Jing Xi1,2, Bilal Hassan3, Ruth G N Katumba1, Karam Khaddour4, Akshay Govindan5,6, Jingqin Luo7, Jiayi Huang8, Jian L Campian9. 1. Department of Medicine Division of Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St Louis, MO, 63110, USA. 2. Department of Internal Medicine, Washington University School of Medicine, 666 S. Euclid Ave, Campus Box#8056, St. Louis, MO, 63110, USA. 3. Trinity Health, 20555 Victor Parkway, Livonia, MI, 48152, USA. 4. Department of Internal Medicine, Division of Hematology/Oncology, University of Illinois at Chicago, 820 S Wood Street (MC 675) Suite 100, Chicago, IL, 60612, USA. 5. University College, Washington University in St. Louis, St. Louis, MO, 63110, USA. 6. Washington University in St. Louis, One Brookings Drive, St. Louis, MO, 63130, USA. 7. Department of Surgery and Siteman Cancer Center Biostatistics Core, Division of Public Health Sciences, Washington University School of Medicine, 666 S. Euclid Ave, Campus Box #8100, St. Louis, USA. 8. Department of Radiation Oncology, Washington University School of Medicine, 4921 Parkview Place, Campus Box #8224, St Louis, MO, 63110, USA. 9. Department of Medicine Division of Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St Louis, MO, 63110, USA. campian.jian@wustl.edu.
Abstract
BACKGROUND: Differentiating 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. METHODS: Patients 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. RESULTS: 78 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. CONCLUSION: Our 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.
BACKGROUND: Differentiating 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. METHODS:Patients 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. RESULTS: 78 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. CONCLUSION: Our 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.
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Authors: Jian L Campian; Xiaobu Ye; Douglas E Gladstone; Prakash Ambady; Thomas R Nirschl; Ivan Borrello; Marc Golightly; Karen E King; Matthias Holdhoff; Judith Karp; Charles G Drake; Stuart A Grossman Journal: J Neurooncol Date: 2015-06-13 Impact factor: 4.130
Authors: Aaron T Wild; Xiaobu Ye; Susannah G Ellsworth; Jessica A Smith; Amol K Narang; Tanu Garg; Jian Campian; Daniel A Laheru; Lei Zheng; Christopher L Wolfgang; Phuoc T Tran; Stuart A Grossman; Joseph M Herman Journal: Am J Clin Oncol Date: 2015-06 Impact factor: 2.339
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