Table 3.

Case series with targeted therapy based on NGS screening.

Series	Approach	Therapy decision criteria	Outcome parameters	Results/Signs of activity	Comment
Lazaridis et al. [126]	Retrospective, mostly 2nd relapse n = 41 gliomas screened, 36/41 with actionable target, 18/36 with targeted therapy	NGS panel, IHC panel, Seq (TERT), FISH (CCDKN2A/B) Known BBB penetration Molecular tumor board decision	PFS/OS of 16 rGBM with vs. 16 without targeted therapy	mPFS 3.8 vs. 2.0 months PFS6 25 vs. 20% mOS 13 vs. 4 months (P < 0.05) High PFS > 7 months and PFS2‐PFS1 > 5 months in Dabrafenib/trametinib (n = 2) Cabozantinib (n = 2)	Reproduced the known activity of BRAF inhibitors Median 1 prior treatment Precision therapy aspect of Cabozantinib difficult to analyze due to the multikinase activity including VEGFR inhibition
Renovanz et al. [122]	Prospective n = 262 GBM screened, 41 treated based on NGS results, 36 evaluable for response	NGS panel, RNA seq, IHC panel Biomarker‐guided ranked molecular tumor board decision	PFS2/PFS1 ratio ≥ 1.3 MCBS score	mPFS 2.5 months 13/36 with PFS2/PFS1 > 1.3 3/6 mTOR‐pathway/everolimus 3/4 FGFR‐TACC fusion/erdafitinib 3/4 FLT missense or EGFR amp/regorafenib 1/5 EGFR/afatinib 1/5 TMB/nivolumab 2/8 EGFR amp + missense/ABT414 MCBS score 1 (PFS ≥ 6 months, or ORR > 60% or ORR 20–60% and DoR ≥ 9 months) in n = 5 (2 × Everolimus, 2 × Erdafitinib, 1 × ABT414)	Some signs of activity with FGFR‐fusion or mTOR‐directed therapy > 2 lines of prior treatment Large cohort, also reporting on other CNS tumor entities
Blumenthal et al. [124]	Retrospective n = 43 (GBM, AA), 41/43 with actionable targets, 13/43 treated	NGS panel Treatment decision by physician's choice	Response, duration of treatment, mOS	no response with EGFR, MEK, CDK4/6, or mTOR‐directed therapy mOS 4.6 months, longest OS 10 months (EGFR‐directed afatinib)	No clear signs of activity, even with combination treatment Median 1 prior treatment Small and heterogenous cohort
Byron et al. [125]	Prospective 16/20 patients analyzed 13/16 with IDHwt GBM	WES RNA seq IHC panel Molecular tumor board decision	PFS, feasibility: molecularly based treatment decision within 35 days	15/16 recommendations within time frame 7/16 received recommended therapy PFS ~ 3 months n = 1 GBM with PFS > 12 months; PFS2/PFS1 = 3.7: Olaparib, trametinib and carboplatin	Feasibility of approach shown Sign of activity in a single GBM patient
Padovan et al. [123]	Retrospective N = 417 GBM screened, 343 with actionable targets, 36 with targeted therapy	NGS panel Clinical trials or off‐label compassionate use, decision criteria not reported	PFS2/PFS1 ratio ≥ 1.3 Objective response rate (PR + CR)	mPFS 2.1 months 7/36 with PFS2/PFS1 > 1.3 4/9 dabrafenib/trametinib 2/4 FGFR3/erdafitinib 1/1 MET/capmatinib 0/1 ROS1/entrectinib 3 objective responses (2 dabrafenib/trametinib, 1 entrectinib)	Largest GBM cohort Reproduced known activity of BRAF inhibitors Starting form second‐line treatment Median of targeted therapy lines was 3