Search

Background The impact of anti-angiogenic therapy (AAT) on patients with glioblastoma (GBM) is unclear due to a disconnect between radiographic findings and overall survivorship. MR spectroscopy (MRS) can provide clinically relevant information regarding tumor metabolism in response to AAT. This review explores the use of MRS to track metabolic changes in patients with GBM treated with AAT. Methods We conducted a systematic literature review in accordance with PRISMA guidelines to identify primary research articles that reported metabolic changes in GBMs treated with AAT. Collected variables included single or multi-voxel MRS acquisition parameters, metabolic markers, reported metabolic changes in response to AAT, and survivorship data. Results Thirty-five articles were retrieved in the initial query. After applying inclusion and exclusion criteria, 11 studies with 262 patients were included for qualitative synthesis with all studies performed using multi-voxel 1H MRS. Two studies utilized 31P MRS. Post-AAT initiation, shorter-term survivors had increased choline (cellular proliferation marker), increased lactate (a hypoxia marker), and decreased levels of the short echo time (TE) marker, myo-inositol (an osmoregulator and gliosis marker). MRS detected metabolic changes as soon as 1-day after AAT, and throughout the course of AAT, to predict survival. There was substantial heterogeneity in the timing of scans, which ranged from 1-day to 6–9 months after AAT initiation. Conclusions Multi-voxel MRS at intermediate and short TE can serve as a robust prognosticator of outcomes of patients with GBM who are treated with AAT.

Background There is a need to establish biomarkers that distinguish between pseudoprogression (PsP) and true tumor progression in patients with glioblastoma (GBM) treated with chemoradiation. Methods We analyzed magnetic resonance spectroscopic imaging (MRSI) and dynamic susceptibility contrast (DSC) MR perfusion data in patients with GBM with PsP or disease progression after chemoradiation. MRSI metabolites of interest included intratumoral choline (Cho), myo-inositol (mI), glutamate + glutamine (Glx), lactate (Lac), and creatine on the contralateral hemisphere (c-Cr). Student T-tests and area under the ROC curve analyses were used to detect group differences in metabolic ratios and their ability to predict clinical status, respectively. Results 28 subjects (63 ± 9 years, 19 men) were evaluated. Subjects with true progression (n = 20) had decreased enhancing region mI/c-Cr (P = .011), a marker for more aggressive tumors, compared to those with PsP, which predicted tumor progression (AUC: 0.84 [0.76, 0.92]). Those with true progression had elevated Lac/Glx (P = .0009), a proxy of the Warburg effect, compared to those with PsP which predicted tumor progression (AUC: 0.84 [0.75, 0.92]). Cho/c-Cr did not distinguish between PsP and true tumor progression. Despite rCBV (AUC: 0.70 [0.60, 0.80]) and rCBF (AUC: 0.75 [0.65, 0.84]) being individually predictive of tumor response, they added no additional predictive value when combined with MRSI metabolic markers. Conclusions Incorporating enhancing lesion MRSI measures of mI/c-Cr and Lac/Glx into brain tumor imaging protocols can distinguish between PsP and true progression and inform patient management decisions.

Background Determining failure to anti-angiogenic therapy in recurrent glioblastoma (GBM) (rGBM) remains a challenge. The purpose of the study was to assess treatment response to bevacizumab-based therapy in patients with rGBM using MR spectroscopy (MRS). Methods We performed longitudinal MRI/MRS in 33 patients with rGBM to investigate whether changes in N-acetylaspartate (NAA)/Choline (Cho) and Lactate (Lac)/NAA from baseline to subsequent time points after treatment can predict early failures to bevacizumab-based therapies. Results After stratifying based on 9-month survival, longer-term survivors had increased NAA/Cho and decreased Lac/NAA levels compared to shorter-term survivors. ROC analyses for intratumoral NAA/Cho correlated with survival at 1 day, 2 weeks, 8 weeks, and 16 weeks. Intratumoral Lac/NAA ROC analyses were predictive of survival at all time points tested. At the 8-week time point, 88% of patients with decreased NAA/Cho did not survive 9 months; furthermore, 90% of individuals with an increased Lac/NAA from baseline did not survive at 9 months. No other metabolic ratios tested significantly predicted survival. Conclusions Changes in metabolic levels of tumoral NAA/Cho and Lac/NAA can serve as early biomarkers for predicting treatment failure to anti-angiogenic therapy as soon as 1 day after bevacizumab-based therapy. The addition of MRS to conventional MR methods can provide better insight into how anti-angiogenic therapy affects tumor microenvironment and predict patient outcomes.