Number Of Lesions Research Articles

A phase II exploratory trial of adebrelimab in combination with chemotherapy and concurrent radiotherapy as a first-line treatment for oligo-metastatic extensive-stage small-cell lung cancer.

TPS8131 Background: Oligometastasis of extensive-stage small-cell lung cancer (ES-SCLC) is an intermediate state between local and extensive metastasis, characterized by reduced metastatic potential and a limited number of metastatic sites, which makes local treatment of each lesion possible. Multiple clinical studies have shown that adding local therapy to standard systemic therapy can improve the prognosis of patients with oligometastatic disease. The PD-L1 inhibitor adebrelimab combined with chemotherapy has become one of the standard regimens for first-line treatment of ES-SCLC. Based on these, we hypothesize that in patients with oligometastatic ES-SCLC at risk of early progression, the early addition of chest radiotherapy and stereotactic radiotherapy (SBRT) for metastatic lesions to first-line treatment with adebrelimab combined with chemotherapy may be expected to achieve local control, thereby improving survival benefits. Methods: This is a prospective, single-arm, multicenter, phase II exploratory trial. Patients will be eligible if they are 18 to 75 years of age; have histopathologically or cytologically confirmed ES-SCLC with the number of metastatic lesions of ≤ 5 and organ metastasis of ≤ 3 (i.e. oligometastases); have an ECOG PS of 0-1; and have no previous systemic treatment. The treatment period in this trial is subdivided into induction therapy, concurrent chemoradiotherapy, and consolidation and maintenance therapy. In the induction setting, patients will receive two 3-week cycles of adebrelimab (20 mg/kg on day 1), carboplatin (AUC of 5 mg/mL per min on day 1)/cisplatin (75 mg/m2 on day 1), and etoposide (100 mg/m2 on days 1-3). Patients who achieve partial response or stable disease after induction therapy will then receive concurrent chemoradiotherapy, of which chemotherapy regimen is the same as the induction setting. Radical IMRT radiotherapy (2.5-3 Gy/f, total dose 45-55 Gy) will be performed for the primary tumor in the chest and lymph node region, and SBRT radiotherapy will be given to metastatic lesions. Prophylactic cranial irradiation is optional. After the end of chemoradiotherapy, patients will receive 1-2 cycles of consolidation treatment with the same regimen as induction treatment, followed by adebrelimab monotherapy (20 mg/kg on day 1, q3w) as maintenance treatment until disease progression, intolerance toxicity, or up to 2 years of adebrelimab. The total cycle number of chemotherapy is 4-6. The primary endpoint is progression-free survival (PFS), and secondary endpoints are objective response rate, duration of response, overall survival (OS), 6-month and 1-year PFS rates, 1-year and 2-year OS rates, and safety. The trial is under recruitment, and a total of 62 patients are planned to be enrolled. Clinical trial information: NCT06177925 .

Comparison of Positive Predictive Values of Biparametric MRI and Multiparametric MRI-directed Transrectal US-guided Targeted Prostate Biopsy.

Background Biparametric MRI (bpMRI) of the prostate is an alternative to multiparametric MRI (mpMRI), with lower cost and increased accessibility. Studies investigating the positive predictive value (PPV) of bpMRI-directed compared with mpMRI-directed targeted biopsy are lacking in the literature. Purpose To compare the PPVs of bpMRI-directed and mpMRI-directed targeted prostate biopsies. Materials and Methods This retrospective cross-sectional study evaluated men who underwent bpMRI-directed or mpMRI-directed transrectal US (TRUS)-guided targeted prostate biopsy at a single institution from January 2015 to December 2022. The PPVs for any prostate cancer (PCa) and clinically significant PCa (International Society of Urological Pathology grade ≥2) were calculated for bpMRI and mpMRI using mixed-effects logistic regression modeling. Results A total of 1538 patients (mean age, 67 years ± 8 [SD]) with 1860 lesions underwent bpMRI-directed (55%, 849 of 1538) or mpMRI-directed (45%, 689 of 1538) prostate biopsy. When adjusted for the number of lesions and Prostate Imaging Reporting and Data System (PI-RADS) score, there was no difference in PPVs for any PCa or clinically significant PCa (P = .61 and .97, respectively) with bpMRI-directed (55% [95% CI: 51, 59] and 34% [95% CI: 30, 38], respectively) or mpMRI-directed (56% [95% CI: 52, 61] and 34% [95% CI: 30, 39], respectively) TRUS-guided targeted biopsy. PPVs for any PCa and clinically significant PCa stratified according to clinical indication were as follows: biopsy-naive men, 64% (95% CI: 59, 69) and 43% (95% CI: 39, 48) for bpMRI, 67% (95% CI: 59, 75) and 51% (95% CI: 43, 59) for mpMRI (P = .65 and .26, respectively); and active surveillance, 59% (95% CI: 49, 69) and 30% (95% CI: 22, 39) for bpMRI, 73% (95% CI: 65, 89) and 38% (95% CI: 31, 47) for mpMRI (P = .04 and .23, respectively). Conclusion There was no evidence of a difference in PPV for clinically significant PCa between bpMRI- and mpMRI-directed TRUS-guided targeted biopsy. © RSNA, 2024 Supplemental material is available for this article.

