Kuncman Łukasz, Orzechowska Magdalena, Stawiski Konrad, Masłowski Michał, Ciążyńska Magdalena, Gottwald Leszek, Milecki Tomasz, Fijuth Jacek
Department of Radiotherapy, Medical University of Lodz, 90-419 Lodz, Poland.
Department of Molecular Carcinogenesis, Medical University of Lodz, 90-419 Lodz, Poland.
Cancers (Basel). 2022 Aug 9;14(16):3844. doi: 10.3390/cancers14163844.
The optimal sequence of chemoradiotherapy with immunotherapy is still not established. The patient’s immune status may play a role in determining this order. We aim to determine the kinetics of a multi-potential haemopoietic factor FMS-related tyrosine kinase 3 ligand (Flt-3L) during chemoradiotherapy. Our pilot, a single arm prospective study, enrolled patients with rectal cancer who qualified for neoadjuvant chemoradiotherapy. Blood samples for Flt-3L were collected before and every second week of chemoradiotherapy for a complete blood count every week. The kinetics of Flt-3L were assessed using Friedman’s ANOVA. A multiple factor analysis (MFA) was performed to find relevant factors affecting levels of serum Flt-3L during chemoradiotherapy. FactoMineR and factoextra R packages were used for analysis. In the 33 patients enrolled, the level of Flt-3L increased from the second week and remained elevated until the end of treatment (p < 0.01). All patients experienced Grade ≥2 lymphopenia with a nadir detected mostly in the 5/6th week. MFA revealed the spatial partitioning of patients among the first and second dimensions (explained by 38.49% and 23.14% variance). The distribution along these dimensions represents the magnitude of early changes of Flt-3L. Patients with the lowest values of Flt-3L change showed the highest lymphocyte nadirs and lowest dose/volume parameters of active bone marrow. Our hypothesis-generating study supports the concept of early initiation of immuno-therapy when the concentration of Flt-3L is high and no lymphopenia has yet occurred.
免疫疗法与放化疗的最佳顺序尚未确定。患者的免疫状态可能在确定此顺序中发挥作用。我们旨在确定多能造血因子FMS相关酪氨酸激酶3配体（Flt-3L）在放化疗期间的动力学变化。我们的初步研究是一项单臂前瞻性研究，纳入了符合新辅助放化疗条件的直肠癌患者。在放化疗前以及放化疗的每第二周采集用于检测Flt-3L的血样，每周进行一次全血细胞计数。使用Friedman方差分析评估Flt-3L的动力学变化。进行多因素分析（MFA）以找出影响放化疗期间血清Flt-3L水平的相关因素。使用FactoMineR和factoextra R软件包进行分析。在纳入的33例患者中，Flt-3L水平从第二周开始升高，并一直持续升高至治疗结束（p<0.01）。所有患者均出现≥2级淋巴细胞减少，最低点大多出现在第5/6周。多因素分析显示患者在第一维和第二维之间的空间划分（分别由38.49%和23.14%的方差解释）。沿这些维度的分布代表Flt-3L早期变化的幅度。Flt-3L变化值最低的患者淋巴细胞最低点最高，活跃骨髓的剂量/体积参数最低。我们这项产生假设的研究支持在Flt-3L浓度高且尚未出现淋巴细胞减少时尽早开始免疫治疗的概念。
