2634 - A Pilot Phase 2 Study Evaluating Dose De-Escalation in Whole Brain Radiation Therapy with Simultaneous Integrated Boost for Patients with Brain Metastases

M. Weisman¹, C. A. Curtis², N. Agrawal¹, G. L. Jensen³, L. Boyd³, A. P. Kamer⁴, R. C. Zellars⁵, G. Watson¹, T. Lautenschlaeger¹, and K. Shiue⁶; ¹Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, ²Indiana University School of Medicine, Indianapolis, IN, ³Indiana University, Indianapolis, IN, ⁴Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, ⁵Indiana University Department of Radiation Oncology, Indianapolis, IN, ⁶Department of Radiation Oncology, Indiana University, Indianapolis, IN

Purpose/Objective(s): This study reports a pilot phase 2 trial evaluating de-escalation of whole brain radiation therapy (WBRT) dose with escalation to gross disease (BMET) via simultaneous integrated boosts (SIB) in patients with metastatic brain cancer. SIB to BMETs has shown to have improved local control (LC), and similar trials of WBRT with SIB studies have shown comparative LC. There have been concerns that WBRT can lead to early cognitive decline, which becomes more important as these patients are living longer. We report the results of in-brain distant failure (IBDF) and LC, as well as cognitive outcomes. Materials/

Methods: Adult patients with pathologically confirmed primary solid tumor malignancy and imaging evidence of = 30 cc of BMETs (individual lesions = 5 cc) who have dsGPA estimated survival (OS) of at least 6 months were enrolled and treated with WBRT to 25 Gy with SIBs of 42 Gy, all in 10 daily fractions. The primary objective was IBDF in the non-SIB volumes at 6 months. Secondary objectives included LC of the SIB BMETs at 6 months and evaluation of neurocognitive function utilizing the Hopkins Verbal Learning Test-Revised (HVLT-R) at 6 months.
Results: Between 9/2017 and 5/2022, 20 patients were enrolled. Although 20 patients were enrolled, 9 patients had evaluable data with a median follow up of 8.8 months. The median BMETs present for evaluable patients at the time of treatment was 8 (inner quartiles 6, 11), with up to 25 lesions boosted. Four patients (44.4%; 95% CI: 0.14-0.79) had an IBDF by 6 months, exceeding our historical estimate of 20%. At 6 months, 100% of patients had LC of their SIB BMET. The 6-month OS was 100% in evaluable patients and 70% in all enrolled patients. The HVLT-R tests of available patient data showed raw score mean changes in baseline to 6 month total recall, delayed recall, recognition discrimination, and retention (%) scores of -0.75, -1.38, -2.12, and -13.50, respectively. No patients had G3-5 treatment-related toxicities and 9 out of 20 patients (45%) had a total of 14 G3-5 overall adverse events.
Conclusion: IBDF was higher than expected in this patient cohort, while SIB of BMETs resulted in excellent LC and was well tolerated. The results of this study are difficult to interpret given only 45% of patients were deemed evaluable; despite use of dsGPA for eligibility criteria, many patients did not survive to 6 months. The high 6-month IBDF proportion could be explained by the overall small sample size in this pilot trial. WBRT with SIB to multiple brain mets was feasible, though additional study of dose de-escalated WBRT is warranted.