Risk Of Progression In Patients Research Articles

Application of CALL score for prediction of progression risk in patients with COVID-19 at university hospital in Turkey.

BackgroundThe CALL score was developed as a predictive model for progressive disease. We aimed to validate and/or improve the performance of CALL score in our hospital settings.MethodsAdult patients with polymerase chain reaction‐confirmed COVID‐19 were included in this retrospective observational study. Clinical and laboratory characteristics (including complete blood count, CRP, ferritin, LDH, fibrinogen, d‐dimer) were obtained. ROC analysis was used for the evaluation of CALL score's performance. Cox regression analyses were performed for the selection of new parameters for improving CALL score.ResultsOverall, 256 patients were enrolled in the study. The median age was 54 (IQR, 22.5), 134 (52%) were women, 155 (61%) had at least one comorbidity, 60 (23%) had severe disease. The AUC value for CALL score for predicting progression to severe COVID‐19 was 0.59 (95% CI 0.50‐0.66). D‐dimer on admission was associated with progressive disease (HR = 1.2 CI 95% 1.02‐1.40), (P < .027).ConclusionThe performance of the CALL score in our patient population was low compared with the original study. We found an additional parameter for predicting progressive COVID‐19 disease, D‐dimer, which may guide future studies to develop new scoring systems for predicting progressive disease.

Incidence of immune-related adverse events with pembrolizumab in advanced melanoma and correlation with treatment response: A single institution review of irAEs.

e21519 Background: Anti-PD-1 therapy has become a mainstay of advanced melanoma treatment. However, associated irAEs are common and contribute to significant delays or cessation of treatment. In this retrospective cohort study, we aim to characterize the real-world irAE profile of pembrolizumab at our institution and its prognostic implications. Methods: We evaluated unresectable stage III-IV melanoma patients treated with pembrolizumab between 2011 and 2016 at the University of Arizona Cancer Center (UACC). Information regarding demographics, treatment, irAEs, and hospitalizations were recorded. Adverse events were graded using the common terminology criteria for adverse events v.4.0 (CTCAE). Results: Seventy-three patients were identified, 4 (5.5%) with unresectable stage III and 69 (94.5%) with stage IV melanoma. The median age was 68; 48 (65.8%) patients were male and 25 (34.2%) were female. Nineteen patients (26.0%) had a preexisting autoimmune disorder. 171 irAEs were identified in 58 of the patients. 141 (82.5%) were Grade 1, 24 (14.0%) were Grade 2, and 6 (3.5%) were Grade 3. Incidence and time to onset of significant events is displayed in Table. Eleven (15%) patients were hospitalized, and 8 patients (11.0%) stopped treatment due to an irAE. Sixteen (84.2%) patients with a preexisting autoimmune condition experienced an irAE versus 78% of patients without an autoimmune condition. Twelve patients (75%) had an exacerbation of their autoimmune condition. Response could be assessed in 67 patients . 30 patients of the 67 (45%) had a CR or a PR and 37 patients (55%) had progressive disease (PD). 58 of 67 (87%) experienced an irAE. 29 (50%) of the 58 irAE patients had PD, while 8 (88.9%) of the 9 non-irAE patients had PD. The relative risk of progression in patients who experienced an irAE versus who did not was 0.56 (95% CI: 0.39-0.79, p= 0.001). Conclusions: Experience with pembrolizumab at our institution suggests a similar irAE profile compared to landmark trials, though we observed a higher percentage of patients who required discontinuation of pembrolizumab (11% versus 5% in Phase III trials). In our retrospective study, the risk for progression was significantly higher in patients without irAE versus with any irAE, suggesting that development of irAE could be a positive prognostic sign.[Table: see text]

Using advanced analysis of multifocal visual-evoked potentials to evaluate the risk of clinical progression in patients with radiologically isolated syndrome

This study aimed to assess the role of multifocal visual-evoked potentials (mfVEPs) as a guiding factor for clinical conversion of radiologically isolated syndrome (RIS). We longitudinally followed a cohort of 15 patients diagnosed with RIS. All subjects underwent thorough ophthalmological, neurological and imaging examinations. The mfVEP signals were analysed to obtain features in the time domain (SNRmin: amplitude, Latmax: monocular latency) and in the continuous wavelet transform (CWT) domain (bmax: instant in which the CWT function maximum appears, Nmax: number of CWT function maximums). The best features were used as inputs to a RUSBoost boosting-based sampling algorithm to improve the mfVEP diagnostic performance. Five of the 15 patients developed an objective clinical symptom consistent with an inflammatory demyelinating central nervous system syndrome during follow-up (mean time: 13.40 months). The (SNRmin) variable decreased significantly in the group that converted (2.74 ± 0.92 vs. 4.07 ± 0.95, p = 0.01). Similarly, the (bmax) feature increased significantly in RIS patients who converted (169.44 ± 24.81 vs. 139.03 ± 11.95 (ms), p = 0.02). The area under the curve analysis produced SNRmin and bmax values of 0.92 and 0.88, respectively. These results provide a set of new mfVEP features that can be potentially useful for predicting prognosis in RIS patients.

