tbuckley/cabot-search huggingface dataset:
Abstract P3-15-03: Clinical benefit, toxicity, and cost of metastatic breast cancer drug therapies: Visualizing randomized and non-randomized evidence
Authors: J Silberholz, L Vahdat, D Bertsimas
Journal: Cancer Research (2018)

Abstract Background: Given the rapidly expanding size of the clinical trial literature for metastatic breast cancer (MBC) clinical trials, oncologists need tools that enable them to efficiently review the settings and results of previous studies. Methods: We searched the Cochrane Central Register of Controlled Trials and PubMed to identify clinical trials testing MBC drug therapies. Key eligibility criteria included &amp;gt;90% of patients enrolled in trial having MBC, therapeutic clinical trials, and Phase II or III studies with at least 10 patients at a dosage level. From each study, we extracted information about clinical benefit and toxicity of drug therapies, and we further estimated the costs of all drug therapies. We built a web-based visualization tool that presents the results of all studies testing a given drug combination, stratified based on patients' receptor statuses and prior exposure to therapy. The tool presents both aggregate and study-level results, and reports both unadjusted study results and standardized results based on key patient characteristics in the study populations. Results: We included 1,783 studies containing 2,549 treatment arms and 170,515 patients in the visualization tool. The tool reports information on 77 HER-2-directed therapies, 101 hormonal therapies, and 675 undirected therapies. The visualization tool has been made publicly accessible for patients and doctors to access at http://cancertrials.info. Discussion: We believe this tool will make literature reviews significantly more efficient for oncologists, enabling them to better leverage insights from the clinical trial literature when making treatment decisions. Citation Format: Silberholz J, Vahdat L, Bertsimas D. Clinical benefit, toxicity, and cost of metastatic breast cancer drug therapies: Visualizing randomized and non-randomized evidence [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-15-03.
Testosterone nadir and PSA recurrence-free survival in men with intermediate and high-risk localized prostate cancer undergoing definitive radiotherapy and androgen deprivation therapy.
Authors: Bryant Alex, Rana R. McKay, A. Karim Kader, J Kellogg Parsons, John Paul Einck, Christopher J. Kane, Arno James Mundt, James Don Murphy, Brent Shane Rose
Journal: Journal of Clinical Oncology (2018)

100 Background: There is limited data on the relationship between testosterone level during androgen deprivation and clinical outcomes of localized prostate cancer treated with hormone therapy and radiation therapy (RT). Here we investigate the association between testosterone nadir during androgen deprivation therapy and prostate-specific antigen (PSA) response and survival. Methods: Using a nationwide Veterans Affairs database, we identified 899 patients with intermediate- or high-risk localized prostate adenocarcinoma diagnosed between 2000 and 2015 and treated with gonadotropin-releasing hormone agonists and RT. All patients had total testosterone measurements while receiving hormone therapy and between 6 weeks and 6 months after the start of hormone therapy. Using univariable and multivariable models we examined the effect of testosterone nadir on 3-month post-treatment PSA, PSA recurrence-free survival, and prostate cancer-specific survival. Multivariable models included age at diagnosis, Gleason score, tumor stage, anti-androgen therapy, hormone therapy duration, comorbidity, BMI, and pre-treatment PSA. Results: Of the 899 patients with testosterone data, 481 patients had a testosterone nadir of &lt; 20 ng/dL, 305 had a nadir between 20 and 49 ng/dL, and 113 had a nadir ≥50 ng/dL. Higher testosterone nadir was associated with higher 3-month post-treatment PSA on univariable (Spearman rho = 0.22, p &lt; 0.001, n = 651) and multivariable (ß = 0.03, 95% CI 0.01-0.05, p = 0.004) analysis. In multivariable Cox regression, higher testosterone nadir was associated with an increased risk of PSA recurrence (hazard ratio [HR] 1.43 per 10-fold increase in testosterone nadir, 95% CI 1.07-1.90, p = 0.01, n = 715) but not prostate cancer-specific mortality (HR 1.45, 95% CI 0.87-2.42, p = 0.16, n = 891). Conclusions: Higher nadir testosterone levels in intermediate- or high-risk localized prostate cancer patients undergoing hormone therapy is associated with higher 3-month post-treatment PSA and inferior PSA recurrence-free survival, though there was no significant effect on prostate cancer-specific mortality.
DOES REPORTING OF GLOBAL LONGITUDINAL STRAIN IMPACT CLINICAL DECISIONS IN PATIENTS UNDERGOING ECHOCARDIOGRAPHY AS PART OF CHEMOTHERAPY MONITORING?
Authors: Mahmoud Ali, Waleed Al-Darzi, Aria Bryan, Namita Joseph, Asaad Nakhle, Ayush Motwani, Meredith Mahan, Karthikeyan Ananthasubramaniam
Journal: Journal of the American College of Cardiology (2018)
Maintaining public confidence in doctors—at what cost?
Authors: Christoph Lees
Journal: BMJ (2018)

