Special radiobiological features of second cancer risk after particle radiotherapy.

In absolute terms: second cancer risks from radiotherapy of first cancers in adults are small compared to the benefits from radiotherapy but this is not so for radiotherapy of childhood cancers. Moreover, the radiation dose dependence of cancer induction differs between organs and tissues. The organ-specific dose dependence of second cancer risks may indicate the existence of different radiobiological mechanisms. As an inevitable consequence of the age dependence of organ sensitivity to second cancer induction, the organ/tissue weighting factors which have been proposed by ICRP for calculating effective dose (the dose unit Sv) and for risk estimation in the general population should not be used in medical radiation exposures. In adult cancer radiotherapy, the most common unwanted effect is local tumour recurrence whereas both, severe late normal tissue damage and radiation-induced second cancers are rare, around 1% of locally controlled cancer patients. In childhood cancers, local failures are rare (<10% in some cancers) yet second cancers are more common than uncontrolled primaries. The main reason for considering particle radiotherapy for childhood cancers is the possibility to exploit their physical characteristics to reduce the radiation exposure to organs and tissues close to and distant from the primary cancer which is to be targeted. However, the relative biological effectiveness of the radiation doses within the proton beam is not a constant and the relative biological effectiveness of the neutrons is not known as far as the mechanisms of late normal tissue damage and second cancer risk are concerned. In view of the highly charged discussions of the potential risks of treatment-induced seecond cancers from the neutron contamination of exposure doses in out-of-PTV critical organs a comprehensive European project called ANDANTE was performed which integrated the disciplines of radiation physics, molecular biology, systems biology modelling and epidemiology in order to investigate the RBE of induction of cancer from exposure to neutrons compared to photons. Since out-of-field "effective" neutron doses from proton therapy are smaller than the photon stray doses whichever reasonable RBE is chosen for comparison, and since the absolute risk of radiation-induced second cancer rates are in the order of 1% in the cohorts of adult patients who have been treated in the past with methods which caused relatively high out-of-field doses to large body volumes, it is highly unlikely that such patients treated in future with highly conformal particle therapy are at a higher radiation-induced second cancer risk than those patients treated with photons and described before. Still, the potential risks of second cancers from scattered proton radiotherapy for childhood cancers may cause concern. Yet, the overall risk of undesired consequences of radiation exposure of children which are more complex and manifold than in adult patients (including developmental, neurocognitive, hormonal and growth impairment effects) are likely to be very much reduced by the better focussing of the radiation dose in the target offered by particle radioherapy. This benefit may far outweigh the still hypothetical second cancer risk from particle radiotherapy in pediatric radiotherapy.