Presence Of New Lesions Research Articles

Comparison between lymecycline with multidrug therapy and standard multidrug regimen (WHO-MDT) in the treatment of multibacillary leprosy patients: a retrospective cohort study.

Hansen's disease or leprosy is a chronic, infectious disease that has locally and globally afflicted all populations. Despite standard treatment with multidrug therapy (WHO-MDT), the incidence of drug resistance has been an increasingly prevalent global problem in leprosy management. This study compared the effectiveness between lymecycline with WHO-MDT and standard WHO-MDT in leprosy treatment. The research is a retrospective cohort study at a tertiary hospital from January 2011 to July 2021. Pre- and post-treatment bacillary index, presence of new lesions, nerve function impairment, and leprosy reactions were obtained through chart review. The results showed a significant difference in bacteriological index (BI) in both groups at the end of the treatment. However, a higher reduction in BI was noted for the lymecycline group. For the group that took WHO-MDT alone, BI decreased by 0.7 (P < 0.001) whereas patients who took lymecycline and WHO-MDT had a BI difference of 3 (P < 0.001) upon completion of treatment. A significant decrease in the recurrence of lesions (P = 0.006) and nerve function impairment (P = 0.038) was also noted in the lymecycline group whereas there was no significant difference in leprosy reactions between the two groups. Lymecycline 600 mg daily for 3 months can be used as an adjunct in cases of leprosy resistance and treatment failure among multibacillary patients. Lymecycline significantly reduced bacillary index, recurrence of skin lesions, and nerve function impairment through its possible immunomodulatory, antiapoptotic, and neuroprotective effects.

RELATIONSHIP OF ARTERIAL STIFFNESS AND BASELINE CEREBRAL SMALL VESSEL DISEASE SCORE, WITH THE OCCURRENCE OF NEW LESIONS AFTER 2 YEARS OF FOLLOW-UP, INDEPENDENTLY OF BP CONTROL

Objective: Hypertension is a prominent determinant of cerebral small vessel disease (cSVD). The aim of this study was to assess in subjects with a recent lacunar stroke, the factors associated with the occurrence of new lesions of cSVD after 2 years of follow-up. Design and method: Patients with a recent small subcortical infarct according to STRIVE criteria were consecutively included in this prospective study. Clinical BP was measured after 5 min of rest in a sitting position using a validated semiautomatic device (OMRON Digital Automatic Blood Pressure Monitor Model HEM-907XL, Kyoto, Japan). Three measurements of BP were averaged to determine values of clinical BP at baseline and at 3, 6, 12 and 24 months of follow-up. 24h-Ambulatory blood pressure monitoring (ABPM) was performed after hospital discharge within 30 days after stroke onset and after 2-years follow-up. The aortic pulse wave velocity (aPWV), the augmentation index (AIx) and 24h brachial and central BP (24h-ABPM) were measured by means of a Mobil-O-Graph PWV (IEM, Stolberg, Germany) device. The AIx was normalized for heart rate of 75 bpm (AIX75). Brain MRI was performed using a Phillips Achieva 1.5 T MRI at admission and at 2-years follow-up. Results: A total of 103 patients, aged 67.04 (10.9) years, 30.4% female, were included. Follow-up MRI was acquired in 92 patients. Backwards stepwise logistic regression analysis showed that 24h-PWV (OR 1.44 CI 95% 1.01-2,06 p = 0.044) and cSVD score (OR 2.3 CI 95% 1.41-3.77, p = 0.001) were associated with the presence of new lesions. Significance for 24h-PWV was lost after introducing age in de model, and only cSVD score remained significant (OR 2.33 CI95% 1.34-3.98, p = 0.002). The presence of new lesions was not significantly different between patients with or without BP control defined by BP &lt; 130/80 mm Hg during the 24h-ABPM. Conclusions: In subjects with a lacunar stroke, 24h-PWV and cSVD score were associated significantly with the presence of new lesions after 2 year of follow-up, independently of BP control

Comparison of response from RECIST1.1 and abstraction in real-world patients with lung cancer.

