The risk of brain metastases (BM) in limited stage SCLC (LS-SCLC) can be significantly reduced by PCI. BM often leads to a deterioration of quality of life (QoL) and response to treatment is poor. This, in combination with the high risk of BM in ES-SCLC, was the basis for this randomized trial, performed by the EORTC Radiation Oncology and Lung Cancer Groups.
Materials/Methods
Patients (18–75 years; WHO ≤ 2) with confirmed ES-SCLC who responded after 4–6 cycles of chemotherapy, were randomized to receive PCI (doses ranging from 20 Gy/5 fractions to 30 Gy/12 fractions) or no PCI. The primary endpoint was the cumulative incidence of symptomatic BM. CT or MRI scanning of the brain was performed whenever ≥1 pre-defined “key-symptoms” were present. The study was sized to detect a hazard ratio of 0.44 with 80% power and 2-sided 5% significance (52 events, 287 patients). QoL data (QLQ-C30 and QLQ-BN20 were collected at fixed timepoints. Primary quality of life (QoL) endpoints were global health status, hair loss, fatigue, role, cognitive and emotional functioning. QoL scales range from 0–100: for function higher values represent better function, for symptoms higher values indicate greater symptom burden. Clinical significance is a 10-point difference, statistical significance is p ≤ 0.01.
Results
Between February 2001 and March 2006, 286 patients entered the study. Residual disease was present in 76% and at distant sites in 71% of cases. The baseline characteristics were well balanced between the two arms. Treatment compliance was good, with only 6% of patients not treated and 3% of patients interrupting treatment in the PCI-arm. PCI significantly reduced the risk of symptomatic brain metastases (Gray p < 0.0001, HR = 0.27, 95% CI = 0.16–0.44). The 1-year cumulative incidence of symptomatic BM was 14.6% on PCI (95% CI = 8.3–20.9) compared to 40.4% in the control group (95% CI = 32.1–48.6). There was no impact of PCI on extra-cranial progression rates (Gray p > 0.1). However, PCI significantly prolonged progression-free survival time (p = 0.0218, HR = 0.76, 95% CI = 0.59–0.96) and overall survival (p = 0.0033, HR = 0.68, 95% CI = 0.52–0.88). Survival at 1 year was 27.1% for the PCI and 13.3% for the control arm. Main side effects of PCI were hair loss and fatigue (at 6 weeks–3 months), but there was no significant difference in global health status (p = 0.10), role, cognitive and emotional functioning.
Conclusions
PCI results in a significant reduction of the risk of symptomatic brain metastases in improved disease-free and overall survival. PCI should be offered to all patients with ES-SCLC who respond to chemotherapy.
1VU University Medical Center, Amsterdam, The Netherlands
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