Neuro-cognitive (HVLT-R total recall) functioning in localized vs. metastatic small-cell lung cancer with or without hippocampus sparing PCI: Results from a phase III trial

Objective: Multicenter randomized phase III trial (NCT01780675) to investigate memory functioning and safety after PCI with or without hippocampus sparing in Small Cell Lung Cancer (SCLC) (25 Gy/ 10 fractions) using the Hopkins Verbal Learning Test-Revised (HVLT-R). We here report on the differences between localized (stage I-III) vs. metastatic (stage IV) patients. Methods: Primary endpoint: decline in HVLT-R total recall at 4 months. Decline of 5 or more out of a possible 36 points was considered a failure. Results: 168 patients were randomized. Median follow-up: 24.6 months. Median age: 64 years, 51% female, performance score WHO 0-1: 93%. Stage distribution: 70% localized, 30% metastatic. Localized disease: at 4 months, 27 % in both treatment arms had a decline of ≥ 5 points of HVLT-R total recall (p=1.00); at 8 months: 34 % and 22 % in PCI and HA-PCI (p=0.40). Metastatic disease: at 4 months, 33 % in both treatment arms had a decline of ≥ 5 points (p=1.00); at 8 months: 33 % and 50 % in PCI and HA-PCI (p=1.00). No difference in the incidence of brain metastases between PCI and HA-PCI in localized or metastatic SCLC were observed. No patients developed isolated brain metastases in the hippocampal avoidance region. There were no statistically significant differences in the overall survival (OS) between PCI and HA-PCI, neither in localized, nor in metastatic disease. Conclusion: HA-PCI did not affect neuro-cognitive decline compared to standard PCI, both in localized and in metastatic SCLC. No increase in brain metastases was observed. Regular PCI remains the standard of care.