e21194 Background: Treatment response in clinical trials with solid tumors is measured by applying RECIST1.1 to radiographic images. However, response in real-world data (RWD) studies is based on information abstracted from clinician's notes. Differences in these two approaches can lead to bias when comparing response in trials to RWD. This study investigates the relationship between response from (1) certified radiologists applying RECIST1.1 to images from routine care and (2) electronic health records (EHR) notes-abstraction in the same patients. Methods: The nationwide Flatiron Health (FH) EHR-derived de-identified database was used to identify patients diagnosed with advanced non-small-cell lung cancer (aNSCLC) on/after Jan 1, 2011, with a visit in the FH network within 90 days of diagnosis, first line treatment (1L), and ≥1 radiographic image both at baseline (8 weeks before or at 1L start) and during 1L. RECIST1.1 and response abstraction were applied retrospectively to images and EHR notes obtained from routine care, respectively. For each patient, time-point responses were determined by RECIST1.1 (rwRECIST) and abstraction (rwR) and dichotomized as unconfirmed best overall response (BOR, complete+partial response = responder, all others = non-responder), and confirmed BOR if patients had an additional assessment. Results: We included 157 patients (59% on chemotherapy, 15%/12% on cancer immunotherapy combination/alone, 10% on targeted therapies). Patients had an image taken every 11 weeks (median). All images were readable and 75% were optimal quality. Response rate was lower by rwRECIST than rwR (unconfirmed: 48% vs 59%; confirmed: 34% vs 55%). Concordance in BOR between rwRECIST and rwR was 68%/60% for unconfirmed/confirmed response. Disagreement between rwRECIST and rwR was higher than inter-reader variability between radiologists and was mainly in one direction (rwR higher, Table). The disagreement was driven by patients deemed responders by abstraction who did not meet the -30% target lesion size cutoff specified by RECIST1.1 or presence of new lesions. Conclusions: RECIST1.1 can be applied to images from aNSCLC routine oncology care, although limited by image availability and less frequent assessment than trials. Differences were observed in response measured by rwRECIST and by abstraction. [Table: see text]

Accuracy of Two Visual Criteria for the Assessment of Caries around Restorations: A Delayed-Type Cross-Sectional Study

The aim of this study was to compare the performance of two visual criteria used for the detection of caries around restorations in permanent teeth. In this delayed-type cross-sectional study, the study sample was randomly allocated to one of two visual criteria for the assessment of restorations as follows: (a) International Dental Federation (FDI) criteria, considers marginal staining, marginal adaptation, and caries recurrence and (b) Caries Associated with Restorations or Sealants (CARS) criteria, defined by the International Caries Classification and Management System. A calibrated examiner assessed the restorations using two reference standards as follows: (i) for restorations requiring operative interventions (repair/replacement), the restoration was partially or totally removed and the presence or absence of carious tissue was assessed; and (ii) for restorations requiring nonoperative intervention, follow-up for a period of 1 year was recommended to allow identification of the presence of new lesions not detected at baseline. The sensitivity, specificity, area under receiver operating characteristic curve (Az), and accuracy of the criteria were assessed. The study included 305 restorations. The FDI marginal staining parameter had the lowest Az value (Az = 0.501), while similar sensitivity was observed between the CARS (62.0%), FDI presence of caries (65.0%), and FDI marginal adaptation (74.0%) parameters. CARS exhibited the highest specificity (88.3%) and accuracy (85.6%). The CARS criteria exhibited better specificity and accuracy in detecting caries around restorations, followed by the FDI criteria for caries recurrence and marginal adaptation. Considering marginal staining or combining multiple marginal features to assess secondary caries resulted in an increased risk of false-positive outcomes and overtreatment.

Improving the detection of new lesions in multiple sclerosis with a cascaded 3D fully convolutional neural network approach.

Longitudinal magnetic resonance imaging (MRI) has an important role in multiple sclerosis (MS) diagnosis and follow-up. Specifically, the presence of new lesions on brain MRI scans is considered a robust predictive biomarker for the disease progression. New lesions are a high-impact prognostic factor to predict evolution to MS or risk of disability accumulation over time. However, the detection of this disease activity is performed visually by comparing the follow-up and baseline scans. Due to the presence of small lesions, misregistration, and high inter-/intra-observer variability, this detection of new lesions is prone to errors. In this direction, one of the last Medical Image Computing and Computer Assisted Intervention (MICCAI) challenges was dealing with this automatic new lesion quantification. The MSSEG-2: MS new lesions segmentation challenge offers an evaluation framework for this new lesion segmentation task with a large database (100 patients, each with two-time points) compiled from the OFSEP (Observatoire français de la sclérose en plaques) cohort, the French MS registry, including 3D T2-w fluid-attenuated inversion recovery (T2-FLAIR) images from different centers and scanners. Apart from a change in centers, MRI scanners, and acquisition protocols, there are more challenges that hinder the automated detection process of new lesions such as the need for large annotated datasets, which may be not easily available, or the fact that new lesions are small areas producing a class imbalance problem that could bias trained models toward the non-lesion class. In this article, we present a novel automated method for new lesion detection of MS patient images. Our approach is based on a cascade of two 3D patch-wise fully convolutional neural networks (FCNNs). The first FCNN is trained to be more sensitive revealing possible candidate new lesion voxels, while the second FCNN is trained to reduce the number of misclassified voxels coming from the first network. 3D T2-FLAIR images from the two-time points were pre-processed and linearly co-registered. Afterward, a fully CNN, where its inputs were only the baseline and follow-up images, was trained to detect new MS lesions. Our approach obtained a mean segmentation dice similarity coefficient of 0.42 with a detection F1-score of 0.5. Compared to the challenge participants, we obtained one of the highest precision scores (PPVL = 0.52), the best PPVL rate (0.53), and a lesion detection sensitivity (SensL of 0.53).

