tbuckley/cabot-search huggingface dataset:
Sequential intravesical gemcitabine and docetaxel in the treatment of BCG-naive patients with non-muscle invasive bladder cancer.
Authors: Lewis Thomas, Ryan Steinberg, Kenneth Gerard Nepple, Michael A. O'Donnell
Journal: Journal of Clinical Oncology (2019)

469 Background: Bacillus Calmette-Guerin (BCG) is the standard of care for patients with new non-muscle invasive bladder cancer (NMIBC) after transurethral tumor resection. While BCG has been compared to single agent intravesical chemotherapy as first-line therapy, few studies exist comparing BCG to sequential intravesical chemotherapy regimens. The objective of this work was to determine the efficacy of sequential intravesical gemcitabine and docetaxel (Gem/Doce) in BCG naïve patients with NMIBC. Methods: Patients without prior BCG exposure who underwent Gem/Doce intravesical treatments were retrospectively identified. These patients had been treated with 6 weekly instillations of gemcitabine (1 gram of gemcitabine in 50 ml of sterile water) followed immediately by docetaxel (37.5 mg of docetaxel in 50 mL of saline). Patients without recurrence then underwent maintenance therapy with monthly instillations for two years. Treatment success was defined as no bladder cancer recurrence and no cystectomy. Survival analysis was performed using the Kaplan Meier method. Results: 30 patients were treated with a median follow-up of 18 months. Eighty percent (n=24) of patients had high risk disease. Median age was 78 years old. The most common indications for Gem/Doce therapy were “advanced age/frailty” (n=15), “immunosuppression” (n=4), and “BCG Shortage” (n=4). Treatment success was 96% at 3 months, 89% at 1 year, and 89% at 2 years. No patients progressed or required cystectomy. Treatments were generally well tolerated, with only one patient unable to finish induction and two patients declining maintenance. Side-effects included urinary urgency/frequency (30%), dysuria (26%), and hematuria (23%). A need for dose reduction or delay was uncommon (16%). The all-cause mortality rate was 3.5% at 1 year, and 16.5% at 2 years. Neither bladder cancer nor the treatments were the cause of any of the deaths. Conclusions: Sequential intravesical gemcitabine and docetaxel is an effective treatment for BCG naïve NIMBC. Treatments are generally well tolerated even in a frail and comorbid patient population. Further evaluation of this combination therapy for BCG naïve disease is warranted.
Abstract P108: Wnt Pathway Gene Expression is Associated With Greater Arterial Stiffness
Authors: Allison L Kuipers, Emma Barinas-Mitchell, Cara S Nestlerode, Victor W Wheeler, Iva Miljkovic, Joseph M Zmuda
Journal: Circulation (2019)

The wingless (Wnt) pathway is known to regulate many systems, including embryonic development, bone mineralization, and cancer. Now there is emerging evidence from Basic and our own Population research that Wnt pathway activation is associated with cardiovascular disease (CVD) pathologies, including atherosclerosis and arterial stiffening. However, research on this association in humans is still under-studied and limited in scope. As such, we aimed to survey the entire Wnt signaling pathway for association with subclinical CVD, using a custom gene expression panel (Nanostring, Seattle, WA) of 43 Wnt genes with previous Basic research evidence for a role in vascular disease. We ran this panel in stabilized peripheral blood RNA from 369 African Ancestry men in the Tobago Health Study (mean age 64 years, range 51-89 years). Subclinical CVD assessments were completed at the same study visit as the blood draw, including: arterial stiffness measured by brachial-ankle pulse-wave velocity; atherosclerosis measures of carotid plaque and intima-media thickness via B-mode ultrasonography; and vascular calcification measured by computed tomography in the chest (coronary) and abdomen (aorta). Gene expression was measured in counts per sample, was normalized to housekeeping genes, and the background signal was subtracted. All gene expression and outcome measures were transformed to normality after excluding any extreme outliers. Fourteen Wnt genes showed variable expression in our sample and were tested individually as predictors of subclinical CVD using multiple linear or logistic regression, as appropriate. A conservative Bonferroni-corrected alpha (0.05/14 genes = 0.0036) was used to account for multiple comparisons in unadjusted models. Associations passing this threshold were then adjusted for common CVD risk factors including age, height, weight, hypertension, pulse, diabetes, smoking, alcohol intake, and sedentary lifestyle. After full adjustment, expression of APC, WNT signaling pathway regulator ( APC ) and transcription factor 4 ( TCF4 ) showed significant association with arterial stiffness (P=0.012 for both). When entered into a single model (Spearman r=0.14, P=0.007), APC and TCF4 expression were independently associated with arterial stiffness (P=0.004 for both), such that higher expression of APC , but lower expression of TCF4 , was associated with greater arterial stiffness. No other tested genes or subclinical CVD measures passed both the conservative unadjusted alpha level and the full model adjustment. This study represents the first test of the association between broad Wnt signaling pathway gene expression and subclinical CVD. While APC and TCF4 have shown some association with vascular pathologies in Basic research, this is the first study to establish the association of their expression with human arterial stiffness.