Development and Validation of a Machine Learning Model to Explore Tyrosine Kinase Inhibitor Response in Patients With Stage IV EGFR Variant–Positive Non–Small Cell Lung Cancer

An end-to-end efficacy evaluation approach for identifying progression risk after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy in patients with stage IV EGFR variant-positive non-small cell lung cancer (NSCLC) is lacking. To propose a clinically applicable large-scale bidirectional generative adversarial network for predicting the efficacy of EGFR-TKI therapy in patients with NSCLC. This diagnostic/prognostic study enrolled 465 patients from January 1, 2010, to August 1, 2017, with follow-up from February 1, 2010, to June 1, 2020. A deep learning (DL) semantic signature to predict progression-free survival (PFS) was constructed in the training cohort, validated in 2 external validation and 2 control cohorts, and compared with the radiomics signature. An end-to-end bidirectional generative adversarial network framework was designed to predict the progression risk in patients with NSCLC. The primary end point was PFS, considering the time from the initiation of therapy to the date of recurrence, confirmed disease progression, or death. A total of 342 patients with stage IV EGFR variant-positive NSCLC receiving EGFR-TKI therapy met the inclusion criteria. Of these, 145 patients from 2 of the hospitals (n = 117 and 28) formed a training cohort (mean [SD] age, 61 [11] years; 87 [60.0%] female), and the patients from 2 other hospitals comprised 2 external validation cohorts (validation cohort 1: n = 101; mean [SD] age, 57 [12] years; 60 [59.4%] female; and validation cohort 2: n = 96, mean [SD] age, 58 [9] years; 55 [57.3%] female). Fifty-six patients with advanced-stage EGFR variant-positive NSCLC (mean [SD] age, 52 [11] years; 26 [46.4%] female) and 67 patients with advanced-stage EGFR wild-type NSCLC (mean [SD] age, 54 [10] years; 10 [15.0%] female) who received first-line chemotherapy were included. A total of 90 (26%) receiving EGFR-TKI therapy with a high risk of rapid disease progression were identified (median [range] PFS, 7.3 [1.4-32.0] months in the training cohort, 5.0 [0.6-34.6] months in validation cohort 1, and 6.4 [1.8-20.1] months, in validation cohort 2) using the DL semantic signature.The PFS decreased by 36% (hazard ratio, 2.13; 95% CI, 1.30-3.49; P < .001) compared with that in other patients (median [range] PFS, 11.5 [1.5-64.2] months in the training cohort, 10.9 [1.1-50.5] in validation cohort 1, and 8.9 [0.8-40.6] months in validation cohort 2. No significant differences were observed when comparing the PFS of high-risk patients receiving EGFR-TKI therapy with the chemotherapy cohorts (median PFS, 6.9 vs 4.4 months; P = .08). In terms of predicting the tumor progression risk after EGFR-TKI therapy, clinical decisions based on the DL semantic signature led to better survival outcomes than those based on radiomics signature across all risk probabilities by the decision curve analysis. This diagnostic/prognostic study provides a clinically applicable approach for identifying patients with stage IV EGFR variant-positive NSCLC who are not likely to benefit from EGFR-TKI therapy. The end-to-end DL-derived semantic features eliminated all manual interventions required while using previous radiomics methods and have a better prognostic performance.

Short-Term Risk for Progression in Patients with Smoldering Multiple Myeloma: The Impact of CD56 Expression

The identification of risk factors for progression is critical in the clinical management and appropriate follow up of patients with Smoldering Multiple Myeloma (SMM). The early identification of patients with possible short-term progression to Multiple Myeloma (MM) could lead to anticipate the treatment. Several prognostic score identify in SMM patients the main risk factors for progression to MM. The two most used risk stratification models in SMM are the Mayo Clinic model, based on the tumor burden and the free light chains ratio, and the Spanish PETHEMA group model based on the immunophenotyped to identify abnormal plasma cells (PCs) and the reduction of the unevolved immunoglobulins. However, significant discrepancies between these two clinical models currently used in clinical practice has been recently underlined. For this reason, new parameters to identify possible new parameters for progression in SMM need to be defined. The aim of this study was to validate the main prognostic score and to investigate the possible role of the immunphenotype as risk factor for progression in a monocentric cohort of patients with SMM. We retrospectively evaluated a cohort of SMM patients admitted to a single haematological center (Hematology and BMT Unit, University Hospital of Parma) between 2014 and 2018. We analyzed a total cohort of 80 patients diagnosed with SMM according to the IMWG recently updated diagnostic criteria. All patients analysed underwent to Bone Marrow (BM) examination and imaging evaluation was performed in order to exclude the presence of bone disease and/or focal lesions. Both immunophenotypic and FISH analysis were performed of BMPCs. The median age of the SMM patients analysed was 68 years (range 36-93 years). Median percentage of BMPCs was 15% (range 10-40%) in the entire population. Median serum M-protein was 2 g/dL (range: 0.17-4.5). FLC ratio value was available in 66 patients: in 47 (71%) the ratio was unbalanced, 26 (39%) had a FLC ratio ≤ 0.125 or ≥ 8 and in 6 (9%) it was &amp;gt; 20. The presence of a reduction of one or two uninvolved immunoglobulins occurred in 61% of the entire population. The median follow up time was 27 months (range 0 - 76 months) for whole population. Overall 22 patients of the entire cohort progressed to MM with a median the time to progression (TTP) of 22 months. Firstly, we validated the currently score of progression in our cohort of SMM patients. By univariate analysis we found that percentage of BMPCs, abnormal FLC ratio and presence of immunoparesis were significantly correlated with progression to active MM (p&amp;lt;0.005 for each variable). Any significant correlation was not observed with age, sex, Ig isotype and light chain's type (p=NS). Afterwards, we study and confirm the significance of the risk stratification models. "Pethema" (p=0.0002), "20-2-20" Mayo score (p=0.0005) and also the "Danish score" (p= 0.0173) turned out statistically significant. Then, we investigate the possible role of immunophenotype in the risk of progression. Dividing the population-based on CD56 expression, we found that the median TTP in CD56- SMM patients was 21 months as compared to 34 months in CD 56+ SMM patients (p= 0.08). Moreover CD56- patients progressed without a significant increase of the monoclonal component (p=0.48) as compared to those CD56+ SMM patients (p=0.023). Finally, a relationship between CD56 expression and the hyperdiploidy was wound finding that CD56- SMM patients had a significant lower presence of hyperdiploidy as compared to those with CD56+ BMPCs (p=0.024) In conclusion, our data indicate that in SMM patients the factors, which mostly impact on the short-term risk of progression to active MM, are the entity of the PCs infiltrate, the immunoparesis and abnormal FLC ratio. Therefore, we identified the absence of CD56 expression by BMPCs as a possible factor for a more aggressive disease regardless to the tumoral burden. Disclosures Giuliani: Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Participation in congresses, Research Funding; Janssen Pharmaceutical: Membership on an entity's Board of Directors or advisory committees, Other: Clinical study sponsorship; participation in congresses, Research Funding; Millennium Pharmaceutical: Other: Clinical study sponsorship, Research Funding; GSK: Other: Clinical study sponsorship, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Other: Participation in congresses.

