Carbon ion beam therapy for cancer treatment: A systematic review of effectiveness and safety for selected indications

Project leader: Gregor Goetz
Project team: Gregor Götz, Marija Mitic
Duration: October 2017 – February 2018
Suggested by: Main Association of the Austrian Social Security Institutions
Publication: LBI-HTA Project report No. 101: https://eprints.aihta.at/1174/

Language: English (with German summary)

Background:

In recent decades, many cancer therapy centres, using large and costly accelerators, were constructed internationally to implement a new form of cancer treatment using charged particles. In Austria, MedAustron - planned approximately two decades ago - aimed at focusing on research and at treating cancer patients with charged particles (proton and carbon ion radiotherapy) [1]. The centre started treating cancer patients with particle therapy a year ago, with approximately 30 treated patients by now, and ambitious plans for the future: MedAustron aims at treating 1.000 patients/per year with protons and carbon-ions by 2020 [2].

Carbon ion radiotherapy (CIRT) is claimed to be both more effective and safer than conventional radiotherapy due to its physical dose distribution and its higher relative biological effectiveness (RBE). Additionally, CIRT is expected to have a higher local control of the tumour than conventional radiotherapy while minimising the probability of damaging the surrounding healthy tissues [3, 4]. On the contrary, the higher RBE to be found in CIRT leads to a higher ionization density, generating high linear energy transfer (LET), and can be described as a two-edged sword: some of those differences may constitute advantages, while others may be disadvantages. That is to say; CIRT may also have its negative aspects for certain indications, since a) the treated volume extends the gross tumour volume and thus, healthy tissues may be affected by high LET and b) tumours may be intertwined with, or embedded in, healthy tissues [5]. Thus, it is necessary to elaborate for which indications CIRT should be used as well as whether CIRT is more effective and safer than conventional cancer treatment.

Aims of the project:

The project aims at elaborating possible cancer types, being an indication for carbon ion therapy. As such, clinical studies, analysing the use of CIRT for specific cancer types, will be identified through a systematic literature search and will be reviewed and reported in this project.

Furthermore, a systematic analysis of the literature on the effectiveness (mortality, morbidity) and safety of CIRT for selected indications (e.g., head and neck, lung, prostate, gynecologic, liver tumours) will be conducted.

Research questions:

1.      According to clinical studies, for which tumour types is CIRT currently used?

2.      What is the evidence that CIRT is more or equally effective, or safer, than conventional radiotherapy in selected indications?

Inclusion criteria (PICO):

Methods:

The following procedure will be used for the Systematic Review:

• Firstly, a systematic literature search was conducted in the following four databases:

o    Cochrane (CENTRAL)

o    Centre for Research and Dissemination (CRD)

o    Embase

o    Ovid MEDLINE

o    Clinical Trial Registries and CIRT-Centre websites

• Secondly, an additional handsearch was conducted in references
• Finally, study selection, data extraction and assessing the methodological quality of the studies will be performed by two independent researchers.

o    Screening: GG screened the abstracts. MM will screen the excluded studies.

o    Critical appraisal (=risk of bias assessment) will be conducted by two researchers (GG, MM).

o    Data will be extracted by GG and controlled by MM. For each indication the methodologically best available evidence will be included for data extraction.

o    Assessing the strength of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

Time schedule/ milestones:

References

1.  Wild C, Hintringer K, Narath M. Hadronentherapie: Protonen und Kohlenstoff-Ionen. Eine Übersicht: Refundierungsstatus, Evidenz und Forschungsstand. Wien2013.

2. MedAustron. Zweiter Behandlungsraum ab sofort in Betrieb. 2017; Available from: https://www.medaustron.at/de/node/439.

3. Fukumura A, Tsujii H, Kamada T, Baba M, Tsuji H, Kato H, et al. Carbon-ion radiotherapy: clinical aspects and related dosimetry. Radiat Prot Dosimetry. 2009;137(1-2):149-55.

4. Combs SE, Kieser M, Rieken S, Habermehl D, Jäkel O, Haberer T, et al. Randomized phase II study evaluating a carbon ion boost applied after combined radiochemotherapy with temozolomide versus a proton boost after radiochemotherapy with temozolomide in patients with primary glioblastoma: The CLEOPATRA Trial. BMC Cancer. 2010;10(1):478.

5. Leroy R, Benahmed N, Hulstaert F, Mambourg F, Fairon N, Van Eycken L, et al. Hadron therapy in children - an update of the scientific evidence for 15 paediatric cancers . Synthesis. Belgian Health Care Knowledge Centre (KCE); 2015 [10/09/2017]; Available from: https://kce.fgov.be/sites/default/files/atoms/files/KCE_235CsHadron%20therapy_Synthesis.pdf.>