Post-PRRT scans: which scans to make and what to look for

AimThe aim of this study was to evaluate the clinical utility of SPECT/CT (imaging of uptake in tumor lesions and additional findings) and the additional value of planar imaging in order to simplify clinical imaging protocols and decrease patients burden.Materials and methodsOne hundred consecutive patients with metastatic neuroendocrine tumor (NET) treated with PRRT were included. Post-therapy imaging was performed 24 h after each PRRT cycle by both whole-body planar imaging and abdominal- and thoracic SPECT/CT. All images were evaluated for (1) the presence of new lesions, (2) discordant lesions between the two acquisitions (planar or SPECT), (3) location of lesions on SPECT (abdominal, thoracic, or both), and (4) additional findings on non-contrast enhanced CT imaging.ResultsIn total 368 PRRT cycles including post-therapy imaging were performed in 100 patients. 45 patients had abdominal disease only, whilst in 55 patients the disease was observed on both abdominal and thoracic SPECT. 16 patients had known bone lesions that were visible only on planar imaging as these were out of range of the SPECT/CT. During PRRT, one patient developed multiple new bone metastases after the second cycle of PRRT, which were visible on both planar and SPECT/CT images. In 11 patients additional findings were found on CT images, the most common and relevant being bowel obstruction, pleural effusion, and ascites. Patients who developed ascites during PRRT appeared to do extremely poor; a post-hoc analysis showed that overall survival was 13.2 months in patients that showed ascites during PRRT at any moment and 37.9 months in patients without ascites (p < 0.001).ConclusionFrom a clinical point of view, thoracoabdominal SPECT/CT imaging is the preferred method for post-PRRT imaging; planar imaging had no added value over SPECT/CT in this cohort. In patients with abdominal disease only on baseline imaging, SPECT/CT of the abdomen only might be sufficient for imaging during the PRRT course. All accompanying CT images should be reviewed for additional findings, especially ascites, which is suggested to be a poor prognostic factor in patients receiving PRRT.

Clinical and radiological effectiveness of natalizumab extended dosage interval in patients with relapsing multiple sclerosis

Natalizumab (NTZ) is a very effective treatment approved for highly active multiple sclerosis. The main risk of treatment with NTZ is the possibility of developing progressive multifocal leukoencephalopathy, which is related to JC virus positivity and the number of NTZ infusions. This risk decreases with the extended dosage interval (EDI), which involves 9 or fewer infusions/year. However, it is a matter of controversy as to whether EDI remains effective in reducing recurrences and the presence of new lesions in magnetic resonance imaging (MRI). A prospective observational study was conducted from 1 April 2019 to 30 June 2021, following up patients on NTZ treatment who switched to EDI. Patients should have at least one MRI six months after the start of EDI. The presence of attacks or MRI activity (new lesions in T2) during the EDI was recorded. Twenty-three patients with a mean age of 43.5 ± 9.4 years were included. The median number of NTZ infusions was 68 (minimum, 25; maximum, 127). The median interval between the start of the EDI and the last MRI was 14 months (minimum, 6; maximum, 25), and 23 months from the last medical follow-up visit (minimum, 7; maximum, 28). Two patients (8.7%) presented with attacks and two others (8.7%) showed MRI activity. EDI with NTZ maintains high clinical and activity effectiveness in MRI.

