Reliability of predicting low-burden (≤ 2) positive axillary lymph nodes indicating sentinel lymph node biopsy in primary operable breast cancer - a retrospective comparative study with PET/CT and breast MRI.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in early breast cancer patients with low-burden axillary metastasis (≤ 2 positive nodes). This study aimed to determine the diagnostic performances of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and breast magnetic resonance imaging in detecting axillary lymph node (ALN) metastases and the reliability to predict ALN burden. METHODS: A total of 275 patients with primary operable breast cancer receiving preoperative PET/CT and upfront surgery from January 2001 to December 2022 in a single institution were enrolled. A total of 244 (88.7%) of them also received breast MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT and breast MRI were assessed. The predictive values to determine ALN burden were evaluated using radio-histopathological concordance. RESULTS: PET/CT demonstrated a sensitivity of 53.4%, specificity of 82.1%, PPV of 65.5%, NPV of 73.5%, and accuracy of 70.9% for detecting ALN metastasis, and the corresponding values for MRI were 71.8%, 67.8%, 56%, 80.8%, and 69.2%, respectively. Combining PET/CT and MRI showed a significantly higher PPV than MRI (72.7% vs 56% for MRI alone, p = 0.037) and a significantly higher NPV than PET/CT (84% vs 73.5% for PET/CT alone, p = 0.041). For predicting low-burden axillary metastasis (1-2 positive nodes), the PPVs were 35.9% for PET/CT, 36.7% for MRI, and 55% for combined PET/CT and MRI. Regarding patients with 0-2 positive ALNs in imaging, who were indicated for SLNB, the predictive correctness was 96.1% for combined PET/CT and MRI, 95.7% for MRI alone, and 88.6% for PET/CT alone. CONCLUSIONS: PET/CT and breast MRI exhibit high predictive values for identifying low-burden axillary metastasis in patients with operable breast cancer with ≦ 2 positive ALNs on imaging.

Diagnostic accuracy of pre-operative breast magnetic resonance imaging (MRI) in predicting axillary lymph node metastasis: variations in intrinsic subtypes, and strategy to improve negative predictive value-an analysis of 2473 invasive breast cancer patients.

BACKGROUND: The value and utility of axillary lymph node (ALN) evaluation with MRI in breast cancer were not clear for various intrinsic subtypes. The aim of the current study is to test the potential of combining breast MRI and clinicopathologic factors to identify low-risk groups of ALN metastasis and improve diagnostic performance. MATERIAL AND METHODS: Patients with primary operable invasive breast cancer with pre-operative breast MRI and post-operative pathologic reports were retrospectively collected from January 2009 to December 2021 in a single institute. The concordance of MRI and pathology of ALN status were determined, and also analyzed in different intrinsic subtypes. A stepwise strategy was designed to improve MRI-negative predictive value (NPV) on ALN metastasis. RESULTS: 2473 patients were enrolled. The diagnostic performance of MRI in detecting metastatic ALN was significantly different between intrinsic subtypes (p = 0.007). Multivariate analysis identified tumor size and histologic type as independent predictive factors of ALN metastases. Patients with HER-2 (MRI tumor size ≤ 2 cm), or TNBC (MRI tumor size ≤ 2 cm) were found to have MRI-ALN-NPV higher than 90%, and these false cases were limited to low axillary tumor burden. CONCLUSION: The diagnostic performance of MRI to predict ALN metastasis varied according to the intrinsic subtype. Combined pre-operative clinicopathologic factors and intrinsic subtypes may increase ALN MRI NPV, and further identify some groups of patients with low risks of ALN metastasis, high NPV, and low burdens of axillary disease even in false-negative cases.

Structural insights into ligand recognition and selectivity of somatostatin receptors.