Safety and efficacy of camrelizumab and apatinib in combination with IMRT in unresectable hepatocellular carcinoma: A non-randomised phase 2 study.

e16157 Background: This study aimed to assess the efficacy and safety of combining Camrelizumab (an anti-programmed death 1 antibody) and Apatinib (a tyrosine kinase inhibitor) with intensity-modulated radiotherapy (IMRT) in patients with unresectable hepatocellular carcinoma (HCC). Methods: This non-randomized phase 2 study enrolled patients with unresectable HCC who were either systemic treatment-naïve or refractory/intolerant to first-line targeted therapy. The enrolled patients received IMRT at a dose of 50-60 Gy in 25-30 fractions, with the target volume encompassing all visible lesions. Patients were administered Camrelizumab intravenously at a dose of 200 mg every 3 weeks and Apatinib orally a dose of 250 mg once daily during IMRT, continuing for 2 years or until unacceptable toxicity or disease progression. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), local control (LC) rate, overall survival (OS) and adverse events. Results: From October 2020 to January 2024, 33 patients were included in the preliminary analysis (31 men and 2 women; median age, 57 years [range, 39-77 years]). Among them, 30 patients were diagnosed with BCLC stage C (90.9%). The median number of lesions was one (range, 1-5), with a median tumor diameter of 6.0 cm (range, 2.6-16.0 cm). Tumor thrombus was observed in 22 cases (66.7%), and lymph node metastases was found in 6 cases (18.2%). The ORR based on RECIST 1.1 and modified RECIST criteria were 78.8% and 90.9%, respectively, with a complete response (CR) rate of 12.1% and 54.5%, respectively. The median follow-up time was 20.0 months (range, 3.3-38.6 months). The LC rate at 2 years was 88.3% (95% CI, 68.1-96.1%). The median PFS was 17.5 months (95% CI, 12.6-NA), and the PFS rate at 2 years was 43.9% (95% CI, 26.1-73.8%). The median OS was 25.9 months (95% CI, 14.0-NA), and OS rate at 2 years was 58.5% (95% CI, 41.9-81.6%). According to CTCAE 5.0, grade 3-4 treatment-related adverse events were observed in 27 patients (81.8%), with the most common being thrombocytopenia (42.5%), leukopenia (33.3%) and hypertension (39.4%). No treatment-related deaths occurred. Conclusions: The combination of systematic therapies involving Camrelizumab and Apatinib with local-regional treatment of IMRT showed promising outcomes and manageable toxicities in patients with unresectable HCC. These findings warrant to be confirmed in phase 3 prospective studies. Clinical trial information: ChiCTR2000035052.

Diagnostic performance of Cu64-dotatate-PET/CT or Ga68-dotatate-PET/CT with 18F-fluorodeoxyglucose (FDG)-PET/CT for neuroendocrine tumor evaluation.

e16285 Background: Neuroendocrine tumors (NETs) may be imaged for theranostics with somatostatin receptor (SSTR)-PET/CT like Cu64- or Ga68-dotatate-PET/CT. NETs may also be imaged with 18F-Fluorodeoxyglucose (FDG)-PET/CT based on disease state and insurance coverage. FDG+ and SSTR- disease predicts poor response to Lu177-dotatate therapy, making both scans of possible value. The diagnostic performance of performing both PET/CT studies in close temporal proximity in NET patients is assessed. Methods: This NIH-funded and IRB-approved imaging trial provided FDG- and SSTR-PET/CT in NET patients with RECIST 1.1 measurable disease. A board-certified nuclear radiologist documented detection of the primary NET (if not resected), local, and distant metastatic disease. Each PET/CT pair was assessed for FDG- and SSTR-PET/CT discordant lesions, with location of discordant uptake tabulated. Results: 30 individuals completed FDG-PET/CT and SSTR-PET/CT with either Cu64-dotatate (n = 15) or Ga68-dotatate (n = 15). Studies were performed within 2.4 days average (range 1-10 days). Primary NET site was bowel (n = 15), pancreas (n = 7), lung (n = 7) and unknown (n = 1), with tumor grade 1 (n = 11), grade 1-2 (n = 1), grade 2 (n = 17) and grade 3 (n = 1). Primary NET was detected on FDG-PET/CT in 7/12 cases (58.3%) and on SSTR-PET/CT in 12/12 cases (100%), significantly higher ( p= 0.017). Primary NET was surgically resected in the remaining 18 cases. Local metastases were detected on FDG-PET/CT in 12/30 cases (40%) and on SSTR-PET/CT in 19/30 cases (63.3%), significantly higher ( p= 0.006). Distant metastases were detected on FDG-PET/CT in 19/30 cases (63.3%) and on SSTR-PET/CT in 24/30 cases (80%), trending significantly higher ( p= 0.057). Discordant detection (yes/no for any disease) of primary, local, and/or distant disease was seen in 13/30 cases (43.3%). An equal number of lesions were detected between FDG- and SSTR-PET/CT in 4/30 cases (13.3%), more lesions on FDG-PET/CT in 1/30 (3.4%), and more lesions on SSTR-PET/CT in 25/30 (83.3%). For SSTR-PET/CT, more lesions were detected in the liver (n = 16), lymph nodes (n = 15), bone (n = 6) and bowel (n = 5) than on paired FDG-PET/CT. Disease was exclusively detected on SSTR-PET/CT in 5/30 (16.7%), and in no case on FDG-PET/CT. FDG-PET/CT showed 2/30 (6.7%) cases with exclusively FDG+ liver disease, both in patients with primary lung NETs (2/7, 28.9%). Conclusions: SSTR-PET/CT showed superior detection of primary and locoregional disease, and detected more distant disease sites than FDG-PET/CT. Discordant uptake between PET/CT studies was identified in nearly half of cases, with highest discordance noted in liver and lymph nodes. Discordant FDG+ and SSTR- disease was only seen in patients with primary lung NET, which is a negative prognostic factor for Lu177-dotatate therapy, and may justify the need for having both scans in this group.

