tbuckley/cabot-search huggingface dataset:
Clinical features and outcomes of tumor lysis syndrome in patients with genitourinary cancers.
Authors: Jue Wang, Bryan Leung
Journal: Journal of Clinical Oncology (2019)

533 Background: Genitourinary (GU) cancers account about 20% of all human cancer in the United States. Tumor lysis syndrome (TLS) is an oncologic emergency with few treatment options. While TLS has been extensively documented in patients with hematological malignancies, it is rarely described in patients with GU cancers. The objective of this study was to investigate the clinical characteristics and outcomes of TLS, a rare but life-threatening complication in GU cancers. Methods: Systematic review of the literature and pooled analysis of published cases of TLS in GU cancers. Results: A total of 180 patients with TLS in solid tumor were included in our study. The median age was 57 years (8-94). Male: female ratio was 1.7. The most common sites were gastrointestinal (29%); followed by genitourinary (22%); lung (16%); melanoma (11%), breast cancer (8.3%). Liver metastasis was documented in 70% of study subjects. TLS occurred as a consequence of cancer therapy in 68% of subjects; and spontaneously in 32% of subjects. Older age and liver metastasis predict high mortality. The clinical features, treatment and outcomes of TLS in 40 cases of GU cancers including testicular germ cell tumor (TGCT) (n=14), renal cell carcinoma (n=10), prostate cancer (n=15), penile cancer (n=1) and urothelial carcinoma (n=3) were compared. The mortality rate of TLS were 50% in TGCT, 70% in renal cell carcinoma, 64% in prostate cancer 67% in urothelial carcinoma. Conclusions: TLS in GU cancers is associated with very high mortality. TLS should be considered on the differential diagnosis, when evaluating renal failure and electrolyte derangement in patients with metastatic GU cancers with liver metastases. The clinical features and outcomes of TLS in genitourinary cancers. [Table: see text]
Association between immune-related adverse events (irAEs) and clinical outcomes (CO) in advanced urothelial cancer patients (pts) treated with immunotherapy (IO).
Authors: Julie M. Shabto, Dylan J Martini, Yuan Liu, Deepak Ravindranathan, Meredith R Kline, Elise Hitron, Greta Russler, Sarah Caulfield, Haydn Kissick, Mehrdad Alemozaffar, Kenneth Ogan, Wayne Harris, Viraj A. Master, Bradley Curtis Carthon, Omer Kucuk, Mehmet Asim Bilen
Journal: Journal of Clinical Oncology (2019)

472 Background: The increasing use of IO agents in the treatment of urothelial cancer has revealed irAEs during therapy. We investigated whether there is an association between treatment-related irAEs and CO in urothelial cancer pts treated with IO. Methods: We performed a retrospective analysis of 67 urothelial cancer pts treated with PD-1/PD-L1 inhibitors at Winship Cancer Institute from 2015-2018. Overall survival (OS) and progression free survival (PFS) were calculated from first IO dose to date of death or hospice referral and clinical or radiographic progression, respectively. Objective response (OR) was defined as partial or complete response per RECISTv1.1. Treatment-related irAEs were determined from clinic notes. The univariate association between irAE and clinical outcomes was generated using chi-square test and Fisher’s exact test. Results: The median age was 70 and 79.1% were men. 41.8% of pts had received 2 or more prior lines of therapy. Nine pts (13.4%) experienced irAEs including infusion reactions, rashes, and joint pain. Median follow-up from date of first dose of IO was 15 months (95% CI: 11-18 months). The overall death rate for pts who experienced irAE was 0%, while it was 62% for pts who did not experience irAE ( p&lt;0.001) (Table). Conclusions: Experiencing irAEs was associated with lower death rate and progression rate and higher rate of OR in this cohort. These findings should be validated in a larger study. Univariate association of irAEs with CO. [Table: see text]
