Photons - Radiobiological issues related to the risk of second malignancies

Photons are widely used in radiotherapy and while they are low LET radiation, can still pose a risk in developing second malignant neoplasms (SMN). Due to the physics of photons that allow distribution of energy outside the target volume, out-of-field irradiation is an important component of SMN risk assessment. The epidemiological evidence supporting this risk should be augmented with radiobiological justifications for a better understanding of the underlying processes. There are several factors that impact second cancer risk which can be analysed from a radiobiological perspective: age at irradiation, type of irradiated tissue, irradiated volume, treatment technique, previous irradiation/radiological investigations. Age-dependence has a radiobiological foundation given by the higher radiosensitivity of children as compared to adult patients. However, in its 2013 report, UNSCEAR advises against generalisation of the effects of childhood radiation exposure, given the fact that these effects are strongly organ dependent. Furthermore, the age-dependent radiation sensitivity has a bimodal distribution, since aging cells present an increase in the oxidative stress, which can promote premalignant cells. Non-targeted effects such as radiation-induced genomic instability, bystander or abscopal effects could also impact on the risk of SMN. Recent studies show that beside the known cellular changes, bystander effects can be manifested through increased cell proliferation, which could be a culprit for SMN development. Furthermore, new evidence on the existence of tumour-specific cancer stem cells that are long-lived and more quiescent and radioresistant than non-stem cancer cells can raise questions about their association with SMN risk.