Efficacy and safety of stem cell transplantation for multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials

Multiple sclerosis (MS) is a common autoimmune neurological disease affecting patients’ motor, sensory, and visual performance. Stem Cell Transplantation (SCT) is a medical intervention where a patient is infused with healthy stem cells with the purpose of resetting their immune system. SCT shows remyelinating and immunomodulatory functions in MS patients, representing a potential therapeutic option. We conducted this systematic review and meta-analysis that included randomized control trials (RCTs) of SCT in MS patients to investigate its clinical efficacy and safety, excluding observational and non-English studies. After systematically searching PubMed, Web of Science, Scopus, and Cochrane Library until January 7, 2024, nine RCTs, including 422 patients, were eligible. We assessed the risk of bias (ROB) in these RCTs using Cochrane ROB Tool 1. Data were synthesized using Review Manager version 5.4 and OpenMeta Analyst software. We also conducted subgroup and sensitivity analyses. SCT significantly improved patients expanded disability status scale after 2 months (N = 39, MD = − 0.57, 95% CI [− 1.08, − 0.06], p = 0.03). SCT also reduced brain lesion volume (N = 136, MD = − 7.05, 95% CI [− 10.69, − 3.4], p = 0.0002). The effect on EDSS at 6 and 12 months, timed 25-foot walk (T25-FW), and brain lesions number was nonsignificant. Significant adverse events (AEs) included local reactions at MSCs infusion site (N = 25, RR = 2.55, 95% CI [1.08, 6.03], p = 0.034) and hematological disorders in patients received immunosuppression and autologous hematopoietic SCT (AHSCT) (N = 16, RR = 2.33, 95% CI [1.23, 4.39], p = 0.009). SCT can improve the disability of MS patients and reduce their brain lesion volume. The transplantation was generally safe and tolerated, with no mortality or significant serious AEs, except for infusion site reactions after mesenchymal SCT and hematological AEs after AHSCT. However, generalizing our results is limited by the sparse number of RCTs conducted on AHSCT. Our protocol was registered on PROSPERO with a registration number: CRD42022324141.

Multiparametric Characterization and Spatial Distribution of Different MS Lesion Phenotypes.

MS lesions exhibit varying degrees of axonal and myelin damage. A comprehensive description of lesion phenotypes could contribute to an improved radiologic evaluation of smoldering inflammation and remyelination processes. This study aimed to identify in vivo distinct MS lesion types using quantitative susceptibility mapping and susceptibility mapping-weighted imaging and to characterize them through T1-relaxometry, myelin mapping, and diffusion MR imaging. The spatial distribution of lesion phenotypes in relation to ventricular CSF was investigated. MS lesions of 53 individuals were categorized into iso- or hypointense lesions, hyperintense lesions, and paramagnetic rim lesions, on the basis of their appearance on quantitative susceptibility mapping alone, according to published criteria, and with the additional support of susceptibility mapping-weighted imaging. Susceptibility values, T1-relaxation times, myelin and free water fractions, intracellular volume fraction, and the orientation dispersion index were compared among lesion phenotypes. The distance of the geometric center of each lesion from the ventricular CSF was calculated. Eight hundred ninety-six MS lesions underwent the categorization process using quantitative susceptibility mapping and susceptibility mapping-weighted imaging. The novel use of susceptibility mapping-weighted images, which revealed additional microvasculature details, led us to re-allocate several lesions to different categories, resulting in a 35.6% decrease in the number of paramagnetic rim lesions, a 22.5% decrease in hyperintense lesions, and a 17.2% increase in iso- or hypointense lesions, with respect to the categorization based on quantitative susceptibility mapping only. The outcome of the categorization based on the joint use of quantitative susceptibility mapping and susceptibility mapping-weighted imaging was that 44.4% of lesions were iso- or hypointense lesions, 47.9% were hyperintense lesions, and 7.7% were paramagnetic rim lesions. A worsening gradient was observed from iso- or hypointense lesions to hyperintense lesions to paramagnetic rim lesions in T1-relaxation times, myelin water fraction, free water fraction, and intracellular volume fraction. Paramagnetic rim lesions were located closer to ventricular CSF than iso- or hypointense lesions. The volume of hyperintense lesions was associated with a more severe disease course. Quantitative susceptibility mapping and susceptibility mapping-weighted imaging allow in vivo classification of MS lesions into different phenotypes, characterized by different levels of axonal and myelin loss and spatial distribution. Hyperintense lesions and paramagnetic rim lesions, which have the most severe microstructural damage, were more often observed in the periventricular WM and were associated with a more severe disease course.

Pulmonary lesion after surgery for renal cancer: progression or new primary?

To investigate clinical and radiological differences between kidney metastases to the lung (RCCM +) and metachronous lung cancer (LC) detected during follow-up in patients surgically treated for Renal Cell Carcinoma (RCC). cM0 surgically-treated RCC who harbored a pulmonary mass during follow-up were retrospectively scrutinized. Univariate logistic regression assessed predictive features for differentiating between LC and RCCM + . Multivariable analyses (MVA) were fitted to predict factors that could influence time between detection and histological diagnosis of the pulmonary mass, and how this interval could impact on survivals. 87% had RCCM + and 13% had LC. LC were more likely to have smoking history (75% vs. 29%, p < 0.001) and less aggressive RCC features (cT1-2: 94% vs. 65%, p = 0.01; pT1-2: 88% vs. 41%, p = 0.02; G1-2: 88% vs. 37%, p < 0.001). The median interval between RCC surgery and lung mass detection was longer between LC (55months [32.8-107.2] vs. 20months [9.0-45.0], p = 0.01). RCCM + had a higher likelihood of multiple (3[1-4] vs. 1[1-1], p < 0.001) and bilateral (51% vs. 6%, p = 0.002) pulmonary nodules, whereas LC usually presented with a solitary pulmonary nodule, less than 20mm. Univariate analyses revealed that smoking history (OR:0.79; 95% CI 0.70-0.89; p < 0.001) and interval between RCC surgery and lung mass detection (OR:0.99; 95% CI 0.97-1.00; p = 0.002) predicted a higher risk of LC. Conversely, size (OR:1.02; 95% CI 1.01-1.04; p = 0.003), clinical stage (OR:1.14; 95% CI 1.06-1.23; p < 0.001), pathological stage (OR:1.14; 95% CI 1.07-1.22; p < 0.001), grade (OR:1.15; 95% CI 1.07-1.23; p < 0.001), presence of necrosis (OR:1.17; 95% CI 1.04-1.32; p = 0.01), and lymphovascular invasion (OR:1.18; 95% CI 1.01-1.37; p = 0.03) of primary RCC predicted a higher risk of RCCM + . Furthermore, number (OR:1.08; 95% CI 1.04-1.12; p < 0.001) and bilaterality (OR:1.23; 95% CI 1.09-1.38; p < 0.001) of pulmonary lesions predicted a higher risk of RCCM + . Survival analysis showed a median second PFS of 10.9years (95% CI 3.3-not reached) for LC and a 3.8years (95% CI 3.2-8.4) for RCCM + . The median OS time was 6.5years (95% CI 4.4-not reached) for LC and 6years (95% CI 4.3-11.6) for RCCM + . Smoking history, primary grade and stage of RCC, interval between RCC surgery and lung mass detection, and number of pulmonary lesions appear to be the most valuable predictors for differentiating new primary lung cancer from RCC progression.

