Maximum resection and immunotherapy improve glioblastoma patient survival: a retrospective single-institution prognostic analysis

Eiichi Ishikawa,Takao Tsurubuchi,Hidehiro Kohzuki,Hiroyoshi Akutsu,Masashi Mizumoto,Masahide Matsuda,Hideyuki Sakurai,Akira Matsumura,Shingo Takano,Narushi Sugii

doi:10.1186/s12883-021-02318-1

Abstract

Glioblastoma (GBM) is a refractory disease with a poor prognosis and various methods, including maximum resection and immunotherapy, have been tested to improve outcomes. In this retrospective study we analyzed the prognostic factors of 277 newly diagnosed GBM patients over 11 years of consecutive cases at our institution to evaluate the effect of these methods on prognosis. Various data, including the extent of removal (EOR) and type of adjuvant therapy, were examined and prognostic relationships were analyzed. The median overall survival (OS) of the entire 277-case cohort, 200 non-biopsy cases, and 77 biopsy cases was 16.6 months, 19.7 months, and 9.7 months, respectively. Gross total removal (GTR; 100% of EOR) was achieved in 32.9% of the cases. Univariate analysis revealed younger age, right side, higher Karnofsky performance status, GTR, intraoperative magnetic resonance imaging (MRI) use for removal, proton therapy, combination immunotherapy, and discharge to home as good prognostic factors. Intraoperative MRI use and EOR were closely related. In the multivariate analysis, GTR, proton therapy, and a combination of immunotherapies, including autologous formalin-fixed tumor vaccine, were the significant prognostic factors. A multivariate analysis of 91 GTR cases showed that immunotherapy contributed to prognostic improvements. The median OS and 5-year OS % values were 36.9 months and 43.3% in GTR cases receiving immunotherapy. In conclusion, GTR, proton therapy, and immunotherapy were good prognostic factors in single-center GBM cases. Tumor vaccine therapy for GTR cases achieved a notably high median survival time and long-term survival ratio, indicating its usefulness in GTR cases.

Highlights

Glioblastoma (GBM) is generally a refractory disease with a poor prognosis for the majority of patients [1]
Ishikawa et al BMC Neurol (2021) 21:282 In March 2013, we started a double-blinded, randomized phase IIb/III trial of autologous formalin-fixed tumor vaccine (AFTV) with standard chemotherapy and temozolomide (TMZ) for newly diagnosed GBM to evaluate the efficacy of AFTV for prevention of recurrence and/ or cure of residual tumor burden (UMIN000010602) [13] and, since October 2020, GBM patients who had grosstotal removal (GTR), resulting in no residual gadolinium enhancement, or subtotal removal (STR) are enrolled in a double-blinded, randomized phase III trial of AFTV
Univariate analysis revealed that younger age, right side, higher Karnofsky Performance Status (KPS), GTR, intraoperative magnetic resonance imaging (MRI) use for removal, p53 status, proton therapy, combination immunotherapy, and discharge to home were good prognostic factors

Summary

Introduction

Glioblastoma (GBM) is generally a refractory disease with a poor prognosis for the majority of patients [1]. In March 2013, we started a double-blinded, randomized phase IIb/III trial of autologous formalin-fixed tumor vaccine (AFTV) with standard chemotherapy and temozolomide (TMZ) for newly diagnosed GBM to evaluate the efficacy of AFTV for prevention of recurrence and/ or cure of residual tumor burden (UMIN000010602) [13] and, since October 2020, GBM patients who had grosstotal removal (GTR), resulting in no residual gadolinium enhancement, or subtotal removal (STR) are enrolled in a double-blinded, randomized phase III trial of AFTV. In a double-blinded, randomized phase II trial of dendritic cell vaccine ICT-107, GBM patients who had undergone GTR, resulting in no residual gadolinium enhancement, or STR were enrolled. In a phase 3 trial of autologous tumors featuring lysate-pulsed, dendritic cell vaccine (DCVax®-L) with standard therapy for newly diagnosed GBM, 63% of enrolled cases were GTR cases [17] and the median overall survival (OS) of the overall ITT population (according to blinded interim data) was 23.1 months from the time of surgery. None of the currently published papers examines the superiority of immunotherapies in a phase III clinical study

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