Change In Lesion Size Research Articles

Intralesional betamethasone versus oral propranolol for localized infantile hemangiomas of the lip

Infantile hemangiomas (IHs) of the lips are associated with an increased risk of incomplete involution and ulceration, causing disfigurement. Treatment with oral propranolol (OPT) has credible efficacy but takes months to complete. Thus, this study aimed to investigate the efficacy of intralesional betamethasone injection (IBI) as an alternative treatment for protruding localized IHs of the lips. To investigate the efficacies of OPT and IBI, we designed a prospective, noninferiority, parallel-group study. The primary outcome assessed was treatment response rate. Secondary outcome assessments included lesion size changes and surgical rate. Additionally, complication rates and treatment durations of OPT and IBI were compared. The treatment response rate of IBI was not inferior to that of OPT (95.7% vs. 76.0%, respectively; a difference of 19.7%, 95% confidence interval [CI], -4.4% to 41.6%). The average surgical rate in the IBI group was significantly lower than that in the OPT group (8.7% vs. 40%, respectively; p=0.012), and the average duration of treatment for IBI was shorter than that of OPT (2.1 months vs. 6.3 months, respectively; p<0.001). There were no severe adverse drug events in either group. If not managed properly, small, localized lip IHs may cause disfigurement in a child. Our study demonstrated that IBI is as effective as OPT in treating protruding localized lip IHs. Moreover, IBI treatment has a shorter duration and lower surgical rate than OPT. With proper care, IBI is an effective treatment modality for small and localized lip IHs.

LI-RADS threshold growth based on tumor growth rate can improve the diagnosis of hepatocellular carcinoma ≤ 3.0cm.

Despite the revision of threshold growth (TG) in the Liver Imaging Reporting and Data System (LI-RADS) version 2018, the appropriate time period between the two examinations for TG has not been determined. We compared the accuracy of LI-RADS with TG based on tumor growth rate for the diagnosis of hepatocellular carcinoma (HCC) with that of LI-RADS v2018 based on the original TG. Patients who underwent preoperative MRI for focal solid lesions (≤ 3.0cm) were retrospectively evaluated. Three readers measured the size of each lesion on prior CT/MRI and index MRI, with tumor growth rate defined as the percent change in lesion size per month. In addition to the original TG (≥ 50% size increase within ≤ 6months), the modified TG based on tumor growth rates ≥ 10%/month (TG-10%), ≥ 20%/month (TG-20%), and ≥ 30%/month (TG-30%) were evaluated. The accuracies of these evaluation methods for LI-RADS category 5 HCC were compared using generalized estimation equations. A total of 508 lesions from 370 patients were evaluated. Compared with LI-RADS v2018 with the original TG, the accuracy of LI-RADS with TG-10% was significantly higher (85.0% vs. 80.7%, p < .001), whereas the accuracies of LI-RADS with TG-20% (81.3% vs. 80.7%, p = .404) and TG-30% (79.3% vs. 80.7%, p = .052) were not significant. The sensitivity of LI-RADS with TG-10% was higher than that of LI-RADS v2018 (79.0% vs. 72.5%, p < .001), whereas their specificities were not significantly different (96.6% vs. 96.6%, p > .999). TG-10% improved the sensitivity of LI-RADS by detecting additional hepatocellular carcinomas underestimated due to short-term follow-up. Threshold growth based on tumor growth rate can be clinically useful in the diagnosis of hepatocellular carcinoma, by improving the sensitivity of LI-RADS. • The diagnostic accuracy of Liver Imaging Reporting and Data System (LI-RADS) v2018 was not significantly affected by the time interval between prior and index assessments of threshold growth. • In the 334 hepatocellular carcinomas, the frequency of threshold growth was significantly higher using tumor growth rate ≥ 10%/month (TG-10%) than original threshold growth (53.3% vs. 18.0%, p < .001). • Compared with LI-RADS v2018 with the original threshold growth, LI-RADS with TG-10% had significantly higher accuracy (85.0% vs. 80.7%, p < .001) and sensitivity (79.0% vs. 72.5%, p < .001) but asimilar specificity (96.6% vs. 96.6%, p > .999).

Potential value of ctDNA monitoring in metastatic HR + /HER2 − breast cancer: longitudinal ctDNA analysis in the phase Ib MONALEESASIA trial

BackgroundThere is increasing interest in the use of liquid biopsies, but data on longitudinal analyses of circulating tumor DNA (ctDNA) remain relatively limited. Here, we report a longitudinal ctDNA analysis of MONALEESASIA, a phase Ib trial evaluating the efficacy and safety of ribociclib plus endocrine therapy (ET) in Asian patients with hormone receptor–positive, human epidermal growth factor receptor-2–negative advanced breast cancer.MethodsMONALEESASIA enrolled premenopausal and postmenopausal Japanese and postmenopausal non-Japanese Asian patients. All patients received ribociclib with ET (letrozole, fulvestrant, or tamoxifen with goserelin). ctDNA was analyzed using a targeted next-generation sequencing panel of 572 cancer-related genes and correlated by best overall response (BOR).ResultsFive hundred seventy-four cell-free DNA samples from 87 patients were tested. The most frequently altered genes at baseline included PIK3CA (29%) and TP53 (22%). Treatment with ribociclib plus ET decreased ctDNA in most patients at the first on-treatment time point, regardless of dose or ET partner. Patients with partial response and stable disease had lower ctDNA at baseline that remained low until data cutoff if no progressive disease occurred. Most patients with progressive disease as the best response had higher ctDNA at baseline that remained high at the end of treatment. For patients with partial response and stable disease with subsequent progression, ctDNA increased towards the end of treatment in most patients, with a median lead time of 83 days (14–309 days). In some patients with BOR of partial response who experienced disease progression later, specific gene alterations and total ctDNA fraction increased; this was sometimes observed concurrently with the development of new lesions without a change in target lesion size. Patients with alterations in PIK3CA and TP53 at baseline had shorter median progression-free survival compared with patients with wild-type PIK3CA and TP53, 12.7 and 7.3 months vs 19.2 and 19.4 months, respectively (P = .016 and P = .0001, respectively).ConclusionsHigher ctDNA levels and PIK3CA and TP53 alterations detected at baseline were associated with inferior outcomes. On-treatment ctDNA levels were associated with different patterns based on BOR. Longitudinal tracking of ctDNA may be useful for monitoring tumor status and detection of alterations with treatment implications.Trial registrationClinicalTrials.gov NCT02333370. Registered on January 7, 2015.