Clinical evaluation of deep learning-enhanced lymphoma pet imaging with accelerated acquisition.

This study aims to evaluate the clinical performance of a deep learning (DL)-enhanced two-fold accelerated PET imaging method in patients with lymphoma. A total of 123 cases devoid of lymphoma underwent whole-body 18F-FDG-PET/CT scans to facilitate the development of an advanced SAU2Net model, which combines the advantages of U2Net and attention mechanism. This model integrated inputs from simulated 1/2-dose (0.07 mCi/kg) PET acquisition across multiple slices to generate an estimated standard dose (0.14 mCi/kg) PET scan. Additional 39 cases with confirmed lymphoma pathology were utilized to evaluate the model's clinical performance. Assessment criteria encompassed peak-signal-to-noise ratio (PSNR), structural similarity index (SSIM), a 5-point Likert scale rated by two experienced physicians, SUV features, image noise in the liver, and contrast-to-noise ratio (CNR). Diagnostic outcomes, including lesion numbers and Deauville score, were also compared. Images enhanced by the proposed DL method exhibited superior image quality (P<0.001) in comparison to low-dose acquisition. Moreover, they illustrated equivalent image quality in terms of subjective image analysis and lesion maximum standardized uptake value (SUVmax) as compared to the standard acquisition method. A linear regression model with y=1.017x + 0.110 ( ) can be established between the enhanced scans and the standard acquisition for lesion SUVmax. With enhancement, increasedsignal-to-noise ratio (SNR), CNR, and reduced image noise were observed, surpassing those of the standard acquisition. DL-enhanced PET images got diagnostic results essentially equavalent to standard PET images according totwo experienced readers. The proposed DL method could facilitate a 50% reduction in PET imaging duration for lymphoma patients, while concurrently preserving image quality and diagnostic accuracy.

Surgical marker navigation system in breast conserving surgery and excision of non-palpable lesions: first Spanish single-center experience.

Due to the establishment of screening mammography for breast cancer detection, the number of non-palpable lesions has increased. Thus, an optimal localization system is mandatory for the excision of non-palpable breast tumors. The aim of the study is to report the feasibility Surgical Marker Navigation (SMN) system Sirius Pintuition® for the excision of non-palpable breast tumors and non-palpable axillary lymph nodes. A retrospective observational study of patients undergoing breast-conserving surgery and lymph node excision guided by SMN between December 2022 and May 2023 was performed. A total of 84 patients underwent excision of non-palpable breast tumors (77; 91.7%) or non-palpable axillary lymph-nodes (7; 8.3%) using SMN. In total, 94 markers were placed, in 74 patients (88.1%) only one marker was placed, whereas in 10 patients (11.9%) two markers were placed to correctly localize the lesion in the operating room. Most markers were placed using ultrasonographic guidance (69; 82.1%). Seventy-seven patients underwent breast-conserving surgery (91.7%) and 7 (8.3%) lymph node excision. In 10 cases (11.9%), the marker was accidentally displaced during surgery due to the use of magnetized instruments, although the specimen could be removed. In sum, all the markers were removed from the patients, although the marker retrieval rate, as we defined it (percentage of patients in whom the initial excised specimen contained the marker divided by the total number of patients), was 88.1%. The use of Sirius Pintuition® SMN for non-palpable breast tumors and non-palpable lymph nodes is feasible, with a retrieval rate of 88.1%.

The number needed to biopsy for cutaneous melanoma in academic dermatology clinics.

A standard metric for melanoma detection is the number needed to biopsy (NNB). This metric has been used to evaluate practicing dermatologists, dermatology advanced practice professionals, and primary care providers. This metric, however, has rarely been applied to residency clinics. We aimed to determine the NNB at the University of Colorado residency clinics. Moreover, we sought to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on NNB. This study is a retrospective analysis of biopsies performed from 2016 to 2022 at the Denver Health Medical Center and the Rocky Mountain Regional Veteran Affairs dermatology clinics. Differential diagnosis at the time of biopsy was searched for keywords including melanoma, melanoma in situ, and lentigo maligna. Skin biopsies that included re-excisions were excluded. The NNB was subsequently generated by dividing the number of biopsied lesions with suspected melanoma by the number of histologically confirmed melanomas. The data was further separated by pre-COVID-19 (2016-February 2020), COVID-19 shutdown period (March 2020-July 2020), and post-COVID-19 (March 2020-present). Demographic data, including age, sex, race, and Fitzpatrick type, were collected. There were 2230 biopsies with suspected melanoma in the differential diagnosis at both clinic sites from 2016 to 2022. Of these, 362 were histologically confirmed melanoma. Total NNB was 6.16. The pre-COVID-19 NNB was 5.86, and the post-COVID-19 NNB was 6.91. Residency clinics have NNB similar to published values of practicing dermatologists. Furthermore, within these clinics, the impact of the COVID-19 pandemic was appreciated by a relative, although statistically insignificant, increase in NNB.