A Case of Ectopic Cushing’s Syndrome From a Large Cell Neuroendocrine Lung Tumor With Small Cell Component/Features

Abstract Background: Endogenous Cushing’s syndrome is uncommon in clinical practice. Survival of patients with new onset ectopic Cushing’s syndrome at relapse of small cell lung cancer has been found to be poor, with death occurring within an average of 27.3 days. Case Report: A 61-year-old African American male was seen by endocrinology service for inpatient evaluation of refractory hypokalemia of three months duration requiring recurrent potassium replacement with oral and intravenous therapy. He was inpatient for depressive symptoms and suicidal ideation. His admission lab showed hypokalemia of 2.7 mmol/L associated with elevated serum ACTH and serum cortisol. Past medical history is significant for unresectable large cell neuroendocrine neoplasm of the lung with small cell components/features diagnosed two years prior during lung cancer screening. He received chemotherapy with cisplatin/etoposide at diagnosis. He however had recurrence one year later with distant metastases. He was re-treated with cisplatin/etoposide in addition to palliative radiation therapy to painful bone met in his right hand. Three months prior to admission, imaging showed progression of the cancer with presence of new lesions in the liver for which he received one cycle of Nivolumab monotherapy. Social history was significant for 30-pack year smoking history. Physical exam findings were significant for: elevated blood pressure 167/96 mmHg, tachycardia of 107 bpm, oxygen saturation of 95% on 3-liters of intranasal oxygen, cachexia, absent buffalo hump, absent striae and decreased power in both lower limbs. Lab on supplementation showed serum potassium of 3.6, Serum magnesium of 2.0 and creatinine clearance greater than 60 Serum cortisol was 116.1 (5-25) mcg/dl and ACTH was 268.0 (9-52) pg/ml. An MRI by the referring team did not show a pituitary lesion. Patient was diagnosed with Cushing’s syndrome due to ectopic ACTH-production from a large cell neuroendocrine lung tumor with small cell component/features. Chart review showed his onset of hypokalemia occurred at the same time that imaging showed progression of the tumor three months prior. He was started on Ketoconazole and his cortisol level reduced to 14.0 within forty-eight hours with associated correction and stabilization of hypokalemia. The plan was to “block and replace” cortisol so that oncology could re-start chemotherapy. However, the patient developed acute respiratory decompensation requiring continuous BiPAP. Chest imaging showed progression of lung lesions with post obstructive pneumonia. The patient’s family opted for comfort measures and he was transferred to hospice care where he passed on ten days later. Conclusion: In the setting of lung cancer, new onset paraneoplastic Cushing’s syndrome may have prognostic implications. Clinicians should be aware of this, provide treatment for hypercortisolism and refer early to palliative care.

Effectiveness and Adverse Events of Use of Natalizumab in a Brazilian Cohort of Patients With Multiple Sclerosis

PurposeNatalizumab (NTZ) is a monoclonal antibody with confirmed efficacy in white populations with recurrent-remitting multiple sclerosis (RRMS); there are few studies, however, in mixed-race populations. Real-world studies of NTZ are needed to better understand the drug's effectiveness. This study evaluated the effectiveness and adverse events of NTZ in a cohort of Brazilian patients with MS, as well as the impact of clinical and demographic factors on patient response to treatment. MethodsThis multicenter, Brazilian observational study was conducted from January 2011 until December 2016 and included patients with RRMS (McDonald criteria 2005 and 2010) aged ≥18 years treated with NTZ for at least 3 months. Demographic, clinical, and radiologic data were obtained from medical records and during follow-up visits. The primary outcomes investigated were the absolute number of relapses and annualized rate of relapses, change in Expanded Disability Status Scale value, and presence of new lesions on magnetic resonance imaging after starting NTZ treatment; the occurrence and type of adverse events were also analyzed. In addition, the impact of demographic and clinical prognostic factors and radiologic activity on the effectiveness of NTZ was measured. Descriptive and univariate statistical analyses used a significance level of P < 0.05. ResultsThe study enrolled 56 patients; 64% were women, and 36% were of African descent. There was a significant reduction in the mean absolute number (P = 0.001) and in the annualized rate (P = 0.001) of relapses and in the radiologic activity of the disease (P = 0.001). Furthermore, 71% of patients showed no increase in Expanded Disability Status Scale score after 1 year of treatment. The effectiveness of NTZ was not associated with the presence of clinical and demographic prognostic factors, and the most frequent adverse events during the use of NTZ were gastrointestinal symptoms; there were no cases of progressive multifocal leukoencephalopathy. ImplicationsAccording to patients' reports and clinicians’ observations regarding clinical and radiologic benefits and tolerability to adverse events, the use of NTZ was favorable in this Brazilian MS cohort, regardless of the presence of unfavorable prognostic factors.

Overall survival benefit of continuing immune checkpoint inhibitors treatment post dissociated response in patients with advanced lung cancer.

