tbuckley/cabot-search huggingface dataset:
Let Us Not Forget the Long-term Safety Concerns of Sacubitril/Valsartan—Reply
Authors: Milton Packer
Journal: JAMA Cardiology (2017)

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Cisplatin with or without rucaparib after preoperative chemotherapy in patients with triple negative breast cancer: Final efficacy results of Hoosier Oncology Group BRE09-146.
Authors: Kathy Miller, Yan Tong, David R Jones, Tom Walsh, Michael A. Danso, Cynthia X. Ma, Paula Silverman, Mary-Claire King, Sunil S. Badve, Susan M. Perkins
Journal: Journal of Clinical Oncology (2015)

1082 Background: Patients (pts) with triple negative breast cancer (TNBC) with residual disease after neoadjuvant therapy have a high risk of recurrence. Methods: Pts with BRCA mutations and/or TNBC with lymph node (LN) or > 2 cm of invasive disease after anthracycline (A) and/or taxane (T) neoadjuvant therapy were assigned 1:1 to cisplatin (C: 75 mg/m2D1 q3 wks x 4) +/- rucaparib (R: 24-30 mg IV D1,2,3 q3 wks x 4 followed by R 30 mg IV or 100 mg orally wkly for 24 wks). BROCA analysis identified deleterious germline mutations. Pharmacokinetic sampling to assess R exposure was obtained during IV and oral dosing. The primary objective was 2-yr DFS. Results: From Feb 2010 to May 2013, 128 pts were enrolled. Median tumor size at surgery was 1.9 cm (0-11.5) with median LN involvement 1 (0-38); median Residual Cancer Burden (RCB) score was 2.6. Neoadjuvant therapy included A in 57% and T in 91%. 86.7% of pts received radiation therapy prior to entry. BROCA identified deleterious mutations (8 BRCA 1, 12 BRCA 2, 2 BRIP1) in 22/101 (22%) pts. 8 pts randomized to C and 1 to CR did not start therapy. Toxicity was similar in both arms. Despite frequent dose reductions (21% of pts.) and delays (43.8% of pts), 73% of pts completed planned C. R dose reduction was uncommon (6%). 11 pts (17.5%) assigned to CR did not begin R monotherapy; 51% of pts completed the planned 24 wks. Rucaparib exposure was limited with median(min,max) concentration 275(82,4694) ng/mL post-infusion on Day 3. Exposure was less during oral maintenance (median concentration 47(19,185) ng/mL two hours post-treatment). 2-yr DFS was similar in both arms (C-58.3%, CR-63.1%; p = 0.43). In an exploratory analysis of patients receiving A-containing neoadjuvant therapy, 2-year DFS was significantly improved with CR (55.9% vs. 69.9%; p = 0.04). Mutation status did not impact DFS. Conclusions: The addition of low dose R did not impact the toxicity of cisplatin or improve 2-yr DFS. The dose of R used in this study was substantially less than the current phase II monotherapy dose (600 mg orally twice daily) and may not have been sufficient to inhibit PARP activity. Clinical trial information: NCT01074970.
Protracted administration of low doses of temozolomide (TMZ) in the treatment of relapse glioblastoma (GBM) enhances the antitumor activity of this agent
Authors: A. D’Amico, M. Gabbani, S. Dall’oglio, L. Cristofori, S. Turazzi, E. Sanzone, S. Maluta
Journal: Journal of Clinical Oncology (2006)

