tbuckley/cabot-search huggingface dataset:
A test utilising diagnostic and on-treatment biomarkers to improve prediction of response to endocrine therapy in breast cancer.
Authors: Arran Turnbull, Yan Lee, Dominic Pearce, Carlos Martinez-Perez, Sonya Uddin, Hannah Webb, Anu Fernando, Jeremy Thomas, Lorna Renshaw, Andrew Sims, Mike Dixon
Journal: Journal of Clinical Oncology (2016)

555 Background: Identifying breast cancer (BC) patients likely to recur on endocrine therapy (ET) is a major challenge. Many multigene classifiers are available for predicting prognosis. These are used at diagnosis to determine whether adjuvant ET alone is sufficient for estrogen receptor (ER) positive patients to remain disease-free, or if additional therapy is required. We developed a test measuring diagnostic IL6ST and 2 week proliferation, either at transcript level or by immunohistochemistry (IHC), which accurately predicts neoadjuvant response (NR), recurrence free survival (RFS) and BC specific survival (BCS). Methods: We compared predictions using our test with those of established clinicopathological markers or estimations of multigene classifier scores (OncotypeDX, EndoPredict, Prosigna, MammaPrint) before and/or on-treatment with aromatase inhibitors (AIs) in BC patients. We analysed diagnostic and 2 week biopsies from 3 patient cohorts: A: n = 73, treated in a single centre with neoadjuvant (3 months) then adjuvant letrozole, B: n = 44, treated in another centre with neoadjuvant anastrozole (3 months), and C: n = 84, received 2 weeks of AIs prior to surgery and continued adjuvantly. NR was determined using periodic tumour ultrasound. Patients in cohorts A and C had 10 years follow-up. Results: Prediction accuracy of NR at 3 months was poor (30-70%) with all methods tested using pre-treatment biopsies alone. On-treatment was associated with improved predictive power, however the most accurate predictions all utilised IL6ST level at diagnosis and a proliferation marker (MCM4 or Ki67) on-treatment (70-96%). Improvements were also observed with outcome prediction: P = 0.0005 (RFS) and P = 0.0002 (BCS) in series A and P < 0.0001 for both RFS and BCS in series C, assessed by IHC. Hazard ratios calculated using our test ranged from 2.9-8.0 (95%CI 0.2-33), significantly higher than with all other methods tested either pre- or on-treatment (HR: 0.5-2.0, 95%CI 0.1-11). Conclusions: Estimating IL6ST at diagnosis and proliferation at 2 weeks outperforms all current predictive classifiers and clinical tools for both short term (NR) and long term (RFS and BCS) outcomes.
Implementation of Medical Homes in Federally Qualified Health Centers
Authors: Justin W. Timbie, Claude M. Setodji, Amii Kress, Tara A. Lavelle, Mark W. Friedberg, Peter J. Mendel, Emily K. Chen, Beverly A. Weidmer, Christine Buttorff, Rosalie Malsberger, Mallika Kommareddi, Afshin Rastegar, Aaron Kofner, Lisa Hiatt, Ammarah Mahmud, Katherine Giuriceo, Katherine L. Kahn
Journal: New England Journal of Medicine (2017)

From 2011 through 2014, the Federally Qualified Health Center Advanced Primary Care Practice Demonstration provided care management fees and technical assistance to a nationwide sample of 503 federally qualified health centers to help them achieve the highest (level 3) medical-home recognition by the National Committee for Quality Assurance, a designation that requires the implementation of processes to improve access, continuity, and coordination.
Clinicopathological characteristics and treatment outcomes in patients with stage I-III invasive lobular carcinoma of the breast (ILC) treated at the National Cancer Centre Singapore.
Authors: Joycelyn Jie Xin Lee, Fuh-Yong Wong, Benita Tan, Swee Ho Lim, Sze Huey Tan, Joanne YY Ngeow, Rebecca Alexandra Dent
Journal: Journal of Clinical Oncology (2016)

