Positive Lesions Research Articles

Emerging diagnostic methods and imaging modalities in cushing's syndrome.

Endogenous Cushing's syndrome (CS) is a rare disease characterized by prolonged glucocorticoid excess. Timely diagnosis is critical to allow prompt treatment and limit long-term disease morbidity and risk for mortality. Traditional biochemical diagnostic modalities each have limitations and sensitivities and specificities that vary significantly with diagnostic cutoff values. Biochemical evaluation is particularly complex in patients whose hypercortisolemia fluctuates daily, often requiring repetition of tests to confirm or exclude disease, and when delineating CS from physiologic, nonneoplastic states of hypercortisolism. Lastly, traditional pituitary MRI may be negative in up to 60% of patients with adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (termed "Cushing's disease" [CD]) whereas false positive pituitary MRI findings may exist in patients with ectopic ACTH secretion. Thus, differentiating CD from ectopic ACTH secretion may necessitate dynamic testing or even invasive procedures such as bilateral inferior petrosal sinus sampling. Newer methods may relieve some of the diagnostic uncertainty in CS, providing a more definitive diagnosis prior to subjecting patients to additional imaging or invasive procedures. For example, a novel method of cortisol measurement in patients with CS is scalp hair analysis, a non-invasive method yielding cortisol and cortisone values representing long-term glucocorticoid exposure of the past months. Hair cortisol and cortisone have both shown to differentiate between CS patients and controls with a high sensitivity and specificity. Moreover, advances in imaging techniques may enhance detection of ACTH-secreting pituitary adenomas. While conventional pituitary MRI may fail to identify microadenomas in patients with CD, high-resolution 3T-MRI with 3D-spoiled gradient-echo sequence has thinner sections and superior soft-tissue contrast that can detect adenomas as small as 2 mm. Similarly, functional imaging may improve the identification of ACTH-secreting adenomas noninvasively; Gallium-68-tagged corticotropin-releasing hormone (CRH) combined with PET-CT can be used to detect CRH receptors, which are upregulated on corticotroph adenomas. This technique can delineate functionality of adenomas in patients with CD from patients with ectopic ACTH secretion and false positive pituitary lesions on MRI. Here, we review emerging methods and imaging modalities for the diagnosis of CS, discussing their diagnostic accuracy, strengths and limitations, and applicability to clinical practice.

The Value of Targeting CXCR4 With 68Ga-Pentixafor PET/CT for Subtyping Primary Aldosteronism.

Primary aldosteronism (PA) is one of the leading causes of secondary hypertension, and its diagnostic subtyping consistently presents a clinical challenge. This study aimed to investigate the potential of 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT) in PA classification and its applicability in guiding the development of clinical treatment plans by increasing the sample size. We prospectively enrolled 120 patients with either PA or nonfunctional adenoma (NFA) for analysis. All patients underwent 68Ga-Pentixafor PET/CT. Of these, 11 patients underwent adrenal venous sampling (AVS), 77 underwent adrenalectomy, 76 received pathological diagnoses, and 71 underwent immunohistochemical detection of aldosterone synthase (CYP11B2). Immunohistochemistry for C-X-C chemokine receptor 4 (CXCR4) was performed in 62 cases. Follow-up was conducted for all patients. Among the 120 patients, 66 were diagnosed with aldosterone-producing adenoma (APA), 33 with idiopathic hyperaldosteronism (IHA), and 21 with NFA. For APA patients, the sensitivity, specificity, and accuracy of visual analysis using 68Ga-Pentixafor PET/CT were 92.40%, 94.40%, and 93.33%, respectively. Furthermore, for APA patients with a nodule greater than 1 cm in diameter, when the maximum standard uptake value was 7.3 or greater, the specificity was 100%; and for APA patients with a nodule less than 1 cm in diameter, 68Ga-Pentixafor PET/CT also exhibited high sensitivity. AVS was successfully performed in 5 patients. Among the 5 patients, the concordance rate between the AVS and 68Ga-Pentixafor PET/CT for PA subtyping was 60%. In the 77 patients who underwent adrenalectomy, 61 PET/CT scans displayed positive lesions, all of which benefited from the surgery. Additionally, the concordance rate between 68Ga-Pentixafor PET/CT imaging and CYP11B2 was 81.69%. 68Ga-Pentixafor PET/CT is a reliable and noninvasive functional imaging technique that demonstrates high accuracy in classifying PA and provides valuable guidance for clinical treatment decision-making.

