Carbon ion radiotherapy decreases the impact of tumor heterogeneity on radiation response in experimental prostate tumors.

OBJECTIVE

To quantitatively study the impact of intrinsic tumor characteristics and microenvironmental factors on local tumor control after irradiation with carbon ((12)C-) ions and photons in an experimental prostate tumor model.

MATERIAL AND METHODS

Three sublines of a syngeneic rat prostate tumor (R3327) differing in grading (highly (-H) moderately (-HI) or anaplastic (-AT1)) were irradiated with increasing single doses of either (12)C-ions or 6 MV photons in Copenhagen rats. Primary endpoint was local tumor control within 300 days. The relative biological effectiveness (RBE) of (12)C-ions was calculated from the dose at 50% tumor control probability (TCD50) of photons and (12)C-ions and was correlated with histological, physiological and genetic tumor parameters.

RESULTS

Experimental findings demonstrated that (i) TCD50-values between the three tumor sublines differed less for (12)C-ions (23.6-32.9 Gy) than for photons (38.2-75.7 Gy), (ii) the slope of the dose-response curve for each tumor line was steeper for (12)C-ions than for photons, and (iii) the RBE increased with tumor grading from 1.62 ± 0.11 (H) to 2.08 ± 0.13 (HI) to 2.30 ± 0.08 (AT1).

CONCLUSION

The response to (12)C-ions is less dependent on resistance factors as well as on heterogeneity between and within tumor sublines as compared to photons. A clear correlation between decreasing differentiation status and increasing RBE was found. (12)C-ions may therefore be a therapeutic option especially in patients with undifferentiated prostate tumors, expressing high resistance against photons.