Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) for small cell lung cancer reduces hippocampal atrophy compared to conventional PCI

Abstract

Background Reducing radiation dose to the hippocampus with hippocampal avoidance prophylactic cranial irradiation (HA-PCI) is proposed to prevent cognitive decline. It has, however, not been investigated whether hippocampal atrophy is actually mitigated by this approach. Here, we determined whether HA-PCI reduces hippocampal atrophy. Additionally we evaluated neurotoxicity of (HA-)PCI to other brain regions. Finally, we evaluated associations of hippocampal atrophy and brain neurotoxicity with memory decline. Methods High quality research MRI scans were acquired in the multicenter, randomized phase 3 trial NCT01780675. Hippocampal atrophy was evaluated 4 months (57 HAPCI patients and 46 PCI patients) and 12 months (28 HAPCI patients and 27 PCI patients) after (HA-)PCI. We additionally studied multimodal indices of brain injury. Memory was assessed with the Hopkins Verbal Learning Test Revised (HVLT-R). Results HA-PCI reduced hippocampal atrophy at 4 months (1.8% for HA-PCI and 3.0% for PCI) and at 12 months (3.0% for HA-PCI and 5.8% for PCI). Both HA-PCI and PCI were associated with considerable reductions of gray matter and normal appearing white matter, increases of white matter hyperintensities and brain aging. There were no significant associations between hippocampal atrophy and memory. Conclusions HA-PCI reduces hippocampal atrophy at 4 and 12 months compared to regular PCI. Both types of radiotherapy are associated with considerable brain injury. We did not find evidence for excessive brain injury after HA-PCI relative to PCI. Hippocampal atrophy was not associated with memory decline in this population as measured with HVLT-R. The usefulness of HA-PCI is still subject to debate.

Self-Reported Cognitive Function and Quality of Life in Patients With SCLC in the Hippocampal Avoidance Prophylactic Cranial Irradiation Versus Prophylactic Cranial Irradiation Randomized Phase 3 Trial (NCT01780675)

“…The detailed magnetic resonance imaging acquisition and radiation treatment procedures have been previously described. 14 , 15 Briefly, patients were irradiated with a total dose of 25 Gy in 10 fractions, five times a week. The mean dose of the hippocampal avoidance zone of the HA-PCI was limited to 8.5 Gy.…”

“…Furthermore, no differences were found for other additional cognitive outcomes, despite an observed reduction in hippocampal atrophy in the HA-PCI compared with the PCI arm. 15 Nevertheless, both treatment modalities were associated with considerable brain injury. 15 Here, we report the study's secondary objectives: comparing patients’ QoL, in particular their self-reported cognitive performance (SRCF) between HA-PCI and PCI.…”

“… 15 Nevertheless, both treatment modalities were associated with considerable brain injury. 15 Here, we report the study's secondary objectives: comparing patients’ QoL, in particular their self-reported cognitive performance (SRCF) between HA-PCI and PCI.…”

Prophylactic cranial irradiation in small cell lung cancer: an update

“…Moreover, fewer patients in the NCT01780675 trial completed their neurocognitive tests (45 in PCI; 56 in HA-PCI), versus the patients in the PREMER trial (68 in PCI and 69 in HA-PCI); this difference may have affected the results. A follow-up imaging study of the NCT01780675 trial revealed no evidence of excessive brain injury after HA-PCI, and HA-PCI reduced hippocampal atrophy in contrast to regular PCI [38]. A multicentre phase II trial evaluating the impact of HA-PCI administered concurrently with CRT in patients with LS-SCLC revealed that the probability of neurocognitive function decline in concurrent HA-PCI was similar to that reported in patients receiving sequential PCI without hippocampal avoidance, suggesting that concurrent HA-PCI in LS-SCLC is a feasible option [39].…”

Dosimetric comparison of helical tomotherapy and volumetric modulated arc therapy in hippocampal avoidance whole‐brain radiotherapy

“…With the prolonging of patients’ OS, the neurocognitive impairment caused by WBRT is receiving more and more attention 8 . A study has pointed out that WBRT could control intracranial tumor well, but radiotherapy could damage hippocampal neural stem cells, thus influencing hippocampal functions and brain tissue repair, which is the major cause of cognitive disorders, such as memory loss 9 . RTOG 0933 carried out a multicenter phase II clinical test to compare WBRT with and without hippocampal avoidance.…”