Change In Lesion Size Research Articles

Morphologic Predictors and Temporal Characteristics of Conversion from Nonexudative to Exudative Age-Related Macular Degeneration in the Fellow Eye

To describe the systemic and ocular features of fellow eyes' association with nonexudative neovascularization (NV) based on OCT angiography (OCTA) and to identify longitudinal morphologic changes associated with progression to exudation. Cohort study of contralateral eye in patients with neovascular age-related macular degeneration (nAMD) in 1 eye. Patients with nAMD in one eye were eligble for inclusion and enrolled between June 2015 and Jan 2017. The study eye was the contralateral eye that was free of nAMD with a minimum follow-up of 1 year. Progressive multimodal imaging was performed on both eyes. Nonexudative NV was detected on OCTA in the study eye and quantitative changes analyzed. Nonexudative NV eyes were divided into progression to exudation or not during a minimum of 12 months follow-up. Association between systemic and ocular characteristics with nonexudative NV were determined. Change in OCTA size, vessel density, and vessel length density were compared between visits as predictors of progression to exudation. Among 229 study eyes, 21 (9.1%) had nonexudative NV detected on OCTA at baseline. Hyperlipidemia (adjusted odds ratio [AOR], 1.3; 95% confidence interval [CI], 1.10-3.20; P= 0.04), triglycerides (AOR,2.84 per mmol/L; 95% CI, 1.06-4.35 per mmol/L; P= 0.02), and baseline lesion size in the presenting eye (AOR, 1.6 per 500 μm; 95% CI, 1.21-3.25 per 500 μm; P= 0.03) were associated significantly with nonexudative NV in the study eye. In the study eye nonexudative NV group, 8 (38%) progressed to exudation, with a mean timeto exudation of 377 ± 138 days. The progressor group had larger baseline NV size (1834 ± 552.8 μm vs. 910± 461.7 μm; P < 0.01), higher increase in vessel density/year (8.3 ± 4.1%/year vs. 1.1 ± 2.5%/year; P ≤ 0.01), and higher increase in vessel length density/year (15.6 ± 10.6% vs. 1.9 ± 3.6%; P= 0.02). The change in lesion size per year was similar in both groups. Patients with nonexudative NV in the study eye had significant differences in ocular and systemic characteristics. More than a third of study eyes with nonexudative NV at baseline progressed to exudation, suggesting that close monitoring is essential. OCT angiography features associated with exudation include a larger baseline lesion size, increase in vessel density, and vessel length density.

Evaluation of Month-24 Efficacy and Safety of Epimacular Brachytherapy for Previously Treated Neovascular Age-Related Macular Degeneration

Although anti-vascular endothelial growth factor (VEGF) treatment offers better outcomes than the natural history of neovascular age-related macular degeneration (ARMD), a less burdensome, less expensive, and more durable treatment is needed. To assess the efficacy and safety of epimacular brachytherapy (EMB) for chronic, active, neovascular ARMD. The Macular Epiretinal Brachytherapy vs Ranibizumab (Lucentis) Only Treatment (MERLOT) pivotal device trial was conducted at 24 National Health Service hospitals across the UK. Patients who had neovascular ARMD and received intravitreal ranibizumab were enrolled between November 10, 2009, and January 30, 2012. Eligible patients were randomized 2:1 and were stratified by lens status and angiographic lesion type to receive either EMB plus as-needed ranibizumab or as-needed ranibizumab monotherapy. Participants were followed up monthly for 24 months and then assessed at a final visit at month 36. Masking of participants and clinicians was not possible, but best-corrected visual acuity (BCVA) and imaging were analyzed by masked assessors. Analysis followed the intent-to-treat approach. Pars plana vitrectomy with 24 Gy EMB plus as-needed ranibizumab vs as-needed ranibizumab monotherapy. Coprimary outcomes were the number of as-needed ranibizumab injections and the mean change in Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA with a noninferiority margin of -5 ETDRS letters. Secondary outcomes were the percentage of participants losing fewer than 15 ETDRS letters and gaining 0 or more or 15 or more ETDRS letters and the mean change in angiographic total lesion size, choroidal neovascularization size, and foveal thickness on optical coherence tomography. Of 363 participants, 329 (90.6%) completed 24 months of follow-up (222 participants in the EMB group and 107 in the ranibizumab group). The mean (SD) age of the combined groups was 76.5 (7.4) years. The mean (SD) number of ranibizumab injections was 9.3 (6.7) in the EMB group and 8.3 (4.5) in the ranibizumab group, with a difference of 1.0 injection (95% CI, -0.3 to 2.3; P = .13). The mean (SD) BCVA change was -11.2 (15.7) ETDRS letters in the EMB group and -1.4 (10.9) ETDRS letters in the ranibizumab group, with a difference of 9.8 ETDRS letters (95% CI, -6.7 to -12.9). In the EMB group, 65.6% of participants (160 of 244) lost fewer than 15 ETDRS letters vs 86.6% (103 of 119) in the ranibizumab group, with a difference of 21% (95% CI, 12.4%-29.5%; P < .001). Microvascular abnormalities occurred in 20 of 207 eyes (9.7%) in the EMB group and 1 of 97 eyes (1.0%) in the ranibizumab group. These abnormalities occurred outside the foveal center, and there were no unexpected safety concerns. The MERLOT trial found that despite the acceptable safety of EMB, it did not reduce the number of ranibizumab injections and was associated with worse visual acuity than anti-VEGF treatment alone; these results do not support EMB use as an adjunct treatment for chronic, active neovascular ARMD. ClinicalTrials.gov Identifier: NCT01006538.

