Advanced radiotherapeutic treatment techniques limit the cognitive morbidity associated with whole-brain radiotherapy (WBRT) for brain metastasis through avoidance of hippocampal structures. However, achieving durable intracranial control remains challenging.

We conducted a single-institution single-arm phase II trial of hippocampal-sparing whole brain irradiation with simultaneous integrated boost (HSIB-WBRT) to metastatic deposits in adult patients with brain metastasis. Radiation therapy consisted of Intensity-Modulated Radiation Therapy delivering 20 Gy in 10 fractions over 2-2.5 weeks to the whole brain with a simultaneous integrated boost of 40 Gy in 10 fractions to metastatic lesions. Hippocampal regions were limited to 16 Gy. Cognitive performance and cancer outcomes were evaluated.

A total of 50 patients, median age of 60 years (IQR 54-65), were enrolled. Median progression free survival was 2.9 months (95% CI: 1.5-4.0) and overall survival was 9 months. As expected, poor survival and end of life considerations resulted in a high exclusion rate from cognitive testing. Nevertheless, mean decline in Hopkins Verbal Learning Test-Revised delayed recall (HVLT-R DR) at 3 months after HSIB-WBRT was only 10.6% (95% CI, -36.5% to 15.3%). Cumulative incidence of local and intracranial failure with death as a competing risk was 8.8% (95% CI, 2.7% to 19.6%) and 21.3% (95% CI, 10.7% to 34.2%) at 1 year, respectively. Three grade 3 toxicities consisting of nausea, vomiting, necrosis or headache were observed in 3 patients. Multidimensional Fatigue Inventory (MFI)-20 scores remained stable for evaluable patients at 3 months.

HVLT-R DR after HSIB-WBRT was significantly improved as compared to historical outcomes in patients treated with traditional WBRT, while achieving intracranial control similar to patients treated with WBRT plus stereotactic radiosurgery (SRS). This technique can be considered in select patients with multiple brain metastasis who cannot otherwise receive SRS.