"Children are not just little adults," said Mahajan, medical director for the University of Texas MD Anderson Proton Therapy Center (Houston, TX). "The proportions of their body are different, both on the outside and the inside." Brain development, for example, occurs rapidly during a child's first three years, and the increased radiosensitivity of the brain – and other maturing organs and tissues – must be accounted for when planning proton treatments.

Paediatric patients can present with a large variety of tumours, with varying radiosensitivity and location. Another issue is that the tumour size must be considered relative to the patient size, with a 5 cm mass, for example, representing a large proportional volume in a small child. The same goes for any planned margins: "A 1 cm margin may not be a big deal in an adult, but it could well be in a baby," explained Mahajan, who has been treating paediatric patients with protons at the MD Anderson Proton Therapy Center since it opened in 2006.

Minimizing uncertainties

The conformality of proton therapy comes hand-in-hand with the requirement for highly accurate tumour delineation, patient set-up and beam delivery. Treatment plans must pay particular attention to reducing dose to normal tissue, and any normal structures observed on imaging should be delineated for avoidance. For example, it's possible to map functional areas in the brain using functional MRI and then design a beam arrangement to avoid these areas. If possible, information regarding the different susceptibility of tissue at different development should also be incorporated into the treatment plan.

A key part of the set-up process for paediatric patients relates to reducing anxiety. This requires a dedicated therapy team and close liaison with anaesthetists and other specialists. At MD Anderson, around 60% of paediatric patients are under 10, with half of these five years or less. While anaesthesia is generally required for all under the age of five, reduced anxiety may remove the need for sedation in some older children.

Mahajan also pointed out that most external immobilization equipment is designed to fit adults, and that children under the age of five cannot use a bite block. It's important, therefore, to have access to masks and other body immobilization kit that can accommodate smaller patients.

The MD Anderson team uses daily kV imaging to increase the accuracy of patient set-up. Mahajan emphasises the importance of using appropriate structures – whether bones or fiducials – for alignment. "We need to be careful about what is used to set up the patient and its relationship to the tumour," she said.

Another option would be to use volumetric imaging for patient set-up. As such, Mahajan is hoping to install a diagnostic quality CT scanner in the treatment room. While daily CT can reduce the size of the planned target volume (PTV) margins, she emphasized that this must be weighed up against the increased dose delivered, as well as the additional set-up time and patient anxiety. It's important to use the lowest dose and smallest field size possible. Ultimately, it may be feasible to employ alternative, non-ionizing methods for image-guidance, such as surface mapping or MRI.

4D and 5D issues

As well as accurate daily set-up, intra-fractional movement arising from respiration, bladder filling, bowel gas and other organ motion must also be addressed. Motion management options reflect those under development for proton therapy in general and include the use of internal target volumes (ITV), gating and tracking. Mahajan pointed out that it's difficult to develop large programmes to evaluate such techniques in children. "I'm going to see how they do this for adults, and copy and adapt it for use in children," she said.

Currently, Mahajan treats most paediatric patients using passive scattering, but she is starting to use scanned proton beams for some cases. She explained that the pencil beam on MD Anderson's proton therapy system currently doesn't have a penumbra trimmer, so while it delivers more conformal target dose, the out-of-field dose may be a little higher in many cases. To address this, the physics team is developing an aperture that will be incorporated into the scanning beam. Once this is installed, many more children will receive scanned pencil beam treatments.

Finally, said Mahajan, one must consider changes that occur within the tumour or patient between fractions – the so-called 5th dimension. She noted that paediatric tumours can develop particularly rapidly, resulting in tight time constraints for starting treatment. Once therapy has begun, tumours may well shrink and the patient may lose or gain weight. Monitoring such changes and performing adaptive re-planning can help reduce dose to normal structures.

The number of paediatric proton cases is growing year-on-year. The proportion of extracranial treatment sites is also increasing, with more treatments in motion-prone areas such as the thorax, abdomen and pelvis. To maximize the potential benefits of particle therapy for paediatric patients, we need to incorporate lessons from both the photon and the adult proton worlds, Mahajan concluded.