Efficacy and safety of ponatinib in heavily pretreated leukemia patients in the PACE trial: 3-year results.
Authors: Jorge E. Cortes, Dong Goo Kim, Javier Pinilla-Ibarz, Philipp D. Le Coutre, Ronald Paquette, Charles Chuah, Franck E. Nicolini, Jane Apperley, Hanna Jean Khoury, Moshe Talpaz, John F. DiPersio, Michele Baccarani, Stephanie Lustgarten, Frank G. Haluska, Francois Guilhot, Michael W.N. Deininger, Andreas Hochhaus, Timothy P. Hughes, Neil P. Shah, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2015)

e18052 Background: Ponatinib is an approved oral tyrosine kinase inhibitor (TKI) with potent activity against native BCR-ABL and resistant mutants, including T315I. Methods: PACE (NCT01207440) evaluated the efficacy and safety of ponatinib (starting dose 45 mg once daily) in patients (pts) with CML or Ph+ ALL resistant/intolerant to dasatinib/nilotinib or with T315I. Of 449 pts, 58% received ≥3 prior TKIs. Arterial occlusive events (AOEs) led to recommended dose reduction in Oct 2013. Exposure-adjusted incidence rates of new AOEs were calculated as (number of first events in interval)/(total exposure for interval in patient-years) x 100. Rates for later intervals exclude pts with prior events. Results: As of Oct 6, 2014: 33% of all pts and 45% of CP-CML pts remained on study. Median follow-up: 34.2 (0.148.6) months overall; 38.4 (0.148.6) months for CP-CML pts. Main reasons for discontinuation: progression (21% overall, 9% CP-CML); AEs (15% overall, 17% CP-CML). In CP-CML pts, 59% achieved MCyR, 39% achieved MMR or better, and 22% achieved MR4.5; estimated 3-year MCyR maintenance, PFS, and OS were 83%, 61%, and 82%, respectively. In AP-CML, BP-CML, and Ph+ ALL pts, estimated 3-year OS was 59%, 9%, and 16%, respectively. Treatment-emergent AEs in ≥30% of pts: thrombocytopenia 43%; abdominal pain 42%; rash 41%; constipation 37%; headache 37%; dry skin 36%; fatigue 30%. AOE rate (serious AOE rate): 22% (17%), including cardiovascular 12% (8%); cerebrovascular 8% (6%); peripheral vascular 8% (6%). Venous thromboembolic event (VTE) rate (serious VTE rate): 5% (4%). Of 99 pts with AOEs, 42 remained on study and 33 were still in MCyR. Exposure-adjusted incidence rates of new AOEs (events per 100 patient-years): 14.5 in Year 1; 14.1, Year 2; 10.8, Year 3; of new VTEs: 3.5 in Year 1; 1.8, Year 2; 1.8, Year 3. A year after recommended dose reduction, 61 (95%) of 64 CP-CML pts maintained MCyR, 44 (94%) of 47 CP-CML pts maintained MMR, and 5 (7%) of 70 ongoing pts without a prior AOE had an AOE. Conclusions: Ponatinib continues to show deep, durable responses in heavily pretreated pts, particularly those with CP-CML. A year after recommended dose reduction to mitigate safety risks, responses were maintained and incidence of new AOEs was low. Clinical trial information: NCT01207440.
