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A validated integrated clinical and molecular glioblastoma long-term survival-predictive nomogram

Authors
  • Ferguson, Sherise D1
  • Hodges, Tiffany R2
  • Majd, Nazanin K3
  • Alfaro-Munoz, Kristin3
  • Al-Holou, Wajd N4
  • Suki, Dima1
  • de Groot, John F3
  • Fuller, Gregory N5
  • Xue, Lee1
  • Li, Miao1
  • Jacobs, Carmen1
  • Rao, Ganesh6
  • Colen, Rivka R7
  • Xiu, Joanne8
  • Verhaak, Roel9
  • Spetzler, David8
  • Khasraw, Mustafa10
  • Sawaya, Raymond1
  • Long, James P11
  • Heimberger, Amy B1
  • 1 Departments of Neurosurgery, The University of Texas MD Anderson Cancer Center, USA , (United States)
  • 2 Department of Neurosurgery, Seidman Cancer Center & University Hospitals—Cleveland Medical Center, USA , (United States)
  • 3 Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, USA , (United States)
  • 4 Department of Neurosurgery, University of Michigan Medical School, USA , (United States)
  • 5 Departments of Anatomic Pathology and Neuroradiology, The University of Texas MD Anderson Cancer Center, USA , (United States)
  • 6 Department of Neurosurgery, Baylor College of Medicine, USA , (United States)
  • 7 Hillman Cancer Center, Department of Radiology, University of Pittsburg, USA , (United States)
  • 8 Caris Life Sciences, USA , (United States)
  • 9 The Jackson Laboratory for Genomic Medicine, USA , (United States)
  • 10 Tisch Brain Tumor, Department of Neurosurgery Duke University Medical Center, USA , (United States)
  • 11 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, USA , (United States)
Type
Published Article
Journal
Neuro-oncology Advances
Publisher
Oxford University Press
Publication Date
Oct 31, 2020
Volume
3
Issue
1
Identifiers
DOI: 10.1093/noajnl/vdaa146
PMID: 33426529
PMCID: PMC7780842
Source
PubMed Central
Keywords
Disciplines
  • AcademicSubjects/MED00300
  • AcademicSubjects/MED00310
License
Unknown

Abstract

Background Glioblastoma (GBM) is the most common primary malignant brain tumor in adulthood. Despite multimodality treatments, including maximal safe resection followed by irradiation and chemotherapy, the median overall survival times range from 14 to 16 months. However, a small subset of GBM patients live beyond 5 years and are thus considered long-term survivors. Methods A retrospective analysis of the clinical, radiographic, and molecular features of patients with newly diagnosed primary GBM who underwent treatment at The University of Texas MD Anderson Cancer Center was conducted. Eighty patients had sufficient quantity and quality of tissue available for next-generation sequencing and immunohistochemical analysis. Factors associated with survival time were identified using proportional odds ordinal regression. We constructed a survival-predictive nomogram using a forward stepwise model that we subsequently validated using The Cancer Genome Atlas. Results Univariate analysis revealed 3 pivotal genetic alterations associated with GBM survival: both high tumor mutational burden ( P = .0055) and PTEN mutations ( P = .0235) negatively impacted survival, whereas IDH1 mutations positively impacted survival ( P < .0001). Clinical factors significantly associated with GBM survival included age ( P < .0001), preoperative Karnofsky Performance Scale score ( P = .0001), sex ( P = .0164), and clinical trial participation ( P < .0001). Higher preoperative T1-enhancing volume ( P = .0497) was associated with shorter survival. The ratio of TI-enhancing to nonenhancing disease (T1/T2 ratio) also significantly impacted survival ( P = .0022). Conclusions Our newly devised long-term survival - predictive nomogram based on clinical and genomic data can be used to advise patients regarding their potential outcomes and account for confounding factors in nonrandomized clinical trials.

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