We are in a terrible rut with regulation, medical misadventure, and the criminal law, as shown by the recent case of Hadiza Bawa-Garba and Jack Adcock1 and that of David Sellu, whose conviction for manslaughter was quashed in 2016.2 The General Medical Council seemingly regards its duty as ensuring that public confidence in doctors is maintained. Its …
Abstract P1-15-02: Benefit of adjuvant chemotherapy in disease-free survival for T1N0 triple negative breast cancer
Authors: Z Morante, G De la Cruz-Ku, J Pinto, J Araujo, H Fuentes, D Enriquez, R Luque, E Eyzaguirre, A Saavedra, M Luján, S Neciosup, H Gomez
Journal: Cancer Research (2018)

Abstract Background: Although chemotherapy is not recommended in low-risk early breast cancer, triple-negative breast cancers (TNBC) have twice risk of recurrence despite an aggressive treatment. In this study we evaluated the role of chemotherapy in the outcome of T1N0 TNBC patients in terms of disease-free survival (DFS) and overall survival (OS). Methods: We evaluated a retrospective cohort T1N0 TNBC patients diagnosed between 2000 to 2014 at the Instituto Nacional de Enfermedades Neoplasicas (Lima-Peru). Survival rates differences were assessed by Log-rank test and prognostic factors were identified using the Cox proportional hazards model. Results: We identified 123 T1N0 TNBC patients. The median age was 51 years (range: 28-85), where 38.5% were premenopausal. Thirty-six (29.3%) were pT1a/b and 87 were pT1c (70.7%). ACT was administered more frequently in pT1c patients (74.7% vs 55.6%; P=0.036). Locoregional relapse and distant metastases rates were 8.3% vs 19.5% and 5.6% vs 16.1% for tumors pT1a/b and pT1c, respectively. The median of follow-up was 8.8 years. Independent prognostic factors were pT stage and treatment with ACT. In relation to pT stage, DFS rates were 97% vs 78% (at 5-years) and 97% vs 70% (at 8-years) for pT1a/b vs pT1c patients, respectively (HR=4.8; 95%CI:1.46-17.0; P=0.015). In the other hand, patients treated with ACT had a better outcome with DFS rates to 5-years of 86% vs 74% and 8-years of 81% vs 65% (HR: 0.41, 95%CI: 0.17-0.97, p=0.043). Our study had not statistical power to evaluate benefit of ACT in pT1a/b patients. In cases with pT1c tumors, treatment with ACT was the only factor associated with a better DFS (HR=0.29, 95%CI: 0.11-0.77, p=0.012). Because the low mortality in our cohort, OS was not evaluable. Conclusions: Treatment with adjuvant chemotherapy reduces the recurrence risk in 71% among pT1cN0 TNBC. Citation Format: Morante Z, De la Cruz-Ku G, Pinto J, Araujo J, Fuentes H, Enriquez D, Luque R, Eyzaguirre E, Saavedra A, Luján M, Neciosup S, Gomez H. Benefit of adjuvant chemotherapy in disease-free survival for T1N0 triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-15-02.
TRANSCATHETER MICROWAVE ABLATION CAN PRODUCE DEEP CIRCUMFERENTIAL PERIVASCULAR ABLATION AND EFFECTIVE RENAL DENERVATION WITHOUT SIGNIFICANT ARTERIAL INJURY
Authors: Pierre Cheng Qian, Michael Barry, Juntang Lu, Ashraf Mina, Joshua Ryan, Sushil Bandodkar, Shirley Alvarez, Virginia James, John Ronquillo, Winny Varikatt, Zoe Clayton, James Chong, Sara Al Raisi, Pramesh Kovoor, Jim Pouliopoulos, Alistair McEwan, Aravinda Thiagalingam, Stuart Thomas
Journal: Journal of the American College of Cardiology (2018)
Correlation of circulating tumor DNA (ctDNA) assessment with tissue-based comprehensive genomic profiling (CGP) in metastatic urothelial cancer (mUC).
Authors: Bradley Alexander McGregor, Jon Chung, Paulo Gustavo Bergerot, Brady Forcier, Petros Grivas, Toni K. Choueiri, Jeffrey S. Ross, Siraj Mahamed Ali, Philip J. Stephens, Vincent A. Miller, Jeffrey P. Gregg, Gary R. MacVicar, Todd Michael Bauer, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2018)

