Circulating Blood Counts Predict Response, Survival in Recurrent Glioblastoma Treated with Bevacizumab
Key findings
- This retrospective study examined circulating blood counts in 84 adults who received bevacizumab for recurrent glioblastoma
- Increases in eosinophil counts were significantly associated with improved overall survival (OS) during bevacizumab treatment and radiographic response to the drug
- Elevations in lymphocyte counts prior to radiographic response predicted improved OS, and this association was maintained even after controlling for known prognostic markers, including MGMT promoter methylation and steroid use
- Changes in platelet counts differed before and after evidence of radiographic response, with decreases corresponding with response to treatment and increases preceding evidence of progressive disease
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Bevacizumab is one of the most commonly prescribed salvage therapies for recurrent glioblastoma. However, the response varies, and it is unclear which patients are most likely to benefit. Even in responders, reduction in tumor size may be only transient, and radiographic monitoring of tumor progression is difficult because of alterations in contrast permeability.
Identification of a blood-based biomarker to guide the management of glioblastoma is an active area of investigation. Massachusetts General Hospital researchers previously demonstrated that bone marrow toxicity, reflected by changes in circulating white blood cell counts, predicted overall survival (OS) in patients with newly diagnosed glioblastoma treated with standard chemoradiation (published in the Journal of Neurosurgery).
The team recently extended its findings, showing that changes in circulating blood counts in patients treated with bevacizumab for recurrent disease are potential biomarkers of treatment response and survival. The report was published in Neuro-Oncology Advances by Eugene J. Vaios, MD, MBA, former resident at Mass General, Brian V. Nahed, MD, MSc, associate director of the Neurosurgery Residency Program, and Jorg Dietrich, MD, PhD, director of the Cancer & Neurotoxicity Clinic and Brain Repair Research Program at the Mass General Cancer Center and Department of Neurology.
Study Cohort
The researchers studied 84 adults who were newly diagnosed with grade IV glioblastoma between November 19, 2004, and January 6, 2015, who underwent surgical resection and were treated with standard chemoradiation including adjuvant temozolomide, followed by at least two cycles of bevacizumab for recurrent disease.
The primary endpoint was OS after initiation of bevacizumab.
Overall Outcomes
Median OS was 192 days. On multivariate analysis, MGMT promoter methylation, increases in red blood cells during treatment and increases in eosinophils during treatment predicted improved OS.
Eosinophils
- The 12-month OS rate was 6% and 41% for patients in the first and fourth quartiles of eosinophils (P < 0.0001), respectively
- This corresponded to a median OS of 173 days and 314 days (P < 0.0001)
- Patients in the first and fourth quartiles had a median change in eosinophil counts of −80% and 260% from baseline
Outcomes in Bevacizumab Responders
48 patients (57%) had radiographic evidence of treatment response to bevacizumab (defined as more than 20%–25% decrease of the contrast-enhancing mass).
Platelets
- Changes in platelet counts differed before and after the radiographic response (P = 0.014)
- Decreases in platelet counts corresponded with the response to treatment and increases preceded evidence of progressive disease
Lymphocytes
- The 12-month OS rate was 0% and 44% for patients in the first and fourth quartiles of lymphocytes
- This corresponded to median OS of 151 days and 332 days (P < 0.0001)
- Patients in the first and fourth quartiles had a median change in lymphocyte counts of −52% and 89% from baseline
On multivariate analysis, increases in lymphocyte counts remained significantly associated with improved OS (P = 0.04), even after adjustment for known prognostic markers, including MGMT promoter methylation and steroid use.
Toward the Future
The association between increases in eosinophil and lymphocyte counts and improved survival may reflect changes in the local tumor environment and the patient's antitumor immune response. Changes in platelet counts may reflect changes in the tumor microenvironment as well as tumor–platelet interactions.
The association between increases in red blood cell counts and improved OS suggests red blood cells could be a surrogate marker for bone marrow function after cessation of temozolomide.
Hopefully, prospective studies will confirm that peripheral blood counts can serve as biomarkers for clinical outcomes in patients with recurrent glioblastoma who receive bevacizumab.
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