tbuckley/cabot-search huggingface dataset:
Routine staging radiology is not needed for all breast cancer patients
Authors: M. R. Kell, C. Healy, Z. Martin, R. Downey, S. Potter-Bierne, T. F. Gorey, F. Flannigan, M. Stokes
Journal: Journal of Clinical Oncology (2006)

10648 Background: Early stage breast carcinoma is unlikely to have undergone metastatic spread at the time of presentation. The utility of routine staging liver ultrasound (LUS) and bone scan (BS) in early stage disease is unclear. We postulate that early stage breast cancer patients do not need routine radiological staging. Methods: We studied 200 patients with a diagnosis of invasive breast carcinoma. 100 with symptomatic breast cancer (SBC) and 100 with screen detected (SD). Patients’ histology, tumour markers (CEA, CA 15.3), hormone receptor status, CXR, LUS and BS results were reviewed. Results: All patients underwent curative surgery for early stage invasive breast cancer. 3 patients had liver metastases diagnosed by LUS. Two of these patients were from the SBC and one from SD (grade ≥2, mean tumour size 2.2 cm). 4 patients had bony metastases diagnosed by BS. Three of these were from the SBC and one from SD (grade ≥2, mean tumour size 3.2 cm.). No patients with low-grade T1 tumours had signs of metastasis on BS or US. Conclusions: The incidence of metastatic disease is very low in newly diagnosed early stage breast carcinoma. Our results suggest that patients with low-grade T1 tumours do not need staging BS or US. No significant financial relationships to disclose.
Optimal endocrine therapy for breast cancer patients 45-50 years of age at diagnosis.
Authors: Gwen Dackus, Katarzyna Józwiak, Gabe S. Sonke, Elsken Van Der Wall, Paul J. van Diest, Sabine Siesling, Michael Hauptmann, Sabine C. Linn
Journal: Journal of Clinical Oncology (2016)

551 Background: Aromatase inhibitors (AI) are superior to tamoxifen (TAM) in postmenopausal estrogen receptor positive (ER+) breast cancer patients. TAM is standard of care for premenopausal ER+ patients. The SOFT/TEXT trials showed, however, that ovarian function suppression combined with the AI exemestane significantly improves disease-free survival compared to TAM in premenopausal patients. Evidence on perimenopausal women at breast cancer diagnosis is scarce as they are usually excluded from studies. We therefore aim to provide evidence for the optimal treatment of ER+ breast cancer patients 45-50 years of age, using data from the population-based Netherlands Cancer Registry (NCR). Methods: All pre-menopausal Dutch women, without prior history of malignancy, diagnosed between 2004-2007 at age 45-50 years with an ER+, non-metastatic, primary invasive breast cancer for which they received chemotherapy and endocrine treatment, were identified through the NCR. Cox proportional hazards regression was used to calculate hazard ratios (HR) according to the time-dependent percentage of endocrine treatment duration during which an AI was used, categorized into < 25%, 25%-75% or > 75%. Analyses were adjusted for chemotherapy, trastuzumab use, lymph node status, grade, progesterone receptor, HER2 status, and clinical T stage. Results: A total of 346 events were observed in 2387 patients. Recurrence-free survival (RFS) was significantly improved for patients who received an AI > 75% of treatment duration (adjusted HR 0.59; 95% Confidence Interval 0.42-0.83; P = 0.002) compared to patients who received AI < 25% of treatment duration. No difference was observed between the 25-75% and < 25% groups. There was a significant trend with increasing percentage of the use of AI (p = 0.001). Conclusions: An AI for > 75% of treatment duration significantly improves RFS and should be considered in ER+ breast cancer patients aged 45-50 years at diagnosis.
Relative energy deficiency in sport (RED-S)
Authors: Siobhan M Statuta, Irfan M Asif, Jonathan A Drezner
Journal: British Journal of Sports Medicine (2017)

Relative energy deficiency in sport (RED-S) is the result of insufficient caloric intake and/or excessive energy expenditure. Consequences of this low-energy condition can alter many physiological systems, including metabolism, menstrual function, bone health, immunity, protein synthesis, and cardiovascular and psychological health1 (figure 1).



Figure 1 
Spoke and wheel figure (from Mountjoy et al 1). RED-S, relative energy deficiency in sport. 