Somatostatin receptors (SSTRs) play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone, and thus are considered as targets for treating multiple tumors. Despite great progress made in therapeutic development against this diverse receptor family, drugs that target SSTRs still show limited efficacy with preferential binding affinity and conspicuous side-effects. Here, we report five structures of SSTR2 and SSTR4 in different states, including two crystal structures of SSTR2 in complex with a selective peptide antagonist and a non-peptide agonist, respectively, a cryo-electron microscopy (cryo-EM) structure of Gi1-bound SSTR2 in the presence of the endogenous ligand SST-14, as well as two cryo-EM structures of Gi1-bound SSTR4 in complex with SST-14 and a small-molecule agonist J-2156, respectively. By comparison of the SSTR structures in different states, molecular mechanisms of agonism and antagonism were illustrated. Together with computational and functional analyses, the key determinants responsible for ligand recognition and selectivity of different SSTR subtypes and multiform binding modes of peptide and non-peptide ligands were identified. Insights gained in this study will help uncover ligand selectivity of various SSTRs and accelerate the development of new molecules with better efficacy by targeting SSTRs.

18F-Fluorodeoxyglucose PET/CT for Early Prediction of Outcomes in Patients with Advanced Lung Adenocarcinomas and EGFR Mutations Treated with First-Line EGFR-TKIs.

This study aims to investigate the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in early prediction of response and survival following epithelial growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy in patients with advanced lung adenocarcinomas and EGFR mutations. Thirty patients with stage IIIB/IV lung adenocarcinomas and EGFR mutations receiving first-line EGFR-TKIs were prospectively evaluated between November 2012 and May 2015. EGFR mutations were quantified by delta cycle threshold (dCt). 18F-FDG PET/CT was performed before and 2 weeks after treatment initiation. PET response was assessed based on PET Response Criteria in Solid Tumors (PERCIST). Baseline and percentage changes in the summed standardized uptake value, metabolic tumor volume (bsumMTV and ΔsumMTV, respectively), and total lesion glycolysis of ≤5 target lesions/patient were calculated. The association between parameters (clinical and PET) and non-progression disease after 3 months of treatment in CT based on the Response Evaluation Criteria in Solid Tumors Version 1.1 (nPD3mo), progression-free survival (PFS), and overall survival (OS) were tested. The median follow-up time was 19.6 months. The median PFS and OS were 12.0 and 25.3 months, respectively. The PERCIST criteria was an independent predictor of nPD3mo (p = 0.009), dCt (p = 0.014) and bsumMTV (p = 0.014) were independent predictors of PFS, and dCt (p = 0.014) and ΔsumMTV (p = 0.005) were independent predictors of OS. 18F-FDG PET/CT achieved early prediction of outcomes in patients with advanced lung adenocarcinomas and EGFR mutations receiving EGFR-TKIs.

The impact of body mass index (BMI) on MRI diagnostic performance and surgical management for axillary lymph node in breast cancer.

BACKGROUND: We hypothesized that different BMI might have different impact on pre-operative MRI axillary lymph node (ALN) prediction accuracy and thereby subsequent surgical lymph node management. The aim of this study is to evaluate the effect of BMI on presentation, surgical treatment, and MRI performance characteristics of breast cancer with the main focus on ALN metastasis evaluation. METHODS: The medical records of patients with primary invasive breast cancer who had pre-operative breast MRI and underwent surgical resection were retrospectively reviewed. They were categorized into 3 groups in this study: underweight (BMI < 18.5), normal (BMI of 18.5 to 24), and overweight (BMI > 24). Patients' characteristics, surgical management, and MRI performance for axillary evaluation between the 3 groups were compared. RESULTS: A total of 2084 invasive breast cancer patients with a mean age of 53.4 ± 11.2 years were included. Overweight women had a higher rate of breast conserving surgery (56.7% vs. 54.5% and 52.1%) and initial axillary lymph node dissection (15.9% vs. 12.2% and 8.5%) if compared to normal and underweight women. Although the post-operative ALN positive rates were similar between the 3 groups, overweight women were significantly found to have more axillary metastasis on MRI compared with normal and underweight women (50.2% vs 37.7% and 18.3%). There was lower accuracy in terms of MRI prediction in overweight women (65.1%) than in normal and underweight women (67.8% and 76.1%). CONCLUSION: Our findings suggest that BMI may influence the diagnostic performance on MRI on ALN involvement and the surgical management of the axilla in overweight to obese women with breast cancer.

