Value of turbo spin echo-based diffusion-weighted imaging in the differential diagnosis of benign and malignant solitary pulmonary lesions.

To quantitatively assess the diagnostic efficacy of multiple parameters derived from multi-b-value diffusion-weighted imaging (DWI) using turbo spin echo (TSE)-based acquisition techniques in patients with solitary pulmonary lesions (SPLs). A total of 105 patients with SPLs underwent lung DWI using single-shot TSE-based acquisition techniques and multiple b values. The apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM) parameters, and lesion-to-spinal cord signal intensity ratio (LSR), were analyzed to compare the benign and malignant groups using the Mann-Whitney U test and receiver operating characteristic analysis. The Dstar values observed in lung cancer were slightly lower than those observed in pulmonary benign lesions (28.164 ± 31.950 versus 32.917 ± 34.184; Z = -2.239, p = 0.025). The LSR values were significantly higher in lung cancer than in benign lesions (1.137 ± 0.581 versus 0.614 ± 0.442; Z = - 4.522, p < 0.001). Additionally, the ADC800, ADCtotal, and D values were all significantly lower in lung cancer than in the benign lesions (Z = - 5.054, -5.370, and -6.047, respectively, all p < 0.001), whereas the f values did not exhibit any statistically significant difference between the two groups. D had the highest area under the curve (AUC = 0.887), followed by ADCtotal (AUC = 0.844), ADC800 (AUC = 0.824), and LSR (AUC = 0.789). The LSR, ADC800, ADCtotal, and D values did not differ statistically significantly in diagnostic effectiveness. Lung DWI using TSE is feasible for differentiating SPLs. The LSR method, conventional DWI, and IVIM have comparable diagnostic efficacy for assessing SPLs.

Attention pyramid pooling network for artificial diagnosis on pulmonary nodules.

The development of automated tools using advanced technologies like deep learning holds great promise for improving the accuracy of lung nodule classification in computed tomography (CT) imaging, ultimately reducing lung cancer mortality rates. However, lung nodules can be difficult to detect and classify, from CT images since different imaging modalities may provide varying levels of detail and clarity. Besides, the existing convolutional neural network may struggle to detect nodules that are small or located in difficult-to-detect regions of the lung. Therefore, the attention pyramid pooling network (APPN) is proposed to identify and classify lung nodules. First, a strong feature extractor, named vgg16, is used to obtain features from CT images. Then, the attention primary pyramid module is proposed by combining the attention mechanism and pyramid pooling module, which allows for the fusion of features at different scales and focuses on the most important features for nodule classification. Finally, we use the gated spatial memory technique to decode the general features, which is able to extract more accurate features for classifying lung nodules. The experimental results on the LIDC-IDRI dataset show that the APPN can achieve highly accurate and effective for classifying lung nodules, with sensitivity of 87.59%, specificity of 90.46%, accuracy of 88.47%, positive predictive value of 95.41%, negative predictive value of 76.29% and area under receiver operating characteristic curve of 0.914.

Subsolid Nodules: Significance and Current Understanding.

Subsolid nodules are heterogeneously appearing and behaving entities, commonly encountered incidentally and in high-risk populations. Accurate characterization of subsolid nodules, and application of evolving surveillance guidelines, facilitates evidence-based and multidisciplinary patient-centered management.

