tbuckley/cabot-search huggingface dataset:
Evolving epidemiology of lung cancer in California: 1990-2014.
Authors: Kevin Pan, Amy Klapheke, Rosemary Donaldson Cress, Tianhong Li
Journal: Journal of Clinical Oncology (2018)

e18724 Background: Over the last few decades, there have been tremendous advances in the knowledge, technology, and treatment for lung cancer. The objective of this study was to analyze the impact of these advances on the epidemiology of lung cancer in California. Methods: Using data from the California Cancer Registry, we analyzed annual trends in lung cancer incidence, diagnosis, staging, and survival during 1990 to 2014. Changes in age-adjusted incidence and mortality were assessed by demographics and histologic subtype. Changes in stage at diagnosis were analyzed over the study period to determine possible stage migration patterns. For patients diagnosed with metastatic disease, relative 5-year survival was calculated overall and by histologic subtype. Results: A total of 335,478 primary lung cancer cases were identified between 1990 and 2014. The lung cancer incidence dropped 47.3% from 80.1 to 42.2 cases per 100,000 patient-years, representing an annual decrease of 2.4% (95% CI: -2.6%, -2.2%). Mortality decreased 46.0% from 76.0 to 42.9 per 100,000 patient-years, representing an annual percent decrease of 0.8 (95% CI: -1.1%, -0.5%). Males experienced a 57.5% drop in incidence compared to a 34.3% decrease in women. Incidence was highest among non-Hispanic blacks, while Asians/Pacific Islanders and Hispanics had the lowest. Adenocarcinoma was the most commonly diagnosed histology and had the smallest decrease in incidence. The proportion of cases diagnosed at the remote stage increased by about 8%, while unstaged diagnoses decreased over time. Over the study period, survival improved for patients diagnosed with adenocarcinoma, but there was no significant improved in survival for patients with SCLC or squamous cell carcinoma. Conclusions: There has been steadily decrease in the incidence and mortality of lung cancer in California between 1990 and 2014. While adenocarcinoma remains the predominant histological type, its survival rate had been improved after 2004, which coincides with the treatment advances of molecularly targeted therapy and chemotherapy. Further improvement in lung cancer epidemiology by lung cancer screening and immunotherapy is highly anticipated.
Abstract 16684: Divergent Left Ventricular Remodeling Pathways in Chronic Primary and Secondary Mitral Regurgitation
Authors: Daisuke Onohara, Weiwei Shi, Roberto Hernandez-Merlo, Vinod H Thourani, Eric L Sarin, Robert A Guyton, Muralidhar Padala
Journal: Circulation (2016)

Introduction: Left ventricular (LV) dilatation and its transition to decompensatory heart failure (HF) differs in patients with primary and secondary mitral regurgitation (MR). Mapping the temporal...
TCT-489 Use of a Percutaneous Left Ventricular Assist Device for Patients with Cardiogenic Shock
Authors: Waqas Malick, Shayan Nabavi Nouri, Koji Takeda, Veli Topkara, Ellie Coromilas, Dimitri Karmpaliotis, Hiroo Takayama, Yoshifumi Naka, Paolo Colombo, Manish Parikh, Susheel Kodali, Philip Green, Torsten Vahl, Ziad Ali, Martin Leon, Jeffrey W. Moses, Ajay Jayant Kirtane, Arthur Reshad Garan
Journal: Journal of the American College of Cardiology (2018)
Phase 1b study of TAK-659 + nivolumab (nivo) in patients (pts) with advanced solid tumors.
