title: Association between treatment-related lymphopenia and overall survival in elderly patients with newly diagnosed glioblastoma.
abstract: Management of patients with glioblastoma (GBM) often includes radiation (RT) and temozolomide (TMZ). The association between severe treatment-related lymphopenia (TRL) after the standard chemoradiation and reduced survival has been reported in GBM patients with the median age of 57. Similar findings were described in patients with head and neck, non-small cell lung, and pancreatic cancers. This retrospective study is designed to evaluate whether elderly GBM patients (age ≥65) develop similar TRL after RT/TMZ and whether such TRL is associated with decreased survival. Serial total lymphocyte counts (TLC) were retrospectively reviewed in patients (age ≥65) with newly diagnosed GBM undergoing RT/TMZ and associated with treatment outcomes. Seventy-two patients were eligible: median KPS 70, median age 71 years (range 65-86) with 56 % of patients >70 years, 53% female, 31% received RT ≤45 Gy. Baseline median TLC was 1100 cells/mm(3) which fell by 41% to 650 cells/mm(3) 2 months after initiating RT/TMZ (p < 0.0001). Patients with TLC <500 cells/mm(3) at 2 months had a shorter survival than those with higher TLCs with a median overall survival of 4.6 versus 11.6 months, respectively. Multivariate analysis revealed a significant association between TRL and survival (HR 2.76, 95% CI 1.30-5.86, p = 0.008). Treatment-related lymphopenia is frequent, severe, and an independent predictor for survival in elderly patients with GBM. These findings add to the body of evidence that immunosuppression induced by chemoradiation is associated with inferior clinical outcomes. Prospective studies are needed to confirm these findings suggesting that immune preservation is important in this cancer.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St Louis, MO, 63110, USA.
authors.forename: Joe S
authors.initials: JS
authors.lastname: Mendez
authors.affiliation: Department of Medicine, Oncology Division, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St Louis, MO, 63110, USA.
authors.forename: Ashwin
authors.initials: A
authors.lastname: Govindan
authors.affiliation: Department of Medicine, Oncology Division, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St Louis, MO, 63110, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Leong
authors.affiliation: Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St Louis, MO, 63110, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO, 63110, USA.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Medicine, Oncology Division, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St Louis, MO, 63110, USA. jcampian@dom.wustl.edu.
authors.forename: Jian L
authors.initials: JL
authors.lastname: Campian
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects*; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D008231:Lymphopenia / Q000209:etiology / Q000401:mortality* / Q000473:pathology; D008297:Male; D060787:Neoplasm Grading; D011379:Prognosis; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D015996:Survival Rate; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Chemotherapy; Glioblastoma; Lymphopenia; Radiation; Treatment-related toxicities