Serial lung mass volume ratios as prognostic indicators of neonatal respiratory morbidity in fetal pulmonary malformations

Several studies have shown that the congenital pulmonary airway malformation volume ratio is a useful prognosticator of neonatal outcome in prenatally diagnosed lung lesions. However, there remains a lack of consensus on which congenital pulmonary airway malformation volume ratio values have the best predictive value because of operator dependence, inherent changes in lung lesion size throughout gestation, and the widespread use of maternal steroids. This study sought to determine the association between serial congenital pulmonary airway malformation volume ratio measurements and neonatal outcomes among fetuses with lung malformations. This was a retrospective cohort study of fetuses with a prenatally diagnosed lung malformation managed at 2 major fetal centers from January 2010 to December 2021. Prenatal variables, including prospectively measured congenital pulmonary airway malformation volume ratio measurements (initial, maximum, and final), were analyzed. The results were correlated with 3 outcome measures, namely surgical resection before 30 days of life, a need for supplemental O2 at birth, and endotracheal intubation at birth. Statistical analyses were performed using receiver operating characteristic curve analyses, Welch 2 sample t tests, and multivariable logistic regressions (P<.05). There were 123 fetuses with isolated lung lesions identified. Eight (6.5%) had hydrops. The mean initial congenital pulmonary airway malformation volume ratio was 0.67±0.61 cm2 at 22.9±3.9 weeks' gestation. The mean maximum congenital pulmonary airway malformation volume ratio was 1.08 ± 0.94 cm2 at 27.0 ± 4.0 weeks' gestation. The mean final congenital pulmonary airway malformation volume ratio was 0.58±0.60 cm2 at 33.2±4.1 weeks' gestation. At a mean gestational age at delivery of 38.3±2.6 weeks, 15 (12.2%) underwent neonatal lung resection for symptomatic disease. In a multivariable regression, all 3 congenital pulmonary airway malformation volume ratio measurements showed a significant correlation with neonatal lung resection (P<.001). Optimal congenital pulmonary airway malformation volume ratio cutoffs were established based on an initial congenital pulmonary airway malformation volume ratio of ≥0.8 cm2, maximum congenital pulmonary airway malformation volume ratio of ≥1.5 cm2, and a final congenital pulmonary airway malformation volume ratio of ≥1.3 cm2 with associated areas under the curve of 0.89, 0.97, and 0.93, respectively. The final congenital pulmonary airway malformation volume ratio had the highest specificity for predicting surgical lung resection in the early postnatal period. Measuring congenital pulmonary airway malformation volume ratios throughout pregnancy in fetuses with pulmonary malformations has clinical value for prenatal counseling and planning care transition after delivery. Fetuses with a final congenital pulmonary airway malformation volume ratio of more than 1.3 cm2 are likely to require neonatal surgery and therefore should be delivered at tertiary care centers with a neonatal intensive care unit and pediatric surgical expertise.

Clinical evaluation of resin infiltration treatment masking effect on hypomineralised enamel surfaces

BackgroundResin infiltration is a micro-invasive treatment for molar incisor hypomineralisation (MIH). In this study it was aimed to evaluate the masking effect of resin infiltration treatment (ICON) on hypomineralised enamel surface of permanent anterior teeth by using laser fluorescence, spectrophotometer, and cross-polarisation photography.MethodsA total of 116 permanent central incisors in 37 patients were included in the study. The resin infiltration treatment (Icon®) was applied to the teeth with MIH; the healthy teeth received no treatment (control). Hypomineralised enamel lesions were evaluated by ICDAS II criteria. DIAGNOdent Pen was used to assess the lesions and healthy enamel surface quantitatively. Colour changes in enamel lesions were evaluated by using a spectrophotometer (VITA EasyShare). Each enamel lesion was imaged using a cross-polarization technique before and after treatment. All photos were assessed using Image J to evaluate the changes in lesion size. Enamel lesions were evaluated before; immediately after; 1; 3; and 6 months after treatment. Statistical significance was set as p < 0.05.ResultsAfter the resin infiltration, significant decreases were found in the mean DIAGNOdent values for the treatment group (p < 0.05). The colour differences before and after treatment significantly differed in all follow-ups (p < 0.05). In the treatment group, lesion areas decreased significantly after treatment (p < 0.05).ConclusionsThe resin infiltration treatment has a masking effect on MIH lesions without cavities, with stable outcomes after six months. The cross-polarization photography technique may be use to evaluate the lesion size instead of photography with flash.Trial registration.NCT04685889 (registered 28 December 2020).