Giant Cell Tumour of the Small Bones of Hand and Foot.

Introduction Giant cell tumor (GCT) orbony tumor mainly involving long bones of arms and legsis very rarely associated with the small bones of hands and feet. Due to its nonspecific signs and symptoms, it is not easy to diagnose based on clinical findings; therefore, histopathological evidence is required to confirmit. Method A total of 16 patients with positive histopathological bone lesions enriched with giant cells were included in our study. After a complete evaluation of their case records, the required radiological assessment was carried out. Campanacci's method of staging was used to evaluate the advancement of lesions. The Musculoskeletal Tumour Society (MSTS) score was recorded postoperatively. All the patients were followed up for a mean duration of 2.8 years until they were lost to follow-up. Result The result of the current study shows that 62.5% of our patients presented in their twenties and 81.25% of patients came at a reasonably advanced stage. Hand and foot were involved in 1:1 cases. Patients were treated by one of the following options: extended curettage with bone graft or cement, wide excision, or en bloc resection. Phenol, a neoadjuvant, was used in all patients. Two of our patients (6.25%) who underwent curettage with bone graft showed up with recurrence during follow-up - one was then treated with wide excision and the other with amputation. Conclusion Giant cell tumors should undoubtedly be aggressively approached with the goal of preserving limb function while reducing recurrence risk to as minimal as possible. GCT of hand is more aggressive comparatively and should be treated accordingly.

Characterization and Prevalence of Pediatric Ramp Lesions Associated with Anterior Cruciate Ligament Tears.

Background: Ramp lesions correspond to posterior meniscocapsular tears of the medial meniscus and are common with anterior cruciate ligament (ACL) tears. They cannot be recognized easily on preoperative magnetic resonance imaging (MRI) scans and are difficult to visualize even using standard arthroscopic approaches. We aim to (1) characterize and evaluate the prevalence of ramp lesions in pediatric patients at a major tertiary children's hospital, providing important insights into demographics, diagnosis, treatment, and functional disability and (2) evaluate the efficacy of MRI in its diagnosis.
 Materials and Methods: We retrospectively reviewed patients under 21 years old undergoing posterior medial meniscal injuries and anterior cruciate ligament ruptures with arthroscopic examination and positive ramp lesions from 2018 to 2021. Patient demographics (including gender and age), initial presentation, physical examination findings, mechanism of injury, pre-operative radiologic findings, and treatment were collected and reviewed via electronic medical record. Exclusion criteria included patients over 18 years old, patients, that did not have an MRI, and patients that were not treated surgically.
 Results: There were 117 patients that met the inclusion criteria out of 690 patients. The mean age at diagnosis was 15.6±1.6 years and the mean BMI was 26.7±6.4. 83% of injuries occurred secondary to sporting activities. Ramp lesions were only detected on preoperative MRI in 63% of cases, suspected in 3%, and not detected in 33%. The sensitivity of the MRI was 63%.
 Conclusions: Ramp lesions were found in 117/690 (16.9%) of patients undergoing ACL reconstruction. MRI had a low sensitivity rate of 63%. During ACL reconstruction, a careful review of the posteromedial compartment is important to recognize less obvious trauma. Lack of treatment may lead to continued instability and risk of complications in these patients.

AI-based detection of contrast-enhancing MRI lesions in patients with multiple sclerosis

BackgroundContrast-enhancing (CE) lesions are an important finding on brain magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) but can be missed easily. Automated solutions for reliable CE lesion detection are emerging; however, independent validation of artificial intelligence (AI) tools in the clinical routine is still rare.MethodsA three-dimensional convolutional neural network for CE lesion segmentation was trained externally on 1488 datasets of 934 MS patients from 81 scanners using concatenated information from FLAIR and T1-weighted post-contrast imaging. This externally trained model was tested on an independent dataset comprising 504 T1-weighted post-contrast and FLAIR image datasets of MS patients from clinical routine. Two neuroradiologists (R1, R2) labeled CE lesions for gold standard definition in the clinical test dataset. The algorithmic output was evaluated on both patient- and lesion-level.ResultsOn a patient-level, recall, specificity, precision, and accuracy of the AI tool to predict patients with CE lesions were 0.75, 0.99, 0.91, and 0.96. The agreement between the AI tool and both readers was within the range of inter-rater agreement (Cohen’s kappa; AI vs. R1: 0.69; AI vs. R2: 0.76; R1 vs. R2: 0.76). On a lesion-level, false negative lesions were predominately found in infratentorial location, significantly smaller, and at lower contrast than true positive lesions (p < 0.05).ConclusionsAI-based identification of CE lesions on brain MRI is feasible, approaching human reader performance in independent clinical data and might be of help as a second reader in the neuroradiological assessment of active inflammation in MS patients.Critical relevance statementAl-based detection of contrast-enhancing multiple sclerosis lesions approaches human reader performance, but careful visual inspection is still needed, especially for infratentorial, small and low-contrast lesions.Graphical

