tbuckley/cabot-search huggingface dataset:
Trends in the incidence and outcomes of C<i>lostridioides</i> <i>difficile</i> infection in hematological cancers: A nationwide analysis.
Authors: Fateeha Furqan, Raseen Tariq, Nicolas Goldstein, Sanjana Kashinath, Saad Jamshed, Sahil Khanna
Journal: Journal of Clinical Oncology (2019)

e18244 Background: Clostridioides difficile infection (CDI) has higher incidence in cancer patients. To characterize the extent of CDI burden among hematologic cancer patients, we used the National Hospital Discharge Survey (NHDS) to report the incidence and outcomes of CDI. Methods: NHDS data from 2001-2010 were analyzed using diagnosis codes to identify patients with hematologic cancers and CDI. Demographics and discharge information were compared amongst hematologic cancer patients with and without CDI. Logistic regression models were runto estimate the impact of CDI on hematologic cancer patient outcomes, using STATA 12.0. Results: During the years 2001-2010, about 3.7 million patients (weighted data) were discharged with hematologic cancer. Among them, the incidence of CDI was 2.3%. Hematologic cancer patients with CDI were younger (mean age 66 vs 68 years), more likely to be men (66% vs 64.5%), to be of white race (68.1% vs 67.7%) and to have emergent admissions (73% vs 69%), all p values &lt; 0.001. CDI incidence in these patients showed a steeper increase than non-cancer patients, with highest incidence in 2008-2009. Hematologic cancer patients with CDI had a longer mean Length of stay (16.9 vs 7.1 days; adjusted odds ratio (aOR) 9.5, 95% CI 9.4-9.6), all cause hospital mortality (11.3% vs 6.3%; aOR 1.92, 95% CI 1.88-1.97) and discharge to a care facility (28.4% vs 18.8%; aOR 2.06, 95% CI 2.02-2.10) compared to non-CDI cancer patients. Conclusions: CDI incidence is higher in patients with hematologic malignancy. They also have worse outcomes including overall mortality, longer hospitalizations and discharge to healthcare facility. These patients warrant closer screening and prompt treatment of CDI as they are at greater risk of unfavorable outcomes. [Table: see text]
Evaluation of racial disparities in the treatment of United States veterans with pancreatic cancer.
Authors: Theodore Seth Thomas, Suhong Luo, Jesse W. Keller, Kristen Marie Sanfilippo, Kenneth Robert Carson
Journal: Journal of Clinical Oncology (2019)

e18148 Background: Recent studies have demonstrated racial disparities in pancreatic ductal adenocarcinoma (PDAC) treatment. Black patients with PDAC are less likely to undergo surgery or receive systemic therapy compared to white patients. One explanation for this may be access to healthcare. The aim of this study is to evaluate racial disparities in treatment of PDAC patients in a cohort of United States Veterans with equal insurance access. Methods: This study is a multicenter, retrospective cohort study. The VA Central Cancer Registry was used to identify patients diagnosed with PDAC from Oct 1st, 1998-Dec 31 st , 2014. This cohort was divided into surgically resected and advanced/unresectable groups. The primary outcome for the surgery cohort is the association between race and receipt of adjuvant therapy. The metastatic cohort includes patients with stage III/IV without surgery record. The primary outcome is the association between race and recorded chemotherapy within 6 months of diagnosis. Primary outcomes were assessed using multivariable logistic regression controlling for age and comorbidities. Associations between race and survival for each sub-cohort were assessed using cox proportional hazards analysis. Results: The surgery cohort consisted of 1,835 patients of whom 356 (19%) were black and 1,433 (78%) were white, with 660 (36%) receiving adjuvant treatment. There was no association between race and receipt of adjuvant treatment (OR 1.00, 95% CI 0.78-1.28). There was no difference in survival up to 3 years in white patients compared to black patients (HR 0.99, 95% CI 0.86-1.14). The metastatic disease cohort consisted of 7,983 patients of whom 1,610 (20%) were black and 6150 (78%) were white, with 2,885 (36%) receiving chemotherapy. There was no association between race and receipt of chemotherapy in patients with advanced disease (OR 1.02, 95% CI 0.91-1.15). There was no difference in survival up to 1 year in white patients compared to black patients (HR 0.96, 95% CI 0.90-1.01). Conclusions: This study failed to demonstrate an association between race and adjuvant therapy or systemic therapy administration. There was no difference in overall survival in this cohort. Previously described racial disparities in the treatment of advanced PDAC do not extend to the equal insurance access VA Health Care System.
