2106 - Clinical Outcomes of Brain Metastases with Infiltrative Growth Pattern Treated with Zero-Margin Radiosurgery

Purpose/Objective(s): Pathologic studies suggest that brain metastases from melanoma and small cell lung cancer (SCLC) demonstrate a microscopic infiltrative growth pattern (IGP) potentially extending beyond contrast enhancement on MRI or CT. In contrast, histologies such as non–small cell lung cancer and breast cancer are thought to lack this infiltrative growth pattern (nIGP). Concern that IGP may result in microscopic disease beyond visible tumor has historically limited the use of 0 mm planning target volume (PTV) stereotactic radiosurgery (SRS) due to potential undercoverage. In this retrospective study, we compared local control outcomes between IGP and nIGP histologies treated with zero-margin SRS.

Materials/Methods:

We analyzed patients treated with SRS for brain metastases at a single institution between 2015 and 2022. Melanoma and SCLC tumors were categorized as IGP; all other histologies were categorized as nIGP. Gross tumor volume (GTV) was contoured as the contrast-enhancing lesion on T1-weighted post-contrast MRI or CT simulation. Treatments were planned using zero-margin, single-isocenter, LINAC-based radiosurgery. Local failure was defined as a =25% increase in maximum tumor diameter (minimum increase of 3 mm) or histopathologic confirmation of viable tumor at salvage surgery. Local control was estimated using the Kaplan–Meier method, and associations were evaluated using Cox proportional hazards regression fit with robust standard errors clustered by patient. Analyses were performed on a per-tumor basis.

Results:

830 tumors with IGP and 2503 tumors with nIGP were identified from 594 patients. Local control for the entire cohort was 97% at 6 months and 94% at 12 months. 12-month local control of IGP vs. n-IGP tumors was 90% vs. 96% (p <0.001). 1-year toxicity of IPG vs nIPG was 98% in both groups (p=0.717). On Cox multivariable analysis, tumor volume (HR 1.016, p=0.037), tumor histology (Melanoma HR 2.913, p =0.003) (SCLC HR 4.125, p=0.003) (Breast HR 2.239, p=0.013) (Colorectal HR 4.773, p=0.014) (Unknown Primary HR 4.598, p=0.020), and dose regimen (5 Gy x 5 HR 3.709, p=0.010) (6 Gy x 5 HR 2.830, p<0.001) were found to be independent predictors of local control.

Conclusion:

In this study, where all tumors were treated with 0 mm PTV margin radiosurgery, brain metastases with an infiltrative growth pattern were associated with inferior local control compared with non-infiltrative histologies. Future studies, including UAB 2507, which randomizes patients undergoing radiosurgery to 0 mm vs. 2 mm PTV margin, will provide further insight into whether tumors with IGP benefit from margin in radiosurgery.