Multishot Diffusion-Weighted MRI of the Breast With Multiplexed Sensitivity Encoding (MUSE) and Shot Locally Low-Rank (Shot-LLR) Reconstructions.

BACKGROUND: Diffusion-weighted imaging (DWI) has shown promise to screen for breast cancer without a contrast injection, but image distortion and low spatial resolution limit standard single-shot DWI. Multishot DWI methods address these limitations but introduce shot-to-shot phase variations requiring correction during reconstruction. PURPOSE: To investigate the performance of two multishot DWI reconstruction methods, multiplexed sensitivity encoding (MUSE) and shot locally low-rank (shot-LLR), compared to single-shot DWI in the breast. STUDY TYPE: Prospective. POPULATION: A total of 45 women who consented to have multishot DWI added to a clinically indicated breast MRI. FIELD STRENGTH/SEQUENCES: Single-shot DWI reconstructed by parallel imaging, multishot DWI with four or eight shots reconstructed by MUSE and shot-LLR, 3D T2 -weighted imaging, and contrast-enhanced MRI at 3T. ASSESSMENT: Three blinded observers scored images for 1) general image quality (perceived signal-to-noise ratio [SNR], ghosting, distortion), 2) lesion features (discernment and morphology), and 3) perceived resolution. Apparent diffusion coefficient (ADC) of the lesion was also measured and compared between methods. STATISTICAL TESTS: Image quality features and perceived resolution were assessed with a mixed-effects logistic regression. Agreement among observers was estimated with a Krippendorf's alpha using linear weighting. Lesion feature ratings were visualized using histograms, and correlation coefficients of lesion ADC between different methods were calculated. RESULTS: MUSE and shot-LLR images were rated to have significantly better perceived resolution (P < 0.001), higher SNR (P < 0.005), and a lower level of distortion (P < 0.05) with respect to single-shot DWI. Shot-LLR showed reduced ghosting artifacts with respect to both MUSE (P < 0.001) and single-shot DWI (P < 0.001). Eight-shot DWI had improved perceived SNR and perceived resolution with respect to four-shot DWI (P < 0.005). DATA CONCLUSION: Multishot DWI enables increased resolution and improved image quality with respect to single-shot DWI in the breast. Shot-LLR reconstructs multishot DWI with minimal ghosting artifacts. The improvement of multishot DWI in image quality increases with an increased number of shots. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

High-risk lesions diagnosed at MRI-guided vacuum-assisted breast biopsy: imaging characteristics, outcome of surgical excision or imaging follow-up.

BACKGROUND: To evaluate imaging characteristics, outcome of surgical excision or imaging follow-up on high-risk lesions diagnosed at MRI-guided vacuum-assisted breast biopsy (MRI-VABB). METHODS: We retrospectively reviewed 598 lesions undergoing 9-gauge MRI-VABB from January 2015 to April 2018 to identify high risk breast lesions. We collected patient demographics, breast MRI BI-RADS descriptors, histopathological diagnosis at MRI-VABB and surgical excision, frequency of upgrade to malignancy and imaging follow-up of high-risk lesions. The x2 test and Fisher exact tests were performed for univariate analysis. RESULTS: 114 patients with 124/598 findings (20.7%) had high-risk lesions at MRI-VABB, including atypical ductal hyperplasia (ADH) (21/124, 16.9%), lobular neoplasia (40/124, 32.3%), radial scar/complex sclerosing lesion (RS/CSL) (13/124, 10.5%), papillary lesions (49/124, 39.5%), and flat epithelial atypia (FEA) (1/124, 0.8%). 84/124 (67.7%) high-risk lesions were excised. 19/84 (22.6%) were upgraded to malignancy (7 invasive cancer, 12 DCIS). The upgrade rate for ADH and lobular neoplasia was 7/18 (38.9%) and 9/31 (29.0%), respectively. The upgrade rate for RS/CSL was 1/10 (10%). Of the 25 papillary lesions excised, 2 (8%) demonstrated pathologic atypia and were upgraded to DCIS. The other 23 papillary lesions had no upgrade or atypia. Excised high-risk lesions showing upgrade varied from 0.4 to 6 cm in length (mean 1.6 cm). There was a non-significant trend (p = 0.054) between larger lesion and upgrade to malignancy; however, there were no other specific imaging features to predict malignancy upgrade. CONCLUSIONS: There were no specific MRI imaging characteristics of high-risk lesions to predict malignancy upgrade. Therefore, surgical excision is recommended for high-risk lesions, especially ADH or lobular neoplasia.

