Histopathology and Clinical Implication of Treatment-related Image Changes After Surgical Resection of Brain Metastases Previously Treated with Gamma Knife Radiosurgery

Abstract INTRODUCTION The true pathology and clinical implication of treatment-related image changes (TRICs) after stereotactic radiosurgery (SRS) for brain metastases (BM) have not been established. This study compared the surgical pathology and outcomes of intracranial metastatic lesions featured as TRICs or progressive disease (PD) in advanced magnetic resonance imaging (MRI).METHODS A total of 86 patients who underwent surgical resection of brain metastases previously treated with gamma knife radiosurgery (GKS) from 2009 to 2019 were retrospectively reviewed and classified by MRI findings and histopathology.RESULTS Among 54 patients with TRICs in preoperative MRI, the histopathology of pure radiation necrosis (RN) was confirmed in 19 patients (TRIC-RN) and mixed or predominant viable tumor cells in 35 patients (TRIC-PD). Thirty-two patients diagnosed with PD exhibited the metastatic histology well correlated with imaging (PD-PD). The TRIC-PD group showed larger prescription isodose volume (9.4 cm3) than the TRIC-RN (4.06 cm3, p=0.014) group and shorter time interval from GKS to preoperative MRI diagnosis related to neurological deficits (median 4.07 months) than the PD-PD group (median 8.77 months, p=0.004). Significant differences in progression-free survival were confirmed among the three groups (p<0.001) but not between TRIC-RN and TRIC-PD (post hoc test, p=1.00), whereas no significant difference was observed in overall survival (p=0.067). CONCLUSIONS The brain metastatic lesions diagnosed as TRICs after GKS frequently contained viable tumor cells, while they exhibited the benign prognosis as RN after surgical resection. These findings suggest that TRICs on advanced MRI can serve as a prognostic factor, regardless of the histologic heterogeneity.