Independent Predictors Of Progression Research Articles

Extracellular volume-based scoring system for tracking tumor progression in pancreatic cancer patients receiving intraoperative radiotherapy

ObjectivesTo investigate the value of extracellular volume (ECV) derived from portal-venous phase (PVP) in predicting prognosis in locally advanced pancreatic cancer (LAPC) patients receiving intraoperative radiotherapy (IORT) with initial stable disease (SD) and to construct a risk-scoring system based on ECV and clinical-radiological features.Materials and methodsOne hundred and three patients with LAPC who received IORT demonstrating SD were enrolled and underwent multiphasic contrast-enhanced CT (CECT) before and after IORT. ECV maps were generated from unenhanced and PVP CT images. Clinical and CT imaging features were analyzed. The independent predictors of progression-free survival (PFS) determined by multivariate Cox regression model were used to construct the risk-scoring system. Time-dependent receiver operating characteristic (ROC) curve analysis and the Kaplan–Meier method were used to evaluate the predictive performance of the scoring system.ResultsMultivariable analysis revealed that ECV, rim-enhancement, peripancreatic fat infiltration, and carbohydrate antigen 19-9 (CA19-9) response were significant predictors of PFS (all p < 0.05). Time-dependent ROC of the risk-scoring system showed a satisfactory predictive performance for disease progression with area under the curve (AUC) all above 0.70. High-risk patients (risk score ≥ 2) progress significantly faster than low-risk patients (risk score < 2) (p < 0.001).ConclusionECV derived from PVP of conventional CECT was an independent predictor for progression in LAPC patients assessed as SD after IORT. The scoring system integrating ECV, radiological features, and CA19-9 response can be used as a practical tool for stratifying prognosis in these patients, assisting clinicians in developing an appropriate treatment approach.Critical relevance statementThe scoring system integrating ECV fraction, radiological features, and CA19-9 response can track tumor progression in patients with LAPC receiving IORT, aiding clinicians in choosing individual treatment strategies and improving their prognosis.Key PointsPredicting the progression of LAPC in patients receiving IORT is important.Our ECV-based scoring system can risk stratifying patients with initial SD.Appropriate prognostication can assist clinicians in developing appropriate treatment approaches.Graphical

Long-term outcomes of neoadjuvant endocrine therapy versus chemotherapy in luminal HER2-breast cancer

Introduction. Neoadjuvant endocrine therapy (NET) is an effective treatment modality that can downsize breast tumors in a cohort of postmenopausal women with HR-positive HER2-negative breast cancer. A lack of data regarding efficacy of NET vs neoadjuvant cytotoxic chemotherapy (NCT) leads to limited usage of NET despite its favorable toxicity profile. Perioperative endocrine therapy is mainly used for the elderly or patients with comorbidities that limit their access to NCT. The COVID-19 pandemic led to increased data of NET efficacy. Nevertheless, long-term outcomes of NET application are underrepresented in literature. Objective. Assessment of long-term outcomes in patients treated with neoadjuvant endocrine therapy (NAT) versus neoadjuvant cytotoxic chemotherapy in a cohort of postmenopausal women with HR-positive HER2-negative breast cancer. Materials and methods. We retrospectively evaluated the results of treatment of 154postmenopausal patients with luminal HER2-breast cancer who were treated with neoadjuvant systemic therapy (NET or NCT) at the State Medical Institution «St. Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)» from 01.01.2019 to 31.11.2020. We analyzed data on radiological, pathomorphological and long-term treatment outcomes (rate of locoregional and overall recurrence) in two groups.Results. 154 patients received neoadjuvant hormone therapy (n=78) or neoadjuvant chemotherapy (n=76). The clinical response was evaluated according to the RECIST criteria after 12 weeks and after study treatment using MMG. Partial or complete radiological response was achieved in 41.0% (n=32) in the NET group vs 69.7% (n=53) in the NCT group (p&lt;0.001). All patients included in the study underwent surgery. A complete pathologic response was observed in 9.2% (n=7) of patients in the chemotherapy group, and in 0% of patients in the endocrine therapy group (p=0.006). Median follow-up was 46.2 months. Progression was recorded in 23.2% (n=29) of participants, with no significant benefit of NCT over NET in the frequency of locoregional relapses (NET n=8 (10.3%) vs NCT n=4 (5.3%)) (p= 0.369) or the occurrence of distant metastases NAT n=8 (10.3%) vs NCT n=13 (17.1%)) (p=0.216). Multivariate analysis showed that only pathologic lymph node status (ypN2–3) was an independent predictor of progression (p=0.007, OR=3.2; 95%CI: 1.380-7.422). Conclusions. Long-term outcomes after neoadjuvant hormone therapy are comparable with chemotherapy in the group of postmenopausal women with luminal HER2-breast cancer. The small sample size and limited follow-up period are significant limitations of our work.

Efficacy of Platinum-based Chemotherapy in Patients With Metastatic Urothelial Carcinoma With Variant Histology.