The RED-S concept has been adapted from a previously identified syndrome, the female athlete triad, which affects active women with low-energy availability, menstrual dysfunction and low bone mineral density.2 Emerging data suggest there may be a parallel syndrome in undernourished male athletes with resulting hypogonadotropic hypogonadism and impairment of bone health.3 RED-S is a comprehensive model depicting a low-energy status in physically active women or men.

A 29-year-old male runner presents for evaluation with concerns of fatigue and poor athletic performance. Over the past year, he has focused on his training, running approximately 72 miles per week and performing yoga 3 days per week. He also has revised his diet to eat ‘healthy’ and avoid alcohol, and subsequently lost 21 lbs. The …
Validity of Cardiovascular Data From Electronic Sources
Authors: Faraz S. Ahmad, Cheeling Chan, Marc B. Rosenman, Wendy S. Post, Daniel G. Fort, Philip Greenland, Kiang J. Liu, Abel N. Kho, Norrina B. Allen
Journal: Circulation (2017)

Background: Understanding the validity of data from electronic data research networks is critical to national research initiatives and learning healthcare systems for cardiovascular care. Our goal was to evaluate the degree of agreement of electronic data research networks in comparison with data collected by standardized research approaches in a cohort study. Methods: We linked individual-level data from MESA (Multi-Ethnic Study of Atherosclerosis), a community-based cohort, with HealthLNK, a 2006 to 2012 database of electronic health records from 6 Chicago health systems. To evaluate the correlation and agreement of blood pressure in HealthLNK in comparison with in-person MESA examinations, and body mass index in HealthLNK in comparison with MESA, we used Pearson correlation coefficients and Bland-Altman plots. Using diagnoses in MESA as the criterion standard, we calculated the performance of HealthLNK for hypertension, obesity, and diabetes mellitus diagnosis by using International Classification of Diseases, Ninth Revision codes and clinical data. We also identified potential myocardial infarctions, strokes, and heart failure events in HealthLNK and compared them with adjudicated events in MESA. Results: Of the 1164 MESA participants enrolled at the Chicago Field Center, 802 (68.9%) participants had data in HealthLNK. The correlation was low for systolic blood pressure (0.39; P &lt;0.0001). In comparison with MESA, HealthLNK overestimated systolic blood pressure by 6.5 mm Hg (95% confidence interval, 4.2–7.8). There was a high correlation between body mass index in MESA and HealthLNK (0.94; P &lt;0.0001). HealthLNK underestimated body mass index by 0.3 kg/m 2 (95% confidence interval, –0.4 to –0.1). With the use of International Classification of Diseases, Ninth Revision codes and clinical data, the sensitivity and specificity of HealthLNK queries for hypertension were 82.4% and 59.4%, for obesity were 73.0% and 89.8%, and for diabetes mellitus were 79.8% and 93.3%. In comparison with adjudicated cardiovascular events in MESA, the concordance rates for myocardial infarction, stroke, and heart failure were, respectively, 41.7% (5/12), 61.5% (8/13), and 62.5% (10/16). Conclusions: These findings illustrate the limitations and strengths of electronic data repositories in comparison with information collected by traditional standardized epidemiological approaches for the ascertainment of cardiovascular risk factors and events.
Human Brucella melitensis infections in southern Vietnam
Authors: J.I. Campbell, N.P.H. Lan, P.M. Phuong, L.B. Chau, None Trung Pham Duc, C. Guzmán-Verri, N. Ruiz-Villalobos, T.P.T. Minh, P.M. Muñoz Álvaro, E. Moreno, G.E. Thwaites, M.A. Rabaa, N.V.V. Chau, S. Baker
Journal: Clinical Microbiology and Infection (2017)
A Population-Based Study of Serum Antioxidant Levels in Barrett's Oesophagus
Authors: SJ Murphy, LA Anderson, RG Peter Watson, BT Johnston, H Comber, J McGuigan, JV Reynolds, LJ Murray
Journal: Endoscopy (2006)

