Health Technology Assessment of Carbon-ion Beam Radiotherapy: A Systematic Review of Clinical Effectiveness and Safety for 54 Oncological Indications in 12 Tumour Regions

Abstract

Background/Aim: Due to the unique physical dose distribution of carbon-ion radiotherapy (CIRT), CIRT can be regarded as a novel tumour irradiation technique-potentially advantageous for various tumour types. Yet it is unclear in how far, superiority or inferiority can be claimed when comparing CIRT to standard irradiation. This study aimed to assess the scientific evidence regarding the effectiveness and safety of CIRT. Materials and Methods: A systematic literature review was performed using the European Network for Health Technology Assessment (EUnetHTA) Core Model ® for rapid relative effectiveness assessment. The literature search for clinical outcome studies on CIRT was performed using four databases [Cochrane (Central), Centre for Research and Dissemination (CRD), Embase and OVID MEDLINE]. The Cochrane Risk of Bias Tool (for randomised controlled trials) and the Institute of Health Economics (IHE-18) Checklist (for observational studies) were used to assess the risk of bias of the included studies. The evidence synthesis was restricted to 54 oncological indications in 12 broad tumour regions and studies with a low or moderate risk of bias, published between 2005 and 2017. Results: Twenty-seven studies were eligible for the qualitative synthesis of the evidence regarding the effectiveness and safety of CIRT: One randomised controlled trial that primarily focused on the feasibility of CIRT, three case-control studies, three before-and after-studies with a focus on quality of life, and 20 further studies of case series. Overall, insufficient scientific evidence was found for superiority or inferiority of CIRT when compared to standard irradiation for 13/54 oncologicaI indications in 7/12 tumour regions (skull base tumours, brain cancer, cancer in the ear-nose-throat region, bone and soft-tissue tumours, lung cancer, prostate cancer, gastrointestinal tumours). No scientific evidence was found for the remaining 41/54 oncological indications. Conclusion: CIRT is undoubtedly, theoretically, a promising cancer treatment. To date, however, it lacks randomised controlled trials assessing the long-term effectiveness and harms associated with the use of CIRT. CIRT must be considered as an experimental treatment due to the lack of high-quality clinical research. Carbon-ion radiotherapy (CIRT) is a novel therapy for treating cancer. CIRT has raised the expectation of achieving higher local control while lowering the probability of damaging surrounding healthy tissues. This is realised by the focused physical distribution of the radiation beams and a high linear energy transfer associated with CIRT (1). CIRT is, however, often described as a two-edged sword (2), highlighting the need to differentiate its application for different oncological indications. That is to say, CIRT may also affect healthy tissues and increase the risk of severe injury to critical organs. Within the past decades, internationally, numerous cancer therapy centres offering CIRT have been established (3). Currently, CIRT is offered at 11 cancer thera...

Particle therapy tumour outcomes: An updated systematic review

“…Only English language publications were included in our systematic review, and important studies may have been excluded. Our conclusions regarding CIT concur with Goetz et al 62 that though CIT is a promising cancer treatment, neither superiority or inferiority can be claimed when compared to conventional treatment options. The unique biological as well as physical properties of carbon ions mean that CIT needs to be integrated into translational treatment programs in novel ways in order to exploit their maximum potential such as eliciting an enhanced immune response.…”

Evolution of Care of Orbital Tumors with Radiation Therapy

“…Until 2016, approximately 21,580 patients were recorded to have been treated with CIRT internationally. 8 For ocular tumors, CIRT has been delivered to choroidal melanoma and lacrimal gland tumors with an acceptable morbidity and sufficient local control, but experience is very limited. [9][10][11] Key Structures, Dose Tolerance, and Toxicity…”

“…Medium-sized melanomas with a height of less than 8 mm and a diameter of less than 16 mm can be treated with I-125 brachytherapy (minimum tumor dose of 85 Gy) and proton radiotherapy (►Figs. [7][8][9][10] with eye preservation or enucleation, Interestingly, no difference in mortality has been observed between patients with medium-sized melanomas treated with brachytherapy versus enucleation. 48 Furthermore, high-dose radiation therapy for uveal melanomas has shown comparable survival outcomes to those of surgery.…”

Three discipline collaborative radiation therapy (3DCRT) special debate: The United States needs at least one carbon ion facility

“…The authors acknowledge that although the current clinical evidence supporting the use of carbon ion therapy is compelling, it is incomplete . The pioneering investigations at LBNL showed that fractionated delivery of heavy ion therapy, generally as a boost at relatively low doses, was well tolerated across diverse tumor sites, including locally advanced prostate cancer, bone and soft tissue sarcomas, and head and neck tumors of the salivary gland and paranasal sinus .…”