Role of imaging biomarkers in mutation-driven non-small cell lung cancer

Table 1 Targetable genotypes in non-small cell lung cancer with Food and Drug Administration-approved targeted therapies

Molecular alteration	Approved targeted therapies
EGFR	Afatinib
	Dacomitinib
	Erlotinib
	Gefitinib
	Osimertinib
ALK	Alectinib
	Brigatinib
	Ceritinib
	Crizotinib
	Lorlatinib
ROS1	Crizotinib
	Entrectinib
BRAF	Dabrafenib + trametinib
NTRK	Larotrectinib
	Entrectinib

EGFR: Epidermal growth factor receptor; ALK: Anaplastic lymphoma kinase; ROS1: c-ROS oncogene 1; NTRK: Neurotrophic receptor tyrosine kinase.

Table 2 Commonly used platforms for detection of mutations in non-small cell lung cancer

Testing technique	High sensitivityin detecting	Lower sensitivityin detecting
Direct gene sequencing		BRAF
Requires high tumor cellularity		EGFR
Largely replaced by newer techniques		HER2
		KRAS
Allele specific sequencing	BRAF
Detects predefined abnormalities	EGFR
Allows for multiplex testing	HER2
	KRAS
	METex14 skipping
Next Generation sequencing	BRAF	ALK
Can detect novel mutations	EGFR	RET
Allows for multiplex testing	HER2	ROS1
Can be costly and time consuming	KRAS	NTRK
	METex14 skipping	MET amplification
Fluorescent in situ hybridization	ALK
	RET
	ROS1
	NTRK
	MET amplification
Immunohistochemistry Also used to detect PD-L1 protein expression	ALKROS1	NTRK fusion

Table 3 Summary of reported clinicopathologic biomarkers in select molecular genotypes in non-small cell lung cancer¹

Clinicopathologic features	EGFR-mutant	ALK-rearranged	ROS1-rearranged	BRAF V600E-mutant	MET exon 14 skipping
Age	Younger	Younger	Younger	No specific age predilection	Older compared to another mutated NSCLC
Race	More common in Asian populations	More common in Caucasian populations	No specific racial predilection	No specific racial predilection	No specific racial predilection
Smoking history	Minimal to no smoking history	Minimal to no smoking history	Minimal to no smoking history	Minimal to no smoking history; positive smoking history in non-V600E mutation	Both smokers and non-smokers
Tumor histology	Adenocarcinoma	Adenocarcinoma	Adenocarcinoma	Adenocarcinoma	Increased incidence of METex14 skipping with sarcomatoid histology

¹Data collected from several sources[40,54,63,65,66,71].

Table 4 Summary of reported imaging biomarkers in select molecular genotypes in non-small cell lung cancer¹

Imaging feature	EGFR mutation	ALK rearrangement	ROS1 rearrangement	METex14 skipping mutation
Primary tumor	Increased ground-glass components	Purely solid lesion	Purely solid lesion	Multifocal primary lung cancers
	Presence of air bronchograms (pneumonic appearance)
		Peripheral predilection	Peripheral predilection	Peripheral predilection
Metastatic patterns	Diffuse lung metastases	Lymphangitic carcinomatosis	Lymphangitic carcinomatosis	Oligometastatic disease
		Pleural and pericardial metastasis	Pleural metastases
		Intrathoracic and distant lymphadenopathy	Intrathoracic and distant lymphadenopathy
	Lytic bone metastases	Sclerotic bone metastases	Sclerotic bone metastases	Lytic bone metastases
	High rates of brain metastases	High rates of brain metastases	High rates of brain metastases, but lower compared to EGFR and ALK	High rates of brain metastases, but lower compared to EGFR and ALK

¹Data collected from several sources[54,63,65,66,71]. EGFR: Epidermal growth factor receptor; ALK: Anaplastic lymphoma kinase.