Rosner G L, Clegg S T, Prescott D M, Dewhirst M W
Department of Community and Family Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Int J Hyperthermia. 1996 Mar-Apr;12(2):223-39. doi: 10.3109/02656739609022511.
A stochastic model describing the probability of cell survival as a function of thermal exposure was developed and fit to data arising from studies of CHO cell survival under hyperthermic conditions. This model characterizes the separate risks of temperature-induced cell death and induction of thermotolerance during heating. Tumour cells are assumed to be affected independently of each other by hyperthermia. Tumour geometry, perfusion and power deposition affect hyperthermia-induced temperature distributions in tumours, producing nonuniform temperatures. Two tumours may respond to hyperthermia slightly differently because of differences in tumour geometry, perfusion, power deposition, or by chance alone and the approach presented here incorporates chance and these other factors explicitly.
(1) the time-temperature history is important for estimating tumour cell survival; (2) tumour temperature heterogeneity leaves more surviving cells at a given T90 temperature than would be expected if the entire tumour were uniformly heated to that same temperature; and (3) changes in the shape of the temperature distribution because of tumour geometry and perfusion distribution greatly influence cell survival between tumours, even when the standard temperature descriptors, such as T90, are fixed. The simulations also showed a modest effect on cell kill attributable to varying the lengths of the warm-up and the cool-down periods. These simulations indicate that these types of sensitivity studies can be used to investigate relationships between various modifiers of temperature distributions achieved when treating tumours with hyperthermia and to assess their potential therapeutic impact in clinical trials.
建立了一个随机模型，该模型将细胞存活概率描述为热暴露的函数，并与在高温条件下CHO细胞存活研究中产生的数据相拟合。该模型描述了加热过程中温度诱导的细胞死亡风险和热耐受诱导的单独风险。假设肿瘤细胞彼此独立地受到热疗的影响。肿瘤的几何形状、灌注和功率沉积会影响热疗在肿瘤中诱导的温度分布，产生不均匀的温度。由于肿瘤几何形状、灌注、功率沉积的差异，或者仅仅是偶然因素，两个肿瘤对热疗的反应可能略有不同，这里提出的方法明确纳入了偶然性和这些其他因素。
（1）时间-温度历程对于估计肿瘤细胞存活很重要；（2）在给定的T90温度下，肿瘤温度的异质性会使存活细胞比整个肿瘤均匀加热到相同温度时预期的更多；（3）由于肿瘤几何形状和灌注分布导致的温度分布形状变化会极大地影响肿瘤之间的细胞存活，即使标准温度描述符（如T90）是固定的。模拟还显示，改变预热和冷却期的长度对细胞杀伤有适度影响。这些模拟表明，这类敏感性研究可用于研究热疗治疗肿瘤时实现的各种温度分布调节剂之间的关系，并评估它们在临床试验中的潜在治疗影响。
