Table 2.

US guided DOT clinical trials performed in > 100 subjects.

1 st Author	Year Pub.	Patients {lesions}	Objectives	Key Results
Zhu, Qu	2010	162 {173}	Differentiating Tis/T1 vs T2–4 cancer vs. benign	Thb > 2x greater cancer vs. benign, US-DOT: T1 cancer, sens 92 %, spec 93 %, PPV 81 %, NPV 97 % T2–T4 cancer, sens 75 %, spec 93 %, PPV 69 %, NPV 95 % THb threshold of 82 μM
Zhu, Qu	2016	288 {297}	Quantify THb for a wide range of malignant and benign diseases Compare breast cancer diagnosis of conventional US, DOT alone and in conjunction with conventional US Correlation THb, HbO2 and Hb with histologic, nuclear grades	Conventional US and DOT, sens 96.6 %–100 %, spec 77.3 %–83.3 %, PPV 52.7 %–59.4 %, NPV 99.0 %–100 % THb moderately correlated with tumor histologic grade and nuclear grade; HbO2 moderately correlated with tumor nuclear grade THb threshold of 80μM THb lower threshold (THb < 50 μM) was employed, biopsy recommendations for 4A and 4B lesions decreased by an average of 45 %
You, SS	2010	198 {214}	THb cancer vs. benign, operating characteristic	US-DOT: sens 83.9 %, spec 66.7 %, acc 72.6 %, PPV 75.6 %, NPV 77.1 %
Zhu, Qi	2011	205 {214}		11 % cancers were non-vascular but had elevated THb; 26 % of benign lesions were vascular by color Doppler but low THb
			Color Doppler vs. US-DOT	THb threshold of 140μM
Kim, MJ	2011	111 {122}	Inter-observer agreement	Interobserver agreement in BI-RADS final assessment with US and US-DOT (almost perfect; κ = 0.8618) was improved compared with US alone (substantial agreement, κ = 0.6574). AUC under the ROC curve did not show significant differences between US and combined US and US-DOT
Zhi, W	2012	102 {136}	Compare conventional US and US-guide DOT in differentiating malignant solid breast lesions vs. benign.	US and US-DOT: Sens 100 %, spec 93.9 %, PPV 91.5 %, 100 %, Acc 96.3 %
Zhi, W	2018	447 {455}	To investigate THC characteristics and its association with clinical pathologic findings	THb significantly greater in ER−, PR− than in ER+, PR + cancers (p = .005 and p = .01, respectively) and that cancers with axillary lymph node metastases or lymphovascular invasion had higher average THb (p = .042 and p = .043, respectively).