Patterns of Inpatient Care and Outcomes for Multiple Myeloma in 2014: A National Inpatient Sample Analysis
Authors: Prabhjot Singh Bedi, Manoj P Rai, Justin D. Kaner, Samanjit Kaur Kandola, Ahmad Alratroot, Mark Mujer, Supratik Rayamajhi, Shilpa Kavuturu, Nishant Tageja, Heather Laird-Fick, Marwan S Abougergi, Stanley M. Marks
Journal: Blood (2018)
Abstract P377: Racial and Socioeconomic Trends in Cardiovascular Disease Risk Scores From 1999-2014
Authors: Emily M Bucholz, Holly C Gooding, Donald M Lloyd-Jones, Sarah D De Ferranti
Journal: Circulation (2019)

Background: Atherosclerotic cardiovascular disease (ASCVD) incidence and mortality have declined in over the last decade; however, important racial and socioeconomic disparities in ASCVD risk exist. Little is known about trends in these disparities over time and the interplay between these factors. Methods: Data from the 1999-2014 NHANES were used to estimate temporal trends in 10-year AHA/ACC ASCVD risk in U.S. adults aged ≥20 years without prevalent ASCVD by race/ethnicity, income, and education. Trends in ASCVD risk were evaluated using linear regression with an interaction term between survey year and race/ethnicity, income, or education. Results: Of the 34,543 adults (weighted to 179 million) included in the study, 73.4% (standard error [SE] 1.1) were white, 11.9% (SE 0.7) black, and 14.7% (SE 0.9) Hispanic; 20.6% (SE 0.6) lived below the federal poverty line and 42.3% (SE 0.8) had a high school education or less. White adults had higher ASCVD risk scores on average than black or Hispanic adults (p&lt;0.001) throughout the study period. Mean ASCVD risk scores were initially higher in low-income adults but decreased over time (p=0.001) while scores remained stable for higher-income adults (p=0.85; p for interaction=0.002) such that by 2011-2014, ASCVD risk scores were similar for low- and higher-income adults (p=0.22). Mean ASCVD risk scores decreased over time in less-educated adults and increased in more-educated adults (p=0.007 and p=0.020, respectively; p for interaction &lt;0.001). When stratified by race, the decrease in ASCVD risk among low income adults and less-educated adults occurred exclusively in white adults (p=0.005 and p=0.018, respectively). Mean risk scores remained stable over time in black and Hispanic adults regardless of education or income. Conclusions: Differences in ASCVD risk by income and education narrowed over time, but this phenomenon was only observed in white adults. Low-income and less-educated black and Hispanic adults did not experience the same reductions in cardiovascular risk.
Sporadic angiomyolipomas (AMLs) growth kinetics while on everolimus (SAGE).
Authors: Daniel M. Geynisman, Brian T. Kadow, Brian M. Shuch, Stephen A. Boorjian, Surena F. Matin, Edward Rampersaud, Daniel McClean, Barton N Milestone, Elizabeth R. Plimack, Matthew R. Zibelman, Alexander Kutikov, Marc C. Smaldone, David Chen, Rosalia Viterbo, Shreyas Joshi, Richard E. Greenberg, Lois Malizzia, Thomas McGowan, Eric A. Ross, Robert Uzzo
Journal: Journal of Clinical Oncology (2019)

560 Background: Level I evidence exists demonstrating the efficacy of the mTOR inhibitor everolimus (EVE) in decreasing tumor volume of syndromic angiomyolipomas (AMLs) among patients with Tuberous Sclerosis. No prospective data are available regarding the effect of mTOR inhibition on growth kinetics in patients with sporadic AMLs. Methods: We conducted a multi-institutional, prospective, phase 2 trial with an optimal two-stage Simon design in patients presenting with &gt; 3cm sporadic AMLs who were candidates for surgical or percutaneous intervention. Response was defined as ≥25% volumetric reduction of the AML. Planned enrollment was 43 patients to test the null hypothesis at a 5% level of significance with 80% power. Baseline, 4- and 6-month volumetric analysis was performed by dynamic contrast-enhanced MRI (DCE-MRI). Patients