Phase III Study of Prophylactic Cranial Irradiation vs. Observation in Patients with Stage III Non–small-cell Lung Cancer: Neurocognitive and Quality of Life Analysis of RTOG 0214

Article Outline

• Purpose/Objective(s)
• Materials/Methods
• Results
• Conclusions
• Copyright

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Purpose/Objective(s) 

There are scant data from randomized trials regarding the effects of prophylactic cranial irradiation (PCI) on neurocognitive function (NF) and quality of life (QOL). The primary endpoint of RTOG 0214 showed no overall survival (OS) benefit for PCI in Stage III non–small-cell lung cancer (NSCLC). This analysis focuses on the secondary objectives to determine the impact of PCI on the incidence of central nervous system metastases (CNS mets), NF, and QOL.

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Materials/Methods 

Patients with Stage III NSCLC who completed definitive therapy without progression were eligible. Patients were randomized to PCI (30 Gy at 2 Gy/fraction q/day) or observation. Mini-mental status exam (MMSE), activities of daily living scale (ADLS), and Hopkins Verbal Learning Test (HVLT) were used to assess NF. The EORTC QLQC30 and QLQBN20 were used to assess QOL. The Kaplan-Meier method with the log–rank test was used for OS and disease-free survival (DFS). The logistic regression model was used for the incidence of CNS mets. The p values from t test adjusted by Hommel's stagewise rejective procedure were reported for NF and QOL tools. The cutoff of neurologic deterioration evaluated by MMSE and HVLT was calculated using reliable change index at 1 year from baseline. For QOL, a 10 point (of 100) change was considered clinically relevant.

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Results 

This study opened in September 2002 and closed due to slow accrual in August 2007. Total accrual was 356 patients (of the targeted 1,058), of whom 340 were eligible. One-year OS (75.6% vs. 76.9%; p = 0.86) and 1 year DFS (56.4% vs. 51.2%; p = 0.11) for PCI vs. observation, respectively, were not significantly different. However, the incidence of CNS mets at 1 year was 7.7% vs. 18% for PCI vs. observation (p = 0.004). There were no significant differences at 1 year between the two arms in any component of the EORTC QLQC30 or QLQBN20 (all adjusted p values > 0.05), though a trend for greater decline in patient-reported cognitive functioning with PCI was noted. There were no differences in MMSE (p = 0.60) or ADLS (p = 0.88). However, for HVLT, there was greater decline in immediate recall (p = 0.03) and delayed recall (p = 0.008) in the PCI arm at 1 year. No clear differences at 1 year emerged in NF or QOL between patients < = 60 or >60 years on either arm (all adjusted p values > 0.05). These results were the same when patients with and without CNS mets were compared.

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Conclusions 

The PCI in Stage III NSCLC significantly decreases the risk of CNS mets without significant differences in OS or DFS. There were no significant differences in global cognitive function (on MMSE) or QOL following PCI, but there was a significant decline in memory (on HVLT). This study provides prospective data regarding the relative benefits and risks of PCI in this setting and the need to use sensitive cognitive assessments.