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Updated: Sep 1, 2025
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Precision neuro-oncology: a pilot analysis of personalized treatment in recurrent glioma
Lazaros Lazaridis1,2,3,4, Teresa Schmidt1,2,3,4, Christoph Oster1,2,3,4
1Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Division of Clinical Neurooncology, University Medicine Essen, University Duisburg-Essen, Essen, Germany.
Purpose:
When brain cancer relapses, treatment options are scarce. The use of molecularly matched targeted therapies may provide a feasible and efficacious way to treat individual patients based on the molecular tumor profile. Since little information is available on this strategy in neuro-oncology, we retrospectively analyzed the clinical course of 41 patients who underwent advanced molecular testing at disease relapse.
Methods:
We performed Sanger sequencing, targeted next generation sequencing, and immunohistochemistry for analysis of potential targets, including programmed death ligand 1, cyclin D1, phosphorylated mechanistic target of rapamycin, telomerase reverse transcriptase promoter mutation, cyclin-dependent kinase inhibitor 2A/B deletion, or BRAF-V600E mutation. In selected patients, whole exome sequencing was conducted.
Results:
The investigation included 41 patients, of whom 32 had isocitrate dehydrogenase (IDH) wildtype glioblastoma. Molecular analysis revealed actionable targets in 31 of 41 tested patients and 18 patients were treated accordingly (matched therapy group). Twenty-three patients received molecularly unmatched empiric treatment (unmatched therapy group). In both groups, 16 patients were diagnosed with recurrent IDH wildtype glioblastoma. The number of severe adverse events was comparable between the therapy groups. Regarding the IDH wildtype glioblastoma patients, median progression-free survival (mPFS) and median overall survival (mOS) were longer in the matched therapy group (mPFS: 3.8 versus 2.0 months, p = 0.0057; mOS: 13.0 versus 4.3 months, p = 0.0357).
Conclusion:
These encouraging data provide a rationale for molecularly matched targeted therapy in glioma patients. For further validation, future study designs need to additionally consider the prevalence and persistence of actionable molecular alterations in patient tissue.
Insights
Molecularly matched targeted therapy shows promise for relapsed brain cancer. Patients receiving matched therapy for IDH wildtype glioblastoma had significantly longer progression-free and overall survival compared to those receiving unmatched treatment.
Area of Science:
- Neuro-oncology
- Genomics
- Targeted Therapy
Background:
- Treatment options for relapsed brain cancer are limited.
- Molecularly matched targeted therapy offers a personalized approach based on tumor molecular profiles.
- Limited data exists on this strategy in neuro-oncology.
Purpose of the Study:
- To retrospectively analyze the clinical outcomes of patients with relapsed brain cancer treated with advanced molecular testing.
- To evaluate the efficacy of molecularly matched targeted therapy compared to unmatched empiric treatment.
Main Methods:
- Performed Sanger sequencing, targeted next-generation sequencing, and immunohistochemistry for molecular analysis.
- Analyzed potential targets including PD-L1, cyclin D1, p-mTOR, TERT promoter mutation, CDKN2A/B deletion, and BRAF-V600E.
- Conducted whole exome sequencing in select patients.
Main Results:
- Actionable targets were identified in 31 of 41 patients.
- 18 patients received molecularly matched therapy, while 23 received unmatched empiric treatment.
- In IDH wildtype glioblastoma patients, matched therapy showed significantly longer median progression-free survival (3.8 vs. 2.0 months) and median overall survival (13.0 vs. 4.3 months).
Conclusions:
- Molecularly matched targeted therapy is a promising strategy for glioma patients.
- Further validation is needed, considering the prevalence and persistence of actionable molecular alterations.