Variant urothelial carcinoma (VUC, defined herein as urothelial carcinoma with any histological variant) is frequently observed at an advanced stage. However, the efficacy of systemic chemotherapy against VUC in metastatic disease has rarely been reported. This study assessed the therapeutic response and survival outcomes of platinum-based chemotherapy as first-line treatment in patients with metastatic VUC. We retrospectively analyzed consecutive patients with metastatic bladder and upper urinary tract cancer who received gemcitabine plus cisplatin (or carboplatin) at the University of Occupational and Environmental Health Hospital between November 2008 and November 2022. Progression-free survival and overall survival were evaluated using the Kaplan-Meier method and Cox proportional hazard models. Out of 131 patients recorded, 86 (65.6%) had pure urothelial carcinoma (PUC) and 45 (34.4%) had VUC. The most common variant element was squamous differentiation (44.4%). Compared to those with PUC, patients with VUC showed a comparable objective response rate (33.3% vs. 41.9%, p=0.451) and disease control rate (64.5% vs. 75.6%, p=0.221). They also had poorer progression-free survival (median=4.9 months vs. 7.9 months, p=0.014) and overall survival (median=10.9 months vs. 18.2 months, p=0.037) than those with PUC. On multivariate analysis, VUC was an independent predictor of progression (hazard ratio=1.79; 95% confidence interval=1.19-2.69; p=0.005) and mortality (hazard ratio=1.64; 95% confidence interval=1.08-2.48; p=0.020). Although the response of metastatic VUC to platinum-based chemotherapy was not inferior to that of PUC, VUC had progressed faster than PUC. VUC was significantly associated with a poor prognosis after platinum-based chemotherapy as first-line treatment.

Clinical Outcomes of Patients With Variant Histology of Urothelial Carcinoma After Radical Cystectomy

Purpose: The efficacy of standard chemotherapy or radical cystectomy in patients who have urothelial tumors with variant histology (VH) is very limited in terms of their prognosis. This study aimed to investigate the prognosis of bladder cancer (BC) patients with VH who underwent radical cystectomy (RC).Materials and Methods: We retrospectively evaluated 327 BC patients who underwent RC at Pusan National University Yangsan Hospital between February 2010 and June 2021. VH was categorized into less and more aggressive types according to the patient’s mortality risk relative to pure urothelial carcinoma (PUC). More aggressive types included micropapillary, plasmacytoid, and sarcomatoid variants. Less aggressive types comprised other variant types, including squamous differentiation, glandular differentiation, lipoid, and nested. Small cell carcinoma, pure adenocarcinoma, pure squamous cell carcinoma, and lymphoma BC were excluded from analysis. The progression-free survival (PFS) and overall survival (OS) rates were evaluated using Kaplan-Meier analysis and Cox regression.Results: After the exclusion of nonurothelial tumors, data from 299 patients were available for analysis. We identified 244 (74.6%) and 55 patients (16.8%) with PUC and urothelial carcinoma with VH, respectively. VH patients were categorized as having less aggressive (n=35) and more aggressive (n=20) types. Univariate analysis identified significant differences in PFS (p=0.031) between patients with PUC (n=244) and more aggressive VH (n=20). Multivariate analysis showed that more aggressive VH was significantly associated with OS and PFS. In the Kaplan-Meier analysis, a statistically significant difference was observed between PUC and more aggressive VH in OS and PFS.Conclusions: VH patients with more aggressive types showed more advanced TNM stages at presentation than PUC patients. Pathological upstaging after RC was more common in VH patients. Among VH patients, the presence of a more aggressive VH type can be an independent predictor of progression after RC, with a worse prognosis than that of PUC patients.

Long-term non-progression and risk factors for disease progression among children living with HIV in Botswana and Uganda: A retrospective cohort study

ObjectivesWe utilize a large retrospective study cohort derived from electronic medical records to estimate the prevalence of long-term non-progression (LTNP) and determine the factors associated with progression among children infected with HIV in Botswana and Uganda. MethodsElectronic medical records from large tertiary HIV clinical centers in Botswana and Uganda were queried to identify LTNP children 0-18 years enrolled between June 2003 and May 2014 and extract demographic and nutritional parameters. Multivariate subdistribution hazard analyses were used to examine demographic factors and nutritional status in progression in the pre-antiretroviral therapy era. ResultsBetween the two countries, 14,246 antiretroviral therapy-naïve children infected with HIV were enrolled into clinical care. The overall proportion of LTNP was 6.3% (9.5% in Botswana vs 5.9% in Uganda). The median progression-free survival for the cohort was 6.3 years, although this was lower in Botswana than in Uganda (6.6 vs 8.8 years; P <0.001). At baseline, the adjusted subdistribution hazard ratio (aHRsd) of progression was increased among underweight children (aHRsd 1.42; 95% confidence interval [CI]: 1.32-1.53), enrolled after 2010 (aHRsd 1.32; 95% CI 1.22-1.42), and those from Botswana (aHRsd 2; 95% CI 1.91-2.10). ConclusionsIn our study, the prevalence of pediatric LTNP was lower than that observed among adult populations, but progression-free survival was higher than expected. Underweight, year of enrollment into care, and country of origin are independent predictors of progression among children.

Factors associated with rapid progression in fibrotic interstitial lung disease

BackgroundEarly identification of fibrotic interstitial lung disease (F-ILD) patients with high risk of progression will help initiate early therapeutic intervention and potential improvement of outcomes. This study was designed to assess the predictors of progression in patients with F-ILD. MethodsPatients with F-ILD in Shanghai Pulmonary Hospital between January 1, 2019 and July 31, 2021 were retrospectively analyzed. The patients enrolled were divided into progressive group and non-progressive group according to the specified criteria. Baseline characteristics were collected and a multivariate regression was conducted to identify independent predictors of progression. ResultsOf the 177 F-ILD cases, 87 were enrolled in the progressive group and 90 were in the non-progressive group. The cohort included 11 types of F-ILD, primarily were connective tissue disease-associated interstitial lung disease (CTD-ILD) (43, 24.3 %), idiopathic pulmonary fibrosis (IPF) (39, 22.0 %), interstitial pneumonia with autoimmune features (IPAF) (32, 18.1 %), and unclassifiable (23, 13.0 %). The highest proportion of progression was seen in nonspecific interstitial pneumonia (NSIP) subgroup (66.7 %), followed by IPF (59.0 %) and HP (57.1 %). After adjusting for gender and age, a course of disease longer than 9.5 months (OR: 2.633; 95 % CI: 1.190–5.826, P = 0.017), lymphocyte in peripheral blood more than 2.24 (109/L) (OR: 2.670; 95 % CI: 1.095–6.510, P = 0.031), and emphysema in high-resolution computed tomography (HRCT) (OR: 2.387; 95 % CI: 1.017–5.640, P = 0.046) were independent predictors of progression in F-ILD patients. ConclusionsThis study suggested that in patients with F-ILD, long course of disease, elevated blood lymphocyte and emphysema on HRCT were independent predictors of progression, which may suggest utility in early therapeutic intervention.