Pure Fibrocystic Change Diagnosed at MRI-guided Vacuum-assisted Breast Biopsy: Imaging Features and Follow-up Outcomes.

OBJECTIVE: Fibrocystic change (FCC) is considered one of the most common benign findings in the breast and may be commonly seen on breast MRI. We performed this study to identify MRI characteristics of pure FCC on MRI-guided vacuum-assisted breast biopsy (VABB) without other associated pathologies and describe the findings on MRI follow-up and outcomes. METHODS: A retrospective review was performed for 598 lesions undergoing 9-gauge MRI-guided VABB at our institution from January 2015 to April 2018, identifying 49 pure FCC lesions in 43 patients. The associations between variables and lesion changes on follow-up MRI were analyzed using exact Mann-Whitney tests and Fisher's exact tests. RESULTS: MRI features of pure FCC are predominantly clumped nonmass enhancement (19/49, 39%) or irregular masses with initial fast/late washout kinetics (9/49, 18%). There was no upgrade to high-risk or cancerous lesions among the 11 patients (25.6%) who underwent surgery. There were 22 pure FCC lesions in 19 (44.2%) patients who had follow-up MRI (mean 18.0 months, range 11-41 months) showing regression (13, 59%), stability (8, 36%), or progression (1, 5%) of the lesion size, and no cancers were found on follow-up at the site of the MRI biopsy for fibrocystic changes. No patient demographics or lesion features were associated with lesion regression or stability (P > 0.05). CONCLUSION: Our study shows that MRI features of VABB-proven FCC lesions may mimic malignancy. After VABB of pure FCC, given that adequate sampling has been performed, a 12-month follow-up MRI may be reasonable.

Diffusivity parameters of diffusion tensor imaging and apparent diffusion coefficient as imaging markers for predicting the treatment response of patients with trigeminal neuralgia.

OBJECTIVE: Trigeminal neuralgia (TN) is facial pain that is usually caused by neurovascular compression syndrome and is characterized by suddenly intense and paroxysmal pain. Radiofrequency lesioning (RFL) is one of the major treatments for TN, but the treatment response for RFL is sometimes inconsistent, and the recurrence of TN is not uncommon. This study aimed to estimate the outcome predictors of TN treated with RFL by using the parameters of diffusion tensor imaging (DTI). METHODS: Fifty-one patients with TN who were treated with RFL were enrolled in the study. MRI was performed in all patients within 1 week before surgery. The visual analog scale was used to evaluate symptom severity at three time points: before, 1 week after, and 3 months after RFL. The involved cisternal segment of the trigeminal nerves was manually selected, and the histograms of each of the diffusivity metrics-including the apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD)-were measured. The differences in the means, as well as the kurtosis and skewness of each of the diffusivity metrics between the nonrecurrent and recurrent groups, were then analyzed using the Mann-Whitney U-test. RESULTS: There were significantly lower kurtosis values (a broader peak of the distributional curves) for both FA and ADC in the recurrent group (p = 0.0004 and 0.015, respectively), compared to the nonrecurrent group. The kurtoses of AD and RD, as well as the mean and skewness of all other diffusivity metrics, did not show significant differences between the two groups. CONCLUSIONS: The pretreatment diffusivity metrics of DTI and ADC may be feasible imaging biomarkers for predicting the outcome of TN after RFL. A clarification of the kurtosis value of FA and ADC is helpful for determining the prognosis of patients after RFL.