tbuckley/cabot-search huggingface dataset:
Heterogeneity in Treatment Effects
Authors: Robert A.J. Matthews
Journal: Annals of Internal Medicine (2017)

Letters20 June 2017Heterogeneity in Treatment EffectsRobert A.J. Matthews, MA(Oxon)Robert A.J. Matthews, MA(Oxon)From Aston University, Birmingham, United Kingdom.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L17-0155 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Davidoff's essay (1) on the challenge of heterogeneity in treatment effects is a timely reminder that most clinical trials indicating overall benefit may also be interpreted as merely indicating some efficacy with some patients some of the time ( 2). The author rightly focuses on recent work showing how risk stratification can help cut through this heterogeneity to identify broad subgroups of patients likely to benefit from a treatment ( 3). However, the effectiveness of risk stratification in achieving the ultimate goal—identifying the appropriate treatment for a specific patient—remains unclear. At present, n-of-1 trials remain the only ...References1. Davidoff F. Can knowledge about heterogeneity in treatment effects help us choose wisely? Ann Intern Med. 2017;166:141-2. [PMID: 27820948]. doi:10.7326/M16-1721 LinkGoogle Scholar2. Senn S. Individual response to treatment: is it a valid assumption? BMJ. 2004;329:966-8. [PMID: 15499115] CrossrefMedlineGoogle Scholar3. Kent DM, Nelson J, Dahabreh IJ, Rothwell PM, Altman DG, Hayward RA. Risk and treatment effect heterogeneity: re-analysis of individual participant data from 32 large clinical trials. Int J Epidemiol. 2016. [PMID: 27375287] CrossrefMedlineGoogle Scholar4. Kravitz RL, Duan N, Niedzinski EJ, Hay MC, Subramanian SK, Weisner TS. What ever happened to N-of-1 trials? Insiders' perspectives and a look to the future. Milbank Q. 2008;86:533-55. [PMID: 19120979] doi:10.1111/j.1468-0009.2008.00533.x CrossrefMedlineGoogle Scholar5. Zucker DR, Schmid CH, McIntosh MW, D'Agostino RB, Selker HP, Lau J. Combining single patient (N-of-1) trials to estimate population treatment effects and to evaluate individual patient responses to treatment. J Clin Epidemiol. 1997;50:401-10. [PMID: 9179098] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Aston University, Birmingham, United Kingdom.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L17-0155. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoCan Knowledge About Heterogeneity in Treatment Effects Help Us Choose Wisely? Frank Davidoff Heterogeneity in Treatment Effects Frank Davidoff Metrics 20 June 2017Volume 166, Issue 12Page: 914KeywordsBayesian methodClinical trialsConflicts of interestDecision makingDisclosure ePublished: 20 June 2017 Issue Published: 20 June 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Coeliac disease (CD): The effect of HLA antigens on the age of diagnosis and the presence of autoimmune thyroid disease
Authors: J Matingal, M Kearns, H Grimes, FM Stevens
Journal: Endoscopy (2005)

Aims: To study the frequency of HLA-B8 in coeliacs, and to determine if coeliacs with an atypical HLA profile are less likely to develop ATD than those with the typical HLA-B8, DR3, DQ2 haplotype.
The plinabulin/docetaxel combination to mitigate the known safety concerns of docetaxel.
Authors: Ramon Mohanlal, Osvaldo Rudy Aren, Jonathan Polikoff, Steven D. Reich, William Mikrut, Lan Huang, Lyudmila Bazhenova
Journal: Journal of Clinical Oncology (2016)