Aims: Oxidative stress is implicated in the pathogenesis of Barrett's oesophagus, and previous studies have shown that vitamin C levels are lower in subjects with Barrett's oesophagus compared to controls. However, studies so far have examined small numbers of subjects and were not population-based.
Size does matter: Comparison of activity between anti-EGFR and anti-VEGF based-treatments in RAS wild type colorectal cancer patients, stratified by sizes of metastatic involvement
Authors: Michela Del Prete, Riccardo Giampieri, Luca Cantini, Elena Maccaroni, Alessandro Bittoni, Alessandro Bruschi, Rita Silva Rosa, Renato Bisonni, Lucio Giustini, Miriam Caramanti, Marzia Di Pietro Paolo, Rossana Berardi
Journal: Annals of Oncology (2017)
Acute Myeloid Leukemia, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology
Authors: Margaret R. O'Donnell, Martin S. Tallman, Camille N. Abboud, Jessica K. Altman, Frederick R. Appelbaum, Daniel A. Arber, Vijaya Bhatt, Dale Bixby, William Blum, Steven E. Coutre, Marcos De Lima, Amir T. Fathi, Melanie Fiorella, James M. Foran, Steven D. Gore, Aric C. Hall, Patricia Kropf, Jeffrey Lancet, Lori J. Maness, Guido Marcucci, Michael G. Martin, Joseph O. Moore, Rebecca Olin, Deniz Peker, Daniel A. Pollyea, Keith Pratz, Farhad Ravandi, Paul J. Shami, Richard M. Stone, Stephen A. Strickland, Eunice S. Wang, Matthew Wieduwilt, Kristina Gregory, Ndiya Ogba
Journal: Journal of the National Comprehensive Cancer Network (2017)

Acute myeloid leukemia (AML) is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. This portion of the NCCN Guidelines for AML focuses on management and provides recommendations on the workup, diagnostic evaluation, and treatment options for younger (age <60 years) and older (age ≥60 years) adult patients.
Favorable Cardiovascular Health, Compression of Morbidity, and Healthcare Costs
Authors: Norrina B. Allen, Lihui Zhao, Lei Liu, Martha Daviglus, Kiang Liu, James Fries, Ya-Chen Tina Shih, Daniel Garside, Thanh-Huyen Vu, Jeremiah Stamler, Donald M. Lloyd-Jones
Journal: Circulation (2017)

Background: We examined the association of cardiovascular health at younger ages with the proportion of life lived free of morbidity, the cumulative burden of morbidity, and average healthcare costs at older ages. Methods: The CHA study (Chicago Heart Association Detection Project in Industry) is a longitudinal cohort of employed men and women 18 to 74 years of age at baseline examination in 1967 to 1973. Baseline measurements included blood pressure, cholesterol, diabetes mellitus, body mass index, and smoking. Individuals were classified into 1 of 4 strata of cardiovascular health: favorable levels of all factors, 0 factors high but ≥1 elevated risk factors, 1 high risk factor, and ≥2 high risk factors. Linked Medicare and National Death Index data from 1984 to 2010 were used to determine morbidity in older age. An individual’s all-cause morbidity score and cardiovascular morbidity score were calculated from International Classification of Disease, Ninth Revision codes for each year of follow-up. Results: We included 25 804 participants who became ≥65 years of age by 2010, representing 65% of all original CHA participants (43% female; 90% white; mean age, 44 years at baseline); 6% had favorable levels of all factors, 19% had ≥1 risk factors at elevated levels, 40% had 1 high risk factor, and 35% had ≥2 high risk factors. Favorable cardiovascular health at younger ages extended survival by almost 4 years and postponed the onset of all-cause and cardiovascular morbidity by 4.5 and 7 years, respectively, resulting in compression of morbidity in both absolute and relative terms. This translated to lower cumulative and annual healthcare costs for those in favorable cardiovascular health ( P &lt;0.001) during Medicare eligibility. Conclusions: Individuals in favorable cardiovascular health in early middle age live a longer, healthier life free of all types of morbidity. These findings provide strong support for prevention efforts earlier in life aimed at preserving cardiovascular health and reducing the burden of disease in older ages.
FGF2 from Bone Marrow Stroma Protects Acute Myeloid Leukemia Cells from the FLT3 Inhibitor Quizartinib and Facilitates Acquisition of Resistance Mutations
Authors: Elie Traer, Nathalie Javidi-Sharifi, Jacqueline Martinez, Isabel English, Jennifer Dunlap, Anupriya Agarwal, Tibor J. Kovacsovics, Jeffrey W. Tyner, Melissa Wong, Brian J. Druker
Journal: Blood (2016)
RET rearrangements define a new and rare molecular subtype of metastatic colorectal cancer (mCRC)
Authors: Filippo Pietrantonio, Alexa Schrock, Jeeyun Lee, Alexander Drilon, Jason Christiansen, Vi Chiu, Giovanni Fucà, Federica Morano, Daniele Rossini, Tae Kim Seung, Massimo Milione, Rupal Patel, Vincent Miller, Michele Prisciandaro, Maria Di Bartolomeo, Jeffrey Ross, Andrea Bertotti, Siraj Ali, Livio Trusolino, Alfredo Falcone, Filippo de Braud, Chiara Cremolini
Journal: Annals of Oncology (2017)
Maggie’s cancer centre wins award
Authors: Tom Moberly
Journal: BMJ (2017)