453 Background: Emerging data suggest a role for targeted therapy in patients (pts) with mUC whose tumors contain actionable genomic alterations (GA). Liquid biopsy of ctDNA from blood provides an attractive alternative for CGP in pts in whom tissue-based testing is not feasible. Methods: Hybrid capture-based genomic profiling was performed using FoundationACT assay in a CLIA-certified, CAP-accredited, NY State-approved laboratory. Cell free DNA was extracted from plasma using 20 ml whole blood and underwent CGP of 62 genes. Sequencing was performed to a median unique coverage of 6756× using the Illumina HiSeq 2500/4000 platform. Barcode-based error correction enabled analysis of GA at low allele frequency (AF), including base substitutions and short in/dels (AF≥0.1% for both), rearrangements, and copy number amplification. For several pts, non-temporally matched tissue-based CGP data was available. Comparisons to other CGP datasets of UC ctDNA and tissue were performed. Results: 66 pts with median age 68 (range 29-86) underwent ctDNA assessment as clinical test. There was evidence for ctDNA in 56 pts (85%), and ≥1 GA was noted in 48 pts (73%). The estimated median ctDNA fraction in plasma was 1.9%. In cases with detectable ctDNA, the most frequently altered genes were TP53 (68%), TERT-promoter (38%), PIK3CA (13%), FGFR3 (13%), KRAS (11%), NF1 (6%), ERBB2 (6%). Observed GA frequencies were comparable to prior studies of ctDNA and tissue. Both tissue and ctDNA-based CGP data with clinical correlation was available for several pts. A pt with FGFR3 GA in baseline tumor tissue had disappearance of FGFR3 GA and detection of new TP53 GA in ctDNA after targeted treatment with FGFR3 inhibitor. In a pt with ERBB2 and TP53 GAs in baseline tumor tissue, ctDNA at time of resistance to cisplatin-based therapy showed persistence of ERBB2 and TP53 GAs and new NF1 GA. Conclusions: Most pts with mUC had detectable ctDNA, and frequencies were comparable to prior data sets Detection of potentially targetable GA support further clinical utility assessment. Concordance between tissue and ctDNA in temporally matched samples with clinical annotation warrants further investigation.
Perioperative hypogonadism in men undergoing radical cystoprostatectomy for bladder cancer.
Authors: Woodson Smelser, Eugene Lee, Ajay Nangia, Katherine Glavin, Jeffrey M. Holzbeierlein
Journal: Journal of Clinical Oncology (2018)

