Background: There are currently 82 particle therapy facilities in clinical operation worldwide. A further 37 centers are under construction, respectively in planning. The number of centres worldwide has more than doubled since 2013. There are currently 27 centres operating in Europe alone (2013: 14). With such a large number of treatment centres, it should be assumed that the underlying clinical evidence for patient benefit is convincing. The present update of the LBI-HTA Report 2013 has the task of providing an overview of confirmed indications, i.e. indications that are only recommended under clinical research and excluded indications.

Methods: For the present update of the four LBI-HTA reports from 2013, 2015 and 2018, only a manual search for HTA overviews and systematic reviews was carried in three databases.

Results: The identified reviews unanimously articulate that the existing -mostly retrospective- studies are of low quality and insufficient to make conclusive statements about the added value of proton or carbon ion therapy. The picture remains unchanged compared to 2013. Only a few indications are recommended for proton or carbon ion therapy, more for reasons of plausibility than on the basis of convincing data. These are: chordomas and chondrosarcomas, uveamelanoma (under conditions), paediatric tumours (skull base, brain and head and neck tumours) to avoid secondary tumours. Further indications, with curative intent and not metastatic, are only recommended under conditions of prospective clinical studies: tumours at the base of the skull and in the central nervous system, tumours in the head and neck area (exception oropharynx: G-BA), inoperable lung carcinomas (NSCLC) stages I to IIIb, lymphomas and sarcomas, some gastrointestinal tumours (esophagus, pancreas), inoperable liver cell carcinoma (HCC), prostate carcinoma (with restrictions). Clearly excluded indications are operable HCC, operable NSCLC, NSCLC stage IV, rectal cancer (with exceptions), breast cancer (with exception).

Conclusion: In summary, it can be said that numerous reviews come to the same conclusion, namely that only prospective high-quality primary studies provide information on the superiority or equivalence of proton and carbon ion therapy in clinical endpoints of effectiveness and superiority in safety endpoints such as acute and late toxicity.