ESTRO 2025 - Abstract Book

S734

Clinical - CNS

ESTRO 2025

3839

Digital Poster INDIGO – an innovative proton therapy concept for low-grade glioma patients tested multicentrically in a prospective randomized trial Julia Bauer 1,2 , Habiba Sallem 1,2 , Martina Palkowitsch 3,4 , Thomas Tessonnier 1,5 , Christopher Büsch 6 , Bastian von Nettelbladt 1,2 , Hanna Waldsperger 1,2 , Katharina Weusthof 1,2 , Klaus Herfarth 1,2 , Jürgen Debus 1,2,5 , Steffen Löck 3,7,8 , Mechthild Krause 3,4,7 , Semi B. Harrabi 1,2 1 Department of Radiation Oncology and Heidelberg Ion Beam Therapy Center, Heidelberg University Hospital, Heidelberg, Germany. 2 Heidelberg Institute for Radiation Oncology (HIRO), National Center for Radiation Research in Oncology (NCRO), Heidelberg, Germany. 3 OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany. 4 Institute of Radiooncology – OncoRay, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany. 5 Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 6 Institute of Medical Biometry, (IMBI), Heidelberg, Germany. 7 Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany. 8 German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Heidelberg, Germany Purpose/Objective: Low-grade glioma (LGG) patients have a favourable prognosis, making long-term complication-free survival crucial. In this regard, proton therapy (PT) is a promising treatment modality. However, uncertainties in the proton relative biological effectiveness (RBE) and a spatially varying radiosensitivity in the central nervous system can complicate safe treatment. Analysis of late radiation-induced brain injuries observed in follow-up MR imaging have provided clinical evidence for an enhanced radiosensitivity in the periventricular space (PVS) and a variable proton RBE, and predictive models have been proposed for lesion occurrence (1,2). Based on such an innovative voxel-level risk model, we designed a treatment planning (TP) protocol that minimizes brain injury risk while maintaining tumour control. The efficacy of this protocol is being tested in a multicentric clinical trial using a prospective, randomized phase II design (INDIGO: NCT05964569). Material/Methods: The INDIGO protocol randomizes 120 LGG patients into a control and experimental arm, treated with 54 Gy(RBE = 1.1) prescribed to the CTV in 30 fractions. Patients in the experimental arm undergo model-based TP delivering the prescribed dose to an extended GTV and designed to actively spare the PVS while optimizing the dose distribution using a linear-energy-transfer (LET) dependent proton RBE according to the risk model. The primary endpoint is the cumulative incidence of late contrast-enhancing brain lesions (CEBLs), assessed through quarterly contrast enhanced T1-weighted MR imaging over two years following PT. Results: The protocol design study demonstrated the feasibility of efficient lesion risk control by dose-de-escalation in the CTV, active PVS sparing, and control of LET-dependent proton RBE for treatment plan optimization, a typical plan is shown in figure 1. At the time of abstract submission, 20 patients have been enrolled (N control =9, N exp =11), achieved risk minimization is reported in figure 2. As expected, both the clinical and oncological outcomes have been excellent thus far. Short-term follow up MR imaging has showed neither evidence of CEBLs nor any signs for local failure in the experimental arm. A more reliable assessment – especially on the radiation induced side effects – will be made after the completion of the 2y-follow-up period. Conclusion: INDIGO assesses the efficacy of the first TP protocol that uses a voxel-level risk model to individually modulate the physical dose distribution for PT. Trial outcome is expected to change clinical practice in view of a general dose de escalated outside the GTV and a targeted sparing of the periventricular space for LGG patients.