Abstract

Background

Thermal dose in clinical hyperthermia reported as cumulative equivalent minutes (CEM) at 43 °C (CEM43) and its variants are based on direct thermal cytotoxicity assuming Arrhenius ‘break’ at 43 °C. An alternative method centered on the actual time–temperature plot during each hyperthermia session and its prognostic feasibility is explored.

Methods and materials

Patients with bladder cancer treated with weekly deep hyperthermia followed by radiotherapy were evaluated. From intravesical temperature (T) recordings obtained every 10 secs, the area under the curve (AUC) was computed for each session for T > 37 °C (AUC > 37 °C) and T ≥ 39 °C (AUC ≥ 39 °C). These along with CEM43, CEM43(>37 °C), CEM43(≥39 °C), T_mean, T_min and T_max were evaluated for bladder tumor control.

Results

Seventy-four hyperthermia sessions were delivered in 18 patients (median: 4 sessions/patient). Two patients failed in the bladder. For both individual and summated hyperthermia sessions, the T_mean, CEM43, CEM43(>37 °C), CEM43(≥39 °C), AUC > 37 °C and AUC ≥ 39 °C were significantly lower in patients who had a local relapse. Individual AUC ≥ 39 °C for patients with/without local bladder failure were 105.9 ± 58.3 °C-min and 177.9 ± 58.0 °C-min, respectively (p = 0.01). Corresponding summated AUC ≥ 39 °C were 423.7 ± 27.8 °C-min vs. 734.1 ± 194.6 °C-min (p < 0.001), respectively. The median AUC ≥ 39 °C for each hyperthermia session in patients with bladder tumor control was 190 °C-min.

Conclusion

AUC ≥ 39 °C for each hyperthermia session represents the cumulative time–temperature distribution at clinically defined moderate hyperthermia in the range of 39 °C to 45 °C. It is a simple, mathematically computable parameter without any prior assumptions and appears to predict treatment outcome as evident from this study. However, its predictive ability as a thermal dose parameter merits further evaluation in a larger patient cohort.

中文翻译：

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中度临床放疗热疗中的热剂量定量：曲线下温度-时间面积（AUC）的回顾

摘要

背景

临床热疗中的热剂量报告为在43°C（CEM43）时的累积当量分钟（CEM），其变体基于直接热细胞毒性，假定Arrhenius在43°C时“破裂”。探索了一种替代方法，该方法以每次高温治疗期间的实际时间-温度图为中心，并探讨了其预后可行性。

方法和材料

对每周进行深层热疗然后放疗的膀胱癌患者进行了评估。从膀胱内的温度（T）的记录得到每10秒，曲线（AUC）下的面积计算每个会话Ť  > 37℃（AUC> 37℃）和Ť  ≥39℃（AUC≥39℃ ）。这些与CEM43，CEM43（> 37°C），CEM43（≥39°C），T_均值，T _min和T _max一起用于膀胱肿瘤控制。

结果

在18位患者中进行了74次高热疗程（中位数：每位患者4次疗程）。两名患者膀胱衰竭。对于局部和总结性高温疗程，局部患者的T_均值，CEM43，CEM43（> 37°C），CEM43（≥39°C），AUC> 37°C和AUC≥39°C显着降低复发。有/无局部膀胱衰竭的患者的单个AUC≥39°C分别为105.9±58.3°C-min和177.9±58.0°C-min（p  = 0.01）。相应的总AUC≥39°C分别为423.7±27.8°C-min和734.1±194.6°C-min（p  <0.001）。膀胱肿瘤控制患者每次热疗的中位AUC≥39°C为190°C-min。

结论

每次高温治疗的AUC≥39°C代表临床定义的中度高温在39°C至45°C范围内的累积时间-温度分布。这是一个简单的，数学上可计算的参数，没有任何先前的假设，并且似乎可以预测治疗结果，如本研究所示。但是，其作为热剂量参数的预测能力值得在较大的患者队列中进一步评估。