Intrinsic and extrinsic tumor characteristics are of minor relevance for the efficacy of split-dose carbon ion irradiation in three experimental prostate tumors

Abstract

Objective: To quantify the impact of tumor-associated resistance factors on local tumor control after split doses of carbon ( 12 C-) ions or photons in an experimental prostate tumor model. Material and methods: Three sublines (AT1, H, HI) of syngeneic rat prostate tumors (R3327) differing in growth rate, differentiation and hypoxic status were irradiated with split doses of either 12 C-ions or 6 MV photons. Dose–response curves were determined for the endpoint local tumor control within 300 days. The relative biological effectiveness (RBE) of 12 C-ions was calculated from the TCD 50 -values (dose at 50% control probability) of photons and 12 C-ions. Results: Experimental findings demonstrated: (i) The RBE was highest for the least differentiated AT1-tumor (2.39 ± 0.16 (AT1) vs 2.06 ± 0.11 (H) and 2.03 ± 0.17 (HI)). (ii) TCD 50 -values between the three tumor sublines differed much less for 12 C-ions (26.0–37.9 Gy) than for photons (53.7–90.6 Gy). (iii) While the slope of the dose–response curves for photons and 12 C-ions were very similar for the AT1- and H-tumors, the histologically heterogeneous HI-tumor showed a shallow dose–response curve for photons, which is transformed into a steep dose–response curve after 12 C-ion irradiation. Conclusion: The response to carbon ion irradiations is much less dependent on biological differences between and within the tumor-sublines. Tumors showing a high resistance against photon treatments, also exhibit the largest RBE for carbon ions. Carbon ions could therefore be of clinical advantage for the treatment of tumors with known resistance factors against photons.