Establishment and validation of multiclassification prediction models for pulmonary nodules based on machine learning.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. This study aimed to establish novel multiclassification prediction models based on machine learning (ML) to predict the probability of malignancy in pulmonary nodules (PNs) and to compare with three published models. METHODS: Nine hundred fourteen patients with PNs were collected from four medical institutions (A, B, C and D), which were organized into tables containing clinical features, radiologic features and laboratory test features. Patients were divided into benign lesion (BL), precursor lesion (PL) and malignant lesion (ML) groups according to pathological diagnosis. Approximately 80% of patients in A (total/male: 632/269, age: 57.73 ± 11.06) were randomly selected as a training set; the remaining 20% were used as an internal test set; and the patients in B (total/male: 94/53, age: 60.04 ± 11.22), C (total/male: 94/47, age: 59.30 ± 9.86) and D (total/male: 94/61, age: 62.0 ± 11.09) were used as an external validation set. Logical regression (LR), decision tree (DT), random forest (RF) and support vector machine (SVM) were used to establish prediction models. Finally, the Mayo model, Peking University People's Hospital (PKUPH) model and Brock model were externally validated in our patients. RESULTS: The AUC values of RF model for MLs, PLs and BLs were 0.80 (95% CI: 0.73-0.88), 0.90 (95% CI: 0.82-0.99) and 0.75 (95% CI: 0.67-0.88), respectively. The weighted average AUC value of the RF model for the external validation set was 0.71 (95% CI: 0.67-0.73), and its AUC values for MLs, PLs and BLs were 0.71 (95% CI: 0.68-0.79), 0.98 (95% CI: 0.88-1.07) and 0.68 (95% CI: 0.61-0.74), respectively. The AUC values of the Mayo model, PKUPH model and Brock model were 0.68 (95% CI: 0.62-0.74), 0.64 (95% CI: 0.58-0.70) and 0.57 (95% CI: 0.49-0.65), respectively. CONCLUSIONS: The RF model performed best, and its predictive performance was better than that of the three published models, which may provide a new noninvasive method for the risk assessment of PNs.

[Clinical Application of Robotic Assisted Bronchoscopy 
in Peripheral Pulmonary Nodule Biopsy].

With the popularization of chest computed tomography (CT) lung cancer screening, the detection rate of peripheral pulmonary nodules is increasing day by day. Some patients could make clear diagnoses and receive early treatment by obtaining biopsy specimens. Transbronchial lung biopsy (TBLB) is one of the non-surgical biopsy methods for peripheral pulmonary nodules, which has less trauma and lower incidence of complications compared to percutaneous thoracic needle biopsy (PTNB). However, the diagnostic rate of TBLB is about 70%, which is still inferior to that of PTNB, which is about 90%. Since 2018, robot assisted bronchoscopy systems have been applied in clinical practice. This article reviews their application in further improving the diagnostic rate of peripheral pulmonary nodules by TBLB.
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Diagnostic yield using electromagnetic navigation bronchoscopy for peripheral pulmonary nodules <2 cm.

BACKGROUND: Although electromagnetic navigation bronchoscopy (ENB) is highly sensitive in the diagnosis of peripheral pulmonary nodules (PPNs), its diagnostic yield for subgroups of smaller PPNs is under evaluation. OBJECTIVES: Diagnostic yield evaluation of biopsy using ENB for PPNs <2 cm. DESIGN: The diagnostic yield, sensitivity, specificity, positive predictive value, and negative predictive value of the ENB-mediated biopsy for PPNs were evaluated. METHODS: Patients who had PPNs with diameters <2 cm and underwent ENB-mediated biopsy between May 2015 and February 2020 were consecutively enrolled. The final diagnosis was made via pathological examination after surgery. RESULTS: A total of 82 lesions from 65 patients were analyzed. The median tumor size was 11 mm. All lesions were subjected to ENB-mediated biopsy, of which 29 and 53 were classified as malignant and benign, respectively. Subsequent segmentectomy, lobectomy, or wedge resection, following pathological examinations were performed on 64 nodules from 57 patients. The overall sensitivity, specificity, positive predictive value, and negative predictive value for nodules <2 cm were 53.3%, 91.7%, 92.3%, and 51.2%, respectively. The receiver operating curve showed an area under the curve of 0.721 (p < 0.001). Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value were 62.5%, 100%, 100%, and 42.9%, respectively, for nodules with diameters equal to or larger than 1 cm; and 30.8%, 86.7%, 66.7%, and 59.1%, respectively, for nodules less than 1 cm. In the subgroup analysis, neither the lobar location nor the distance of the PPNs to the pleura affected the accuracy of the ENB diagnosis. However, the spiculated sign had a negative impact on the accuracy of the ENB biopsy (p = 0.010). CONCLUSION: ENB has good specificity and positive predictive value for diagnosing PPNs <2 cm; however, the spiculated sign may negatively affect ENB diagnostic accuracy. In addition, the diagnostic reliability may only be limited to PPNs equal to or larger than 1 cm.