Effect of Combined Use of Oral Prednisolone and Propranolol in the Treatment of Infantile Hemangioma: A Single Center Study

Background : Infantile hemangioma is a benign vascular tumor. Considerable controversy exists as to the management of hemangiomas. The purpose of this study was to see the efficacy and safety of orally administered prednisolone and propranolol in combination for treatment of potentially disfiguring or functionally threatening hemangiomas&#x0D; Materials and methods: In this prospective study, thirty two patients of hemangioma with age range of 1 month to 5 years were included who were treated with oral propranolol (1 mg/kg/ day in two divided doses) and oral prednisolone (2 mg/Kg/ day in single dose) in combination. This study was conducted in outpatient Department of Pediatric Surgery of Chattogram Medical College Hospital from January 2016 to December 2017. Changes in size and color of lesions were the two evaluating factors to see the efficacy of the treatment. Therapeutic response was graded as excellent, good, poor and no response.&#x0D; Results: Overall therapeutic response was 92.62% (29 patients). Excellent response was noted in 21 patients (65.62%) and in 3 patients (9.38%) there was no response. Range of treatment period was 6 to 20 weeks. No side effects except excessive weight gain was noted (6.25%).&#x0D; Conclusion: Combined use of low dose oral prednisolone and propranolol is more effective and safe for treatment of hemangioma.&#x0D; Chatt Maa Shi Hosp Med Coll J; Vol.18 (2); July 2019; Page 23-26

Natural History of Epithelioid Hemangioendothelioma of the Liver: CT Findings of 15 Cases

Little is known about the natural history of epithelioid hemangioendothelioma (EHE) of the liver. This study aimed to assess the natural history of hepatic EHE by evaluating CT findings of patients with pathologically proven hepatic EHE during follow-up without treatment. CT findings of 15 patients (seven men and eight women; median age, 56 years) with pathologically proven hepatic EHE were retrospectively evaluated. The median interval between the baseline and final CT was 36 months (range, 6-144 months). The maximal diameter of the largest hepatic lesion on the baseline CT and the diameter of the same lesion on the final CT were recorded. Change in size of the largest lesion between the two studies was classified as enlargement, no change, and reduction. When a patient with the largest lesion showing reduction developed a new hepatic lesion on the final CT, it was referred to as "unpredictable growth". CT revealed multiple hepatic lesions in all patients. Enlargement, no change, and reduction of the largest lesion were observed in four, five, and six patients, respectively. Unpredictable growth was observed in five patients. During the follow-up of untreated patients with hepatic EHE, spontaneous regression and appearance of a new hepatic lesion were occasionally observed in the same patient.

Effect of Intravenous Zoledronic Acid on Tibiofemoral Cartilage Volume Among Patients With Knee Osteoarthritis With Bone Marrow Lesions

A proof-of-principle study suggested that intravenous zoledronic acid may reduce knee pain and the size of bone marrow lesions in people with knee osteoarthritis, but data from large trials are lacking. To determine the effects of intravenous zoledronic acid on knee cartilage volume loss in patients with symptomatic knee osteoarthritis and bone marrow lesions. A 24-month multicenter, double-blind placebo-controlled randomized clinical trial conducted at 4 sites in Australia (1 research center and 3 hospitals). Adults aged 50 years or older with symptomatic knee osteoarthritis and subchondral bone marrow lesions detected by magnetic resonance imaging (MRI) were enrolled from November 2013 through September 2015. The final date of follow-up was October 9, 2017. Intravenous infusion with either 5 mg of zoledronic acid in a 100-mL saline solution (n = 113) or a placebo saline solution (n = 110) at baseline and 12 months. The primary outcome was absolute change in tibiofemoral cartilage volume assessed using MRI over 24 months (the minimum clinically important difference [MCID] has not been established). Three prespecified secondary outcomes were change in knee pain assessed by a visual analog scale (0 [no pain] to 100 [unbearable pain]; MCID, 15) and the Western Ontario and McMaster Universities Osteoarthritis Index (0 [no pain] to 500 [unbearable pain]; MCID, 75) over 3, 6, 12, 18, and 24 months and change in bone marrow lesion size over 6 and 24 months (the MCID has not been established). Of 223 participants enrolled (mean age, 62.0 years [SD, 8.0 years]; 52% were female), 190 (85%) completed the trial. Change in tibiofemoral cartilage volume was not significantly different between the zoledronic acid group and the placebo group over 24 months (-878 mm3 vs -919 mm3; between-group difference, 41 mm3 [95% CI, -79 to 161 mm3]; P = .50). No significant between-group differences were found for any of the prespecified secondary outcomes, including changes in knee pain assessed by a visual analog scale (-11.5 in the zoledronic acid group vs -16.8 in the placebo group; between-group difference, 5.2 [95% CI, -2.3 to 12.8]; P = .17), changes in knee pain assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (-37.5 vs -58.0, respectively; between-group difference, 20.5 [95% CI, -11.2 to 52.2]; P = .21), and changes in bone marrow lesion size (-33 mm2 vs -6 mm2; between-group difference, -27 mm2 [95% CI, -127 to 73 mm2]; P = .60) over 24 months. Adverse events were more common with zoledronic acid than with placebo (96% vs 83%, respectively) and consisted mainly of acute reactions (defined as symptoms within 3 days of administration of infusion; 87% vs 56%). Among patients with symptomatic knee osteoarthritis and bone marrow lesions, yearly zoledronic acid infusions, compared with placebo, did not significantly reduce cartilage volume loss over 24 months. These findings do not support the use of zoledronic acid in the treatment of knee osteoarthritis. anzctr.org.au Identifier: ACTRN12613000039785.