Implications of Lairage and Environmental Enrichment on Behavioral Responses and Skin Lesions in Finishing Pigs in a Slaughterhouse.

Different resources, such as environmental enrichment, are being evaluated in order to minimize animal stress and promote better conditions during the life cycle of animals, as consumers are increasingly concerned about animal welfare issues. Lairage represents an important stage in the swine production chain and is directly related to animal welfare. The aim of this study was to evaluate the effect of lairage time in the slaughterhouse and environmental enrichment on the level of skin lesions and behavioral responses in pigs. A total of 648 finishing pigs of both sexes were assessed before and after lairage at the slaughterhouse with a five-point scale (0 = none, to 4 = ≥16 superficial lesions or >10 deep lesions). After lairage (after slaughter), lesions were also classified according to their source (mounting, fighting, and handling). Pigs were distributed into two treatments groups during lairage: with environmental enrichment (EE) on the pen, with hanging metal chains, and with no enrichment (NE). Behavior was monitored during the first four hours of lairage. Proportional odds, mixed linear model for longitudinal data, and non-parametric Wilcoxon signed rank tests were used to analyze the relation between treatments, skin lesions, and behavior. The simple metal chains did not affect skin lesion score or pigs' behavior (p > 0.05), whereas lairage duration influenced standing (SA), sitting (S), lying (L), idleness (I), and drinking water (D) (p < 0.001). The main source of skin lesions was handling, which did not differ between treatments (EE and NE) (p > 0.05). It was observed that the severity of the lesions (highest scores of 3, 4, and 5) increased in the different anatomical regions of the pigs when compared before and after slaughter, with the exception of the frontal area, which was the same (p = 0.7547). Lairage time has a proportional relation with skin lesions, and hanging chains at the slaughterhouse pens was not enough to reduce the number of lesions and to change pig behavior.

Comprehensive characterization of circulating tumor cells and cell-free DNA in patients with metastatic melanoma.

Advances in therapeutic approaches for melanoma urge the need for biomarkers that can identify patients at risk for recurrence and to guide treatment. The potential use of liquid biopsies in identifying biomarkers is increasingly being recognized. Here, we present a head-to-head comparison of several techniques to analyze circulating tumor cells (CTCs) and cell-free DNA (cfDNA) in 20 patients with metastatic melanoma. In this study, we investigated whether diagnostic leukapheresis (DLA) combined with multimarker flow cytometry (FCM) increased the detection of CTCs in blood compared to the CellSearch platform. Additionally, we characterized cfDNA at the level of somatic mutations, extent of aneuploidy and genome-wide DNA methylation. Both CTCs and cfDNA measures were compared to tumor markers and extracranial tumor burden on radiological imaging. Compared to the CellSearch method applied on peripheral blood, DLA combined with FCM increased the proportion of patients with detectable CTCs from 35% to 70% (P = 0.06). However, the median percentage of cells that could be recovered by the DLA procedure was 29%. Alternatively, cfDNA mutation and methylation analysis detected tumor load in the majority of patients (90% and 93% of samples successfully analyzed, respectively). The aneuploidy score was positive in 35% of all patients. From all tumor measurements in blood, lactate dehydrogenase (LDH) levels were significantly correlated to variant allele frequency (P = 0.004). Furthermore, the presence of CTCs in DLA was associated with tumor burden (P < 0.001), whereas the presence of CTCs in peripheral blood was associated with number of lesions on radiological imaging (P < 0.001). In conclusion, DLA tended to increase the proportion of patients with detectable CTCs but was also associated with low recovery. Both cfDNA and CTCs were correlated with clinical parameters such as LDH levels and extracranial tumor burden.

A Prospective Multicenter Study on the Additive Value of Contrast-Enhanced Ultrasound for Biopsy Decision of Ultrasound BI-RADS 4 Breast Lesions

ObjectiveThe main aim of this study was to determine whether the use of contrast-enhanced ultrasound (CEUS) could improve the categorization of suspicious breast lesions based on the Breast Imaging Reporting and Data System (BI-RADS), thereby reducing the number of benign breast lesions referred for biopsy. MethodsThis prospective study, conducted between January 2017 and December 2018, enrolled consenting patients from eight teaching hospitals in China, who had been diagnosed with solid breast lesions classified as BI-RADS 4 using conventional ultrasound. CEUS was performed within 1 wk of diagnosis for reclassification of breast lesions. Histopathological results obtained from core needle biopsies or surgical excision samples served as the reference standard. The simulated biopsy rate and cancer-to-biopsy yield were used to compare the accuracy of CEUS and conventional ultrasound (US). ResultsAmong the 1490 lesions diagnosed as BI-RADS 4 with conventional ultrasound, 486 malignant and 1004 benign lesions were confirmed based on histology. Following CEUS, 2, 395, and 211 lesions were reclassified as CEUS-based BI-RADS 2, 3, and 5, respectively, while 882 (59%) remained as BI-RADS 4. The actual cancer-to-biopsy yield based on US was 32.6%, which increased to 43.4% when CEUS-based BI-RADS 4A was used as the cut-off point to recommend biopsy. The simulated biopsy rate decreased to 73.4%. Overall, in this preselected BI-RADS 4 population, only 2.5% (12/486) of malignant lesions would have been miscategorized as BI-RADS 3 using CEUS-based reclassification. The diagnostic accuracy, sensitivity, and specificity of contrast-enhanced ultrasound reclassification were 57.65%, 97.53%, and 38.35%, respectively. ConclusionOur collective findings indicate that CEUS is a valuable tool in further triage of BI-RADS category 4 lesions and facilitates a reduction in the number of biopsies while increasing the cancer-to-biopsy yield.

