Headline: Adding hippocampal avoidance to prophylactic cranial irradiation for patients with small cell lung cancer does not clearly add neuroprotection in a phase 3 trial.
The Study: Data has been mixed on whether hippocampal avoidance reduces neurocognitive toxicity when delivering PCI for SCLC. The randomized, phase 3 PREMER trial found that HA-PCI resulted in less decline in delayed free recall compared to standard PCI. In NRG CC003, 392 patients receiving 25 Gy in 10 fractions PCI for mostly limited stage (70%) SCLC were randomized to conventional whole brain treatment or hippocampal avoidance. Fewer than half (47%) took memantine. The trial sought to determine if HA-PCI resulted in non-inferior intracranial recurrence and less neurocognitive failure as measured by delayed recall on the HVLT-R. At 12 months, HA-PCI resulted in similar intracranial recurrence (14.2% v 14.8%). At 6 months, there was also no difference in the co-primary endpoint of deterioration in the HVLT-R DR with HA-PCI (26% v 30%). However, a battery of three standardized neurocognitive tests were also performed at baseline, 3, 6, 12, and 24 months. When failure on any of these was counted as neurocognitive failure, HA-PCI did significantly reduce the risk of neurocognitive failure. Curiously, hippocampal avoidance resulted in significantly greater deterioration on a second neurocognitive test the Controlled Oral Word Association. More curiously, memantine was associated with a significantly higher risk of neurocognitive failure. Altogether, it feels like interpreting these results is a neurocognitive test in itself.
TBL: In NRG CC003, HA-PCI resulted in non-inferior intracranial recurrence. It did not meet the primary endpoint of reduced HVLT-R DR deterioration at 6 months, and secondary neurocognitive outcomes were conflicting. | Gondi, ASTRO 2023
The Study: Data has been mixed on whether hippocampal avoidance reduces neurocognitive toxicity when delivering PCI for SCLC. The randomized, phase 3 PREMER trial found that HA-PCI resulted in less decline in delayed free recall compared to standard PCI. In NRG CC003, 392 patients receiving 25 Gy in 10 fractions PCI for mostly limited stage (70%) SCLC were randomized to conventional whole brain treatment or hippocampal avoidance. Fewer than half (47%) took memantine. The trial sought to determine if HA-PCI resulted in non-inferior intracranial recurrence and less neurocognitive failure as measured by delayed recall on the HVLT-R. At 12 months, HA-PCI resulted in similar intracranial recurrence (14.2% v 14.8%). At 6 months, there was also no difference in the co-primary endpoint of deterioration in the HVLT-R DR with HA-PCI (26% v 30%). However, a battery of three standardized neurocognitive tests were also performed at baseline, 3, 6, 12, and 24 months. When failure on any of these was counted as neurocognitive failure, HA-PCI did significantly reduce the risk of neurocognitive failure. Curiously, hippocampal avoidance resulted in significantly greater deterioration on a second neurocognitive test the Controlled Oral Word Association. More curiously, memantine was associated with a significantly higher risk of neurocognitive failure. Altogether, it feels like interpreting these results is a neurocognitive test in itself.
TBL: In NRG CC003, HA-PCI resulted in non-inferior intracranial recurrence. It did not meet the primary endpoint of reduced HVLT-R DR deterioration at 6 months, and secondary neurocognitive outcomes were conflicting. | Gondi, ASTRO 2023