Copy number analysis to identify tumor suppressor genes associated with enzalutamide (Enza) resistance and poor prognosis in metastatic castration-resistant prostate cancer (mCRPC) patients.
Authors: Xiangnan Guan, Duan-Chen Sun, Eric Lu, Joshua A. Urrutia, Robert Evan Reiter, Matthew Rettig, Christopher P. Evans, Primo Lara, Martin Gleave, Tomasz M. Beer, George V. Thomas, Jiaoti Huang, Zheng Xia, Joshi J. Alumkal
Journal: Journal of Clinical Oncology (2019)

5011 Background: Although enza prolongs life in mCRPC pts, the development of drug resistance and subsequent disease progression is nearly universal. Seeking to clarify molecular mechanisms that underlie enza resistance, we analyzed whole genome sequencing (WGS) and RNA sequencing (seq) of tumors obtained from patients with enza-naive or -resistant mCRPC. Methods: One hundred and one men with mCRPC who underwent image-guided biopsy and subsequent WGS were included (n = 64 with enza-naive and n = 37 with enza-resistant mCRPC). The differential copy number alteration (CNA) events enriched in enza-resistant vs. naïve samples were determined, and the prognostic significance of differential CNAs was assessed. RNA-seq data were evaluated to confirm that CNAs correlated with changes in gene expression of relevant loci and to identify potentially druggable targets selectively activated in tumors with specific CNAs. Results: Copy number loss was more common than gain in enza-resistant tumors. Specifically, we identified 123 protein-coding genes that were more commonly lost in enza-resistant samples—eight of which were previously described tumor suppressor genes. There was a strong concordance of copy number loss and reduced mRNA expression of these genes. We identified one gene from this list of eight genes whose copy number loss was associated with poor overall survival (median overall survival from date of CRPC was 19.1 months in tumors with gene loss vs. 42.0 months in intact tumors, hazard ratio 3.8 [1.46–9.8], log-rank p = 0.003). Finally, Master Regulator analysis determined that tumors with copy number loss of this poor prognosis gene had activation of several potentially targetable factors, including the kinases Akt and PLK1. Conclusions: Copy number loss of specific tumor suppressor genes is associated with enza resistance in mCRPC patients. Previously unappreciated molecular subsets of enza-resistant CRPC were identified, including one subset associated with poor clinical outcome.