e12005 Background: Increasing evidence suggests that ILC differs from invasive ductal carcinoma (IDC) but even within ILC there is significant heterogeneity. We aim to identify prognostic factors in our cohort of ILC patients (pts). Methods: 371 pts with stage I-III ILC diagnosed between October 1991 and May 2015 were included. Cox regression analysis was used to evaluate the association between clinicopathological characteristics, treatment received and survival outcomes. Results: Median age at diagnosis was 54 years (range 33.8-84.9) and most pts were Chinese (77%). 204 (69%) of tumors were ER+/PR+/HER2-, 56 (19%) ER+/PR-/HER2-, 20 (7%) ERany/PRany/HER2+, and 17 (5%) ER-/PR-/HER2- (triple negative). 150 (40.4%) had stage I disease, 114 (30.7%) stage II disease and 107 (28.8%) had stage III disease. 242 pts (65%) had a mastectomy while 129 (35%) had breast conserving surgery. 159 (43%) received chemotherapy (24 as neoadjuvant, 135 as adjuvant), 236 (64%) adjuvant radiotherapy and 306 (82%) adjuvant hormonal therapy. Median overall survival (OS) was 17 years (95% CI 14.3–not estimable). In multivariable analysis, in addition to TNM staging, pts with screen-detected cancers were also shown to have significantly better disease-free survival (DFS) (HR 0.47, 95% CI 0.230–0.975) and OS (HR 0.09, 95% CI 0.012–0.655) compared to those with clinically-detected cancers. Prior use of oral contraceptives (OCP) was also associated with improved DFS (HR 0.22, 95% CI 0.081–0.620) and OS (HR 0.10, 95% CI 0.014–0.744). Among 306 pts who had adjuvant endocrine therapy, 222 (73%) used tamoxifen while 82 used other hormonal options. Use of tamoxifen was associated with a poorer DFS compared to other hormonal adjuvants (HR 2.18, 95% CI 0.936–5.066) although this did not reach statistical significance (p = 0.07). Conclusions: ILC are heterogenous in their clinicopathological characteristics and survival outcomes. Interval cancers are associated with a worse prognosis while OCP use is associated with better survival, though our study is limited by cohort size. Future studies should evaluate molecular heterogeneity to help us better tailor treatment choices.
Can big data tell us what clinical trials don't? Screening colonoscopy to prevent colorectal cancer in individuals aged 70-79 years.
Authors: Xabier Garcia-Albeniz, John Hsu, Michael Bretthauer, Miguel Hernan
Journal: Journal of Clinical Oncology (2016)

1563 Background: Colonoscopy screening can prevent colorectal cancer (CRC) through removal of polyps. There are no completed randomized controlled trials of screening colonoscopies to date, and ongoing trials exclude subjects aged 75 years or older. Medicare, however, reimburses screening colonoscopies without upper age limit since 2001. We use over a decade experience of Medicare beneficiaries to evaluate the effectiveness of screening colonoscopy to prevent CRC in individuals aged 70-74 and 75-79. Methods: We performed a large-scale, population-based study emulating the design of a clinical trial including Medicare beneficiaries from years 2004-2012. We evaluate the effect of screening colonoscopy versus no screening on 8-year risk of CRC, stage at diagnosis and 30-day risk of adverse events. Results: We included 1,891,671 Medicare beneficiaries. In the 70-74 age group, the 8-year risk of CRC (95% CI) was 2.22% (2.03, 2.41) in the colonoscopy screening arm and 2.67% (2.62, 2.72) in the no screening arm; absolute risk difference -0.45% (-0.25, -0.64). In the 75-79 age group, the 8-year risk of CRC (95% CI) was 2.90% (2.65, 3.16) in the colonoscopy screening arm and 3.06% (3.00, 3.11) in the no screening arm; risk difference -0.15% (-0.41, 0.10). The proportion of CRC cases in Stage 0 was 14.1% for screening colonoscopy vs. 8.0% for no screening, in Stage I 37.6% vs. 24.5%, in Stage II 20.2% vs. 26.7%, in Stage III 21.5% vs. 24.0 and in Stage IV 6.7% vs. 16.8% (results were similar across age groups). The excess 30-day risk of any adverse event requiring hospitalization or a visit to the emergency department was 5.7 adverse events per 1,000 individuals (95% CI 4.6-6.8) in the 70-74 age group and 10.7 adverse events per 1,000 individuals (95% CI 9.0-12.4) in the 75-79 group. Conclusions: Our findings suggest a relevant benefit of screening colonoscopy for the prevention of CRC in beneficiaries aged 70-74 years, and a smaller benefit in older beneficiaries. The risk of adverse events was low, but greater among older individuals.
Abstract 13016: SIRT6 Plays an Essential Role in Regulating IGF Signaling and Aging Associated Cardiac Failure
Authors: Nagalingam R Sundaresan, Prabhakaran Vasudevan, Lei Zhong, Gene Kim, Sadhana Samant, P. V. Ravindra, Vinodkumar B Pillai, Vishwas Parekh, Madhu Gupta, John M Cunningham, Raul Mostoslavsky, Mahesh P. Gupta
Journal: Circulation (2011)