Prediction of Mild Cognitive Impairment Progression to Alzheimer’s Disease Based on Diffusion Tensor Imaging-Derived Diffusion Parameters: Construction and Validation of a Nomogram

Introduction: The aim of the study was to construct and validate a nomogram that combines diffusion tensor imaging (DTI) parameters and clinically relevant features for predicting the progression of mild cognitive impairment (MCI) to Alzheimer’s disease (AD). Method: A retrospective analysis was conducted on the MRI and clinical data of 121 MCI patients, of whom 32 progressed to AD during a 4-year follow-up period. The MCI patients were divided into training and validation sets at a ratio of 7:3. DTI features were extracted from MCI patient data in the training set, and their dimensionality was reduced to construct a radiomics signature (RS). Then, combining the RS with independent predictors of MCI disease progression, a joint model was constructed, and a nomogram was generated. Finally, the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to evaluate the diagnostic and clinical efficacy of the nomogram based on the data from the validation set. Result: The AUCs of the RS in the training and validation sets were 0.81 and 0.84, with sensitivities of 0.87 and 0.78 and specificities of 0.71 and 0.81, respectively. Multiple logistic regression analysis showed that the RS, clinical dementia rating scale score, and Alzheimer's disease assessment scale score were the independent predictors of progression and were thus used to construct the nomogram. The AUCs of the nomogram in the training and validation sets were 0.89 and 0.91, respectively, with sensitivities of 0.78 and 0.89 and specificities of 0.90 and 0.88, respectively. DCA showed that the nomogram was the most valuable model for predicting the progression of MCI to AD and that it provided greater net benefits than other analysed models. Conclusion: Changes in white matter fibre bundles can serve as predictive imaging markers for MCI disease progression, and the combination of white matter DTI features and relevant clinical features can be used to construct a nomogram with important predictive value for MCI disease progression.

Impact of age >70 years on oncological outcomes in patients with non-muscle-invasive bladder cancer treated with Bacillus Calmette-Guérin.

To evaluate the impact of age on oncological outcomes in a large contemporary cohort of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adequate Bacillus Calmette-Guérin (BCG). We performed an Institutional Review Board-approved retrospective study analysing patients with NMIBC treated with adequate BCG at our institution from 2000 to 2020. Adequate BCG was defined as per United States Food and Drug Administration (FDA) guidelines as being receipt of at least five of six induction BCG instillations with a minimum of two additional doses (of planned maintenance or of re-induction) of BCG instillations within a span of 6 months. The study's primary outcome was to determine if age >70 years was associated with progression to MIBC cancer or distant metastasis. The cumulative incidence method and the competing-risk regression analyses were used to investigate the association of advanced age (>70 years) with progression, high-grade (HG) recurrence and cancer-specific mortality (CSM). Overall, data from 632 patients were analysed: 355 patients (56.2%) were aged ≤70 years and 277 (43.8%) were >70 years. Age >70 years did not adversely affect either cumulative incidence of progression or HG recurrence (P = 0.067 and P = 0.644, respectively). On competing-risk regression analyses, age >70 years did not emerge as an independent predictor of progression or HG recurrence (sub-standardised hazard ratio [SHR] 1.57, 95% confidence interval [CI] 0.87-2.81, P = 0.134; and SHR 1.05, 95% CI 0.77-1.44, P = 0.749). Not unexpectedly, patients in the older group did have higher overall mortality (P < 0.001) but not CSM (P = 0.057). Age >70 years was not associated with adverse oncological outcomes in a large contemporary cohort of patients receiving adequate intravesical BCG for NMIBC. BCG should not be withheld from older patients seeking for bladder sparing options.

Histologic margin status is a predictor of relapse in lentigo maligna melanoma

Most surgical margins for lentigo maligna melanomas reported in the literature are clinical and not histologic. We sought to determine whether histologic margin status is an independent predictor of progression. Clinicopathologic information of 268 invasive lentigo maligna melanomas diagnosed from 1990-2019 were analyzed. Statistical analyses were performed using Cox proportional hazards model and Boruta method. A total of 75% of the lesions were located on the head and neck. The range of follow-up for all patients was 0 to 31.8years (median, 10.2years). Time to local recurrence ranges from 0 to 20years (median, 3years). Progression developed in 54 (20.1%) of 268 patients. Local recurrence was seen only in 36 (13.4%), both local recurrence and subsequent metastasis in 7 (2.6%), and only metastasis in 11 (4.1%) of 268 patients. Histologic margin status (positive and close/<3mm) and tumor site (head and neck location) significantly correlated with worse progression-free survival. Single institution and retrospective study. Histologic margin status is the strongest predictor of progression for lentigo maligna melanoma. Patients with positive or close/<3mm histologic margins should consider a re-excision due to the increased risk of relapse.

Maintenance therapy with carfilzomib, pomalidomide, and dexamethasone (KPd) in high-risk myeloma patients (pts): A phase 2 study with a safety run-in.