Poster 288: The Effect of Time Delay From Biopsy to Second-Stage Implantation on Return to Sport and Clinical Outcomes following Autologous Chondrocyte Implantation

Objectives: Expansion of chondral defect size and clinical outcomes in patients with cartilage lesions are thought to be modulated by several risk factors. Previous studies suggest that time delay until implantation may be a risk factor for an increase in the number and size of chondral lesions at the time of implantation. Reports on the effect of time delay on clinical outcomes, however, remain limited. Therefore, the purpose of this study was to evaluate the effect of time delay from cartilage biopsy to implantation on patient satisfaction, return to sport (RTS), and clinical outcomes following autologous chondrocyte implantation. Methods: A retrospective review was performed among patient who underwent autologous chondrocyte implantation (ACI) and matrix-associated autologous chondrocyte implantation (MACI) at a single institution between the years 2012 to 2020 with minimum 2-year clinical follow-up. Clinical outcomes were measured using the Visual Analog Scale (VAS) for pain and satisfaction and the Knee Injury and Osteoarthritis Outcome Score (KOOS; subscores: symptoms, pain, sport, and quality of life (QOL)). Time delay was calculated as the elapsed time between cartilage biopsy and implantation. Cartilage lesions were categorized based on the Outerbridge classification of chondral lesions. The number of high-grade lesions (Outerbridge grade 3 or 4) and size of lesions were analyzed at time of biopsy and implantation. T-tests or non-parametric tests and Chi-squared tests were used to analyze continuous variables and categorical variables, respectively. A one-way ANOVA was used to compare outcomes based on RTS status, using a post-hoc Tukey’s HSD test for multiple comparisons. Bivariate linear regression was used to determine the impact of the time interval from biopsy to implantation on the change in size of the largest high-grade lesion and RTS. Results: A total of 36 patients, mainly female (55.6%) aged 29.25 (± 9.49) with a mean follow-up of 6.51 ± 2.5 years were included in our analysis. Thirteen patients (36.1%) did not RTS. Of the 23 patients (63.9%) who returned to sport, 11 (30.6%) returned at their preoperative level or higher, and 12 (33.3%) returned at a lower level. VAS pain scores were significantly higher in patients who did not RTS vs those who did (42.85 vs. 9.35, p &lt;0.001). All KOOS subscores (Symptom: 56.54 vs. 81.96, Pain: 72.22 vs. 91.74, Sports: 40.38 vs. 79.3, QOL: 35.58 vs. 70.38, p &lt;0.001) were significantly lower in patients who did not RTS compared to those who returned. Increase in time delay from biopsy to implantation was associated with an increase in VAS pain score (OR [95% CI]; 1.42 [0.16 to 2.69], p=0.02) and inversely related to KOOS pain scores (OR [95% CI]; -1.01 [-1.83 to -0.01], p= 0.01. Furthermore, when comparing time from biopsy to implantation and expansion of the largest highgrade lesion, it was found that for every month increase in time, lesion surface area increased by 0.588 cm2; however, this correlation did not reach significance (p=0.09). The number of high-grade lesions at time of implantation were significantly higher in those that returned to sport at a lower level than those who did not return (1.67 vs. 1.23, p=0.02). The average surface area of the defect at biopsy and implantation were 3.13 cm2 and 4.38 cm2 respectively. The number of patients who had an increase in the number of high-grade lesions from biopsy to implantation was significantly higher in those who returned to sport at a lower level compared to those who did not return (4 vs. 1, p=0.05). Logistic regression demonstrated no significant relationship between time interval and rate of return to sport (p=3.59). No other associations were observed between time from biopsy to implantation and clinical outcomes. Conclusions: An increase in time delay from biopsy to graft implantation is associated with worse pain after surgery. Both the number of high-grade lesions at the time of implantation and an increase in time delay were not associated with lower rates of return to sport. Further studies are needed to evaluate the effects of time delay until implantation and its potential role as a risk factor for worse clinical outcomes in patients undergoing autologous chondrocyte implantation procedures. [Table: see text]

High-Resolution Network with Dynamic Convolution and Coordinate Attention for Classification of Chest X-ray Images.

The development of automatic chest X-ray (CXR) disease classification algorithms is significant for diagnosing thoracic diseases. Owing to the characteristics of lesions in CXR images, including high similarity in appearance of the disease, varied sizes, and different occurrence locations, most existing convolutional neural network-based methods have insufficient feature extraction for thoracic lesions and struggle to adapt to changes in lesion size and location. To address these issues, this study proposes a high-resolution classification network with dynamic convolution and coordinate attention (HRCC-Net). In the method, this study suggests a parallel multi-resolution network in which a high-resolution branch acquires essential detailed features of the lesion and multi-resolution feature swapping and fusion to obtain multiple receptive fields to extract complicated disease features adequately. Furthermore, this study proposes dynamic convolution to enhance the network's ability to represent multi-scale information to accommodate lesions of diverse scales. In addition, this study introduces a coordinate attention mechanism, which enables automatic focus on pathologically relevant regions and capturing the variations in lesion location. The proposed method is evaluated on ChestX-ray14 and CheXpert datasets. The average AUC (area under ROC curve) values reach 0.845 and 0.913, respectively, indicating this method's advantages compared with the currently available methods. Meanwhile, with its specificity and sensitivity to measure the performance of medical diagnostic systems, the network can improve diagnostic efficiency while reducing the rate of misdiagnosis. The proposed algorithm has great potential for thoracic disease diagnosis and treatment.