Venous Thromboembolism Following Pegaspargase in Adults Receiving Antithrombin Supplementation: A Single Center Characterization of Risk Factors and an Assessment of Supplementation Practice
Authors: Craig W. Freyer, Alex Ganetsky, Mitchell E. Hughes, Tracy M. Krause, Colleen Timlin, Noelle V. Frey, Elizabeth O. Hexner, Alison W. Loren, James K. Mangan, Mary Ellen Martin, Shannon R. McCurdy, Alexander E. Perl, David L. Porter, Selina Luger
Journal: Blood (2018)
Early Utilization Patterns of the New Medicare Procedure Codes for Advance Care Planning
Authors: Emmanuelle Belanger, Lacey Loomer, Joan M. Teno, Susan L. Mitchell, Deepak Adhikari, Pedro L. Gozalo
Journal: JAMA Internal Medicine (2019)

Assessment of First-Year Use of Medicare's Advance Care Planning Billing CodesAdvance care planning (ACP) conversations occur infrequently among patients and their health care professionals, and when they do occur, the context is often a stressful clinical situation. 1,2 Advance care planning conversations that occur too late (or not at all) can result in care that is invasive, expensive, and not aligned with patients' wishes.To encourage health care professionals to initiate ACP discussions, Medicare began reimbursing for ACP services on January 1, 2016, under a separate billing code.Our study aims to characterize the first year of ACP code use and to describe beneficiary characteristics associated with receipt of ACP services.Methods | For this retrospective observational analysis, we used Medicare fee-for-service Parts A and B claims, the Medicare coverage and denominator files, and US Census Bureau data.All beneficiaries in New England (Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont) continuously enrolled in Parts A and B in 2016 were included in this sample.Beneficiaries who died during the study year were included until their death.The authors have access to Medicare claims data under an agreement between Healthcentric Advisors and the Centers for Medicare & Medicaid Services for use of these data to evaluate improvement in care quality.Institutional review board review is not required in these circumstances, per organizational policy.Our primary outcome was the number of Medicare feefor-service beneficiaries with an ACP claim in 2016.Secondary outcomes included beneficiary-level estimates of having a claim and the number of beneficiaries whose ACP service occurred during their annual wellness visit.We used χ 2 tests to compare beneficiary characteristics by ACP claim status.Using multivariable logistic regression, we identified variables associated with a beneficiary having any ACP claim, adjusting for age, sex, race/ethnicity, state of residence, dual-eligibility status (for Medicare and Medicaid), median income of resi-dence, and the presence of certain chronic conditions.Findings were considered significant at P < .05(2-sided).
What Should I Know About Opioids?
Authors: Michael A. Incze, Scott Steiger
Journal: JAMA Internal Medicine (2019)

What Are Opioids?Opioids are a group of substances derived from the plant-based chemical opium.Today many opioids are artificially created to have stronger orlonger-lastingeffects.Opioidsincludebothprescriptionmedications andillicitdrugs.Examplesincludemorphine,hydrocodone,oxycodone, codeine, hydromorphone, tramadol, fentanyl, and heroin.Opioids are addictive.Over time people's bodies require more and more opioid to achieve the same effects.Withdrawal symptoms can appear if opioids are not taken regularly.Opioids can cause death by slowing breathing and causing extreme sedation.
“Management Migration” in United States patients diagnosed with localized prostate cancer from 2010-2015.