8001 Background: High-risk pts derive survival benefit from combination maintenance (PI and IMiD) strategies. We have evaluated the safety and efficacy of the next generation PI (carfilzomib) and IMiD (pomalidomide) in combination with dexamethasone in high-risk myeloma (NCT03756896). Methods: Newly diagnosed high-risk myeloma pts that have achieved ≥PR post-ASCT were included. High-risk myeloma was defined by the presence of t(4;14) in 27.6%, t(14;16) in 17.2%, del17p in 58.6% pts by FISH or CTG or presence of ≥20% circulating cells (pPCL) in 6.9%. Double-hit myeloma (as defined by presence of ≥2 high-risk cytogenetic abnormalities including gain of 1q) was seen in 58.6% of pts. Each cycle is 28 days. Carfilzomib 20/56 mg/m2 IV was given on days 1,8,15 and pomalidomide 2 mg PO on days 1 to 21 and dexamethasone 40 mg PO was administered on days of carfilzomib. Statistical analysis was conducted using SAS Version 9.4. Results: After the safety run in the first 3 pts, 26 additional pts were enrolled. Median age was 60 years (range, 46−75); 58.6% male and 58.6% black. At diagnosis, 65.5% had RISS stage 3 disease. 54.5% of whites and 64.7% of blacks had double-hit disease. Median time from diagnosis and from transplant to study entry was 9.3 (range, 6.08-12.42) and 2.89 (range, 2-8.51) months, respectively. At study entry, ≥CR and ≥VGPR rates were 24.1% and 68.9%, respectively, which deepened to 79.3% and 100% while on study. The median time to best response was 2.07 months (range, 1.22-14.26). Of the 15 pts with available MRD data, MRD (10-5) and (10-6) were achieved in 80% and 53.3%, respectively. After a median follow-up of 25.8 months, 36 month PFS was 63.2% (95% CI 38.3-80.3%) and 36 month OS was 72.4% (44.2-88.0%). Double-hit disease was an independent predictor for progression and death. Among these high risk patients, RISS did not show any statistical significance. While there is no PFS difference by race, the 36 month OS for black pts was inferior compared to whites (61.1% [23.1-84.7%] vs 85.7% [33.4%-97.9%], log rank 0.05). At data cut-off, 37.9% of pts were still receiving treatment; most common reason for permanent treatment discontinuation was progressive disease (27.6%). Among the 6 pt deaths, the most common cause of death was progressive disease (83.3%). Most common (≥20%) TEAEs were fever (37.9%), fatigue (34.5%), diarrhea (27.6% [G3/4, 3.4%]), nausea (24.1%), cough (20.7%), muscle cramps (20.1%), acneiform rash (20.1%). TEAEs of interest were cardiac (10.3% [G3/4, 3.4%]), cataracts (17.2% [G3/4, 17.2%]), neutropenia (6.9% [G3/4, 6.9%]) and anemia (10.3% [G3/4, 0%]). Conclusions: In pts with high-risk myeloma, KPd maintenance deepened responses. MRD negativity (10-5) was attained in 80% of pts. Despite the encouraging results in this cohort of high-risk patients, PFS and OS among double-hit pts remains poor, warranting newer strategies aimed at remission sustenance. Clinical trial information: NCT03756896 .

MP55-05 BASELINE 4K SCORE PREDICTS PROGRESSION ON ACTIVE SURVEILLANCE IN PROSTATE CANCER INDEPENDENTLY OF CLINICAL INFORMATION AND PIRADS SCORE

