Department of Radiotherapy, The Netherlands Cancer Insititute, Amsterdam, The Netherlands.
Department of Surgical Oncology, The Netherlands Cancer Insititute, Amsterdam, The Netherlands.
Radiat Res. 2021 Jul 1;196(1):23-30. doi: 10.1667/RADE-20-00226.1.
Currently, all soft tissue sarcomas (STS) are irradiated by the same regimen, disregarding possible subtype-specific radiosensitivities. To gain further insight, cellular radiosensitivity was investigated in a panel of sarcoma cell lines. Fourteen sarcoma cell lines, derived from synovial sarcoma, leiomyosarcoma, fibrosarcoma and liposarcoma origin, were submitted to clonogenic survival assays. Cells were irradiated with single doses from 1-8 Gy and surviving fraction (SF) was calculated from the resulting response data. Alpha/beta (α/β) ratios were inferred from radiation-response curves using the linear-quadratic (LQ)-model. Cellular radiosensitivities varied largely in this panel, indicating a considerable degree of heterogeneity. Surviving fraction after 2 Gy (SF2) ranged from 0.27 to 0.76 with evidence of a particular radiosensitive phenotype in only few cell lines. D37% on the mean data was 3.4 Gy and the median SF2 was 0.52. The median α/β was 4.9 Gy and in six cell lines the α/β was below 4 Gy. A fairly homogeneous radiation response was observed in myxoid liposarcoma cell lines with SF2 between 0.64 and 0.67. Further comparing sarcomas of different origin, synovial sarcomas, as a group, showed the lowest SF2 values (mean 0.35) and was significantly more radiosensitive than myxoid liposarcomas and leiomyosarcomas (P = 0.0084 and 0.024, respectively). This study demonstrates a broad spectrum of radiosensitivities across STS cell lines and reveals subtype-specific radiation responses. The particular cellular radiosensitivity of synovial sarcoma cells supports consideration of the different sarcoma entities in clinical studies that aim to optimize sarcoma radiotherapy.
目前,所有软组织肉瘤(STS)都采用相同的方案进行放疗,而忽略了可能存在的亚型特异性放射敏感性。为了进一步深入了解,本研究在一组肉瘤细胞系中研究了细胞放射敏感性。将源自滑膜肉瘤、平滑肌肉瘤、纤维肉瘤和脂肪肉瘤的 14 种肉瘤细胞系进行克隆存活测定。用 1-8 Gy 的单剂量照射细胞,根据得出的反应数据计算存活分数(SF)。使用线性二次(LQ)模型从辐射反应曲线推断 α/β(α/β)比值。该面板中的细胞放射敏感性差异很大,表明存在相当大的异质性。SF2 范围为 0.27 至 0.76,仅少数细胞系中存在特定的放射敏感表型。平均数据的 D37%为 3.4 Gy,SF2 的中位数为 0.52。中位 α/β 为 4.9 Gy,有 6 种细胞系的 α/β 值低于 4 Gy。黏液样脂肪肉瘤细胞系的辐射反应相当均匀,SF2 在 0.64 至 0.67 之间。进一步比较不同起源的肉瘤,滑膜肉瘤作为一个整体,SF2 值最低(平均值为 0.35),比黏液样脂肪肉瘤和平滑肌肉瘤更敏感(P=0.0084 和 0.024,分别)。本研究表明 STS 细胞系中存在广泛的放射敏感性,并揭示了亚型特异性的辐射反应。滑膜肉瘤细胞的特殊细胞放射敏感性支持在旨在优化肉瘤放射治疗的临床研究中考虑不同的肉瘤实体。