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

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.

The Impact of Stereotactic or Whole Brain Radiotherapy on Neurocognitive Functioning in Adult Patients with Brain Metastases: A Systematic Review and Meta-Analysis

“…Other impaired cognitive constructs in the WBRT studies were EF (29–38%), fine motor coordination (31%), information processing speed (28%), and verbal fluency (7–32%). Even though Westover et al [41] observed a decline in 17% of their patients ( N = 18) regarding L&M performance, on the group level, no significant changes from baseline were found for the other cognitive constructs [41]. Nevertheless, large variations in mean relative change were found for all cognitive constructs (L&M, information processing speed, EF, and verbal fluency).…”

Simultaneous stereotactic radiosurgery of multiple brain metastases using single-isocenter dynamic conformal arc therapy: a prospective monocentric registry trial

“…This also includes patients who have been treated with WBRT for multiple BMs. As a result, BM patients are now more frequently affected by a treatmentassociated long-term neurocognitive decline; therefore, current approaches are trying to preserve cognitive function following WBRT [10,11,[14][15][16][17][18][19][20]. The ongoing multicentric HIPPORAD (NOA-14) trial addresses this approach (results are pending) [16].…”

Management of Brain and Leptomeningeal Metastases from Breast Cancer

“…Moreover, Gondi et al have suggested a remarkable benefit in speaking, memory, and patient-reported symptoms, including fatigue and interference in daily living, following WBRT associated with memantine [ 31 ]. Westover et al have investigated, in a single-arm phase II trial, the hippocampal-sparing WBRT with a simultaneous integrated boost (HSIB-WBRT) delivered to BM in 50 patients reporting a median decline in Hopkins Verbal Learning Test-Revised delayed recall (HVLT-R DR) at three months of 10.6%, a cumulative incidence of intracranial recurrence of 8.8%, and a median OS of nine months [ 32 ].…”