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

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 on 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%), epidermal growth factor receptor 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. Conclusions: In-depth molecular analysis of tumor tissue may guide targeted therapy also in brain tumor patients and considerable antitumor effects might be observed in selected cases. However, future studies to corroborate our results are needed.

Lessons learned: the first consecutive 1000 patients of the CCCMunichLMU Molecular Tumor Board.

PURPOSE: In 2016, the University of Munich Molecular Tumor Board (MTB) was implemented to initiate a precision oncology program. This review of cases was conducted to assess clinical implications and functionality of the program, to identify current limitations and to inform future directions of these efforts. METHODS: Charts, molecular profiles, and tumor board decisions of the first 1000 consecutive cases (01/2016-03/2020) were reviewed. Descriptive statistics were applied to describe relevant findings. RESULTS: Of the first 1000 patients presented to the MTB; 914 patients received comprehensive genomic profiling. Median age of patients was 56 years and 58% were female. The most prevalent diagnoses were breast (16%) and colorectal cancer (10%). Different types of targeted or genome-wide sequencing assays were used; most of them offered by the local department of pathology. Testing was technically successful in 88%. In 41% of cases, a genomic alteration triggered a therapeutic recommendation. The fraction of patients receiving a tumor board recommendation differed significantly between malignancies ranging from over 50% in breast or biliary tract to less than 30% in pancreatic cancers. Based on a retrospective chart review, 17% of patients with an MTB recommendation received appropriate treatment. CONCLUSION: Based on these retrospective analyses, patients with certain malignancies (breast and biliary tract cancer) tend to be more likely to have actionable variants. The low rate of therapeutic implementation (17% of patients receiving a tumor board recommendation) underscores the importance of meticulous follow-up for these patients and ensuring broad access to innovative therapies for patients receiving molecular tumor profiling.

Routine application of next-generation sequencing testing in uro-oncology-Are we ready for the next step of personalised medicine?

AIM OF THE STUDY: Next-generation sequencing (NGS) might represent a valuable diagnostic tool to identify somatic alterations and enable personalised medicine in uro-oncology. We aim to determine feasibility and impact of routine NGS in clinical practice. METHODS: Tumours from patients with genitourinary cancers were subjected to NGS. Results were discussed in a dedicated molecular tumour board. Statistical analyses included chi-square test and Mann-Whitney U test. RESULTS: Between 2017 and 2020, 65 patients with advanced genitourinary cancers were consecutively enrolled. Number of tests increased (28 tests in 2020) and diagnostic turnaround time for generating output decreased (17.5 days [range 13-35]). Median patient's age was 62 years (range 33-84), and most NGS assays were performed upon start of systemic treatment (range 0-6 of treatment lines). 62/66 sequenced samples generated a report. Fifty samples (80.6%) showed at least one molecular alteration. Most prevalent alterations were TP53 (32.3%), PIK3CA (14.5%) and TMPRSS2-ERG (9.7%). Sequencing revealed potentially druggable targets in 29 samples (46.8%). Based on NGS results, six patients underwent therapy change, whereas for three patients, coverage of recommended off-label therapy was denied by health insurances. CONCLUSIONS: NGS is increasingly feasible in clinical routine for patients with genitourinary cancers. Number of performed analyses is constantly growing, and turnaround time to therapy recommendation is decreasing. While the majority of tumours harbour clinically relevant mutations, alterations related to urologic cancers are underrepresented, thus treatment changes occurred only in a minority of patients. Further, access to target agents remains a considerable obstacle in the consequent implementation of precision uro-oncology.