The association between change in bone marrow lesion size and change in tibiofemoral cartilage volume and knee symptoms - results from the ZAP2 trial

Purpose: Subchondral bone marrow lesions (BMLs) are an early sign of knee osteoarthritis (OA) that predicts both cartilage loss and symptomatic progression of OA. Previous studies have suggested targeting BMLs in short-term structure modification trials. A key hypothesis is that shrinkage of BMLs is associated with reduced cartilage loss and improved knee symptoms, but this has been debated. This study used data from a multicentre randomised controlled trial (ZAP2), in which all participants had symptomatic knee OA and BMLs, and the aim was to describe the association between change in BMLs and change in tibiofemoral cartilage volume and knee symptoms.

Longitudinal ultra-high field MRI of brain lesions in neuromyelitis optica spectrum disorders

BackgroundIn neuromyelitis optica spectrum disorder (NMOSD), clinical disability in NMOSD patients is relapse-related and progressive phase is rare. This observation raises the question whether there is any radiographic disease activity. The aim of present study was to determine the longitudinal changes in cerebral lesion number, lesion size, lesion-to-venule relationship, and morphological patterns of lesions in NMOSD using multiparametric 7T MR imaging. We also aimed to assess brain volume changes in NMOSD. MethodsA cohort of 22 patients with NMOSD underwent high-resolution 3D-susceptibility weighted imaging (SWI) and 2D-gradient-echo (GRE-T2*) weighted imaging on 7T MRI of brain at baseline and after ~2.8 years of follow-up. Morphologic imaging characteristics, and signal intensity patterns of lesions were recorded at both time points. Lesions were classified as "iron-laden" if they demonstrated hypointense signal on GRE-T2* images and/or SWI as well as hyperintense signal on quantitative susceptibility mapping (QSM). Lesions were considered "non-iron-laden" if they were hyperintense on GRE-T2*/SWI and isointense or hyperintense on QSM. Additionally, fractional brain parenchymal volume (fBPV) was computed at both time points. ResultsA total of 169 lesions were observed at baseline. At follow-up, 6 new lesions were found in 5 patients. In one patient, a single lesion could not be detected on the follow-up scan. No appreciable change in lesion size and vessel-lesion relationship was observed at follow up. All lesions demonstrated hyperintense signal intensity on GRE-T2* weighted images and isointense signal on QSM at both time points. Therefore, these lesions were considered as non-associated with iron pathology. Additionally, no significant change in brain volume was observed: fBPV 0.78 ± 0.06 at baseline vs. 0.77 ± 0.05 at follow up, p>0.05. ConclusionCerebral lesions in NMOSD patients remain ‘inert’ and do not show any substantial variations in morphological characteristics during a 2–3-year follow-up period.

Renal tumor biopsy to reduce overtreatment of renal oncocytomas.

623 Background: Up to 30% of renal masses are benign tumours, the most common of which is renal oncocytomas (RO). Our practice is to offer renal tumour biopsy (RTB) for small renal masses (SRM; ≤4cm) as part of a multi-disciplinary pathway. Our objective was to determine whether RTB influenced the management of RO. Methods: Retrospective descriptive analysis of the management of all sporadic cases with a histological diagnosis of RO (biopsy or surgical) at a high-volume tertiary centre from January/2012 to June/2019. Results: 170 patients (66% male; median age 67 years; median age-related Charlson comorbidity index 3) were diagnosed with 177 RO (median size 36mm). 70% (124) of RO were diagnosed using tumour biopsy (median size 33mm), of which 116 (93.4%) embarked on active surveillance (AS; 101) or watchful waiting (15). 53 (30%) RO were diagnosed after surgical excision (median size 50mm; 15 partial and 38 radical nephrectomies), of which 4 lesions were initially managed with AS. Median follow-up on AS was 20 months (2 to 84 months), with a median decrease in estimated glomerular filtration rate of 3 ml/min/1.73m2 over this period. 79% of RO on AS were SRMs. Median overall lesion size change was 1.1mm/year during follow up. Overall 62.6% of lesions grew, a quarter of which at a rate &gt;5mm/year. Nine cases of RO on AS changed to intervention due to lesion growth or patient choice. No metastases were reported in the whole cohort. Three patients on AS died (stroke, respiratory arrest secondary to food inhalation, and unknown cause). One patient who had had surgical excision of RO died of unknown cause. Conclusions: Surgical risks for benign renal lesions are not different to those taken for renal cell carcinoma. RTB reduces the use of unnecessary surgery and its incumbent morbidity for benign renal lesions, such as RO. AS is a safe management option for patients with RO and can be used to reduce overtreatment-associated harm.