1572 Background: The efficacy of temozolomide (TMZ) is strictly related to the possibility to reach and maintain high and prolonged cellular drug concentrations in the target tissue. Evidence exists demonstrating that the achievement of this goal and the subsequent activity of TMZ are categorically schedule dependent. Aim of the present randomized phase II study is to verify whether a treatment schedule with TMZ appropriately modified induces better response rates along with a decrease of mielotoxicity as compared to the conventional one. Methods: Twenty patients (5 F/15 M), median age of 53 years (range 35–74), median Karnofsky PS 90 (range 70–100), with GBM in progression after surgery and adjuvant RT have been treated as follows: Schedule A - TMZ for 5 days in a 28-day cycle, at the dose of 150 mg/m 2 /d at the first cycle and of 200 mg/m 2 /d thereafter, up to a total of 8 cycles. Schedule B - TMZ for 7 days alternating with 7 days of rest up to a total of 12 cycles: the starting dose of TMZ at the first cycle was 50 mg/m 2 /d with progressive serial dose escalations of 25 mg/m 2 /d in the subsequent ones until the achievement of the dose of 150 mg/m 2 /d at the 5 th cycle, and then keeping this regimen until the 12 th cycle. Results: They are summarized in the table : Severe thrombocytopenia and stomatitis have been observed only in patients treated with Schedule A. Conclusions: These preliminary results, which deserve to be confirmed in a larger sample size, indicate that the treatment with TMZ on alternate week basis is strongly interesting and promising. In spite of the modality and the small number of patients included in this study, which doesn’t allow a direct comparison between two different treatments, it should be noted that schedule B achieved a 2-year OS and PFS rate of 40% and 20% respectively, compared to 10% and 0% of schedule A. [Table: see text] No significant financial relationships to disclose.
Noninvasive Detection of Ibrutinib Resistance in Non-Hodgkin Lymphoma Using Cell-Free DNA
Authors: Florian Scherer, David M. Kurtz, Aaron M Newman, Alexander Craig, Henning Stehr, Li Zhou, Cynthia Glover, Holbrook Kohrt, Ronald Levy, Maximilian Diehn, Ash A. Alizadeh
Journal: Blood (2016)
Factors associated with life expectancy (LE) &lt; 3 months (mo) among older adults receiving palliative chemotherapy (chemo).
Authors: Arti Hurria, Molly Hardt, William P. Tew, Supriya Gupta Mohile, Cynthia Owusu, Cary P. Gross, Ajeet Gajra, Stuart M. Lichtman, Vani Katheria, Rupal Ramani, Laura Zavala, Heidi D. Klepin
Journal: Journal of Clinical Oncology (2012)

9034 Background: Optimal treatment decision-making for older adults with advanced cancer requires a better understanding of risk factors associated with limited LE. Our objective was to evaluate the factors associated with LE&lt; 3mo among patients (pts) age &gt; 65 who were beginning a new chemo regimen. Methods: We conducted a secondary analysis of a multi-site cohort study of pts ≥65 years receiving chemo (Hurria et al, JCO 2011). This analysis included only pts receiving palliative chemo. Bivariate analysis and multivariate logistic regression were utilized to identify factors associated with LE &lt; 3 mo including: sociodemographics, labs [hemoglobin (Hb), albumin, liver function, creatinine clearance], and geriatric assessment (GA) variables (functional status, social support, comorbidity, psychological, cognitive, and nutritional status). Results: Among 290 pts (median age 72 [range 65-91], 52% female) with advanced cancer (gastrointestinal 28%, lung 31%, breast/gyn 22%, other 19%), 13.4% died within 3 mo of chemo initiation. In bivariate analysis, pts with LE &lt; 3mo were more likely (p&lt;0.05 for each variable) to have lower albumin and Hb, unintentional weight loss, and poorer physical function [defined as need for assistance with instrumental activities of daily living (IADL), lower score on Medical Outcomes Survey (MOS) Physical Health, MD-rated and patient-rated Karnofsky performance status (KPS), and MOS Social Activity score]. Measures of functional status were highly correlated with one another and therefore one functional status measure (in addition to measures significant in bivariate analysis) was included in each multivariate logistic regression. In multivariate analyses, (controlling for age, comorbidity, and line of chemo) poorer physical function (as evaluated by need for assistance with IADLs, MOS Physical &lt;70, or MD-rated KPS &lt;70) and unintentional weight loss were independently associated with LE&lt;3mo (p&lt;0.05). Conclusions: Among older pts with advanced cancer who were prescribed a new chemo regimen for palliative intent, physical function measures (as evaluated by geriatric assessment and MD report) and unintentional weight loss were associated with LE &lt; 3months.
Electrophysiologically Guided Thoracoscopic Surgery for Advanced Atrial Fibrillation
Authors: Antoine H.G. Driessen, Wouter R. Berger, Dean R.P.P. Chan Pin Yin, Femke R. Piersma, Jolien Neefs, Nicoline W.E. van den Berg, Sébastien P.J. Krul, WimJan P. van Boven, Joris R. de Groot
Journal: Journal of the American College of Cardiology (2017)
Putting Patients First by Reducing Administrative Tasks in Health Care: A Position Paper of the American College of Physicians
Authors: Shari M. Erickson, Brooke Rockwern, Michelle Koltov, Robert M. McLean
Journal: Annals of Internal Medicine (2017)