Dissociated response (DR, reduction at baseline or increase < 20% in target lesions compared with nadir in the presence of new lesions) was observed in 20-34% of patients treated with immune checkpoint inhibitors (ICIs). DRs were defined as progression disease (PD) per response evaluation criteria in solid tumors (RECIST v1.1), while evaluation criteria related to immunotherapy incorporated the new lesions into the total tumor burden or conducted further evaluation after 4-8weeks rather than declaring PD immediately. The main objective of this study is to compare survival between people who continuing initial ICIs treatment and those who switched to other anticancer therapy at the time of DR. 235 patients with advanced lung cancer (LC) treated with ICIs were evaluated. Propensity score matching (PSM) was used to minimize potential confounding factors. Post-DR OS, target lesion changes were evaluated. 52 patients had been estimated as DRs. After PSM, the continuing ICIs treatment Post-DR cohort still had a significantly longer median post-DR OS than discontinuing ICIs treatment Post-DR cohort, 10.63months (95% CI 6.27-NA) versus 4.33months (95% CI 1.77-NA), respectively (p = 0.016). Within the limitations of this single-center retrospective analysis, clinically stable patients who were judged by clinicians to be eligible for continuing ICIs treatment post-DR derived apparent OS benefit than discontinuing counterpart.

Pre-therapy visceral metastases in castrate resistant metastatic prostate cancer: Role in tumor progression.

e17586 Background: Visceral metastases in castrate resistant metastatic prostate cancer (mCRPC) are known to develop late in the course of disease and portend a poor prognosis. As patients with visceral metastases still derive a clinical benefit to treatment, understanding patterns of progressive disease (PD) may help differentiate important disease phenotypes in mCRPC. The aim of our study was to evaluate the differences in anatomic sites of PD in patients with pretreatment visceral or bone metastases on time to progression (TTP). Methods: A retrospective review of anonymized patients enrolled in phase 2 and 3 clinical trials was performed. Patients were excluded if lacked Tc bone scan or CT chest, abdomen and pelvis (CT CAP) at baseline. Bone disease was defined by automated bone scan lesion area (BSLA) criteria. All CT CAPs per clinical trial protocol were assessed by RECIST 1.1. Soft tissue PD was noted as target, non-target lesion growth and/or presence of new lesions by anatomic site. Bone PD was defined by &gt; 20% increase in BSLA score. Results: Of the 169 subjects that met our selection criterion, visceral disease was present at baseline in 90 patients (53%). Baseline BSLA score was 90474 mm² in visceral and 80348 mm² in non-visceral patients (p = 0.395). Disease progression occurred in 93 patients (55%). With baseline visceral disease, PD was a result of BSLA in 26 (51%) and visceral disease only in 11 (22%) of patient. Lacking visceral disease at baseline resulted in PD by BSLA in 26 (62%) and visceral disease only in 3 (7%) of patients. There was no significant difference in PFS for baseline visceral/non-visceral involvement; median PFS = 4.5 months in visceral; median PFS = 4.34 months in non-visceral (HR = 1.28; p = 0.244). Conclusions: Patients with visceral disease may still derive a similar clinical benefit from treatment to those without. While the presence of baseline visceral disease was associated with higher rates of PD by visceral involvement, PD by bone disease remained the most common cause of PD regardless of presence of baseline visceral metastases.

Hyperprogressive Disease upon Immune Checkpoint Blockade: Focus on Non-small Cell Lung Cancer.

Describe the controversial aspects of hyperprogressive disease (HPD) definition, mechanisms, and biomarkers. Although immune checkpoint inhibitors (ICIs) demonstrated a survival benefit in non-small cell lung cancer (NSCLC), an acceleration of tumor growth during ICI, defined as HPD, was reported in ~ 13-26% of NSCLC patients and correlated with worse survival compared with conventional progression. Different criteria have been used for HPD definition. The main limitation for the use of tumor growth rate and tumor growth kinetics variations is its inapplicability for patients without a pre-baseline imaging or progressing on non-measurable lesions. On the contrary, time to treatment failure and clinical criteria (i.e., worsening of performance status, presence of new lesions, or metastatic spread to different sites) can be useful in the above-mentioned settings but do not consent an assessment of tumor growth before ICI initiation. Several mechanisms of HPD have been proposed so far, involving both adaptive and innate immunity or based on cell-autonomous signals of cancer growth triggered by ICI. The characterization of HPD biomarkers and the identification and validation on large series of one or more mechanistic explanations for the HPD phenomenon are of paramount significance to avoid detrimental immunotherapy in a subgroup of patients and exploit novel therapeutic targets for future immunotherapy combinations. HPD occur in a subgroup of NSCLC patients treated with ICI. Several definitions and mechanisms have been proposed and a consensus on HPD criteria and biological bases is currently lacking.

Role of soft tissue metastases on tumor progression in castrate-resistant metastatic prostate cancer.

