Neutron Therapy: From Radiobiological Expectation to Clinical Reality

The radiobiological data at present available indicate that high LET radiations could bring a benefit in the treatment of some types of tumours (typically slowly growing, well differentiated). Radiobiology also suggests some mechanisms through which this benefit could be achieved: hypoxic gain factor, kinetics gain factor, etc. However, the need for patient selection is clearly apparent. Among the high LET radiations, fast neutrons are the least expensive and the most widely used in therapy. Seventeen centres are today actively involved in neutron therapy, and more than 15,000 patients have been treated so far. Two main difficulties are encountered when reviewing the clinical results of fast neutron therapy. Firstly, as indicated above, patient selection, which depends on the characteristics of the tumour (and of the normal tissues at risk) is important. A lack of proper selection can obscure or worsen the results. Secondly, there is a need for a high physical selectivity with neutrons. Throughout the history of radiation therapy, physical selectivity has been proved to be essential for the outcome of treatment. It becomes even more important with high LET than with low LET radiations, because of a reduction of the differential effect between the different cell populations when increasing LET. Neutron therapy started in the seventies in rather sub-optimal (or even poor) technical conditions. The situation has been significantly improved with the introduction of high energy, hospital-based cyclotrons, with isocentric mounting and variable collimators. However, in many neutron therapy centres today the level of physical selectivity does not yet fully reach the same level as modern photon therapy. The interpretation of the clinical results is then biased and it is difficult to separate what is really due to the high LET characteristics of the beams from that related to the technical treatment conditions. Among the clinical indications for fast neutrons, the following are most commonly recognised: (1) inoperable or recurrent salivary gland tumours, (2) locally extended tumours of the paranasal sinuses, (3) some other tumours of the head and neck area especially with fixed adenopathies, (4) slowly growing, well differentiated soft tissue sarcomas, osteosarcomas and chondrosarcomas, (5) locally extended prostatic adenocarcinomas, (6) palliative treatment of melanomas. The indications for neutron therapy represent about 10-15% of all patients currently referred t