[The role of endoscopy in the management of peripheral pulmonary nodules, part 2: Treatment]. / Place de l'endoscopie dans la gestion des nodules pulmonaires périphériques, partie 2 : traitement.

The management of peripheral lung nodules is challenging, requiring specialized skills and sophisticated technologies. The diagnosis now appears accessible to advanced endoscopy (see Part 1), which can also guide treatment of these nodules; this second part provides an overview of endoscopy techniques that can enhance surgical treatment through preoperative marking, and stereotactic radiotherapy treatment through fiduciary marker placement. Finally, we will discuss how, in the near future, these advanced endoscopic techniques will help to implement ablation strategy.

The use of diagnostic complex robotic-assisted segmentectomy in the management of incidental and screen-detected pulmonary nodules.

OBJECTIVES: Robotic-assisted thoracoscopic surgery (RATS) facilitates complex pulmonary segmentectomy which offers one-stage diagnostic and therapeutic management of small pulmonary nodules. We aimed to explore the potential advantages of a faster, simplified pathway and earlier diagnosis against the disadvantages of unnecessary morbidity in benign cases. METHODS: In an observational study, patients with small, solitary pulmonary nodules deemed suspicious of malignancy by a multidisciplinary team were offered surgery without a pre or intraoperative biopsy. We report our initial experience with RATS complex segmentectomy (using >1 parenchymal staple line) to preserve as much functioning lung tissue as possible. RESULTS: Over a 4-year period, 245 RATS complex segmentectomies were performed; 140 right: 105 left. A median of 2 (1-4) segments was removed. There was no in-hospital mortality and no requirement for postoperative ventilation. Complications were reported in 63 (25.7%) cases, of which 36 (57.1%) were hospital-acquired pneumonia. A malignant diagnosis was found in 198 (81%) patients and a benign diagnosis in 47 (19%). The malignant diagnoses included: adenocarcinoma in 136, squamous carcinoma in 31 and carcinoid tumour in 15. The most frequent benign diagnosis was granulomatous inflammation in 18 cases. CONCLUSIONS: RATS complex segmentectomy offers a precise, safe and effective one-stop therapeutic biopsy in incidental and screen-detected pulmonary nodules.

Shape-Sensing Robotic-Assisted Bronchoscopy versus Computed Tomography-Guided Transthoracic Biopsy for the Evaluation of Subsolid Pulmonary Nodules.

INTRODUCTION: Lung cancer remains the leading cause of cancer death worldwide. Subsolid nodules (SSN), including ground-glass nodules (GGNs) and part-solid nodules (PSNs), are slow-growing but have a higher risk for malignancy. Therefore, timely diagnosis is imperative. Shape-sensing robotic-assisted bronchoscopy (ssRAB) has emerged as reliable diagnostic procedure, but data on SSN and how ssRAB compares to other diagnostic interventions such as CT-guided transthoracic biopsy (CTTB) are scarce. In this study, we compared diagnostic yield of ssRAB versus CTTB for evaluating SSN. METHODS: A retrospective study of consecutive patients who underwent either ssRAB or CTTB for evaluating GGN and PSN with a solid component less than 6 mm from February 2020 to April 2023 at Mayo Clinic Florida and Rochester. Clinicodemographic information, nodule characteristics, diagnostic yield, and complications were compared between ssRAB and CTTB. RESULTS: A total of 66 nodules from 65 patients were evaluated: 37 PSN and 29 GGN. Median size of PSN solid component was 5 mm (IQR: 4.5, 6). Patients were divided into two groups: 27 in the ssRAB group and 38 in the CTTB group. Diagnostic yield was 85.7% for ssRAB and 89.5% for CTTB (p = 0.646). Sensitivity for malignancy was similar between ssRAB and CTTB (86.4% vs. 88.5%; p = 0.828), with no statistical difference. Complications were more frequent in CTTB with no significant difference (8 vs. 2; p = 0.135). CONCLUSION: Diagnostic yield for SSN was similarly high for ssRAB and CTTB, with ssRAB presenting less complications and allowing mediastinal staging within the same procedure.