You have accessJournal of UrologyCME1 Apr 2023MP55-05 BASELINE 4K SCORE PREDICTS PROGRESSION ON ACTIVE SURVEILLANCE IN PROSTATE CANCER INDEPENDENTLY OF CLINICAL INFORMATION AND PIRADS SCORE Helen Hougen, Isildinha M. Reis, Nachiketh S. Prakash, Ruben Blachman-Braun, Jessica Delgado, Chad R. Ritch, Bruno Nahar, Mark L. Gonzalgo, Dipen J. Parekh, Radka Stoyanova, Sandra M. Gaston, Oleksandr Kryvenko, Brandon Mahal, Matthew Abromowitz, Alan Dal Pra, Alan Pollack, and Sanoj Punnen Helen HougenHelen Hougen More articles by this author , Isildinha M. ReisIsildinha M. Reis More articles by this author , Nachiketh S. PrakashNachiketh S. Prakash More articles by this author , Ruben Blachman-BraunRuben Blachman-Braun More articles by this author , Jessica DelgadoJessica Delgado More articles by this author , Chad R. RitchChad R. Ritch More articles by this author , Bruno NaharBruno Nahar More articles by this author , Mark L. GonzalgoMark L. Gonzalgo More articles by this author , Dipen J. ParekhDipen J. Parekh More articles by this author , Radka StoyanovaRadka Stoyanova More articles by this author , Sandra M. GastonSandra M. Gaston More articles by this author , Oleksandr KryvenkoOleksandr Kryvenko More articles by this author , Brandon MahalBrandon Mahal More articles by this author , Matthew AbromowitzMatthew Abromowitz More articles by this author , Alan Dal PraAlan Dal Pra More articles by this author , Alan PollackAlan Pollack More articles by this author , and Sanoj PunnenSanoj Punnen More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003308.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Active surveillance (AS) is the preferred management in low and select intermediate risk prostate cancer patients. Currently, the 4Kscore identifies men with grade group 2+ disease in men with clinical suspicion of prostate cancer but little is known about its utility in men undergoing AS. In this study, we assessed the 4Kscore’s ability to predict tumor progression on men enrolled in a prospective active surveillance protocol. METHODS: We enrolled patients with biopsy-confirmed very low to intermediate risk prostate cancer who elected for AS and obtained prostate MRI, 4Kscore, and targeted +/- systematic biopsy within 1 year of diagnosis and then yearly for 3 years. The 4Kscore was categorized as low (=<20%) and high (=>20%) risk. We estimated cumulative incidence rates of progression over time by the Kaplan-Meier method and used multivariable Cox analyses to assess the association between the 4Kscore and progression while adjusting for NCCN risk at diagnosis, age, PSA density and baseline PIRADS score. RESULTS: The 4Kscore was collected in 166 men at the time of confirmatory biopsy. Over half the patients had a PIRADS 4 or 5 lesions and 4K score of over 20% at baseline. A total of 79 (47.6%) patients progressed during the study period, with 26.5%, 13.3%, 5.4%, and 2.4% progressing at the baseline, 12-month, 24- month, and 36-month visit, respectively. Patients who progressed had higher baseline 4Kscore compared with patients who did not progress (31% IQR 15-59 vs. 14% IQR 8-35, p<0.001; Figure 1a). Patients with a 4Kscore above 20% had higher cumulative incidence of progression by 36 months compared with patients with 4Kscores less than 20% (72.5% [95% CI 60.9-83.1%] vs. 41.0% [95% CI: 28.6-56.3%], p=0.0001, Figure 1b). In a multivariable Cox analysis, 4Kscore above 20% was an independent predictor of progression (HR 1.73, 95% CI: 1.03, 2.88, p=0.037), after adjusting for age, NCCN risk, PSA density and PIRADS score. CONCLUSIONS: Patients with a 4Kscore above 20% have a higher likelihood of progression despite their NCCN risk and MRI findings. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e764 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Helen Hougen More articles by this author Isildinha M. Reis More articles by this author Nachiketh S. Prakash More articles by this author Ruben Blachman-Braun More articles by this author Jessica Delgado More articles by this author Chad R. Ritch More articles by this author Bruno Nahar More articles by this author Mark L. Gonzalgo More articles by this author Dipen J. Parekh More articles by this author Radka Stoyanova More articles by this author Sandra M. Gaston More articles by this author Oleksandr Kryvenko More articles by this author Brandon Mahal More articles by this author Matthew Abromowitz More articles by this author Alan Dal Pra More articles by this author Alan Pollack More articles by this author Sanoj Punnen More articles by this author Expand All Advertisement PDF downloadLoading ...

MP63-15 T1 SUB-STAGING IS ASSOCIATED WITH WORSE ONCOLOGICAL OUTCOMES FOR PATIENTS TREATED WITH BACILLUS CALMETTE-GUERIN OR IMMEDIATE RADICAL CYSTECTOMY.

You have accessJournal of UrologyCME1 Apr 2023MP63-15 T1 SUB-STAGING IS ASSOCIATED WITH WORSE ONCOLOGICAL OUTCOMES FOR PATIENTS TREATED WITH BACILLUS CALMETTE-GUERIN OR IMMEDIATE RADICAL CYSTECTOMY. Roberto Contieri, Wei Shen Tan, Valentina Grajales, Kelly Bree, Patrick Hensley, Charles C. Guo, Neema Navai, Colin P. Dinney, and Ashish M. Kamat Roberto ContieriRoberto Contieri More articles by this author , Wei Shen TanWei Shen Tan More articles by this author , Valentina GrajalesValentina Grajales More articles by this author , Kelly BreeKelly Bree More articles by this author , Patrick HensleyPatrick Hensley More articles by this author , Charles C. GuoCharles C. Guo More articles by this author , Neema NavaiNeema Navai More articles by this author , Colin P. DinneyColin P. Dinney More articles by this author , and Ashish M. KamatAshish M. Kamat More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003321.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: T1 sub-staging has been demonstrated to be of prognostic value in patients with NMIBC treated with intravesical therapy. However, it remains underutilized and has not been included in risk group stratification systems. Herein, we sought to evaluate the prognostic value of T1 substaging in patients treated with Bacillus Calmette-Guerin (BCG) or immediate radical cystectomy (iRC). METHODS: We performed an IRB approved retrospective study analyzing NMIBC patients with pT1 disease treated with either BCG or iRC between 2000 and 2020. Lamina propria (LP) invasion characteristics were classified to either: 1) focal and/or superficial (FS), 2) extensive and/or multifocal (EM), or 3) not specified. Cox regression models, adjusted for tumor and patient characteristics, were used to predict CSS, MFS and PFS. Logistic regression model was used to predict stage >T2 at iRC. RESULTS: A total of 411 T1 HG patients were identified; focal/superficial and extensive/multifocal LP invasion was found in 147 (35.8%) and 149 (36.2%) patients, respectively. Characteristics of LP invasion were not specified in 115 (28%) cases. EM LP invasion was a predictor of both CSS (Hazard ratio (HR): 5.38, 95% CI: 1.8-16.1, p=0.003) and MFS (HR:3.60, 95% CI: 1.51-8.53, p=0.004). Overall, 303 received BCG and 108 underwent iRC. Median follow-up was 49.4 months. Patients with EM LP invasion were significantly more likely to receive iRC (34% vs. 19% p=0.003). Among patients treated with iRC, stage ≥T2 was identified in 21 (19%). T1 substaging was independently associated with upstage at RC (OR: 4.71, 95% CI: 1.06-20.8, p=0.04). Among BCG-treated patients, progression occurred in 41 (13.5%) individuals. EM LP invasion again emerged as an independent predictor of progression after BCG at MV analysis (HR: 5.07, 95% CI: 2-12.55, p<0.001). CONCLUSIONS: Patients with extensive/multifocal LP invasion have poorer CSS and MFS whether treated with BCG or iRC. T1 substaging provides valuable prognostic information and should be reported in pathology reports. Source of Funding: This research was supported by the Wayne B. Duddlesten Professorship in Cancer Research, the Raymond and Maria Floyd Bladder Cancer Research Foundation Grant, NIH/NCI UTMD Anderson SPORE in Genitourinary Cancer (p50CA091846), the Cancer Center Support Grant (NCI Grant P30 CA016672) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e877 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Roberto Contieri More articles by this author Wei Shen Tan More articles by this author Valentina Grajales More articles by this author Kelly Bree More articles by this author Patrick Hensley More articles by this author Charles C. Guo More articles by this author Neema Navai More articles by this author Colin P. Dinney More articles by this author Ashish M. Kamat More articles by this author Expand All Advertisement PDF downloadLoading ...

