bluuebunny/crossref_metadata_2025_split huggingface dataset:
Examining the effect of dementia on hospitalization outcome for GI cancer: A nationwide retrospective analysis.
Authors: Pan Chun-Wei , Pan Wei-Lin , Pinnam Bhanu Siva Mohan Pinnam 
Published: June 2023

e16336 Background: Dementia is a debilitating condition affecting a significant fraction of the elderly, with far-reaching consequences. It is an active field of research, with current emphasis on modifiable risk factors as well as treatment. Considering the limitations that dementia imposes on the management of other medical conditions, we attempt to study its association with, and impact on hospitalizations for gastrointestinal (GI) cancers. Methods: We queried the National Inpatient Sample databases for the years 2016 through 2020, using International Classification of Diseases, tenth revision (ICD-10) codes to include all adult admissions with esophageal, gastric, colorectal, biliary Tract, liver, and pancreatic cancers. We further stratified this cohort based on the presence of a secondary diagnosis of dementia. STATA 17 was used to perform a multivariate regression analysis to compare outcomes in the two cohorts, while adjusting for potential confounders. Results: The study identified 280,180 patients with GI cancer, of whom 4.7% (13,135) had a secondary diagnosis of dementia. The cohort with dementia was found to have a higher proportion of females (47.0%) compared to the non-dementia cohort (40.8%) and a higher median age (77.9 years vs 66.9 years). Additionally, this cohort had a higher prevalence of other medical comorbidities, with 98.2% having a Charlson comorbidity index (CCI) greater than 3 compared to 87.8% in the non-dementia cohort. The primary outcome of the study was in-patient mortality, which was stratified by age groups. In the 41-65 years old group, the mortality rate was higher in the dementia cohort (16.3%) compared to the non-dementia cohort (8.6%), with an adjusted odds ratio (aOR) of 1.96 (95% CI: 1.10-3.48, P<0.05). In the 65-75 years old subgroup, the mortality rate was also higher in the dementia cohort (13.1%) compared to the non-dementia cohort (8.6%), with an aOR of 1.48 (95%CI: 1.14-1.93, P<0.05). In the above-75-year-old subgroup, the mortality was higher in the dementia cohort (11.7%) compared to the non-dementia cohort (8.5%) (aOR: 1.35; 95%CI: 1.16-1.58, P<0.05). Conclusions: Hospitalizations with GI cancer, with a secondary diagnosis of dementia, have higher odds of in-patient mortality compared to those without dementia. This was observed across all age groups. The dementia cohort also had a higher proportion of females and a higher median age, along with a higher prevalence of multiple comorbidities. These findings suggest that individuals with gastrointestinal cancer and dementia face a higher risk of in-patient mortality, highlighting the importance of considering dementia as a part of care planning in patients with GI cancer. [Table: see text]
Establishing functional models of peritoneal carcinomatosis using MicroOrganoSphere (MOS) technology.
Authors: Yousef Abdelrahman M.G. , McCormick Aaron , Smith Amber , Ito Ichiaki , Yousef Mahmoud M.G. , Zeineddine Mohammad A. A. , Helmink Beth A , White Michael , Fournier Keith F. , Delubac Daniel , Shen Xiling , Shen John Paul Y.C. 
Published: June 2023

e16337 Background: Appendiceal adenocarcinomas (AAs) are a rare and heterogeneous mix of tumors for which few preclinical models exist for drug discovery. These tumors are commonly treated with chemotherapy according to best practices developed for colorectal cancer, despite clear evidence that the two cancers are distinctly different in their clinical behavior and molecular profiles. In this study, we created functional tumoroid models (MicroOrganoSpheres or MOS) of peritoneal carcinomatosis from appendix cancer and mesothelioma and used these MOS to test the efficacy of different chemotherapy treatments. Methods: After obtaining informed consent, fresh tumor samples were obtained from 5 patients with peritoneal carcinomatosis undergoing surgical resection at The University of Texas MD Anderson Cancer Center and 5 samples were obtained from previously established PDX models. Tissue was digested using xMRS solution and MOS culture was established. H&E was performed on tissue and paired MOS. Results: Five MOS models were successfully established, including four AA and one primary peritoneal mesothelioma (to our knowledge the first time this has been done from a peritoneal mesothelioma). Four (80%) of the 5 PDX models samples successfully generated MOS. Three out of five from the fresh samples generated p0 MOS, but only one continued to grow (20%). The MOS successfully established from fresh biopsy was a moderately differentiated mucinous adenocarcinoma with GNASR201C and KRASG12R mutation, to our knowledge the first time a Patient Derived Organoid (PDO) model of this disease has been created. Identified failure modes were delayed processing times (>48 hours after extraction in 3 out of 5 clinical samples) and low tumor content in samples. Histologically, the MOS recapitulated several important characteristics of the original patients’ tumors, including degree of differentiation, abundance of mucin, and presence of signet ring features. Response of AA MOS models to chemotherapeutic agents and regimes has been evaluated in one model thus far. AAPDX-13, derived from a low-grade mucinous adenocarcinoma, was tested against common CRC treatments: 5-FU (pIC50 5.90), Oxaliplatin (pIC50 4.51), SN-38 (pIC50 5.16). Relative to the mean from multiple CRC MOS, this was less sensitive to 5FU and more sensitive to irinotecan. Conclusions: Novel MOS models for AA and peritoneal mesothelioma were successfully established. MOS recapitulated key histologic features of AA and mesothelioma. Data acquired from this MOS system can aid in identifying appropriate chemotherapy treatments in select patients where there are no existing preclinical disease models.