470 Background: Radical cystectomy (RC) is associated with significant morbidity, and loss of body weight is a common after RC, even in patients without significant nutritional deficiencies. Prior studies have demonstrated a high prevalence of hypogonadism (HG) in men with cancer and who undergo anesthesia/major surgery. The suppression of testosterone persists up to seven days following surgery. We hypothesize that hypogonadism is prevalent in male patients undergoing RC for bladder cancer (BC), and that it persists in the post-operative period. Methods: We implemented a prospective, IRB-approved trial (Clinical trials.gov # NCT03063125) to prospectively enroll 25 men with no prior history of treatment for HG or other hormonal disorders with a new diagnosis of non-metastatic bladder cancer undergoing RC. Pre-operative total, free testosterone and luteinizing hormone (LH) were obtained. These labs were then repeated on post-operative days 2, 3, 30, and 90. The threshold for normal total testosterone was defined as &gt; 250 ng/dl. Demographic data were recorded. Results: Between March and September 2017, 9 patients have been enrolled into the study. Mean patient age is 68.5 years (52-85). The mean pre-operative total testosterone was 247 ng/dl (range 50-496 ng/dl) and 6/9 (66.7%) patients had HG. Two patients had abnormal pre-operative LH levels (range 21-57 mIU/L). Testosterone decreased by a mean of 99 ng/dl between pre-op assessment and post-operative day 2 [95% CI 66.2, 131.8]; all 6 men who initially had HG remained below 250 ng/dl. Two men moved from eugonadal (347 ng/dl, 316 ng/dl) to hypogonadal (213 ng/dl,192 ng/dl, respectively) by post-operative day 2. At 30 days post-op, the mean T level was 206 ng/dl. No patients had returned to levels at or above their pre-operative baseline and 8/9 (88.9%) had HG (range 40-356 ng/dl). Conclusions: Hypogonadism is prevalent in men undergoing RC; our trial demonstrates a pre- and 30 day post-operative prevalence of 66.7% and 88.9%%. Furthermore, HG persisted beyond the immediate post-operative period. Treatment of peri-operative HG with correction to a eugonadal state may represent a therapeutic intervention to reduce the morbidity associated with radical cystectomy. Clinical trial information: NCT03063125.
KEYNOTE-224: Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib.
Authors: Andrew X. Zhu, Richard S. Finn, Stéphane Cattan, Julien Edeline, Sadahisa Ogasawara, Daniel H. Palmer, Chris Verslype, Vittorina Zagonel, Olivier Rosmorduc, Arndt Vogel, Debashis Sarker, Gontran Verset, Stephen Lam Chan, Jennifer J. Knox, Bruno Daniele, Scot Ebbinghaus, Junshui Ma, Abby B. Siegel, Ann-Lii Cheng, Masatoshi Kudo
Journal: Journal of Clinical Oncology (2018)