Authors: Santino Butler, Idalid Ivy Franco, Amandeep R Mahal, Nina Niu Sanford, Quoc-Dien Trinh, Timothy Rebbeck, Paul L. Nguyen, Anthony Victor D'Amico, Brandon Arvin Virgil Mahal
Journal: Journal of Clinical Oncology (2019)

11 Background: National guidelines have increasingly supported active surveillance/watchful waiting (AS/WW) in low- and favorable intermediate-risk prostate cancer (PCa). It is unknown how these changes have influenced national management patterns across localized PCa. Therefore, we sought to define the U.S. trends in management of localized PCa across National Comprehensive Cancer Network (NCCN) risk groups. Methods: Using the novel and non-public Surveillance, Epidemiology, and End Results Program Prostate with AS/WW Database, we identified 164,760 men diagnosed with localized PCa and actively treated with either AS/WW, radical prostatectomy [RP], or radiation therapy [RT] from 2010-2015. Rates of initial management type over time, stratified by NCCN risk-category, were determined. Multivariable logistic regression defined adjusted odds ratios (AORs) and 95% confidence intervals (CI) for receipt of each initial management type, with year of diagnosis (2010-2015) as the independent variable of interest (Year 2010 = referent). Results: AS/WW utilization increased from 14.5% to 42.1% from 2010-2015 in low-risk disease (AOR 4.50 [95% CI 4.17–4.86, P &lt; 0.001]); conversely, RT and RP decreased from 38.0% to 26.6% (AOR 0.55 [0.51–0.59, P &lt; 0.001]), and from 47.4% to 31.3% (AOR 0.50, [0.47-0.54, P &lt; 0.001]), respectively (all P trends &lt; 0.001). AS/WW increased in intermediate-risk disease from 5.78% to 9.60% (AOR 1.83 [1.67–2.00, P &lt; 0.001]) and RT also decreased from 42.4% to 39.8% (AOR 0.81 [0.77–0.85], P &lt; 0.001; P trends &lt; 0.001)—Yet, there was no change in RP (51.8% vs. 50.6%; AOR 1.03 [0.98–1.09, P = 0.254]). Notably, while RP for high-risk disease increased from 38.0% to 42.8% (AOR 1.41 [1.30–1.53, P &lt; 0.001]), RT decreased from 60.1% to 55.0% (AOR 0.71 [0.65–0.77, P &lt; 0.001]; P trends &lt; 0.001). Conclusions: These findings capture the rapidly shifting landscape of management for localized PCa and are suggestive of “management migration”—where down-trending RP utilization in low-risk disease (in the setting of up-trending AS/WW) may drive non-evidence based management bias toward RP over RT in higher risk disease. These national patterns serve as a targetable trend that should be addressed.
Phase II study of everolimus in combination with octreotide LAR in first line setting for patients with neuroendocrine tumors (I.T.M.O. study): A 4-year update.
Authors: Emilio Bajetta, Laura Catena, Sara Pusceddu, Nicola Fazio, Giusi Blanco, Sergio Ricci, Michele Aieta, Francesca Pucci, Italo Sarno, Giandomenico Di Menna, Lorenzo Dottorini
Journal: Journal of Clinical Oncology (2015)

e15199 Background: We previously presented data of this phase II study showing that the combination of Everolimus and Octreotide LAR for advanced neuroendocrine tumors (NETs), in the first line setting, is an active and safe treatment. At a median follow-up period of 277 days, the median time to progression (TTP) and the overall survival (OS) have not been reached (ASCO 2013 Abs. 4136). Methods: We performed a phase II, multicenter trial using a Simon two-stage minmax design. Patients with advanced well differentiated, previously untreated neuroendocrine tumors of the gastroenteropancreatic (GEP) tract and of the lung, received Octreotide LAR 30 mg every 28 days in combination with Everolimus 10 mg per day, continuously. The primary endpoint was objective response rate (ORR). Currently we performed an analysis of “long responder” patients and of OS and TTP after 4 years. Results: A total of 50 patients (58% males) were enrolled; 36 (72%) of these patients have received treatment for more than 1 year. The median exposure to study drugs is 118 weeks (range 47-242). Currently 4 patients are still taking advantage from the above mentioned treatment. The primary tumor site was: liver 2 pts, pancreas 11 pts, small intestine 8 pts, lung 7 pts and unknown in 8 pts About 70% of these patients had no carcinoid Syndrome and 50% received surgery at the primary tumor site. The ORR was: CR 1 pt, PR 8 (22%) pts, SD 27 (75%) pts. The median TTP is 38 months (95% CI 19 – n.d.). The median OS has not been reached. Conclusions: Everolimus in combination with octreotide LAR has shown to be active in advanced NETs. The current analysis showed a further prolongation of TTP, and a long exposure to the study drug without major side effects in the long term. The treatment with two drugs has induced objective responses , but also long duration SD. Acknowledgements: Italian Trials in Medical Oncology (I.T.M.O.) group, Giacinto Facchetti Foundation and Novartis.