Abstract 10128: The Impact of Replacing the Pooled Cohort Equation With Other CVD Risk Scores on Atherosclerosis Cardiovascular Disease Risk Assessment: MESA
Authors: Waqas Qureshi, Peter Flueckiger, Michael Blaha, Erin D Michos, Veit Sandfort, David M Herrington, Gregory Burke, Joseph Yeboah
Journal: Circulation (2015)

Introduction: The increase in statin eligibility by the new cholesterol guidelines is mostly driven by the Pooled Cohort Equation (PCE) criterion (≥ 7.5% 10yr. PCE). The impact of replacing the PCE with either the modified Framingham risk score (FRS) or the Systematic COronary Risk Evaluation (SCORE) on ASCVD risk assessment and statin eligibility remains unknown. We assessed the comparative benefits of using the PCE, FRS and SCORE for ASCVD risk assessment in the Multi Ethnic Study of Atherosclerosis (MESA). Methods: : 4632 out of 6814 participants (mean age 60±10 years, 47% males, 39% whites, 27% blacks) were included in analysis. Area under the curve (AUC) and decision curve analysis (DCA) were used to compare the three risk scores. [DCA is the plot of net benefit versus probability thresholds; Net Benefit = true positive rate - (false positive rate x weighting factor). Weighting factor = Threshold probability/1-threshold probability]. Results: After a median of 10.2 years, 347 (7.5%) ASCVD events (MI, CHD death, fatal or non-fatal stroke) occurred. All three risk scores had acceptable discriminative ability for incident ASCVD events [(AUC (95% CI) PCE: 0.748(0.722-0.774); FRS: 0.732(0.703-0.761) and SCORE: 0.790(0.764-0.816)]. The SCORE had the best net benefit compared with PCE or FRS across all the probability thresholds considered (0-20%). At the 7.5% probability threshold adopted by the new cholesterol guidelines, SCORE identifies 7 additional people not eligible for statins out of 100 persons eligible under the “treating all” approach compared with PCE (43/100 for SCORE vs. 36/100 for PCE; hence 19% reduction) without missing any true high risk person. Conclusions: At the ACC/AHA recommended 7.5% ASCVD risk threshold, SCORE reduced statin eligibility by 19% compared with the PCE without missing any true high risk person. Validation of our findings in other cohort is needed.
Impact of a same-day breast biopsy program on disparities in time to biopsy.
Authors: Matthew Seidler, Brian Nicholas Dontchos, Sarah Mercaldo, Randy C. Miles, Anand Narayan, Constance Dobbins Lehman
Journal: Journal of Clinical Oncology (2019)

6508 Background: While screening rates have improved among minorities, racial/ethnic disparities in diagnosis and treatment persist. Many steps in the diagnostic pathway can delay tissue diagnosis, and in usual practice breast biopsies are performed days to weeks after biopsy recommendation. The purpose of this study was to identify if racial/ethnic disparities exist in time from biopsy recommendation to biopsy, and if a same-day biopsy program (biopsy on the same day as the recommendation) eliminates these disparities. Methods: After IRB approval, we identified all diagnostic mammogram and ultrasound exams leading to biopsy pre- (September 2016-March 2017) and post- (September 2017-March 2018) implementation of our same-day biopsy program. We compared the distribution of age, race, language, insurance type, days to biopsy and proportion of same-day biopsies in pre- vs. post-implementation groups using the Wilcoxon test (for continuous variables) and the Pearson’s chi-squared test (for categorical variables). Multivariable linear and logistic models were estimated in pre and post periods to assess if days from biopsy recommendation to biopsy (linear) and having a same-day biopsy (logistic) were associated with age, race, language, and insurance type. Results: 663 and 482 patients underwent biopsy during pre- and post-implementation, respectively. Age, race, language, and insurance type were similar between time periods. For all patients, the same-day biopsy program decreased mean time from diagnostic examination to biopsy from 8 (IQR: 4-13) to 0 (IQR: 0-4) days (p &lt; 0.001). During the pre time period, non-white patients and having government insurance were significantly associated with longer days to biopsy (non-white aCoef: 2.30 (95% CI: 0.58-4.03); insurance aCoef: 1.67 (95% CI: 0.02-3.32); p &lt; 0.05), and increasing age and having government insurance were significantly associated with decreased odds of having a same-day biopsy (age aOR: 0.97 (95% CI 0.95-0.99); insurance aOR: 0.35 (95% CI 0.14-0.88); p &lt; 0.05), after adjustment. During the post time period there was no evidence of these disparities. Conclusions: A same-day biopsy program eliminated racial/ethnic disparities in time from breast biopsy recommendation to biopsy.