[Suspected pulmonary nodule in a male heavy smoker: Is biopsy really necessary?] / Nodule pulmonaire suspect chez un grand tabagique : faut-il faire une biopsie ?

INTRODUCTION: Sclerotherapy is a widely used as a lifesaving therapeutic option in cases of upper gastrointestinal bleeding (UGB) due to ruptured gastro-esophageal varices (GOV) in cirrhotic patients, especially when there exists a portosystemic shunt. This endoscopic technique can entail many complications, including systemic and non-thrombotic pulmonary embolism (PE). While multiple pulmonary parenchymal manifestations have been described following sclerotherapy of GOV, to our knowledge no solitary suspicious pulmonary nodule has been described. CASE PRESENTATION: We report the case of 55-year-old man with heavy smoking history who was referred to our pulmonary clinic for work-up of a solitary pulmonary nodule. He was known to have liver cirrhosis with history of massive UGB due to rupture of GOV two months before. He was treated with sclerotherapy by injecting a 3 cc of Histoacryl/lipiodole solution. The post- endoscopic phase was unremarkable. An enhanced CT scan of chest and abdomen performed two months later showed a right upper lobe nodule, even though at that point, the patient was completely asymptomatic. This was ascribed to non-thrombotic PE secondary to sclerotherapy due to complete resolution of the nodule on a CT scan carried out at 2-month follow-up. At that point, his condition did not require any further treatment. CONCLUSION: Solitary pulmonary nodule is one of the radiologic manifestations of PE subsequent to sclerotherapy of GOV. Awareness and radiologic follow-up of this unusual radiologic presentation may prevent unnecessary biopsies.

Developing a multi-institutional nomogram for assessing lung cancer risk in patients with 5-30 mm pulmonary nodules: a retrospective analysis.

Background: The diagnosis of benign and malignant solitary pulmonary nodules based on personal experience has several limitations. Therefore, this study aims to establish a nomogram for the diagnosis of benign and malignant solitary pulmonary nodules using clinical information and computed tomography (CT) results. Methods: Retrospectively, we collected clinical and CT characteristics of 1,160 patients with pulmonary nodules in Guang'an People's Hospital and the hospital affiliated with North Sichuan Medical College between 2019 and 2021. Among these patients, data from 773 patients with pulmonary nodules were used as the training set. We used the least absolute shrinkage and selection operator (LASSO) to optimize clinical and imaging features and performed a multivariate logistic regression to identify features with independent predictive ability to develop the nomogram model. The area under the receiver operating characteristic curve (AUC), C-index, decision curve analysis, and calibration plot were used to evaluate the performance of the nomogram model in terms of predictive ability, discrimination, calibration, and clinical utility. Finally, data from 387 patients with pulmonary nodules were utilized for validation. Results: In the training set, the predictors for the nomogram were gender, density of the nodule, nodule diameter, lobulation, calcification, vacuole, vascular convergence, bronchiole, and pleural traction, selected through LASSO and logistic regression analysis. The resulting model had a C-index of 0.842 (95% CI [0.812-0.872]) and AUCs of 0.842 (95% CI [0.812-0.872]). In the validation set, the C-index was 0.856 (95% CI [0.811-0.901]), and the AUCs were 0.844 (95% CI [0.797-0.891]). Results from the calibration curve and clinical decision curve analyses indicate that the nomogram has a high fit and clinical benefit in both the training and validation sets. Conclusion: The establishment of a nomogram for predicting the benign or malignant diagnosis of solitary pulmonary nodules by this study has shown good efficacy. Such a nomogram may help to guide the diagnosis, follow-up, and treatment of patients.