C-reactive protein (CRP) as a prognostic biomarker in patients with bladder cancer: A meta-analysis.
Authors: Fujiwara Yu , Karol Alexander B. , Reford Emma , Joshi Himanshu , Doroshow Deborah Blythe , Galsky Matt D. 
Published: June 2023

e16502 Background: CRP is an acute phase reactant synthesized by hepatocytes in response to inflammatory cytokines including interleukin-6. Peripheral blood CRP, a routinely measured analyte, may reflect tumor microenvironments skewed towards tumor-promoting inflammation. CRP may therefore represent an attractive biomarker to select patients with bladder cancer (BCa) more likely to benefit from therapies directed at modulating tumor-promoting inflammation. Methods: A systematic review was performed to identify studies reporting outcomes based on pre-treatment CRP values in patients with localized and advanced BCa and urothelial carcinoma (UC). The hazard ratio (HR) of overall survival (OS), cancer-specific survival (CSS), relapse-free survival (RFS), and progression-free survival (PFS) between groups with high and low CRP values as defined in each study was extracted. Meta-analysis using the random-effect model was performed to pool HR. Meta-regression analysis was conducted to assess the relationship between CRP cutoff and HR for OS. Subgroup analyses were performed according to clinical disease state and therapies administered. Heterogeneity was assessed using I2 statistics. Results: Overall, 938 articles were identified at initial screening; 22 studies comprising 2,899 patients were included in the meta-analysis. For OS, 17 datasets from 16 studies were used. High CRP levels were associated with decreased OS (HR=2.03, 95%CI:1.67-2.47, p<0.01) although high heterogeneity was observed (I2=91%). Subgroup analyses according to anticancer interventions showed that high CRP values were related to shorter OS, particularly in patients treated with immune checkpoint blockade (ICB; HR=1.78, 95%CI: 1.47-2.15, p<0.01). In meta-regression analysis, the correlation between CRP cutoff value and OS HR was not observed when all 16 studies were considered (Regression coefficient=0.03, 95%CI: -0.13-0.18, p=0.73). However, CRP cutoff value was significantly associated with the HR for OS (Regression coefficient=-0.21, 95%CI: -0.36 to -0.06, p=0.01) when the analysis was limited to eight studies assessing ICB in advanced BCa/UC. Pooled HR of CSS, RFS, and PFS is shown in Table. Conclusions: High CRP values were associated with poorer clinical outcomes in patients with BCa/UC, particularly among patients with advanced disease treated with ICB. CRP may represent an attractive biomarker to enrich populations more likely to benefit from therapies that modulate tumor-promoting inflammation. [Table: see text]
Comparison of peripheral blood markers in predicting the occurrence of immune-related adverse events in patients with metastatic genitourinary cancer treated with cabozantinib + nivolumab +/- ipilimumab.
Authors: Iannantuono Giovanni Maria , Chandran Elias , Simon Nicholas I. , Ley Lisa , Cordes Lisa M. , Wang Tzu-fang , Girardi Daniel da Motta , Gurram Sandeep , Valera Vladimir , Chalfin Heather , Parnes Howard L. , Nadal Rosa , Niglio Scot Anthony , Boudjadi Salah , Banday Abdul Rouf , Kydd Andre Rashad , Steinberg Seth M. , Apolo Andrea B. 