e20595 Background: Docetaxel is currently approved in non-small cell lung Cancer (NSCLC) after a failure of first line chemotherapy. However, docetaxel has an unfavorable toxicity profile that limits its use. A docetaxel-containing regimen with an improved safety profile would therefore be attractive. Plinabulin, a first-in-class small molecule vascular disruptive agent with potent immuno-oncology effects, is being developed in combination with docetaxel to address this need. Methods: We conducted a Phase 2 study comparing the safety and efficacy of the plinabulin /docetaxel combination (n=90) with docetaxel alone (n=73) in patients with NSCLC entering 2nd or 3rd line therapy. Plinabulin was given intravenously at 20 mg/m2 (n= 40) or 30 mg/m2 (n=50) and docetaxel at 75 mg/m2(n=73). Results: Efficacy results of this study were presented at ASCO 2014. Baseline characteristics for age, gender, ECOG performance score, histology and disease status were comparable between groups. The plinabulin/docetaxel combination improved overall survival, in a subset of patients with large tumors (> 3 cm; HR=0.758, p =0.36), and also had duration of response benefit over docetaxel alone (12.7 vs 1.5 months; P<0.05). We are reporting on the safety profile of plinabulin/ docetaxel combination. Conclusions: In this Phase 2 study, the plinabulin/docetaxel combination mitigated some of the docetaxel toxicities. Most importantly it improved docetaxel dose intensity. The neutropenia benefit was likely due to plinabulin-induced release of cytokines such as IL-1 and IL-6 (data obtained in in-vitro plinabulin studies), which are known to increase neutrophil count. In addition, preliminary results indicated a potential efficacy benefit of the plinabulin/docetaxel combination over docetaxel alone. A global Phase 3 trial with the plinabulin/docetaxel combination vs docetaxel alone is currently underway in the US, China, Australia and New Zealand. Clinical trial information: NCT00630110.Adverse events. Plinabulin/Docetaxel Docetaxel Grade 3/4 Neutropenia * 7 % 25 % Use of G-CSF * 14 % 29 % Sepsis 0 % 3.6 % Severe infections 0 % 3.6 % Asthenia * 13 % 28 % Docetaxel dose reduction due to toxicity * 6 % 20 % *p<0.01; Plinabulin/docetaxel combination vs docetaxel alone.
Benefit of adjuvant chemotherapy and/or trastuzumab in T1ab node-negative human epidermal growth factor receptor 2–positive breast carcinomas: Results of a national multi-institutional study.
Authors: Alexandre de Nonneville, Anthony Goncalves, Christophe Zemmour, Jean-Marc Classe, Monique Cohen, Eric Lambaudie, Fabien Reyal, Sylvia Giard, Roman Rouzier, Richard Villet, Jean-Marie Boher, Gilles Houvenaeghel
Journal: Journal of Clinical Oncology (2016)