Novel electromagnetic navigation bronchoscopy system for the diagnosis of peripheral pulmonary nodules: a prospective, multicentre study.

BACKGROUND: Traditional electromagnetic navigation bronchoscopy (ENB) is a real-time image-guided system and used with thick bronchoscopes for the diagnosis of peripheral pulmonary nodules (PPNs). A novel ENB that could be used with thin bronchoscopes was developed. This study aimed to evaluate the diagnostic yield and the experience of using this ENB system in a real clinical scenario. METHODS: This multicentre study enrolled consecutive patients with PPNs adopting ENB from March 2019 to August 2021. ENB was performed with different bronchoscopes, ancillary techniques and sampling instruments according to the characteristics of the nodule and the judgement of the operator. The primary endpoint was the diagnostic yield. The secondary endpoints included the diagnostic yield of subgroups, procedural details and complication rate. RESULTS: In total, 479 patients with 479 nodules were enrolled in this study. The median lesion size was 20.9 (IQR, 15.9-25.9) mm. The overall diagnostic yield was 74.9% (359/479). A thin bronchoscope was used in 96.2% (461/479) nodules. ENB in combination with radial endobronchial ultrasound (rEBUS), a guide sheath (GS) and a thin bronchoscope was the most widely used guided method, producing a diagnostic yield of 74.1% (254/343). The median total procedural time was 1325.0 (IQR, 1014.0-1676.0) s. No severe complications occurred. CONCLUSION: This novel ENB system can be used in combination with different bronchoscopes, ancillary techniques and sampling instruments with a high diagnostic yield and safety profile for the diagnosis of PPNs, of which the combination of thin bronchoscope, rEBUS and GS was the most common method in clinical practice. TRIAL REGISTRATION NUMBER: NCT03716284.

Serum lncRNA THRIL predicts benign and malignant pulmonary nodules and promotes the progression of pulmonary malignancies.

BACKGROUND: This project aimed to research the significance of THRIL in the diagnosis of benign and malignant solitary pulmonary nodules (SPNs) and to investigate the role of THRIL/miR-99a in malignant SPNs. METHODS: The study groups consisted of 169 patients with SPN and 74 healthy subjects. The differences in THRIL levels were compared between the two groups and the healthy group. The receiver operating characteristic curve (ROC) was utilized to analyze the THRIL's significance in detecting benign and malignant SPN. Pearson correlation and binary regression coefficients represented the association between THRIL and SPN. CCK-8 assay, Transwell assay, and flow cytometry were utilized to detect the regulatory effect of THRIL silencing. The interaction between THRIL, miR-99a, and IGF1R was confirmed by the double luciferase reporter gene. RESULTS: There were differences in THRIL expression in the healthy group, benign SPN group, and malignant SPN group. High accuracy of THRIL in the diagnosis of benign SPN and malignant SPN was observed. THRIL was associated with the development of SPN. The expression of THRIL was upregulated and miR-99a was downregulated in lung cancer cells. The double luciferase report experiment confirmed the connections between THRIL/miR-99a/IGF1R. Silencing THRIL could suppress cell proliferation, migration, and invasion and promote cell apoptosis by binding miR-99a. CONCLUSION: The detection of THRIL in serum is useful for the assessment of malignant SPN. THRIL can regulate the expression of IGF1R through miR-99a, thereby promoting the growth of lung cancer cells and inhibiting apoptosis.

Single Setting Robotic Lung Nodule Diagnosis and Resection.

