Impact of lymphopenia on survival for elderly patients with glioblastoma: A secondary analysis of the CCTG CE.6 (EORTC 26062-22061, TROG08.02) randomized clinical trial

Abstract

Background Lymphopenia may lead to worse outcomes for glioblastoma patients. This study is a secondary analysis of the CCTG CE.6 trial evaluating the impact of chemotherapy and radiation on lymphopenia, and effects of lymphopenia on overall survival (OS). Methods CCTG CE.6 randomized elderly glioblastoma patients (≥ 65 yrs) to short course radiation alone (RT) or short course radiation with temozolomide (RT + TMZ). Lymphopenia (mild-moderate: grade 1-2; severe: grade 3-4) was defined per CTCAE v3.0, and measured at baseline, 1 wk and 4 wks post-RT. Pre-selected key factors for analysis included age, sex, ECOG, resection extent, MGMT methylation, MMSE, and steroid use. Multinomial logistic regression and multivariable Cox regression models were used to identify lymphopenia-associated factors and association with survival. Results 562 patients were analyzed (281 RT vs 281 RT+TMZ). At baseline, both arms had similar rates of mild-moderate (21.4% vs 21.4%) and severe (3.2% vs 2.9%) lymphopenia. However, at 4 weeks post-RT, RT+TMZ was more likely to develop lymphopenia (mild-moderate: 27.9% vs 18.2%; severe: 9.3% vs 1.8%; p<0.001). Developing any lymphopenia post-RT was associated with baseline lymphopenia (p<0.001). Baseline lymphopenia (HR 1.3) was associated with worse OS (HR: 1.30, 95% C.I. 1.05-1.62; p = 0.02), regardless of MGMT status. Conclusions Development of post-RT lymphopenia is associated with addition of TMZ and baseline lymphopenia and not with RT alone in patients treated with short-course radiation. However, regardless of MGMT status, only baseline lymphopenia is associated with worse OS, which may be considered as a prognostic biomarker for elderly glioblastoma patients.

Optimal managements of elderly patients with glioblastoma

“…A Fine-Gray competing risk model of 4975 elderly patients ≥65 years old with glioblastoma from the SEER database demonstrated age ≥ 75 years old, white people, size >5.4 cm, frontal lobe tumor and overlapping lesion were independently associated with more glioblastoma-related death, whereas GTR, chemotherapy and chemoradiation were identified as independently protective factors for glioblastoma-related death ( 75 ). In a secondary analysis of the CCTG CE.6 trial evaluating the impact of lymphopenia, development of lymphopenia was not associated with radiotherapy alone, but baseline lymphopenia was associated with worsened OS ( 76 ). Multiple socioeconomic parameters can influence access to treatment modalities for elderly patients compared with younger patients in different geographic regions of the United States ( 77 ).…”

Preoperative Prognostic Nutritional Index Predict Survival in Patients With Resectable Esophageal Squamous Cell Carcinoma

“…Another calculated element of PNI is the blood lymphocyte count. Lymphocytes are one of the fundamental components of cell-mediated immunity with inhibitory effects on the proliferation and invasion of tumor cells via cytokine-mediated cytotoxicity ( 24 , 25 ). Lymphocyte is an important part of the body's immunity, in which low lymphocyte indicates that the body's immunity is not good or there is a disorder, thereby making the prognosis of patients worse ( 26 ).…”

Radiotherapy for Newly Diagnosed Glioblastoma in the Elderly: What Is the Standard?

“…The reported prognostic factors for GBM-e did not differ from those reported for younger patients. The extent of resection stands as a major prognostic factor for GBM-e [ 12 18 19 20 21 ]. Supratotal (hazard ratio [HR] 0.65; p <0.0001) and gross total resection (HR 0.61; p <0.0001) were shown to significantly lower the risk of death in GBM-e aged ≥65 years compared to biopsy or local excision, which was a consistent finding across all age groups, except for GBM-e aged ≥90 years, based on data from the Surveillance, Epidemiology, and End Results Program [ 18 ].…”

“…In a recent meta-analysis involving 13 retrospective studies, gross total resection significantly improved OS in GBM-e compared with subtotal resection (HR 0.70; p <0.001) [ 19 ]. Performance status also significantly affected OS in newly diagnosed GBM-e, as in younger patients [ 4 12 21 ]. Methylation of the O 6 -methylguanine-DNA methyltransferase ( MGMT ) promoter is a favorable prognostic factor that particularly predicts response to TMZ in GBM-e treated by either TMZ or TMZ-based radiochemotherapy [ 12 22 23 24 25 26 ], as reported by secondary analyses of randomized trials and retrospective series.…”

“…In contrast, promoter methylation of the MGMT gene ( MGMT +) does not appear to impact OS in GBM-e treated by RT alone [ 22 23 24 ]. The presence of lymphopenia has also recently become identified as an unfavorable prognostic factor [ 21 26 ].…”