590 Background: Benefit of adjuvant Trastuzumab-based chemotherapy for node-positive and/or > 1 cm HER2+ breast carcinomas has been clearly demonstrated in randomized clinical trials. Yet, evidences for support adjuvant chemotherapy and/or Trastuzumab (CT+/-T) in pT1abN0 HER2+ tumors are limited. The primary objective of this study was to investigate the impact of adjuvant chemotherapy and/or Trastuzumab on outcome in this subpopulation. Methods: 245 cases of pT1abN0 HER2+ breast cancers were retrospectively identified from a large cohort of 5010 consecutive HER2+ patients who underwent primary surgery at 13 French centers, between Dec 1999 and Jan 2013. The primary endpoint was disease-free survival (DFS). A multivariate Cox model was built including adjuvant CT+/-T, tumor size and hormone receptor (HR) status. Results: A total of 102 cases (42%) were treated with CT+/-T, 23 with chemotherapy alone, 2 with Trastuzumab alone, and 118 (48%) with neither Trastuzumab nor chemotherapy. Patient characteristics were as follows (treated vs. untreated): the median follow-up was 40.07 vs. 52.85 months (p = 0.16). The median age was 53 vs. 58 years. Proportions of pT1a were 29.13 vs. 52.54%, pT1b: 70.87 vs. 47.46%, SBR grade III: 48.39 vs. 19.63%, HR-: 48.03 vs. 32.20%, HR+: 51.97 vs. 67.80%. In this last subgroup, 51.18 vs. 58.47% have had an endocrine therapy (p = 0.25). Adjuvant CT+/-T was associated with a significant 5-year DFS benefit (95% versus 86%; p = 0.049, Log-rank test), which was maintained in multivariate analysis (Hazard Ratio = 0.299; 95% CI [0.10,0.90]; p = 0.033). Exploratory subgroup analysis found this benefit to be significant in pT1b (5-year DFS of 99% versus 87%, p = 0.015) or HR-negative (5-year DFS of 97% versus 72%, p = 0.016) tumors. Conclusions: Adjuvant therapy with chemotherapy and/or Trastuzumab was associated with a significantly reduced risk of recurrence in subcentimetric node negative HER2+ breast cancers. Most of benefit may be driven by pT1b or HR-negative tumors. These data provide additional clues to the issue of adjuvant systemic treatment in these tumors.
A multicenter, cross-sectional research of the adherence to endocrine therapy with selective estrogen receptor modulators (SERMs) in premenopausal women in China.
Authors: Peng Yuan, Anjie Zhu, Binghe Xu, Shusen Wang, Yongmei Yin, Ying Lin, Jin Zhang, Zhongsheng Tong, Xiaojia Wang, Fengxi Su, Xichun Hu, Jifeng Feng, Tao Sun, Xianming Wang, Jinsong Lu, Jun Jiang, Feng Jin, Qingyuan Zhang
Journal: Journal of Clinical Oncology (2016)

e12025 Background: Adjuvant hormonal therapy(HT) significantly improves long-term survival of breast cancer patients with positive hormone receptor. Although international clinical trials have clearly demonstrated the benefit of selective estrogen receptor modulators（SERMs）in premenopausal women with primary breast cancer, little is known about how these drugs are actually used in the general population. At present, there is no data concerning the adherence and reasons of nonadherence in premenopausal women starting tamoxifen or toremifene as adjuvant breast cancer therapy in China. This cross-sectional research was conducted to provide the current prevalence of adherence adjuvant hormonal therapy with SERMs among premenopausal breast cancer patients in China. Methods: 1017 subjects from 10 medical centers of China were initiating tamoxifen or toremifene for primary breast cancer from Jan 2009 to Jun 2010. With longer than 5-year follow-up data, we examined the rate of completing the planned hormone therapy and factors related to discontinuation. Results: Overall adherence decreased to 56.64% by year 5 of therapy. Treatment nonadherence was mainly associated with side effects(34.07%), switching from SERMs to other hormonal therapies(19.61%) and relapse of disease(10.05%). Statistically significant factors associated with adherence of hormone therapy use were age, side effects and safety concerns, disease relapse and switching therapies. Conclusions: Adherence to adjuvant hormonal therapy with SERMs among premenopausal breast cancer survivors in China is suboptimal. Side effects and safety concerns were the leading cause of discontinuation. Further investigation is critical to identify interventions to improve continuation of hormonal therapy.
Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems
Authors: Ken Y Chan, Min J Jang, Bryan B Yoo, Alon Greenbaum, Namita Ravi, Wei-Li Wu, Luis Sánchez-Guardado, Carlos Lois, Sarkis K Mazmanian, Benjamin E Deverman, Viviana Gradinaru
Journal: Nature Neuroscience (2017)
One stop screening for multiple cancer types: 10 year experience of an integrated cancer prevention center.
Authors: Nadir Arber, Ari Leshno, Shiran Shapira, Eliezer Liberman, Eyal Gur, Hanoch Elran, Sarah Kraus, Miri Sror, Amira Harlap-Gat, Lior Galazan, Maayan Jean, Galit Av, Ada Kessler, Arye Blachar, Orit Golan, Shlomi Benjamin, Ravit Geva, Menachem Moshkowitz
Journal: Journal of Clinical Oncology (2016)

