Dr Gondi on Prophylactic Cranial Irradiation With Hippocampal Avoidance in SCLC

Vinai Gondi, MD, director, Radiation Oncology, codirector, Brain Tumor Center, Northwestern Medicine West Region and Proton Center, discusses efficacy and safety findings from the phase 2/3 NRG-CC003 trial (NCT02635009) of prophylactic cranial irradiation in patients with small cell lung cancer (SCLC).

The NRG-CC003 trial investigated the use of prophylactic cranial irradiation with or without hippocampal avoidance in patients with SCLC. This study revealed that the addition of hippocampal avoidance to prophylactic cranial irradiation led to a 23% reduction in the risk of first failure in any cognitive domain compared with standard prophylactic cranial irradiation alone (HR, 0.77; 95% CI, 0.61-0.98; P = .033).

The results of this secondary end point of the NRG-CC003 trial are noteworthy because they parallel the outcomes observed in the phase 3 NRG-CC001 trial (NCT02360215), which evaluated therapeutic whole-brain radiotherapy (WBRT) plus memantine with or without hippocampal avoidance in patients with brain metastases, Gondi says. In the NRG-CC001 trial, the patients who received hippocampal avoidance plus WBRT and memantine experienced a 26% reduction in the risk of cognitive failure vs those who received WBRT plus memantine alone (adjusted HR, 0.74; 95% CI, 0.58-0.95; P = 0.02 ). This consistency between the 2 datasets indicates that the cognitive benefits of preserving hippocampal neurogenesis do not depend on disease histology and that maximally preserving hippocampal neurogenesis is important in all forms of brain irradiation, including partial-brain irradiation, Gondi explains. These findings are under further exploration, Gondi notes.

Regarding the primary end point of the phase 2 portion of the trial, this study showed that hippocampal avoidance during prophylactic cranial irradiation was associated with noninferior intracranial relapse rates vs those observed in patients who underwent standard prophylactic cranial irradiation, which was expected, according to Gondi. These findings affirmed the relative safety of hippocampal avoidance, Gondi says. In addition, this study revealed similar toxicity profiles and survival outcomes between the 2 arms, Gondi concludes.