Aging is the major risk factor for heart failure. However, the molecular mechanisms that link aging with cardiac failure are not yet understood. Previous studies have demonstrated dysregulation of ...
Incidence patterns and survival of gynecological sarcoma in Germany: Analysis of population-based cancer registry data on 2106 women, 2009-2013.
Authors: Klaus Pietzner, Nina Buttmann, Jalid Sehouli, Klaus Kraywinkel
Journal: Journal of Clinical Oncology (2017)

e13058 Background: Sarcoma of the female genital tract are rare tumors. They are described to be associated with a poor prognosis, when compared to gynecogical carcinoma. Aim of this study was to report incidence patterns and survival rates for gynecological sarcoma in Germany. Methods: Clinical data and survival rates for patients with gynecological sarcoma diagnosed in Germany between 2009 and 2013 were extracted from the German national centre for population-based cancer registry data. Incidence patterns and 5-year-relative survival rates were calculated. Results: A total of 2,106 gynecological sarcoma (GS) were eligible for analysis. The uterus was the most common site with 87.2% of all cases. The annual age-standardized incidence rate was 7.7 per 1 million women for all gynecological sarcoma. The median age at diagnosis was 59 years. The prognosis ranged according to site and subtype from a poor 5-year-relative survival of 47.6% (uterine leiomyosarcoma) to a very good 5-year-relative survival of 97.2% (endometrial stromal sarcoma). Conclusions: Despite the rareness of gynecological sarcoma, the size of the dataset allows a differentiation of subtypes according to morphology and site of origin. Clinically relevant differences in incidence and prognosis between subgroups were observed.
Treatment and outcome of patients with relapsed clear cell sarcoma of the kidney (CCSK): A combined SIOP and AIEOP study.
Authors: Saskia L Gooskens, Rhoikos Furtwaengler, Filippo Spreafico, Harm van Tinteren, Jan De Kraker, Gordan M Vujanic, Ivo Leuschner, Aurore Coulomb-Hermine, Jan Godzinski, Gudrun Schleiermacher, Sara Stoneham, Christophe Bergeron, Kathy Pritchard-Jones, Norbert Graf, Marry M van den Heuvel-Eibrink
Journal: Journal of Clinical Oncology (2014)