1555 Background: Cancer is the leading cause of mortality worldwide. Prevention and early detection are the pivotal tools for reducing cancer morbidity and mortality. Methods: We describe the 10 year experience (2006-2015) of an integrated cancer prevention center that provides screening for prevention and early detection of 11 cancer types (table) for healthy individuals (age 20-80 years). Extensive clinical and epidemiological data was obtained from all patients. Peripheral blood DNA was extracted from all participants and the APC I1307K and APC E1317Q polymorphisms were genotyped in all participants. Results: A total of 5022 (49%) men and 5217 (51%) women mean age 47.2±11.5 years were screened. Malignant lesions were detected in 355 (3.5%) of screenees. The most common cancers were skin (159, 1.6%), breast (44, 0.4%), gastrointestinal tract (43, 0.4%), gynecological (31, 0.3%) and male reproductive system (30, 0.3%). Forty four patients (0.4%) had more than one cancer. The APC I1307K and E1317Q variants were detected in 456 (5.6%) and 146 (1.4%) subjects respectively. First degree family member with cancer, I1307K carriership, alcohol intake, female gender, smoking and advanced age were all associated with increased cancer risk (Table). Family history of cancer in first degree relative and advanced age were also associated with increased risk for multiple malignancies. Conclusions: One stop shop screening for 11 common cancers in the setting of a multidisciplinary outpatient clinic is feasible and can prevent and detect cancer at an early stage and improve morbidity and mortality of the number one terrorist world-wide. Clinical trial information: 04-474.Types of cancer evaluated during screening. Skin Oral cavity Thyroid Breast Lung (heavy smokers) Cervix Uterus Prostate Testicles Colon and rectum Lymph nodes Risk factor OR 95% CI for OR Lower Upper Family history of cancer in FDR *3.01 2.4 3.8 APC I1307K *1.93 1.3 2.8 Age *1.06 1.1 1.1 Smoking *1.58 1.2 2.0 Female gender *1.63 1.3 2.1 Alcohol *1.69 1.4 2.1 APC E1317Q 0.64 0.2 1.8 *P value <0.001
Preliminary results of an open labelled phase 2 study evaluating the safety and efficacy of sorafenib in metastatic advanced thyroid cancer
Authors: M. Ahmed, Y. Barbachano, A. M. Riddell, S. Whittaker, K. Newbold, K. Harrington, R. Marais, C. M. Nutting
Journal: Journal of Clinical Oncology (2008)

6060 Background: Sorafenib exerts both anti-tumour and anti-angiogenic effects from tyrosine kinase inhibition (TKI) of BRAF, VEGF, c-kit and RET. This study is designed to assess the activity and safety profile of sorafenib in advanced/metastatic thyroid cancer patients. Methods: Patients with advanced/metastatic medullary (med) or differentiated (diff) thyroid cancer and age >18, PS 0 -1, iodine refractory measurable disease, no prior treatment with TKI, adequate hepatic, renal and haematological function are eligible. The study is IRB/REC and MHRA approved (Eudract 2006–006615–80). Primary end point is best objective overall response (BOR) following 6 months of study drug as determined by modified RECIST criteria incorporating radiological (CT) and biochemical (tumour marker) responses. Secondary end points include BOR at 3, 9 and 12 months, safety and tolerability, biomarkers, and progression free survival. Results: Since May 2007, 18 (10 Med, 8 Diff) patients recruited to the study have commenced the drug. 10 patients have follow up at 3 months and 2 of these patients have follow up at 6 months. The remainder have been on the drug for < 3 months and can not yet be assessed. At 3 months BOR for 9 patients is stable disease (SD) and one patient has demonstrated a partial response (PR). At 6 months 2/2 pts have SD. Biochemically 7 out of 7 assessable patients have demonstrated a PR. Common adverse events (AEs) include diarrhoea (G1/2=50%), hand foot syndrome (G1/2=39%, G3=17%), other skin toxicity (G1/2=44%, G3=6%), alopecia (G1/2=28%), hypertension (G1/2=22%, G3=6%), infection (G1/2=17%, G3=6%) and nausea (G1/2=17%). Three drug related SAEs have been reported (two hospitalisations for non-neutropenic fever associated with infection and one for prolonged hypocalcaemia). 78% of patients have required a dose reduction from the starting dose of 400 mg b.d. Conclusions: Sorafenib appears tolerable and early results suggest promising efficacy in advanced medullary and differentiated thyroid cancers despite dose reductions. No significant financial relationships to disclose.
Etude randomisée comparant l'efficacité de la capsule endoscopique et de l'entéroscopie poussée dans la prise en charge des saignements digestifs inexpliqués
Authors: A de Leusse, K Vahedi, J Edery, C Cellier, Y Bouhnik, R Jian
Journal: Endoscopy (2005)

