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Thermotherapy is a known sensitizer to radiation (Horsman MR, Overgaard J.; Clin. Oncol.; 2007) and is known to lower the α/β of tumors (Datta NR, Bodis S.; Radiother. Oncol.; 2019). The thermal enhancement ratio (TER) of the radiation dose is, however, known to be dependent on the time interval between the radiation and thermal dose delivery, with the highest TER for simultaneous application of the two modalities. Simultaneous ThermoBrachytherapy (STBT) is defined as HDR-BT with simultaneous interstitial thermotherapy assuming the same equivalent dose (EQD) to the target by sensitization and lower physical BT dose (Androulakis I, et al.; Int. J. Hyperth. 2021). In this study we investigated what OAR dose reduction can be expected when HDR-BT only is replaced by STBT in low and intermediate risk prostate cancer (PCa).

The effect of the combined TBT treatment was quantified using the temperature dependent LQ model (Van Leeuwen CM, et al.; Int. J. Hyperth. 2017). We compared the physical HDR-BT fraction dose delivered to 10 previously irradiated PCa patients with a STBT treatment. In the original treatment consisting of 2 fractions,  the prescribed dose was D_p = 13.5 Gy per fraction. For the TBT simulations we assumed 85% of the original HDR-BT dose and added an EQD-optimized simultaneous thermal dose fraction of 1h with a maximum temperature constraint of 47 °C, using the same dose objectives and constraints (Fig. 1). For all tissues we assumed an α/β = 3 Gy. For the target, the temperature dependence of α (α₄₃/α₃₇) and β (β₄₃/β₃₇) was based on PC-3 and DU-145 PCa cell line data (Pajonk F, et al.; Cancer Res.; 2005). As there is limited thermoradiotherapeutic data available on healthy tissues, we investigated α₄₃/α₃₇ and β₄₃/β₃₇ ranging from 1 to the value assigned to PCa . We evaluated the target coverage (V_100%), as well as the urethra D_0.1cc, rectum D_1cc, and bladder D_1cc, accounting for the variability due to different α₄₃/α₃₇ and β₄₃/β₃₇ values. Differences in dose–volume metrics were evaluated for statistical significance using a paired sampled Wilcoxon signed rank test with p < 0.001.

The target objective was reached, with no significant difference in V_100% between the HDR-BT only and STBT plan (0.1%±0.3%). For the OAR, the dose reduction was significant in all cases. For the scenario of equal sensitization of healthy and PCa tissue, the reductions in the urethra D_0.1cc , rectum D_1cc, and bladder D_1cc, were 2.2%±2.3%, 2.7%±2.5%, and 4.7%±2.5%, respectively (Fig. 2). For the scenario of no sensitization of healthy tissue, the reductions were 16.7%±0.1%, 10.7%±0.6%, and 10.8%±0.7%, respectively (Fig. 2).

Our calculations indicate that STBT has the potential to reach the same target coverage with a significantly lower dose to the OAR in monotherapy for low and intermediate risk PCa. For a final conclusion including clinical relevance, more information on the temperature dependence of α and β for normal tissue is needed.