Abstract P1-19-18: Everolimus, letrozole and trastuzumab in hormone receptor-positive, HER2-positive/amplified or mutant metastatic cancer: Evaluating synergy and overcoming resistance

Abstract Background: Combinations of HER2 and aromatase or mTOR inhibitors demonstrated activity in the clinical setting. We hypothesized that the triple combination of HER2 targeted therapy, aromatase and mTOR inhibitor has increased anticancer activity. Methods: We designed a 3+3 dose escalation phase I study of the aromatase inhibitor letrozole 2.5mg PO daily, mTOR inhibitor everolimus 2.5-10mg PO daily and HER2 antibody trastuzumab 4-8mg loading dose followed by 2-4mg maintenance dose IV on day 1 of 21-day cycle in patients with hormone-receptor positive, HER2-positive/amplified or mutant advanced cancers (confirmed by immunohistochemistry and/or FISH and/or next-generation sequencing) with preplanned expansion cohort at for patients with metastatic breast cancer to determine maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), dose limiting toxicities (DLT), overall safety and response (NCT02152943). Results: A total of 32 patients (men, 1; women, 31; HER2 amplification, 28; HER2 mutation, 4; breast cancer, 26; other cancers, 6), median age 55.5 years, median of 5 prior therapies (including letrozole [13] or other aromatase inhibitor [10]; everolimus [3]; trastuzumab [25] or other HER2 targeted therapy [2]) were enrolled in the planned 6 dose levels. The MTD has not been reached and letrozole 2.5mg PO daily, everolimus 10mg PO daily and trastuzumab 8mg loading dose followed by 4mg maintenance dose IV on day 1 of 21-day cycle was declared as RP2D. DLTs included grade 3 (G3) mucositis (1 patient) at dose level 3, and G3 thrombocytopenia, neutropenia (1 patient) at dose level 4. Other G3 or G4 treatment-related toxicities included G4 hyperglycemia in 1 patient, G3 hyperglycemia in 3 patients, G4 anemia in 1 patient, G3 anemia in 2 patients, G3 thrombocytopenia in 1 patient, G3 transaminitis in 1 patient, G3 mucositis in 1 patient and G3 headache in 1 patient. Of 32 patients, 5 (16%) had a partial response (all with heavily-pretreated breast cancer with HER2 amplification [4] or HER2A775_G776insYVMA mutation [1]), 23 (72%) stable disease (SD) including 5 (16%) patients with SD &amp;gt; 12 months (all with heavily-pretreated breast cancer) and 4 (13%) progressed. The median change in size of target lesions per RECIST 1.1. was -5% (-91% to +47%). Median time to treatment failure (TTF) was 4.3 months (95% CI 0.0-9.6). A total of 14 patients had serial plasma collection to assess dynamics of circulating tumor DNA and clonal evolution and the data will be presented at the meeting. Conclusions: The combination of letrozole, everolimus and trastuzumab is well tolerated with encouraging activity in heavily-pretreated patients with HER2-amplified or mutant advanced breast cancer. Citation Format: Alexej Ballhausen, Jennifer J Wheler, Daniel D Karp, Sarina A Piha-Paul, Siqing Fu, Shubham Pant, Apostolia M Tsimberidou, David S Hong, Vivek Subbiah, Veronica R Holley, Helen J Huang, Abeena M Brewster, Kimberly H Koenig, Nuhad K Ibrahim, Funda Meric-Bernstam, Filip Janku. Everolimus, letrozole and trastuzumab in hormone receptor-positive, HER2-positive/amplified or mutant metastatic cancer: Evaluating synergy and overcoming resistance [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-18.

Small (< 4cm) Bosniak renal cysts: association of initial fluid percentage and enhancing solid volume thresholds with future lesion behavior.

Evaluate the fluid percentage (FP) and enhancing solid volume (SV) of small (< 4cm) Bosniak 2F, 3 and 4 renal lesions and the association with Bosniak category at baseline and follow-up. Hospital database was searched from 1/1/2010 to 8/3/2018 for small (< 4cm) Bosniak 2F, 3 and 4 lesions studied with initial and follow-up C+CT/MRI. Two radiologists blindly assigned Bosniak categories to first and last available studies. One radiologist performed volumetric analysis of each lesion, calculating the FP and SV. Association with Bosniak category was explored. 121 patients (84:37 M:F) were identified with 136 renal lesions (84, 37 and 15 Bosniak category 2F, 3 and 4) and followed for 1-12.3years (mean 3.5years). 87% (73/84) of 2F lesions were downgraded or remained stable. 48% (25/52) of 3/4 lesions were downgraded. Higher FP was associated with a lower Bosniak category (p value = 0.0042). Increase in FP was associated with the probability of being downgraded on follow-up (OR 1.03, p value = 0.0036), while increase in fluid volume of lesion was directly associated with change in overall lesion size among lesions that were downgraded (b-estimate = 0.03, p value = 0.0003). All Bosniak 3/4 lesions with initial SV less than 0.05cc were downgraded. FP and SV are useful quantitative surrogates for Bosniak category and future behavior, respectively. Growth of small renal lesions by an increase in fluid volume and FP leads to a downgrade in Bosniak category. Initial SV less than 0.05 cc in Bosniak 3/4 lesions suggests possible future downgrade.