Heterogeneidad del tumor primario en la18F-FDG PET/TC pretratamiento para predecir el pronóstico en pacientes con cáncer de recto sometidos a cirugía tras terapia neoadyuvante

PurposeThis retrospective study aimed to investigate the value of texture features of primary tumors in pretreatment18F-FDG PET/CT in the prediction of response to treatment, progression, and overall survival in patients with rectal cancer who underwent surgery after neoadjuvant therapy (NAT). MethodsPatients with rectal cancer who had pretreatment18F-FDG PET/CT, and underwent surgery after NAT were included in this study. Clinicopathologic features, date of last follow-up, progression, and death were recorded. Textural and conventional PET parameters (maximum standardized uptake value-SUVmax, metabolic tumor volume-MTV, total lesion glycolysis-TLG) were obtained from PET/CT images using LifeX program. Parameters were grouped using Youden index in ROC analysis. Factors predicting the pathological response to treatment, progression, and overall survival were determined using logistic regression and Cox regression analyses. ResultsForty-four patients (26(59%) male, 18 (41%) female; 60.1 ± 11.4 years) with rectal cancer were included in this study. The numbers of patients with responders and non-responders to NAT were15(34.9%) and 28(65.1%), respectively. One patient’ pathology report did not contain the response status to NAT. The median of follow-up duration was 29.9 months. 9(20.5%) showed disease progression, and 8(18.2%) died during the follow-up period. Difference entropy GLCM and correlation GLCM parameters were found as independent predictors for response to NAT. The positivity of surgical margin, intensity interquartile range CONV and AUC-CSHDISC texture parameters were independent predictors of progression, while normalized inverse difference GLCM and LZLGEGLZLM parameters were independent predictorsof mortality. ConclusionThe texture parameters obtained from pretreatment18F-FDG PET/CT have presented a more robust predictive value than conventional parameters in patients with rectal cancer who underwent surgery after NAT.

Prognosis and histology of sporadic synchronous and metachronous meningiomas and comparative analyses with singular lesions

Synchronous or metachronous growth of multiple tumors (≥ 2) is found in up to 20% of meningioma patients. However, biological as well as histological features and prognosis are largely unexplored. Clinical and histological characteristics were retrospectively investigated in 95 patients harboring 226 multiple meningiomas (MMs) and compared with 135 cases of singular meningiomas (SM) using uni- and multivariate analyses. In MM, tumors occurred synchronously and metachronously in 62% and 38%, respectively. WHO grade was intra-individually constant in all but two MMs, and histological subtype varied in 13% of grade 1 tumors. MM occurred more commonly in convexity/parasagittal locations, while SM were more frequent at the skull base (p < .001). In univariate analyses, gross total resection (p = .014) and high-grade histology in MM were associated with a prolonged time to progression (p < .001). Most clinical characteristics and rates of high-grade histology were similar in both groups (p ≥ .05, each). Multivariate analyses showed synchronous/metachronous meningioma growth (HR 4.50, 95% CI 2.26–8.96; p < .001) as an independent predictor for progression. Compared to SM, risk of progression was similar in cases with two (HR 1.56, 95% CI .76–3.19; p = .224), but exponentially raised in patients with 3–4 (HR 3.25, 1.22–1.62; p = .018) and ≥ 5 tumors (HR 13.80, 4.06–46.96; p < .001). Clinical and histological characteristics and risk factors for progression do not relevantly differ between SM and MM. Although largely constant, histology and WHO grade occasionally intra-individually vary in MM. A distinctly higher risk of disease progression in MM as compared to SM might reflect different underlying molecular alterations.

Primary tumor heterogeneity on pretreatment 18F-FDG PET/CT to predict outcome in patients with rectal cancer who underwent surgery after neoadjuvant therapy

PurposeThis retrospective study aimed to investigate the value of texture features of primary tumors in pretreatment 18F-FDG PET/CT in the prediction of response to treatment, progression, and overall survival in patients with rectal cancer who underwent surgery after neoadjuvant therapy(NAT). MethodsPatients with rectal cancer who had pretreatment 18F-FDG PET/CT, and underwent surgery after NAT were included in this study. Clinicopathologic features, date of last follow-up, progression, and death were recorded. Textural and conventional PET parameters(maximum standardized uptake value-SUVmax, metabolic tumor volume-MTV, total lesion glycolysis-TLG) were obtained from PET/CT images using LifeX program. Parameters were grouped using Youden index in ROC analysis. Factors predicting the pathological response to treatment, progression, and overall survival were determined using logistic regression and Cox regression analyses. ResultsForty-four patients (26(59%) male, 18(41%) female; 60.1±11.4 years) with rectal cancer were included in this study. The numbers of patients with responders and non-responders to NAT were 15(34.9%) and 28(65.1%), respectively. One patient’ pathology report did not contain the response status to NAT. The median of follow-up duration was 29.9 months. 9(20.5%) showed disease progression, and 8(18.2%) died during the follow-up period. Difference entropyGLCM and correlationGLCM parameters were found as independent predictors for response to NAT. The positivity of surgical margin, intensity interquartile rangeCONV and AUC-CSHDISC texture parameters were independent predictors of progression, while normalized inverse differenceGLCM and LZLGEGLZLM parameters were independent predictors of mortality. ConclusionThe texture parameters obtained from pretreatment 18F-FDG PET/CT have presented a more robust predictive value than conventional parameters in patients with rectal cancer who underwent surgery after NAT.