Flotufolastat F 18: Diagnostic First Approval.

Flotufolastat F 18 (POSLUMA®) is an 18F-labelled radiohybrid (rh) prostate-specific membrane antigen (PSMA)-targeted imaging agent being developed by Blue Earth Diagnostics, a subsidiary of Bracco Imaging, for prostate cancer imaging. In May 2023, flotufolastat F 18 received its first approval in the USA as a radioactive diagnostic agent for positron emission tomography (PET) of PSMA positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level. This article summarizes the milestones in the development of flotufolastat F 18 leading to this first approval.

Artificial Intelligence‐Supported Video Analysis as a Means to Assess the Impact of DROP‐IN Image Guidance on Robotic Surgeons: Radioguided Sentinel Lymph Node versus PSMA‐Targeted Prostate Cancer Surgery

The introduction of the tethered DROP‐IN gamma probe has enabled targeted robot‐assisted radioguided prostate cancer (PCa) resection of pelvic sentinel lymph nodes (SLNs) and prostate‐specific membrane antigen (PSMA)‐positive lesions. While both procedures use 99mTc‐isotopes, the two vary in signal and background intensity. To understand how the different levels of image guidance impact surgical decision‐making, computer‐vision algorithms are used to extract the DROP‐IN probe kinematic form clinical videos. 44 PCa patients undergo SLN (25) and PSMA‐targeted (19) resections. PSMA‐PET/CT and SPECT/CT create preoperative roadmaps, and intraoperative probe signal intensities are recorded. Using neural network‐based software, probe trajectories are extracted from videos to extract multiparametric kinematics and generate decision‐making and dexterity scores. PSMA‐targeted resections yield significantly lower nodal signal intensities in preoperative SPECT‐CT scans (three‐fold; p = 0.01), intraoperative probe readouts (eight‐fold; p &lt; 0.001), and signal‐to‐background ratios (SBR; two‐fold; p &lt; 0.001). Kinematics assessment reveal that the challenges encounter during PSMA‐targeted procedures converted to longer target identification times and increase in probe pick‐ups (both five‐fold; p &lt; 0.001). This results in a fourfold reduction in the decision‐making score (p &lt; 0.001). Reduced signal intensities and intraoperative SBR values negatively affect the impact that image‐guided surgery strategies have on the surgical decision‐making process.

Bony lesion analysis in carcinoma prostate: methylene diphosphonate bone scan vs. Gallium-68 psma-11 pet/ct.

Prostate cancer is the cause of the highest cancer-related death in males, 5-year survival is 31% in metastatic disease, and bone is a common site of metastases. Bone scintigraphy is a routinely used imaging modality for detecting skeletal metastases. It has variable sensitivity of 52-100%, whereas PSMA PET/CT scans have better sensitivity approaching 100%, so we determined the diagnostic accuracy, sensitivity, and specificity of planar M.D.P. (Methylene diphosphonate) bone scintigraphy. This analytical cross-sectional study was conducted at the N.M. & molecular imaging department of S.I.U.T. Karachi. Bone scans and PSMA-PET/CT scans of all patients who were visited from Janury-2018 to January 2023 were reviewed and interpreted by a nuclear physician& radiologist team. Inclusion criteria were histopathology-proven prostate cancer patients who had a bone scan and PSMA PET/CT scan within one month and had not received any treatment between scans. Among 70 scans, 38 (54.2%) were positive for bone lesions. A total of 18 (47%) patients had positive bony lesions on both PSMA-PET/CT and Bone scintigraphy. Among 38 bone lesions positive patients, in eleven patients, bone lesions were detected only on PET/CT scans, whereas nine were positive only on Bone scans. The mean S.U.V. max of all bony lesions was 19.15 (range 3.2-57.5). The bone scan's sensitivity, specificity, and accuracy were 62.07%, 78.05%, and 62.87%, respectively. PSMA-PET/CT is better than bone Scintigraphy for detecting skeletal metastases. However, outcomes of bone scintigraphy may be improved when Tc-PSMA receptor bone scintigraphy is used.