Association Between Tonsillectomy and Outcomes in Patients With Immunoglobulin A Nephropathy
Authors: Keita Hirano, Keiichi Matsuzaki, Takashi Yasuda, Masako Nishikawa, Yoshinari Yasuda, Kentaro Koike, Shoichi Maruyama, Takashi Yokoo, Seiichi Matsuo, Tetsuya Kawamura, Yusuke Suzuki
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Immunoglobulin A nephropathy is a major cause of end-stage renal disease worldwide; previous methods of medical management, including use of renin-angiotensin system inhibitors and corticosteroids, remain unproven in clinical trials. <h3>Objective</h3> To investigate the possible association between tonsillectomy and outcomes in patients with IgA nephropathy. <h3>Design, Setting, and Participants</h3> This cohort study included 1065 patients with IgA nephropathy enrolled between 2002 and 2004 and divided into 2 groups, those who underwent tonsillectomy and those who did not. Initial treatments (renin-angiotensin system inhibitors or corticosteroids) within 1 year after renal biopsy were also evaluated. A 1:1 propensity score matching was performed to account for between-group differences and 153 matched pairs were obtained. Follow-up concluded January 31, 2014. Analysis was conducted between September 11, 2017, and July 31, 2018. <h3>Exposure</h3> Tonsillectomy. <h3>Main Outcomes and Measures</h3> The primary outcome was the first occurrence of a 1.5-fold increase in serum creatinine level from baseline or dialysis initiation. Secondary outcomes included additional therapy with renin-angiotensin system inhibitors or corticosteroids initiated 1 year after renal biopsy and adverse events. <h3>Results</h3> In 1065 patients (49.8% women; median [interquartile range] age, 35 [25-52] years), the mean (SD) estimated glomerular filtration rate was 76.6 (28.9) mL/min/1.73 m<sup>2</sup>and the median (interquartile range) proteinuria was 0.68 (0.29-1.30) g per day. In all, 252 patients (23.7%) underwent tonsillectomy within 1 year after renal biopsy and 813 patients (76.3%) did not undergo tonsillectomy. The primary outcome was reached by 129 patients (12.1%) during a median (interquartile range) follow-up of 5.8 (1.9-8.5) years. In matching analysis, tonsillectomy was associated with primary outcome reduction (hazard ratio, 0.34; 95% CI, 0.13-0.77;<i>P</i> = .009). In subgroup analyses, benefit associated with tonsillectomy was not modified by baseline characteristic differences. Those undergoing tonsillectomy required fewer additional therapies 1 year following renal biopsy (adjusted hazard ratio, 0.37; 95% CI, 0.20-0.63;<i>P</i> &lt; .001) without increased risks for adverse events, except transient tonsillectomy-related complications. <h3>Conclusions and Relevance</h3> This study found that tonsillectomy was associated with a lower risk of renal outcomes in patients with IgA nephropathy. The potential role of tonsillectomy should be considered for preventing end-stage renal disease in patients with IgA nephropathy.
Real-world treatment patterns, survival, and cost among elderly cervical cancer patients.
