To date, it is unclear for which tumour indications carbon ion radiotherapy (CIRT) should be used and if CIRT is more effective and safe than conventional photon radiotherapy. The project aims at elaborating possible cancer types, being an indication for carbon ion radiotherapy. To this end, clinical studies analysing the use of CIRT for specific cancer types were identified through a systematic literature search and have subsequently been reviewed and reported during this project.

Furthermore, a systematic review on the effectiveness (mortality, morbidity) and safety of CIRT for 54 oncologic indications in 12 parts of the body (i.e., skull base, eyes, brain, ear-nose-throat, lung, gastrointestinal tract, bone and soft tissue, prostate, breast, kidney, nervous system, hematologic cancer) was conducted.

A systematic search was conducted in the following databases: Cochrane (CENTRAL), CRD (HTA, NHS-EED, DARE), Embase and Ovid MEDLINE. Studies focusing on the efficacy or safety of carbon ion radiotherapy (CIRT) were searched for. Additionally, a hand search was conducted on the websites of those cancer therapy centres currently offering CIRT, and the Particle Therapy Co-Operative Group (PTCOG) to identify further relevant published and ongoing studies.

Overall, 56 published studies elaborating on the efficacy and/or safety of CIRT have been identified: The majority of the studies chose samples with CIRT patients suffering from tumours in the brain and skull base, prostate and lung region, with 14, 11 and 9 identified studies in those regions respectively. Ear-nose-throat cancer was another significant cluster, consisting of 7 clinical studies. Less frequent clusters were in the bone and soft tissue and gastrointestinal (GI) regions, with 2 and 4 clinical studies respectively assessing the efficacy and safety of CIRT in those regions of the body. In addition, 1 study was identified including patients with choroidal melanomas (of the eye) in their sample.

Of those 56 studies, 27 clinical studies were eligible for qualitative synthesis of the efficacy and safety of CIRT when compared to standard irradiation: 1 randomised controlled trial focusing on toxicity and feasibility of CIRT/PRT with a high risk of bias using a historical control -but no other controlled study- was found. The other 26 included studies were either prospective case series (n=20) or –less frequently– case control studies (n=3) or single arm before-after studies (n=3), focusing on HRQoL. When assessing the superiority/inferiority of CIRT regarding efficacy and safety on the basis of the selected oncologic endpoints, in comparison to standard irradiation, no scientific evidence was found for 41 indications whilst insufficient scientific evidence was found for 13 indications in 7 regions: skull base: chordomas, chondrosarcomas; brain: glioma grade II, glioma grade III; glioblastoma; ear-nose-throat: sarcomas in the head and neck, tumours in the nasal cavity and paranasal sinus, adenoid cystic salivary gland carcinoma; bone and soft tissue: soft tissue sarcoma; lung: non-small cell lung carcinoma; prostate: prostate carcinoma; gastrointestinal tract: oesophageal carcinoma, rectum carcinoma.

Currently (2018), neither superiority nor inferiority on the basis of the selected endpoints regarding efficacy (OS, CSS, DFS, RFS, PFS, LCR, HRQoL) or safety (acute radiation morbidity, late radiation morbidity) can be concluded from the currently (un)available evidence for 54 oncologic indications. CIRT must, at present, therefore be considered an experimental treatment.