IDH mutation + NTRK fusion

F1L detection increased from 5.8% (zero factors) to 32.8% (four factors), approximating tissue at three factors. The utility of liquid biopsy can be maximized by carefully selecting samples on the basis of conditions that increase the detection rate.

However, recent strides in molecularly targeted therapies have led to landmark FDA approvals, including agents such as vorasidenib for IDH-mutant gliomas, the combination of dabrafenib trametinib for BRAF mutated tumors, and TRK inhibitors for NTRK fusion-positive tumors. While conventional treatments like surgery, radiation, and chemotherapy remain the standard of care for gliomas, the integration of molecular-driven therapies is beginning to shape clinical management strategies. This article explores the evolving role of molecularly targeted treatments in adult primary brain tumors, examining their current applications and future potential.

The availability of molecular markers for gliomas is widespread among Italian centers. The implementation of the molecular criteria for diagnostic and prognostic purposes in gliomas according to WHO 2021 Classification needs to be improved. Moreover, a critical issue for the future will be the search for rare actionable mutations, which is continuously evolving, in light of the use of targeted therapy.

Although the addition of modified FOLFOX (fluorouracil, leucovorin, and oxaliplatin) to active symptom control improved the overall survival of patients with progressing advanced BTC despite gemcitabine plus cisplatin treatment, its efficacy was modest. This review delineates the evolution of systemic therapies in patients with pretreated advanced BTC. By examining past developments and recent advances through prospective trials, it highlights novel approaches that may improve outcomes in this challenging disease.

P2, N=27, Active, not recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

They include larotrectinib/entrectinib/repotrectinib (NTRK fusions), selpercatinib (RET fusions), dabrafenib/trametinib (BRAFV600E mutations), pembrolizumab/dostarlimab (microsatellite instability), pembrolizumab (high tumor mutational burden), and trastuzumab deruxtecan (HER2 3+ expression) (all solid cancers). Pemigatinib is approved for FGFR1-rearranged myeloid/lymphoid neoplasms...For example, BRAFV600E and IDH1/2 mutations; ALK, FGFR, and NTRK fusions; PD-L1 amplification; and CD70 antigens are druggable in both solid and blood malignancies by gene-/immune-targeted therapies/chimeric antigen receptor T cells. Future biomarker-based tissue-agnostic basket studies/approvals should bridge the great divide and include both solid and hematologic cancers.

MGMT promoter methylation testing is the most established molecular marker for response to temozolomide in IDH wild-type glioblastoma and in turn impacts overall survival. Moreover, identification of certain mutations and molecular markers, such as BRAF V600E, hypermutation or elevated tumor-mutational burden and NTRK fusions allow for the use of FDA approved agents that are tumor-agnostic. Finally, molecular testing opens options for clinical trials that are essential for diseases with limited treatment options like gliomas.

Overall, our results suggest that the all-in-one bimodal DNA/RNA panel is reliable for detecting diagnostic gene alterations in accordance with the latest WHO classification. The integrative pathological and molecular strategy could be valuable in confirmation of diagnosis and selection of treatment options for brain tumors.