the physics
Proton therapy is a type of particle therapy (unlike radiotherapy that uses photons which are packets of energy that travel as waves).
Protons are large particles with a positive charge and can only penetrate tissue to a limited depth. Crucially electrons deposit most of their energy at the end of the beam. This is different to radiation energy which has no mass or charge so that it penetrates tissue completely and looses energy along its path. (This is why radiotherapy is given from multiple directions (see radiotherapy section here) to maximise energy released within the tumour and minimize energy released in healthy tissue).
Protons are large particles with a positive charge and can only penetrate tissue to a limited depth. Crucially electrons deposit most of their energy at the end of the beam. This is different to radiation energy which has no mass or charge so that it penetrates tissue completely and looses energy along its path. (This is why radiotherapy is given from multiple directions (see radiotherapy section here) to maximise energy released within the tumour and minimize energy released in healthy tissue).
Graph depicting dose of energy released at given depth for different therapies. Adapted from wikicommons by Cepheiden
|
Illustration of how Bragg peak is used to give maximal dose to tumour tissue and how there is negliable 'exit-dose'. Image in public domain.
|
The depth of penetration of a proton beam, and therefore the depth of release of maximal energy can be controlled by adjusting the energy of the beam. Proton beams release low amounts of energy as they enter the tissue. It then releases maximal energy at the last 3mm of the beam called the ‘Bragg Peak’. The higher the energy of the proton beam the deeper into the tissue the Bragg Peak will occur. After the Bragg Peak the beam has lost nearly all energy so there is no ‘exit dose’ and so no damage to tissue after the Bragg peak.
Despite the different particles involved both radiotherapy and proton therapy damage tumour tissue to the same extent however by using the Bragg Peak proton therapy can theoretically greatly minimise damage to healthy tissue. This is the fundamental advantage of proton therapy.
Despite the different particles involved both radiotherapy and proton therapy damage tumour tissue to the same extent however by using the Bragg Peak proton therapy can theoretically greatly minimise damage to healthy tissue. This is the fundamental advantage of proton therapy.
History
Proton therapy for cancer was first suggested by Robert Wilson in 1946 and it was first used to destroy the pituitary gland for patients with metastatic hormone-sensitive breast cancer. Further use however required the development of 3D imaging (CT, MRI, SPECT etc) and the large scale infrastructure investments to make particle accelerators for clinical use with the fist being built in the 1980s in California. There are now proton therapy centres worldwide with the U.K's first two centres opening in 2018.
How the machine works
The limitations
Proton therapy has been described as the most costly medical device [link to BMJ website]. Two new centres in the U.K. together required £250 million of government funding. Similarly a large and suitable site is needed to house the 200-ton particle accelerator and multiple 100-ton gantries each equivalent to a 3-story house. See the video below to understand the scale of the U.K. project (start at 3.28 for a description of the machine).
There is evidence of benefit of proton therapy in rare childhood cancers and for certain uncommon brain cancers. However, the assumption that proton therapy must be better than standard radiotherapy for common cancers has not yet been validated by clinical trials. However we know the costs per patient are significantly higher than conventional radiotherapy.
Proton therapy receives significant media exposure which means patients can often assume proton therapy must be better than standard care despite the lack of evidence.
This can be worsened by the commercial interest of for-profit hospitals that have made the huge investment to construct a proton therapy centre to maximise patient throughput of patients. This has led to proton therapy being used for common cancers, such as prostate, without an evidence base to support it. According to NICE (U.K’s National Institute of Clinical Excellence) a review of available evidence proton beam therapy is more expensive and produced lower quality of life than stereotactic body radiotherapy and compared with Intensity Modulated Raditothearpy (IMRT), proton beam therapy had a cost per quality-adjusted life year of over $36million.
There is evidence of benefit of proton therapy in rare childhood cancers and for certain uncommon brain cancers. However, the assumption that proton therapy must be better than standard radiotherapy for common cancers has not yet been validated by clinical trials. However we know the costs per patient are significantly higher than conventional radiotherapy.
Proton therapy receives significant media exposure which means patients can often assume proton therapy must be better than standard care despite the lack of evidence.
This can be worsened by the commercial interest of for-profit hospitals that have made the huge investment to construct a proton therapy centre to maximise patient throughput of patients. This has led to proton therapy being used for common cancers, such as prostate, without an evidence base to support it. According to NICE (U.K’s National Institute of Clinical Excellence) a review of available evidence proton beam therapy is more expensive and produced lower quality of life than stereotactic body radiotherapy and compared with Intensity Modulated Raditothearpy (IMRT), proton beam therapy had a cost per quality-adjusted life year of over $36million.
The future
|
Further deployment of proton therapy is limited by clinical evidence due to paucity of clinical trials and vast costs involved. Technoligical progress may reduce the cost, for instance single-room proton therapy units have been developed, see the accompanying company's video.
|
|
Sources
https://www.england.nhs.uk/commissioning/wp-content/uploads/sites/12/2016/07/16020_FINAL.pdf
https://www.oncolink.org/cancer-treatment/proton-therapy/overviews-of-proton-therapy/all-about-proton-therapy
https://www.bmj.com/bmj/section-pdf/187511?path=/bmj/344/7853/Feature.full.pdf
https://www.bbc.co.uk/news/uk-england-manchester-40295279
http://cco.amegroups.com/article/view/11097/11904
https://www.sciencedirect.com/science/article/pii/S187985001630114X
Image: CC 2.0 Licence Taheri-Kadkhoda et al. Radiation Oncology 2008 3:4 doi:10.1186/1748-717X-3-4