Pan-TRK positive uterine sarcoma in immunohistochemistry without neurotrophic tyrosine receptor kinase gene fusions: A case report

Table 1 Oncologic outcomes of TRK inhibitors in NTRK gene fusion positive tumors

Ref.	TRKi	Sample size	Tumor type	Objective response rate (%)	Duration of response (months)	Progression free survival (months)	Overall survival (months)
Demetri et al[9]	Entrectinib	121	Sarcoma, salivary, NSCLC, etc.	61.2	20 (95%CI: 13.0-38.2)	13.8 (95%CI: 23.4-46.4)	33.8 (95%CI: 23.4-46.4)
	Entrectinib	26	Sarcoma	57.7	15.0 (95%CI: 4.6-NE)	10.1 (95%CI: 6.3-13.7)	18.7 (95%CI: 14.5-NE)
Drilon[10]	Larotrectinib	122	Salivary, infantile fibrosarcoma, thyroid cancer, lung cancer, etc.	81	Not reached	Not reached	Not reached
	Entrectinib	54	Sarcoma, lung cancer, mammary analogue secretory carcinoma, etc.	58	10.4	11.2	20.9
Suh et al[11]	Larotrectinib	23	Soft tissue sarcoma	52.2		Not reached	Not reached
	Entrectinib	16	Soft tissue sarcoma	56.3		10.1	16.8
Demetri et al[12]	Larotrectinib	71	Sarcoma, salivary, NSCLC, etc.	87 (95%CI: 77-94)	Not reached	28.3 (95%CI: 16.8-NE)	44.4 (95%CI: 44.4-NE)
	Entrectinib	13	Sarcoma, NSCLC, salivary, breast, thyroid	46 (95%CI: 19-75)	10.3 (95%CI: 4.6-15.0)	11.0 (95%CI: 6.5-15.7)	16.8 (95%CI: 10.6-20.9)

TRKi: Tyrosine receptor kinase inhibitor; NSCLC: Non-small cell lung cancer; CI: Confidence interval; NE: Non-estimable.

Table 2 Comparison of neurotrophic tyrosine receptor kinase diagnostic tools[14,17]

	Sensitivity	Specificity	Detection of all fusions	Detection of fusion partner	Detection of protein expression	Turnaround time	Material required
IHC	Relatively high (NTRK1 and 2: 75%-96%, NTRK3: 50%-70%)	Relatively high	+	-	+	1 day	1 unstained slide
FISH	High	High	One per probe	One per probe	-	1-3 days	3 unstained slide
RNA NGS	High	High	+	+	+	2-4 weeks	15 unstained slide
DNA NGS	Moderate	High	+	+	-	2-4 weeks	10 unstained slide

NTRK: Neurotrophic tyrosine receptor kinase; NGS: Next-generation sequencing; IHC: Immunohistochemistry; FISH: Fluorescent in situ hybridization.