Abstract 2498: miFISH single cell analysis as a potential tool to stratify the progression risk in patients with Atypical Ductal Hyperplasia (ADH)

Abstract We previously studied synchronous ductal carcinomas in situ (DCIS) and invasive ductal carcinomas (IDC) using our novel approach of multiplex interphase Fluorescence in situ Hybridization (miFISH) that allows simultaneous enumeration of copy numbers of up to 20 gene loci per single cell, providing new insights into tumor clonality and intratumor heterogeneity (ITH). A high degree of chromosomal instability was present in DCIS, and we frequently observed a direct clonal evolution from DCIS to IDC. We now ask whether this degree of instability is also present in even earlier potential precursor lesions like atypical ductal hyperplasias (ADH). We are therefore conducting a retrospective study analyzing ADH lesions from patients without synchronous DCIS or IDC (pure ADH) and from patients with ADH adjacent to higher-grade lesions. Using our miFISH assay, we simultaneously assess copy number changes of six oncogenes (COX2 (1q), PIK3CA (3q), MET (7q), MYC (8q), CCND1 (11q), HER2 (17q), ZNF217 (20q)) and six tumor suppressor genes (FHIT (3p), DBC2 (8p), RB1 (13q), CDH1 (16q), TP53 (17q), NF2 (22q), typical for breast tumorigenesis. So far, we have analyzed fifteen pure ADH and five ADH with synchronous DCIS or IDC. The miFISH analysis showed that the majority of all pure ADH displayed a stable diploid genome without any copy number changes observed for the genes tested while only 3/15 (20%) showed changes, namely (i) a COX2 and HER2 gain in a diploid genome, (ii) a CDH1and MET loss in a tetraploid genome and (iii) a COX2 gain in a diploid genome. In the group of ADH with adjacent higher-grade lesions (n=5), all DCIS and IDC lesions analyzed displayed breast cancer specific copy number changes corroborating our previous results. Of note, two of the ADH lesions adjacent to these aberrant DCIS or IDC lesions had normal diploid genomes. Of the remaining three synchronous ADH lesions, one showed a complex gain and loss pattern similar to its adjacent DCIS, the second one was characterized by a simple COX2 gain which was maintained in the adjacent DCIS in addition to a DBC2 loss and MYC gain. The third ADH displayed a tetraploid clone without any gains or losses, while the adjacent IDC revealed a complex gain and loss pattern in its tetraploid genome. Our preliminary data indicate that the majority of pure ADH does not harbor copy number changes. However, there is a small subset of pure ADH revealing gain and loss patterns typical for DCIS and IDC often involving COX2 gain indicating it as an early event. Of note, ADH lesions adjacent to DCIS or IDC tend to display similar changes as their adjacent higher-grade lesions suggesting them as direct precursor lesions. We are currently analyzing more ADH samples and plan to add material from an ADH patient cohort with long-term follow-up to explore whether miFISH can stratify ADH patients into different risk groups. Citation Format: Kiara Whitaker, Jausheng Tzeng, Daniela Hirsch, Irianna Torres, Steven Brower, Gert Auer, Miguel Sanchez, Thomas Ried, Kerstin Heselmeyer-Haddad. miFISH single cell analysis as a potential tool to stratify the progression risk in patients with Atypical Ductal Hyperplasia (ADH) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2498.

1120-P: Association between the Inflammatory Marker GDF-15 and Kidney Disease Progression: Results from the CANVAS Trial