Lung cancer remains the leading cause of cancer-related deaths. Early tissue diagnosis followed by timely therapeutic procedures can have a significant impact on overall survival. While robotic-assisted lung resection is an established therapeutic procedure, robotic-assisted bronchoscopy is a more recent diagnostic procedure that improves reach, stability, and precision in the field of bronchoscopic lung nodule biopsy. The ability to combine lung cancer diagnostics with therapeutic surgical resection into a single-setting anesthesia procedure has the potential to decrease costs, improve patient experiences, and most importantly, reduce delays in cancer care.

All-in-one diagnostic and therapeutic precision thoracic surgery using a hybrid operating theatre: the triple-marking technique.

BACKGROUND: The minimally invasive management of sub-centimetric and often sub-solid lung lesions is quite challenging for thoracic surgeons. As a matter of fact, thoracoscopic wedge resection can often require conversion to thoracotomy when pulmonary lesions cannot be visually identified. Hybrid operating rooms (ORs) can serve as a helpful tool in a multidisciplinary setting, providing real-time lesion imaging and targeting, allowing preoperative or intraoperative percutaneous placement of different lesions targeting techniques to help locate non-palpable lung nodules during video-assisted thoracic surgery. The aim of the study is to assess whether the lung nodule marking using methylene blue, indocyanine green, and gold seeds - the "triple-marking technique" - in the hybrid OR is effective in helping locate non-visible or palpable nodules. METHODS: We conducted a retrospective study on 19 patients with non-palpable lung lesions requiring VATS wedge resection and underwent lesional targeting in the hybrid operating room with different marking systems, including gold seeds placement, methylene blue, or indocyanine green. Lesions were considered non-palpable due to sizing, radiological subsolid aspect, or location and then identified using intraoperative CT scans, also allowing to elaborate needle trajectory. The intraoperative diagnosis was obtained in all of the patients guiding the type of surgery performed. RESULTS: The radio-opaque gold seed marker was used in all of the patients except for two cases that developed intraprocedural pneumothoraces with no major consequences. In these patients, the nodule marking using dyes was still performed and successful in allowing to locate the lesion. Methylene blue and indocyanine green were always used in combination during the dye-targeting phase. Methylene blue appeared to be non-visible in two patients. The indocyanine green was correctly visualized in every patient. We observed the gold seed dislocation in two patients. We were able to identify the lung lesion in all the patients correctly. No conversion was needed. No allergic reactions were observed due to dye administration, and no prophylaxis was performed prior to lesional marking. The lung lesions were visually identified in 100% of the patients thanks to at least one marking technique. CONCLUSIONS: Our experience confirms that the hybrid operating room can represent a suitable tool in helping locate hard-to-find lung lesions in planned VATS resections. Using different techniques, a multiple marking approach seems advisable to maximize the lung lesions detecting rate by direct vision, therefore reducing the VATS conversion rate.

Clinical Characteristics of Human Pulmonary Dirofilariasis in Japan: An Uncommon Differential Diagnosis of a Solitary Pulmonary Nodule.

Human pulmonary dirofilariasis (HPD) is a zoonotic disease caused by Dirofilaria immitis. Most HPD cases are asymptomatic and are either detected during annual health checkups or incidentally identified during the investigation of other diseases, particularly primary or metastatic pulmonary lung cancers. However, the frequency and clinical features of Japanese patients with HPD remain unclear. We analyzed data from the Japanese Medical Abstract Society database and identified 69 cases between 1978 and 2022. The incidence of HPD increased until the 2000s but declined markedly in the 2010s. The incidence is higher in the southwestern region and lower in the northeastern region of Japan. Health checkups are the primary diagnostic opportunities. The Chugoku and Shikoku regions have had high incidence rates per population. The diagnosis of HPD using a noninvasive procedure is typically difficult because of the absence of specific clinical symptoms, and approximately 70% of the cases are detected using video-assisted thoracoscopic surgery. Climate change may increase the incidence of HPD in the northeastern region of Japan, and travel to countries with poor vector control may be a risk factor for HPD transmission. Physicians should consider this parasitic infectious disease when examining patients presenting with solitary lung nodules.