This American College of Physicians (ACP) position paper, initiated and written by ACP's Medical Practice and Quality Committee and approved by the Board of Regents on 21 January 2017, reports policy recommendations to address the issue of administrative tasks to mitigate or eliminate their adverse effects on physicians, their patients, and the health care system as a whole. The paper outlines a cohesive framework for analyzing administrative tasks through several lenses to better understand any given task that a clinician and his or her staff may be required to perform. In addition, a scoping literature review and environmental scan were done to assess the effects on physician time, practice and system cost, and patient care due to the increase in administrative tasks. The findings from the scoping review, in addition to the framework, provide the backbone of detailed policy recommendations from the ACP to external stakeholders (such as payers, governmental oversight organizations, and vendors) regarding how any given administrative requirement, regulation, or program should be assessed, then potentially revised or removed entirely.
The role of social exposure to smoking on smoking cessation in adult cancer survivors.
Authors: Lawson Eng, Dan Pringle, Xin Qiu, Xiaowei Shen, Chongya Niu, Mary Mahler, Oleksandr Halytskyy, Rebecca Charow, Christine Lam, Ravi M. Shani, Jodie Villeneuve, Kyoko Tiessen, M Catherine Brown, Shabbir M.H. Alibhai, Jennifer M. Jones, Doris Howell, David P. Goldstein, Wei Xu, Peter Selby, Geoffrey Liu
Journal: Journal of Clinical Oncology (2013)

9536 Background: We previously described a strong inverse relationship between social smoking exposures (at home, spousal and with peers) and smoking cessation in lung cancer, with adjusted odds ratios (aOR) of 3-8 (Eng et al, ASCO 2012, abst 9032). In the current analysis, we evaluated whether these associations hold true in adult cancers in general, particularly cancers not traditionally known to have smoking as a risk factor. Methods: 616 cancer survivors across multiple cancer sites were surveyed on their smoking, alcohol, and physical activity habits before and at various times after cancer diagnosis. Social smoking exposures were documented. Multivariate logistic regression models evaluated the association of each variable with change in each habit after diagnosis adjusted for significant socio-demographic and clinico-pathological covariates. Results: Median follow-up after diagnosis was 26 months. 15% had breast cancers; 15% gastrointestinal; 20% genitourinary-gynecological; 24% haematological; 36% other. Among current smokers at diagnosis, 56% quit after diagnosis; no ex- or never-smoker restarted. Patients without secondary home smoking exposure were significantly more likely to quit smoking than those with home exposures (aOR=9.5, 95% CI [2.4-37.8]). Similar results were seen in patients with non-smoking spouses versus smoking spouses (aOR=3.7 [1.0-13.4]), and with lack of peer smoke exposure (aOR=3.7 [1.3-10.7]). 63% patients who quit did so in the 1 year period surrounding the diagnosis date (6-months pre or post diagnosis). In comparison, first and second-hand smoking exposures did not affect other modifiable behaviours such as alcohol or physical activity. Patient awareness of quality of life and survival benefits of smoking cessation and receiving smoking cessation counselling were not associated with improved smoking cessation. Conclusions: Secondary smoking exposures are associated with lack of smoking cessation in adult cancer survivors, even in cancers not traditionally linked to smoking. Being diagnosed with cancer may be an important `teachable moment` to help patients quit, but results are strongly influenced by the surrounding social exposure to smoking. PS and GL contributed equally.
Cell-free plasma DNA for the diagnosis and follow-up of prostate cancer patients.
Authors: Marcelo L. Wroclawski, Ary Serpa, Fernando L. A. Fonseca, Oseas Castro Neves Neto, Antônio C. L. Pompeo, Marcos Tobias Machado, Auro Del Giglio
Journal: Journal of Clinical Oncology (2013)

