Characterization of Late Recurrence in Long-Term Survivors of Primary Glioblastoma

Research Article

Austin J Clin Neurol 2015;2(1): 1019.

Characterization of Late Recurrence in Long-Term Survivors of Primary Glioblastoma

Gastrell P1, Woodring S2, McSherry F3, Herndon JE II3, Desjardins A4, Friedman H2 and Peters KB4*

1Duke University School of Medicine, USA

2Deparment of Surgery, Duke University Medical Center, USA

3Department of Biostatistics, Duke University Medical Center, USA

4Department of Neurology, Duke University Medical Center, USA

*Corresponding author: Peters KB, Department of Neurology, Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, P.B: 3624, USA

Received: December 06, 2014; Accepted: February 11, 2015; Published: February 17, 2015


Traditionally, overall survival (OS) in primary glioblastoma (GBM) was dismal with 5% at 2 years, but recent advances have improved OS in this population. Long-term survivors (LTS), while rare, can now be identified and evaluated. In a single-center, retrospective analysis, we identified GBM LTS as defined by survival =5 years from diagnosis. To characterize late recurrence in GBM LTS, we extracted a patient subset that experienced disease/treatment free period =2 years. Demographic data was obtained along with characteristics of late recurrence: location, pathology, associated clinical symptoms, and calculation of time to death from late recurrence. 139 primary GBM patients were identified as long-term survivors from January 1, 1998 to August 31, 2011. 42 (30%) had a late recurrence. 59.5% (n=25) were male and average age was 45.6 yrs (range, 23-66yrs). 57.1% (n=24) had new neurological symptoms to indicate recurrence, but the remaining 42.9% were found to have recurrence on serial MRIs. Median OS was 6.8 yrs (95% CI 6.2, 8 years) and median time to late recurrence was 3.6 yrs (95% CI 3.3, 4.6 yrs). Once patients progressed, median time to death from recurrence was 1.3 yrs (95% CI 1, 1.7 yrs) indicating a more aggressive cancer. GBM LTS can develop late recurrences in their disease trajectory even after a protracted disease/treatment free time period. Continued close monitoring with frequent clinical evaluations and MRI imaging is warranted in this population. Establishment of survivorship programs should be considered for GBM LTS to address disease-related and psychosocial issues.


Primary brain tumors represent 1% of all diagnosed cancers, but the survival rates of patients with the most malignant form of these tumors, GBM(WHO grade IV), continues to be poor with less than 3% of patients surviving at five years’ post diagnosis [1,2]. Gliomas in general are the most commonly diagnosed class of primary brain tumor, while GBM remains the most common of the gliomas [1]. Many environmental factors have been proposed to be associated with an increased risk of GBM, with the only unequivocally associated factor being a history of therapeutic X-ray irradiation, especially prophylactic CNS X-ray irradiation in children diagnosed with acute lymphoblastic leukemia [1].

The standard of care for newly diagnosed GBM involves surgical resection followed by temozolomide concurrent with and after radiotherapy. Despite this aggressive approach, median survival has been prolonged only from 12.1 months to 14.6 months relative to radiotherapy alone and disease recurrence and progression occurs with regular frequency [3]. Prognostic factors associated with prolonged survival have been younger age at time of initial diagnosis and high Karnofsky Performance Score at time of diagnosis [2,4-6]. Other factors associated with a good prognosis for survival have included 06-methylguanine DNA methyltransferase (MGMT) promoter methylation status with longer survival being associated with MGMT promoter methylation and isocitrate dehydrogenase 1 mutation [7-9]. Long-term survival in GBM patients has not been studied extensively, and the definition of long-term survival itself has been variably described as either survival greater than three years or survival greater than five year [4,6].

The characteristics of long term survivorship and late GBM recurrence are vital to an understanding of the prognosis and pathophysiology of late recurrence. Furthermore, these characteristics inform physician and patient expectations in the case of long-term survivorship and determine the need for ongoing patient monitoring and psycho-social support. While patient outcomes following GBS diagnosis and treatment have been studied extensively [4,6], a large study characterizing late GBM recurrence in LTS remains absent from the literature. Therefore, we designed a protocol at the Preston Robert Tisch Brain Tumor Center (PRT-BTC) to identify long-term survivorship in primary GBM and describe the factors associated with survivorship and late recurrence.


Inclusion criteria and data collection

In a retrospective analysis, we identified primary GBM LTS as defined by survival greater than or equal to 5 years from initial GBM diagnosis. Inclusion criteria included a histologically confirmed diagnosis of glioblastoma, treatment at the PRT-BTC between January 1, 1998 and August 31, 2011, ages 18-70 years, and survival of at least 5 years of more following diagnosis of GBM. Clinical characteristics and tumor-related information were collected on all eligible long-term GBM survivors treated at the PRT-BTC, resulting in a population of 139 patients. To characterize late recurrence in GBM LTS, we identified a subgroup of 42 patients who had a diseasefree period for 2 years or greater off therapy before their cancer recurred. Demographic data was obtained from this group along with characteristics of their late recurrence, including tumor location, pathology, KPS at time diagnosis of recurrence, associated clinical symptoms, and calculation of overall survival and time to death from late recurrence.

Statistical analysis

Descriptive statistics were performed on the available demographic characteristics of GBM LTS with recurrence as well as the characteristics of their late recurrence. Kaplan-Meier methods were used to determine and describe median overall survival, median time from the end of treatment to late recurrence, and median time from late recurrence to death. The log-rank test was used to compare patients that were symptomatic at recurrence vs. not symptomatic at recurrence on overall survival and time from late recurrence to death.


Based on the definition of LTS and late recurrence, 42 out of 139 patients (30%) had a late recurrence. Table 1 summarizes the late recurrent patients’ demographic characteristics and the characteristics of their recurrences. Of the 42 patients, 25 (59.5%) were male and 17 (40.5%) were female, and the average age was 45.6 years (range: 23-66 years). Twenty-four patients (57.1%) had neurological symptoms that indicated recurrence, and by August 31st, 2011 32 patients (76.2%) had died.