214 Background: While visceral metastases in castrate resistant prostate cancer (mCRPC) are a negative prognostic factor, patients may still derive treatment benefits. Given varying anatomic sites of tumor may display differing treatment responses we investigated the role of soft tissue metastases in progressive disease (PD) by anatomic site. Methods: A retrospective review of anonymized patients enrolled in phase 3 clinical trials was performed. Patients were excluded if lacked Tc bone scan or CT chest, abdomen and pelvis (CT CAP) on trial. Subjects were included if they had soft tissue disease per RECIST 1.1. Bone disease was defined by automated BSLA criteria. All CT CAPs per clinical trial protocol were assessed by RECIST 1.1. Soft tissue PD was noted as target|nontarget lesion growth and/or presence of new lesions by anatomic site. Bone PD was defined by &gt;20% increase in BSLA score. Results: Of 322 total patients, 138 met criteria of soft tissue disease at baseline. Baseline anatomic sites of metastases per RECIST included: visceral (74, 53.6%), lymph node only (52, 37.7%) and soft tissue bone (12, 7.1%). PD occurred in 46 patients with baseline soft tissue disease; with PD first detected by BSLA (23, 16.7 %), RECIST (19, 13.8 %) or with PD occurring simultaneously by BSLA and RECIST (4, 2.9%). Of the 138 patients with baseline soft tissue disease, PD occurred by RECIST in 25 patients. This occurred due to worsening visceral (11, 68.8%), lymph node (4, 25.0%) or soft tissue bone (1, 6.3%) disease. PD by new lesions only occurred in 9 patients (36.0%), as a result of 77.8% visceral and 22.2% lymph node. Conclusions: In mCRPC with soft tissue disease at baseline, progression by BSLA bone score still accounts for a large portion of PD. Further analyses must be performed to better differentiate disease phenotypes amongst mCRPC with combined visceral/osseous disease.

New MRI lesions and topography at 6 months of treatment initiation and disease activity during follow up in relapsing remitting multiple sclerosis patients

ABSTRACTObjective: The objective of this study was to assess if the presence of new lesions and their topography on the reference MRI have a prognostic value regarding disease activity during the follow up in relapsing remitting multiple sclerosis (RRMS) patients.Methods: Retrospective cohort study that included patients with RRMS who had a reference MRI (performed at 6 months from the onset of a DMT) and radiological and clinical follow up for at least two years. We identified the number of new MRI lesions and their topography at reference MRI and during the follow up. Cox proportional hazards model analysis was used to evaluate the association between new lesions on reference MRI and the appearance of new lesions and/or clinical relapses at 24-month follow-up.Results: 56 patients were included, 13 (23.2%) showed new lesions in the reference MRI. The presence of new lesions at reference MRI predicted the occurrence of new lesions at month 24 (HR 3.1, CI 95% 2.5-5.8). The number of lesions and the infratentorial topography at reference MRI were associated with an increased risk of new radiological activity during follow up (HR 3.5, IC95% 3.1-6.1 and HR 2.4, IC95% 1.9-2.7 respectively).Conclusion: New lesions at the reference MRI in terms of number and topography increase the risk of radiological disease activity during the follow up.

Cholesterol Crystals in Embolic Debris are Associated with Postoperative Cerebral Embolism after Carotid Artery Stenting

Object: We investigated possible associations among the presence of cholesterol crystals in embolic debris, the proportions of debris components, and postoperative cerebral embolism in patients undergoing carotid artery stenting (CAS). Methods: Sixty-seven consecutive procedures were performed for internal carotid artery stenosis with CAS at our hospital between November 2015 and February 2018. Procedures for emergency CAS for stroke in evolution or crescendo transient ischemic attack were excluded (n = 12). The embolic debris from remaining procedures (n = 55) was stained with hematoxylin-eosin and the red blood cells, white blood cells, and fibrin were quantified by color-based segmentation. Cholesterol crystals and calcification were examined histopathologically. Diffusion-weighted imaging (DWI) was performed 1–3 days after CAS, and the images were used to classify procedures according to the presence of new lesions. Results: Of the 55 CAS procedures, new DWI lesions were identified after 32. One patient had symptomatic cerebral embolism. Higher proportions of patients with cholesterol crystals in embolic debris (17 vs. 78%, p < 0.001) and higher proportion of white blood cells (mean 2.3 [0–9.9] vs. 4.2% [0–29.9%], p < 0.01) were observed in the embolic debris of procedures with and without new DWI lesions. Conclusions: Cholesterol crystals were common in the embolic debris from patients with postoperative ischemic lesions after CAS. These results suggest that inflammatory destabilization of the intraplaque lipid component is related to postprocedural DWI lesions.