Development of a dual energy CT based model to assess response to treatment in patients with high grade serous ovarian cancer: a pilot cohort study

BackgroundIn patients with cancer, the current gold standard for assessing response to treatment involves measuring cancer lesions on computed tomography (CT) imaging. The percentage change in size of specific lesions determines whether patients have had a complete/partial response or progressive disease, according to RECIST criteria. Dual Energy CT (DECT) permits additional measurements of iodine concentration, a surrogate marker of vascularity. Here we explore the role of changes in iodine concentration within cancer tissue on CT scans to assess its suitability for determining treatment response in patients with high grade serous ovarian cancer (HGSOC).MethodsSuitable RECIST measurable lesions were identified from the CT images of HGSOC patients, taken at 2 different time points (pre and post treatment). Changes in size and iodine concentration were measured for each lesion. PR/SD were classified as responders, PD was classified as non-responder. Radiological responses were correlated with clinical and CA125 outcomes.Results62 patients had appropriate imaging for assessment. 22 were excluded as they only had one DECT scan. 32/40 patients assessed (113 lesions) had received treatment for relapsed HGSOC. RECIST and GCIG (Gynaecologic Cancer Inter Group) CA125 criteria / clinical assessment of response for patients was correlated with changes in iodine concentration, before and after treatment. The prediction of median progression free survival was significantly better associated with changes in iodine concentration (p = 0.0001) and GCIG Ca125 / clinical assessment (p = 0.0028) in comparison to RECIST criteria (p = 0.43).ConclusionChanges in iodine concentration from dual energy CT imaging may be more suitable than RECIST in assessing response to treatment in patients with HGSOC.Trial RegistrationCICATRIx IRAS number 198179, 14 Dec 2015, https://www.myresearchproject.org.uk/.

Association between neurofilament light chain concentration and lesion size in dogs with meningoencephalitis of unknown origin.

Neurofilament light chain (NfL) is an axonal cytoplasmic protein in neurons. Recently, NfL has shown potential as a diagnostic biomarker in dogs with meningoencephalitis of unknown origin (MUO). However, there have been no studies on the biomarkers of lesion progression and resolution in MUO. To identify the potential of NfL as a biomarker for predicting changes in lesions. Seven dogs with MUO who had undergone two magnetic resonance imaging (MRI) scans were included. The serum NfL levels were measured using a single-molecule array. The relationship between the rate of change in lesion size and the rate of change in serum NfL level was analysed using simple linear regression. To investigate the effect of changes in lesion size on NfL levels, the dogs were divided into two groups depending on the change in lesion size: decreased lesion size group (n = 5) and increased lesion size group (n = 2). Trends in lesion size change were identified in the second MRI compared with the first MRI. A significant positive relationship between the rate of lesion size change and the rate of NfL level change was identified (R2 = 0.9239, p = 0.0006). In the decreased lesion size group (n = 5), all NfL levels in each dog decreased, and in the increased lesion size group (n = 2), all NfL levels in each dog increased. This preliminary study showed a positive relationship between the rate of change in lesion size and rate of change in serum NfL levels. Therefore, the serum NfL level may be a promising biomarker of lesion progression and resolution in MUO.

Evaluation of force time integral, force time current integral and lesion size index in a new force sensing catheter

Abstract Funding Acknowledgements Type of funding sources: None. Background Radiofrequency current remains one of the most important ablation techniques in the EP lab. Creating durable lesions is key to successful ablation. Evaluating lesion quality and progression of lesion growth is difficult as many parameters influence lesion formation. Therefore, several approaches were developed, as monitoring RF duration, power and contact force seems insufficient in clinical practice. Force-time-integral (FTI) and force-time-current-integral (FTCI), as well as the ablation index (AI) and lesion size index (LSI) showed decent results in past studies. Recently, a new force sensing catheter (NFSC) was released. By now, data about lesion formation and correlation with the FTI, FTCI and LSI is lacking with this NFSC. This study aimed to further investigate lesion formation with the NFSC in an ex vivo model. Methods 30 RF-lesions were created using an ex vivo porcine cardiac model with the NFSC catheter. The experimental setup consisted of a saline-filled container, a dispersive electrode, a heated thermostat and a circulation pump to imitate in vivo conditions. Global impedance was kept at 120 Ohm as well as the temperature at 37°C. In a first set of lesions, CF was varied (1g, 5g, 10g, 20g). Three lesions were created in each CF-level with 30W. In a second set of lesion, CF was kept at 10 – 15 g, but ablation power was set to 20W, 30W, 40W, 50W, 60W and 70W. In every power level, three lesions were created. All parameters (power, temperature, global impedance, contact force, lesion size) were measured constantly during application of RF-current, enabling real-time correlation of RF parameters and lesion size. In case of an audible steam pop, RF application was stopped. Results 1640 measurement in 30 lesions were included into the analysis. Mean lesion diameter was 7.82 ± 1.52 mm, mean lesion depth 4.80 ± 1.08 mm. Baseline global impedance (GI) was 138.10 ± 10.93 Ω, mean GI-drop 28.10 ± 8.00 Ω. In average, CF of 12.10 ± 5.87 g was used. Correlations of lesion size, FTI and FTCI are shown in table 1. Interestingly, LSI correlated best with lesion size (r = 0.851 and r = 0.852 for lesion depth and diameter; p&amp;lt;0.001). Figure 1 illustrates a scatter plot of LSI and lesion depth (Figure 1a) and lesion diameter (Figure 1b). Figure 2 shows dynamic changes in lesion depth compared to changes in LSI and FTCI. During RF-application, development of lesion formation and LSI is comparable from approximately second 7 onwards. FTCI is rising in a linear manner, whereas lesion formation increases monoexponentially. Conclusion In the NFSC, lesion size correlates strongest with the LSI in power levels up to 70 Watts. FTI and FTCI also showed decent correlations. Regarding dynamic changes in lesion size, LSI is best comparable to actual lesion growth.

