MD Anderson Phase III Randomized Preoperative Stereotactic Radiosurgery (SRS) vs. Postoperative SRS for Brain Metastases Trial

Abstract

Postoperative stereotactic radiation therapy/radiosurgery (SRT/SRS) is being evaluated in comparison to Preoperative SRT for brain metastases (mets) in a limited number of prospective clinical trials. Our objective is to address the significant knowledge gap concerning the logistics of preoperative SRT in comparison to postoperative SRT in a randomized controlled study. Patients with brain mets with at least 1 surgically operable met were randomized (1:1) to Preop vs Postop SRT. In this abstract, we present non-primary endpoint data on the trial concept and logistics of treatment for this data safety monitoring board reviewed study. Patients enrolled had 1-2 lesions resected and <15 lesions treated at time of SRT to best reflect the standard population that receive SRT and surgery at our institution. From 12/2018 to 12/2022, 99 patients with 1-2 operable brain mets were enrolled and randomized to Preop (n = 49) or Postop (n = 50) SRT. Males represented 56% of the cohort compared to females, and <25% were age 18-49 years, while 27%, 29, and 19% respectively were 50-59, 60-69, and > = 70. The most frequent histologies enrolled were lung (29%), renal cell (15%), melanoma (14%), and breast (11%) cancers. The majority of patients (83%) had 1-4 brain mets on their baseline MRI and 91% subsequently had a single lesion resected. Seventy-nine patients completed both SRT and surgery, while 9% received no therapy due to drop out before study therapy initiation. Among patients receiving both therapies in the combined cohort, 68% received a non-invasive stereotactic radiosurgery instrument to the randomized cavity lesion compared to 32% receiving LINAC based SRT. Treatment of the lesion or cavity with single fraction SRT was 51% in the Preop arm vs 31% in the Postop arm. Multi-fraction (3-5 SRT) was 67% in the Postop cohort in contrast to 47% in the Preop cohort. Time from randomization to RT was 5.6 days and 33.7 days in the Preop and Postop cohorts respectively, and for surgery was 10.2 days vs 12.9 days in the Postop vs Preop cohorts. The average time from RT to surgery was 7.3 days in the Preop arm and 23.5 days in the Postop arm (to allow for incisional healing time). In one of the early initiated randomized prospective cohorts of Preop vs Postop SRT, we demonstrated logistical feasibility with an efficient clinical trial workflow for study treatment. Differences in Preop vs Postop logistics reflect clinical practice differences in time-to-treatment. Therapy with various modalities reflected real-world practice and possibly provider preferences in technique when addressing the nature of delineating cavities and changes in cavity volume with regard to fractionation. Independent of the primary outcomes, our data provides insights in the practical management of patients receiving these two modalities of therapy, and further data at the completion of trial will address relevant primary outcomes.