Protons. A step forward or perhaps only more expensive radiation therapy?

Abstract

In this issue of Acta Oncologica a series of review papers exploring the possible role of clinical application of protons came to the conclusion that protons may be suitable for 15% of the irradiated Swedish cancer population [1]. Having followed the development in radiation therapy for 30 years, I have reflected a bit on these calculations. Much of the progress in the past history of radiation therapy has been technology driven in the sense that when new machines were developed, giving radiation with new obvious advantages, these were simply used by enthusiasts followed by the other institutions in due time. This can be seen for introduction of high voltage radiation, where for example a Van de Graaff machine was built in 1943 in Bergen against the advice from the leaders at the Norwegian Radium Hospital, an institution that acquired high voltage equipment 10 years later [2]. Similarly there was no formal randomized trial proving that the cobalt unit when first introduced yielded better radiation results than conventional radiation. As far as I know the major promoter for its use was the recommendation from prof. Gilbert Fletcher at MD Anderson Cancer Centre [3]. Also the introduction of conformal radiation in the 1990s was more or less conceptually accepted with only few clinical controlled studies, but a series of model treatment planning studies were published [4]. The modern intensity modulated therapy (IMRT) is widely implemented [5] in most countries based on concepts initially largely developed and published in Acta Oncologica by prof. Anders Brahme [6]. Most major departments are currently investing money in equipment, training and research to implement IMRT for selected patient groups. The future focus has the past years been moved more to the biological properties of the cancer cells, i.e. the accurate localization of the part of a tumour that needs a higher dose and the registration of the actual response to exposure for radiation [7/11]. One may therefore ask whether protons represent a new paradigm shift in radiation oncology, making the efforts to implement IMRT obsolete? The background for the proposal is mainly based on the concept that the radiation can be more precisely enveloped around the target volume (tumour with risk volume) with protons than conventional radiation including IMRT techniques. This is a relevant issue as there seems to be a potential doubling of late secondary cancers due to increased integral doses in areas outside the target when using multiple fields in IMRT [12,13]. Recently a treatment planning study indicated much lower lifetime risk for secondary cancer after proton therapy compared with IMRT, but the risk for IMRT was particularly high in children with medulloblastoma [14]. I could not find any specific publications addressing secondary cancer after proton therapy, despite that 43.000 patents have been exposed to this treatment modality [1]. In the papers better shielding of critical normal tissues surrounding the tumour are frequently stated. This is, however, a statement that should be tested as similar claims were put forward when conformal radiation based on CT-delineation of tumours was introduced. In fact it turned out that treatment volumes had to be increased to encompass the visualized tumour, just as often as they could be reduced. There is therefore a clear limit which cannot be passed with any radiation. A safety margin must prevail. Another concern is the response of normal structures included in the irradiated volume if the sparing