Authors: Dejan Juric, Anthony J. Olszanski, Ulka N. Vaishampayan, Cong Li, Shining Wang, Yaping Shou, Yuanxin Rong, John Nemunaitis
Journal: Journal of Clinical Oncology (2018)

e15124 Background: TAK-659 is an investigational, reversible, potent dual inhibitor of SYK and FLT-3. In preclinical studies, TAK-659 in combination with anti-PD-1 resulted in > 50% complete regressions in mice bearing syngeneic tumors (CT-26 colon, A20 lymphoma, MH-22A liver). We report the safety and efficacy of TAK-659 + nivo in pts with advanced solid tumors from this ongoing first-in-human phase 1b study (NCT02834247). Methods: Pts with advanced solid tumors (failed ≥1 prior therapy) were enrolled to receive oral TAK-659 (60–100 mg QD) in a 3+3 schema and nivo 3 mg IV on days 1 and 15 of 28-day cycles. The primary endpoint is maximum tolerated dose (MTD) of TAK-659 + nivo; secondary endpoints include adverse events (AEs) and TAK-659 pharmacokinetics assessed during cycle 1 on days 1 and 15 using non-compartmental analysis. Results: As of 15-Nov-2017, 19 pts (median age 56 yrs [range 23–76]; 32% male; 63% ≥4 prior therapies; 95% stage IV disease; 90% ECOG PS 1) with solid tumors (including breast [26%], ovary [16%], colon, pancreas [each 11%]) received TAK-659 60 mg (n = 6), 80 mg (n = 8), 100 mg (n = 5) and nivo. Pts received a median of 2 cycles (range 1–6); 11 pts discontinued (55% due to progressive disease [PD]). TAK-659 100 mg + nivo exceeded the MTD; 1 pt reported a DLT of Gr 3 pyrexia and 2 pts reported Gr 3 myocarditis and Gr 3 left ventricular systolic dysfunction that were considered nivo-related per investigator. 79% of pts reported AEs including increased AST (53%), increased ALT (47%), anemia, pyrexia (each 42%) and increased amylase (37%). 74% of pts had Gr ≥3 AEs; 32% of pts had Gr ≥3 related AEs including lipase increase and anemia (each 20%); 53% of pts had serious AEs including pyrexia (n = 3), nausea and sepsis (each n = 2). 3 pts had AEs resulting in discontinuation of TAK-659, nivo or both. Two pts died on study due to PD (TAK-659 80 mg and 100 mg + nivo). Following co-administration of TAK-659 + nivo, TAK-659 was absorbed quickly (median tmax ≈ 2 h) with increased plasma exposure over the 60–100 mg dose range. One pt with metastatic breast cancer and ≥6 prior therapies achieved a partial response at cycle 4 and is currently ongoing at cycle 7. Conclusions: TAK-659 100 mg + nivo exceeded the MTD. Further investigation of TAK-659 60 mg and 80 mg cohorts is ongoing. Clinical trial information: NCT02834247.
Treatment patterns for metastatic castration-resistant prostate cancer (mCRPC) in oncology (ONC) urology (URO) practices: Data from the PROCEED registry.
Authors: Nicholas J. Vogelzang, Andrew J. Armstrong, Celestia S. Higano, A. Oliver Sartor, Christopher Michael Pieczonka, Raoul S. Concepcion, Ronald F. Tutrone, Carl A. Olsson, James L. Bailen, David F. Penson, Nancy N. Chang, Jennifer Susan LIll, Robert Claude Tyler, Matthew R. Cooperberg
Journal: Journal of Clinical Oncology (2016)

e16503 Background: Sipuleucel-T (sip-T) is an FDA-approved autologous cellular immunotherapy targeting prostatic acid phosphatase in select men with mCRPC. The phase 4 PROCEED (NCT01306890) registry includes US community and academic ONC and URO practices. Enrollment is complete, and patients (pts) who received sip-T are being followed for adverse events, overall survival (OS), and treatment patterns Methods: PROCEED enrolled men with mCRPC aged ≥ 18 y scheduled to receive sip-T or who had initiated sip-T within the previous 6 mo. Prescribing patterns for mCRPC pre– and post–sip-T were documented in ONC and URO practices. Anticancer interventions (ACIs) post–sip-T, defined as agents with known OS benefit (abiraterone acetate [ABI], enzalutamide [ENZ], docetaxel [DOC], cabazitaxel [CAB], and radium-223), and time to first ACI (tACI), measured from last sip-T infusion, were examined. Results: One hundred ninety-two sites enrolled. Of the 1,902 pts who received ≥ 1 sip-T infusion, 1,248 (65.6%) pts were treated in ONC practices and 654 (34.4%) in URO practices. ONC practices were more likely to prescribe first-generation anti-androgens (p < 0.001), estrogens (p < 0.05), and ketoconazole (p < 0.001) prior to sip-T. Post–sip-T interventions in ONC vs URO practices were ABI (51.0% vs 47.7%), ENZ (38.5% vs 25.7%, p < 0.001), DOC (37.1% vs 24.0%, p < 0.001), and CAB (15.5% vs 4.4%, p < 0.001).MediantACI was shorter in ONC (6.4 mo) compared with URO (8.8 mo) practices (p < 0.001). However, prostate-specific antigen (PSA) levels were similar between groups at first tACI (60.6 ng/mL [ONC] vs 54.4 ng/mL [URO]). Higher baseline alkaline phosphatase and PSA and younger age were associated with shorter tACI. At 2 y post–sip-T, 15.5% of ONC and 23.9% of URO pts had not received an ACI. Conclusions: Pts treated in ONC practices received more secondary hormonal manipulations prior to sip-T. Additionally, these pts were significantly more likely to receive an ACI subsequent to sip-T in a shorter time period. These data suggest a greater propensity for sequencing of mCRPC treatments in ONC practices in pts with similar disease characteristics at the time of sip-T administration. Clinical trial information: NCT01306890.
Prevalence of <i>KRAS</i> and <i>NRAS</i> mutations in patients with metastatic colorectal cancer in Argentina: A multicenter prospective observational study.
Authors: Gabriela Marechal, Ignacio Casarini, Astegiano Mario Gabriel Gabriel, Alejandra Pini, Oscar D. Duarte, Andres Eduardo Flores, Diego Bashkansky, Paul Cifuentes, Indira Venkatasubramanian, Mario Edmundo Barugel
Journal: Journal of Clinical Oncology (2018)

e15608 Background: Analysis of RAS mutations in specific populations is important as it is a predictive biomarker in the selection of RAS WT patients for treatment with EGFRI(s). There are currently no robust RAS (KRAS and NRAS) mutation data available for Argentinian patients with mCRC that we know of. In an effort to help optimize 1st-line treatment in these patients, we conducted a large prospective study to estimate the prevalence of RAS mutations in this population. Methods: Prevalencia de Mutaciones RAS en Argentina (PREMURA) is a descriptive non-interventional epidemiological study conducted over 24 months in Argentinian patients with mCRC to assess the correlations between RAS mutational status and clinical variables (age, gender, stage, metastasis location, and primary tumor site). All mutational analyses were conducted in a centralized lab using RT-PCR techniques. Results: Of the 2119 patients enrolled, 1936 (91.36%) had evaluable data. The majority (1306 [67.5%]) of patients were diagnosed in stage IV. Overall, 863 (45%) patients had left colon tumors, 580 (30%) had right colon tumors, and 396 (20%) had rectal tumors. RAS mutations were detected in 34.6% (31.8% with KRAS and 2.8% of NRAS) patients. The observed KRAS mutations and frequencies were as follows—G12A: 179/ 578 (31%), G12V: 138/ 578 (24%), and G12D: 69/578 (12%). The observed NRAS mutations and frequencies were as follows—Q61K: 7/47 (15%), G12A: 6/47 (13%), G12D and G13D: 5/47 (11%). In multivariate analyses, no significant correlations were found between RAS mutations and assessed clinical variables. Conclusions: To our knowledge, this is the first study with robust data on RAS mutations in patients with mCRC in Argentina. Results showed a low prevalence of mutations compared to other populations, with KRAS G12A being the most frequent. For variables such as primary location, demographic features, and metastatic sites, mutational frequencies were similar to those observed in other populations. The lower prevalence of mutations should be taken into consideration and highlight the importance of RAS testing in Argentina for the selection of best 1st-line treatment option in mCRC.