Introduction: Growth differentiation factor 15 (GDF-15) is a marker of inflammation and cellular injury. Small clinical studies have suggested that SGLT2 inhibitors exert anti-inflammatory effects. We examined the association of baseline GDF-15 with kidney outcomes in patients with type 2 diabetes mellitus (T2DM) participating in the CANagliflozin cardioVascular Assessment Study (CANVAS) study. We also assessed the effect of the SGLT2 inhibitor canagliflozin (CANA) on GDF-15. Methods: The CANVAS trial randomized 4330 people with T2DM at high cardiovascular risk to CANA or placebo. Plasma GDF-15 concentration was measured with GDF-15 Roche Elecsys assay at baseline and follow-up. The association between GDF-15 and the primary kidney outcome (40% eGFR decline, end-stage kidney disease, or renal death) was assessed using multivariable adjusted Cox regression. Linear mixed effects models were used to assess the effect of CANA versus placebo on GDF-15 levels. Results: We included 3557 CANVAS participants with available plasma samples (mean age 62.8 years, 33.1% female, mean eGFR 76.9 ml/min/1.73 m2, median uACR 11.6 mg/g, median GDF-15 1776.0 pg/ml). During a mean follow-up of 5.7 years, 137 kidney outcomes occurred. Higher GDF-15 levels were independently associated with higher risk of kidney events (HR 1.98 [95% CI 1.40 to 2.81] per log increment GDF-15). Treatment with CANA modestly lowered GDF-15 compared to placebo (-2% [95% CI -5 to 0; p=0.046]). The effect of CANA on the kidney outcome (HR 0.56, 95% CI 0.40-0.79) was consistent regardless of baseline GDF-15 levels (p-interaction=0.75). GDF-15 did however not mediate the renal protective effect of CANA (percent mediation 3.9% [95% CI -3.6 to 14.0]). Conclusion: CANA modestly lowers GDF-15, which is independently associated with a higher risk of kidney disease progression in patients with T2DM at high cardiovascular risk. The modest reduction in GDF-15 with CANA did not mediate the renal protective effect of CANA. Disclosure J. Li: Employee; Self; George Institute. T. Sen: None. B. Neal: Research Support; Self; Janssen Research &amp; Development, LLC, Merck Schering Plough, Roche Pharma, Servier, Zydus Pharmaceuticals, Inc. Other Relationship; Self; Abbott, Janssen, Novartis, Pfizer, Roche, and Servier. B.L. Neuen: Research Support; Self; Australian National Health and Medical Research Council Postgraduate Scholarship, Oxford Australia Clarendon Scholarship from the University of Oxford, University Postgraduate Award from UNSW Sydney. Other Relationship; Self; Janssen Research &amp; Development, LLC. V. Perkovic: Other Relationship; Self; See Other Relationship field. D. de Zeeuw: Advisory Panel; Self; AbbVie Inc., Bayer AG, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. K.W. Mahaffey: Consultant; Self; Medscape, Mitsubishi, Myokardia, NIH, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, UCSF. Research Support; Self; Afferent, Amgen, Apple, Inc, AstraZeneca, Cardiva Medical, Inc, Daiichi, Ferring, Google (Verily), Johnson &amp; Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, Sanofi, St. Jude, Tenax. Y. Yavin: Employee; Self; Janssen Research &amp; Development, LLC. N. Rosenthal: None. M.K. Hansen: Employee; Self; Janssen Research &amp; Development, LLC. H.L. Heerspink: Consultant; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim International GmbH, CSL Behring, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mundipharma International, Retrophin, Inc. Funding Janssen Research &amp; Development, LLC

Prediction for Progression Risk in Patients With COVID-19 Pneumonia: The CALL Score.

BackgroundWe aimed to clarify the high-risk factors with multivariate analysis and establish a prediction of disease progression, so as to help clinicians to better choose therapeutic strategy.MethodsAll the consecutive patients with COVID-19 admitted to Fuyang second people’s hospital or the fifth medical center of Chinese PLA general hospital between January 20 and February 22, 2020, were enrolled and their clinical data were retrospectively collected. Multivariate COX regression was used to identify the risk factors associated with progression, and then were incorporated into the nomogram to establish a novel prediction scoring model. ROC was used to assess the performance of the novel model.ResultsOverall, 208 patients were divided into stable group (n=168, 80.8%) and progressive group (n=40,19.2%) based on whether their conditions worsened during the hospitalization Univariate and multivariate analysis showed that comorbidity, older age, lower lymphocyte and higher lactate dehydrogenase at presentation were independent high-risk factors for COVID-19 progression. Incorporating these 4 factors, the nomogram achieved good concordance indexes of 0.86 (95%CI 0.81 - 0.91), and had well-fitted calibration curves. A novel scoring model, named as CALL, was established, and its area under ROC was 0.91 (95% CI 0.86 to 0.94). Using a cutoff value of 6 points, the positive and negative predictive values were 50.7% (38.9% - 62.4%) and 98.5% (94.7% - 99.8%), respectively.ConclusionUsing the CALL score model, clinicians can improve the therapeutic effect and reduce the mortality of COVID-19 with more accurate and reasonable resolutions on medical resources.

Prognostic value of 18F-FDG PET/CT imaging and related factors for patients with classic Hodgkin lymphoma before or after autologous stem cell transplantation

Objective To assess the predictive value of 18F-fluorodeoxyglucose (FDG) PET/CT imaging and relevant factors in the prognosis of patients with classic Hodgkin lymphoma (cHL) before or after autologous stem cell transplantation (ASCT). Methods From January 2008 to June 2017, 55 cHL patients (28 males, 27 females; age: (28.8±9.6) years) confirmed by pathology in Shanghai General Hospital were retrospectively included. 18F-FDG PET/CT imaging was performed before ASCT in 43 cases and after ASCT in 34 cases (22 patients underwent the imaging both before and after ASCT). Patients were divided into positive group (≥4) and negative group (<4) according to 18F-FDG PET/CT imaging results using Deauville 5-point scale. The predictive value of relevant factors in the prognosis was evaluated with progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis and log-rank test. Hazard ratio (HR) was calculated by Cox regression model. Results Of 55 cHL patients, 29 (53%) had a progression of disease after a median follow-up of 8 months, and 11 (20%) patients died after a median follow-up of 29.5 months, with the 3-year PFS rate of 46.4% and OS rate of 84.5%. Significant differences of PFS rate were found between patients with or without B symptoms, between patients with or without large mediastinal mass, between patients with international prognostic score (IPS) of 0-2 and those with IPS of 3-7, among patients with different effect of salvage chemotherapy (complete remission (CR), partial remission (PR) + stable disease (SD), progressive disease (PD)), and between patients with negative or positive PET/CT imaging results before or after ASCT (χ2 values: 5.52-20.01, HR: 2.21(95% CI: 1.56-3.12)-5.51(95% CI: 1.86-16.33), all P<0.05). B symptoms and large mediastinal mass were also prognostic factors for OS rate (HR: 5.28(95% CI: 1.14-24.51) and 4.27(95% CI: 1.24-14.79), both P<0.05). The combination of 18F-FDG PET/CT imaging before and after ASCT was statistically significant for predicting PFS (χ2=11.28, P<0.01). Multivariate survival analysis showed that the risk of progression in patients with positive PET/CT results after ASCT was significantly higher than those with negative results (HR=6.20, P<0.01), and the risk of death in patients with B symptoms was significantly higher than those without B symptoms (HR=5.28, P<0.05). Conclusion 18F-FDG PET/CT imaging results after ASCT have important values for predicting PFS in cHL patients after ASCT, and B symptoms can be used as an important prognostic indicator of OS after ASCT. Key words: Lymphoma; Stem Cells; Transplantation, autologous; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose

Prognosis of progression of chronic generalised periodontitis in patients with bronchiectatic disease

Aim. To analyse the parameters of dental indices and the level of markers of infl ammation and oxidative stress in patients with chronic generalised periodontitis (CGP) with bronchiectatic disease and to develop a mathematical model for assessing the risk of CGP progression in patients with bronchiectatic disease.Materials and methods. A total of 70 patients with mild and moderate CGP were examined, which were divided into the following groups: patients with CGP without general somatic pathology (n = 33), and patients with CGP and bronchiectatic disease (n = 37). The control group consisted of somatically healthy individuals with intact periodontium (n = 40). Dental indices (PMA, PI, Muhlemann, OHI-s), infl ammatory markers (transforming growth factor beta 1 (TGFβ-1), lactoferrin (LF), interleukin-8 (IL-8), C — reactive protein (CRP)), and oxidative stress markers (malondialdehyde (MDA), as well as advanced oxidation protein products (AOPPs), and total superoxide dismutase (SOD)) were analysed in all patients included in the study. The method of binary logical regression was used to create a mathematical model for assessing the risk of CGP progression in patients with bronchiectatic disease.Results. Dental indices and the level of markers of infl ammation and oxidative stress were statistically signifi cantly higher in all patients with CGP as compared to somatically healthy individuals, as well as in patients with CGP and bronchiectatic disease as compared to patients with CGP without general somatic pathology. Positive correlations of different strength between the studied markers of infl ammation and oxidative stress and dental indices were revealed. Based on the results of the correlation matrix data and using the binary logistic regression method, a mathematical model was developed that can be applied for assessing the risk of CGP progression in patients with bronchiectatic disease. The predictors of progression included in the mathematical model were: PI, TGFβ-1 and AOPPs. Conclusion. The data obtained indicate a greater severity of infl ammation and oxidative stress in CGP patients with comorbid pathology in the form of bronchiectatic disease and the infl uence of these processes on the periodontal condition. The proposed mathematical model for assessing the risk of CGP progression in patients with bronchiectatic disease is characterized by a high level of sensitivity and prognostic signifi cance, thus being applicable for use in clinical practice.

Abstract P6-15-07: Impact of increased mammary adiposity on DCIS progression

Abstract Background: The incidence of ductal carcinoma in situ (DCIS) has greatly increased since the introduction of mammographic screening. However, so far, it is still not possible to predict which patient with DCIS will further develop invasive breast cancer. Adipocyte hypertrophy and adipocyte inflammation has been associated with increased risk of developing breast cancer in postmenopausal women and with worse prognosis in breast cancer patients. In this study, we aimed 1) at evaluating the association between mammary adiposity, as assessed by digital pathology, with DCIS progression using a unique case-control series with long-term follow up and 2) study the interaction between DCIS cells and the surrounding adipocytes. Patients and methods: Mammary adipocyte size was measured in surgical specimens of 279 women with primary DCIS. These mammary adipocyte measurements were compared in 109 women with primary DCIS who subsequently developed ipsilateral invasive breast cancer (iIBC) (cases) and 170 women who did not (controls). Patients were matched for age and follow-up duration. Median follow-up time was 12.8 years. Post-menopausal patients were defined as &amp;gt;50 years at diagnosis and represented 220/279 (78,9%) of patients. All patients were treated with breast cancer-conserving surgery only. Intact adipocytes distant from the DCIS lesions were measured (largest diameter and area) using HALO™ image analysis software (Indica Labs, Corrales, NM) on H&amp;E-stained whole slide images of primary DCIS. Given the specific interest in the larger adipocytes, we systematically considered the 75th percentile as unique value for each patient. An average of 4259 adipocytes (min:70, max:21107) was measured per patient. Tissue segmentation was used to measure the adipose area. Adipose triglyceride lipase (ATGL clone 2138, Cell Signaling) immunohistochemistry (IHC) was applied to study ATGL expression in DCIS cells. Her2, ER and COX-2 IHC and RNAseq of microdissected pure DCIS was already available for this series (LL. Visser et al. Clin Can Res 24 (15) 2018). Conditional logistic regression was applied to investigate differences in adipocyte hypertrophy between groups of patients (e.g., cases and controls). Results: Adipocytes were larger and the proportion of adipose tissue was higher in post-menopausal patients (both p&amp;lt;0.001). Mean adipocyte maximum diameter and mean adipocyte area of the 75th percentile ranged from 46.9-115.9 µm and 2016-11336 µm2 respectively. For every 1000 µm2 increase in mean adipocyte area a DCIS patient had a 1.18 increased risk for iIBC (95% CI 1.02-1.36, p= 0.028). DCIS patients with large adipocytes (above the 75th percentile) had a 2.1 increased risk for developing iIBC (95% CI: 1.18-3.72, p=0.011). This observation remained when restricting the analysis to post-menopausal patients (OR 1.19 per 1000 µm2 95% CI 1.01-1.40, p=0.038 and adipocytes above 75th percentile OR 2.2, 95% CI 1.22-3.99, p= 0.009). To further explore the potential interactions between the epithelial cells from DCIS with the adjacent adipocytes, we compared the size of the DCIS-adjacent adipocytes to those away from DCIS lesions. DCIS-adjacent adipocytes showed a reduction in size, suggesting delipidation. Adipose triglyceride lipase (ATGL) is a rate limiting lipase that can release stored free fatty acids (FFA) in DCIS cells for fatty acid ß-oxidation. In a pilot series strong ATGL expression was observed in a subset of DCIS lesions (4 of 25). Conclusion and perspective: This study is the first to demonstrate that mammary adipocyte hypertrophy is associated with an increased risk of progression for patients with DCIS. Our findings might help to distinguish potentially hazardous from harmless DCIS, enabling overtreatment of indolent DCIS. Adipocyte size will be correlated to immunohistochemical expression of ATGL, Her2, ER and COX2 in DCIS, and RNAseq data of pure microdissected DCIS. Citation Format: Mathilde Matthea Machteld Almekinders, Michael Schaapveld, Bram Thijssen, Ingrid Hofland, Marjolijn Mertz, Dennis Peters, Annegien Broeks, Lodewijk Wessels, Wilbert Zwart, Jos Jonkers, Esther Lips, Christine Desmedt, Jelle Wesseling, on behalf of the PRECISION Team. Impact of increased mammary adiposity on DCIS progression [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 P6-15-07.

