Abstract
BackgroundDifferentiating true glioblastoma multiforme (GBM) from pseudoprogression (PsP) remains a challenge with current standard magnetic resonance imaging (MRI). The objective of this study was to explore whether patients’ absolute lymphocyte count (ALC) levels can be utilized to predict true tumor progression and PsP.MethodsPatients were considered eligible for the study if they had 1) GBM diagnosis, 2) a series of blood cell counts and clinical follow-ups, and 3) tumor progression documented by both MRI and pathology. Data analysis results include descriptive statistics, median (IQR) for continuous variables and count (%) for categorical variables, p values from Wilcoxon rank sum test or Fisher’s exact test for comparison, respectively, and Kaplan-Meier analysis for overall survival (OS). OS was defined as the time from patients’ second surgery to their time of death or last follow up if patients were still alive.Results78 patients were included in this study. The median age was 56 years. Median ALC dropped 34.5% from baseline 1400 cells/mm3 to 917 cells/mm3 after completion of radiation therapy (RT) and temozolomide (TMZ). All study patients had undergone surgical biopsy upon MRI-documented progression. 37 had true tumor progression (47.44%) and 41 had pseudoprogression (52.56%). ALC before RT/TMZ, post RT/TMZ and at the time of MRI-documented progression did not show significant difference between patients with true progression and PsP. Although not statistically significant, this study found that patients with true progression had worse OS compared to those with PsP (Hazard Ratio [HR] 1.44, 95% CI 0.86–2.43, P = 0.178). This study also found that patients with high ALC (dichotomized by median) post-radiation had longer OS.ConclusionOur results indicate that ALC level in GBM patients before or after treatment does not have predictive value for true disease progression or pseudoprogression. Patients with true progression had worse OS compared to those who had pseudoprogression. A larger sample size that includes CD4 cell counts may be needed to evaluate the PsP predictive value of peripheral blood biomarkers.
Highlights
Differentiating true glioblastoma multiforme (GBM) from pseudoprogression (PsP) remains a challenge with current standard magnetic resonance imaging (MRI)
Our results indicate that absolute lymphocyte count (ALC) level in GBM patients before or after treatment does not have predictive value for true disease progression or pseudoprogression
We believe a larger sample size with concurrent investigation of other potential biomarkers such as Neutrophil to Lymphocyte Ratio (NLR), MLR, CD4 count, and Tumor-infiltrating lymphocyte (TIL) may yield meaningful findings. To our knowledge, this is the first retrospective study that examined the predictive value of ALC in differentiating PsP from true tumor progression in GBM patients who demonstrated disease progression on MRI with pathological tissue confirmation
Summary
Differentiating true glioblastoma multiforme (GBM) from pseudoprogression (PsP) remains a challenge with current standard magnetic resonance imaging (MRI). Glioblastomas (GBM), an aggressive form of highgrade gliomas (HGG), make up 16% of all primary brain tumors [3]. The current standard treatment for patients with HGG includes surgery followed by three lymphotoxic therapies: temozolomide (TMZ), radiation (RT), and glucocorticoids. These three treatments result in toxicity to lymphocytes and immunosuppressive effects in HGG patients contributing to death. Current standard treatment regimens for brain tumors deliver lymphotoxic radiation doses to 99% of circulating blood resulting in significant lymphopenia and shorter overall survival [8]. TRL in patients with malignant gliomas is common and is associated with significant adverse clinical outcomes [5]. TRL was found to be associated with early disease progression in patients with newly diagnosed squamous head and neck cancer (HNSCC) [12]
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