Lesion formation in irrigated RF-ablation is not linear, but monoexponential

Abstract Funding Acknowledgements Type of funding sources: None. Background Radiofrequency ablation remains one of the most important ablation techniques in the EP lab. Creating durable lesion is difficult, as progression of lesion formation cannot be observed directly. Surrogate parameters, as force-time-integral and indices, as the ablation index or lesion size index, help distinguishing the efficacy of a RF-application, but several deficiencies are known. The aim of this study was to further investigate dynamic changes in ablation parameters and lesion growth in RF-ablation. Methods RF-lesions were created using an ex vivo porcine cardiac model with a force and local impedance sensing catheter. A second catheter was used for lesions up to 70 Watts. The experimental setup consisted of a saline-filled container, a dispersive electrode, a heated thermostat and a circulation pump to imitate in vivo conditions. Global impedance was kept at 120 Ohm as well as the temperature at 37°C. RF-lesions were created using identic values of RF duration and electrode tissue coupling. RF power of 20W, 30W, 40W, and 50W was used in the local impedance sensing catheter, while RF power of 30W, 40W, 50W, 60W, and 70W were used in the second catheter. All parameters (power, temperature, global impedance, ETC, lesion diameter and lesion depth) were measured once per second during application of RF-current, enabling real-time correlation of RF parameters and lesion size. In case of an audible steam pop, RF application was stopped. Results In total, 61 lesions were included in the analysis. Due to at least 60 measurements per lesion, 3321 data points with all ablation parameters (power, temperature, global impedance, lesion diameter and lesion depth) were collected and analyzed. Throughout the application, lesion progression was highest in the first seconds of RF application and showed a slowing approximation to a maximum (Figure 1 and 2). Potential maximum lesion size seems to be defined by selected power level (s. Figure 3). Interestingly, these findings were seen in all power levels from 20 – 70 W (s. Figure 3). 75 % of final lesion size was achieved after 12-25 seconds, depending on selected power levels (s. Figure 4). In high power ablation (&amp;gt; 50 W), 75% of final lesion size was reached significantly earlier compared to lower power levels (20-40 W, s. Figure 4). Conclusion In RF-ablation, lesion growth is not linear. A slowing approximation of lesion diameter and depth to a maximum is observed. This finding should be considered in clinical settings to avoid steam pops and collateral damage due to a long RF duration despite little changes in lesion size. Further investigation is needed for a surrogate parameter, which is able to assess declining lesion growth after the first seconds of RF-application.

Local impedance changes are a suitable real time surrogate for lesion formation in RF-ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background Radiofrequency current remains one of the most important techniques for catheter ablation. Creating durable lesions is key for sufficient and safe procedures. Several possibilities were tested for estimating the progress of lesion formation. For instance, force-time-integral, ablation index and lesion size index are used to assess quality of RF-application and, therefore, lesion size and durability. Nevertheless, recovered conduction after acute conduction block remains an issue in RF-ablation. The aim of this study was to evaluate local impedance (LI) changes as real time surrogate for lesion formation. Methods RF-lesions were created using an ex vivo porcine cardiac model and a force and local impedance sensing catheter. The experimental setup consisted of a saline-filled container, a dispersive electrode, a heated thermostat and a circulation pump to imitate in vivo conditions. Global impedance was kept at 120 Ohm as well as the temperature at 37°C. RF-lesions were created using identic values of RF duration and contact force. RF power (20W, 30W, 40W, 50W) and level of electrode-tissue-coupling were also systematically varied between minor and full coupling. In minor ETC-level, only the distal end of the catheter is in contact with the tissue. In full ETC-level, the whole catheter tip is in contact with the tissue. All parameters (power, temperature, global and local impedance, contact force, ETC, lesion size) were measured constantly during application of RF-current, enabling real-time correlation of RF parameters and lesion size. In case of an audible steam pop, RF application was stopped. Results Including a total of 8654 measurements into the analysis, maximum diameter and depth were 9.51 ± 1.91 mm and 7.29 ± 2.50 mm in average. Local impedance correlated well with lesion depth (r= 0,78, p&amp;lt;0,001), as well as lesion diameter (r=0,652, p&amp;lt;0,001, Figure 1). After significant declines of LI at the beginning of RF-application, it slowly approximates a minimum. Lesion size on the other hand, rises exponentially in first seconds and gets closer to a maximum after more than 25 seconds. This relationship is illustrated in Figure 2. With decreasing lesion growth at the end of RF-application, LI changes decrease to low level (Figure 3). Conclusion Lesion formation in RF-ablation is not linear during application of RF current. Local impedance changes seem to be a suitable real-time surrogate for assessing changes in lesion size during ablation.