Treatment (tx) characteristics of patients (pts) with locally advanced or metastatic urothelial cancer (mUC) receiving atezolizumab (atezo) monotherapy in United States clinical practice.
Authors: Shivani K. Mhatre, Ching-Yi Chuo, Alicia K. Morgans, Osama E. Rahma, Russell Kent Pachynski, Jorge Martinalbo, Nicole N. Davarpanah, Jessica Davies
Journal: Journal of Clinical Oncology (2019)

381 Background: Atezo (anti–PD-L1) was the first immune checkpoint inhibitor approved for mUC. Here, we describe pt characteristics, time on tx (TOT) and distribution of tx cycles for pts receiving atezo in clinical practice, to complement data from clinical trial setting. Methods: Pts diagnosed with mUC who initiated atezo monotherapy in the first-line (1L) or second-line and beyond (2L+; prior platinum tx) settings on or before Jun 30, 2017, were identified from the US-based Flatiron Health electronic health record–derived database. Tx data were analyzed through Mar 31, 2018. TOT was defined as time from first to last atezo administration, plus 1 cycle length. Median TOT was calculated by tx line using the Kaplan-Meier method. Tx cycles were calculated by the number of atezo doses received during TOT. Corresponding results from global atezo clinical trials are presented. Results: Real-world data (RWD) from 312 pts (n = 102, 1L; n = 210, 2L+) met the study selection criteria (Table). Median TOT was 3 and 3.5 months in the 1L and 2L+ settings, respectively, with 95% CIs overlapping with the trial TOT data. A median of 4 cycles (IQR, 2-7, 1L; 2-9, 2L+) was administered in both settings. Conclusions: This is the first study of RW atezo use in mUC. The TOT with atezo observed in a US RW setting and the clinical setting (IMvigor210/IMvigor211) was similar. [Table: see text]
Impact of expression of Nuclear Factor Kappa B in locally advanced cervical caner patients treated with definitive chemoradiation on treatment outcomes.