Clinical performance of Xpert Bladder Cancer (BC) Monitor, a mRNA-based urine test, in active surveillance (AS) patients with recurrent non-muscle-invasive bladder cancer (NMIBC): results from the Bladder Cancer Italian Active Surveillance (BIAS) project

To investigate the clinical performance of a new mRNA-based urine test, aiming to avoid unnecessary follow-up cystoscopy in patients under active surveillance (AS) for recurrent NMIBC. This is a prospective cohort study enrolling patients with history of low-grade (LG) NMIBC, who developed a recurrence during the follow-up and underwent AS. Their urinary samples were analyzed by Xpert BC Monitor (Cepheid, Sunnyvale, CA, USA). The primary endpoint was to investigate if Xpert BC Monitor could avoid unnecessary cystoscopy during the follow-up period. Its sensitivity, specificity, PPVs and NPVs were calculated. A cutoff of 0.4 "linear discriminant analysis" (LDA) was optimized for the AS setting. The cohort consisted of 106 patients with a mean age of 72 ± 9.52 and a median follow-up from AS start of 8.8 (range 0-56.5) months. No statistically significant difference was found for the mean age, smoker status, lesion size, and number of lesions with a cutoff of 0.4. Of 106 patients, 22 (20.8%) were deemed to require treatment because of cystoscopic changes in size and/or number of lesions during the follow-up period. Using a cutoff value of < 0.4, 34 (33.7%) cystoscopies could be avoided due to low LDA value, missing 2/22 (9%) failures, none with high-grade (HG) NMIBC. Further research on larger population remains mandatory before its clinical use. Xpert BC Monitor seems to be a reliable assay, which might avoid unnecessary cystoscopies without missing HG NMIBC when its cutoff is optimized for the AS setting.

1382PD - Relation between objective tumour shrinkage and progression-free survival (PFS) in the NETTER-1 population

BackgroundNETTER-1 demonstrated that Radioligand Therapy (RLT) with LUTATHERA® significantly prolongs PFS in progressive midgut neuroendocrine tumor patients compared to 60mg octreotide (Oct). In oncology, treatment efficacy has often been associated with early reduction of tumor size. As RLT differs from traditional treatments, we sought to verify whether objective tumor shrinkage predicts duration of PFS by assessing the relations between changes in lesion size and treatment efficacy, evaluated by PFS among NETTER-1 patients. MethodsPost-hoc analyses were performed on the NETTER-1 population on local tumor imaging assessments on the full analyses set (n=231) with data cut-off date on June 30th, 2016. The best response (change from baseline in sum of target lesion diameters) during 3 intervals after treatment onset was used as a covariate in a Cox regression, thus differentiating whether the time corresponds to an event or a censoring. One interval corresponded to 150 days, i.e. a month prior to 4th injection; 180 days matched the 4th injection and the last interval was set to no limit. ResultsFor patients treated with Oct, Cox regression showed a HR of 0.914 [95% CI: 0.860 – 0.971], p=0.0034. This suggests that the risk of disease progression decreases by 9% for each incremental percentage of shrinkage. Among the patients treated with Lu, Cox regression showed a HR of 1.006 [0.982 – 1.03] p=0.6236, suggesting that LUTATHERA® prolonged PFS even when tumor objective response was undetected during treatment cycles. As a sensitivity, a 180-day-limit and no-limit (i.e. using the best response up to time of censoring/event) were also applied. With the 180-day-limit, HRs were 0.952 [0.904 - 1.003], p=0.0652 and 1.013 [0.991-1.037], p=0.2523 for Oct and Lu, respectively; similarly the no-limit, HRs were 0.952 [0.922, 0.982] p=0.0023 and 1 [0.984, 1.017] p=0.9713. ConclusionsDurable response of LUTATHERA® treatment goes beyond objective tumor shrinkage. This study conveys crucial information on the patient’s management with respect to LUTATHERA®: treatment benefit of 4 cycles should not be assessed only by objective tumor shrinkage. Clinical trial identificationNETTER-1: NCT01578239. Legal entity responsible for the studyAdvanced Accelerator Applications. FundingAdvanced Accelerator Applications. DisclosureM.E. Pavel: Advisory / Consultancy: Novartis. P. Broberg: Full / Part-time employment: Advanced Accelerator Applications. M. Caplin: Advisory / Consultancy, Speaker Bureau / Expert testimony: Advanced Accelerator Applications. P. Ruszniewski: Speaker Bureau / Expert testimony: Advanced Accelerator Applications. P. Santoro: Full / Part-time employment: Advanced Accelerator Applications. L. Ravasi: Full / Part-time employment: Advanced Accelerator Applications. All other authors have declared no conflicts of interest.

