The predicted relative risk of premature ovarian failure for three radiotherapy modalities in a girl receiving craniospinal irradiation

In girls and young women, irradiation of the ovaries can reduce the number of viable ovarian primordial follicles, which may lead to premature ovarian failure (POF) and subsequently to sterility. One strategy to minimize this late effect is to reduce the radiation dose to the ovaries. A primary means of reducing dose is to choose a radiotherapy technique that avoids irradiating nearby normal tissue; however, the relative risk of POF (RRPOF) due to the various therapeutic options has not been assessed. This study compared the predicted RRPOF after craniospinal proton radiotherapy, conventional photon radiotherapy (CRT) and intensity-modulated photon radiotherapy (IMRT). We calculated the equivalent dose delivered to the ovaries of an 11-year-old girl from therapeutic and stray radiation. We then predicted the percentage of ovarian primordial follicles killed by radiation and used this as a measure of the RRPOF; we also calculated the ratio of the relative risk of POF (RRRPOF) among the three radiotherapies. Proton radiotherapy had a lower RRPOF than either of the other two types. We also tested the sensitivity of the RRRPOF between photon and proton therapies to the anatomic position of the ovaries, i.e., proximity to the treatment field (2 <= RRRPOF <= 10). We found that CRT and IMRT have higher risks of POF than passive-scattering proton radiotherapy (PRT) does, regardless of uncertainties in the ovarian location. Overall, PRT represents a lower RRPOF over the two other modalities.