10041 Background: Clear Cell Sarcoma of the Kidney (CCSK) is an uncommon pediatric renal tumor. Relapses occur in about 15% of the patients. Detailed clinical information on relapsed CCSK is scarce. The current study aims to describe outcome of patients with relapsed CCSK treated according to recent European protocols, in order to find a rational for creating future international CCSK relapse treatment protocols. Methods: We analysed prospectively collected data of all CCSK patients who developed a relapse after complete response to initial therapy, entered onto International Society of Pediatric Oncology (SIOP) and Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) trials between 1992 and 2012. Results: Thirty-seven of 237 CCSK patients (16%) treated according to SIOP and AIEOP protocols developed a relapse. Median time from initial diagnosis to relapse was 17 months (range, 5.5 months - 6.6 years). 35/37 relapses (95%) were metastatic; the most common sites of relapse were brain (n = 13), lungs (n = 7) and bone (n = 5). Relapse treatment consisted of chemotherapy (n = 30), surgery (n = 19) and/or radiotherapy (n = 18), followed by high dose chemotherapy and autologous bone marrow transplantation (ABMT) in 14 patients. 22/37 patients (59%) achieved a second complete remission (CR); 15 of whom (68%) developed a second relapse. Five-year event-free survival (EFS) after relapse was 18% (95% CI: 4-32%) and 5-year overall survival (OS) was 26% (95% CI: 10-42%). Conclusions: In this largest series of relapsed CCSK patients ever described, overall outcome is poor. Relapses tend to occur late, so extensive follow-up is desirable. Most relapses are metastatic and brain relapses are more common than previously recognized. Intensive treatment aiming for local control, followed by high dose chemotherapy and ABMT, seems to be of benefit to enhance survival. Novel development of targeted therapy is urgently required.
Vibrio cholerae O1 with ctxB7 variant genotype acquired qnrVC mediated ciprofloxacin resistance in Yavatmal, India
Authors: P. Kumar, P. Yadav, D.G. Deshmukh, P.A. Bulle, D. Singh, N. Singh, K.K. Sharma, M. Jain, K.V. Ingole, A.K. Goel, P.K. Yadava
Journal: Clinical Microbiology and Infection (2017)
RAS Association Domain Family Member 4 (RASSF4): A New Potent Tumor Suppressor in Multiple Myeloma
Authors: Eva De Smedt, Ken Maes, Stefan Verhulst, Hui Lui, Alboukadel Kassambara, Anke Maes, Dirk Hose, Karine Breckpot, Jerome Moreaux, Elke De Bruyne
Journal: Blood (2016)
Functional and Pain Score Improvement with Vertebroplasty in De Novo Multiple Myeloma in a Public Institution in Mexico
Authors: Jorge Carlos Torres, Ramiro Espinoza, Silvia Alarcon, Nidia Zapata, Eduardo Cervera, Alejandro Sosa, Magnolia Vieyra, Javier Espinoza, Luis Sosa, Luis Oñate, Juan José Lahuerta, Manuel Aguilar
Journal: Blood (2016)
SHIVA: Randomized phase II trial comparing molecularly targeted therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer—PFS ratio from patients who crossed-over.
Authors: Christophe Le Tourneau, Maud Kamal, Cecile Mauborgne, Fabrice Mulot, Jean-Pierre Delord, Anthony Goncalves, Celine Gavoille, Coraline Dubot, Nicolas Isambert, Mario Campone, Olivier Tredan, Francesco Ricci, Marie Alt, Delphine Loirat, Marie-Paule Sablin, Xavier Paoletti, Vincent Servois, Lisa Belin
Journal: Journal of Clinical Oncology (2016)

