In a phase II/III trial (NRG-CC003) reported in the Journal of Clinical Oncology, Gondi et al found that hippocampal avoidance (HA) in prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC) did not improve delayed recall failure but was associated with benefits in reducing overall neurocognitive function (NCF) toxicity and was noninferior in risk for intracranial relapse (ICR) compared with no HA.
Study Details
In the open-label trial, 393 patients from sites in the United States and Canada who had no brain metastases and responded to chemotherapy were randomly assigned between December 2015 and June 2022 to HA-PCI (n = 197) or PCI alone (n = 196). The primary outcome measures were 12-month ICR (assessed with noninferiority design in phase II portion) and 6-month Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall (DR) failure (phase III portion).
Key Points
Median follow-up was 17.0 months among all patients and 30.8 months among surviving patients. The 12-month ICR rate was 14.7% in the HA-PCI group vs 14.8% in the PCI-alone group, establishing noninferiority (P < .0001).
At 6 months, the HVLT-R DR deterioration rate was 25.5% in the HA-PCI group vs 30.0% in the PCI-alone group (P = .28). However, the addition of HA to PCI reduced the risk of failure in any NCF test (adjusted hazard ratio [HR] = 0.78, 95% confidence interval [CI] = 0.61–0.99, P = .039).
The addition of HA to PCI was not associated with any significant longitudinal change in any health-related quality of life domain, no significant difference in overall survival (adjusted HR = 0.88, 95% CI = 0.67–1.14, P = .33), and no significant difference in grade ≥ 3 toxicity (30.7% vs 31.4%, P = .88).
The investigators concluded: “Although the study did not meet its primary end point of DR preservation, HA during PCI reduces the risk of overall neurocognitive toxicity with noninferior ICR risk and similar survival.”
Vinai Gondi, MD, of Northwestern University Feinberg School of Medicine, Chicago, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was funded by grants from the National Cancer Institute. For full disclosures of all study authors, visit ascopubs.org.
