Estimate of the uncertainties in the relative risk of secondary malignant neoplasms following proton therapy and intensity-modulated photon therapy

Abstract

Theoretical calculations have shown that proton therapy can reduce the incidence of radiation-induced secondary malignant neoplasms (SMN) compared with photon therapy for patients with prostate cancer. However, the uncertainties associated with calculations of SMN risk had not been assessed. The objective of this study was to quantify the uncertainties in projected risks of secondary cancer following contemporary proton and photon radiotherapies for prostate cancer. We performed a rigorous propagation of errors and several sensitivity tests to estimate the uncertainty in the ratio of relative risk (RRR) due to the largest contributors to the uncertainty: the radiation weighting factor for neutrons, the dose-response model for radiation carcinogenesis and interpatient variations in absorbed dose. The interval of values for the radiation weighting factor for neutrons and the dose-response model were derived from the literature, while interpatient variations in absorbed dose were taken from actual patient data. The influence of each parameter on a baseline RRR value was quantified. Our analysis revealed that the calculated RRR was insensitive to the largest contributors to the uncertainty. Uncertainties in the radiation weighting factor for neutrons, the shape of the dose-risk model and interpatient variations in therapeutic and stray doses introduced a total uncertainty of 33% to the baseline RRR calculation.

Figure 1

Functions of the various radiation weighting factors (w_R) for neutrons used to convert absorbed dose to equivalent dose from neutrons examined in this work.

Figure 2

The ratio of relative risk (RRR), defined as the ratio of ERR for protons (ERR_proton) to that for intensity-modulated photon therapy (ERR_IMRT), of the medium patient for various dose-response models. Error bars represent the uncertainty in RRR due to variations in stray radiation exposures from proton therapy and IMRT in a population of ten prostate cancer patients. The response models were LNT, linear no-threshold; LEXP(10), linear-exponential rolling off at 10 Sv; LPLAT(10), linear-plateau rolling off at 10 Sv; LEXP(40), linear-exponential rolling off at 40 Sv; and LPLAT(40), linear-plateau rolling off at 40 Sv.