The Impact of PSMA-PET on Oncologic Control in Prostate Cancer Patients Who Experienced PSA Persistence or Recurrence.

Background: Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is currently recommended to restage prostate cancer (PCa) and to guide the delivery of salvage treatments. We aim to evaluate the oncologic outcomes of patients with recurrent PCa who received PSMA-PET. Methods: 324 hormone-sensitive PCa with PSA relapse after radical prostatectomy who underwent PSMA-PET in three high-volume European Centres. Patients have been stratified as pre-salvage who never received salvage treatments (n = 134), and post-salvage, including patients who received previous salvage therapies (n = 190). Patients with oligorecurrent (≤3 lesions), PSMA-positive disease underwent PSMA-directed treatments: salvage radiotherapy (sRT) or Metastases-directed therapy (MDT). Patients with polirecurrent (>3 lesions) PSMA-positive disease were treated with systemic therapy. Patients with negative PSMA-PET were treated with sRT or systemic therapies or observation. The primary outcome of the study was Progression-free survival (PFS). Secondary outcomes were: Metastases-free survival (MFS) and Castration Resistant Pca free survival (CRPC-FS). Results: median follow up was 23 months. In the pre-salvage setting, the PFS, MFS and CRPC-FS estimates at 3 years were 66.2% vs. 38.9%, 95.2% vs. 73.7% and 94.9% vs. 93.1% in patients with negative vs. positive PSMA-PET, respectively (all p ≥ 0.2). In the post-salvage setting, the PFS, MFS and CRPC-FS estimates at 3 years were 59.5% vs. 29.1%, 92.7% vs. 65.1% and 98.8% vs. 88.8% in patients with negative vs. positive PSMA-PET, respectively (all p ≤ 0.01). At multivariable analyses, a positive PSMA-PET was an independent predictor of progression (HR = 2.15) and metastatic disease (HR 2.37; all p ≤ 0.03). Conclusion: PSMA-PET in recurrent PCa detects the site of recurrence guiding salvage treatments and has a prognostic role in patients who received previous salvage treatments.

Association between leucocyte telomere length and the risk of atrial fibrillation: An updated systematic review and meta-analysis.

Advancing age is the most important risk factor of atrial fibrillation (AF). The shortening of telomere length is a biomarker of biologic aging. There is an increasing body of evidence that leucocyte telomere length (LTL) is associated with the risk of AF development. However, the results in these studies were controversial. The current systematic review and meta-analysis was conducted to examine the role of LTL in predicting the incidence of AF. Observational studies reporting the association between LTL and the risk of AF were retrieved through 25th June, 2022 from PubMed and Embase. A total of twelve studies including 18,293 patients were included in the present analysis. Leucocyte telomere shortening was found to be an independent predictor of AF as a continuous variable in both univariate [OR:2.14; 95%CI(1.48,3.10); P<0.0001] and multivariate analyses [OR:1.41;95%CI(1.11,1.79); P=0.005], as well as categorical variable in multivariate analysis [OR:1.53; 95%CI(1.04,2.27); P=0.03]. Furthermore, leucocyte telomere shortening was significantly associated with recurrent AF [OR:4.32;95%CI(2.42,7.69); P<0.00001] but not new-onset AF [OR:1.14; 95%CI(0.90,1.45); P=0.29]. Leucocyte telomere shortening was also associated with an increased risk of persistent AF [OR:14.73;95%CI (3.16,68.67); P=0.0006] and paroxysmal AF [OR:2.74;95%CI(1.45,5.18); P=0.002]. Besides, LTL was an independent predictor for progression from paroxysmal AF to persistent AF [OR:3.2;95%CI(1.66,6.18); P=0.0005]. Differences between males [OR:1.99; 95%CI(1.29,3.06); P=0.002] and females [OR:0.86; 95%CI (0.29,2.56);P=0.79] were observed. Leucocyte telomere shortening predicts the risk of AF, especially recurrent AF. The predictive value is more prominent in males than in females. Shortening in LTL can predict the progression from paroxysmal to persistent AF.

Prospective identification of prognostic factors for patients with early failure of advanced ovarian cancer who undergo primary cytoreductive surgery followed by chemotherapy: The AGO-OVAR 19/FRAGILE study (NCT02828618).

