ESTRO 2025 - Abstract Book

S4416

Late-breaking abstracts

ESTRO 2025

University Hospital Würzburg, Würzburg, Germany. 11 Clinic of Radiotherapy (Radiooncology), University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. 12 Department of Radiotherapy and Oncology, University Hospital, Goethe University Frankfurt, Frankfurt, Germany. 13 Department of Radiation Oncology, Krankenhaus Nordwest, Frankfurt, Germany. 14 Department of Radiation Oncology, Staedtisches Klinikum Dessau, Brandenburg Medical School Theodor Fontane, Dessau, Germany. 15 Department of Radiation Oncology, University Hospital Halle (Salle), Halle, Germany. 16 Department of Radiation Oncology, Klinikum Wolfsburg, Wolfsburg, Germany. 17 Department of Radiation Oncology, 17. radprax MVZ Nordrhein GmbH, Wuppertal, Germany. 18 Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway. 19 Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway. 20 Department of Neuroradiology, Medical Center - University of Freiburg, Freiburg, Germany. 21 Department of Psychosomatic Medicine and Psychotherapy, Medical Center - University of Freiburg, Freiburg, Germany Purpose/Objective The HIPPORAD trial aimed to assess the effect on neurocognitive functions and oncological outcome of whole brain radiation therapy (WBRT) with simultaneous integrated boost (SIB), with versus without hippocampal avoidance in patients with multiple brain metastases. Material/Methods This prospective, multicentre, randomized, double-blind trial (DRKS00004598) included patients with 4-10 brain metastases (≥5 mm), enrolled across 13 centres in Germany (1). Participants were randomized 1:1 to receive WBRT+SIB with hippocampal avoidance (HA-WBRT+SIB, arm A) or WBRT+SIB without hippocampal avoidance (arm B). Treatment consisted of WBRT (30 Gy) with SIB of 51 Gy to metastases and 42 Gy to brainstem metastases and resection cavities, delivered in 12 fractions, 5x/week. The primary endpoint was the change in neurocognitive function, measured using the Verbal Learning and Memory Test (VLMT), 3 months post treatment. Secondary endpoints consisted of neurocognitive function at 9 and 18 months, anxiety and depression levels, quality of life, and oncological outcomes. Results Between August 2 nd , 2016, and September 7 th , 2021, 170 patients were enrolled and 136 randomized to HA WBRT+SIB (n=67) or WBRT+SIB (n=69). At 3 months, 38 patients in arm A and 42 in arm B had been treated per protocol, were known to be alive and included in the primary analysis. No significant difference was observed in overall learning performance between arms (p=0.83). VLMT-scores declined at 3 months in both groups. Scores increased at 9 months, with HA-WBRT+SIB showing an improved trend in comparison to WBRT+SIB. By 18 months, scores returned to baseline in both arms. Patients receiving HA-WBRT+SIB experienced lower depression rates at 3 (p=0.047) and 18 months (p=0.048). At one year, distant intracranial progression rate was 22% in both arms, while the local progression rate was 4% in arm A and 12% in arm B. Time to hippocampal tumour progression did not differ significantly between arms (p=0.98). Neurological death rate at one year was 4% in Arm A and 12% in Arm B. Treatment-related serious adverse events occurred in 3% and 6% of patients, respectively. Conclusion This trial is the first to show that hippocampal avoidance during WBRT may reduce depression rates. Changes in verbal memory were comparable between arms, with a tendency towards improved values in the HA-WBRT+SIB arm at 9 months. By 18 months, neurocognitive recovery was seen in both groups. HA-WBRT+SIB was safe, achieved high intracerebral tumour control and low neurological mortality rates.

Keywords: brain metastases, hippocampus, depression

References Grosu AL, Frings L, Bentsalo I, Oehlke O, Brenner F, Bilger A, Fennell JT, Rothe T, Schneider-Fuchs S, Graf E, Schmoor C, Beck J, Becker G, Bock M, Egger K, Urbach H, Lahmann C, Popp I. Whole-brain irradiation with hippocampal sparing and dose escalation on metastases: neurocognitive testing and biological imaging (HIPPORAD) - a phase II prospective randomized multicenter trial (NOA-14, ARO 2015-3, DKTK-ROG). BMC Cancer. 2020 Jun 8;20(1):532. doi: 10.1186/s12885-020-07011-z.