Incremental value of 99m Tc-MIBI single-photon emission computed tomography/computed tomography fusion imaging for the diagnosis of secondary hyperparathyroidism.

To assess the added value of 99m Tc-MIBI single-photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging over dual-phase scintigraphy in the diagnosis of secondary hyperparathyroidism (SHPT). This retrospective study included 23 patients with SHPT. The diagnostic efficacy of 99m Tc-MIBI dual-phase scintigraphy and SPECT/CT fusion imaging was analyzed and compared based on the result of postoperative pathology and follow-up. To evaluate the diagnostic ability of 99m Tc-MIBI dual-phase scintigraphy, the volume and radioactive count of parathyroid lesions were assessed using the region of interest method. A total of 79 hyperplastic parathyroid glands and two thyroid tissues were surgically removed from 23 SHPT patients and 13 normal parathyroid glands were preserved. 99m Tc-MIBI SPECT/CT fusion imaging showed higher sensitivity and accuracy than 99m Tc-MIBI dual-phase scintigraphy [sensitivity, 77.2% (61/79) vs 46.8% (37/79); accuracy, 80.4% (74/92) vs 54.3% (50/92), respectively], but comparable specificity [100% (13/13)). Among 61 positive lesions detected by 99m Tc-MIBI SPECT/CT fusion imaging, 37 were dual-phase scintigraphy positive and 24 were dual-phase scintigraphy false negative. The radioactivity counts and radioactivity per unit volume in dual-phase scintigraphy positive were higher than that in dual-phase scintigraphy false negative ( P < 0.05), but the volume of parathyroid lesions between the two groups had no significant difference ( P > 0.05). Compared with 99m Tc-MIBI dual-phase scintigraphy, 99m Tc-MIBI SPECT/CT fusion imaging has incremental value in the diagnosis of SHPT. The low uptake of MIBI in the whole gland and low MIBI uptake per unit volume are easy to cause dual-phase scintigraphy false negative.

Evaluation of the efficacy and safety of ultrasound guided injection of carbon nanoparticles as a preoperative localizing tool of non-palpable breast cancer and sentinel lymph nodes detection

Objective This study aimed to measure the efficacy of using carbon nanoparticles in the preoperative localization of early breast cancer (BC) cases as well as in the detection of sentinel lymph nodes in Egypt. In addition, the purpose of the study was to determine whether the efficacy of carbon nanoparticles outweighs their high price and additional shipping fees. Material and methods The current pilot study enrolled 16 early BC patients, particularly those eligible for breast-conserving surgery. All patients underwent standardized injection techniques. The operating surgeons provided comprehensive intraoperative findings and postoperative histopathological reports of the excised tissues. Results After neoadjuvant chemotherapy (NAC), downstaging of the study subjects was achieved until reaching the TNM stage of T1N1M0 and T1N0M0 in 2 cases (12.5%) and 14 cases (87.5%), respectively. Ultrasound-guided injection of carbon nanoparticles was done, followed by surgical excision on the same day or the day after injection. Eleven patients had positive mass lesions preoperatively, with a mean tumoral size of less than 1 cm in maximum dimension. Moreover, 6 out of the 11 patients showed positive black staining intraoperatively with an accuracy of 68.75%. Postoperative histopathological examination (the gold standard) of axillary specimens revealed that 3 out of 16 of the study population have positive tumor-infiltrated lymph nodes. However, only 2 of these cases demonstrated intra-operative black staining, with the black dye’s positive and negative predictive values of staining being 100% and 92.2%, respectively. Conclusions Preoperative carbon nanoparticle suspension injection is a safe and effective method for adequate tumoral localization in BC patients. Nevertheless, this pilot study did not provide strong evidence for the adequacy of sentinel lymph node detection due to the small sample size, high cost, and extra shipping fees of the carbon nanoparticles.

Isolation and characterization of emerging Mpox virus from India.