Beta-adrenergic reactivity of erythrocytes and the progression of heart failure in patients after myocardial infarction

Aim. To identify the associations between beta-adrenergic reactivity of erythrocytes and the progression of heart failure (HF) in patients after myocardial infarction (MI).Material and methods. The study included 50 patients with HF and history of MI 6 months ago. To determine the level of sympathoadrenal system activity, we analyzed beta-adrenergic reactivity by changing the osmotic resistance of erythrocytes by use of adrenoceptor blocking agent.Results. The frequency of HF progression after index MI was 26% (n=13). All patients were divided into 2 groups depending on the presence/absence of HF progression in the postinfarction period. When determining beta-adrenergic reactivity, it was found that patients with HF progression compared with patients without it had the higher level of beta-adrenergic reactivity of membrane (β-ARM) of erythrocytes: 58,8 (50,9; 78,0) CU and 46,8 (38,0; 66,3) CU, p=0,025). A ROC analysis made it possible to establish the β-ARM level ≥49,53 CU a cut-off point, which can be considered as a marker of HF progression in patients after MI (sensitivity 92,3%, specificity 62,2%). This level of β-ARM is associated with a more than five-fold increase of HF progression risk in patients after MI (OR 5,48; 95% CI 1,28-23,37; p=0,024).Conclusion. In patients with HF and MI history, there is a decrease in the adrenergic reactivity of erythrocyte cell membrane, which is reflected by an increase of β-ARM above normal range of 20 CU. At the same time, β-ARM in patients with HF progression compared with patients without it is significantly increased. Established cut-off point of β-ARM (≥49,53 CU) allows predicting the HF progression with high sensitivity and specificity.

Risk of Progression in Patients with Smoldering Myeloma

Background: Smoldering multiple myeloma (SM) is a heterogenous clinical entity with a variable rate of progression to symptomatic multiple myeloma (MM). Identification of demographic characteristics and outcomes of SM patients have been hampered by the lack of specific ICD code for SM. Here, we analyzed the National Cancer Database (NCDB) for this purpose, which covers &gt;70% of cancer patients in the U.S. Methods: We reviewed patients in the NCDB who were diagnosed with MM between 2010 and 2014. Patients who did not receive any treatment within 3 months after the diagnosis and still alive were considered to have had SM (Ravindran et al. Blood Cancer J. 2016). Initiation of systemic treatment was considered as a surrogate of progression to symptomatic MM. Overall survival (OS) of SM patients was calculated from initiation of systemic treatment after they progressed to MM, estimated by the Kaplan-Meier method, and compared with the log-rank test. Cumulative incidence of progression from SM to MM was calculated with death as a competing risk and compared with the Gray's test. Multivariable Cox and logistic regression analysis were performed to identify independent predictors of OS and progression to MM, respectively. Results: We reviewed 68,234 patients and identified 12,984 patients with SM. Among SM patients, 3002 (23%) were black, 6796 (52%) were male, and median age at diagnosis was 69 years (range: 22 - 90). SM patients' insurance types were private for 4164 (32%), Medicare for 7420 (57%), Medicaid for 669 (5%), and 260 (2%) were uninsured. Majority of the cases were reported from non-academic hospitals (59%). Patient and treatment characteristics are summarized in Table 1. SM was diagnosed in black patients a median of 4 years younger than in white patients (median age 66 vs 70 years, p&lt;0.0001). Charlson comorbidity index was 2 or more for 325 (11%) black and 629 (7%) white patients (p&lt;0.0001). Median annual household income of white patients was higher than black patients (p&lt;0.0001). Median time to progression from SM to MM was 4.5 months (range: 3 - 64). Progression to MM was seen in 3144 (24%) patients during median follow-up of 39 months. All SM patients received chemo- or immunotherapy after progression and 867 (7%) underwent hematopoietic cell transplant. Four-year cumulative incidence of progression to MM for SM patients at ages of &lt;60 vs 60-70 and &gt;70 years was 34% (95% CI: 32 - 35) vs 28% (95% CI: 26 - 29, p&lt;0.0001) and 18% (95% CI: 17 - 19, p&lt;0.0001), respectively (Figure 1A). Four-year cumulative incidence of progression to MM for patients of black and white race was 24.5% (95% CI: 23 - 26) and 24.4% (95% CI: 24 - 25), respectively (p=0.99) (Figure 1B). Four-year cumulative incidence of progression to MM for patients who were diagnosed between 2010-2012 and 2013-2014 was 25% (95% CI: 24 - 26) and 24% (95% CI: 23 - 25), respectively (p=0.17) (Figure 1D). On multivariable analysis, each 10-year decrease in age (OR 1.06, 95% CI: 1.05 - 1.06, p&lt;0.0001), white vs black race (OR 1.02, 95% CI: 1.00 - 1.04, p=0.027), and each 1-year decrease in diagnosis year (OR 1.01, 95% CI: 1.00 - 1.01, p=0.015) were associated with progression to MM, however male vs female gender (OR 1.01, 95% CI: 0.99 - 1.02, p=0.26) was not statistically significant. Four-year OS of SM patients after progression and MM patients without known preceding SM who received treatment were 63% (95% CI: 61 - 65) and 54% (95% CI: 54 - 55), respectively (p&lt;0.0001). Figure 2 shows OS of the patients with SM in several subgroups. Four-year OS of SM patients after progression to MM at ages of &gt;70 vs 60-70 and &lt;60 years were 44% (95% CI: 40 - 48) vs 67% (95% CI: 63 - 71, p&lt;0.0001) and 76% (95% CI: 73 - 80, p&lt;0.0001), respectively (Figure 2A). On multivariable analysis, each 1-year increase in age (HR 1.04, 95% CI: 1.03 - 1.05, p&lt;0.0001), each 1 increase in Charlson comorbidity score (HR 1.30, 95% CI: 1.19 - 1.42, p&lt;0.0001), academic vs non-academic hospital (HR 0.79, 95% CI: 0.69 - 0.90, p=0.0005), and immunotherapy vs no immunotherapy (HR 0.71, 95% CI: 0.59 - 0.86, p=0.0004) were statistically significant predictors of OS (Table 2). Conclusion: Taken together, our result shows higher rate of MM progression in younger SMM patients than old ones as well as earlier age of SMM diagnosis in Blacks. Also, this study highlights the importance of known SMM stage before MM in prolonging survival which can be indicative of benefit from screening programs. Disclosures Metheny: Incyte: Speakers Bureau; Takeda: Speakers Bureau. Malek:Celgene: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Medpacto: Research Funding; Janssen: Speakers Bureau; Amgen: Speakers Bureau; Adaptive: Consultancy.