PO-03-066 LOCAL IMPEDANCE CHANGES ARE A SUITABLE REAL TIME SURROGATE FOR LESION FORMATION IN RF-ABLATION

Radiofrequency current remains one of the most important techniques for catheter ablation. Creating durable lesions is key for sufficient and safe procedures. Several possibilities were tested for estimating the progress of lesion formation. For instance, force-time-integral, ablation index and lesion size index are used to assess quality of RF-application and, therefore, lesion size and durability. Nevertheless, recovered conduction after acute conduction block remains an issue in RF-ablation. The aim of this study was to evaluate local impedance (LI) changes as real time surrogate for lesion formation. RF-lesions were created using an ex vivo porcine cardiac model and a contact force and LI sensing catheter. The experimental setup consisted of a saline-filled container, a dispersive electrode, a heated thermostat and a circulation pump to imitate in vivo conditions. Global impedance was kept at 120 Ohm as well as the temperature at 37°C. RF-lesions were created using identic values of RF duration and contact force. RF power (20W, 30W, 40W, 50W) and level of electrode-tissue-coupling were also systematically varied between minor and full coupling. All parameters (power, temperature, global and local impedance, contact force, ETC, lesion size) were measured constantly during 60 seconds of RF-application, enabling real-time correlation of RF parameters and lesion size. In case of an audible steam pop, RF application was stopped. Including a total of 8654 measurements into the analysis, maximum diameter and depth were 9.51 ± 1.91 mm and 7.29 ± 2.50 mm in average. LI correlated well with lesion depth (r= 0,78, p<0,001), as well as lesion diameter (r=0,652, p<0,001). After significant declines of LI at the beginning of RF-application, it slowly approximates a minimum. Lesion size on the other hand, rises exponentially in first seconds and gets closer to a maximum after more than 25 seconds. With decreasing lesion growth at the end of RF-application, LI changes decrease to low level (Figure 1). Lesion formation in RF-ablation is not linear during application of RF current. Local impedance changes seem to be a suitable real-time surrogate for assessing changes in lesion size during ablation.

AB-452672-2 ULTRA-LOW TEMPERATURE CRYOABLATION VERSUS ULTRA-LOW TEMPERATURE CRYOABLATION COMBINED WITH PULSED FIELD ABLATION IN A SWINE VENTRICULAR INFARCT MODEL

Treatment of ventricular arrhythmias with radiofrequency (RF) catheter ablation can be limited by insufficient lesion size and depth, especially within diseased myocardium. A recent investigation using a force-sensing RF catheter (30 watts / 30 seconds) described average lesion depths of 5.1 mm within healthy tissue and 2.0 mm within scar. To compare catheter ablation lesion size measurements using ultra-low temperature cryoablation (ULTC) versus pulsed field cryoablation (ULTC combined with pulsed field ablation, PFCA) in both healthy and infarcted myocardium in an in-vivo swine model. An anterior infarct was created in three swine using 120 minute left anterior descending balloon occlusion. After one month, endocardial lesions were placed in the left ventricle using a linear, deflectable ablation catheter (Figure, Panel A) capable of delivering ULTC or PFCA lesions (Adagio Medical, Irvine, CA). The ULTC system utilizes pressurized nitrogen at -196 degrees C to deliver lesions. Electroanatomic mapping was used to differentiate healthy from infarcted tissue and to ensure non-overlapping lesions. One animal received ULTC only (freeze-thaw-freeze lesions at each ablation site, both freezes two minutes) and two animals received PFCA (single two-minute freeze with 4kV biphasic, bipolar PFA pulses delivered during the freeze). Animals were euthanized after lesion delivery and gross measurements of lesion size were performed. A total of 8 ULTC and 15 PFCA lesions were delivered. Lesion size was slightly larger in healthy compared to infarcted tissue, although all lesions were clinically substantial (Figure, Panel B). While there was no significant difference in median lesion size between ULTC and PFCA (Figure, Panels C and D), PFCA resulted in significantly more transmural lesions within ventricular scar compared to ULTC alone (67% versus 0%, p = 0.02). In total, 35% of all lesions were transmural. Maximal single lesion depth was 17 and 20.5 mm with ULTC and PFCA, respectively. Maximal single lesion width was 22 mm for both ULTC and PFCA. Ultra-low temperature cryoablation resulted in clinically substantial lesions in both healthy and infarcted ventricular myocardium. Addition of pulsed field ablation to ultra-low temperature cryoablation allowed ablation time per lesion to be halved without significant change in lesion size.

PO-03-064 BASELINE LOCAL IMPEDANCE AND CHANGES IN LOCAL IMPEDANCE ARE PREDICTORS OF ELECTRODE TISSUE COUPLING IN RF-ABLATION

Radiofrequency (RF) current remains the most used ablation technology in the EP lab. Durable lesion formation without collateral tissue damage is key for obtaining efficient and safe procedures. RF power, duration and contact force (CF) are considered as main determinants of lesion size. Recently published data show that electrode tissue coupling (ETC) is another important parameter of lesion formation. This ex vivo model was created to investigate local impedance (LI) changes and lesion size when alternating ETC-levels. RF-lesions were created using a CF and LI sensing catheter in an ex vivo porcine cardiac model. The experimental setup consisted of a saline-filled container, a dispersive electrode, a heated thermostat and a circulation pump to imitate in vivo conditions. Global impedance was kept at 120 Ohm as well as the temperature at 37°C. RF-lesions were created using identic values of RF duration and contact force. RF power of 20W, 30W, 40W, and 50W was used. The ETC levels were systematically varied between minor and full coupling. In minor ETC-level, only the distal end of the catheter is in contact with the tissue. In full ETC-level, the whole catheter tip is in contact with the tissue. All parameters (power, temperature, global and local impedance, CF, ETC, lesion size) were measured constantly during RF-application, enabling real-time correlation of all parameters and lesion size. 8654 measurements of lesion depth and diameter were analyzed after creating 72 lesions. Lesion depth and diameter in full ETC-level were significantly higher compared to minor ETC-level (s. Table 1). Interestingly, lesions in lower power levels (20-30 Watt), but full ETC-level became wider and deeper than lesions in high power levels (40-50 Watts), but minor ETC-level (s. Figure 1). These observations were made despite shorter RF-duration (54.00 ± 13.07 s vs. 47.11 ± 17.57 s, p=0.032) in lesions with full ETC-level due to higher incidence of steam pops (14 vs. 6 steam pops, p = 0.032). Baseline LI and LI-drop were significantly higher in full ETC-level (Figure 1), but no relevant difference was observed in baseline GI. Baseline LI and LI changes during ablation provide information about ETC-levels and interaction of the RF ablation catheter with cardiac tissue. ETC-levels, as predicted by LI, had a significantly higher impact on RF lesion size than RF power or RF-duration. Therefore, LI should be monitored during RF ablation for estimating ETC-levels and lesion formation.Tabled 1Table 1. Lesion size and impedance changes in different ETC-levels.Minor ETC (n=36)Full ETC (n=36)p-valueMaximum diameter [mm]8.48 ± 1.6110.54 ± 1.63<0.001Maximum depth [mm]5.13 ± 0.999.45 ± 1.45<0.001Start LI [Ω]236.89 ± 26.42300.67 ± 21.61<0.001Start GI [Ω]150.61 ± 21.61151.33 ± 23.680.893LI-drop [Ω]-53.61-125.53<0.001GI-drop [Ω]-21.33-33.44<0.001 Open table in a new tab

