Treatment of Elderly Patients With Glioblastoma

Zarnett, Oren; Sahgal, Arjun; Gosio, Jessica; Perry, James; Berger, Mitchel S.; Chang, Susan M.; Das, Sunit

doi:10.1001/jamaneurol.2014.3739

Cited by 88 publications

(55 citation statements)

References 30 publications

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“…Although treatment for GBM patients has evolved, many of the trials leading to today’s standard of care initially excluded patients in their 60's and 70's [10]. Today’s standard of care remains maximum safe tumor resection, standard course RT of 60 Gy in 30 daily fractions over six weeks, and concurrent and adjuvant TMZ chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Accelerated Hypofractionated Radiotherapy in the Era of Concurrent Temozolomide Chemotherapy in Elderly Patients with Glioblastoma Multiforme

Greer¹,

Pannullo²,

Smith³

et al. 2017

Cureus

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IntroductionPatients with glioblastoma multiforme (GBM) over age 65 represent nearly half of those diagnosed per annum. They have a different tumor markers profile, physiologic reserve, and a median survival as low as three to four months. An optimal treatment strategy in older GBM patients remains undefined, with many patients receiving radiation in 30 treatments over six weeks, a regimen based on trials originally excluding patients over age 70. Recent studies have suggested reducing the number of treatments to 10-15 over two to three weeks with similar efficacy. We present an elderly population of patients treated with six radiation treatments.MethodsAfter IRB approval, we reviewed the electronic medical records of 20 consecutive patients over the age 60 at diagnosis with GBM, treated with maximally safe neurosurgical resection, and adjuvant hypofractionated radiation (HFRT) and temozolomide (TMZ) between 2012 and 2015. HFRT was given every other weekday for two weeks, in a total of six fractions (6 × 6 Gy to contrast-enhancing tumor +5 mm and 6 × 4 Gy to fluid-attenuated inversion recovery (FLAIR) +2 cm) with concurrent TMZ (75 mg/m2 daily), followed by adjuvant TMZ (150-200 mg/m2 in 5/28 days). The response was assessed using the Macdonald and Revised Assessment in Neuro-Oncology (RANO) criteria, radiology reports, physician notes, and tumor board consensus notes. Descriptive statistics, overall survival (OS), progression-free survival (PFS), toxicity, and steroid use were calculated and compared to the historical controls of patients treated with a six-week radiation regimen of 60 Gy in 30 fractions with TMZ. ResultsThe median age at diagnosis was 70.5 years (range: 61 - 82 years). Median pre-radiation Karnofsky performance scale (KPS) was 60 (range: 40 - 90). The median preoperative maximum gross tumor diameter on MRI was 3.6 cm (range: 1.8 - 6 cm). Six patients (30%) had a gross total resection (GTR), eight (40%) had a subtotal resection (STR), and six (30%) had biopsy only. The median progression-free survival was five months (95% (confidence interval) CI: 2.8, 16.4) and median OS of 14 months (95% CI: 5.0, upper limit not estimable). Of the 19 patients tested for isocitrate dehydrogenase-1 (IDH), 100% were negative. Of the eight patients who had MGMT methylation status results, four (50%) were positive for O6-methylguanine-DNA methyltransferase (MGMT) methylation. In the 18 patients who completed radiation, the HFRT treatment was well tolerated without any Grade 3/4 acute toxicities.ConclusionsThe accelerated adjuvant course of HFRT with TMZ used for the elderly with GBM decreases radiation treatment days to six. It was well tolerated in patients over 60 years of age and provided similar OS, PFS, minimal toxicity, and decreased steroid usage compared to historical controls treated with six or even two to three weeks of radiotherapy.

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Section: Discussionmentioning

confidence: 99%

Accelerated Hypofractionated Radiotherapy in the Era of Concurrent Temozolomide Chemotherapy in Elderly Patients with Glioblastoma Multiforme

Greer¹,

Pannullo²,

Smith³

et al. 2017

Cureus

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“…That shorter os is likely multifactorial and reflects differing tumour biology in elderly patients, as well as differences in treatment patterns and tolerance of therapy [6][7][8] . Many elderly or frail patients are unable to tolerate combined chemoradiotherapy, and toxicities-including severe fatigue, myelosuppression, and infections-are common 9 .…”

Section: Introductionmentioning

confidence: 99%

Treatment and Outcomes for Glioblastoma in Elderly Compared with Non-elderly Patients: A Population-Based Study