received EVE 10mg for four 28-day cycles, at which point EVE was discontinued in those with &lt; 25% volumetric reduction. Those with ≥ 25% volumetric reduction received two additional cycles of EVE. Dose reductions and interruptions were allowed to 5 mg QOD. Conservative stopping rules were established for toxicity, given the benign nature of AMLs. Results: The early stopping rules for both efficacy and toxicity were invoked. We enrolled 20 patients (median age = 68) from 5 centers with 21 sporadic AMLs. 11/20 (55%) patients completed 4 cycles of EVE, while 7/20 (35%) completed 6 cycles. Median days on treatment was 88 (2 cycles). 4/20 (20%) patients were withdrawn due to toxicity, while 8/20 (40%) withdrew due to personal preference. Dose reductions were required in 6/20 (30%) patients, and 5/20 (25%) patients had grade 3 toxicities which resolved upon discontinuation or dose reduction of EVE. At 4-month MRI, 10/16 (62.5%) patients had a ≥25% reduction in volume (mean = 54.1% decrease). At 6-month MRI, 8/12 (66.6%) patients had a ≥25% reduction in volume (mean = 51.5% decrease). Conclusions: EVE was effective in reducing tumor volume in patients with sporadic AMLs but was associated with a high rate of treatment termination due to patient preference or prespecified AEs. Neoadjuvant EVE may be useful in potentiating surgical resection of large or anatomically complex AMLs. Clinical trial information: NCT02539459.
Pembrolizumab (pembro) in heavily pretreated metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Marcus Marie Moses, Elisa Ledet, Charlotte Manogue, Brian E. Lewis, Pedro C. Barata, A. Oliver Sartor, Jodi Lyn Layton
Journal: Journal of Clinical Oncology (2019)

255 Background: KEYNOTE-199 has shown PSA responses of 11% to pembro in mCRPC. This study aims to further evaluate pembro in heavily pre-treated mCRPC patients (pts) correlating clinical outcomes with somatic and germline mutational burden. Methods: Single-institution retrospective analysis of mCRPC pts treated with pembro with germline panel testing and baseline ctDNA analysis using Guardant360 (Redwood City, CA). Baseline clinical annotation was collected and correlated with ctDNA data and clinical outcomes; ctDNA annotations included amplification (amp) and somatic mutation (mut; allele fraction ≥0.3%). Clinical outcomes were assessed after 3 cycles defined as: PSA≥50% PSA decline) or PSA≥30 response. Results: 27 mCRPC pts were treated with pembro between Oct 2016 and June 2018, median age 69 (56-82), 70% Caucasian, 26% African-American, and 4% Other, 70% Gleason 8-10, 59% bone-only, 22% bone+tissue, and 19% bone+LN metastases, were included. Pembro was given after a median 5 CRPC therapies with a median initial PSA of 76.1 ng/mL (4.85-1160), median treatment duration of 1.4 months (0-24.3). Prior treatments include abiraterone (n = 27), enzalutamide (n = 17), docetaxel (n = 19), and provenge (n = 16). 18 pts had ctDNA testing both pre- and post-pembro with a median time from testing to pembro of 0.9 months (0-3.9) and a median time from pembro to NGS testing of 0.7 months (0-2.6). Pre-pembro NGS had the following cfDNA alterations: 74% AR (mut = 8, amp = 8, both = 4), 55% TP53, and 0% DNA repair. ctDNA allelic fraction decrease occurred in 50% (6/12) of pts with AR mutations. 55% (15/27) of pts completed ≥3 cycles of pembro with the following responses: PSA≥50 13% and PSA≥30 20%. Two PSA complete responders (CR) (PSA &lt; 0.01) had germline pathogenic alterations (BLM or MSH2). One of these pts was bone only; the other had radiographic CR. The MSH2 germline tumor was MSI-H and lacked MSH2/MSH6 on immunohistochemistry. The other PSA CR was not assessed given limited tissue. Conclusions: 33% of pts evaluated, achieved a PSA decline of ≥30% al response or greater signifying there is a subset of mCRPC pts that can benefit from pembro. Further evaluation is necessary to determine predictive biomarkers for this patient population.
