ESTRO 2024 - Abstract Book

S5329

Radiobiology - Tumour biology

ESTRO 2024

Center [2]. For the proton irradiations, the tumor was positioned at the center of a 20 mm spread-out Bragg peak. Under oxic condition the anesthetized animals inhaled 100 % oxygen and under hypoxic conditions, the tumor supplying-vessels were additionally clamped with a compression bandage 10 min before and during irradiation to induce acute hypoxia. Dose response curves were derived using local tumor control within 300 days after irradiation as biological endpoint. RBE and OER were quantified based on TCD 50 (dose at 50 % local tumor control probability). To investigate the effects of the photon and proton treatments on the tumor microenvironment and immune system, histological changes at different time points were analyzed in tumors treated with a curative dose that resulted in local tumor control of all tumors within a dose-response curve treatment group.

Results:

Irradiations under hypoxic conditions increased tumor control doses for both photons and protons leading to OER values significantly larger than 1. However, the OER of protons was found to be slightly lower than for photons. Accordingly, the proton RBE was slightly higher in hypoxic than in oxic conditions. At the histological level, proton irradiation with a single fraction of the curative dose caused an initial increase in γ-H2AX positive cells, indicating increased DNA damage compared to untreated tumors. However, this DNA-damage was repaired within one day after irradiation. This damage was associated with a decrease in BrdU-positive cells, showing a decreased amount of proliferating cells. The fraction of pimonidazole-positive areas was diminished approximately three weeks after irradiation indicating partial reoxygenation. Further histological analysis including the response to photon irradiation is ongoing.

Conclusion:

While the increased RBE of protons was confirmed, the hypoxia-induced effect on radioresistance was found to be slightly smaller for protons than for photons. Therefore, protons might be more effective in acute hypoxic tumors as expressed by the slightly higher RBE relative to oxic conditions. Histological analysis revealed enhanced DNA damage, decreased proliferation as well as partly reoxygenation after proton irradiation. Comparison with the photon treatment arm is ongoing.

Keywords: Hypoxia, proton radiotherapy, dose response

References:

[1] Wenzl, T. and J. J. Wilkens (2011). "Modelling of the oxygen enhancement ratio for ion beam radiation therapy." Phys Med Biol 56(11): 3251-3268. [2] Glowa, C., et al. (2016). "Carbon ion radiotherapy decreases the impact of tumor heterogeneity on radiation response in experimental prostate tumors." Cancer Lett 378(2): 97-103.

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