Lymphocyte Count Kinetics and the Effect of Different Radiotherapy Techniques on Radiation-Induced Lymphopenia in Patients with Breast Cancer Receiving Hypofractionated Postmastectomy Radiotherapy

Abstract

Radiation-induced lymphopenia (RIL) is associated with poor prognosis in solid tumors. This study aimed to describe the lymphocyte kinetics in patients with breast cancer receiving hypofractionated postmastectomy radiotherapy (RT) and to investigate the association of different RT techniques with RIL. We assessed 607 patients who received hypofractionated postmastectomy RT for breast cancer in our prospective clinical database from 8 hospitals. All patients received irradiation to the chest wall and supraclavicular fossa. RT techniques included integrated RT with the photon-based intensity modulated techniques to irradiate all target volumes (integrated RT) and a hybrid approach combining photon irradiation to supraclavicular nodes and electron irradiation to the chest wall (hybrid RT). Peripheral lymphocyte counts (PLC) were tested prior to RT (baseline), weekly during RT, at 1, 2 weeks, 3, 6 months after RT, and then every 6 months. Grade 3+ RIL was defined as PLC nadir during RT of <0.5 ×103/ml. Mean PLC was compared by the t test. Univariate, multivariate, and propensity score matching (PSM) analyses were used to evaluate the effect of different RT techniques on grade 3+ RIL. During RT, 121 (19.9%) of patients had grade 3+ RIL. The PLC started to recover at 1 week and reached baseline levels 1 year after RT. A greater proportion of the patients treated with the integrated RT (90/269, 33.5%) developed grade 3+ PLC compared with those receiving hybrid RT (31/338, 9.2%, P < 0.001). After conducting PSM, multivariate analyses showed lower baseline PLC (HR = 0.15, P<0.001) and RT technique (the integrated RT vs. hybrid RT, HR = 4.76, P<0.001) were independent risk factors for grade 3+ RIL. The PLC in patients receiving the integrated RT after RT were higher than that in those receiving hybrid RT (p<0.05). RT technique affect the risk of and recovery from RIL, which may impact survival. Choosing appropriate RT technique to minimize RIL might be considered to benefit their outcomes.