Abstract CT018: Safety and efficacy of three PARP inhibitors (PARPi) combined with the ataxia telangiectasia- and Rad3-related kinase inhibitor (ATRi) camonsertib in patients (pts) with solid tumors harboring DNA damage response (DDR) alterations

Abstract Introduction: ATRi and PARPi combinations kill tumor cells via synergistic modulation of complementary DDR pathways but clinical utility is limited by overlapping toxicities. A genome-wide CRISPR-Cas9 screen identified DDR alterations that sensitize tumors to the ATRi camonsertib (cam) plus PARPi. Based on preclinical models, tolerability and efficacy of cam plus PARPi given intermittently at low doses in pts with solid tumors with DDR alterations, including BRCA-mutated PARPi-resistant cancers, was evaluated. Methods: Pts (≥ 18 yrs) with relapsed/refractory (r/r) solid tumors with DDR alterations were treated with cam plus talazoparib (tala), niraparib (nira), or olaparib (ola) in 2 phase I trials (NCT04497116, NCT04972110). An adaptive BOIN design was used to optimize dose/schedule. Endpoints were safety, recommended phase II dose (RP2D), pharmacokinetics (PK), response (RECIST v1.1 [confirmed/unconfirmed], CA 125, or PSA), clinical benefit rate (CBR; RECIST/tumor marker response or treatment duration ≥ 16 wk), and ctDNA molecular response rate (MRR; best reduction in mean variant allele frequency [mVAF] ≥ 50%). Results: As of Nov 2022, 99 pts were enrolled (61 with ≥ 3 prior lines of therapy, 36 PARPi-pretreated); 43, 27, 29 pts in tala, nira, and ola combinations, respectively. Tumors included ovarian (n=20), prostate (n=13), breast (n=17), bile duct (n=3); most common genotypes were ATM (n=26), BRCA1 (n=19), and BRCA2 (n=33). Grade 3+ toxicities included reversible myelosuppression (neutropenia, anemia, and thrombocytopenia in 35%, 28%, and 14% of pts overall; 33%, 16%, and 11% at preliminary RP2Ds), fatigue (3%), and alkaline phosphatase increase (2%). Two pts discontinued treatment due to drug-related toxicity. Forty pts remain on therapy, up to 63 wks. Preliminary RP2Ds: cam 80 mg QD (d 5-7) + tala 0.25 mg QD, 1 wk on/1 wk off; cam 80 mg QD + nira 100 mg QD, 2 d on/5 d off; cam 50 mg QD + ola 100 mg BID, 3 d on/4 d off. As of abstract submission, response rate was 13% in 85 evaluable pts; CBR was 49%. Responders included pts with ovarian (n=6), bile duct (n=2), and breast, pancreatic, and carcinoma of unknown primary (n=1 each) cancers harboring alterations in BRCA1/2 (n=9), IDH1 (n=1), and ATM (n=1). Of 30 evaluable PARPi-pretreated pts, response rate was 23% and CBR was 52%. MRR was 64% (14/22 evaluable); change in mVAF correlated with a change in target lesion size (r=0.63, P=0.001). PK of each drug in the combination was consistent with respective monotherapy PK. Conclusion: Combination of cam plus PARPi at low doses on intermittent schedules was generally well-tolerated with clinical activity in DDR-aberrant tumors, including those pretreated with PARPi. RP2D optimization and translational correlative studies are ongoing. Citation Format: Timothy A. Yap, Siddhartha Yadav, Benjamin Herzberg, Benedito A. Carneiro, Elisa Fontana, Martin Højgaard, Michael J. Pishvaian, Ruth Plummer, Theresa L. Werner, Vaibhav Sahai, Stephanie Lheureux, Elizabeth K. Lee, Niharika B. Mettu, Gregory M. Cote, Joseph D. Schonhoft, Victoria Rimkunas, Ian M. Silverman, Marisa Wainszelbaum, Gerson Peltz, Adrian J. Fretland, Kezhen Fei, Danielle Ulanet, Insil Kim, Maria Koehler, Ezra Rosen, Michael Cecchini. Safety and efficacy of three PARP inhibitors (PARPi) combined with the ataxia telangiectasia- and Rad3-related kinase inhibitor (ATRi) camonsertib in patients (pts) with solid tumors harboring DNA damage response (DDR) alterations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT018.