Tony Barwell

Maggie’s Oldham, the latest centre opened by the cancer charity Maggie’s, has won the Building Project of the Year 2017 award at the Constructing Excellence Awards North West.

The Maggie Keswick Jencks Cancer Caring Centres Trust, known as Maggie’s, provides free practical, emotional, and social support to people …
A model to predict axillary nodal pathologic complete response following neoadjuvant chemotherapy for breast cancer.
Authors: Olga Kantor, Lynn McNulty, Katharine Yao, Ted A. James
Journal: Journal of Clinical Oncology (2016)

1047 Background: Several recent trials have suggested feasibility of sentinel node biopsy (SNB) in the neoadjuvant setting. Selection of patients suitable for this approach is controversial. We sought to develop a clinical model to predict which patients benefit from SNB following neoadjuvant therapy. Methods: The National Cancer Data Base was used to identify 19115 patients with clinically node positive (cN+) breast cancer who underwent neoadjuvant chemotherapy (NAC) followed by breast surgery and axillary lymph node dissection (ALND) between 2010-2013. Patients were randomly assigned to a 70% testing or 30% validation cohort for model development. A predictive model was built based on significant preoperative factors associated with pathologic nodal response (pN0) as well as additional points for clinical breast response. Results: Using the testing cohort (n = 13396), multivariate regression was used to identify predictors of pN0 based on preoperatively determined patient, facility, and tumor factors. Younger age (OR 1.39 for < 50y/o), triple negative (OR 2.68), Her2 positive (OR 4.33), high grade (OR 1.76), ductal histology (OR 1.67), cN1 vs cN2 tumors (OR 1.28), and extent of pathologic breast response (OR 20.37) were all significant independent predictors of pN0 on adjusted analysis. The odds ratios translated into points for the model, which was adjusted to a 10 point scale correlating to a stepwise increase in pN0 response (5.9%-82.0%). The validation cohort was used for confirmation (4.6%-78.5%). The area under the curve for the ROC curves for the testing and validation cohorts was 0.789 and 0.793, respectively (p < 0.01). Conclusions: Our model incorporates known preoperative factors to stratify the likelihood of pN0 response in patients with cN+ disease who undergo NAC. For patients with high scores, SNB may be considered over ALND as they have a higher likelihood of negative nodes at pathology. Score Testing Cohort N (%pN0) Validation Cohort N (%pN0) 1 50 (5.9%) 15 (4.6%) 2 224 (9.1%) 85 (8.3%) 3 106 (11.5%) 32 (8.7%) 4 458 (15.9%) 195 (15.7%) 5 349 (21.9%) 174 (24.4%) 6 327 (30.1%) 150 (28.1%) 7 635 (40.6%) 248 (40.9%) 8 186 (50.0%) 88 (53.0%) 9 386 (73.1%) 172 (74.5%) 10 952 (82.0%) 395 (78.5%)
Intention‐to‐treat survival benefit of liver transplantation in patients with hepatocellular cancer
Authors: Quirino Lai, Alessandro Vitale, Samuele Iesari, Armin Finkenstedt, Gianluca Mennini, Gabriele Spoletini, Maria Hoppe‐Lotichius, Giovanni Vennarecci, Tommaso M. Manzia, Daniele Nicolini, Alfonso W. Avolio, Anna Chiara Frigo, Ivo Graziadei, Massimo Rossi, Emmanouil Tsochatzis, Gerd Otto, Giuseppe M. Ettorre, Giuseppe Tisone, Marco Vivarelli, Salvatore Agnes, Umberto Cillo, Jan Lerut
Journal: Hepatology (2017)

