Proton Beam Therapy for Cancer in Children and Adults: A Health Technology Assessment.

Background: Proton beam therapy has potential to reduce late toxicity in cancer treatment by reducing the risk of damage to surrounding healthy tissues. We conducted a health technology assessment of proton beam therapy, compared with photon therapy, for children and adults with cancer requiring radiotherapy. Our assessment included an evaluation of safety, effectiveness, cost-effectiveness, the budget impact of publicly funding the construction and use of proton beam therapy in Ontario, and patient preferences and values.

Methods: We performed a systematic literature search of the clinical evidence to retrieve systematic reviews and selected and reported results from one review that was recent, high quality, and relevant to our research question. We complemented the chosen systematic review (published in 2019) with a literature search to identify randomized controlled trials published after the review. We assessed the risk of bias of each included study using the Risk of Bias in Systematic Reviews (ROBIS) tool and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and also analyzed the budget impact of publicly funding proton beam therapy in cancer patients in Ontario. To contextualize the potential value of proton beam therapy, we spoke with 10 people with cancer (or their caregivers) who had either received or were considering proton beam therapy.

Results: We included one systematic review of the clinical evidence reporting on 215 publications on proton beam therapy in children and adults across 19 tumour categories/conditions. Compared with photon therapy, proton beam therapy may result in fewer adverse events but similar overall survival and progression-free survival in children with brain tumours (GRADE: Low), adults with esophageal cancer (GRADE: Low to Very low), head and neck cancer (GRADE: Low to Very low), and prostate cancer (GRADE: Low). Proton beam therapy may result in similar adverse events, overall survival, and progression-free survival in adults with brain tumours (GRADE: Low), breast cancer (GRADE: Low), gastrointestinal cancer (GRADE: Very low), liver cancer (GRADE: Moderate to Very low), lung cancer (GRADE: Moderate to Very low), and ocular tumours (GRADE: Low). There was insufficient evidence to evaluate the effectiveness and safety of proton beam therapy in other pediatric tumours, as well as bladder cancer, bone cancer, lymphoma, and benign tumours in adults.The economic evidence suggests that proton beam therapy may be cost-effective in pediatric populations with medulloblastoma; however, studies were based on limited clinical evidence. In other indications, the cost-effectiveness of proton beam therapy is unclear. The 5-year budget impact of funding a four-room proton beam therapy centre in Ontario would be $124.8 million, resulting in a cost per patient of $48,217, including both capital investment and operational costs, compared to the current average cost of $326,800 to send patients out of country. Funding a one-room proton beam therapy centre that would treat selected Ontario patients and patients from other Canadian provinces would have a lower budget impact of $15.2 million over the next 5 years. If we assume building proton beam therapy centres would substitute for new photon therapy centres, then the 5-year budget impact could be further reduced to approximately $13 million (one room) or $94.8 million (four rooms). The people we interviewed who had received proton beam therapy reported positive responses to the treatment. They chose to have proton beam therapy because they believed it to be safer and to have fewer long-term side effects than photon therapy. However, accessing proton beam therapy in the United States was often challenging, with logistical and emotional burdens. Patients and families valued the opportunity to receive effective treatment close to family and other emotional supports.

Conclusions: Proton beam therapy may be as effective as conventional radiation therapy, and it may cause fewer side effects, especially for children with brain tumours and for adults with certain types of cancer. Based on published economic evidence, proton beam therapy is likely cost-effective compared with photon therapy in children with medulloblastoma, but cost-effectiveness is unclear in children and adults with other clinical indications. We estimate that publicly funding a proton beam therapy centre in Ontario would result in additional costs of $124.8 million over the next 5 years, but with a six- to seven-fold reduction in the per-patient cost compared with current spending. People with cancer and caregivers with whom we spoke were generally supportive of having proton beam therapy available in Ontario.