Baseline Central Visual Field Defect as a Risk Factor For NTG Progression: A 5-Year Prospective Study.

This 5-year follow-up study on normal-tension glaucoma (NTG) patients demonstrated that those with baseline central visual field (VF) defect progress at a more increased rate compared with those with peripheral field defect. The purpose of this study was to investigate the clinical characteristics, including 24-hour ocular perfusion pressure and risk of progression in patients with baseline central VF defect, as compared with those with peripheral VF defect in NTG. This was a prospective, longitudinal study. A total of 65 NTG patients who completed 5 years of follow-up were included in this study. All the enrolled patients underwent baseline 24-hour intraocular pressure and blood pressure monitoring via 2-hourly measurements in their habitual position and had ≥5 reliable VF tests during the 5-year follow-up. Patients were assigned to two groups on the basis of VF defect locations at baseline, the central 10 degrees, and the peripheral 10- to 24-degree area. Modified Anderson criteria were used to assess global VF progression over 5 years. Kaplan-Meier analyses were used to compare the elapsed time of confirmed VF progression in the two groups. Hazard ratios for the association between clinical risk factors and VF progression were obtained by using Cox proportional hazards models. There were no significant differences between the patients with baseline central and peripheral VF defects in terms of demography, clinical, ocular and systemic hemodynamic factors. Eyes with baseline defects involving the central fields progressed faster (difference: βcentral=-0.78 dB/y, 95% confidence interval=-0.22 to -1.33, P=0.007) and have 3.56 times higher hazard of progressing (95% confidence interval=1.17-10.82, P=0.025) than those with only peripheral defects. NTG patients with baseline central VF involvement are at increased risk of progression compared with those with peripheral VF defect.

Invited Commentary Re: Early Chemical Thromboprophylaxis does not Increase the Risk of Intracranial Hematoma Progression in Patients with Isolated Severe Traumatic Brain Injury.

Invited Commentary Re: Early Chemical Thromboprophylaxis does not Increase the Risk of Intracranial Hematoma Progression in Patients with Isolated Severe Traumatic Brain Injury.

Persistent confirmed low-grade dysplasia in Barrett's esophagus is a risk factor for progression to high-grade dysplasia and adenocarcinoma in a US Veterans cohort.

Patients with Barrett's esophagus (BE) and low-grade dysplasia (LGD) are at increased risk of esophageal adenocarcinoma (EAC), although many regress to nondysplastic BE. This has significant clinical importance for patients being considered for endoscopic eradication therapy. Our aim is to determine the risk for progression in patients with confirmed persistent LGD. We performed a single-center retrospective cohort study of patients with BE and confirmed LGD between 2006 and 2016. Confirmed LGD was defined as LGD diagnosed by consensus conference with an expert GI pathologist or review by an expert GI pathologist and persistence as LGD present on subsequent endoscopic biopsy. The primary outcome was the incidence rate of HGD (high-grade dysplasia)/EAC. Secondary outcomes included risk factors for dysplastic progression. Risk factors for progression were assessed using univariate and multivariate analysis with logistic regression. Of 69 patients (mean age 65.2 years) with confirmed LGD were included. In total, 16 of 69 patients (23.2%) with LGD developed HGD/EAC during a median follow-up of 3.74 years (IQR, 1.24-5.45). For persistent confirmed LGD, the rate was 6.44 (95% confidence interval (CI), 2.61-13.40) compared to 2.61 cases per 100 patient-years (95% CI, 0.83-6.30) for nonpersistent LGD. Persistent LGD was found in only 29% of patients. Persistent LGD was an independent risk factor for the development of HGD/EAC (OR 4.18; [95% CI, 1.03-17.1]). Persistent confirmed LGD, present in only 1/3 of patients, was an independent risk factor for the development of HGD/EAC. Persistence LGD may be useful in decision making regarding the management of BE.