The debate about the best approach to select patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT) is still ongoing. This study aims to identify the best variables allowing to discriminate between "high-" and "low-benefit" patients. To do so, the concept of intention-to-treat (ITT) survival benefit of LT has been created. Data of 2,103 adult HCC patients consecutively enlisted during the period 1987-2015 were analyzed. Three rigorous statistical steps were used in order to create the ITT survival benefit of LT: the development of an ITT LT and a non-LT survival model, and the individual prediction of the ITT survival benefit of LT defined as the difference between the median ITT survival with (based on the first model) and without LT (based on the second model) calculated for each enrolled patient. Four variables (Model for End-Stage Liver Disease, alpha-fetoprotein, Milan-Criteria status, and radiological response) displayed a high effect in terms of delta benefit. According to these risk factors, four benefit groups were identified. Patients with three to four factors ("no-benefit group"; n = 405 of 2,103; 19.2%) had no benefit of LT compared to alternative treatments. Conversely, patients without any risk factor ("large-benefit group"; n = 108; 5.1%) yielded the highest benefit from LT reaching 60 months.The ITT transplant survival benefit presented here allows physicians to better select HCC patients waiting for LT. The obtained stratification may lead to an improved and more equitable method of organ allocation. Patients without benefit should be de-listed, whereas patients with large benefit ratio should be prioritized for LT. (Hepatology 2017;66:1910-1919).
Phase I study to evaluate the tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) of PM01183 (Lurbinectedin) in combination with olaparib in patients with advanced solid tumors.
Authors: Andres Poveda, Ana Oaknin, Ignacio Romero, Angel Guerrero, Lorena Fariñas-Madrid, Victor Rodriguez-Freixinos, Arturo Soto-Matos, Carlos Peris, Marisa Teruel, Raquel Lopez-Reig, Jose Antonio Lopez-Guerrero
Journal: Journal of Clinical Oncology (2017)

5573 Background: PM01183 (Lurbinectedin) is a new anticancer drug that exerts antitumor activity through inhibition of trans-activated transcription and modulation of tumor microenvironment and is highly active in platinum resistant ovarian cancer. (Poveda A et al. ASCO 2014.abstr #5505). Olaparib (AZD2281, KU-0059436) is a polyadenosine 5’diphosphoribose (poly [ADP ribose]) polymerase (PARP) inhibitor of PARP-1,-2 and-3 with proven antitumoral activity in homologous recombination deficient tumors. The combination of PM01183 and Olaparib has shown synergistic activity in cell-lines, independent of BRCA mutation status. Methods: This phase I study evaluates the safety, PK and PD of PM1183 in combination with short course of Olaparib tablet formulation [days (d) 1-5] a cycle of 21 d, through a 3+3 dose escalation design (NCT02684318) Patients with advanced or metastatic solid tumors without established standard therapeutic alternatives were selected. Primary endpoints: safety (MTD, DLT and RP2D). Secondary endpoints: PK and PD (western blot analysis of RAD51 and p-gH2AX) profiles at 0h,4.5h, 6.5h and 24h at first cycle of treatment. Results: 20 patients were enrolled from Nov 2015 to Sep 2016 (15 ovarian, 5 endometrial) to 5 dose levels. 19/20 were evaluable for toxicity. Two dose limiting toxicities (DLTs) (both grade 4 neutropenia ≥ 4 days) occurred at the highest dose level (PM01183 2 mg/m2 iv d1 + Olaparib 250 mg [BID] oral on d 1-5. Grade 3 toxicities occurred in 30% of patients, including grade 3 neutropenia (6%) and grade 3 asthenia (10%). PK data are available from 19 patients. Median of PM01183 total clearance (11.0 L/h) is the same as when PM01183 is given as single agent. Clearance of Olaparib (7 L/h) is consistent with results reported elsewhere (5.1 – 8.6 L/h). PD: An overall increase of RAD51 and p-gH2AX was observed, being particularly evident in 56% of patients. Conclusions: The Recommended Dose for Phase II (RP2D) was PM01183 1,5 mg/m2 iv d1 + Olaparib 250 mg BID on d 1-5. This combination is feasible and without evidence of drug-drug interactions. A phase-II study at RP2D is ongoing. Clinical trial information: NCT02684318.
Limitations Concerning the Association of Physician Sex and Patient Outcomes
Authors: Mark W. Friedberg, Walid F. Gellad, Vinay Prasad
Journal: JAMA Internal Medicine (2017)

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