Incidence of Clinically Relevant Solitary Pulmonary Nodules Utilizing a Universal Health Care System.

INTRODUCTION: Solitary pulmonary nodules (SPNs) are common, but the clinical relevance of these nodules is unknown. Utilizing current screening guidelines, we sought to better characterize the national incidence of clinically important SPNs within the largest universal health care system in the nation. MATERIALS AND METHODS: TRICARE data were queried to identify SPNs for ages 18-64 years. SPNs that had been diagnosed within a year with no prior oncologic history were included to ensure true incidence. A proprietary algorithm was applied to determine clinically significant nodules. Further analysis characterized incidence by age grouping, gender, region, military branch, and beneficiary status. RESULTS: A total of 229,552 SPNs were identified with a 60% reduction seen after application of the clinical significance algorithm (N = 88,628). The incidence increased in each decade of life (all P < 0.01). Adjusted incident rate ratios were significantly higher for SPNs detected in the Midwest and Western regions. The incident rate ratio was also higher in females (1.05, confidence interval [CI] 1.018, P = 0.001) as well as non-active duty members (dependents = 1.4 and retired = 1.6, respectively, CIs 1.383-1.492 and 1.591-1.638, P < 0.01). The incidence calculated per 1,000 patients overall was 3.1/1,000. Ages 44-54 years had an incidence of 5.5/1,000 patients, which is higher than the previously reported incidence of < 5.0 nationally for the same age group. CONCLUSIONS: This analysis represents the largest evaluation of SPNs to date combined with clinical relevance adjustment. These data suggest a higher incidence of clinically significant SPNs starting at an age of 44 years in nonmilitary or retired women localized to the Midwest and Western regions of the United States.

A combined diagnostic model based on circulating tumor cell in patients with solitary pulmonary nodules.

BACKGROUND: Although many prediction models in diagnosis of solitary pulmonary nodules (SPNs) have been developed, few are widely used in clinical practice. It is therefore imperative to identify novel biomarkers and prediction models supporting early diagnosis of SPNs. This study combined folate receptor-positive circulating tumor cells (FR+ CTC) with serum tumor biomarkers, patient demographics and clinical characteristics to develop a prediction model. METHODS: A total of 898 patients with a solitary pulmonary nodule who received FR+ CTC detection were randomly assigned to a training set and a validation set in a 2:1 ratio. Multivariate logistic regression was used to establish a diagnostic model to differentiate malignant and benign nodules. The receiver operating curve (ROC) and the area under the curve (AUC) were calculated to assess the diagnostic efficiency of the model. RESULTS: The positive rate of FR+ CTC between patients with non-small cell lung cancer (NSCLC) and benign lung disease was significantly different in both the training and the validation dataset (p < 0.001). The FR+ CTC level was significantly higher in the NSCLC group compared with that of the benign group (p < 0.001). FR+ CTC (odds ratio, OR, 95% confidence interval, CI: 1.13, 1.07-1.19, p < 0.0001), age (OR, 95% CI: 1.06, 1.01-1.12, p = 0.03) and sex (OR, 95% CI: 1.07, 1.01-1.13, p = 0.01) were independent risk factors of NSCLC in patients with a solitary pulmonary nodule. The area under the curve (AUC) of FR+ CTC in diagnosing NSCLC was 0.650 (95% CI, 0.587-0.713) in the training set and 0.700 (95% CI, 0.603-0.796) in the validation set, respectively. The AUC of the combined model was 0.725 (95% CI, 0.659-0.791) in the training set and 0.828 (95% CI, 0.754-0.902) in the validation set, respectively. CONCLUSIONS: We confirmed the value of FR+ CTC in diagnosing SPNs and developed a prediction model based on FR+ CTC, demographic characteristics, and serum biomarkers for differential diagnosis of solitary pulmonary nodules.