For cancer patients who have multiple brain metastases, tailoring whole-brain radiotherapy so that it avoids the hippocampus preserves memory and quality of life for at least 6 months, according to a report published online Oct. 27 in the Journal of Clinical Oncology.
Injury to the compartment of neural stem cells located in the subgranular zone of the hippocampal dentate gyrus is thought to suppress the formation of new memory and to impair recall, and injury to this region by relatively low doses of radiotherapy is thought to account for radiation-induced early cognitive decline. Researchers performed a multicenter phase II trial to determine whether sparing this region would prevent such cognitive decline. They assessed 100 patients who had brain metastases of nonhematopoietic malignancies and underwent irradiation of the whole-brain parenchyma minus the “hippocampal avoidance regions” that had been designated using advanced imaging techniques, said Dr. Vinai Gondi of the Cadence Brain Tumor Center and CDH Proton Center, Warrenville, Ill., and his associates.
The study participants underwent cognitive assessment at baseline and at regular intervals following radiotherapy, as well as assessment of health-related quality of life. Their results were compared with those of 208 historical control subjects who had received standard whole-brain radiotherapy without hippocampal avoidance in an unrelated clinical trial. The radiation-sparing technique, which reduced the mean dose to the neural stem compartment by an estimated 80%, produced significant memory preservation that persisted for up to 6 months of follow-up. The mean probability of cognitive deterioration at 4 months was only 7%, compared with 30% in the historical control group.
The hippocampal-sparing technique also preserved physical, social/family, emotional, and functional well-being, as assessed by the patient and his or her family, the investigators said (J. Clin. Oncol. 2014 Oct. 27 [doi:10.1200/JCO.2014.57.2909]).
The risk that metastases would develop in the nonradiated hippocampus was considered low, as only three patients (4.5%) developed such metastases. Previously, investigators have predicted that the risk would be closer to 10%, but they appear to have overestimated the actual risk, Dr. Gondi and his associates said.
These promising results require further validation in phase III trials. Studies are now underway to assess whether further reducing the radiation dose to the hippocampal area may improve outcomes even more, and future studies also are being planned to assess whether hippocampal avoidance prevents longer-term cognitive decline, beyond the 6-month mark established in this study, the investigators added.
This study was supported by the National Cancer Institute’s Radiation Therapy Oncology Group and Community Clinical Oncology Program. Dr. Gondi reported having no financial disclosures; his associates reported numerous ties to industry sources.