Norman

Laing

2017

Current Oncology

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Purpose Elderly patients make up a large percentage of the individuals newly diagnosed with glioblastoma (gbm), but they face particular challenges in tolerating standard therapy, and compared with younger patients, they experience significantly shorter survival. We set out to compare clinical characteristics, treatment patterns, and outcomes in a non-elderly group (<65 years) and an elderly group (≥65 years) of patients diagnosed with gbm.Methods This retrospective population-based study used a province-wide cancer registry to identify patients with a new diagnosis of gbm within a 6-year period (2006)(2007)(2008)(2009)(2010)(2011)(2012). Of the 138 patients identified, 56 (40.6%) were 65 years of age or older. Demographic characteristics, treatment patterns, and overall survival (os) in the elderly and non-elderly groups were compared. Predictors of os were determined using multivariate analysis.Results Elderly patients were more likely to present with a poor performance status (Eastern Cooperative Oncology Group ≥ 2), to undergo biopsy without resection, and to receive whole-brain or hypofractionated radiotherapy. Compared with non-elderly patients, the elderly patients were less likely to receive adjuvant temozolomide. Survival time was significantly shorter in the elderly than in the non-elderly patients (7.2 months vs. 11.2 months). In multivariate analysis, surgical resection, hypofractionated radiotherapy (compared with whole-brain or conventional radiotherapy), and chemotherapy were predictive of os in older patients. Among elderly patients receiving radiation, survival was improved with the use of combined therapy compared with the use of radiation only (11.3 months vs. 4.6 months). ConclusionsOverall survival was shorter for elderly patients with gbm than for non-elderly patients; the elderly patients were also less likely to receive intensive surgical or adjuvant therapy. Our population-based analysis demonstrated improved os with surgical resection, hypofractionated radiotherapy, and temozolomide, and supports the results of recent clinical trials demonstrating a benefit for combination chemoradiotherapy in older patients.

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“…Nevertheless, chemotherapy with TMZ alone is put forth as an acceptable alternative to RT in elderly patients with GBM [32,33,34,35]. The NOA trial examined and compared patients who received TMZ-alone ( n = 195) versus RT-alone ( n = 178) for malignant astrocytoma.…”

Section: Discussionmentioning

confidence: 99%

“…Yin et al [32] also demonstrated the non-inferiority of TMZ to RT-alone in improving the overall survival in elderly, however at an increased risk of grade 3-4 toxicities. Zarnett et al [33], in their systematic review, concluded that elderly patients with MGMT promoter methylation are more likely to receive the greatest benefit from TMZ-alone regimen over RT. Metcalfe et al [36] in a retrospective cohort analysis study showed that the addition of adjuvant TMZ followed by concurrent TMZ with RT improves the overall survival in patients with newly diagnosed GBM who are 70 years or above.…”

Section: Discussionmentioning

confidence: 99%

Temozolomide with or without Radiotherapy in Patients with Newly Diagnosed Glioblastoma Multiforme: A Meta-Analysis

2017

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Background/Aim: The current meta-analysis evaluated the survival outcomes of newly diagnosed glioblastoma patients treated with radiotherapy (RT) alone and with RT + temozolomide (TMZ). Methods: Relevant studies were identified by an extensive literature search in Medline, Current Contents and Cochrane databases by 2 independent reviewers using the terms “glioblastoma multiforme/glioblastoma, TMZ, radiation therapy/RT and survival.” Results: Results revealed a median survival of 13.41-19 months in the combined treatment group, as opposed to 7.7-17.1 months in the RT-alone group. Progression-free survival (PFS) was also significantly different between the 2 groups (RT + TMZ, 6.3-13 months; RT-alone, 5-7.6 months). While there was no significant difference in the 6-month survival and 6-month PFS rates between the RT + TMZ and RT groups (pooled OR 0.690; p = 0.057 and OR 0.429, p = 0.052, respectively), the 1-year survival and 1-year PFS rates showed significant difference (OR 0.469; p = 0.030 and OR 0.245, p < 0.001, respectively). Conclusions: Concomitant RT + TMZ is more effective and improves the overall survival and PFS in patients with newly diagnosed glioblastoma.

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Treatment of Elderly Patients With Glioblastoma

Cited by 88 publications

References 30 publications

Accelerated Hypofractionated Radiotherapy in the Era of Concurrent Temozolomide Chemotherapy in Elderly Patients with Glioblastoma Multiforme

Accelerated Hypofractionated Radiotherapy in the Era of Concurrent Temozolomide Chemotherapy in Elderly Patients with Glioblastoma Multiforme

Treatment and Outcomes for Glioblastoma in Elderly Compared with Non-elderly Patients: A Population-Based Study

Temozolomide with or without Radiotherapy in Patients with Newly Diagnosed Glioblastoma Multiforme: A Meta-Analysis

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