High intensity focused ultrasound treatment for adenomyosis: comparison of efficacy based on MRI features

Objective To compare the clinical efficacy of High intensity-focused ultrasound(HIFU) for different types of adenomyosis classified by magnetic resonance imaging (MRI). Methods A total of 227 patients with adenomyosis who underwent HIFU treatment in Suining Central Hospital from January 2014 to December 2019 were included. Based on the preoperative pelvic MRI examination and Kishi isometric classification method, the patients were divided into 4 types according to the location of lesions. There were 82 cases of type I (endogenous type), 75 cases of type II (exogenous type), 34 cases of type III (nodular type), and 36 cases of type IV (heterogeneous type). The results of HIFU treatment for four types of adenomyosis and intraoperative adverse effects were analyzed. The changes of lesion size, dysmenorrhea, and menstrual volume were analyzed at 3 and 6 months after the operation. Result (1) adverse effects: All patients successfully accepted HIFU treatment under sedation and analgesia. Grade A adverse effects occurred in 51 cases (22.47%) and grade B adverse effects in 3 cases (1.32%). The incidence of adverse effects in type I–IV patients was 21.95%, 22.66%, 23.53%, and 30.56%, respectively. There was no significant difference in the incidence of grade A and B adverse effects in all types, and no grade C–F adverse effects occurred. (2) Ablation effect: The ablation rate of type III(nodular type)patients was (74.7 ± 20.3) %, which was significantly higher than that of the other three types (p < .05). (3) Changes in lesion size: the lesion size of all patients decreased after treatment and the reduction rate gradually increased with time. At 6 months after the operation, the lesion reduction rate of type III patients was (70.8 ± 14.8) %, higher than that of the other three types patients (p < .05). There was no significant difference in the reduction rate of type I, type II and type IV. (4) Remission of menorrhagia: At 6 months after the operation, the total remission rate of type III patients was 100%, while the total remission rate of type IV patients (65.4%, 17/26) that was lower than that of type I, II and III patients(p < .05). (5) Dysmenorrhea relief: At 6 months after the operation, the total dysmenorrhea relief rate of type III patients was 100% and the complete relief rate (28.1%, 18/31) was higher than that of the other three types, which was significant differences (p < .05). Conclusions HIFU is safe and effective in the treatment of different types of adenomyosis, the therapeutic effect of HIFU in patients with type III adenomyosis is better than that of the other three types.

Infarct growth velocity predicts early neurological outcomes in single subcortical infarction

In single subcortical infarction (SSI), changes in lesion size are a major determinant of early neurological deterioration. We evaluated the association between END and infarct growth velocity (IGV) in patients with SSI. We included consecutive patients with SSI who underwent MRI within 24 h of symptom onset between 2010 and 2020. END was defined as an increase of ≥ 2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 in the motor NIHSS score. IGV was calculated using the following formula: IGV (mL/h) = diffusion-weighted imaging volume (mL)/time to MRI (h). A total of 604 patients with SSI were evaluated. Multivariable logistic regression analysis showed that IGV remained significant after adjusting for confounders (aOR = 1.34, 95% CI 1.12–1.61). In a subgroup analysis based on the type of SSI, only patients with distal SSI showed an association between IGV and END (aOR = 1.64, 95% CI 1.24–2.16). In patients with proximal SSI, IGV did not show any statistical association with END. In conclusion, IGV was positively associated with END in patients with SSI. IGV should be interpreted differently in clinical settings depending on the location of the SSI lesion.

Is dienogest a convenient treatment option for cesarean scar endometriosis or should it be treated surgically?

ObjectivesEndometriosis-related conditions such as subcutaneous endometriosis have been frequently seen in recent years, and dienogest or surgical excision is generally preferred as a treatment option. Our aim in this study is to determine which treatment option will be more effective in reducing the symptoms of patients with cesarean scar endometriosis.Study designThis prospective study was performed with 21 patients diagnosed with cesarean scar endometriosis. The demographic features of the patients, lesion sizes before and after medical and surgical treatment, VAS scores and Ca-125 levels were recorded. VAS scores and lesion sizes were compared before-after medical treatment and before-after surgery in same group. ResultsA total of 18 women were identified, with a mean age of 32.3 ± 5.7 years. No significant decrease in lesion size was observed in the 1st and 6th-month controls after the use of dienogest (p > 0,05), while a significant decrease in VAS scores was detected (p < 0,05). After surgery, the decrease in both lesion size and VAS scores was found statistically significant (p < 0,05). ConclusionDienogest, which is frequently used in the medical treatment of pelvic and ovarian endometriosis, reduces pain minimally in cesarean scar endometriosis but does not provide a change in lesion size. Therefore, surgical treatment of cesarean scar endometriosis seems to be more effective in reducing pain and decreasing the size of the lesions.

Radiological and clinical features of multinodular and vacuolating neuronal tumor (MVNT)

BackgroundTo investigate the imaging findings and clinical features of multinodular and vacuolating neuronal tumor (MVNT).MethodsWe retrospectively sought for cases that have suspicious imaging findings for MVNT through the hospital information system. The patients’ demographics and clinical symptoms were extracted. All available images were re-examined.ResultsHeadache was the most common complaint (n = 7). Other complaints included seizure, stroke-like symptoms and numbness. Conventional MRI revealed that all lesions consisted of tiny, sharply marginated, round or ovoid nodules following the gyral contour. These nodules were hyperintense on T2 and FLAIR WI, hypointense on T1 WI. All lesions were characterized by a lack of enhancement and diffusion restriction. Mass effect and peripheral edema were not observed. MVNT presented as an incidental finding in one case who complained gynecomastia and had pituitary adenoma on pituitary MRI. All lesions were supratentorial—mostly on the right side (10/11)—and located in subcortical white matter. Follow-up MRI was available for 11 patients with a mean of 14.8 months (3–40 months). No change in lesion size and morphology was observed in these follow-up images.ConclusionsRadiological and clinical follow-up data suggest MVNT may exhibit indolent behavior. If asymptomatic, patients can be followed by imaging alone. Surgery should be considered for symptomatic patients.