Concordance between PD-L1 assays for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC).
Authors: Matthew Labriola, Jason Zhu, Sachica Cheris, Xin Liu, Kathryn Perkinson, Zuowei Su, Shannon McCall, Jiaoti Huang, Rajan T. Gupta, Andrew J. Armstrong, Daniel J. George, Tian Zhang
Journal: Journal of Clinical Oncology (2019)

e14259 Background: Immune checkpoint inhibitors (ICIs) are standard of care for mRCC and mUC patients (pts). PD-L1 status is gaining importance as a predictive biomarker, particularly for cisplatin-ineligible mUC. PD-L1 positivity is defined differently by PD-L1 assay and tumor type, with limited concordance studies. Given real-world limitations in PD-L1 testing, assay concordance studies are needed to distinguish positive (pos)/negative (neg) results and treatment selection. We compared Dako 28–8 and Ventana SP142 assays in mRCC and Dako 22C3 and Ventana SP263 assays in mUC. Methods: 32 pts with mRCC and 18 pts with mUC who had received ICI therapy at Duke Cancer Institute were identified. FFPE archival tumor samples for pts with mRCC were evaluated with Dako 28–8 and Ventana SP142 PD-L1 immunohistochemistry (IHC) assays. For pts with mUC, FFPE archival tumor samples were evaluated with Dako 22C3 and Ventana SP263 PD-L1 IHC assays. Scoring was validated by two pathologists using the scoring system for each assay. PD-L1 status was subsequently correlated to best RECIST response (objective response rate (ORR) defined as stable disease or better). Results: Tissue was obtained from primary tissue in 72% of mRCC cases and in 61% of mUC cases, with remainder from metastatic biopsies. The majority of mRCC cases (29/32, 91%) were concordant between Dako 28-8 and Ventana SP142 assays (8 cases pos and 21 cases neg), with 3 discordant cases (1 case pos for Dako 28-8 but neg for Ventana SP142 and 2 cases neg for Dako 28-8 but pos for Ventana SP142), all from primary tissue. The majority of mUC cases (17/18, 94%) were also concordant between Dako 22C3 and Ventana SP263 assays (2 pos cases and 15 neg cases), with 1 indeterminate Dako 22C3 test on a metastatic biopsy due to background lymph node. In mRCC, the ORR for PD-L1 pos cases was 45% (5/11) versus 33% (8/24) for PD-L1 neg cases. In mUC, the ORR for PD-L1 positive cases was 50% (1/2) versus 31% (5/16) for PD-L1 neg cases. Conclusions: There was strong concordance between the clinically meaningful PD-L1 assays chosen for comparison in both mRCC and mUC. mUC results were limited by low PD-L1 expression in this cohort. Although PD-L1 status does not fully predict for response to ICIs, this suggests that PD-L1 testing could be used interchangeably for the majority of cases when selecting ICI treatment in mRCC and mUC.
Prognostic factors at diagnosis of prostate cancer by race and ethnicity at a large academic center.
