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

Sherise D Ferguson; Tiffany R Hodges; Nazanin K Majd; Kristin Alfaro-Munoz; Wajd N Al-Holou; Dima Suki; John F de Groot; Gregory N Fuller; Lee Xue; Miao Li; Carmen Jacobs; Ganesh Rao; Rivka R Colen; Joanne Xiu; Roel Verhaak; David Spetzler; Mustafa Khasraw; Raymond Sawaya; James P Long; Amy B Heimberger

doi:10.1093/noajnl/vdaa146

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

Neurooncol Adv. 2020 Oct 31;3(1):vdaa146. doi: 10.1093/noajnl/vdaa146. eCollection 2021 Jan-Dec.

Authors

Sherise D Ferguson¹, Tiffany R Hodges², Nazanin K Majd³, Kristin Alfaro-Munoz³, Wajd N Al-Holou⁴, Dima Suki¹, John F de Groot³, Gregory N Fuller⁵, Lee Xue¹, Miao Li¹, Carmen Jacobs¹, Ganesh Rao⁶, Rivka R Colen⁷, Joanne Xiu⁸, Roel Verhaak⁹, David Spetzler⁸, Mustafa Khasraw¹⁰, Raymond Sawaya¹, James P Long¹¹, Amy B Heimberger¹

Affiliations

¹ Departments of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
² Department of Neurosurgery, Seidman Cancer Center & University Hospitals-Cleveland Medical Center, Cleveland, Ohio, USA.
³ Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁴ Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
⁵ Departments of Anatomic Pathology and Neuroradiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁶ Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.
⁷ Hillman Cancer Center, Department of Radiology, University of Pittsburg, Pittsburg, Pennsylvania, USA.
⁸ Caris Life Sciences, Irving, Texas, USA.
⁹ The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
¹⁰ Tisch Brain Tumor, Department of Neurosurgery Duke University Medical Center, Durham, North Carolina, USA.
¹¹ Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

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.

Keywords: glioblastoma; long-term survival; nomogram; outcome; prediction.

Grants and funding

UL1 TR003167/TR/NCATS NIH HHS/United States