Impact of HA-PCI on self-reported cognitive functioning and brain metastases in small-cell lung cancer: Pooled findings of NCT01780675 and PREMER trials
Zeng H, Schagen SB, Hendriks LEL, Sánchez-Benavides G, Jaspers JPM, Manero RM, Lievens Y, Murcia-Mejía M, Kuenen M, Rico-Oses M, Albers EAC, Samper P, Houben R, de Ruiter MB, Dieleman EMT, López-Guerra JL, De Jaeger K, Couñago F, Lambrecht M, Calvo-Crespo P, Belderbos JSA, De Ruysscher DKM, Rodríguez de Dios N.
Abstract
Background: Cognitive decline is an arising concern in patients who need cranial irradiation. We used the pooled longitudinal individual patient data of two phase III trials: NCT01780675 and PREMER to investigate whether hippocampal avoidance (HA)-PCI is associated with improved self-reported cognitive functioning (SRCF) compared with PCI without increasing brain metastases (BM) development within the HA area.
Methods: Patients with stage I-IV small cell lung cancer (SCLC) were randomized to PCI or HA-PCI. SRCF was assessed and contrast enhanced brain magnetic resonance imaging (MRI) was performed at baseline and up to 24 months follow-up. SRCF and BM incidence after (HA)-PCI were compared between arms. Self reported cognitive impairment was defined as SCRF < 75.
Results: In total, 318 patients were randomized. Longitudinal generalized estimating equation (GEE) analysis showed that HA-PCI neither had a significant impact on SRCF (β = 1.41, p = 0.52) nor on cognitive impairment (OR 0.81, 95 %CI 0.53-1.25, p = 0.34). The median follow up was 41.7 (95 %CI 35.7-47.6) months, during which 61 patients developed BM (PCI arm: 30, HA-PCI arm: 31, p = 0.9). BM site was solitary in 15 patients (PCI arm: 7, HA-PCI arm: 8, p = 0.8). Nine of the 61 patients had BM within the HA area (PCI arm: 4, HA-PCI arm: 5, p = 1.0). The BM incidence was not significantly different between arms (subdistribution hazard ratio [sHR] 1.03, 95 %CI 0.62-1.70, p = 0.91).
Conclusion: HA-PCI did not preserve longitudinal SRCF but did also not increase the risk of BM. Additional strategies should be investigated to further improve the therapeutic ratio of PCI.
Trials registration: ClinicalTrials.gov (NCT01780675) ClinicalTrials.gov (NCT02397733).
Reference
Zeng H, Schagen SB, Hendriks LEL, Sánchez-Benavides G, Jaspers JPM, Manero RM, Lievens Y, Murcia-Mejía M, Kuenen M, Rico-Oses M, Albers EAC, Samper P, Houben R, de Ruiter MB, Dieleman EMT, López-Guerra JL, De Jaeger K, Couñago F, Lambrecht M, Calvo-Crespo P, Belderbos JSA, De Ruysscher DKM, Rodríguez de Dios N. Impact of HA-PCI on self-reported cognitive functioning and brain metastases in small-cell lung cancer: Pooled findings of NCT01780675 and PREMER trials. Lung Cancer. 2024 Nov 23;199:108036. doi: 10.1016/j.lungcan.2024.108036. Epub ahead of print. PMID: 39615412.