Mpox (previously known as Monkeypox) has recently re-emerged, primarily through human-to-human transmission in non-endemic countries including India. Virus isolation is still considered as the gold standard for diagnosis of viral infections. Here, the qPCR positive skin lesion sample from a patient was inoculated in Vero E6 cell monolayer. Characteristic cytopathic effectexhibiting typical cell rounding and detachment was observed at passage-02. The virus isolation was confirmed by qPCR. The replication kinetics of the isolate was determined that revealed maximum viral titre of log 6.3 PFU/mL at 72 h postinfection. Further, whole genome analysis through next generation sequencing revealed that the Mpox virus (MPXV) isolate is characterized by several unique SNPs and INDELs. Phylogenetically, it belonged to A.2 lineage of clade IIb, forming a close group with all other Indian MPXV along with few from USA, UK, Portugal, Thailand and Nigeria. This study reports the first successful isolation and phenotypic and genotypic characterization of MPXV from India.

Functional preservation benefits of minimal surgery for extramammary Paget's disease.

As extramammary Paget's disease (EMPD) sometimes invades and metastasizes from the skin to the mucosa, radical surgical resection of these lesions is often difficult. The purpose of this study was to analyse the association between surgical margins and survival as well as the benefit of functional preservation over complete resection, in patients with EMPD. We retrospectively analysed 230 patients diagnosed with EMPD between 1969 and 2020. Patient and treatment characteristics were recorded. Since our centre is a specialized hospital and almost all patients were referred from other hospitals, we reviewed their referral letters. Prognostic factors and survival time were also analysed. Among 230 patients, 78 (33.9%) had positive margins. The presence of margin positive lesions increased the local recurrence rate but was not significantly correlated with survival. Of all the patients who had received a thorough explanation about the surgical procedure in the referring hospital, 43.8% were scheduled for surgeries that would result in functional impairment, and all of them had function-preserving surgeries at our hospital with a 10-year survival rate of 100%. Our result suggest that less invasive surgery preserves anogenital and urethral function may be an acceptable option for EMPD treatment.

The efficacy of 99mTc-HYNIC-PSMA SPECT/CT in detecting primary lesions and metastasis in newly diagnosed prostate cancer.

Compared with PET/CT or PET/MRI, SPECT/CT is cheaper and more readily accessible. This study was designed to investigate the efficacy of 99mTc-HYNIC-PSMA SPECT/CT in detecting primary tumors and metastases in patients with newly diagnosed prostate cancer (PCa). A retrospective analysis of 31 patients with pathologically proven PCa was performed at Shanghai General Hospital from November 2020 to November 2021. Planar whole-body imaging was performed on all patients with a SPECT/CT scan of PSMA-positive regions 3-4 h after intravenous injection of 740 MBq 99mTc-HYNIC-PSMA. Positive PSMA uptake lesions were evaluated, and SUVmean and SUVmax were measured in each lesion. Associations between SPECT/CT parameters and clinicopathologic factors (tPSA and Gleason Score) were analyzed. The diagnostic capability of SPECT/CT parameters, tPSA, and GS in distant metastatic detection was evaluated by logistic regression. The SUVmean and SUVmax of the high-risk stratification subgroups (tPSA>20 ng/ml, GS ≥8, and tPSA >20 ng/ml and GS≥8) were higher than those of the low-moderate risk stratification subgroups, with sensitivities of 92% and 92%, respectively. Neither SPECT/CT parameters (SUVmean, SUVmax) nor clinicopathologic factors (tPSA, GS) had high sensitivity (80%, 90%, 80%, and 90%, respectively, P <0.05) in distant metastatic prediction. For both the guideline tPSA level (20 ng/ml) and the cut-off level (84.3 ng/ml), the difference in the distant metastasis detection rate between the low predicted tPSA group and the high predicted tPSA group was statistically significant (0% vs. 47.62%, P = 0.005; 9.09% vs. 88.89%, P = 0.000, respectively). Twenty patients with pathological 99mTc-PSMA avid only in the prostate beds underwent radical prostatectomy. Seven of them underwent lymph node dissection, a total of 35 lymph nodes were removed, and no lymph nodes were detected with metastasis, which was consistent with 99mTc-HYNIC-PSMA SPECT/CT. 99mTc-HYNIC-PSMA SPECT/CT is effective in the risk stratification and distant metastasis detection of primary PCa patients. It is of great value in guiding treatment strategies.

