Predictors of survival and effect of short (40 Gy) or standard-course (60 Gy) irradiation plus concomitant temozolomide in elderly patients with glioblastoma: a multicenter retrospective study of AINO (Italian Association of Neuro-Oncology)

Abstract

The efficacy of temozolomide (TMZ) plus radiation therapy (RT) in elderly patients with glioblastoma is unclear. We performed a large multicenter retrospective study to analyze prognostic factors and clinical outcome in these patients. Inclusion criteria were age ≥65 years, newly histologically confirmed glioblastoma, ECOG PS 0-2, adjuvant treatment with RT plus TMZ. We enrolled 237 patients; the average age was 71 and ECOG PS was 0-1 in 196 patients; gross total resection was performed in 174 cases. MGMT was analyzed in 151 persons and was methylated in 56 %. IDH1 was assessed in 100 patients and was mutated in 6 %. Seventy-one patients were treated with RT 40 Gy and 166 with RT 60 Gy. Progression-free survival and overall survival (OS) were 11.3 and 17.3 months, respectively. Overall survival was 19.4 vs 13.8 months for patients treated with RT 60 Gy and 40 Gy (p = 0.02); OS was 17.7 versus 16.1 months for patients treated with gross total resection vs partial surgery (p = 0.02); OS was 21.2 versus 13.6 months for methylated and unmethylated MGMT (p < 0.001). On multivariate analysis, gross total resection, RT 60 Gy, methylated MGMT and ECOG PS 0-1 were independent predictors of longer survival. Twenty-five patients (10 %) had grade 3-4 haematological toxicity during the concomitant treatment. We showed that, in elderly patients in good clinical condition treated with concomitant treatment, standard-course irradiation might be more effective than short-course irradiation. Methylated MGMT remains the most important prognostic factor.

Radiotherapy plus temozolomide in elderly patients with glioblastoma: a “real-life” report

“…However, this randomized trial was conducted before the era of TMZ. Recently, Lombardi et al [ 11 ] published a large multicenter retrospective study comparing short (HFRT; 40 Gy, 15 sessions) or standard-course (60 Gy, 30 sessions) irradiation plus concomitant TMZ in elderly (≥ 60 years) GBM patients (Table 3 ). Patients receiving HFRT were older ( p = 0.07).…”

“… Minniti et al [ 33 ] 2012 Prospective 71 >70 > 60 HFRT + TMZ and TMZ 12.4 Grade 3–4 hematologic toxicity occurred in15% of patients. Minniti et al [ 31 ] 2015 Retrospecitve 127 ≥ 65 ≥ 60 RT + TMZ and TMZ 12 No difference in overall survival or progression free survival between standard RT and HFRT HFRT + TMZ and TMZ 12.5 (ns) Lombardi et al [ 11 ] 2015 Retrospecitve 237 ≥65 ECOG PS 0–2 HFRT + TMZ 13.8 Potential advantage of standard RT over HFRT for “moderate” elderly patients with good clinical status and extensive surgery RT + TMZ 19.4 (p = 0.02) Perry et al[ 14 ] 2017 Prospective 562 ≥65 ECOG PS 0–2 HFRT 7.6 The addition of TMZ (concomitant and adjuvant) to HFRT resulted in longer overall survival than HFRT alone HFRT + TMZ and TMZ 9.3 (p < 0.001) Present study 2017 Retrospective 104 ≥ 70 ≥ 30 HFRT 3.9 (p < 0.05)* Potential benefit of combining TMZ with RT in an unselected cohort, irrespective of MGMT promoter status. HFRT + TMZ 5.5 RT + TMZ 9.6 (ns)** HFRT alone …”

IL‐17A promotes cell migration and invasion of glioblastoma cells via activation of PI3K/AKT signalling pathway

“…Glioblastoma, known as glioblastoma multiforme (GBM), is the most common type of primary malignant tumours in adult brain with a mean survival rate ranging from 13.2 to 14.6 months and a 5‐year survival rate of 9.8% . Approximately 23 000 cases were newly diagnosed with GBM each year, and patients’ age has been identified as the most important prognostic factor for survival in patients with GBM in the United States . Prognosis for patients with GBM is extremely poor because of high invasiveness of GBM.…”

Advances in the treatment of newly diagnosed glioblastoma

“…GB patients over the age of 65 years and those patients with a KPS less than or equal to 60 represent a clinically important group of patients that develop significant toxicity, and there is no prospective evidence of significant benefit from the EORTC-NCIC regimen in these patients. In two retrospective studies of newly diagnosed GB patients aged 65 years and older, including 291 and 237 GB patients respectively, patients with a good performance status (KPS 70 or greater) and a maximal tumor resection significantly benefitted from the EORTC-NCIC regimen [ 21 , 22 ]. The Nordic trial randomized patients aged 60 years and older to standard radiotherapy (60 Gy in 30 fractions), hypofractionated radiotherapy (34 Gy in 10 fractions), and standard adjuvant dosing of temozolomide, and demonstrated that hypofractionated radiotherapy and standard dose temozolomide alone were associated with better outcomes in patients over the age of 70 years compared to standard radiotherapy [ 23 ].…”

“…The ANOCEF trial demonstrated improved survival outcomes compared to historical outcomes for supportive care alone [ 24 ]. In the ANOCEF trial and the retrospective studies of elderly GB patients referenced above, MGMT promoter methylation was associated with superior survival outcomes [ 21 , 22 , 24 ]. The NOA-08 was a randomized phase III trial comparing dose-intense temozolomide versus standard radiotherapy in patients over the age of 65 years and those with a KPS greater than or equal to 60 [ 25 ].…”