{Reference Type}: Journal Article
{Title}: Phase I trial of dose escalation for preoperative stereotactic radiosurgery for patients with large brain metastases.
{Author}: Murphy ES;Yang K;Suh JH;Yu JS;Stevens G;Angelov L;Vogelbaum MA;Barnett GH;Ahluwalia MS;Neyman G;Mohammadi AM;Chao ST;
{Journal}: Neuro Oncol
{Volume}: 0
{Issue}: 0
{Year}: 2024 Apr 24
{Factor}: 13.029
{DOI}: 10.1093/neuonc/noae076
{Abstract}: <B>BACKGROUND: </B>Single session stereotactic radiosurgery (SRS) or surgical resection alone for brain metastases larger than 2 cm results in unsatisfactory local control. We conducted a phase I trial for brain metastases(>2cm) to determine the safety of preoperative SRS at escalating doses.<BR><B>METHODS: </B>Radiosurgery dose was escalated at 3 Gy increments for 3 cohorts based on maximum tumor dimension starting at: 18 Gy for >2-3 cm, 15 Gy for >3-4 cm, and 12 Gy for >4-6 cm. Dose limiting toxicity (DLT) was defined as grade III or greater acute toxicity.<BR><B>RESULTS: </B>A total of 35 patients/36 lesions were enrolled. For tumor size >2-3 cm, patients were enrolled up to the second dose level (21 Gy); for >3-4 cm and >4-6 cm cohorts the third dose level (21 Gy and 18 Gy, respectively) was reached. There were 2 DLTs in the >3-4 cm arm at 21Gy. The maximum tolerated dose (MTD) of SRS for >2-3 cm was not reached; and was 18 Gy for both >3-4 cm arm and >4-6 cm arm. With a median follow-up of 64.0 months, the 6- and 12-month local control rates were 85.9% and 76.6%, respectively. One patient developed grade 3 radiation necrosis at 5 months. The 2-year rate of leptomeningeal disease (LMD) was 0%.<BR><B>CONCLUSIONS: </B>Preoperative SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size demonstrates acceptable acute toxicity. The phase II portion of the trial will be conducted at the maximum tolerated SRS doses.