Local Ablative Therapy Combined With Pembrolizumab in Patients With Synchronous Oligometastatic Non-Small Cell Lung Cancer: A Recursive Partitioning Analysis

Purpose: This study aimed to evaluate the efficacy of local ablative therapy (LAT) combined with pembrolizumab in patients with synchronous oligometastatic non-small cell lung cancer (NSCLC) and to identify patients who would most benefit from LAT.Methods and Materials: We retrospectively identified patients diagnosed with synchronous oligometastatic NSCLC (≤5 metastatic lesions and ≤3 organs involved) and treated with first-line pembrolizumab between January 2017 and December 2022. Patients who underwent LAT, including surgery or radiotherapy at all disease sites, were compared with those who did not undergo LAT. A recursive partitioning analysis (RPA) model was developed using prognostic factors for progression-free survival (PFS).Results: Among the 258 patients included, 78 received LAT with pembrolizumab and 180 received pembrolizumab alone. The median follow-up duration was 15.5 months (range, 3.0–71.2). In the entire cohort, LAT was independently associated with significantly improved PFS (hazard ratio [HR], 0.64; P = 0.015) and overall survival (OS) (HR, 0.61; P = 0.020). In the propensity score-matched cohort (N = 74 in each group), the median PFS was 19.9 months and 9.6 months, respectively (P = 0.003), and the median OS was 42.2 months and 20.5 months, respectively (P = 0.045), for the LAT and non-LAT groups. Based on the RPA model, incorporating the number of metastatic lesions, performance status, and PD-L1 expression level, patients were stratified into three risk groups with distinct PFS. LAT significantly improved PFS and OS in the low- and intermediate-risk groups; however, no difference was observed in the high-risk group. LAT was more effective as a consolidative treatment following pembrolizumab initiation than as an upfront therapy.Conclusion: LAT combined with pembrolizumab was associated with higher PFS and OS compared to pembrolizumab alone in selected patients with synchronous oligometastatic NSCLC. The RPA model could serve as a valuable clinical tool for identifying appropriate patients for LAT.

Gross and Histopathological Study of Postscabietic Nodules

Background: Nodular postscabietic scabies refer to the persistent intermittent signs of scabies that are seen in active and post-treatment period that might last for months. The spectrum of clinico-morphological ranges that can be observed with sarcoptic nodules is broad, and most of the entity's criteria can be elicited histopathologically and pathologically. The management of such nodules may be a challenge. They are commonly treated through local application of corticosteroids or injection of corticosteroids to nodules but the response to treatment is less than clent and relapses are very frequent. The objective of this study was to illuminate which of these features prevail and which ones fade in scarred sites which undergo postscabietic nodule development. The time span between August 2021 to May 2022 was allowed to collect samples from patients with (1-60) years old and full of scabies burrows who visit teaching hospitals and private dermatology clinics in Kut, Wasit Province, Iraq. Treat groups were split into 30 females, and 20 males; with persistent itchy nodular lesions of scabies demonstrated clinically and histopathologically. Everity grade scabies was evaluated by the number of lesions and rated it as severity of itching. Long-term treatment with topical glucocorticoids for 14 days in every age. Tissue from the blisters of patient was obtained after medication. The specimens were washed, fixed and cut to 4-5 µm and stained with H&amp;E. The staining allowed us to observe the fragments of tissues under light microscope with different magnification power. We have observed excessive males and the prevalence of SCABies were more in a young adult group in comparison with other age groups. It was found that lesions with wiry projections tended to persist for two weeks to 52 weeks and the number of nodules had varied from one to fourteen lesions. Examination of Histopathological slide showing acanthosis in 80, histolymphocytic infiltration in 76, and eosinophilia in 100 of total cases in the whole period. After the scabitic nodule loop, the body experiences a hypersensitivity reaction. From the three hundred cases examined microscopically, most (80%) of them were found to be characterized by acanthotic epidermis and diffuse dense dermal lymphocytic infiltration. Neutrophilic reaction, epithelioid-granulomatous inflammation and eosinophilia have been diagnosed in 76 % sight upon while 100 % of other nodules have shown eosinophilia.