Prospective comparison of [18F]AlF-NOTA-octreotide PET/MRI to [68Ga]Ga-DOTATATE PET/CT in neuroendocrine tumor patients

BackgroundFluorine-18-labeled SSAs have the potential to become the next-generation tracer in SSTR-imaging in neuroendocrine tumor (NET) patients given their logistical advantages over the current gold standard gallium-68-labeled SSAs. In particular, [18F]AlF-OC has already shown excellent clinical performance. We demonstrated in our previous report from our prospective multicenter trial that [18F]AlF-OC PET/CT outperforms [68Ga]Ga-DOTA-SSA, but histological confirmation was lacking due to ethical and practical reasons. In this second arm, we therefore aimed to provide evidence that the vast majority of [18F]AlF-OC PET lesions are in fact true NET lesions by analyzing their MR characteristics on simultaneously acquired MRI. We had a special interest in lesions solely detected by [18F]AlF-OC (“incremental lesions”).MethodsTen patients with a histologically confirmed neuroendocrine tumor (NET) and a standard-of-care [68Ga]Ga-DOTATATE PET/CT, performed within 3 months, were prospectively included. Patients underwent a whole-body PET/MRI (TOF, 3 T, GE Signa), 2 hours after IV injection of 4 MBq/kg [18F]AlF-OC. Positive PET lesions were evaluated for a corresponding lesion on MRI. The diagnostic performance of both PET tracers was evaluated by determining the detection ratio (DR) for each scan and the differential detection ratio (DDR) per patient.ResultsIn total, 195 unique lesions were detected: 167 with [68Ga]Ga-DOTATATE and 193 with [18F]AlF-OC. The DR for [18F]AlF-OC was 99.1% versus 91.4% for [68Ga]Ga-DOTATATE, significant for non-inferiority testing (p = 0.0001). Out of these 193 [18F]AlF-OC lesions, 96.2% were confirmed by MRI to be NET lesions. Thirty-three incremental lesions were identified by [18F]AlF-OC, of which 91% were confirmed by MRI and considered true positives.ConclusionThe DR of [18F]AlF-OC was numerically higher and non-inferior to the DR of [68Ga]Ga-DOTATATE. [18F]AlF-OC lesions and especially incremental lesions were confirmed as true positives by MRI in more than 90% of lesions. Taken together, these data further validate [18F]AlF-OC as a new alternative for SSTR PET in clinical practice.Trial registration ClinicalTrials.gov: NCT04552847. Registered 17 September 2020, https://beta.clinicaltrials.gov/study/NCT04552847

Negative estrogen receptor expression assessed by 18F-FES PET in metastatic breast cancer with ER-positive primary tumor.

1034 Background: The 18F-fluoroestradiol positron emission tomography/computed tomography (18F-FES PET/CT) technique provides a convenient method to evaluate the overall estrogen receptor (ER) expression in metastatic breast cancer (MBC) patients. There are long debates on the characteristics and treatment strategy of patients with positive primary ER lesion but negative ER expression in metastatic disease. 18F-FES PET offers an opportunity to answer this question. Methods: This study enrolled MBC patients with ER-positive primary tumor who received 18F-FES PET/CT in our center. Descriptive statistics were used in clinicopathologic characteristics and compared with Chi square test or t test. Progression‐free survival (PFS) was estimated by Kaplan-Meier method and compared by log-rank test. Results: 16.46% (52/314) patients with an ER-positive primary tumor had negative ER expression assessed by 18F-FES for MBC prior to receiving first-line systemic therapy. The rate of ER-negativity tested by 18F-FES was negatively co-related with levels of ER expression in early stage, with a positive to negative conversion in 2 of 3 (46.3%) ER-low (ie, ER 1%-9%) tumors, 7 of 10 (70.0%) ER-moderate (ie, ER 10%-49%) tumors, 16 of 114 (14.0%) ER-high (ie, ER 50%-95%) tumors, and 1 of 8 (12.5%) ER-very high (ie, ER &gt; 95%) tumors (p &lt; 0.001). Chemotherapy (83.33%, 40/48) was the most common treatment strategy afterward, among which capecitabine monotherapy (64.29%, 27/42) was a dominant alternative. PFS was significantly prolonged with capecitabine alone versus other chemotherapy (median PFS: 13.14 vs 6.21 months, p = 0.035). Conclusions: 18F-FES could identify negative conversion of ER in MBC which occurred frequently. Patients with lower ER expression in the primary lesion were more likely to have negative ER expression in the metastasis. In real-world clinical practice, chemotherapy was the primary choice by most physicians and capecitabine monotherapy had shown good efficacy.