e16058 Background: Cell free plasma DNA (CF–pDNA) may have diagnostic and prognostic value in patients with Prostate Cancer (PCa). Methods: We included 133 men with PCa and 33 controls. PCa patients had blood drawn every 3 months for 2 years. CFpDNA was measured by spectrophotometry. Results: CF-pDNA had an area under the curve of 0.824 with a sensitivity of 66.2%, a specificity of 87.9% ,a positive and negative likelihood ratios of 5.46 and 0.39, respectively. There was no statistical significant correlation between CF-pDNA levels at study entry with PSA, Gleason score, stage and biochemical recurrence free survival(BRFS). However, with a mean follow up of 13.5 months, we observed significantly shorter BRFS for patients with at least one value above 140 ng/ mL of CF-pDNA during follow up (p= 0.048). Conclusions: CF-pDNA is a potentially valuable biomarker for PCa diagnosis and may have a prognostic role during follow-up of patients with PCa.
Nondisruptive mutations of TP53 and overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) patients (p).
Authors: Enric Carcereny Costa, Jordi Bertran-Alamillo, Miguel Angel Molina-Vila, Radj Gervais, Bartomeu Massuti, Laura Bonanno, Teresa Moran, Margarita Majem, Enriqueta Felip, M. Rosario Garcia-Campelo, Alain Vergnenegre, Santiago Viteri Ramirez, Amaya Gasco, Luciano Wannesson, Clara Mayo-de las Casas, Laia Pujantell-Pastor, Adolfo G. Favaretto, Niki Karachaliou, Rafael Rosell
Journal: Journal of Clinical Oncology (2013)

11029 Background: The tumor suppressor TP53 is the most commonly mutated gene in lung cancer. Early-stage NSCLC p with TP53 mutations may have worse prognosis and be more radio/chemoresistant. However, few studies have addressed the issue of TP53 mutations in advanced NSCLC. We have retrospectively examined the influence of TP53 mutations on OS in 241 advanced NSCLC p. Methods: 99 EGFR-wild-type (wt), chemotherapy-treated p from 5 European hospitals and 142 EGFR-mutated (mut), erlotinib-treated p from two clinical studies were included. Exons 5, 6, 7 and 8 of TP53were analyzed by high resolution melting (HRM). All mutated samples were reconfirmed by sequencing. Mutations were classified as disruptive or non-disruptive based on their predicted effects on the function of the p53 protein. Results: TP53 mutations were detected in 31% of EGFR-wt and 24% of EGFR-mut p. OS results are available for 57 EGFR-wt p and 90 EGFR-mut p. Among EGFR-wt p, OS was 22 months (m) for p without TP53 mutations, 20m for p with disruptive TP53 mutations, and 9 m for p with non-disruptive TP53 mutations (P=0.09). Among EGFR-mut p, OS was 31 m for p without TP53 mutations, not reached for p with disruptive TP53 mutations, and 15 m for p with non-disruptive TP53 mutations (P=0.05). Complete OS results for all 241 p will be presented. Conclusions: Non-disruptive mutations in the TP53 gene are associated with shorter OS in advanced NSCLC p, both in EGFR-wt p treated with chemotherapy and in EGFR-mut p treated with erlotinib.These p could benefit from treatment to reactivate mutant p53.
The Minneapolis-Manchester Quality of Life Instrument (MMQL): Reliability and validity of the Adult Form (AF).
Authors: Alysia Bosworth, Elizabeth L. Goodman, Eric Wu, Liton Francisco, Leslie L. Robison, Smita Bhatia
Journal: Journal of Clinical Oncology (2013)