#198 Different patterns of renal thrombotic microangiopathy

Abstract Background and Aims Thrombotic microangiopathy (TMA) is a renal lesion often associated with microangiopathic hemolysis. However, there are cases of TMA that present without hemolysis, hematuria or even proteinuria, sometimes being an incidental histopathological finding. In these situations, little is known about the long-term effects on renal function. The aim of our study is to describe the clinical and histopathological presentation of patients with renal TMA biopsied in our center, focusing on those without hemolysis and with low clinical suspicion of TMA. Method We conducted a retrospective observational unicentric study. Clinical and histological parameters were collected from patients biopsied between 2015 and 2023, whose renal biopsy (RB) showed TMA, with a minimum follow-up of 6 months. We excluded renal transplant recipients. Results Data were collected from 41 patients (17 men, 24 women), with a mean age at the time of RB of 54 ± 16 years and a mean eGFR of 80 ± 23 ml/min/1.72 m2. 12 of them (29%) had chronic kidney disease (CKD). Twenty-seven patients (66%) did not have hemolysis at diagnosis. Compared to patients with hemolysis, they were of older age (58 vs 47 years, p = 0.030) and had higher prevalence of CKD (41% vs 7%, p = 0.028). They had a milder clinical presentation, with lower creatinine (168 vs 419 μmol/L, p = 0.029), lower need for renal replacement therapy (RRT) (4% vs 50%, p = 0.001), less hematuria (33% vs 79%, p = 0.008) and proteinuria (67% vs 100%, p = 0.035). Histologically, patients without hemolysis had less fibrosis (56% vs 86%, p = 0.084) and fewer chronic TMA lesions (double contours, wrinkling of the basement membrane) (52% vs 93%, p = 0.009), despite delayed renal biopsy compared to patients with hemolysis (99 ± 118 vs 28 ± 30 days since clinical presentation, p = 0.036). The causes of TMA that were most commonly associated with the absence of hemolysis were drugs (89% without hemolysis) and glomerulopathies such as IgA nephropathy, minimal change disease and fibrillary glomerulonephritis (100% without hemolysis). Within this group of patients without hemolysis, 13 (32%) had a low clinical suspicion of TMA, defined as the absence of hemolysis, hypertension and predisposing factors, in some cases being an incidental finding in the RB. As expected, they also had a mild presentation and did not require RRT. In some cases, they even presented without proteinuria (7 patients, 64%). When comparing the severity of the lesions in renal tissue with patients with high clinical suspicion of TMA, patients with low clinical suspicion presented a similar prevalence of mesangiolysis, vascular damage and a similar proportion of affected glomeruli. Chronic TMA lesions were present in both groups (Table 1). When analysing the evolution of renal function, there are several confounding factors to consider (higher prevalence of CKD in patients without hemolysis, targeted treatment in patients with hemolysis, different time of follow-up between groups...). In our results, there were no statistically significant differences in the evolution of creatinine and proteinuria between groups, even when TMA was an incidental finding. In our sample, these findings were not attributable to a larger number of other histopathological lesions in patients with low suspicion of TMA, as there were no differences between groups (see Table 1). Conclusion Renal TMA should be suspected even in the absence of hemolysis, hypertension or proteinuria, as in our sample one third of diagnoses were incidental and their mild presentation may have delayed renal biopsy. The severity of histological lesions and the evolution of renal function in these cases are comparable to those of patients with a high clinical suspicion. Therefore, its prompt identification, etiological study and treatment are equally important. Currently, we have insufficient data to provide the different clinical scenarios in which TMA should be suspected. However, based on our findings, in the presence of drugs TMA should be considered in the differential diagnosis along with Acute Interstitial Nephritis, even in the absence of urinary abnormalities.

#2183 Does thrombotic microangiopathy drive the occurrence and pattern of cerebrovascular disease in malignant hypertension?

Abstract Background and Aims Malignant hypertension (MHT) is characterized by diffuse microvascular damage caused by severe hypertension, often presenting with multiple organ involvement. Cerebrovascular injury, occurring in both acute and chronic forms, stands as a hallmark of the disease, being identified in up to half of patients. Thrombotic microangiopathy (TMA), defined as the association of mechanical hemolytic anemia with thrombocytopenia, also emerges as a frequent complication in MHT patients. However, the potential contribution of TMA to cerebrovascular disease remains unexplored. The secondary objective of this study was to provide a comprehensive description of the patterns of cerebrovascular injury occurring in MHT, with a focus on acute ischemic strokes (AIS). Method We retrospectively assessed the brain MRI of patients admitted to the kidney intensive care unit at Tenon hospital for malignant hypertension during the 2017-2023 period. Brain MRIs were performed on a systematic basis regardless of neurological symptoms and were independently reviewed by two trained specialists in a blinded fashion. Patterns of acute cerebrovascular disease, defined as AIS, intracerebral hematoma (ICH) or posterior reversible encephalopathy syndrome (PRES), were systematically assessed. Number of AIS lesions, their size and localization were recorded. Underlying chronic cerebral small vessel disease (CSVD) was defined as presence of lacunes, white matter hyperintensities, cerebral microbleeds or perivascular spaces. Severity of the chronic cerebrovascular disease was measured using a validated CSVD score. Results A total of 60 patients were admitted for malignant hypertension, with a mean age of 42.9 years. 40 patients (66.7%) presented with severe acute kidney injury. Cerebrovascular disease, either acute or chronic, was found in 42 patients (70.0%). Underlying chronic CSVD was present in 33 patients (55.0%). Acute patterns of injury occurred in 27 patients (45.0%). AIS was the most frequent (33.3%), followed by PRES (21.7%). Only one patient presented with ICH. Among patients with AIS, 14 (70%) presented with multiple simultaneous lesions. Of note, most patients with AIS exhibited diffuse encephalopathy syndrome (60.0%) rather than focal deficit (40.0%). Systemic TMA was present at admission in 34 patients (56.7%). In an exploratory data analysis, presence of AIS on brain MRI was associated with the presence of underlying CVSD (p = 0.013), but not with the presence of TMA at admission (p = 0.79). No association was found between TMA and PRES (p = 0.22). Conclusion Our study confirmed the high incidence of cerebrovascular disease during MHT. Most notably, 1 in 3 patients presented with AIS. TMA did not appear to increase the incidence nor to influence the pattern of brain injury.

Prognostic Implications of 68Ga-FAPI-46 PET/CT-Derived Parameters on Overall Survival in Various Types of Solid Tumors.