209 Background: Immunotherapy approaches, including immune checkpoint blockade, have shown initial promising results in HCC. Anti PD-1 therapy with pembrolizumab has demonstrated antitumor activity and manageable safety in multiple cancers. KEYNOTE-224 (NCT02702414), an open label, phase 2 trial assessed the efficacy and safety of pembrolizumab in pts with advanced HCC previously treated with sorafenib. Methods: Eligible pts were age ≥18 y with confirmed HCC, radiographic progression after sorafenib and disease not amenable to curative treatment, Child Pugh A, ECOG PS 0-1 and predicted life expectancy &gt; 3 mo. Pts received pembrolizumab 200 mg Q3W for 2 y or until disease progression, unacceptable toxicity, withdrawal of consent or investigator decision. Response was assessed every 9 wk (RECIST v1.1, central review). Primary endpoint was ORR (RECIST v1.1, central review). Secondary endpoints included DOR, DCR, PFS, OS, and safety and tolerability. Data cutoff date was Aug 24, 2017. Results: Of 104 treated pts, 23 continued therapy (median follow up 8.4 mo, range 0.4-13.6). Median age of pts was 68y (range 43-87), 21.2% were HBV + , 26% were HCV + , 94.2% were Child Pugh A, 79.8% had PD on sorafenib and 63.5% had extrahepatic disease. ORR was 16.3% (95% CI, 9.8 to 24.9) and similar across subgroups with different etiology. Median time to response was 2.1 mo (range 1.8-4.8) and 94% of responders were estimated to have a response duration ≥6 mo. Best responses were CR in 1 patient (1.0%), PR in 16 (15.4%), SD in 47 (45.2%) and PD in 34 (32.7%); DCR was 61.5%. Median PFS was 4.8 mo (95% CI, 3.4 to 6.6) and median OS (9.4 to NA) was not reached. The 6 mo PFS and OS rates were 43.1% and 77.9%, respectively. Treatment related (TR) AE occurred in 73.1% of pts; fatigue (21.2%) and increased aspartate aminotransferase (12.5%) were seen in ≥10% of pts and grades 3-5 TRAE in 25% including 1 death (ulcerative esophagitis). No cases of HBV/HCV flare occurred; immune mediated hepatitis occurred in 3 (2.9%) pts. Conclusion: Pembrolizumab treatment resulted in durable responses and favorable PFS and OS in pts with advanced HCC previously treated with sorafenib. Safety was generally comparable to that established for pembrolizumab monotherapy. Clinical trial information: NCT02702414.
Shortlisted teams are announced for 10th BMJ Awards
Authors: Zosia Kmietowicz
Journal: BMJ (2018)

If the finalists for The BMJ Awards 2018 are anything to go by, the past 12 months have seen some unique innovation, collaboration, and leadership throughout the NHS.

The shortlisted teams will gather in London on 10 May for a morning’s judging followed by “Excellence in Healthcare,” an afternoon programme with speakers including Bruce Keogh, former medical director of NHS England. The day will conclude with a glittering awards evening at the Park Plaza Westminster Hotel.

Some 250 teams entered the 2018 …
GMC chair’s reply to Nick Ross’s second letter regarding Hadiza Bawa-Garba
Authors: Terence Stephenson
Journal: BMJ (2018)

The following is a letter of 12 February 2018 from the chair of the General Medical Council in reply to Nick Ross’s letter of 5 February 2018 (posted 8 February 2018).12

Dear Nick,

After your meeting and exchange of correspondence with Charlie Massey in recent weeks, I welcome the opportunity to respond to the points you raise in your letter to me of 5 February 2018.12

I have read in full the court judgments and GMC decisions taken around the Bawa-Garba case, and I am keen to shed some light on our role and how it fits in a law abiding and democratic society.

I understand that you find the decision taken in this case hard to accept. I also recognise the anxiety felt in parts of my profession. We have publicly acknowledged that concerns about manslaughter by gross negligence convictions, and this subsequent judgment, could make doctors less candid about errors and that this case has set us back in our goal to support doctors as the best way of protecting patients. We are working hard to overcome this and the considerable misunderstanding and frustration, which are not entirely grounded in fact.

At the heart of this tragic case, a person was convicted in …
IMPACT OF PAST AND CURRENT SMOKING ON THE RISK OF FUTURE CARDIOVASCULAR EVENTS IN ANGIOGRAPHIED CORONARY PATIENTS WITH TYPE 2 DIABETES
Authors: Christoph Saely, Christina Lins, Daniela Zanolin, Andreas Leiherer, Alexander Vonbank, Axel Muendlein, Philipp Rein, Heinz Drexel
Journal: Journal of the American College of Cardiology (2018)
SAS doctors are those most worried about job security, survey finds
Authors: Abi Rimmer
Journal: BMJ (2014)

Staff, associate specialist, and specialty (SAS) doctors are more worried about job security than doctors in other branches of practice, a BMA survey has found.1

