4 Glioma (GBM, IDH-wildtype) — Caso MTB

library(readr); library(dplyr); library(gt)
som <- read_csv("data/gbm_variants_somatic.csv")
germ <- read_csv("data/gbm_variants_germline.csv")

```{{=include}} templates/clinical_gbm.md

gt(som) |> tab_caption("GBM-01 — Somatic variants (tiering AMP/ASCO/CAP, ESCAT)")

GBM-01 — Somatic variants (tiering AMP/ASCO/CAP, ESCAT)
gene	variant_cDNA	variant_protein	effect	vaf	depth	copy_number	tier_amp_ascocap	escat	evidence_summary
EGFR	EGFRvIII (ex2-7 del)	p.Glu6_Ala273del	Oncogenic activation	0.21	450	12	Tier IA (biomarker)	II-B	Common GBM driver; investigational EGFRvIII-directed trials.
EGFR	amplicon	—	Amplification	NA	NA	12	Tier IA (biomarker)	II-B	High-level amplification; supports EGFR-targeted trial eligibility.
TERT	c.-124C>T (C228T)	promoter	Promoter activation	0.28	600	NA	Tier IIIC	Not ranked	Prognostic; not directly actionable.
PTEN	c.389G>A	p.R130Q	Loss-of-function	0.34	520	loss	Tier IIC	III	PI3K/AKT pathway activation; no approved targeted therapy in GBM.
CDKN2A/B	homozygous deletion	—	Loss-of-function	NA	NA	0 copies	Tier IIIC	III	Cell-cycle deregulation; may inform CDK pathway trial eligibility.
NF1	c.2033C>A	p.S678*	Truncating	0.12	480	NA	Tier IIIC	III	RAS/MAPK activation; occasional MEK inhibitor trials.
PDGFRA	gain	—	Copy number gain	NA	NA	4	Tier IIIC	III	May expand RTK pathway trial options.

gt(germ) |> tab_caption("GBM-01 — Variant-like segnali germinali (non validati, da confermare)")

GBM-01 — Variant-like segnali germinali (non validati, da confermare)
gene	variant_cDNA	variant_protein	classification	reportable	note
CHEK2	c.470T>C	p.I157T	VUS (research-only)	No	Detected on tumor-only; do not return clinically without matched normal.
DPYD	none	—	No pathogenic variants	N/A	No fluoropyrimidine toxicity alleles observed.

Avviso

Caveat tumor-only — eventuali VUS non vanno riportati clinicamente; serve conferma su sangue/saliva in caso di sospetto germinale.

Biomarker / Profilo	Farmaco / Strategia	Setting	Evidenza / Note 2025
EGFR amp + vIII	Trial con inibitori EGFR/RTK	Recidiva / arruolamento trial	Opzione più promettente se disponibile trial; nessun standard consolidato.
MET (amp / exon14 / fusioni)	Tepotinib, Capmatinib, Vebreltinib (solo in trial)	Recidiva con alterazione MET	Segnali clinici di beneficio (casi e basket trial). Priorità alta se presente.
ALK / ROS1 / NTRK fusioni	Lorlatinib (ALK/ROS1), Entrectinib / Larotrectinib (ROS1/NTRK)	Recidiva; preferibilmente trial	Risposte documentate in case report. Uso sperimentale o off-label selezionato.
Nessun target disponibile	Regorafenib	Recidiva non eleggibile a trial	Efficacia e tollerabilità confermate; opzione sistemica di riferimento.
Edema / sintomi severi	Bevacizumab	Palliativo / in combinazione	Controllo sintomi e riduzione steroidi; non migliora OS.
IO (CPS~10, MSS, TMB-low)	Anti-PD-1/PD-L1 (solo trial)	Sperimentale	Razionale debole in assenza di ipermutazione; non standard.