Significance of molecular diagnostics for therapeutic decision-making in recurrent glioma

Abstract

Background Targeted therapies have substantially improved survival in cancer patients with malignancies outside the brain. Whether in-depth analysis for molecular alterations may also offer therapeutic avenues in primary brain tumors remains unclear. We herein present our institutional experience for glioma patients discussed in our interdisciplinary Molecular Tumor Board (MTB) implemented at the Comprehensive Cancer Center Munich (LMU). Methods We retrospectively searched the database of the MTB for all recurrent glioma patients after previous therapy. Recommendations were based upon next-generation sequencing results of individual patient’s tumor tissue. Clinical and molecular information, previous therapy regimens and outcome parameters were collected. Results Overall, 73 consecutive recurrent glioma patients were identified. In the median, advanced molecular testing was initiated with the third tumor recurrence. The median turnaround time between initiation of molecular profiling and MTB case discussion was 48 ± 75 days (range: 32 - 536 days). Targetable mutations were found for 50 recurrent glioma patients (68.5%). IDH1 mutation (27/73; 37%), EGFR amplification (19/73; 26%) and NF1 mutation (8/73; 11%) were the most detected alterations and a molecular-based treatment recommendation could be made for all of them. Therapeutic recommendations were implemented in 12 cases (24%) and one third of these heavily pretreated patients experienced clinical benefit with at least disease stabilization. Conclusion In-depth molecular analysis of tumor tissue may guide targeted therapy also in brain tumor patients and considerable anti-tumor effects might be observed in selected cases. However, future studies to corroborate our results are needed.

High costs, low quality of life, reduced survival, and room for improving treatment: an analysis of burden and unmet needs in glioma

“…Beyond avoiding toxicities, molecular diagnostics may increase the precision of diagnosis and treatment choice. While molecular profiling and targeting are still relatively new in clinical practice for glioma, several recent studies have supported the notion that molecularly guided therapy is feasible and provides clinical benefit, including in glioblastoma and recurrent glioma ( 24 , 200 , 201 ). A guideline on rational molecular testing of gliomas, glioneural, and neuronal tumors also argued for molecular testing to target therapy but cautioned that only a handful of targets had sufficient evidence available to justify testing for them in standard care ( 202 ).…”

Repeat surgery of recurrent glioma for molecularly informed treatment in the age of precision oncology: A risk–benefit analysis

“…To our knowledge, only one comparable analysis has been described in the literature. In a study by Blobner et al [31] the rate of actionable targets identified in glioma patients was 69%, but also included IDH mutations (30%), which was regarded as pre-known in our analysis, making the rate of 'novel' mutations similar in both studies (at about 40% to 50%). Of note, in the study by Blobner et al, only 17% of all patients (n = 72) could commence targeted therapy, which is slightly lower than our study (30%).…”

DSC-PWI presurgical differentiation of grade 4 astrocytoma and glioblastoma in young adults: rCBV percentile analysis across enhancing and non-enhancing regions

“…As we move further into the era of personalized and targeted therapies, the insights from our study could play an increasingly important role in shaping treatment strategies. This, in turn, hopefully will positively influence the disease course and enhance the quality of life for patients [ 3 – 6 ]. An illustrative example of potential clinical applicability of results in new patients with unknown diagnosis is shown in Fig.…”

“…This term is now reserved exclusively for IDH-wildtype grade 4 astrocytic tumors [1]. A noninvasive differentiation of these grade 4 astrocytic tumors could have significant implications for patient management [2][3][4][5][6][7]. Astrocytoma grade 4 has been less extensively studied compared to its grade 2-3 counterparts, remaining a major radiological challenge.…”