Preservation of Neurocognitive Function (NCF) with Conformal Avoidance of the Hippocampus during Whole-Brain Radiotherapy (HA-WBRT) for Brain Metastases: Preliminary Results of Phase III Trial NRG Oncology CC001

Hippocampus‐avoidance whole‐brain radiation therapy with a simultaneous integrated boost for multiple brain metastases

“…In comparison, dose escalation through SIBs has the biological advantage of fractionation for both normal and tumor tissue and ensures better HA. 14 The combination with relevant systemic therapies, including novel immune checkpoint inhibitors, did not alter tumor control significantly, but a definite statement is not possible because of the low number of patients involved.…”

“…The analysis was approved by the local ethics committee. Patients were included if they had at least 4 brain metastases of solid tumors (range, [4][5][6][7][8][9][10][11][12][13][14][15][16], no metastases within the hippocampus or within a distance of 7 mm from the hippocampus, and no leptomeningeal disease or acute neurologic symptoms demanding an immediate start of radiation therapy and were not eligible for inclusion in the HIPPORAD trial (eg, because of insufficient language skills for neurocognitive testing, depression, or a refusal to collaborate). Prior radiation treatment to the brain (stereotactic fractionated radiotherapy, 6 × 5 Gy; radiosurgery, 20 Gy) was allowed if the treated areas showed local control and were not located in the hippocampus or within 7 mm of the hippocampus.…”

“…Prior radiation treatment to the brain (stereotactic fractionated radiotherapy, 6 × 5 Gy; radiosurgery, 20 Gy) was allowed if the treated areas showed local control and were not located in the hippocampus or within 7 mm of the hippocampus. Patients were treated with HA-WBRT (30 Gy in 12 fractions, dose to 98% of the hippocampal volume [D98%] ≤ 9 Gy, dose to 2% of the hippocampal volume [D2%] ≤ 17Gy, mean dose ≤ 10 Gy) and an SIB with 51 or 42 Gy in 12 fractions (according to the size and location) on multiple brain metastases (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) and/or resection cavities (0-2). Pre-irradiated metastases or resection cavities were treated with 30 Gy in 12 fractions without further dose escalation.…”

Treatment of Radiation-Induced Cognitive Decline in Adult Brain Tumor Patients

“…This trial (RTOG 0933) compared decline in HVLT-DR in patients treated with hippocampal avoidance to the decline in HVLT-DR in historical control patients. An initial report of a trial looking at WBRT plus memantine versus WBRT with hippocampal avoidance plus memantine (CC001) showed that time to cognitive decline was longer in the hippocampal avoidance arm [90••]. There are multiple additional clinical trials underway investigating the utility of hippocampal avoidance in patients with brain metastases from breast cancer, non-small-cell lung cancer, small-cell lung cancer, and glioblastoma.…”

Management of the Brain in Small Cell Lung Cancer: Are Patients Paying a Lot Now Instead of a Little Later?

“…Hippocampal avoidance cranial RT was recently reported to predict for longer time to neurocognitive failure in a randomized study of more than 500 patients with BM from any primary site. 16 In addition, neuroprotective drugs, including memantine (which is currently recommended in the National Comprehensive Cancer Network guidelines for patients receiving PCI 17 ) and donepezil, may reduce the neurocognitive decline from cranial RT. 18 Whether PCI can and should be omitted has come to the forefront as results from a Japanese trial in ES-SCLC have challenged the dogma that PCI improves survival in SCLC.…”