2477 Strongyloidiasis Presenting as Isolated Hepatic Mass in an Immunocompetent Host: A Case Report

INTRODUCTION: Strongyloidiasis is caused by an infection with Strongyloides stercoralis. Manifestations range from absent to minimal symptoms in immunocompetent persons to a hyperinfection syndrome in immunocompromised persons. Hepatobiliary complications have been described as granulomatous hepatitis and biliary obstruction. We report a case of strongyloidiasis presenting as a solitary hepatic mass in an immunocompetent patient. CASE DESCRIPTION/METHODS: A 27-year-old woman with no past medical history or medications and recent travel to Costa Rica presented with intermittent right upper quadrant pain after trauma while skiing. She had no hepatomegaly, tenderness, or signs of chronic liver disease on exam. Laboratory analysis showed WBC 24.7 103/mL, absolute eosinophils 15,314 cells/mL, AST 21 U/L, ALT 35 U/L, ALP 106 IU/L, albumin 3.9 g/dL, and total bilirubin 0.3 mg/dL. Strongyloides IgG was positive. Stool was unremarkable. CEA, AFP, and CA 19-9 levels were normal. Abdominal US revealed a hepatic mass. MRI confirmed a 5 × 6 cm lesion in the inferior and anterior right lobe (Figure 1). The patient received ivermectin for strongyloidiasis. Repeat MRI at 4 weeks showed no change in lesion size. To prepare for lesion excision, the patient underwent CT imaging at 7 weeks. This showed a significant decrease in mass size to 3 × 2.5 cm (Figure 2). Surgery was deferred. MRI at 15 weeks showed continued resolution of the mass to a long axis of 2.5 cm. Marked lesion improvement with ivermectin alone was felt consistent with strongyloidiasis. DISCUSSION: Chronic strongyloidiasis affects 30 million people worldwide, with clinical significance mediated by equilibrium between human host and helminthic parasite. Most people are asymptomatic or have nonspecific gastrointestinal symptoms. Hepatic presentation is exceedingly rare and has been associated with immunocompromise and dissemination. To our knowledge, only one case of immunocompetent hepatic presentation has been reported. 1 In the presently described case, a large hepatic lesion in a healthy woman with marked eosinophilia was initially evaluated for a neoplastic process. Strongyloides consideration and testing was key to obtaining the diagnosis. Imaging also expanded our understanding of the range of possible radiographic findings in this disease. Physicians should be aware of chronic strongyloidiasis as they consider the differential for hepatic masses in immunocompetent patients.

Can the MOCART Scoring System Correlate with Patient Reported Foot and Ankle Outcome Scores After Ankle Cartilage Repair Procedures?

Category:Ankle, Arthroscopy, SportsIntroduction/Purpose:The magnetic resonance observation of cartilage repair tissue (MOCART) scoring system was developed and modified to allow for assessment of articular cartilage repair tissue in the foot and ankle. The purpose of this study was to evaluate the intra- and inter-rater reliability of the MOCART score following a variety of surgical procedures to repair chondral injuries within the ankle joint as well as to correlate these scores to clinically relevant functional outcomes scores. By correlating functional outcome scores with each variable evaluated by the MOCART scoring system as well as the presence of edema and cysts postoperatively, we aimed to identify the radiographic parameters most closely associated with clinical outcomes.Methods:Patients treated for a chondral injury after August 2006 by a fellowship-trained foot and ankle surgeon at our institution were included if their postoperative MRI and Foot and Ankle Outcome Score (FAOS) were completed within 5 months of one another. Surgical interventions used to stimulate reparative cartilage formation included osteochondral graft transplantation, debridement, microfracture, microfracture augmented by bone marrow aspirate concentrate (BMAC), juvenile particulate cartilage implantation, or another adjunctive therapy like micronized allogenic cartilage extracellular matrix. Two radiologists (R1-R2) independently reviewed and scored each MRI using the MOCART system. A total MOCART score ranging between 0 and 100 was calculated for each patient. In addition, the presence or absence of postoperative cysts and edema was documented. Inter- and intra- rater reliability were calculated using Intraclass Correlation Coefficients (ICC), and MOCART scores were correlated with FAOS to test for relative functional and clinical relevance. Correlations were calculated as Pearson Correlation Coefficients.Results:Forty-six patients (average age 35 +/- 13.49) under the care of nine different surgeons met inclusion criteria. Average follow-up was 18 months. For overall MOCART score, intra-rater ICC = 0.87 (p<0.01) for R1 and ICC = 0.78 (p<0.01) for R2. Inter-rater reliability ICC = 0.55 – 0.69 for total MOCART score (p<0.01). Overall MOCART score negatively correlated with pre-to-postoperative differences in FAOS subcategories. Correlation coefficients ranged from -0.09 to -0.48 for these variables. This correlation was significant (p<0.01) for the difference in the FAOS Pain and Activities of Daily Living subcategories. In addition, change in FAOS Pain subcategory (r = 0.42; p=0.01) and lesion size (r=0.45; p<0.01) had a moderate but significant correlation with the presence of postoperative cysts (r = 0.42; p=0.01).Conclusion:Intra-rater reliability for an overall MOCART score was relatively strong for each rater while the correlation between raters ranged from strong to moderate. As such, an overall MOCART score appears to be a somewhat reproducible measure. Weak to moderate negative correlational coefficients between the overall MOCART score and postoperative FAOS scores and changes in FAOS scores indicated the MOCART score may be limited in its ability to predict clinical outcomes. Finally, presence or absence of a postoperative cyst may be a useful category that significantly helps predict changes in FAOS pain as well as the size of the lesion preoperatively.

Natural Progression and Factors Predicting Growth of Retroperitoneal Schwannoma.

Although knowledge of the natural history of retroperitoneal schwannoma, including growth rate, would be useful when determining the indications and timing of surgical treatment for such nonpalpable tumors, the existing evidence is unclear. We examined the natural history of retroperitoneal schwannoma and assessed whether magnetic resonance imaging (MRI) and clinical findings predict future growth. Among patients with retroperitoneal schwannoma treated in our department during the period from January 1, 2015 through December 31, 2015, eight who underwent follow-up assessment by MRI and did not undergo tumor resection for longer than 1 year were enrolled. Changes in lesion size were examined in relation to selected clinical and MRI findings. In cases of pressure erosion in the vertebral body, change in the size of the intraosseous region was compared to change in the size of the whole lesion. Median absolute growth rate (AGR) was 1.9 cm3 per year, median relative growth rate (RGR) was 5.6% per year, and median tumor volume doubling time (VDT) was 3.1 years. AGR, RGR, and VDT were not associated with any clinical variable. RGR and VDT values in the intraosseous region were about twice those of the whole lesions. The growth rates of retroperitoneal schwannomas varied. Additionally, no MRI or clinical findings predicted growth of retroperitoneal schwannoma. Therefore, careful follow-up is necessary for this tumor type, especially for lesions with bone erosion.