Final survival data from a randomized phase II trial comparing high-dose with standard-dose twice-daily (BID) thoracic radiotherapy (TRT) in limited stage small-cell lung cancer (LS SCLC).

8512 Background: Concurrent chemotherapy and TRT is standard treatment of LS SCLC. BID TRT of 45 Gy/30 fractions is the most recommended schedule. Trials report 5-year survival rates of up to 36%, illustrating that some are cured but also need for better treatment. Many treatment failures are due to relapses within TRT fields, and it has been proposed that higher TRT doses might improve local control and consequently survival. However, high-dose once-daily (QD) TRT of 66-70 Gy do not prolong survival. We investigated whether high-dose BID TRT of 60 Gy/40 fractions was tolerable and improved survival compared with the established 45 Gy schedule (NCT02041845). Primary analyses presented at ASCO 2020 showed that the trial was highly positive for the primary endpoint, 2-year survival (60 Gy: 74.2%, 45 Gy: 48.1%, OR 3.09 [95% CI 1.62-5.89]; p=0.0005). We now present updated and final survival data. Methods: Patients ≥18 years with PS 0-2, confirmed SCLC, LS according to the IASLC definition after PET CT staging received 4 courses of platinum/etoposide and were randomized to receive 60 Gy or 45 Gy to PET CT positive lesions. TRT started concurrently with the 2nd chemotherapy course. Responders were offered QD prophylactic cranial irradiation of 25-30 Gy. All patients were followed for 5 years or until death. Results: 170 eligible patients were randomized at 22 Scandinavian hospitals from 2014-2018 (60 Gy: n=89, 45 Gy: n=81). Median age was 65, 31.2% were ≥70 years, 57.1% women, 89.4% had PS 0-1, 83.5% stage III disease, 7.6% pleural effusion and 20.0% ≥5% weight loss last three months before enrollment. Baseline patient and disease characteristics and TRT planning target volumes were well balanced between treatment arms. Completion rates of chemotherapy (60 Gy: 92.1%, 45 Gy: 87.7%) and TRT (60 Gy: 96.6%, 45 Gy: 91.4%) were similar. Patients on the high-dose arm did not experience more grade 3-4 esophagitis (60 Gy: 21.2%, 45 Gy: 18.2%; p=0.83) or pneumonitis (60 Gy: 3.4%, 45 Gy: 0.0%; p=0.39), other grade 3-4 toxicity or treatment related deaths. The 60 Gy group had numerically longer PFS (median PFS 60 Gy: 18.6 months [95% CI 11.6-25.6], 45 Gy: 10.9 months [95% CI 8.7-13.2], HR 0.76 [95% CI 0.53-1.08]; p=0.13). Results for the primary endpoint remain unchanged. The higher TRT dose significantly prolonged survival (median OS 60 Gy: 43.5 months [95% CI 30.4-56.6], 45 Gy: 22.6 months [95% CI 17.2-28.0], HR 0.69 [0.48-0.99]; p=0.043) and provided higher 4.5 year survival rate (60 Gy: 41.6% [95% CI 30.4-56.6], 45 Gy: 28.4% [95% CI 18.9-39.5], OR: 1.79 [95% CI 0.95-3.41]). 5-year survival rates will be presented at the meeting. Conclusions: Compared with LS SCLC patients who received standard TRT, patients receiving high-dose BID TRT of 60 Gy did not experience more toxicity, had a substantial prolongation of survival and a much higher long term survival rate. Clinical trial information: NCT02041845 .

Rational clinical approach to transient ischaemic attack, stroke and associated mimics: A retrospective cohort study.