Tardive dyskinesia risk with first‐ and second‐generation antipsychotics in comparative randomized controlled trials: a meta‐analysis
Authors: Maren Carbon, John M. Kane, Stefan Leucht, Christoph U. Correll
Journal: World Psychiatry (2018)

Tardive dyskinesia (TD) risk with D2/serotonin receptor antagonists or D2 receptor partial agonists (second-generation antipsychotics, SGAs) is considered significantly lower than with D2 antagonists (first-generation antipsychotics, FGAs). As some reports questioned this notion, we meta-analyzed randomized controlled studies (RCTs) to estimate the risk ratio (RR) and annualized rate ratio (RaR) of TD comparing SGAs vs. FGAs and SGAs vs. SGAs. Additionally, we calculated raw and annualized pooled TD rates for each antipsychotic. Data from 57 head-to-head RCTs, including 32 FGA and 86 SGA arms, were meta-analyzed, yielding 32 FGA-SGA pairs and 35 SGA-SGA pairs. The annualized TD incidence across FGA arms was 6.5% (95% CI: 5.3-7.8%) vs. 2.6% (95% CI: 2.0-3.1%) across SGA arms. TD risk and annualized rates were lower with SGAs vs. FGAs (RR=0.47, 95% CI: 0.39-0.57, p<0.0001, k=28; RaR=0.35, 95% CI: 0.28-0.45, p<0.0001, number-needed-to-treat, NNT=20). Meta-regression showed no FGA dose effect on FGA-SGA comparisons (Z=-1.03, p=0.30). FGA-SGA TD RaRs differed by SGA comparator (Q=21.8, df=7, p=0.003), with a significant advantage of olanzapine and aripiprazole over other non-clozapine SGAs in exploratory pairwise comparisons. SGA-SGA comparisons confirmed the olanzapine advantage vs. non-clozapine SGAs (RaR=0.66, 95% CI: 0.49-0.88, p=0.006, k=17, NNT=100). This meta-analysis confirms a clinically meaningfully lower TD risk with SGAs vs. FGAs, which is not driven by high dose FGA comparators, and documents significant differences with respect to this risk between individual SGAs.
Atypical neurofibromas in neurofibromatosis 1 (NF1): Clinical, imaging and pathologic characteristics.
Authors: Christine Higham, Sucharita Bhaumik, Eva Dombi, Andrea Baldwin, Markku Miettinen, Anne Goodwin, Joanne Derdak, Brigitte C. Widemann
Journal: Journal of Clinical Oncology (2016)

11035 Background: NF1 is a tumor predisposition syndrome caused by mutations in the NF1tumor suppressor and associated with development of benign and malignant peripheral nerve sheath tumors (MPNST). MPNST often develop in pre-existing plexiform neurofibromas (PN) and have poor prognosis. Atypical neurofibromas (ANF) have been described a precursor lesions for MPNST, making early detection and management of ANF a possible strategy to prevent MPNST. Little is known about the presentation and natural history of ANF. Our aim was to characterize ANF and identify approaches for management of these lesions. Methods: Patients with NF1 and PN are followed on the NCI NF1 Natural History study with clinical evaluations, whole body MRI with volumetric analysis of total PN burden, and fluorodeoxy-glucose (FDG) PET. Concerning lesions (distinct nodular, well demarcated, > 3cm,lacking central dot sign) underwent biopsy or resection if they were associated with rapid growth or symptoms. ANF diagnosis was established by pathology. Results: Of154 patients, 24 patients underwent biopsy/resection of concerning lesions. In 17 patients (10M/7F; median age 20 yrs, range 7-51, median total PN burden 1700ml) pathology confirmed 24 ANF (5 neck, 4 chest, 5 abdomen/pelvis, 10 extremity). On MRI all ANF appeared as distinct nodular lesions and were FDG-avid (median SUVmax of 7.2, range 2.7-16.7). 11 ANF were associated with pain, 5 with weakness, 12 were palpable, and 8 had no clinical signs. With median follow-up time of 2.3 years (0-9.9 yrs), completely resected ANF (n = 10) have not recurred, but 2 partially resected ANF demonstrated re-growth. One ANF transformed into high-grade MPNST 3 years after biopsy and resulted in patient’s death. 3 patients had a history of MPNST in a different location prior to ANF diagnosis, and 3 after ANF diagnosis. Conclusions: In NF1 patients with substantial PN burden, most ANF were first noted on MRI based on nodular appearance. Lesion growth, PET avidity, and pain should raise concern for ANF. Complete resection of ANF may reduce the risk for malignant transformation. Longitudinal monitoring will allow to more completely describe ANF. An international cohort has been established to further characterize ANF.
