Sokol Olga, Frederiksen Anders Tobias, Sitarz Mateusz, Sørensen Brita Singers, Santina Elham, Smith Christopher, Warmenhoven John-William, Davídková Marie, Michaelidesová Anna Jelínek, Danilová Irina, Zahradníček Oldřich, Leite Amélia Maia, de Marzi Ludovic, Pouzoulet Frederic, Olko Paweł, Miszczyk Justyna, Orzechowska Barbara, Papalanis Eleftherios, Hariri Mehran, Spiegelberg Diana, Stenerlöw Bo, Dasu Alexandru, Bodenstein Elisabeth, Beyreuther Elke, Pawelke Jörg, Pfitzmann Dorothee, Kirkby Karen, Henthorn Nicholas, Durante Marco
GSI Helmholtz Centre for Heavy Ion Research, Darmstadt, Germany.
Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
Clin Transl Radiat Oncol. 2025 May 11;53:100978. doi: 10.1016/j.ctro.2025.100978. eCollection 2025 Jul.
This study presents a multi-center comparison of in vitro cell survival measurements and RBE calculations following proton irradiations conducted under harmonized experimental conditions across six European institutions participating in the INSPIRE framework.
V79-4 cells were irradiated using spread-out Bragg peak (SOBP) proton fields of two configurations delivering 6 and 8 Gy with widths of 6 and 4 cm, respectively. Each center adhered to a standardized protocol, utilizing the same phantom design to minimize uncertainties related to sample positioning. X-ray reference irradiations were also performed to assess cell radiosensitivity across the participating centers.
Despite the consistent protocol, significant inter-institutional variability was observed in the survival measurements. For both treatment plans, the largest variation was detected in the most distal points of the SOBP (coefficients of variation of 43 % and 60 % for the 6 Gy and 8 Gy plans, respectively). Kruskal-Wallis statistical test confirmed the significant differences between the centers for each of the measured position in the proton field for both SOBP configurations. Discrepancies were observed in calculated RBE data as well, albeit preserving the expected trend for the values to slightly increase towards the distal edge of the SOBP (up to 1.5 and 1.3 for the 6 Gy and 8 Gy plans, respectively).
The results of the study highlight the minimal biological variation one could expect performing proton RBE measurements in well-aligned experimental conditions and challenges in conducting large-scale, multi-center radiobiological experiments and inter-comparisons between literature data sets.
本研究对六个参与INSPIRE框架的欧洲机构在统一实验条件下进行质子辐照后的体外细胞存活测量和相对生物效应(RBE)计算进行了多中心比较。
使用两种配置的扩展布拉格峰(SOBP)质子束对V79 - 4细胞进行辐照,分别提供6 Gy和8 Gy的剂量,束流宽度分别为6 cm和4 cm。每个中心都遵循标准化方案,使用相同的模体设计以尽量减少与样品定位相关的不确定性。还进行了X射线参考辐照,以评估各参与中心的细胞放射敏感性。
尽管方案一致,但在存活测量中仍观察到显著的机构间差异。对于两种治疗计划,在SOBP的最远端点检测到最大差异(6 Gy和8 Gy计划的变异系数分别为43%和60%)。Kruskal - Wallis统计检验证实,对于两种SOBP配置,质子束中每个测量位置的中心之间存在显著差异。在计算的RBE数据中也观察到差异,尽管保留了值向SOBP远端边缘略有增加的预期趋势(6 Gy和8 Gy计划分别高达1.5和1.3)。
该研究结果突出了在良好对齐的实验条件下进行质子RBE测量时可能预期的最小生物学差异,以及在进行大规模多中心放射生物学实验和文献数据集之间的相互比较时所面临的挑战。