Topical Recombinant Human Nerve Growth Factor (Cenegermin) for Neurotrophic Keratopathy: A Multicenter Randomized Vehicle-Controlled Pivotal Trial

To evaluate the efficacy and safety of topical cenegermin (recombinant human nerve growth factor) in patients with neurotrophic keratopathy. Multicenter, randomized, double-masked, vehicle-controlled trial. Patients with neurotrophic persistent epithelial defect with or without stromal thinning. The NGF0214 trial, conducted among 11 sites in the United States, randomized 48 patients 1:1 to cenegermin 20 μg/ml or vehicle eye drops, 6 drops daily for 8 weeks of masked treatment. Follow-up was 24 weeks. Safety was assessed in all patients who received study drug. Efficacy was assessed by intention to treat. The primary end point was healing of the neurotrophic lesion (persistent epithelial defect or corneal ulcer) after 8 weeks of masked treatment. Masked central readers measured neurotrophic lesions in randomized clinical pictures, then assessed healing status conventionally (<0.5 mm of fluorescein staining in the greatest dimension of the lesion area) and conservatively (0-mm lesion staining and no other residual staining). Secondary variables included corneal healing at 4 weeks of masked treatment (key secondary end point), overall changes in lesion size, rates of disease progression, and changes in visual acuity and corneal sensitivity from baseline to week8. Conventional assessment of corneal healing showed statistically significant differences at week 8: compared to 7 of 24 vehicle-treated patients (29.2%), 16 of 23 cenegermin-treated patients (69.6%) achieved less than 0.5 mm of lesion staining (+40.4%; 95% confidence interval [CI], 14.2%-66.6%; P= 0.006). Conservative assessment of corneal healing also reached statistical significance at week 8: compared to 4 of 24 vehicle-treated patients (16.7%), 15 of 23 cenegermin-treated patients (65.2%) achieved 0 mm of lesion staining and no other residual staining (+48.6%; 95% CI, 24.0%-73.1%; P < 0.001). Moreover, the conservative measure of corneal healing showed statistical significance at week 4 (key secondary end point). Compared to vehicle, cenegermin-treated patients showed statistically significant reductions in lesion size and disease progression rates during masked treatment. Cenegermin was well tolerated; adverse effects were mostly local, mild, and transient. Cenegermin treatment showed higher rates of corneal healing than vehicle in neurotrophic keratopathy associated with nonhealing corneal defects.

Arterial subtraction images of gadoxetate-enhanced MRI improve diagnosis of early-stage hepatocellular carcinoma

Background & AimsAlthough gadoxetate disodium-enhanced magnetic resonance imaging (MRI) shows higher sensitivity for diagnosing hepatocellular carcinoma (HCC), its arterial-phase images may be unsatisfactory because of weak arterial enhancement. We investigated the clinical effectiveness of arterial subtraction images from gadoxetate disodium-enhanced MRI for diagnosing early-stage HCC using the Liver Imaging Reporting and Data System (LI-RADS) v2018. MethodsIn 258 patients at risk of HCC who underwent gadoxetate disodium-enhanced MRI in 2016, a total of 372 hepatic nodules (273 HCCs, 18 other malignancies, and 81 benign nodules) of 3.0 cm or smaller were retrospectively analyzed. Final diagnosis was assessed histopathologically or clinically (marginal recurrence after treatment or change in lesion size on follow-up imaging). The detection rate for arterial hyperenhancement was compared between ordinary arterial-phase and arterial subtraction images, and the benefit of arterial subtraction images in diagnosing HCC using LI-RADS was assessed. ResultsArterial subtraction images had a significantly higher detection rate for arterial hyperenhancement than ordinary arterial-phase images, both for all hepatic nodules (72.3% vs. 62.4%, p <0.001) and HCCs (91.9% vs. 80.6%, p <0.001). Compared with ordinary arterial-phase images, arterial subtraction images significantly increased the sensitivity of LI-RADS category 5 for diagnosis of HCC (64.1% [173/270] vs. 55.9% [151/270], p <0.001), without significantly decreasing specificity (92.9% [91/98] vs. 94.9% [93/98], p = 0.155). For histopathologically confirmed lesions, arterial subtraction images significantly increased sensitivity to 68.8% (128/186) from the 61.3% (114/186) of ordinary arterial-phase images (p <0.001), with a minimal decrease in specificity to 84.8% (39/46) from 89.1% (41/46) (p = 0.151). ConclusionsArterial subtraction images of gadoxetate disodium-enhanced MRI can significantly improve the sensitivity of early-stage HCC diagnosis using LI-RADS, without a significant decrease in specificity. Lay summaryGadoxetate disodium-enhanced magnetic resonance imaging is an imaging technique with a high sensitivity for the diagnosis of hepatocellular carcinoma. However, arterial-phase images may be unsatisfactory because of weak arterial enhancement. We found that using arterial subtraction images led to clinically meaningful improvements in the diagnosis of early-stage hepatocellular carcinoma.