Safety and feasibility of outpatient induction chemotherapy with CPX-351 in selected older adult patients with newly diagnosed AML.
Authors: Timothy Edward Kubal, Christopher Salamanca, Rami S. Komrokji, David A Sallman, Kendra Lynn Sweet, Eric Padron, Alan F. List, Jeffrey E. Lancet
Journal: Journal of Clinical Oncology (2018)

e19013 Background: Liposomal Daunorubicin and Cytarabine (Vxyeos) was recently approved for the treatment of Therapy Related Acute Myeloid Leukemia and AML with Myelodysplastic Related Changes having demonstrated superior overall survival (OS) when compared to traditional daunorubicin + cytarabine induction (7+3). Beyond improved OS, there are other potential benefits. While 7+3 requires hospitalization, Vyxeos is delivered over 90 minutes on days 1, 3 and 5. With a goal of reducing the duration of hospitalization, we piloted outpatient induction chemotherapy with Vyxeos. Methods: The Inpatient/Outpatient (IPOP) program involves close monitoring of patients who receive traditionally inpatient chemotherapy as outpatients. Candidates for Vyxeos induction were screened for IPOP. Those with increased risk for tumor lysis including white count > 50K, increased creatinine/uric acid, active cardiopulmonary symptoms, ECOG > 2, or those who lacked a caregiver or were unable to reside within 60 minutes of the treating facility were excluded. Eligible patients received Vyxeos through IPOP. Daily CBC, CMP, uric acid, and phosphorus were performed and patients were evaluated each day. On day 6, each patient was admitted to the hospital for continued care. Results: Twenty-two patients received a full course of induction with Vyxeos. Fourteen (64%) received induction in IPOP and 8 received inpatient induction (Median Age: 68.6,65.1 respectively). 1 of 14 outpatients (7%) was admitted on day 2 of induction due to hypotension and a fall. The remaining 13 outpatients (93%) tolerated outpatient Vyxeos and were hospitalized on day 6 as planned for continued care. One patient who received Vyxeos as an inpatient died prior to Day 30. Mean hospitalization duration was 28.3 and 30.5 days for IPOP and Inpatient delivery respectively. Conclusions: In this pilot study, outpatient delivery of liposomal daunorubicin and cytarabine in selected patients appears to be both feasible and safe, significantly reducing the length of hospitalization for induction chemotherapy. Future analyses will study longer-term patient outcomes and financial implications utilizing this approach.
A phase 1 safety study of SBP-101, a polyamine metabolic inhibitor, for pancreatic ductal adenocarcinoma (PDA).