The present study was performed to identify the individual clinical features and risk factors most strongly associated with the diagnosis of transient neurological symptoms with a cerebrovascular cause (transient ischaemic attack (TIA) or stroke), as compared to common TIA mimics (including retinal ischaemia, migraine and seizure). In a retrospective cohort study, consecutive patients presenting with transient neurological symptoms to TIA clinic in Royal Adelaide Hospital were included. Clinical features and risk factors were recorded in a standardised form, categorised into subgroups, and analysed using descriptive statistics and diagnostic performance indicators, such as sensitivity, specificity and likelihood ratios. For 218/1273 individuals diagnosed with stroke, the three features with the highest positive likelihood ratio were the presence of diffusion weighted imaging positive lesion on magnetic resonance imaging (23.66, 95% confidence interval (CI) 14.35-51.08), extracranial carotid atherosclerosis (3.98, 95% CI 1.19-6.87) and a history of peripheral vascular disease (3.33, 95% CI 1.64-6.27). For TIA, the three features with the highest positive likelihood ratio were extracranial carotid atherosclerosis (3.98, 95% CI 1.19-8.27), presence of atrial fibrillation (2.43, 95% CI 1.54-3.46) and pre-existing anticoagulant therapy (2.39, 95% CI 1.61-3.29). For stroke and TIA, the respective features with the lowest negative likelihood ratios were limb weakness (0.71, 95% CI 0.65-0.77) and hypertension (0.66, 95% CI 0.49-0.84). The present study demonstrated that specific clinical features and risk factors were associated with the final diagnosis at TIA clinic. These clinical features may assist with diagnosis of TIA in centres without access to a vascular neurologist.

Persistent HPV infection after conization of cervical intraepithelial neoplasia—— a systematic review and meta-analysis

ObjectiveTo systematically evaluate several factors of persistent human papillomavirus (HPV) infection following conization in patients with cervical intraepithelial neoplasia (CIN).MethodsPubMed, EMBASE and the Cochrane Library were searched from January 1, 1998 to September 10, 2021. Random-effects models for meta-analyses were used and pooled relative risks with 95% confidence intervals were reported. Literature screening, data extraction, and assessment of the risk of bias in the included studies were conducted independently by two researchers. Data analysis was performed with Stata software, version 12.0.ResultsA total of 28 studies were included in this study. Meta-analysis revealed that surgical margin and residual disease were positively correlated with persistent HPV infection after conization. Compared with patients infected with other types of HPV, CIN patients with HPV 16 had a higher persistent infection rate (OR = 1.967, 95% CI (1.232–3.140), P < 0.05).ConclusionsCIN patients who are postmenopausal, have positive surgical margins and residual lesions, and are positive for HPV 16 are prone to persistent HPV infection after conization.

An Interactive App with Multi-parametric MRI – Whole-Mount Histology Correlation for Enhanced Prostate MRI Training of Radiology Residents

To validate the educational value of a newly created learning application in enhancing prostate MRI training of radiologists for detecting prostate cancer using an observer study. An interactive learning app, LearnRadiology, was developed using a web-based framework to display multi-parametric prostate MRI images with whole-mount histology for 20 cases curated for unique pathology and teaching points. Twenty new prostate MRI cases, different from the ones used in the web app, were uploaded on 3D Slicer. Three radiologists (R1: radiologist; R2, R3: residents) blinded to pathology results were asked to mark areas suspected of cancer and provide a confidence score (1-5, with 5 being high confidence level). Then after a minimum memory washout period of 1 month, the same radiologists used the learning app and then repeated the same observer study. The diagnostic performance for detecting cancers before and after accessing the learning app was measured by correlating MRI with whole-mount pathology by an independent reviewer. The 20 subjects included in the observer study had 39 cancer lesions (13 Gleason 3+3, 17 Gleason 3+4, 7 Gleason 4+3, and 2 Gleason 4+5 lesions). The sensitivity (R1: 54%→64%, P=0.08; R2: 44%→59%, P=0.03; R3: 62%→72%, P=0.04) and positive predictive value(R1: 68%→76%, P=0.23; R2: 52%→79%, P=0.01; R3: 48%→65%, P=0.04) for all 3 radiologists improved after using the teaching app. The confidence score for true positive cancer lesion also improved significantly (R1: 4.0±1.0→4.3±0.8; R2: 3.1±0.8→4.0±1.1; R3: 2.8±1.2→4.1±1.1; P<0.05). The web-based and interactive LearnRadiology app learning resource can support medical student and postgraduate education by improving diagnostic performance of trainees for detecting prostate cancer.

Imaging Chronic Active Lesions in Multiple Sclerosis: a Consensus Statement from the North America Imaging in Multiple Sclerosis Cooperative (P11-3.009)

Imaging Chronic Active Lesions in Multiple Sclerosis: a Consensus Statement from the North America Imaging in Multiple Sclerosis Cooperative (P11-3.009)