Neurocognition and Quality of Life for Hypofractionated Stereotactic Radiotherapy (HFSRT) of the Resection Cavity vs. Whole-Brain Radiotherapy (WBRT) Following Brain Metastasis Resection – Results of the ESTRON Randomized Phase 2 Trial

Purpose/Objective(s)

The ESTRON randomized phase 2 trial compared post-operative hypofractionated stereotactic radiotherapy (HFSRT) of the resection cavity following brain metastases (BM) resection with post-operative whole-brain radiotherapy (WBRT) in patients with 1-10 BM. We previously presented local control (LC), intracranial control (IC) and overall survival (OS). Neurocognitive function and quality of life were pre-specified secondary endpoints.

Materials/Methods

Neurocognitive testing included the Hopkins Verbal Learning Test-Revised (HVLT-R) total recall (TR) and delayed recall (DR). A drop of ≥ 5 points from baseline in HVLT-R total recall was considered clinically relevant. Health-related Quality of Life (hr-QoL) was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C15 PAL questionnaire and brain module (BN-20). All Assessments were performed at baseline, 6-8 weeks after treatment and three-monthly afterwards for 12 months.

Results

Fifty-four patients were randomized; HFSRT n = 27, WBRT n = 27. HFSRT provided 3-year LC of 96% with similar IC and OS between groups, as reported previously. Median baseline HVLT-R score was 24.0 (Q1-Q3 = 18-27) in the HFSRT-group vs. 26.0 (Q1-Q3 = 22-28) in the WBRT-group for TR subscale and 8.0 (Q1-Q3 = 5-10, HFSRT-group) vs. 9.5 (Q1-Q3 = 8-12, WBRT-group) for DR subscale. A drop of ≥ 5 points from baseline occurred in 5 patients (18.5%) in the HFSRT-group vs. 8 patients (29.6%) in the WBRT group (risk difference 0.11, 95% CI = [-0.34 to 0.12], P = 0.34). Maximum change in median HVLT-R TR score was +8.3% (Q1-Q3 = 23-34, HFSRT-group) vs. -11.5% (Q1-Q3 = 18-28, WBRT-group) at 31 weeks from baseline (P = 0.079). At no timepoint did the median HVLT-R TR score decline from baseline in the HFSRT-group. For DR subscale, median change from baseline was +17.6% (Q1-Q3 = 8-12, HFSRT-group) vs. -15.8% (Q1-Q3 = 4-10, WBRT-group) at 31 weeks (P = 0.246). Overall hr-QoL (QLQ-C15 PAL) was similar in both groups. Regarding functional subscales, in the WBRT-group a relevant increase in nausea/vomiting (mean +33.3, standard deviation (SD) = 13.4 points, P = 0.001) and appetite loss (mean +40.3, SD = 32.6 points, P < 0.001) was observed 7 weeks from baseline with no respective change in the HFSRT-group. The other functional scales of QLQ-C15 PAL and BN-20 were not relevantly different between groups.

Conclusion

While providing excellent local control, HFSRT following BM resection preserves neurocognition more effectively than WBRT, with differences most pronounced at 7 months from baseline. Overall hr-QoL was similar, although WBRT acutely worsened nausea and appetite loss.