2535 Background: Several studies used the ratio of progression-free survival (PFS) on genotype-matched treatment to PFS on genotype-unmatched treatment to assess the efficacy of therapy guided by patients’ tumor molecular profiling [von Hoff et al., JCO 2010; Tsimberidou et al., CCR 2012]. We evaluated the PFS ratio from patients included in the SHIVA trial who crossed-over [Le Tourneau et al., Lancet Oncol 2015] (NCT01771458). Methods: The primary endpoint of the SHIVA trial was to compare PFS on molecularly targeted agents (MTAs) based on tumor molecular profiling and treatment at physician’s choice (TPC) in patients with any kind of cancer who had failed standard-of-care therapy. Experimental treatment included only marketed MTAs given outside their indications according to a pre-specified treatment algorithm. Patients were allowed to cross-over at disease progression. Response was evaluated according to RECIST 1.1 at randomization and at cross-over. We evaluated the proportion of patients with a PFS ratio (PFS2 on MTA/PFS1 on TPC) > 1.3 among the patients who crossed-over from the TPC arm to the MTA arm, using each patient as his/her own control. Patients with a censored PFS2 were considered as having progressive disease. Results: Among 741 patients enrolled in the SHIVA trial, 197 were randomized, and 95 crossed-over at disease progression, including 70 patients from TPC arm to MTA arm and 25 patients from MTA arm to TPC arm. Two patients crossed-over in the control arm without disease progression. Among the 68 patients who crossed-over from TPC arm to MTA arm with disease progression, median PFS1 was 2.0 months and median PFS2 was 2.1 months. The PFS ratio exceeded 1.3 in 35% of patients [95%CI: 24 - 46], including 20% of patients with PFS ratio > 2. The PFS ratio was 1-1.3, 0.7-1.0 and < 0.7 in 13%, 25%, and 26% of patients, respectively. Conclusions: We report a PFS ratio > 1.3 in 35% of patients who crossed-over from the TPC arm to the MTA arm in the randomized SHIVA trial, suggesting a clinical benefit of the evaluated histology-agnostic approach in this subgroup of patients. Clinical trial information: NCT01771458.
ЛІКУВАННЯ АНЕМІЇ У ХВОРИХ НА ХРОНІЧНІ ЗАПАЛЬНІ ЗАХВОРЮВАННЯ КИШЕЧНИКА
Authors: T.I. Boyko, O.V. Sorochan, M.V. Stoykevich, N.M. Mosalova, T.N. Tolstikova
Journal: GASTROENTEROLOGY (2014)

Одним із частих системних проявів хронічних запальних захворювань кишечника є анемічний синдром, що значно погіршує якість життя хворих, асоціюється з тяжкістю перебігу хвороби та резистентністю до лікування. Анемія у хворих на хронічні запальні захворювання кишечника має мультифакторну природу та пов’язана з втратою крові внаслідок кишкових кровотеч, недостатнім надходженням та абсорбцією нутрієнтів, а також з основним запальним процесом. Найчастіше спостерігається поєднання залізодефіцитної анемії та анемії хронічного захворювання. Стаття присвячена лікуванню анемічного синдрому у хворих на хронічні запальні захворювання кишечника залежно від типу анемії та рівня гепсидину-25 у сироватці крові.
Tolerability and effectiveness of pertuzumab-containing neoadjuvant (NA) regimens vs. AC-TH for HER2-positive (+) localized breast cancer (BC).
Authors: Laura Spring, Andrzej Niemierko, Amy H. Comander, Kerry Lynn Reynolds, Susan A. Sajer, Jennifer Shin, Elena F Brachtel, Michelle Connolly Specht, Barbara L. Smith, Alphonse G. Taghian, Jeffrey M. Peppercorn, Steven J. Isakoff, Beverly Moy, Aditya Bardia
Journal: Journal of Clinical Oncology (2016)

586 Background: Based on improvement in pathologic complete response (pCR) in the NEOSPHERE and TRYPHAENA studies, the FDA approved NA pertuzumab with trastuzumab (HP) and chemotherapy for HER2+ localized BC. These studies demonstrated higher pCR rate with THP (docetaxel+HP) as compared to TH (pCR 45.8 vs. 29%), and high pCR rates with FEC (5-fluorouracil, epirubicin and cyclophosphamide)-THP (pCR 54.7%) and TCHP (docetaxel, carboplatin+HP, pCR 63.6%). However, in the US, doxorubicin/cyclophosphamide (AC) given in a dose-dense fashion is favored over FEC, though there is no data comparing AC-THP with AC-TH or TCHP. Here we report outcomes for pertuzumab-containing NA regimens and compare effectiveness and toxicity with AC-TH. Methods: We reviewed patients treated at our institution with either a NA pertuzumab-containing regimen or AC-TH from 2011 to 2015 for HER2+ BC. pCR was defined as ypT0/is ypN0. Fisher’s exact test and logistic regression analysis were used for statistical analysis. Results: Eighty patients with stage II-III HER2+ BC were included in the analysis (stage II = 77.5%). All patients had surgery, with 62.5% receiving a mastectomy. pCR rate was higher with AC-THP and TCHP as compared to THP and AC-TH, but was associated with higher toxicity requiring dose interruptions or a change in regimen (table 1). No statistically significant decreases in LVEF were seen during NA therapy. After controlling for ER status, age, and stage, AC-TH was associated with a much lower pCR rate than AC-THP (OR = 0.39), though statistically not significant (p = 0.15). CEP17 duplication was associated with high pCR rates with AC-THP (80%) as compared to other regimens. Conclusions: AC-THP and TCHP resulted in the highest pCR rates with similar tolerability overall. Comparative effectiveness of various neoadjuvant regimens is an understudied area and additional studies of predictive biomarkers, such as CEP17, are needed to help personalize neoadjuvant regimens for localized HER2+ breast cancer. AC-THP (n = 31) THP (n = 17) TCHP (n = 15) AC-TH (n = 17) pCR 64.5% 41.8% 60% 41.2% pCR in tumors with CEP duplication 80% 28.6% 66.7% 25% % planned cycles completed 71% 94.1% 73.3% 64.7%
Patients may have been put at risk from £6m patient data mix-up, review says
Authors: Adrian O’Dowd
Journal: BMJ (2017)