Abstract WMP47: Cholesterol Crystals in Embolic Debris Correlate Postoperative Silent Cerebral Embolism in Carotid Artery Stenting

Introduction: Very few studies have investigated the relationship between the histopathology of the embolic debris in embolic protection devises and postoperative cerebral embolism in carotid artery stenting (CAS). The aim of this study was to evaluate embolic debris and its association with clinical, laboratory, and neurointerventional findings in patients treated by CAS due to internal carotid stenosis. Hypothesis: Cholesterol crystals in embolic debris are associated with postoperative cerebral embolism in CAS. Methods: All embolic debris was stained with hematoxylin-eosin. Embolic debris underwent quantitative analysis to quantify three main components: red blood cells, white blood cells and fibrin, by color based segmentation. Histopathological assessment included presence of calcifications, cholesterol crystals, foamy cells, and endothelial cells. Diffusion weighted image (DWI) was evaluated 1 to 3 days after CAS, and patients were classified by presence of new lesions on DWI after CAS. Exclusion criteria were emergency CAS for stroke in evolution or crescendo transient ischemic attack. Results: From November 2015 to April 2017, 40 patients were treated in our hospital by CAS due to internal carotid artery stenosis. Exclusion criteria were fulfilled in 5 patients. 24 patients had new lesions on DWI after CAS and 11 patients did not have those. Single patient had symptomatic cerebral embolism. Patients with new lesions on DWI after CAS had higher rate of cholesterol crystal in embolic debris (80% vs 18%, p&lt;0.01) and higher rate of patients taking strong statin on admission (71% vs 18%, P=0.02) than those without new lesions on DWI after CAS. There is no significant difference with blood levels of LDL-cholesterol [111 mg/dl (79-197) vs 108 mg/dl (62-167); p=0.85]. Main components of embolic debris were not significantly different between two groups. Conclusion: Cholesterol crystals in embolic debris and treatment history of dyslipidemia were significantly associated with post-operative high intensity lesion on DWI in CAS.

Persistent lesion hyperintensity on brain diffusion-weighted MRI is an early sign of intravascular lymphoma

A 63-year-old man presented with right-sided hemianopia and unsteady gait. Brain MRI revealed multiple hyperintense infarct-like lesions on diffusion-weighted images (DWI). Hyperintensity persisted in some of these lesions even after...

Effects of diazoxide in multiple sclerosis

Objective:The aim of this study was to test the safety of diazoxide and to search for signs of efficacy in patients with relapsing-remitting multiple sclerosis (RRMS).Methods:In this multicenter, randomized, placebo-controlled, double-blind trial (treatment allocation was concealed), 102 patients with RRMS were randomized to receive a daily oral dose of diazoxide (0.3 and 4 mg/d) or placebo for 24 weeks (NCT01428726). The primary endpoint was the cumulative number of new T1 gadolinium-enhancing lesions per patient, recorded every 4 weeks from week 4 to week 24. Secondary endpoints included brain MRI variables such as the number of new/enlarging T2 lesions and the percentage brain volume change (PBVC); clinical variables such as the percentage of relapse-free patients, relapse rate, and change in the Expanded Disability Status Scale score; and safety and tolerability.Results:Diazoxide was well-tolerated and it produced no serious adverse events other than 1 case of Hashimoto disease. At the 2 doses tested, diazoxide did not improve the primary endpoint or the MRI and clinical variables related to the presence of new lesions or relapses. Patients treated with diazoxide showed reduced PBVC compared with the placebo group, although such changes could be confounded by the higher disease activity of the treated group and the vascular effects of diazoxide.Conclusion:At the doses tested, oral diazoxide did not decrease the appearance of new lesions evident by MRI. The effects in slowing the progression of brain atrophy require further validation.Classification of evidence:This study provides Class I evidence that for patients with RRMS, diazoxide (0.3 and 4 mg/d) does not significantly change the number of new MRI T1 gadolinium-enhancing lesions.

The components of progression as explanatory variables for overall survival in the Response Evaluation Criteria in Solid Tumours 1.1 database

