Development and Prospective Validation of an Ultrasound Prediction Model for the Differential Diagnosis of Benign and Malignant Subpleural Pulmonary Lesions: A Large Ambispective Cohort Study

Abstract

ObjectiveTo develop and prospective validate an ultrasound (US) prediction model to differentiate between benign and malignant subpleural pulmonary lesions (SPLs).MethodsThis study was conducted retrospectively from July 2017 to December 2018 (development cohort [DC], n = 592) and prospectively from January to April 2019 (validation cohort [VC], n = 220). A total of 18 parameters of B-mode US and contrast-enhanced US (CEUS) were acquired. Based on the DC, a model was developed using binary logistic regression. Then its discrimination and calibration were verified internally in the DC and externally in the VC, and its diagnostic performance was compared with those of the existing US diagnostic criteria in the two cohorts. The reference criteria were from the comprehensive diagnosis of clinical-radiological-pathological made by two senior respiratory physicians.ResultsThe model was eventually constructed with 6 parameters: the angle between lesion border and thoracic wall, basic intensity, lung-lesion arrival time difference, ratio of arrival time difference, vascular sign, and non-enhancing region type. In both internal and external validation, the model provided excellent discrimination of benign and malignant SPLs (C-statistic: 0.974 and 0.980 respectively), which is higher than that of “lesion-lung AT difference ≥ 2.5 s” (C-statistic: 0.842 and 0.777 respectively, P <0.001) and “AT ≥ 10 s” (C-statistic: 0.688 and 0.641 respectively, P <0.001) and the calibration curves of the model showed good agreement between actual and predictive malignancy probabilities. As for the diagnosis performance, the sensitivity and specificity of the model [sensitivity: 94.82% (DC) and 92.86% (VC); specificity: 92.42% (DC) and 92.59% (VC)] were higher than those of “lesion-lung AT difference ≥ 2.5 s” [sensitivity: 88.11% (DC) and 80.36% (VC); specificity: 80.30% (DC) and 75.00% (VC)] and “AT ≥ 10 s” [sensitivity: 64.94% (DC) and 61.61% (VC); specificity: 72.73% (DC) and 66.67% (VC)].ConclusionThe prediction model integrating multiple parameters of B-mode US and CEUS can accurately predict the malignancy probability, so as to effectively differentiate between benign and malignant SPLs, and has better diagnostic performance than the existing US diagnostic criteria.Clinical Trial Registrationwww.chictr.org.cn, identifier ChiCTR1800019828.

Can Ultrasound and Contrast-Enhanced Ultrasound Help Differentiate between Subpleural Focal Organizing Pneumonia and Primary Lung Malignancy?

“…Benign lesions are usually wedge-shaped, whereas malignant lesions are mostly spherical or irregular [ 22 ]. However, judgment of morphology is often subjective.…”

“…Blood supply forms were divided into single-phase wave arterial, three-phase wave arterial, venous, and mixed spectra. Based on other researchers’ investigations [ 22 ], we introduced the concept of the angle between the lesion border and thoracic wall. As long as one angle was obtuse, the lesion was classified as obtuse ( Figure 2 ).…”

“…The entry mode of the contrast medium was divided into five types at the beginning of the enhancement: (1) punctate type: one or more local areas of the lesion showed punctate enhancement; (2) centripetal type: enhancement began at the periphery of the lesion and gradually extended to the center; (3) diffuse type: the entire lesion was uniformly enhanced; (4) dendritic type: contrast agent microbubbles began at the base of the lesion and developed into dendritic vessels, which enhanced and gradually expanded; and (5) disordered and irregular type: unrestricted vessel-like enhancement at multiple places [ 22 , 23 ] ( Figure 3 ).…”

Utility of high-frequency B-mode and contrast-enhanced ultrasound for the differential diagnosis of benign and malignant pleural diseases: a prospective study

“…CEUS lacks the respiratory motion artifacts of Doppler US ( 14 ). Moreover, it facilitates parameter quantification using a time-enhancement curve, and it is good at distinguishing between benign and malignant diseases of the lung and liver ( 15 , 16 ). However, its diagnostic utility in terms of differentiating between benign and malignant thickened pleurae remains unclear.…”

Application of neck ultrasound in the diagnosis of sarcoidosis

“…Contrast-enhanced ultrasound (CEUS) is a new technique used for real-time assessment of tissue perfusion. It has been widely used to evaluate liver, kidney, pancreas, spleen, ovarian, thyroid, breast, prostate and even lung lesions in the current clinical practice [ 13 – 15 ]. It has been widely performed in identification of sentinel lymph node in breast cancer patients [ 16 – 19 ].…”