9570 Background: Cancer survivors are at risk for deficits in health-related quality of life (HRQL). Youth (8-12y) and adolescent (13-20y) versions of the MMQL have been developed to address survivor-specific issues and are currently in use; the MMQL-AF has now been developed to assess HRQL in cancer survivors aged 21-55y, enabling cross-sectional and longitudinal assessment of childhood cancer survivors as they age. Methods: The MMQL-AF was administered to 499 adults: 65 patients undergoing cancer therapy, 107 off therapy, 327 healthy controls (matched on sex, age, education). Factor analysis was performed; items with factor loadings ≥0.40 were retained. The following psychometric properties were evaluated: internal consistency reliability (Cronbach’s alpha), construct validity (concurrent administration of SF-36), known-groups validity (score comparisons across the 3 groups), and stability (intraclass correlations from patients completing MMQL-AF twice, 2 weeks apart). Results: Among patients, 46% had hematological malignancies, 33% were males, 64% were non-Hispanic whites; median age was 40y. Factor analysis resulted in retention of 44 items across 6 scales: social functioning (n=9), physical functioning (n=12), cognitive functioning (n=7), outlook on life (n=4), body image (n=5), and psychological functioning (n=7).Internal consistency was 0.8-0.9 for scales and 0.95 overall.The MMQL-AF distinguished between known groups; healthy controls scored significantly higher (better HRQL) than patients on 4 of 6 scales. Off-therapy patients scored higher than on-therapy patients on physical functioning.The MMQL-AF scales correlated highly with SF-36 scales hypothesized to tap similar domains (all P values &lt;0.001), demonstrating construct validity.Intraclass correlations were 0.82-0.95 for scales and 0.98 overall (all P values &lt;0.001), indicating high stability. Conclusions: MMQL-AF is a reliable and valid self-report instrument for measuring multi-dimensional HRQL in cancer survivors aged 21-55y. Development of this instrument ensures availability of a tool that can assess HRQL from 8-55y, thus addressing needs of childhood cancer survivors as they age.
Rare lymphoma is linked to breast implants, US officials conclude
Authors: Michael McCarthy
Journal: BMJ (2017)

The US Food and Drug Administration has concluded that a rare type of non-Hodgkin’s lymphoma, anaplastic large cell lymphoma (ALCL), is linked to breast implants.

“All of the information to date suggests that women with breast implants have a very low but increased risk of developing ALCL compared to women who do not have breast implants,” the agency said in an advisory published online on 21 March.1

The FDA had recognized a possible association between the lymphoma and breast implants in 2011 but concluded that additional information was needed to determine what factors increased the risk. Last …
The “Double Whammy”: Effects of erythropoiesis stimulating agents (ESAs) when administered to patients with both end stage renal disease (ESRD) and cancer.
Authors: Michael Dickson, Brian Chen, Peter Georgantopoulos, Charles L. Bennett, John Bian, Virginia Noxon, Mae Thamer, Dennis J Cotter
Journal: Journal of Clinical Oncology (2015)

e17623 Background: Clinical trials have identified increased risks of venous thromboembolism and mortality with ESA administration to cancer patients and increased risks of arterial thrombosis with ESA administration to ESRD patients. No empirical data has evaluated the potential association between ESA administration with severe toxicity among patients who have both ESRD and cancer. The underlying hypothesis is that these toxicities appear to be related to achieving or targeting high hemoglobin levels. Methods: A large private health insurance database (2001 – 2012) was evaluated. Due to important changes in reimbursement policy, three separate time periods were evaluated: 2001 – 2005 (when clinical practice guidelines promoted aggressive ESA use); 2006 – 2010 (when randomized trials reported increased risk related to high ESA doses and high hematocrit targets, and an FDA Black Box warning was issued); and 2011 – 2012 (when the FDA mandated a Risk Evaluation and Mitigation Strategy for ESA use among cancer patients on chemotherapy, and when ESRD Prospective Payment System was implemented, whereby ESAs were bundled and its use declined significantly). We examined whether patients with both cancer and ESRD had higher access to ESA therapy, received higher ESA doses, and were more likely to be hospitalized for ESA-related adverse events compared to patients with cancer only Results: See table below. Conclusions: ESA administration to cancer patients with ESRD is consistently associated with elevated rates of CHF, stroke, MI, or VTE. These toxicities may be dose-related rather than hemoglobin-related. ESA use ESA dosing Hospitalization within 1 year of ESA therapy % Mean (units) Median (units) MI % CHF % Stroke % VTE % Other % 2001-2005 Cancer only 9.1 12,306 7,000 0.8 3.1 0.4 2.9 67.4 Cancer & ESRD 40.0 42,819 14,000 7.2 35.6 2.8 6.4 94.0 Total claims 469,646 230,246 28,791 2006-2010 Cancer only 6.9 10,253 5,000 0.8 3.1 0.7 3.3 70.3 Cancer & ESRD 23.8 28,584 7,000 7.7 33.1 5.1 6.8 92.4 Total claims 831,684 257,821 40,628 2011-2012 Cancer only 1.4 9,249 4,000 1.5 4.2 1.2 3.6 81.7 Cancer & ESRD 11.5 42,258 8,500 5.6 34.4 4.1 7.2 96.4 Total claims 372,961 49,976 2,725