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

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.

Effects of Reoperation Timing on Survival among Recurrent Glioblastoma Patients: A Retrospective Multicentric Descriptive Study

“…A few studies and one meta-analysis did examine time dependence of reoperation [88][89][90][91] but yielded no clear conclusion. Only recently, the work by Clavreul et al published in 2022 evaluated time to the first recurrence by analyzing patients from French glioblastoma biobanks, also showing better outcomes in patients defined as having long (≥18 months) times after the initial surgery (13.0% of all 338 included patients) [92]. Our cohort validates their observation, although they cannot be completely comparable groups of patients.…”

Classification and Application of the Personalized Glioblastoma Organoids

“…Even though, in French, a glioblastoma biobank existed which is able to analyze and share the data about the second-line therapies of glioblstoma currently used in clinical situations regardless of the exact effect of these therapies, this biobank contribute a lot in providing suggestions or evaluation results to the clinical second-line therapy [4]. However, obviously, the glioblastoma biobank still maintains several points out of reach, such as the lack of appropriate models can be used for evaluating the effect of certain therapy before applying it on the patient which show none benefit to promote individualized therapy.…”

“…Newly diagnosed patients usually maintain satisfactory treatment outcomes after the surgery followed by the chemo and radiotherapy, however, even though those therapies were proved to be effective in prolonging patients' lives, the possibilities of tumor recurrence or even death after first-line or secondline therapy [3], which account for a larger proportion of all the patients, which can be reflect in the investigation of the survival outcomes. The median overall survival after first-line surgery is approximately twice about that of second-line surgery [4].The decreasing of the median survival after first therapy progression compared with the counterpart after second-line surgery, also indicates the aggressiveness and refractory property of the recurrent glioblastoma.…”

A comparison study of dynamic [18F]Alfatide II imaging and [11C]MET in orthotopic rat models of glioblastoma

“…Glioblastoma multiforme (GBM), the most malignant form of astrocytoma, represents a paramount challenge in neuro-oncology due to its aggressive spreading growth pattern and complex pathophysiology (Burko et al 2023 ; Wang et al 2023 ). The current standard treatment modalities for GBM include surgical resection followed by adjuvant radiation therapy and chemotherapy with temozolomide (Clavreul et al 2022 ; Raue et al 2023 ). Despite these interventions, the clinical outcome for GBM patients remains poor (Petkovic et al 2023 ).…”