Authors: Tamer Refaat, Eric Donald Donnelly, Sean Sachdev, Prarthana Dalal, Vamsi Parimi, Ahmed Elgowily, Samar Elachy, Irene B. Helenowski, Jeffrey Gross, John Robert Lurain, Jonathan Blake Strauss, Gayle Woloschak, Jian-Jun Wei, William Small
Journal: Journal of Clinical Oncology (2015)

e16589 Background: This study aimed to validate previous report by Garg et al. that demonstrated an association between pretreatment Nuclear factor kappa B (NFkB) expression in locally advanced cervical cancer patients treated definitively with concurrent chemoradiation (CRT) and treatment outcomes; including overall survival (OS), progression free survival (PFS), distant metastases free survival (DMFS), and local-regional control (LC). Methods: This IRB approved study included locally advanced cervical cancer patients treated definitively and consecutively with CRT. Evaluation of cytoplasmic immunoreactivity for NFkB was performed, applying the same immunohistochemical (IHC) staining protocol of Garg et al., and scored semi-quantitatively by 3 pathologists, blinded to the treatment outcomes, and incorporated both the intensity and percentage of immunoreactivity in invasive carcinoma (H-score). Treatment-outcomes were reviewed and reported. Outcomes were stratified by NFkB overexpression. OS, PFS, LC, and DMFS rates were obtained via the Kaplan-Meier method and differences between groups were evaluated by the log-rank test. Results: Fifteen (53.6%), and 13 patients (46.4%) had NFkB H-index >180 and < 180, respectively. The mean age was 51 + 10 years, and the 5-year OS, PFS, LC, and DMFS for the entire cohort were 57.18%, 48.07%, 72.11%, and 62.85%, respectively. For patients with pretreatment NFKB H-index >180, and < 180, the 5-year OS were 49.45% (CI: 19.53%, 73.81%), and 64.10% (CI: 28.18%, 85.55%) (P-value = 0.34), PFS were 39.29% (CI: 11.43%, 66.87%), and 57.69% (CI: 24.95%, 80.42%) (P-value = 0.21), LC were 78.57% (CI: 47.25%, 92.54%), and 69.23% (CI: 37.34%, 87.18%) (P-value = 0.86), and DMFS were 49.11% (CI: 14.00%, 77.32%), and 76.92% (CI: 44.21%, 91.91%) (P-value = 0.18), respectively. There was a trend toward a worse DMFS, PFS, and OS that was not statistically significant. Conclusions: This study demonstrated that in spite of applying the same IHC protocol, pretreatment NFkB overexpression was not significantly associated with poor treatment outcomes in locally advanced cervical cancer patients treated definitively with CRT.
Comparing costs of radical cystectomy versus trimodal therapy for patients diagnosed with localized muscle-invasive bladder cancer.
Authors: Daniel Phillips, Tamer Dafashy, Yong Shan, Mohamed Danny Ray-Zack, Hogan K Hudgins, Usama Jazzar, Douglas S. Tyler, Stephen J. Freedland, Todd A. Swanson, Jacques G. Baillargeon, Jim C. Hu, Sapna Kaul, Ashish M. Kamat, John L. Gore, Hemalkumar B Mehta, Stephen Bentley Williams
Journal: Journal of Clinical Oncology (2019)

e16021 Background: Earlier studies on the cost of muscle-invasive bladder cancer treatments lack granularity and are limited to 180 days. The objective of this study is to compare the one-year costs associated with trimodal therapy versus radical cystectomy, accounting for survival and intensity effects on total costs. Methods: This cohort study used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Data analysis was performed from March 5, 2018 through December 4, 2018. A total of 2,963 patients aged 66-85 years diagnosed with clinical stage T2-4a muscle-invasive bladder cancer from January 1, 2002 through December 31, 2011. Total Medicare costs within one year of diagnosis following radical cystectomy versus trimodal therapy were compared using inverse probability of treatment-weighted (IPTW) propensity score models, which included a two-part estimator to account for intrinsic selection bias. Results: Median costs were significantly higher for trimodal therapy than radical cystectomy in 90 days ($83,754 vs. $68,692; median difference $11,805, 95% CI $7,745 to $15,864), 180 days ($187,162 vs. $109,078; median difference $62,370, 95% CI $55,581 to $69,160), and 365 days ($289,142 vs. $148,757; median difference $109,027, 95% CI $98,692 to $119,363), respectively. Outpatient care, radiology, medication expenses and pathology/laboratory costs contributed largely to the higher costs associated with trimodal therapy. On IPTW-adjusted analyses, patients undergoing trimodal therapy had $129,854 (95% CI $115,793-$145,299) higher costs compared with radical cystectomy one year after diagnosis. Conclusions: Compared to radical cystectomy, trimodal therapy was associated with higher costs among patients with muscle-invasive bladder cancer. Extrapolating cost figures resulted in nationwide excess spending of $444 million for trimodal therapy compared with radical cystectomy for patients diagnosed in 2017.