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. 2022 Nov 9;14(22):5510.
doi: 10.3390/cancers14225510.

Management of Recurrent Glioblastomas: What Can We Learn from the French Glioblastoma Biobank?

Anne Clavreul  1   2 , Lila Autier  3   4 , Jean-Michel Lemée  1   2 , Paule Augereau  4 , Gwénaëlle Soulard  1 , Luc Bauchet  5   6 , Dominique Figarella-Branger  7   8 , Philippe Menei  1   2 , Fgb Network; Collaborators of the FGB network
Collaborators, Affiliations

Management of Recurrent Glioblastomas: What Can We Learn from the French Glioblastoma Biobank?

Anne Clavreul et al. Cancers (Basel). .

Abstract

Safe maximal resection followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ) is universally accepted as the first-line treatment for glioblastoma (GB), but no standard of care has yet been defined for managing recurrent GB (rGB). We used the French GB biobank (FGB) to evaluate the second-line options currently used, with a view to defining the optimal approach and future directions in GB research. We retrospectively analyzed data for 338 patients with de novo isocitrate dehydrogenase (IDH)-wildtype GB recurring after TMZ chemoradiotherapy. Cox proportional hazards models and Kaplan-Meier analyses were used to investigate survival outcomes. Median overall survival after first surgery (OS1) was 19.8 months (95% CI: 18.5-22.0) and median OS after first progression (OS2) was 9.9 months (95% CI: 8.8-10.8). Two second-line options were noted for rGB patients in the FGB: supportive care and treatments, with systemic treatment being the treatment most frequently used. The supportive care option was independently associated with a shorter OS2 (p < 0.001). None of the systemic treatment regimens was unequivocally better than the others for rGB patients. An analysis of survival outcomes based on time to first recurrence (TFR) after chemoradiotherapy indicated that survival was best for patients with a long TFR (≥18 months; median OS1: 44.3 months (95% CI: 41.7-56.4) and median OS2: 13.0 months (95% CI: 11.2-17.7), but that such patients constituted only a small proportion of the total patient population (13.0%). This better survival appeared to be more strongly associated with response to first-line treatment than with response to second-line treatment, indicating that the recurring tumors were more aggressive and/or resistant than the initial tumors in these patients. In the face of high rates of treatment failure for GB, the establishment of well-designed large cohorts of primary and rGB samples, with the help of biobanks, such as the FGB, taking into account the TFR and survival outcomes of GB patients, is urgently required for solid comparative biological analyses to drive the discovery of novel prognostic and/or therapeutic clinical markers for GB.

Keywords: IDH wild-type; prognosis; recurrent glioblastoma; reoperation; survival; systemic treatment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Second-line options and systemic treatment regimens used, by TFR: short TFR (≤6 months), intermediate TFR (7 to 17 months) and long TFR (≥18 months). (A) Frequency of five types of second-line options (supportive care, repeat radiotherapy, reoperation, systemic treatment alone or inclusion in a clinical trial) in the short TFR, intermediate TFR and long TFR groups. (B) Frequency of the six main types of systemic treatment regimen used (TMZ, nitrosourea, bevacizumab, bevacizumab plus TMZ, bevacizumab plus nitrosourea and bevacizumab plus irinotecan) in the short TFR, intermediate TFR and long TFR groups. Abbreviations: TFR, time to first recurrence; TMZ, temozolomide.
Figure 2
Figure 2
Kaplan–Meier curves for survival stratified for TFR: short TFR (≤6 months, n = 210), intermediate TFR (7 to 17 months, n = 84) and long TFR (≥18 months, n = 44). (A) PFS1, (B) OS1, (C) PFS2, and (D) OS2. Abbreviations: OS1, overall survival after first surgery; OS2, overall survival after first progression; PFS1, progression-free survival after first surgery; PFS2, progression-free survival after first progression; TFR, time to first recurrence.
Figure 3
Figure 3
Survival outcomes for patients on systemic treatment. (A,B) Kaplan–Meier curves for survival stratified for systemic treatment with reoperation (n = 32) and systemic treatment without reoperation (n = 195) ((A) PFS2; (B) OS2). (C,D) Kaplan–Meier curves for survival stratified for the six most frequent systemic treatment regimens: TMZ rechallenge (n = 32), nitrosourea monotherapy (n = 32), bevacizumab alone (n = 36) or combined with TMZ (n = 14), nitrosourea (n = 80) and irinotecan (n = 33) ((C) PFS2; (D) OS2). Abbreviations: OS2, overall survival after first progression; PFS2, progression-free survival after first progression; TMZ, temozolomide.
Figure 4
Figure 4
Kaplan–Meier curves for survival stratified for reoperation with Gliadel® (n = 26) and reoperation with systemic treatment (n = 32) ((A) PFS2; (B) OS2). Abbreviations: OS2, overall survival after first progression; PFS2, progression-free survival after first progression.
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