5556 Background: Standard treatment for advanced ovarian cancer (aOC) includes primary cytoreductive surgery followed by chemotherapy (PDS &gt; CTX). There is strong evidence that this strategy is accompanied by high risk for early failure in some patients (pts) but prospective multicenter data for this specific question are lacking. Methods: 64 AGO-sites prospectively registered pts with suspected aOC and collected following variables prior to start of therapy: age, Charlson Comorbidity Index (CCI), timed up and go test (TUG), ASA and ECOG performance score, weight, height, estimated ascites, albumin, creatinine, hemoglobin, leucocytes, platelets, CA125, patient reported outcome measures according to EORTC QLQ-C30 and OV28, hospital anxiety and depression score (HADS), physician-assessed suspected FIGO IV stage, abdominal pain requiring treatment, abdominal bloating, dyspnea and required palliative paracentesis (ascites, pleural effusions). Treatment followed according to investigator’s decision. Primary objective was to predict the unfavorable event of death or progression within 10 months after primary diagnosis. We applied univariate and multiple logistic regression with stepwise variable selection after multiple imputation of missing data in order to identify relevant predictors. Results: 223 pts with aOC FIGO IIIB to IVB and PDS were analyzed. Median age was 63 years (range 31-86). 52 (23.3%) pts experienced progression or death within 10 months from time of enrolment. In univariate regression, age (odds ratio (OR) 1.612 per 10 years), ASA (III vs I/II: OR 3.217), TUG (OR 1.087), body height (OR 0.541 per 10cm), ECOG (1 vs 0 OR 2.326, 2-3 vs 0 OR 4.102), estimated ascites ( &gt; 500cc vs. none OR 2.811), paracentesis (OR 1.991), platelets (upper limit of normal (ULN) vs norm or &lt; lower limit of normal (LLN) OR 1.998), albumin ( &lt; LLN vs norm or &gt; ULN OR 2.053), creatinine ( &gt; ULN vs norm OR 3.969) and baseline QoL single-item subscales appetite loss (“very much” vs “not at all” OR 2.611), constipation (“quite a bit” vs “not at all” OR 4.903), and multi-item subscales global health status (OR 0.982 per 1 point) and nausea/vomiting (OR 1.013 per 1 point) were significant (p &lt; 0.05). Multiple logistic regression identified age (OR 1.459 per 10 years), ASA (III vs I/II: OR 2.427), constipation (“quite a bit” vs “not at all” OR 3.786) and global health (OR: 0.985 per 1 point) as independent predictors of progression or death within 10 months after primary diagnosis (p &lt; 0.05). Conclusions: A significant proportion of aOC pts undergoing PDS &gt; CTX are at high-risk for early failure. The finding of independent risk factors including self-ratings of QoL at time of diagnosis should be confirmed and tested against other models to facilitate a more tailored treatment of high-risk pts and design of future trials in aOC. Clinical trial information: NCT02828618.

1130-P: A Prospective Cohort Study on the Predictive Value of Controlled Attenuation Parameter Measured by FibroScan to the Transition of Metabolic Status

Aims: Our previous study validated that controlled attenuation parameter (CAP) was a sensitive surrogate marker for evaluating metabolic derangement. However, prospective studies are needed to assess its usefulness for transition of metabolic status over time. In this study, predictive effect of CAP and its change over time was investigated by following up of medical staff volunteered for MAFLD study over 3 years. Subjects and Methods: Volunteers were recruited from our hospital to undergo FibroScan examination in 2018 and followed up in 2021. Anthropometric data, CAP and hematological indices for metabolic profiles and insulin resistance were collected. Metabolic syndrome (MetS) components were scored. CAP≥238 dB/m denoted hepatic steatosis. Number of MetS component increased by 1 or more was denoted ‘progression’ , whereas decreased by 1 or more denoted ‘regression’ of metabolic status. Results: A total of 922 subjects volunteered for FibroScan examination in 2018, and 466 of them were followed in 2021. At baseline, the median age was 49.0 years, BMI was 23.3kg/m2, waist circumference was 80cm. CAP were 240 (216, 275) dB/m, LSM were 3.9 (3.4, 4.7) Kpa, 242 (51.9%) subjects were with CAP≥238 dB/m. During the follow up, 124 (26.6%) subjects had progression, while 81 (17.3%) had regression of metabolic status. Logistic regression showed that CAP at baseline [1.0 (1.001, 1.011) , P = 0.019], change in waist circumference [1.1 (1.047, 1.165) , P = 0.000] and change in CAP [1.0 (1.004, 1.0150) , P = 0.001] were independent predictors for progression. In contrast, CAP at baseline [1.012 (1.006, 1.018) , P= 0.000], change in waist circumference [0.9 (0.857, 0.967) , P = 0.002] and change in LSM [0.813 (0.667, 0.990) , P = 0.040] were significant in predicting regression of metabolic status. Conclusions: CAP at baseline, changes in CAP and waist circumference are useful surrogate markers for predicting transition of metabolic status over time. Disclosure J.Li: None. Z.Huang: None. W.Deng: None. Z.Zhang: None. Y.Li: None. Funding National Natural Science Foundation of China (82070918)

Predicting progression to severe COVID-19 using the PAINT score

ObjectivesOne of the major challenges in treating patients with coronavirus disease 2019 (COVID-19) is predicting the severity of disease. We aimed to develop a new score for predicting progression from mild/moderate to severe COVID-19.MethodsA total of 239 hospitalized patients with COVID-19 from two medical centers in China between February 6 and April 6, 2020 were retrospectively included. The prognostic abilities of variables, including clinical data and laboratory findings from the electronic medical records of each hospital, were analysed using the Cox proportional hazards model and Kaplan–Meier methods. A prognostic score was developed to predict progression from mild/moderate to severe COVID-19.ResultsAmong the 239 patients, 216 (90.38%) patients had mild/moderate disease, and 23 (9.62%) progressed to severe disease. After adjusting for multiple confounding factors, pulmonary disease, age > 75, IgM, CD16+/CD56+ NK cells and aspartate aminotransferase were independent predictors of progression to severe COVID-19. Based on these five factors, a new predictive score (the ‘PAINT score’) was established and showed a high predictive value (C-index = 0.91, 0.902 ± 0.021, p < 0.001). The PAINT score was validated using a nomogram, bootstrap analysis, calibration curves, decision curves and clinical impact curves, all of which confirmed its high predictive value.ConclusionsThe PAINT score for progression from mild/moderate to severe COVID-19 may be helpful in identifying patients at high risk of progression.