Broadcaster: BBC One
Review by Ella Yabsley
A study published on the Lancet Oncology website in January 2016 reported that proton beam therapy was as effective as traditional photon radiotherapy for the treatment of paediatric medulloblastoma (a childhood brain cancer). The paper also suggests proton radiotherapy reduces toxicity towards normal tissues (compared to photon radiotherapy) and could improve long-term health outcomes for children with malignant brain cancer. At the present time, the NHS are paying for eligible patients to receive proton treatment abroad. From 2019, two new NHS proton beam therapy facilities will be opened in London and Manchester (more by private institutions).
This video file (11 mins), a combination of several shorter pieces from Breakfast News, gives background to the development including an interview with a paediatric oncologist who explains what the study does, and does not, show. It is a (relatively) large study but the observations appear not to be a surprise to those working in the field; the interest may be linked to the controversy surrounding the Ashya King case.
So what is the difference between photon and proton radiotherapy? Both techniques involve targeting a beam of particles at a tumour, destroy DNA and inhibit cancer cell replication. Photon radiotherapy uses X-ray (photon) beams. Photons are high-energy light particles with no mass; they penetrate directly and entirely through the body, administering a dose of radiation along a path to both healthy and cancerous tissue.
Proton radiotherapy involves pointing a beam of protons, hydrogen atoms with their electron removed, at a tumour. Protons are heavy, positively charged particles, when accelerated through matter at high speeds (0.66* the speed of light) energy is released in the form of ionising radiation. Protons are propelled by alternating electromagnetic fields inside a particle accelerator called a cyclotron, a machine weighing around the same as a jumbo jet. When an accelerated proton enters tissue it loses velocity and eventually stops, the position of the proton at its slowest point (just before stopping) is where it releases the maximum amount of energy. This maximum release of energy is known as the Bragg peak. The properties of an accelerated proton are such that at the point of entry through healthy tissue, only a small amount of radiation is administered (entrance dose). Conversely, the maximum energy dose is administered at the exact position of the tumour, after releasing its energy the proton will stop, preventing any further damage to healthy tissues. X-rays pass straight straight through the body, damaging healthy tissue on exit (exit dose); protons do not administer an exit dose. Proton radiotherapy has less side effects than photon radiotherapy as damage to healthy tissue is reduced (check out this video animation which summarises proton radiotherapy).
Radiotherapy-related side effects are typically unavoidable, traditional radiotherapy may also lead to secondary cancer formation. Patients who have undergone radiotherapy may have side effects ranging from hormonal deficits, neurocognitive impairment, pulmonary, endocrine, gastrointestinal and hearing problems (ototoxicity). In the case of paediatric cancers, young children undergoing traditional irradiation therapy are at risk of damaging rapidly-developing tissues and organs. The results of the phase ll clinical trail from Yock et al show that proton therapy may be a more attractive candidate than traditional radiotherapy for the treatment of paediatric medulloblastoma. None of the patients in the trial developed endocrine, gastrointestinal or pulmonary system damage (commonly seen after photon radiotherapy). Most of the patients, however, still developed late-effecting ototoxicity. Proton therapy does not alleviate all late-effecting sequelae associated with traditional radiotherapy (photon), but it does reduce some of the major side effects.
Post-surgery, radiotherapy is still the most effective treatment to prevent the return of cancer. The Lancet Oncology research does not provide a great deal of new information, however it is a well established study with a good sized cohort (n=59) of patients with paediatric medulloblastoma. It is important to note that traditional proton radiotherapy still has adequate toxicity levels. Photon radiation has seen its share of improvement in recent years with the aid of computer-assisted techniques such as three-dimensional imaging. Three-dimensional conformal radiation therapy (3DCRT) uses imaging to construct an in silico ‘mould’ of a tumour. This 3D image is then used in combination with photon radiotherapy. Intensity-modulated radiotherapy (IMRT) has the capacity to adjust the shape, size and intensity of X-rays to match the shape of the tumour. Image-guided radiotherapy (IGRT) is IMRT with an extra scanner; this technique can monitor the movement of the patient in real-time via a feedback mechanism, allowing tumour targeting to be ultimately precise.
Yock et al (2016) Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: a phase 2 single-arm study Lancet Oncology DOI: http://dx.doi.org/10.1016/S1470-2045(15)00167-9
Munck af Rosenschöld et al (2016) A Retrospective Evaluation of the Benefit of Referring Paediatric Cancer Patients to an External Proton Therapy Centre Paediatric Blood & Cancer 63:262-269 (subscription required)
Olsen et al (2007) Proton therapy – A systematic review of clinical effectiveness Radiotherapy and Oncology 83:123-132
Nutting et al (2011) Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial Lancet Oncology 12:127-136
Webb (2005) The effect on IMRT conformality of elastic tissue movement and a practical suggestion for movement compensation via the modified dynamic multileaf collimator (dMLC) technique Physics in Medicine and Biology 50:1163-1190
Proton beam cancer therapy ‘effective with fewer side effects’ (BBC)
Proton beam centres ‘to treat 1,500 patients a year (BBC)
Proton beam therapy Q&A: What is it and how is it different to radiotherapy to treat cancer? (Independent)