Tumoral fibroblast activation protein expression is associated with proliferation and angiogenesis and can be visualized by PET/CT. We examined the prognostic value of [68Ga]Ga-fibroblast activation protein inhibitor (FAPI) (68Ga-FAPI)-46 PET/CT for different tumor entities in patients enrolled in 2 prospective imaging studies (NCT05160051, n = 30; NCT04571086, n = 115). Methods: Within 4 wk, 145 patients underwent 68Ga-FAPI-46 and [18F]FDG (18F-FDG) PET/CT. The association between overall survival (OS) and sex, age, tumor entity, total lesion number, highest SUVmax, and the presence of each nodal, visceral, and bone metastasis was tested using univariate Cox regression analysis. Multivariate analyses were performed for prognostic factors with P values of less than 0.05. Results: In the univariate analysis, shorter OS was associated with total lesion number and the presence of nodal, visceral, and bone metastases on 68Ga-FAPI-46 PET/CT (hazard ratio [HR], 1.06, 2.18, 1.69, and 2.05; P < 0.01, < 0.01, = 0.04, and = 0.02, respectively) and 18F-FDG PET/CT (HR, 1.05, 2.31, 1.76, and 2.30; P < 0.01, < 0.01, = 0.03, and < 0.01, respectively) and with SUVmax on 68Ga-FAPI-46 PET/CT (HR, 1.03; P = 0.03). In the multivariate analysis, total lesion number on 68Ga-FAPI-46 PET/CT was an independent risk factor for shorter OS (HR, 1.05; P = 0.02). In patients with pancreatic cancer, shorter OS was associated with total lesion number on 68Ga-FAPI-46 PET/CT (HR, 1.09; P < 0.01) and bone metastases on 18F-FDG PET/CT (HR, 31.39; P < 0.01) in the univariate analysis and with total lesion number on 68Ga-FAPI-46 PET/CT (HR, 1.07; P = 0.04) in the multivariate analyses. In breast cancer, total lesion number on 68Ga-FAPI-46 PET/CT (HR, 1.07; P = 0.02), as well as bone metastases on 18F-FDG PET/CT (HR, 9.64; P = 0.04), was associated with shorter OS in the univariate analysis. The multivariate analysis did not reveal significant prognostic factors. In thoracic cancer (lung cancer and pleural mesothelioma), the univariate and multivariate analyses did not reveal significant prognostic factors. Conclusion: Disease extent on 68Ga-FAPI-46 PET/CT is a predictor of short OS and may aid in future risk stratification by playing a supplemental role alongside 18F-FDG PET/CT.

Deep learning ensembles for detecting brain metastases in longitudinal multi-modal MRI studies

Metastatic brain cancer is a condition characterized by the migration of cancer cells to the brain from extracranial sites. Notably, metastatic brain tumors surpass primary brain tumors in prevalence by a significant factor, they exhibit an aggressive growth potential and have the capacity to spread across diverse cerebral locations simultaneously. Magnetic resonance imaging (MRI) scans of individuals afflicted with metastatic brain tumors unveil a wide spectrum of characteristics. These lesions vary in size and quantity, spanning from tiny nodules to substantial masses captured within MRI. Patients may present with a limited number of lesions or an extensive burden of hundreds of them. Moreover, longitudinal studies may depict surgical resection cavities, as well as areas of necrosis or edema. Thus, the manual analysis of such MRI scans is difficult, user-dependent and cost-inefficient, and – importantly – it lacks reproducibility. We address these challenges and propose a pipeline for detecting and analyzing brain metastases in longitudinal studies, which benefits from an ensemble of various deep learning architectures originally designed for different downstream tasks (detection and segmentation). The experiments, performed over 275 multi-modal MRI scans of 87 patients acquired in 53 sites, coupled with rigorously validated manual annotations, revealed that our pipeline, built upon open-source tools to ensure its reproducibility, offers high-quality detection, and allows for precisely tracking the disease progression. To objectively quantify the generalizability of models, we introduce a new data stratification approach that accommodates the heterogeneity of the dataset and is used to elaborate training-test splits in a data-robust manner, alongside a new set of quality metrics to objectively assess algorithms. Our system provides a fully automatic and quantitative approach that may support physicians in a laborious process of disease progression tracking and evaluation of treatment efficacy.

A Prospective Study of the Diagnostic Performance of Photon-Counting CT Compared With MRI in the Characterization of Renal Masses.

The aim of this study was to assess the interreader reliability and per-RCC sensitivity of high-resolution photon-counting computed tomography (PCCT) in the detection and characterization of renal masses in comparison to MRI. This prospective study included 24 adult patients (mean age, 52 ± 14 years; 14 females) who underwent PCCT (using an investigational whole-body CT scanner) and abdominal MRI within a 3-month time interval and underwent surgical resection (partial or radical nephrectomy) with histopathology (n = 70 lesions). Of the 24 patients, 17 had a germline mutation and the remainder were sporadic cases. Two radiologists (R1 and R2) assessed the PCCT and corresponding MRI studies with a 3-week washout period between reviews. Readers recorded the number of lesions in each patient and graded each targeted lesion's characteristic features, dimensions, and location. Data were analyzed using a 2-sample t test, Fisher exact test, and weighted kappa. In patients with von Hippel-Lindau mutation, R1 identified a similar number of lesions suspicious for neoplasm on both modalities (51 vs 50, P = 0.94), whereas R2 identified more suspicious lesions on PCCT scans as compared with MRI studies (80 vs 56, P = 0.12). R1 and R2 characterized more lesions as predominantly solid in MRIs (R1: 58/70 in MRI vs 52/70 in PCCT, P < 0.001; R2: 60/70 in MRI vs 55/70 in PCCT, P < 0.001). R1 and R2 performed similarly in detecting neoplastic lesions on PCCT and MRI studies (R1: 94% vs 90%, P = 0.5; R2: 73% vs 79%, P = 0.13). The interreader reliability and per-RCC sensitivity of PCCT scans acquired on an investigational whole-body PCCT were comparable to MRI scans in detecting and characterizing renal masses. PCCT scans have comparable performance to MRI studies while allowing for improved characterization of the internal composition of lesions due to material decomposition analysis. Future generations of this imaging modality may reveal additional advantages of PCCT over MRI.