Authors: Changxia Shao, Jinghua He, Chizoba Nwankwo, Karen Stein, Stephen Michael Keefe
Journal: Journal of Clinical Oncology (2019)

e18226 Background: Limited chemotherapy data is available for elderly cervical cancer patients (pts). This study aimed to investigate real-world use of systemic therapies, survival, and costs among elderly pts in U.S. Methods: Pts who aged 65+ years and initially diagnosed with cervical cancer between 2007 and 2013 were identified using the SEER-Medicare data. Regimens were classified into 3 mutually-exclusive categories, i.e. cisplatin (Cis), carboplatin (Car), and Other based therapies. Chemotherapy within 90 days of surgery or radiation therapy were not considered as first line (1L) systemic therapy. All costs were converted to 2016 US dollars. Results: A total of 1 651 eligible pts were identified with 430 (26%) being stage IV at diagnosis. Among pts received systemic therapies, the median overall survival (OS) was 14 m from 1L initiation and 10 m from 2L initiation. Among 225 pts who received 1L, 58% pts received Cis-based therapy, and 17% pts received Car-based therapy. Car + paclitaxel was the most commonly used regimen (44%). Among 73 pts who received 2L, 34% and 15% pts received Cis- and Car-based therapy, respectively. Pts with 2L therapy received a variety of regimens with the top 3 being Car + paclitaxel (19%), gemcitabine (11%), and topotecan (9.6%). Median duration of treatment (DOT) was 4-6 m across line of therapies (LOTs), yet median time to next treatment (TTNT) ranged 10-32 m for 1L, and 9-11 m for 2L. The average per person per month (PPPM) costs were 7.1k for 1L and 8.8k for 2L with primary drivers of spending being outpatient and emergency room visits. Conclusions: Elderly pts with advanced cervical cancer requiring chemotherapy had poor prognosis and had no standard of care for 2L therapy. Per-patient economic burden is substantial for both 1L and 2L therapy, exceeding 7k dollars per month. [Table: see text]
Comprehensive report of anti-CD19 chimeric antigen receptor T cells (CAR-T) associated non-relapse mortality (CART-NRM) from FAERS.
Authors: Kartik Anand, Ethan Burns, Dahlia Sano, Sai Ravi Pingali, Jason Westin, Loretta J. Nastoupil, Hun Ju Lee, Felipe Samaniego, Simrit Parmar, Michael Wang, Misha Hawkins, Sherry Adkins, Luis Fayad, Raphael Steiner, Ranjit Nair, Sairah Ahmed, Nathan Hale Fowler, Sattva Swarup Neelapu, Swaminathan Padmanabhan Iyer
Journal: Journal of Clinical Oncology (2019)

2540 Background: CAR-T cells targeting CD19 positive B-cells have improved outcomes for relapsed/refractory non-Hodgkin lymphoma (NHL) and B-cell acute lymphoblastic leukemia (B-ALL). CAR-T emergent toxicities for FDA approved therapies leading to non-progression related death have been reported in the pivotal studies. However, they are underreported and there remains a need to obtain a comprehensive report of NRM emergent with anti-CD19 CAR-T. Methods: We retrospectively searched FDA adverse events reporting system (FAERS) for all adverse events (AE) related to “Tisagenlecleucel(T)” and “Axicabtagene ciloleucel(AC)” reported from 2013-2018. FAERS contains AEs from clinical trials and standard of care patients. All cases with the outcome of death were analyzed. Results: Total numbers of anti-CD19 CAR-T pts reported were 636, out of which 288 cases received “T” and 348 received “AC”. Out of total 129 total deaths, 95 died due to non-disease progression. Patient characteristics are summarized in Table. CART-NRM for entire cohort was 15%; 21% for “T” and 10% for “AC”. Major toxicities reported include CRS, hematological, cardiovascular, neurological and infectious. Difference in mortality is likely related to different patient population, diagnoses and the CAR-T construct. Conclusions: CART-NRM remains considerably high at 15%. Our analysis highlights the major toxicities and informs the potential opportunities for interventions to reduce mortality. We will present updated data with comparative analysis of published clinical studies at the upcoming ASCO Meeting in Chicago. [Table: see text]
Profile of cancer caregivers among adult Indian rural cancer patients: A prospective survey.
