Willem J A Witlox1, Bram L T Ramaekers2, Benjamin Lacas3, Cecile Le Pechoux4, Jean-Pierre Pignon3, Alexander Sun5, Si-Yu Wang6, Chen Hu7, Mary Redman8, Vincent van der Noort9, Ning Li10, Matthias Guckenberger11, Harm van Tinteren9, Harry J M Groen12, Manuela A Joore13, Dirk K M De Ruysscher14. 1. Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre (MUMC), The Netherlands. Electronic address: willem.witlox@mumc.nl. 2. Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre (MUMC), The Netherlands. 3. Department of Biostatistics and Epidemiology, Gustave Roussy, University Paris-Saclay, Villejuif, France; Oncostat U1018, Inserm, University Paris-Saclay, labeled Ligue Contre le Cancer, Villejuif, France. 4. Department of Radiation Oncology, Gustave Roussy, Paris-Saclay University, Villejuif, France. 5. Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Canada. 6. Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China. 7. NRG Oncology Statistics and Data Management Center, Philadelphia, United States; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States. 8. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, United States. 9. Department of Biometrics, Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands. 10. Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China. 11. Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. 12. Department of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands. 13. Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre (MUMC), The Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands. 14. Department of Radiation Oncology (Maastro Clinic), Maastricht University Medical Center(+), GROW Research Institute, Maastricht, The Netherlands.
Abstract
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.
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.
Authors: Annemarie C Eggen; Nadine M Richard; Ingeborg Bosma; Mathilde Jalving; Natasha B Leighl; Geoffrey Liu; Kenneth Mah; Randa Higazy; David B Shultz; Anna K L Reyners; Gary Rodin; Kim Edelstein Journal: Neurooncol Pract Date: 2021-09-07