Published: June 2023

e16506 Background: Peripheral blood markers (PBM) have been demonstrated to be prognostic and/or predictive for cancer patients (pts) treated with immune checkpoint inhibitors (ICI). Initial evidence has shown their potential role in predicting the occurrence of immune-related adverse events (IrAE) in pts treated with single-agent ICI. We explored the potential role of different PBM in predicting IrAE in metastatic genitourinary cancer (mGU) pts treated with an ICI-based combination. Methods: We retrospectively evaluated 60 mGU pts treated with Cabozantinib + Nivolumab +/- Ipilimumab (CaboNivo +/- Ipi) in a phase I study at the National Cancer Institute. We retrieved their demographics, the occurrence of IrAE, and the baseline values of different PBM (neutrophil/lymphocyte ratio [NLR], neutrophil/eosinophil ratio [NER], lymphocyte/monocyte ratio [LMR], monocyte/lymphocyte ratio [MLR], platelet/lymphocyte ratio [PLR], systemic immune-inflammation index [SII] [N/L*P], and HALP score [albumin*hemoglobin*L/P]). We evaluated PBM based on the presence or absence of IrAE using the Wilcoxon rank sum test followed by multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve analyses were used to investigate an optimal cut-off for PBM suitable for prediction. Results: The median age of pts was 58.5 years (interquartile range [IQR] 46 - 67), and 13 (21.7%) were female. Twenty (33.3%) pts developed at least one IrAE. Baseline median values of PMB are summarized in the Table. A multivariable logistic regression model showed after backward elimination that only NER had the potential to predict IrAE (p = 0.033; Odds Ratio = 0.989 per unit [95% Confidence Interval 0.979 - 0.999]) and thus, we further investigated the predictive potential of NER for the development of IrAE following CaboNivo +/- Ipi. The ROC curve suggested that an optimal cut-off value for NER was 30.647 (area under the ROC = 0.6351). Accordingly, we classified pts with high NER ( > 30.647) as not having IrAE vs low NER (≤ 30.647) as having IrAE. Using this classification, 24/37 (64.9%) of those without (w/o) IrAE and 14/20 (80%) of those with an IrAE could simultaneously be correctly predicted by NER alone. Conclusions: A baseline low NER value was an independent factor associated with a higher probability of developing IrAE in mGU pts treated with CaboNivo +/- Ipi. Prospective validation on a larger cohort of pts is needed. [Table: see text]
Real-world treatment sequencing and outcomes for patients with advanced renal cell carcinoma treated with cabozantinib after first-line checkpoint inhibitor-based combination therapy: Results from the CARINA study.
Authors: Nathan Paul D. , Allison Jennifer , Charnley Natalie , Griffiths Richard , Michael Agnieszka , Moore Kathryn , Sharma Anand , Szabados Bernadett , Venugopal Balaji , Ali Jamshed , Perrot Valérie , Prendergast Áine , Klair Bhupinder , Larkin James 
Published: June 2023

e16512 Background: Real-world data are required to guide the optimal sequencing of therapies for advanced renal cell carcinoma (aRCC) when first-line (1L) checkpoint inhibitor (CPI)-based combinations are used. CARINA is a retrospective, non-interventional study of treatment sequencing and outcomes in patients with aRCC who progressed to second-line (2L) treatment after 1L CPI-based combination therapy. Methods: Electronic prescribing records and hospital medical records from nine participating UK specialist centers were reviewed to identify patients (aged ≥ 18 years) with a diagnosis of aRCC who received 2L therapy after 1L CPI-based combination therapy in line with UK National Health Service funding policy. The primary objective was to describe the treatment pathways of patients with aRCC who received 1L CPI-based combination and subsequent therapy. Secondary objectives included descriptive analysis of: duration of treatment (DoT), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Here we report a descriptive analysis of outcomes for subgroups who received 2L cabozantinib or other 2L therapies. Results: Between April 2015 and June 2022, data were collected from 281 patients (163 patients received 2L cabozantinib and 118 received other 2L therapies after 1L CPI-based therapy). Overall, mean (standard deviation [SD]) age at aRCC diagnosis was 59.4 (10.1) years, 76.5% were male and 87.5% had clear-cell aRCC (including those with a clear-cell component). In the 2L cabozantinib and other 2L therapies subgroups, the most common 1L regimens were ipilimumab + nivolumab (79.1% and 60.2%, respectively), axitinib + avelumab (9.8% and 22.0%) and pembrolizumab + axitinib (9.8% and 9.3%). Outcomes of 2L treatment for the 2L cabozantinib and other 2L therapies subgroups are shown in the Table. Conclusions: Among patients with aRCC who progressed to 2L treatment after 1L CPI-based therapy, the most common 1L therapies were ipilimumab + nivolumab followed by axitinib + avelumab. DoT and ORR were numerically better with 2L cabozantinib than with other 2L therapies, demonstrating the antitumor effect of 2L cabozantinib after 1L CPI-based therapy. Clinical trial information: NCT04957160 . [Table: see text]
Plasma KIM-1 for preoperative prediction of renal cell carcinoma versus benign renal masses, and association with clinical outcomes.
