What Test
Should I Order?

Aiding in establishing diagnosis/stratification

EGFR, ALK, ROS1, BRAF, MET exon 14 skipping, RET, PD-L1, (category 1)
-KRAS (especially G12C), NTRK 1/2/3, ERBB2 mut/amplification, MET amplification, TMB, RET, TP53, KEAP1, STK11, NF1, SETD2, RBM10, ARID1A, PIK3CA, SMARCA4, RB1, CDKN2A, PTEN, AKT1
Fusions: CD74–NRG1, SLC3A2–NRG1, EZR–ERBB4, TRIM24–BRAF, and KIAA1468–RET

NCCN Recommendation: EGFR, ALK, ROS1, BRAF, MET exon 14 skipping, RET, PD-L1, (category 1)
-KRAS (especially G12C), NTRK 1/2/3, ERBB2 mut/amplification, MET amplification, TMB, RET

Prognosis

EGFR, ALK, ROS1, BRAF, MET exon 14 skipping, RET, PD-L1, (category 1)
-KRAS (especially G12C), NTRK 1/2/3, ERBB2 mut/amplification, MET amplification, TMB, RET, TP53, KEAP1, STK11, NF1, SETD2, RBM10, ARID1A, PIK3CA, SMARCA4, RB1, CDKN2A, PTEN, AKT1
Fusions: CD74–NRG1, SLC3A2–NRG1, EZR–ERBB4, TRIM24–BRAF, and KIAA1468–RET

Prognosis is based on predicting response to specific therapy

Selecting therapy

EGFR, ALK, ROS1, BRAF, MET exon 14 skipping, RET, PD-L1, (category 1)
-KRAS (especially G12C), NTRK 1/2/3, ERBB2 mut/amplification, MET amplification, TMB, RET, TP53, KEAP1, STK11, NF1, SETD2, RBM10, ARID1A, PIK3CA, SMARCA4, RB1, CDKN2A, PTEN, AKT1
Fusions: CD74–NRG1, SLC3A2–NRG1, EZR–ERBB4, TRIM24–BRAF, and KIAA1468–RET

Targeted mutations: EGFR, BRAF, KRAS(G12C), TMB, PIK3CA, PTEN, AKT1
Targetable fusions: ALK, RET, ROS1, NTRK1, NRG1, ERBB4, BRAF, FGFR

Follow-up and minimal residual disease (MRD)

Mutations: EGFR, TP53, KEAP1, STK11, NF1, SETD2, RBM10, ARID1A, PIK3CA, SMARCA4, RB1, CDKN2A, PTEN, AKT1

Plasma-based testing should be considered at progression on EGFR TKIs for the T790M mutation.
-Minimal residual disease and relapse