TY - JOUR
T1 - Impact of HA-PCI on self-reported cognitive functioning and brain metastases in small-cell lung cancer
T2 - Pooled findings of NCT01780675 and PREMER trials
AU - Zeng, Haiyan
AU - Schagen, Sanne B.
AU - Hendriks, Lizza E.L.
AU - Sánchez-Benavides, Gonzalo
AU - Jaspers, Jaap P.M.
AU - Manero, Rosa María
AU - Lievens, Yolande
AU - Murcia-Mejía, Mauricio
AU - Kuenen, Marianne
AU - Rico-Oses, Mikel
AU - Albers, Elaine A.C.
AU - Samper, Pilar
AU - Houben, Ruud
AU - de Ruiter, Michiel B.
AU - Dieleman, Edith M.T.
AU - López-Guerra, José Luis
AU - De Jaeger, Katrien
AU - Couñago, Felipe
AU - Lambrecht, Maarten
AU - Calvo-Crespo, Patricia
AU - Belderbos, José S.A.
AU - De Ruysscher, Dirk K.M.
AU - Rodríguez de Dios, Núria
N1 - Funding Information:
We sincerely thank all the researchers of the Dutch-Flemish trial (NCT01780675) and the Spanish trial (PREMER/NCT02397733) for their efforts to conduct these trials successfully and the patients to participate in this trial. We sincerely thank all the funders for their support of this study: Scholarship of China Scholarship Council (Grant No.: CSC 201909370087), Sichuan Province's Tianfu Emei Plan (Grant No.: 2548), KWF Kankerbestrijding (grant No.: NKI 2013-6096), Vlaamse Liga tegen Kanker, and IWT Agentschap voor Innovatie door Wetenschap en Technologie (grant No.: IWT-TBM-130262).
Funding Information:
This research was supported by the following grant: Scholarship of China Scholarship Council (Grant No.: CSC 201909370087); Sichuan Province\u2019s Tianfu Emei Plan (Grant No.: 2548); KWF Kankerbestrijding: grant NKI 2013\u20106096; Vlaamse Liga tegen Kanker; IWT Agentschap voor Innovatie door Wetenschap en Technologie: grant IWT\u2010TBM\u2010130262. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2024
PY - 2025/1/1
Y1 - 2025/1/1
N2 - 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).
AB - 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).
KW - Brain metastases (BM)
KW - Hippocampal avoidance-prophylactic cranial irradiation (HA-PCI)
KW - Self-reported cognitive functioning (SRCF)
KW - Small cell lung cancer (SCLC)
U2 - 10.1016/j.lungcan.2024.108036
DO - 10.1016/j.lungcan.2024.108036
M3 - Article
SN - 0169-5002
VL - 199
JO - Lung Cancer
JF - Lung Cancer
M1 - 108036
ER -