte dynamics over the course of RT and the subsequent follow-up period for HNC patients.
放射性淋巴细胞减少症（RIL）是头颈部癌（HNC）患者接受放射治疗（RT）时常见的并发症，其严重程度与较差的生存结果相关。
本研究旨在开发一种针对患者的建模方法，以模拟放疗期间及放疗后淋巴细胞动力学，并评估不同放疗方案的淋巴细胞保护效果。
本研究纳入了17例接受单侧质子或光子照射的HNC患者。使用HEDOS模型计算循环淋巴细胞的剂量，该模型考虑了照射侧的淋巴结、食管、自动分割的双侧颈动脉和颈静脉、骨骼肌、脂肪、皮肤、致密骨、松质骨、红骨髓和其他骨骼。开发了一个针对患者的模型来模拟淋巴细胞动力学，该模型考虑了辐射对循环淋巴细胞和淋巴结的损伤。收集放疗前、放疗期间和放疗后每周的绝对淋巴细胞计数（ALC），以估计患者特定参数。评估了四种不同的放疗方案——常规分割、大分割、立体定向体部放疗（SBRT）和FLASH——以比较它们的淋巴细胞保护效果。
与光子放疗相比，接受质子放疗的患者3级和4级RIL发生率低17.1%。质子治疗中循环淋巴细胞的平均剂量为1.28±0.37 Gy（相对生物效应），光子治疗为3.12±0.75 Gy。针对患者的模型捕捉到了三种不同的ALC动力学模式：平台期、正常恢复和不完全恢复，模拟值与观察值之间的均方误差（MSE）为0.024±0.025（均值±标准差）。平均而言，质子FLASH放疗中有42.72%的循环淋巴细胞接受的剂量超过0.1 Gy（相对生物效应），显著低于光子FLASH放疗中的81.94%。在放疗后3个月时，大分割放疗、SBRT和FLASH放疗的ALC水平分别比常规放疗高6.5%、20.2%和29.9%。放疗后1年时，所有治疗方案的大多数患者基线ALC至少恢复了70%。
已开发出一种针对患者的方法，用于对头颈部癌患者放疗过程及后续随访期间的淋巴细胞动态进行建模。