MON-039 SMALL KIDNEY SIZE RELATIVE TO BODY MASS IS A RISK FACTOR FOR RENAL FUNCTION DETERIORATION IN IGA NEPHROPATHY PATIENTS

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. However, identifying IgAN patients at higher risks for renal function decline is still a challenge. Recent investigations have proposed kidney size to be a risk factor for renal function decline in kidney transplantation recipients. Therefore, this study aimed to investigate whether kidney size has an effect on renal function deterioration rate in patients with IgAN. Retrospective analysis was preformed from electronic medical records of 516 biopsy-proven IgAN patients. Kidney length was considered as the longest longitudinal diameter from sonographic measurements obtained at the time of biopsy. The average length of both kidneys was divided by body mass index for each individual to make adjustments for subject size (BMI-adjusted kidney size). Renal outcome was defined as a composite of a ≥ 50% decline in estimated glomerular filtration rate (eGFR) from baseline or the onset of end-stage renal disease. The mean age of the patients was 40.4 ± 12.1 years and 211 patients (40.9%) were male. The mean eGFR was 79.6 ± 28.3 mL/min/1.73 m2 and the average kidney length was 102.8 ± 8.8 mm at baseline. The median follow-up duration was 51 months. When the patients were grouped into tertiles based on BMI-adjusted kidney size, renal outcome occurred in 30 (17.0%), 25 (14.0%), and 12 (7.4%) patients in the 1st, 2nd, and 3rd tertile groups, respectively. The amount of proteinuria was lowest and eGFR was highest in the BMI-adjusted kidney size group. Multivariate Cox proportional analysis revealed that the risk of renal outcome significantly lower in the 3rd tertile group as compared to the 1st tertile group (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.21-0.93; P = 0.031). Additionally, the risk of incident CKD significantly decreased as the BMI-adjusted kidney size increased (HR, 0.55; 95% CI, 0.36-0.86; P = 0.008). These results remained robust even after adjustments were made for confounding factors including baseline eGFR and proteinuria. Small kidney size could be a risk factor for renal function decline in IgA nephropathy patients. Simple sonographic kidney size measurements may help stratifying progression risk in patients with IgA nephropathy.

Risk Scores in Patients with Chronic Kidney Disease

Assessing the risk of adverse outcomes associated with chronic kidney disease (CKD) is important for physicians and affected patients alike. Categorizing CKD according to the cause-GFR category-albuminuria category (CGA)-classification system proposed by KDIGO already provides a semi-quantitative assessment of risks. The more recent development of the "Tangri"-formula provides a means to quantify the risk of progression for patients with CKD stage G3a-G5 (eGFR 10 - 59 ml/min/1.73 m2) to kidney failure requiring kidney replacement therapy. To use this formula, the variables age, sex, eGFR and albuminuria are required (4-variable equation). An extended formula with the additional parameters calcium, phosphate, bicarbonate and albumin (8-variable equation) allows an even more precise estimation of progression risk. In patients with advanced CKD, stage G4 or higher (GFR category ≥ 4, i. e. eGFR < 30 ml/min/1.73 m2), models recently developed by the CKD-prognosis consortium can not only be used to predict the risk of kidney failure but also the risk of cardiovascular disease events and death. The risk estimators can be accessed through websites (http://kidneyfailurerisk.com, http://www.ckdpcrisk.org/lowgfrevents/) and via downloading of the respective "apps". These novel tools may prove useful for health care decisions and as a basis for discussions with CKD patients.

Sa1139 – Risk of Dysplastic Progression in Patients with Barrett's Esophagus Indefinite for Dysplasia: A Systematic Review and Meta-Analysis

Sa1139 – Risk of Dysplastic Progression in Patients with Barrett's Esophagus Indefinite for Dysplasia: A Systematic Review and Meta-Analysis

Individual patient risk of progression of urinary bladder papillary tumors estimated from biomarkers at initial transurethral resection of bladder tumor.

To determine if individual, instead of group, patient progression risk could be predicted using p53, Ki67 and CK20 biomarker percentage values at initial transurethral resection of bladder tumor specimens. This was an observational study where biomarkers were measured with no knowledge of tumor outcome. Initial bladder tumor specimens were classified as non-invasive and invasive to sub-epithelium (pT1). Percentages of stained biomarker cells were tested as progression predictors from non-invasive to pT1 and pT1 to pT2. Progression probability was correlated with biomarker percentages resulting in a regression equation. We studied 112 patients (median age = 67, range 37-91, males 83/112 (73%), with median follow-up of 39months (range 1.7-140). Mean biomarker values were higher in stage pT1 than in non-invasive (all p < 0.001). Cut-off points separating progression from non-progression groups in stage pT1 were higher than in non-invasive for all biomarkers. Correlation R values for progression probability vs. biomarker percentages varied from 0.7 to 0.9 (all p < 0.001), regression slopes from 0.1 to 0.8 and intercepts from 11 to 35. A novel individual progression probability was calculated as the product of biomarker percentage of stained cells and slope, plus the prevalence-adjusted intercept. Identification of individual risk of progression in patients with non-muscle-invasive bladder tumors was possible using p53- and Ki67-derived progression probability using a regression equation. Combining biomarker-derived progression probability to tumor stage pT1 improves progression to pT2 predictive accuracy.