Authors: Tejas Suresh, Qi Gao, Sanjay Goel, Benjamin Adam Gartrell
Journal: Journal of Clinical Oncology (2015)

e16104 Background: Baseline prognostic factors vary by race in newly diagnosed prostate cancer (PCa). Relative to non-Hispanic Black (NHB) and non-Hispanic White (NHW) men, little is known about prognostic factors at diagnosis of PCa in Hispanic (H) men. Published data suggests that sociodemographic characteristics of H men are more similar to those of NHB, while stage at diagnosis is more similar to NHW. We sought to compare sociodemographic, clinical and pathological prognostic factors in men of different races in a diverse cohort of patients at a large, academic medical center. Methods: The Montefiore Medical Center (MMC) Cancer Registry was used to identify a cohort of patients diagnosed with PCa at MMC in the years 2006 and 2007. Patients were classified by self-identified race/ethnicity as H, NHB or NHW. Patient characteristics obtained included age at diagnosis, socioeconomic score (SES), Gleason score, stage at diagnosis and PSA at diagnosis. Individual patient charts were reviewed. Pearson Chi-square test or Fisher’s exact test was used for categorical variables, while ANOVA or Kruskal-Wallis test was used for continuous variables. All analysis was performed using SAS 9.3 (Cary, NC). Results: 537 patients with newly diagnosed PCa were identified among which 141 were classified as H, 268 as NHB and 128 as NHW. The age at diagnosis was similar across the three groups (H 63.6, NHB 64.3, NHW 65.3, p = 0.38). More H (94%) and NHB (89%) were below the mean SES as compared to NHW (55%) (p < 0.0001). The median PSA (7.5, 7.2 and 7.1, p = 0.78) and mean Gleason score (6.7, 6.7 and 6.6, p = 0.20) were similar in H, NHB and NHW, respectively. Locally advanced disease (T3, T4 or N+) was more common in H (29.0%) and NHB (22.2%) than NHW (9.3%) (p < 0.0001). Additionally, metastatic disease was more common in H (9.2%) and NHB (7.5%) than NHW (0.8%) (p = 0.01). Conclusions: At our center, minority patients diagnosed with PCa during the years for which data were available had less favorable SES and were more likely to have locally advanced or metastatic disease.
Phase II trial of nivolumab (nivo) plus ipilimumab (ipi) in patients with SMARCB1-deficient kidney malignancies.
Authors: Pavlos Msaouel, Rebecca Slack-Tidwell, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2019)

TPS677 Background: The potent tumor suppressor SMARCB1 (also known as INI-1, hSNF5, or BAF47) is inactivated in all cases of renal medullary carcinoma (RMC) and renal cell carcinoma unclassified with medullary phenotype (RCCU-MP), as well as most malignant rhabdoid tumors (MRT) of the kidney. Although rare, these kidney malignancies are highly lethal and often occur in young patients. The role of immune checkpoint inhibitor therapy remains to be prospectively defined in tumors harboring SMARCB1 defects. Although a case report noted efficacy of single-agent Nivo in a patient with RMC (Beckermann et al J Immunother Cancer, 2017), there were no durable responses in subsequent cases (Sodji et al. J Immunother Cancer, 2017). We hypothesize that the combination of anti-PD1 (Nivo) with anti-CTLA4 (Ipi) immune checkpoint inhibitor therapy will lead to more potent antitumor responses compared to those reported with single-agent Nivo. Methods: This single-arm phase II trial will test the efficacy of Nivo + Ipi in up to 30 patients with SMARCB1-negative RMC, RCCU-MP, and adult-onset kidney MRTs. Any number of prior therapies is allowed. Patients will be treated with Ipi 1 mg/kg + Nivo 3 mg/kg every 3 weeks x4 doses followed by maintenance Nivo 480 mg every 4 weeks for up to 2 years. Ongoing monitoring for safety and futility will be implemented per the method of Thall et al. (Stat Med, 1995; 14:357-79) using cohorts of 10 patients each. The primary endpoint is objective response rate (ORR) and the trial objective is to achieve a similar or greater ORR compared with the historical ORR of 29% achieved in our institution using conventional cytotoxic chemotherapies. Secondary endpoints include progression-free survival, overall survival, and disease control rate. To evaluate potential biomarkers for treatment response, correlative analyses will be performed in tumor tissue and peripheral blood samples obtained i) pre- treatment (baseline) up to 6 weeks (42 days) prior to initiation of treatment on Day 1, ii) after completion of the combination therapy (Nivo + Ipi) phase, and iii) upon disease progression. At the time of the abstract submission, 2 patients have been enrolled on this study. Clinical trial information: NCT03274258.