Failings by a company contracted by the government to transfer important medical records onwards has led to around 1700 cases where patients could have been harmed as a result, the public spending watchdog has concluded.

The National Audit Office published its report on 27 June after it looked into how NHS Shared Business Services handled unprocessed clinical correspondence.1 The agency, a joint venture between the Department of Health for England and the French IT company Sopra Steria, was contracted by the government to run some back-office operations in the NHS in England.1

Large amounts of important data on patients, including test results and diagnoses, were delayed in error between 2011 and 2016 by Shared Business Services before they were delivered …
Disparities in the ameliorative effects of bariatric surgery on endometrial cancer risk biomarkers.
Authors: Faina Linkov, Sharon Goughnour, Robert P. Edwards, Anna Lokshin, Ramesh Ramanathan, Giselle G Hamad, Dana H. Bovbjerg
Journal: Journal of Clinical Oncology (2016)

e13038 Background: The risk of endometrial cancer (EC), the most common gynecologic cancer in the US, is strongly linked to obesity. Recent evidence suggests that the risk of EC is reduced by bariatric surgery, but the mechanisms are as yet unknown. We tested the hypothesis that bariatric surgery results in the amelioration of blood levels of EC risk biomarkers representing three etiological pathways (inflammation, insulin resistance/ metabolic factors, and steroid hormones). We further explored possible racial disparities in the biomarker changes after bariatric surgery between European American (EA) and African American (AA) women. Methods: Serum samples from 107 female bariatric surgery candidates (23.4%AA), (21 - 72 yrs) were obtained presurgery (T1) and 6 mo post-surgery (T2). Biomarkers (measured by Luminex) were chosen based on association with EC in prospective studies and included: leptin, IL1RA, IL-6, SHBG, IGFBP1&2, C-peptide, insulin, adiponectin, and CRP. Results: Independent linear regression models adjusting for age and baseline BMI, as well as baseline levels of each EC risk biomarker showed significant main effect relationships between change in BMI and ameliorative effects on multiple biomarkers including SHBG, C-peptide, insulin, IGFBP1,IGFBP2, adiponectin, CRP, leptin,IL1Ra, and IL-6 (p’s < 0.05). Significant interactions with race were seen for several biomarkers (TNF-α, IGFBP1, IGFBP2, adiponectin, and IL1Ra). When we also controlled for change in BMI (since AA lost significantly less weight), we found that race was a significant predictor for change in CRP and IL1Ra (p < 0.05) showing greater decrease. Conclusions: Reductions in BMI following bariatric surgery were associated with ameliorative effects on EC risk biomarkers. Interestingly, above and beyond those effects, race was a significant predictor for changes in levels of two biomarkers (CRP, IL1Ra) with stronger amelioration occurring in AA women per BMI point lost. These results underscore the need for additional research to examine possible disparities in the benefits of bariatric surgery for the reduction of EC risk in AA and EA women.