Authors: Avinash Vijay Kumar Pandey, Anjana Singh, Shivkant Singh
Journal: Journal of Clinical Oncology (2019)

e18019 Background: There is lack of information regarding Cancer Caregivers who play predominant role in assisting patients during active treatment and follow –up in India. Aim: To identify profile of cancer caregivers Objectives: To identify, social, economic, familial variables of cancer caregivers of adult cancer patients by prospective survey/questionnaire. Methods: All consecutive individual adult (age≥18 years) patients diagnosed with cancer and registered in Medical Oncology OPD were enrolled for Cancer caregiver questionnaire based survey between July 2018 and October 2018.Primary caregiver was defined as person of first degree relative who has greatest responsibility of daily patient care. Patient was asked to name single preferred primary caregiver in case of multiple first degree relatives available. Results: Of 517 patients enrolled, 456 (88%) were rural.491 (95%) had primary caregivers, while 26(5%) had secondary caregivers only. 295(57%) had 3-4 caregivers, while 117 (23%) had 5-7 caregivers in predominantly joint family population (75%). Among primary caregivers, son 287 (58%) was the preferred choice, followed by brothers, 50 (10%). Only 61 (12%), chose female as primary caregivers. Only 36/281 (13%) married men and 71/215 (33%) married women chose their spouse as primary caregiver. 326 (63%) of primary caregivers had monthly income equivalent to $70-140, while 16% and 9% had between $140-280 and less than $70 respectively.131 (25%) of caregivers were graduate,186 (35%) passed secondary school, while only 25 (4.8%) were illiterate. Conclusions: Majority of rural Indian cancer patients have access to multiple caregivers. Young males are the preferred choice as primary caregiver. Primary caregivers are economically poor but literate.
Efficacy and cost-effectiveness of HER2+ early breast cancer therapies.
Authors: Marcos Fonseca Magalhães Filho, Pedro Nazareth Aguiar, Benjamin Haaland, Auro Del Giglio, Gilberto Lopes
Journal: Journal of Clinical Oncology (2019)

e18380 Background: Human Epidermal Growth Factor Receptor 2 (HER2) overexpression occurs in up to 25% of breast cancer (BC) cases. Patients with HER2+ tumors have a poor prognosis even when the disease is detected at an early stage with a recurrence rate of 15-19%. The aim of this study is to assess the best approach (pertuzumab plus trastuzumab [T+P], trastuzumab for 12 months [T12], trastuzumab for 6 months [T6], or T-DM1) in terms of evidence-based medicine and cost-effectiveness. Methods: The authors extracted individual patient data and estimated Invasive Disease-Free Survival (IDFS) and Overall Survival (OS) over a 30-years lifetime horizon. We considered only direct costs from adjuvant treatment as well as recurrence treatment from a Brazilian payer perspective. Heart events were considered for utility and cost analysis. After the base case, the authors assessed cost-effectiveness among N+ patients. In the meta-analysis, we included individual patient data for the intention-to-treat (ITT) population and Bayesian comparisons for subgroup analysis (HR+/HR- and N+/N). Results: We included individual patient data from 12,753 patients. The 4-year IDFS rate was 92.9% for T+P, 89.8% for T12 (HR 1.37, 95%CI 1.16-1.63) and 87.1% for T6 (HR 1.73, 95%CI 1.45-2.06). The 4-year OS rate was 96.7% for T+P, 95% for T12 (HR 1.37, 95%CI 1.07-1.75) and 93% for T6 (HR 1.82, 95%CI 1.42-2.34). T+P, T12 and T6 had similar efficacy among patients with HR+ tumors. T+P and T12 were superior to T6 among HR- patients. T+P was superior to T12 and T6 among N+ patients. T+P, T12 and T6 had similar efficacy among N- patients. In the base case, T+P had an ICER of $332,903 compared to T12. T12 had an ICER of $42,774 compared to T6. Among N+ patients, T+P had an ICER of $308,019 compared to T12. Among patients without complete response after neoadjuvant treatment, T-DM1 had an ICER of $3,233 compared to trastuzumab. Conclusions: T+P had a modest benefit in terms of 4-years IDFS and OS, although it was not cost-effective due to its high cost. T12 remained above the cost-effectiveness threshold compared to T6, but further studies are needed in order to define patients for T6. T-DM1 was cost-effective compared to trastuzumabe for patients who did not achieve complete response after neoadjuvant treatment.