Ad libitum water consumption prevents exercise-associated hyponatremia and protects against dehydration in soldiers performing a 40-km route-march
Authors: Heinrich W. Nolte, Kim Nolte, Tamara Hew-Butler
Journal: Military Medical Research (2019)

It remains unclear if ad libitum water drinking, as a hydration strategy, prevents exercise-associated hyponatremia (EAH) during prolonged exercise. The aim of this study was to determine the incidence of EAH within the broader context of fluid regulation among soldiers performing a 40-km route-march ingesting water ad libitum. Twenty-eight healthy male soldiers participated in this observational trial. Pre- and post-exercise body mass, blood and urine samples were collected. Blood samples were assessed for serum sodium ([Na+]), glucose, creatinine, urea nitrogen (BUN), plasma osmolality, creatine kinase (CK), and plasma arginine vasopressin (AVP) concentrations. Plasma volume (PV) was calculated using hematocrit and hemoglobin. Urine samples were analyzed for osmolality and [Na+]. Water intake was assessed by weighing bottles before, during and after the march. The mean relative humidity was 55.7% (21.9–94.3%) and the mean dry bulb temperature was 27.1 °C (19.5 °C - 37.0 °C) during the exercise. Twenty-five soldiers (72 ± 10 kg) (Mean ± SD) completed the march in 09:11 ± 00:43 (hr:min). Participants consumed 736 ± 259 ml/h of water and lost 2.8 ± 0.9 kg (4.0% ± 1.4%, P < 0.05) of body mass. Significant (pre-march vs. post-march; P < 0.05) decreases in serum [Na+] (141 mmol/L vs. 136 mmol/L), plasma osmolality (303 mOsmol/kg H2O vs. 298 mOsmol/kg H2O), and serum creatinine (111 μmol/L vs. 101 μmol/L) and urine [Na+] (168 mmol/L vs. 142 mmol/L), as well as significant increases in plasma AVP (2 pg/ml vs. 11 pg/ml), plasma CK (1423 U/L vs. 3894 U/L) and urine osmolality (1035 mOsmol/kg H2O vs. 1097 mOsmol/kg H2O) were found. The soldier (72 kg) with the lowest post-exercise sodium level completed the march in 08:38. He drank 800 ml/h, lost 2% body mass, and demonstrated (pre-post) increases in plasma osmolality (294–314 mOsmol/kg H2O), BUN (20–30 mg/dl), AVP (2–16 pg/ml) and PV (41%). His urine osmolality decreased from 1114 mOsmol/kg H2O to 1110 mOsmol/kg H2O. No participants finished the route-march with a serum [Na+] indicating hypernatremia (range, 134–143 mmol/L). Ad libitum drinking resulted in 4% body mass loss with a 2 mmol/L serum [Na+] reduction in conjunction with high urine osmolality (> 1000 mOsmol/kg H2O) and plasma AVP. No single hydration strategy likely prevents EAH, but hypernatremia (cellular dehydration) was not seen despite > 2% body mass losses and high urine osmolality.
Assessment of Treatment Effects By Measurable Residual Disease Monitoring in NPM1-Mutated AML Patients Randomized for Gemtuzumab-Ozogamicin (GO) within the AMLSG 09-09 Trial of the German-Austrian AML Study Group (AMLSG)
Authors: Silke Kapp-Schwoerer, Daniela Weber, Andrea Corbacioglu, Verena I. Gaidzik, Peter Paschka, Jan Krönke, Maria-Veronica Teleanu, Frauke Theis, Frank G. Rücker, Gudrun Göhring, Brigitte Schlegelberger, Walter Fiedler, Thomas Kindler, Thomas Michael Schroeder, Karin Mayer, Michael Lübbert, Mohammed Amen Wattad, Katharina S. Götze, Heinz A. Horst, Elisabeth Koller, Gerald Wulf, Jan Schleicher, Martin Bentz, Jürgen Krauter, Julia Krzykalla, Axel Benner, Richard F. Schlenk, Felicitas Thol, Michael Heuser, Arnold Ganser, Hartmut Döhner, Konstanze Döhner
Journal: Blood (2018)