Les performances de la capsule endoscopique (CE) dans le diagnostic étiologique des saignements digestifs inexpliqués (SDI) sont bien étayées. En revanche, la rentabilité et la place de cette exploration par rapport à l'entéroscopie poussée (EP) restent à préciser car les rares études contrôlées publiées ont comporté la réalisation systématique des deux explorations. Nous avons donc conduit une étude prospective randomisée pragmatique comparant une stratégie basée sur l'une ou l'autre de ces explorations.
Effect of mammographic density change on endocrine responsiveness independent of tumor biology associated with 21-gene recurrence score.
Authors: Sung Gwe Ahn, Hak Woo Lee, Jong Won Lim, Joon Jeong
Journal: Journal of Clinical Oncology (2016)

e12066 Background: Mammographic density reduction is known to be a predictive marker for endocrine responsiveness in estrogen receptor (ER)-positive patients with breast cancer. Also, it is well established that endocrine alone is optimized treatment in the patients with low 21-gene recurrence score. In this study, we investigated the association between RS and mammographic density reduction in terms of endocrine responsiveness. Methods: Among patients with breast cancer in whom 21-gene assay (Oncotype DX Breast Cancer Assay; Genomic Health, Inc., Redwood City, USA) was tested, women who had a baseline mammogram and a follow-up mammogram were identified. Mammographic density was measured by an automated thresholding method and expressed as percent density (PD). The change of PD was calculated as percentage change from baseline to follow-up taken after 1 year endocrine treatment. The association between 21-gene recurrence score and the change of PD was tested as continuous and categorical variables. Results: Between June 2012 and January 2015, 103 patients were eligible. The 21-gene assay assigned 59 (57.3%) patients as low recurrence score, 35 (34.0%) as intermediate recurrence score, and 9 (8.7%) as high recurrence score. The means of baseline PD were not different among the three groups by 21-gene recurrence score (P = 0.709; 21.9 in low recurrence score, 22.1 in intermediate score, and 17.5 in high recurrence score, respectively). When we compared reduction ratio of PD with continuous recurrence score, there is no correlation (P= 0.335). The patients with a relative reduction of PD greater than 20% belonged to the group of PD reduction. The reduction of PD was observed in 29 (28.1%) women. The proportion of PD reduction group was not different across three groups by 21-gene recurrence score (P= 0.380). Even distribution of the patients with PD reduction was noted in three groups. Conclusions: There is no association between 21-gene recurrence score and percent density change in ER-positive women with breast cancer. Our findings imply that mammographic density change reflects endocrine responsiveness independent of tumor biology associated with 21-gene RS.
U.S. Multicenter Clinical Trial of Corneal Collagen Crosslinking for Treatment of Corneal Ectasia after Refractive Surgery
Authors: Peter S. Hersh, R. Doyle Stulting, David Muller, Daniel S. Durrie, Rajesh K. Rajpal, Perry S. Binder, Eric D. Donnenfeld, Daniel Durrie, David Hardten, Peter Hersh, Francis Price, J. Bradley Randleman, David Schanzlin, Walter Stark, R. Doyle Stulting, William Trattler, Steven Trokel
Journal: Ophthalmology (2017)
Mitochondria apoptosis pathway synergistically activated by hierarchical targeted nanoparticles co-delivering siRNA and lonidamine
Authors: Bing-Feng Zhang, Lei Xing, Peng-Fei Cui, Feng-Zhen Wang, Rong-Lin Xie, Jia-Liang Zhang, Mei Zhang, Yu-Jing He, Jin-Yuan Lyu, Jian-Bin Qiao, Bao-An Chen, Hu-Lin Jiang
Journal: Biomaterials (2015)
Nuclear grade and ER/PR expression level on residual tumor after preoperative chemotherapy to predict late recurrence in estrogen receptor-positive breast cancer.
Authors: Madoka Iwase, Naoki Hayashi, Atsushi Yoshida, Yuka Kajiura, Junko Takei, Koyu Suzuki, Seigo Nakamura, Hideko Yamauchi
Journal: Journal of Clinical Oncology (2016)