Authors: Niall C. Tebbutt, Dusan Kotasek, Mitesh J. Borad, Erkut Hasan Borazanci, Sheri Lynn Smith, Ajit K. Shah, Michael J Walker, Michael T. Cullen, Suzanne Gagnon
Journal: Journal of Clinical Oncology (2018)

e16231 Background: SBP-101 (diethyl dihydroxyhomospermine), a polyamine (PA) analogue of spermine, inhibited growth in 6 human PDA cell lines and 3 murine xenograft tumor models. A Phase 1 dose escalation study assessed the safety, tolerability and pharmacokinetics (PK) of SBP-101 in previously treated patients with locally advanced or metastatic PDA. Methods: In a modified 3x3 dose escalation scheme, daily subcutaneous injections of SBP-101 were dosed at 0.05, 0.1, 0.2, 0.4 or 0.8 mg/kg, Monday-Friday for 3 weeks, followed by 5 weeks of observation (1cycle), for 1 or 2 cycles. Safety and tolerability were evaluated by clinical and laboratory assessments. PK was evaluated on Days 1 and 18 of cycle 1. Efficacy was assessed by RECIST criteria and overall survival. Results: Twenty-nine patients were enrolled in 5 cohorts: (1: N = 3; 2: N = 5; 3: N = 4; 4: N = 7; 5: N = 10). Twenty-six had ≥2 prior chemotherapy regimens. Drug-related toxicity in cohorts 1-4 was minimal, although one patient in cohort 4 developed focal pancreatitis at the site of the tumor at 2.3 months. Most common adverse events (AEs) were abdominal pain, constipation, decreased appetite, dehydration, diarrhea, fatigue, nausea and vomiting. Most were grades 1 or 2 or considered unlikely or not related. No drug-related bone marrow suppression or peripheral neuropathy was seen at any dose. No DLTs occurred in cohorts 1-4. Three patients in cohort 5 developed serious adverse events considered dose limiting toxicities: bacterial sepsis with metabolic acidosis (N = 1), hepatic and renal failure with elevated lipase (N = 1) and superior mesenteric vein thrombosis with metabolic acidosis (N = 1). Plasma Cmax and AUC0-t increased linearly with dose. Stable disease occurred in 2 patients each in cohorts 3 and 4, and in 4 patients in cohort 5. Median survival in cohort 3 was 5.9 months. Conclusions: SBP-101 was well tolerated in this study at dose levels 1-4; 0.8 mg/kg exceeded the maximum tolerated dose (MTD). Best tumor response and survival occurred with 0.2 mg/kg/day. The low incidence of AEs below the MTD and absence of bone marrow toxicity or peripheral neuropathy suggest the potential for SBP-101 as an addition to front line treatment for PDA and justify a combination study. Clinical trial information: NCT02657330.
Adolescent Cognitive Aptitudes and Later-in-Life Alzheimer Disease and Related Disorders
Authors: Alison R. Huang, Kiersten L. Strombotne, Elizabeth Mokyr Horner, Susan J. Lapham
Journal: JAMA Network Open (2018)

Low early-life cognitive ability is a potential early marker of dementia risk in later life. Previous studies use only global measures of general intelligence and/or study this relationship in gender-specific samples. The contribution of early-life performance on specific cognitive abilities, such as language, reasoning, and visualization aptitudes, to indicating future dementia risk is unknown.To investigate the association between adolescent cognitive ability and Medicare-recorded Alzheimer disease and related disorders (ADRD) using both general and specific measures of cognitive ability and to explore these associations separately in men and women.Population-based cohort study from the Project Talent-Medicare linked data set, a linkage of adolescent sociobehavioral data collected from high school students in 1960 to participants' 2012 to 2013 Medicare Claims and expenditures data. The association between adolescent cognitive ability and risk of ADRD in later life was assessed in a diverse sample of 43 014 men and 42 749 women aged 66 to 73 years using a series of logistic regressions stratified by sex, accounting for demographic characteristics, adolescent socioeconomic status, and regional effects. Data analysis was conducted from November 2017 to March 2018.Presence of Medicare-reported ADRD.Overall, 1239 men (2.9%) and 1416 women (3.3%) developed ADRD. Lower mechanical reasoning was associated with increased odds of ADRD in men (odds ratio, 1.17; 95% CI, 1.05-1.29), and lower memory for words in adolescence was associated with increased odds of ADRD in women (odds ratio, 1.16; 95% CI, 1.05-1.28). Lower performance on several other language, reasoning, visualization, and mathematic aptitudes in adolescence showed prominent, but weaker, associations with odds of ADRD.This work contributes to the understanding of early-life origins of ADRD risk. The results suggest specific measures of cognitive ability may contribute to very early identification of at-risk subgroups who may benefit from prevention or intervention efforts.