Authors: Xu Wenxin , Mukeria Anush , Gaborieau Valerie , Niman Samuel M. , Liu Xiaowen , Takakura Ayumi , Zaridze David , Freedman Matthew L. , McDermott David F. , Choueiri Toni K. , Catalano Paul J. , Sabbisetti Venkata , Maremanda Krishna , Bonventre Joseph , Pierorazio Phillip , Singla Nirmish , Brennan Paul , Bhatt Rupal Satish 
Published: June 2023

e16518 Background: For patients with suspicious renal masses, it is often unclear which should receive an intervention versus initial surveillance. Both clear cell and papillary renal cell carcinoma overexpress kidney injury molecule-1 (KIM-1) due to their proximal epithelial cell of origin. We investigated whether plasma KIM-1 improves risk stratification of patients with suspicious kidney masses. Methods: Pre-nephrectomy plasma KIM-1 was measured in two independent cohorts of patients with renal masses. Cohort 1, from the prospective K2 trial, included 162 patients found to have ccRCC (cases) and 162 patients with benign renal masses (controls). Cohort 2 included 247 patients with small (cT1a) renal masses from an academic biorepository. Multivariable models were used to assess the relationship between pre-nephrectomy plasma KIM-1, surgical pathology, and subsequent clinical outcomes. Results: In cohort 1, plasma KIM-1 distinguished RCC versus benign masses with AUC-ROC 0.81 (95% CI: 0.76-0.86). In cohort 2 (cT1a renal masses), plasma KIM-1 distinguished RCC versus benign masses with AUC-ROC 0.74 (95% CI: 0.67 to 0.80). Among patients in cohort 2, the prevalence of malignancy was 97% among patients with the highest quartile of KIM-1 compared to 55% among patients with the lowest quartile of KIM-1. Plasma KIM-1 was higher in clear cell RCC and papillary RCC compared to other histologies (p<0.001 in each cohort). Cohort 1 patients had prospective long-term follow-up, and higher pre-nephrectomy KIM-1 was associated with worse metastasis free survival (multivariable MFS HR 1.29 per unit increase in log KIM-1, 95% CI 1.10-1.53) and worse overall survival (multivariable OS HR 1.31 per unit increase in log KIM-1, 95% CI 1.10-1.54). Conclusions: In two independent cohorts of patients with renal masses, elevated baseline plasma KIM-1 is associated with higher risk of malignant pathology, worse metastasis free survival, and higher risk of death. Plasma KIM-1 may be a useful risk stratification tool for patients with suspicious kidney masses.
Renal cell carcinoma with metastasis to the pancreas: Genomic signatures and clinical outcomes.
