title: Bone marrow response as a potential biomarker of outcomes in glioblastoma patients.
abstract: OBJECTIVE Glioblastoma (GBM) is a highly aggressive malignancy that requires a multidisciplinary therapeutic approach of surgery, chemotherapy, and radiation therapy, but therapy is frequently limited by side effects. The most common adverse effect of chemotherapy with temozolomide (TMZ) is myelosuppression. It remains unclear whether the degree of bone-marrow suppression might serve as a biomarker for treatment outcome. The aim of the current study was to investigate whether the degree of bone-marrow toxicity in patients treated with TMZ correlates with overall survival (OS) and MRI-based time to progression (progression-free survival [PFS]). METHODS Complete blood counts and clinical and imaging information were collected retrospectively from 86 cases involving GBM patients who had completed both radiation therapy and at least 6 monthly cycles of chemotherapy with TMZ. RESULTS Using a multivariate Cox proportional hazard model, it was observed that MGMT promoter methylation, wild-type EGFR, younger patient age at diagnosis, and treatment-induced decreases in white blood cell counts were associated with improved OS. The 2-year survival rate was 25% and 58% for patients with increases and decreases, respectively, in white blood cell counts from baseline over 6 months of TMZ treatment. Consistent with the literature, IDH mutation and MGMT promoter methylation were associated with better PFS and OS. IDH mutation and MGMT promoter methylation were not correlated with changes in peripheral red blood cell or white blood cell counts. CONCLUSIONS Decreases in white blood cell counts might serve as a potential biomarker for OS and PFS in malignant glioma patients treated with radiation therapy and TMZ. It remains unclear whether treatment-induced changes in white blood cell counts correlate with drug-induced antitumor activity or represent an independent factor of the altered local and systemic tumor environment. Additional studies will be needed to determine dose dependence for chemotherapy based upon peripheral blood counts.
authors.affiliation: Harvard Medical School; and.|Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Vaios
authors.affiliation: Harvard Medical School; and.|Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Brian V
authors.initials: BV
authors.lastname: Nahed
authors.affiliation: Departments of 2 Biostatistics.
authors.forename: Alona
authors.initials: A
authors.lastname: Muzikansky
authors.affiliation: Harvard Medical School; and.|Hematology-Oncology.
authors.forename: Amir T
authors.initials: AT
authors.lastname: Fathi
authors.affiliation: Harvard Medical School; and.|Neuro-Oncology, and.
authors.forename: Jorg
authors.initials: J
authors.lastname: Dietrich
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology* / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D015996:Survival Rate; D000077204:Temozolomide / Q000494:pharmacology* / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000077204:Temozolomide
keywords: EGFR = epidermal growth factor receptor; GBM = glioblastoma; OS = overall survival; PFS = progression-free survival; TMZ = temozolomide; biomarker; bone marrow; glioblastoma; oncology; overall survival; temozolomide