Patterns of recurrence and outcomes of glioblastoma multiforme treated with chemoradiation and adjuvant temozolomide

Abstract

OBJECTIVES: To assess the patterns of failure and prognostic factors in Brazilian patients with glioblastoma multiforme (GBM) treated with radiotherapy (RT) and concurrent and adjuvant temozolomide (TMZ). METHODS: Patients with diagnosed GBM post-resection received postoperative RT. TMZ was administered concurrently at 75 mg/m 2 /day for 28 consecutive days and adjuvant therapy at 150-200 mg/m 2 /day for 5 days every 28 days. Radiographic failure was defined as any new T1-enhancing lesion or biopsy-confirmed progressive enhancement inside of the radiation field. When possible, patients with recurrence were salvaged with metronomic TMZ, either in combination with a local treatment or alone (surgery or re-irradiation). Several prognostic factors were evaluated for overall survival (OS). Univariate and multivariate analyses were performed to identify significant factors. A p -value <0.05 was considered significant. RESULTS: This study included 50 patients. The median follow-up time was 21 months. The median RT dose was 60 Gy and all patients received concomitant TMZ. During follow-up, 41 (83.6%) failures were observed, including 34 (83%) in-field, 4 (9.7%) marginal, and 3 (7.3%) distant failures. Metronomic TMZ was used as salvage treatment in 22 (44%) cases and in combination with local treatment in 12 (24%) cases. The median OS and progression-free survival times for the entire cohort were 17 and 9 months, respectively. In univariate analysis, the following factors were significant for better OS: maximal surgical resection ( p =0.03), Karnofsky Performance Score (KPS)>70 at diagnosis ( p =0.01), metronomic TMZ treatment ( p =0.038), recursive partitioning analysis class III ( p =0.03), and time to failure >9 months ( p =0.0001). In multivariate analysis, the following factors remained significant for better OS: metronomic TMZ ( p =0.01) and time to failure >9 months ( p =0.0001). CONCLUSION: The median OS of Brazilian patients with GBM treated with RT and TMZ was satisfactory. Although TMZ therapy has become the standard of care for patients with newly diagnosed GBM, the recurrence rate is extremely high. Metronomic TMZ as salvage treatment improved survival in these patients.

Glioblastoma Therapy: Past, Present and Future

“…This SOC includes maximal safe resection, radiotherapy with concurrent (75 mg/m 2 /day × 6 weeks) and adjuvant TMZ (150–200 mg/m 2 /day × 5 days for six 28-day cycles). Since then, similar results (mOS 15–18 months) have been observed in other clinical studies [ 250 , 251 , 252 ]. Despite significant advances in the understanding of the molecular biology and pathophysiology of the GB, SOC has remained unchanged, excepting the possibility of adding or not tumor treating fields (TTFields) [ 13 , 253 , 254 ].…”

OLIG2 expression level could be used as an independent prognostic factor for patients with cerebellar Glioblastoma (cGBM)

“…These results confirmed that adjuvant therapies are beneficial besides surgical resection of tumors as previous reports indicated. 31 Meanwhile, OLIG2 expression level may be used as an indicator for tumor relapse and the effectiveness of adjuvant therapy. Cox regression analysis showed gross total tumor resection, high OLIG2 expression level and adjuvant therapy were independent favorable factors for the OS of cGBM patients.…”

C-methionine-PET-guided Gamma Knife radiosurgery boost as adjuvant treatment for newly diagnosed glioblastomas

“…[4] is treatment approach has increased the OS of patients, but at a closer look, the time at recurrence is very short, with the PFS for this patients being close to 7-9 months. [8,13] At the time of recurrence, patients will require new treatment approaches with new surgeries and different immune and chemoradiation treatments, [3] and this is also detrimental for the neurological status of these patients.…”