Phase II trial of hippocampal-sparing whole brain irradiation with simultaneous integrated boost for metastatic cancer

• DOI: 10.1093/neuonc/noaa092
• Publication Date: 2020-04-23T19:10:37Z
• Authors: Kenneth D Westover; J Travis Mendel; Tu Dan; Kiran Kumar; Ang Gao; Suprabha Pulippar...; Puneeth Iyengar; Lucien Nedzi; Raquibul Hannan; John Anderson; Kevin S Choe; Wen Jiang; Ramzi Abdulrahman; Asal Rahimi; Michael Folkert; Aaron Laine; Chase Presley; C Munro Cullum; Hak Choy; Chul Ahn; Robert Timmerman
• Keywords: Adult; 03 medical and health sciences; 0302 clinical medicine; Brain Neoplasms; Humans; Radiotherapy, Intensity-Modulated; Cranial Irradiation; Middle Aged; Radiosurgery; Hippocampus; 3. Good health

Abstract

Background 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.

Methods 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.

Results A total of 50 patients, median age 60 years (interquartile range, 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: −36.5‒15.3%). Cumulative incidence of local and intracranial failure with death as a competing risk was 8.8% (95% CI: 2.7‒19.6%) and 21.3% (95% CI: 10.7‒34.2%) at 1 year, respectively. Three grade 3 toxicities consisting of nausea, vomiting, and necrosis or headache were observed in 3 patients. Scores on the Multidimensional Fatigue Inventory 20 remained stable for evaluable patients at 3 months.

Conclusions HVLT-R DR after HSIB-WBRT was significantly improved compared with 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 metastases who cannot otherwise receive SRS.