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Abstract
Background and PurposeWhile relative cerebral blood volume (rCBV) may be diagnostic and prognostic for survival in glioblastoma (GBM), changes in rCBV during chemoradiation in the subset of newly diagnosed GBM with subtotal resection and the impact of MGMT promoter methylation status on survival have not been explored. This study aimed to investigate the association between rCBV response, MGMT methylation status, and progression-free (PFS) and overall survival (OS) in newly diagnosed GBM with measurable enhancing lesions.Methods1,153 newly diagnosed IDH wild-type GBM patients were screened and 53 patients (4.6%) had measurable post-surgical tumor (>1mL). rCBV was measured before and after patients underwent chemoradiation. Patients with a decrease in rCBV >10% were considered rCBV Responders, while patients with an increase or a decrease in rCBV <10% were considered rCBV Non-Responders. The association between change in enhancing tumor volume, change in rCBV, MGMT promotor methylation status, and PFS or OS were explored.ResultsA decrease in tumor volume following chemoradiation trended towards longer OS (p=0.12; median OS=26.8 vs. 16.3 months). Paradoxically, rCBV Non-Responders had a significantly improved PFS compared to Responders (p=0.047; median PFS=9.6 vs. 7.2 months). MGMT methylated rCBV Non-Responders exhibited a significantly longer PFS compared to MGMT unmethylated rCBV Non-Responders (p<0.001; median PFS=0.5 vs. 7.1 months), and MGMT methylated rCBV Non-Responders trended towards longer PFS compared to methylated rCBV Responders (p=0.089; median PFS=20.5 vs. 13.8 months).ConclusionsThis preliminary report demonstrates that in newly diagnosed IDH wild-type GBM with measurable enhancing disease after surgery (5% of patients), an enigmatic non-response in rCBV was associated with longer PFS, particularly in MGMT methylated patients.
Highlights
Glioblastoma (GBM) is the most aggressive and treatment resilient primary brain malignancy amongst adults [1, 2]
Twenty-four patients were classified as relative cerebral blood volume (rCBV) Responders (45.3%) and 29 patients were classified as rCBV Non-Responders according to this convention
In direct conflict with our original hypotheses and conventional wisdom, our results demonstrate that IDH wild-type MGMT methylated rCBV Non-Responders exhibiting either had stable or increasing rCBV following CRT experienced significantly improved progression-free survival (PFS)
Summary
Glioblastoma (GBM) is the most aggressive and treatment resilient primary brain malignancy amongst adults [1, 2]. Some studies have suggested that a decrease in rCBV of high-grade glioma following CRT is predictive of improved OS [18, 19] These reports involved a very small number of patients, included both IDH mutant and wild type GBM, included a mixture of gross total and subtotal resection patients, and did not incorporate the assessment of MGMT promoter methylation status, an epigenetic marker known to be strongly associated with increased survival for patients with GBM treated with chemoradiation [20]. While relative cerebral blood volume (rCBV) may be diagnostic and prognostic for survival in glioblastoma (GBM), changes in rCBV during chemoradiation in the subset of newly diagnosed GBM with subtotal resection and the impact of MGMT promoter methylation status on survival have not been explored. This study aimed to investigate the association between rCBV response, MGMT methylation status, and progression-free (PFS) and overall survival (OS) in newly diagnosed GBM with measurable enhancing lesions
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