Authors: Glover Michael , Chiang Ryan S. , Hoerner Christian R. , Khan Osama A. , Kao Chia-Sui , Shah Sumit , Srinivas Sandy , Fan Alice C. , Khaki Ali Raza 
Published: June 2023

e16519 Background: Renal cell carcinoma (RCC) is a diverse disease characterized by several subtypes, mutations, and a broad spectrum of sites of metastasis. Previous publications have established that RCC with pancreatic metastases (PM), a rare subpopulation, has more favorable outcomes, even when other metastases sites are involved. Outcomes in this subpopulation tend to be independent of the traditional IMDC risk stratification. We have previously explored the genomic landscape of RCC with PM. In this analysis, we explore the clinical data and correlation with NGS for a subset of patients treated at our institution. Methods: We identified patients (pts) at our institution with metastatic RCC with PM. Included pts had pathologically confirmed RCC with met to pancreas seen on imaging. All identified pts had NGS performed with Tempus xT assay (DNA-seq of 648 genes at 500x coverage). We also extracted demographic, clinicopathologic, and treatment data for included pts through chart review. We describe baseline characteristics, most prevalent gene mutations on xT and overall survival (OS) from time of diagnosis to death with particular attention of OS stratified by PBRM1 mutation. We also performed a log rank test to compare OS for those with and without PBRM1 mutation. Results: 23 pts with metastatic RCC with PM were identified. Pts included were diagnosed with RCC between 1993 and 2020, median age was 62 years (range 42-78), 48% were female, 70% of white race, 35% with smoking history. All patients had a nephrectomy and 91% had clear cell histology. 6 pts (26%) had de novo metastatic disease (3 [14%] with de novo PM). Median time to metastatic disease was 3.5 years (range 0-15.5 years) and median time to PM was 4.7 years (range 0-15.5 years). The most prevalent genes identified with mutations were VHL (70%), PBRM1 (39%), and SETD2 (32%); TP53 mutations were identified in 2 pts (9%). After a median follow-up of 16 years, 10 pts (43%) were deceased (7 due to RCC, 3 due to other causes), 11 pts were alive (5 without disease and 6 with active disease) and 2 with unknown vital status. Median [m]OS for the whole cohort was 12.7 years, which when stratified by PBRM1 mutation was 8.4 and 12.7 years for those with and without PBRM1 mutation, respectively, though this difference was not statistically significant. Conclusions: In our cohort, patients with RCC and PM had an indolent course with a prolonged survival even after diagnosis of metastatic disease. This effect was independent of PBRM1 mutations or other common mutations. As these patients presented with both de novo PM as well as later in the course, this may represent a unique population, rather than a result of survival bias.
A novel prognostic model for oligometastatic renal cell carcinoma: COMPARZ study post-hoc analysis.
Authors: Anwaier Aihetaimujiang , Zhang Hailiang , Yu Jiacui , Wan Hualin , Ong Su Miin , Tay Hao Zhe , Ye Dingwei 
Published: June 2023

e16521 Background: International metastatic renal cell carcinoma database consortium (IMDC) is the most commonly used prognostic model for metastatic renal cell carcinoma (mRCC), however, its clinical application has been limited due to the cumbersome design and vague recommendation of treatment decisions for patients in the IMDC intermediate risk group. Previous studies indicated the favorable prognosis of oligometastatic RCC, but the definition of oligometastasis has not been clarified. This study aims to construct a new prognostic model of oligometastatic RCC based on the COMPARZ study cohort. Methods: Patients from the COMPARZ study (which was a randomized phase III non-inferiority study comparing pazopanib and sunitinib in advanced RCC or mRCC patients). Patients (N=1038) were divided into two cohorts for models construction respectively, Cohort A (n=293) with primary kidney tumor; Cohort B (n=745) without primary kidney tumor. Multivariate Cox regression analysis was performed to identify the independent prognostic risk factors for each model with overall survival (OS) as primary endpoint. Uno’s C-statistics was utilized to compare the novel risk model with IMDC risk. These models were then used to examine and stratify the patients in IMDC intermediate risk group. Results: In Cohort A, four risk factors were identified independent predictors for short survival. Patients were segregated into the oligo group and the non-oligo group. The concordance index (C-index) for Model A and IMDC risk model was 0.63 (95%CI: 0.59-0.67) and 0.65 (95%CI: 0.61-0.69), respectively (p=0.389). In Cohort B, three risk factors were identified as independent predictors of short survival. Patients were also divided into the oligo group and the non-oligo group. The C-index between Model B and IMDC risk model was 0.62 (95%CI: 0.59-0.64) and 0.61 (95%CI: 0.58-0.64), respectively (p=0.650). For Model A, mOS for non-oligo group was 13.4 months vs NR in oligo group (3y OS: 25.3 vs 51.8%), while for model B, mOS was 18.5 vs NR respectively (3y OS: 24.3 vs 57.5%). With the novel prognostic models, patients in the IMDC intermediate risk group could be further stratified into oligo group (mOS: NR; 3y OS: 55.6%) that had a better outcome than patients in non-oligo group (mOS: 19.2 month; 3y OS: 24.9%; p<0.001). Conclusions: Compared with the current IMDC model, the novel prognostic models of oligometastatic mRCC could well distinguish patients into favorable and poor prognostic groups with fewer risk factors and comparable predictive power. Meanwhile, the novel models can better stratify the IMDC intermediate risk group into oligo and non-oligo groups with significantly different OS outcomes, and is more conductive to the comprehensive treatment of patients with mRCC.