TY - JOUR
T1 - Individual patient data meta-analysis of prophylactic cranial irradiation in locally advanced non-small cell lung cancer
AU - Witlox, Willem J.A.
AU - Ramaekers, Bram L.T.
AU - Lacas, Benjamin
AU - Le Pechoux, Cecile
AU - Pignon, Jean Pierre
AU - Sun, Alexander
AU - Wang, Si Yu
AU - Hu, Chen
AU - Redman, Mary
AU - van der Noort, Vincent
AU - Li, Ning
AU - Guckenberger, Matthias
AU - van Tinteren, Harm
AU - Groen, Harry J.M.
AU - Joore, Manuela A.
AU - De Ruysscher, Dirk K.M.
N1 - Publisher Copyright:
© 2021 The Author(s)
PY - 2021/5
Y1 - 2021/5
N2 - Background: Prophylactic cranial irradiation (PCI) was compared to observation in several randomized trials (RCTs), and a reduction greater than 50% was shown regarding the incidence of brain metastases (BM). However, none of these studies showed an improvement of overall survival (OS), possibly related to relatively small sample sizes and short follow-up. The aim of this meta-analysis was therefore to assess the impact of PCI on long term OS for stage III non-small cell lung cancer (NSCLC) compared to observation based on the pooled updated individual patient RCT data. Methods: Seven RCTs were eligible, and data from the four most recent trials (924 patients) could be retrieved. The log-rank observed minus expected number of events and its variance were used to calculate individual and overall pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) with a fixed effects model. Inter-trial heterogeneity was studied using the I2 test. In addition, the 5-year absolute survival difference between arms was calculated for all endpoints. The pre-specified toxicities were reported descriptively. Results: The median follow-up was 97 months (74–108). Compared to observation, no statistically significant impact of PCI on OS was observed (HR 0.90 [0.76–1.07] p = 0.23, 5-year absolute difference 1.8% [−5.2–8.8]). PCI significantly prolonged progression-free survival (HR 0.77 [0.66–0.91] p = 0.002) and BM-free survival (HR 0.82 [0.69–0.97] p = 0.02). The number of patients with high-grade (≥3) toxicity was 6.4% (21/330) for PCI. Conclusion: No OS benefit by PCI was observed, but PCI prolonged the progression-free survival and BM-free survival at an increased risk of late memory impairment and fatigue.
AB - Background: Prophylactic cranial irradiation (PCI) was compared to observation in several randomized trials (RCTs), and a reduction greater than 50% was shown regarding the incidence of brain metastases (BM). However, none of these studies showed an improvement of overall survival (OS), possibly related to relatively small sample sizes and short follow-up. The aim of this meta-analysis was therefore to assess the impact of PCI on long term OS for stage III non-small cell lung cancer (NSCLC) compared to observation based on the pooled updated individual patient RCT data. Methods: Seven RCTs were eligible, and data from the four most recent trials (924 patients) could be retrieved. The log-rank observed minus expected number of events and its variance were used to calculate individual and overall pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) with a fixed effects model. Inter-trial heterogeneity was studied using the I2 test. In addition, the 5-year absolute survival difference between arms was calculated for all endpoints. The pre-specified toxicities were reported descriptively. Results: The median follow-up was 97 months (74–108). Compared to observation, no statistically significant impact of PCI on OS was observed (HR 0.90 [0.76–1.07] p = 0.23, 5-year absolute difference 1.8% [−5.2–8.8]). PCI significantly prolonged progression-free survival (HR 0.77 [0.66–0.91] p = 0.002) and BM-free survival (HR 0.82 [0.69–0.97] p = 0.02). The number of patients with high-grade (≥3) toxicity was 6.4% (21/330) for PCI. Conclusion: No OS benefit by PCI was observed, but PCI prolonged the progression-free survival and BM-free survival at an increased risk of late memory impairment and fatigue.
KW - Individual patient data meta-analysis
KW - Locally advanced non-small cell lung cancer
KW - Prophylactic cranial irradiation
UR - http://www.scopus.com/inward/record.url?scp=85101846207&partnerID=8YFLogxK
U2 - 10.1016/j.radonc.2021.02.002
DO - 10.1016/j.radonc.2021.02.002
M3 - Article
C2 - 33587968
AN - SCOPUS:85101846207
SN - 0167-8140
VL - 158
SP - 40
EP - 47
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
ER -