Clinical Investigation
Standard (60 Gy) or Short-Course (40 Gy) Irradiation Plus Concomitant and Adjuvant Temozolomide for Elderly Patients With Glioblastoma: A Propensity-Matched Analysis

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Purpose

To evaluate 2 specific radiation schedules, each combined with temozolomide (TMZ), assessing their efficacy and safety in patients aged ≥65 years with newly diagnosed glioblastoma (GBM).

Methods and Materials

Patients aged ≥65 years with Karnofsky performance status (KPS) ≥60 who received either standard (60 Gy) or short-course (40 Gy) radiation therapy (RT) with concomitant and adjuvant TMZ between June 2004 and October 2013 were retrospectively analyzed. A propensity score analysis was executed for a balanced comparison of treatment outcomes.

Results

A total of 127 patients received standard RT-TMZ, whereas 116 patients underwent short-course RT-TMZ. Median overall survival and progression-free survival times were similar: 12 months and 5.6 months for the standard RT-TMZ group and 12.5 months and 6.7 months for the short-course RT-TMZ group, respectively. Radiation schedule was associated with similar survival outcomes in either unadjusted or adjusted analysis. O6-methylguanine-DNA methyltransferase promoter methylation was the most favorable prognostic factor (P=.0001). Standard RT-TMZ therapy was associated with a significant rise in grade 2 and 3 neurologic toxicity (P=.01), lowering of KPS scores during the study (P=.01), and higher posttreatment dosing of corticosteroid (P=.02).

Conclusions

In older adults with GBM, survival outcomes of standard and short-course RT-TMZ were similar. An abbreviated course of RT plus TMZ may represent a reasonable therapeutic approach for these patients, without loss of survival benefit and acceptable toxicity.

Introduction

Glioblastoma (GBM) is increasing among the elderly, and approximately one-third of all patients are aged >65 years (1). Radiation therapy (RT) is generally administered in this population, conferring a median survival from diagnosis of approximately 4 to 10 months 2, 3, 4, 5. Chemotherapy with the alkylating agent temozolomide (TMZ) or hypofractionated courses of RT are treatment options associated with similar survival benefits 6, 7, 8, 9, 10, 11, 12. In a randomized study of 100 patients aged ≥60 years with GBM who received either radical RT (60 Gy) or short-course RT (40 Gy), Roa et al (9) observed a median survival time of 5.1 months and 5.6 months for standard and short-term RT groups, respectively. A median survival time of 6 to 8 months has been reported with doses of 30-37.5 Gy in 6-15 daily fractions in some prospective studies 6, 7, 8.

Radical RT plus TMZ is standard treatment for adult patients with GBM and has been advocated as an effective approach in older patients with a good performance status. Although a few studies have shown promising survival times of 10 to 14 months with this regimen 13, 14, 15, 16, the likely toxicity is of concern, given the limited life expectancy of this patient population. Thus, many physicians may opt for less-aggressive treatment. Using a radiation schedule of 40 Gy in 15 fractions in combination with concomitant and adjuvant TMZ, we previously reported a median overall survival (OS) of 12.4 months and a median progression-free survival (PFS) of 6 months in 70 older patients aged ≥70 years with newly diagnosed GBM (17). This approach was associated with improved quality of life and performance status (18). Owing to results of the above prospective study, this particular regimen is often used at our institution as an alternative to standard radiochemotherapy for older patients with GBM.

To date there are no studies that have evaluated the clinical outcomes and toxicity of different RT schedules in combination with TMZ for older patients with GBM. With this in mind, we compared data from older patients aged ≥65 years with GBM who received standard or short-course RT in conjunction with TMZ. A propensity score analysis was done to adjust for between-group disparities of clinically relevant covariates.

Section snippets

Patients

Data collected from 329 patients aged ≥65 years with newly diagnosed, histologically confirmed GBM and Karnofsky performance status (KPS) ≥60 who received standard or short-course RT plus concomitant and adjuvant TMZ between June 2004 and October 2013 were evaluated in this tri-center, retrospective study. For patients treated at Sant'Andrea Hospital and Neuromed Institute all clinically relevant radiographic, surgical, and pathologic information was drawn from a prospectively maintained

Results

A total of 243 consecutive patients aged ≥65 years with newly diagnosed GBM received chemoradiotherapy between June 2004 and October 2013. Patient characteristics are shown in Table 1. Subjects received either standard (n=127) or short-course (n=116) RT. There were no statistically significant differences between groups in terms of gender, KPS scores, site of tumor, PTV, and MGMT promoter methylation status. However, patients given standard RT-TMZ were more likely to be younger and to undergo

Discussion

Clinical outcomes of this study, in which either standard or short-course RT was delivered with concomitant and adjuvant TMZ to patients aged ≥65 years with GBM, were similar in terms of 1-year survival, PFS, and OS. Hence, a chemoradiotherapeutic regimen of short-course versus standard RT plus TMZ does not seem to compromise patient survival in this context. The above findings are strengthened by propensity score analysis, which addresses potential bias when retrospective data of 2

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  • Cited by (0)

    This study was supported by a grant (C26A12TBP5) from University Sapienza, Rome, Italy (to R.M.E.).

    Conflict of interest: none.

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