Functional brain imaging interventions for radiation therapy planning in patients with glioblastoma: a systematic review

Rationale: This systematic review aims to synthesise the outcomes of different strategies of incorporating functional biological markers in the radiation therapy plans of patients with glioblastoma to support clinicians and further research. Methods: The systematic review protocol was registered on PROSPERO (CRD42021221021). A structured search for publications was performed following PRISMA guidelines. Quality assessment was performed using the Newcastle– Ottawa Scale. Study characteristics, intervention methodology and outcomes were extracted using Covidence. Data analysis focused on radiation therapy target volumes, toxicity, dose distributions, recurrence and survival mapped to functional image-guided radiotherapy interventions. Results: There were 5733 citations screened, with 53 citations (n = 32 studies) meeting review criteria. Studies compared standard radiation therapy planning volumes with functional image-derived volumes (n = 20 studies), treated radiation therapy volumes with recurrences (n = 15 studies), the impact on current standard target delineations (n = 9 studies), treated functional volumes and survival (n = 8 studies), functionally guided dose escalation (n = 8 studies), radiomics (n = 4 studies) and optimal organ at risk sparing (n = 3 studies). The approaches to target outlining and dose escalation were heterogeneous. The analysis indicated an improvement in median overall survival of over two months compared with a historical control group. Simultaneous-integrated-boost dose escalation of 72–76 Gy in 30 fractions appeared to have an acceptable toxicity profile when delivered with inverse planning to a volume smaller than 100 cm3. Conclusion: There was significant heterogeneity between the approaches taken by different study groups when implementing functional image-guided radiotherapy. It is recommended that functional imaging data be incorporated into the gross tumour volume with appropriate technology-specific margins used to create the cl