Comparison of the Efficacy of Two Microsphere Embolic Agents for Transcatheter Arterial Chemoembolization in Hepatocellular Carcinoma Patients.

PurposeTransarterial chemoembolization (TACE) delivers cytotoxic drugs intra-arterially and induces ischemic necrosis by arterial embolization. Embolization is achieved using a variety of agents that differ widely in particle size and range, deformation, and in vivo arterial distribution. The clinical significance of these differences has not been thoroughly characterized. The present study is to compare the efficacy of Embosphere and Embozene microspheres in TACE therapy for hepatocellular carcinoma.Materials and MethodsThis retrospective study includes 108 hepatocellular carcinoma (HCC) patients who received TACE/doxorubicin with Embozene (70 patients) or Embosphere (38 patients) at a single medical center. Patient outcomes, including liver function, tumor size, tumor response, and complications after treatment, were analyzed. The change in total target lesion size and tumor response was evaluated according to embolization agent and clinical characteristics.ResultsThe postoperative glutamate oxaloacetate transaminase (mean, 194.5 vs. 147.5; p=0.032) and bilirubin (mean, 1.11 mg/dL vs. 0.73 mg/dL; p=0.016) were higher among patients treated with Embozene, the decrease in the number (55.86±25.55% vs. 41.81±38.51%, p=0.027) and size (56.37±25.91 mm vs. 43.44±37.89 mm, p=0.001) of liver tumors relative to baseline was greater in these patients than in those treated with Embosphere. These greater antitumor effects were achieved using lower doses of doxorubicin than for treatment with Embozene. Minor complications were more common among patients treated with Embosphere than with Embozene.ConclusionThese results suggest that Embozene is more efficacious than Embosphere for HCC treatment using TACE/doxorubicin.

Response to immunohistochemical markers' conversion after neoadjuvant chemotherapy in breast cancer patients: association between imaging and histopathologic analysis.

Breast ultrasound and mammography were used in the detection of residual tumor after neoadjuvant chemotherapy. The aim of this study was to evaluate the correlation between clinical and pathological responses with breast density and IHC marker conversion to understand how this information might be used in the future to direct treatment. We included 119 patients who underwent CNB and followed NACT. The breast density assessment was based on the mammography examination performed at the time of diagnosis. We evaluated the clinical and pathological responses to NACT by the UICC and Miller-Payne grading systems, respectively. Of 119 patients who met the inclusion criteria, patients with high pre-treatment IHC markers levels showed higher expression of IHC markers regardless of the post-treatment IHC marker level at baseline. However, breast and node tumor sizes before and after NACT were negatively correlated with hormone receptor conversion and positively correlated with Ki-67 conversion (P < 0.05). Patients with low BD were more likely to have a cCR, pCR, TNBC, and postmenopausal status than those with a high BD (P < 0.05). BD was significantly associated with PR and Ki67 conversion but not ER conversion. Our prospective observational study demonstrated that IHC marker conversion could be used to identify lesion size changes and BD. We also found that a high BD was linked to clinical and pathological responses, molecular subtype, and menopausal status. In the future, additional studies are required to validate the predictive value identified by this research.

Clinical outcomes and prognostic factors for cavernous hemangiomas of the spinal cord: a retrospective cohort study

Intramedullary cavernous hemangioma (CH) is a rare vascular lesion that is mainly characterized by the sudden onset of hemorrhage in young, asymptomatic patients, who then experience serious neurological deterioration. Despite the severity of this condition, the therapeutic approach and timing of intervention for CH remain matters of debate. The aim of this study was to evaluate the clinical characteristics of CH patients before and after surgery and to identify prognostic indicators that affect neurological function in these patients. This single-center retrospective study included 66 patients who were treated for intramedullary CH. Among them, 57 underwent surgery and 9 patients received conservative treatment. The authors collected demographic, symptomology, imaging, neurological, and surgical data. Univariate and multivariate logistic regression analyses were performed to identify the prognostic indicators for neurological function. When comparing patients with stable and unstable gait prior to surgery, patients with unstable gait had a higher frequency of hemorrhagic episodes (52.4% vs 19.4%, p = 0.010), as assessed by the modified McCormick Scale. The lesion was significantly smaller in patients who underwent conservative treatment compared with surgery (2.5 ± 1.5 mm vs 5.9 ± 4.1 mm, respectively; p = 0.024). Overall, the patients experienced significant neurological recovery after surgery, but a worse preoperative neurological status was identified as an indicator affecting surgical outcomes by multivariate analysis (OR 10.77, 95% CI 2.88–40.36, p < 0.001). In addition, a larger lesion size was significantly associated with poor functional recovery in patients who had an unstable gait prior to surgery (8.6 ± 4.5 mm vs 3.5 ± 1.6 mm, p = 0.011). Once a hemorrhage occurs, surgical intervention should be considered to avoid recurrence of the bleeding and further neurological injury. In contrast, if the patients with larger lesion presented with worse preoperative functional status, surgical intervention could have a risk for aggravating the functional deficiencies by damaging the thinning cord parenchyma. Conservative treatment may be selected if the lesion is small, but regular neurological examination by MRI is needed for assessment of a change in lesion size and for detection of functional deterioration. AIS = ASIA Impairment Scale; ASIA = American Spinal Injury Association; CH = cavernous hemangioma; EBL = estimated blood loss; JOA = Japanese Orthopaedic Association; mMS = modified McCormick Scale.