HIF1A and neoplasm: While it is possible that this early rise in nrCBV in the present study may also be from continued tumor growth, we speculate that this observation may reflect downstream alterations caused by decreased D-2-HG levels, which could have led to elevated HIF-1α levels and promote increased hypoxic and subsequent proangiogenic signaling.12,13,45 Importantly, this early rise in nrCBV and tumor volume was no longer observed after 2–4 months of treatment, and there was a PFS benefit in patients who exhibited less elevated nrCBV values or < 0% change in nrCBV at this later timepoint.