The BMA received 1217 responses to a survey about doctors’ workload and wellbeing, conducted between 4 and 24 February 2014. The survey covered all branches of practice and received 445 responses …
Enhancer of zeste-homolog 2 (EZH2) expression and clinical outcomes in metastatic castrate resistant prostate cancer (mCRPC).
Authors: Karthik Giridhar, Brian Addis Costello, Carlos Sosa, Haojie Huang, Manish Kohli
Journal: Journal of Clinical Oncology (2018)

350 Background: In prostate cancer, overexpression of EZH2 is associated with disease recurrence, androgen independent growth, cell invasion, and metastases. We evaluated the prognostic significance of EZH2 gene expression in metastatic biopsies from men with CRPC. Methods: EZH2 (RNA) expression was evaluated in two serial metastatic site biopsies in patients (pts) prior to treatment with abiraterone acetate and prednisone (pre-AA/P) and after 12 weeks of treatment (post-AA/P). All pts were enrolled and prospectively followed for clinical outcomes. The primary endpoint was overall survival (OS), defined as the time from CRPC to death or last follow-up. Cox proportional hazard regression analysis was performed on EZH2 expression using normalized fragments per kilobase million (FPKM) &gt; 1 for association with OS and time to treatment failure (TTF). Results: Of 92 enrolled pts, 59 pts had (pre-AA/P) gene expression using RNA-seq, 45 had paired pre and post-AA/P RNA-seq available for analysis. In pre-AA/P samples, the median EZH2 expression was 4.82 FPKMs (range 1.05-38.8). Elevated expression of EZH2 was associated with shorter OS [hazard ratio (HR) 2.58, p = 0.016]. Radiographic progression at 12 weeks was more frequent in high EZH2 tumors compared to low EZH2 tumors (48% vs 20%, p = 0.03, Fisher’s exact test) No statistically significant associations were identified between EZH2 expression and TTF. In paired post-AA/P biopsies, EZH2 expression increased in 13/45 tumors and decreased in 32/45 tumors. The median log2 fold change in EZH2 expression was -1.38 (range -6.7 to 3.1). In post-AA/P biopsies, no associations were identified between an increase in EZH2 expression and OS or TTF. Conclusions: EZH2 expression represents a potential novel prognostic biomarker in mCRPC and warrants further exploration. Clinical trial information: 01953640.
Clinical Benefits Of Long-Term, Low-Dose Erythromycin In Bronchiectasis Are Not Due To Anti-Inflammatory Effects
Authors: A. C. Chen, M. M. Martin, L. Burr, S. Z. Hasnain, R. Lourie, S. D. Bowler, M. A. McGuckin, D. J. Serisier
Journal: American Journal of Respiratory and Critical Care Medicine (2013)
NATIONAL TRENDS IN THE UTILIZATION, COST BURDEN AND OUTCOMES ASSOCIATED WITH USE OF LONG-TERM MECHANICAL CIRCULATORY SUPPORT: 10-YEAR EXPERIENCE
Authors: Byomesh Tripathi, Mark Schneider, Tahir Rizwan, Shilpkumar Arora, Mihir Dave, Harshil Shah, Varun Kumar, Sopan Lahewala, Patel Prashant, Smit Patel, Apurva Badheka, Nileshkumar Patel, Abhishek Deshmukh, Radha Gopalan
Journal: Journal of the American College of Cardiology (2018)
THE ASSOCIATION BETWEEN APPROPRIATE USE CRITERIA AND TRANSTHORACIC ECHOCARDIOGRAPHY FINDINGS
Authors: Tamryn Law, Zachary Bouck, Cindy Yin, Gillian Nesbitt, Amer Johri, Kibar Yared, Jeremy Edwards, Mark Hansen, Rory Weiner, Sacha Bhatia
Journal: Journal of the American College of Cardiology (2018)
I am considering a career in public health medicine. Do I have to have an MPH to enter the specialty?
Authors: Joyce Carter
Journal: BMJ (2004)

<i>Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.</i>