Abstract OBJECTIVE Significant advancements in neurosurgical planning, approach, and practice over the past five decades have improved the surgical management of diffuse low and high-grade gliomas. We sought to evaluate the extent to which LGG survival outcomes have evolved over the past fifty years using glioma registry datasets with histopathological groups defined by WHO diagnostic criteria and supplemented with next generation genome-sequencing. METHODS Three datasets (SEER, TCGA, and GENIE) were used to evaluate trends in prognosis following LGG diagnosis and resection between 1975 and present (GBM as a comparator cohort). The primary outcomes evaluated were longitudinal disease-specific survival and overall survival, with secondary fixed-timepoint outcomes evaluated at 12-months, 24-months, and 60-months. Subjects from SEER were categorized by histology, while subjects from TCGA and GENIE were included based IDH mutation status with available histopathology. RESULTS A total of 39,958 adult patients were included. Overall survival increased for both LGG and GBM between 1975 and 2010, however only LGG outcomes continued to improve following 2010 (2010-; HR=0.955, 95%CI 0.926 to 0.986). Evaluation of the interaction between resection extent and diagnosis year revealed a progressive increase in the survival benefit of GTR in recent years, particularly for LGG. Independent of other available clinical/molecular features and considering the interaction term between year of diagnosis and resection extent, the gap in independent prognostic benefit associated with GTR between LGG and GBM has significantly widened (2010-2020 vs 1990-2000, p<0.05). CONCLUSION Over the past three decades, consistent improvements in LGG outcomes were observed while prognosis following GBM diagnosis has remained largely unchanged following 2010. Notably, we observed increasing prognostic value of achieving GTR particularly in patients with LGG.
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