Defining the role of proton therapy in the optimal management of paediatric patients in Australia and New Zealand

Abstract

Introduction: Optimal management of paediatric patients with tumours may include radiation therapy. Proton therapy, in theory, should achieve superior outcomes. For children referred overseas, multiple factors are taken into consideration. Aim and Methods: The purpose of this article is to provide context to current decision making. The MEDLINE, EMBASE and PubMed databases were searched for relevant literature. Results and Discussion: The delivery of proton therapy is in evolution. Tissue homogeneity, movement and anatomical changes all present a greater challenge for proton therapy compared with photon therapy. Many dosimetry studies are relying on historical data for cost-benefit analyses that do not accurately reflect contemporary photon therapy. The low dose regions generally do not create significant toxicity, whereas moderate dose regions can be reduced by different techniques such as stereotactic radiotherapy and brachytherapy. Neuro-cognitive and neuro-endocrine toxicities are associated with the greatest health cost, so the greatest gain is for tumours within or abutting the central nervous system. Proton therapy does not eliminate the risk of second malignancy. Conclusions:The benefits of proton therapy must be weighed against not just the estimated impact of low and moderate radiation doses on the developing child but the disruptions to the child, and family life. Relative contraindications to proton therapy include when the relevant late toxicities relate to the high radiation dose region, when the tumour volumes encompass whole body sections and when the target is imprecise. Children with base of skull tumours or an inherited risk of cancer (e.g. those with p53 or Rb1 genes) should be considered for proton therapy.

Clinical outcomes following proton therapy for children with central nervous system tumors referred overseas

“…Even under the best circumstances, such support cannot be replicated in another country, within a foreign culture. These concerns have prompted some practitioners to question the wisdom and value of international pediatric referrals for proton therapy …”

Scoping the literature on patient travel abroad for cancer screening, diagnosis and treatment

“…There is discussion of clinical benefits being balanced with potential disruption that travel overseas could cause. 66,67 Little is known about the relative clinical outcomes for particular treatments, institutions, clinicians and localities. There is scant evidence on long or short-term follow-up of patients dispersing to home countries following treatments and the financial cost of states supporting the treatment of patients abroad.…”

A scoping review of patient selection methods for proton therapy

“…3,4 While both modalities offer effective EBRT cancer treatment, PT can reduce normal tissue doses compared to conventional X-ray therapy, thus potentially decreasing radiation-induced complications such as a second primary malignancy. [5][6][7] Despite this, not all patients requiring radiation therapy are offered PT due to patient accessibility, cost, equitable dosimetry with X-ray therapy and uncertainty regarding clinical outcomes following treatment. 3,4 PT is more costly compared to the current, best available conventional radiation.…”

“…9 Currently, the best available evidence for patients being referred to PT is from retrospective analyses of small single-institutional studies, patient case studies, dosimetric studies or literature reviews. 5,10 The lack of 'Gold Standard' randomised control trial data is attributed to methodological and ethical concerns given PT's limited availability, high cost, limited long-term complication data and difficulties with appropriate, blinded patient allocation. 11,12 PT has been reported to be more costeffective compared to conventional X-ray therapy in paediatric patients diagnosed with central nervous system tumours, some patients with head and neck tumours, certain breast cancer patients at high risk of radiationinduced cardiac events and those diagnosed with hepatocellular tumours.…”