Is there any future for high-LET radiation?

In order to judge the possible future of high-LET radiotherapy several physical, biological and clinical aspects are reviewed and discussed. This concerns firstly ongoing improvements of physical selectivity for low-LET radiation. One new approach in this respect are high energy particle beams such as protons or helium ions. Their clinical benefit has been demonstrated for several well selected tumour types or sites (e.g. uveal melanomas). Secondly the specific radiobiological properties of high-LET radiation are reviewed. The rationale for introducing neutron radiotherapy historically was a reduction in OER. However, there is now evidence that all cell populations, in all conditions, tend to respond in a more similar way when exposed to neutrons compared to photons. A reduction in the differences in radiosensitivity can bring an advantage or a disadvantage depending on the tumor characteristics and on the normal tissue at risk. This raises the important problem of patient selection for neutron therapy. High LET radiations were proved to be superior to low-LET radiations for the treatment of some tumour types such as salivary gland tumours, locally extended prostatic adenocarcinoma, or some types of sarcomas. Development of heavy ion therapy programs is justified for some types of tumours requiring the application of high-LET radiations with a high physical selectivity. Finally the clinical consequences of new technological developments for low and high-LET radiations are discussed