Top Line: The simplest way to explain the data on hippocampal-avoidance whole brain radiation (HA-WBRT) is to say...it’s mixed at best.
The Study: This is due in no small part to the limited life expectancies of patients eligible for WBRT. Not to mention, similar to other palliative outcomes, picking a primary endpoint can feel like throwing a dart at a board of potential neurocognitive measurements and timepoints. As a reminder, NRG CC001 reported a win for HA-WBRT among patients with brain mets of mixed histologies—a cynic might say because it cast a wide net with 4 outcomes each measured at 4 timepoints. A recently reported randomized trial from the Netherlands, on the other hand, failed to demonstrate an advantage when HA was added to prophylactic cranial irradiation (PCI). Almost identical to its Dutch counterpart, the Spanish phase 3 PREMER trial included 150 patients with limited (71%) or extensive (29%) stage small cell lung cancer (SCLC) receiving PCI (25 Gy in 10 fractions) were randomized to standard PCI or HA-PCI. The primary endpoint in this case was decline in delayed free recall (a 3+ point decline on a standardized test) at 3 months. As expected, when compared to patients receiving WBRT for extensive brain mets where median survival was 6 months, median survival here was a respectable 21 months. We also appreciate this analysis for imputing patients lost to follow-up as a decline in recall (assuming the worst). Even so, there was a significant advantage in decline in delayed recall after HA-PCI (13%) versus standard PCI (30%). What’s more, this persisted at 6, 12 and 24 months. There were no differences detected in secondary endpoints of quality of life, incidence of brain mets, or survival.
TBL: Among a population with mostly LS-SCLC and a life expectancy measured in years, HA-PCI results in a measurable difference in short-term memory preservation though it doesn’t translate to improved quality-of-life. | Rodríguez de Dios, J Clin Oncol 2021