PurposeProgressive disease (PD) per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 is defined as growth of measurable target lesions, presence of new lesions or unequivocal progression of non-target disease. In this manuscript we explored whether a more refined categorisation of tumour response and/or these components of progression, varying over time, can improve prediction of overall survival (OS) in the RECIST database. MethodsData were randomly selected from 13 randomised clinical trials (3758 patients with breast, lung or colorectal cancer). A maximum of five target lesions contributed to the sum of longest diameters. At each measurement time we determined: best target response as best % improvement from baseline; tumour growth of target lesions as worst % change and worst rate of increase (mm/week) from nadir; presence of new lesions and occurrence of non-target PD. OS was analysed by tumour type using Cox regression, adjusting for baseline sum and including these parameters as time-dependent covariates. Results36% of patients had new lesions, 28% non-target PD and 49% experienced target lesion growth (median strongest growth 1.5mm/week). Regardless of tumour type, presence of new lesions (hazard ratio (HR) ranging 1.5–2.3) and non-target PD (HR 1.5–2.0) were strongly associated with worse OS. The explanatory value of tumour growth for OS was low compared to the other components. ConclusionModelling target lesion tumour growth did not show a marked improvement in OS prediction over and above the other components. These analyses enable a better understanding of the role of each component in PD evaluation. Work is ongoing to incorporate this information into an updated version of RECIST with enhanced prediction of subsequent survival.

DCE-CT in the follow-up of targeted therapy in GISTs

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancy that initiate from the gastrointestinal tract. GISTs most often metastasize to the liver or the peritoneum. The effect of conventional chemotherapy and radiotherapy do only have very limited therapeutic effect in GISTs. However, the introduction of targeted therapy has dramatically changed the management of advanced GISTs when improved tumor control, progression-free survival, and overall survival are considered. The size reduction of GIST lesions during targeted therapy regimens most often is modest and lesions may even enlarge during successful treatment. Progressive disease does not necessitate the presence of new lesions, and the phenomenon of a nodule within a mass may represent progressive disease. So, the most widely used assessment of response of cancer treatment based on the sum of the largest diameter of target lesions (RECIST) (1) may underor overestimate the effect of targeted therapies in GISTs; due to that fact Choi et al. (2) introduced computed tomography (CT) criteria that also focused on changes in lesion attenuation. These criteria which rely on additional CT enhancement are a better predictor of prognosis than criteria which rely only on changes in size. 18-FDG PET has shown to be very sensitive in detecting early response and as a predictor of long-term response to targeted therapy in GIST. PET/CT may combine metabolic and morphologic issues. However, the term PET/CT shall be reserved to protocols that indeed perform diagnostic CT with diagnostic acquisition parameters and a state of the art contrast media policy. A CT scan used for attenuation correction in a “PET/CT” cannot be considered diagnostic. However, due to limited availability and high costs, and due to the fact that up to 20% of GIST lesions on pretreatment scans do not show increased uptake of glucose, in general CE-CT is used as the standard modality in the follow-up of treatment in GISTs supplemented with MRI or PET/CT when needed. The morphological response assessment in GISTs using CT as modality is not only based on size and density measurements. Pseudo progression and pseudo regression have to be evaluated visually and integrated in the final assessment. Since the introduction of DCE-CT by Miles (3) the discipline has evolved dramatically due to enhanced computer power, the development of MDCT, and the development of software tools. In a recent report recommendations and guidelines for DCE-CT are presented (4). It was concluded that DCE-CT scans can robustly assess tumor vascular support and that DCE-CT has reached technical maturity for use in therapeutic trials in oncology. Betz et al. (5), in this issue of Acta Radiologica, present a pictorial review demonstrating that CE-CT easily can be combined with a DCE-CT protocol, so pseudo responses in the follow-up of treatment with targeted agents in GISTs probably can be diminished. DCE-CT can produce a range of physiological parameters that can be displayed as parametric maps, and as shown in (5) be used for quantitative as well as qualitative evaluation. The subjective lesion delineation is an issue that hampers imaging disciplines which rely on signal changes over time in user defined ROIs/VOIs. No guidelines for the delineation of such lesions have yet been agreed upon. Another issue for techniques which rely on time-signal curves to create surrogate molecular imaging markers is the problem with movement artifacts. In the presented manuscript by Betz et al. (5) image registration software that correct for movement artifacts has been included. However, it is obvious that such tools can be improved, especially when tissue near the diaphragm is considered. Although semi-automatic segmentation of a whole lesion volume now is technical possible, and a sample volume in the z-axis that in practice will cover the whole lesion considered, the technique cannot cover the whole body and may serve as complementary to CE-CT as all tumors and metastases do not necessarily behave the same way during treatment. The parameters derived from the DCE-CT discipline depends on the CT system used, acquisition parameters, contrast media policy, and data processing. Although very illustrative parametric color display shows details of tumor characteristics that supplement the findings seen in the corresponding morphological CE-CT, there is a need to have statistics for reproducibility and standards for how to define a ROI in GISTs when considering quantitative measurements. A study that illustrates the impact of the supplementary DCE-CT figures on endpoints as progression-free survival and overall survival compared to morphological response evaluation criteria in longitudinal studies is also warranted. Another important question is if pre-therapeutic DCE-CT figures can act as prognostics in GISTs.