e12049 Background: It is not known which population of estrogen receptor (ER)-positive/HER2-negative breast cancer patients should continue hormonal therapy beyond 5 years to overcome late recurrence. We have shown that nuclear grade (NG)-low/ER-high expression/progesterone receptor (PR)-high expression on surgical specimen might have benefit of extending hormonal therapy beyond 5 years in patients who received preoperative chemotherapy. The aim of this study was to verify our hypothesis that residual tumor on surgical specimen modified by preoperative chemotherapy would be a better predictor of late recurrence than preoperative biopsy specimen. Methods: We assessed retrospectively 467 ER-positive/HER2-negative patients who underwent surgical resection after preoperative chemotherapy and received adjuvant hormonal therapy. NG, and ER/PR expression level were determined by immunohistochemistory on biopsy specimen and surgical specimen. We classified the patients into 3 groups as follows; ER-high/PR-high, ER-high/PR-low, and ER-low/PR-any. We compared distant disease-free survival (DDFS) in each cohort based on the NG-low or high. Results: On the biopsy specimen before chemotherapy, patients with ER-high/PR-high were significantly higher DDFS rate before 5 years than those with ER-high/PR-low regardless of NG-low or high (p = 0.023, and p = 0.000, respectively). However, there was no association of NG and ER/PR expression level with risk of recurrence after 5 years. On the surgical specimen, there was no association of NG and ER/PR expression level with risk of recurrence before 5 years. However, patients with NG-low/ER-high/PR-high turned to have significantly high risk of recurrence after 5 years (p = 0.024). Conclusions: As we hypothesized, our results indicated that NG and ER/PR expression level on residual tumor of surgical specimen after preoperative chemotherapy predict late recurrence better than that on preoperative biopsy specimen. Furthermore, patients with NG-low/ER-high/PR-high on residual tumor who received preoperative chemotherapy were recommended to extend hormonal therapy beyond 5 years.
Place de l'endoscopie thérapeutique dans la prise en charge palliative des cancers du pancréas. A propos d'une expérience tunisienne
Authors: D Gargouri, N Belhadj, A Kilani, A Kochlef, H Elloumi, M Romani, J Kharrat, A Ghorbel
Journal: Endoscopy (2006)

L'endoscopie, par la mise en place de prothèses biliaires et duodénales, constitue une alternative à la chirurgie.
Abstract 13551: Impact of Acetylcholine-provoked Diffuse Coronary Spasm on Clinical Features and Long-term Prognosis of Patients With Coronary Spasm
Authors: Koji Sato, Koichi Kaikita, Hiromi Yoshimura, Naoki Nakayama, Eiji Horio, Keisuke Ohba, Kenichi Tsujita, Shinji Tayama, Seiji Hokimoto, Kunihiko Matsui, Seigo Sugiyama, Hiroshige Yamabe, Hisao Ogawa
Journal: Circulation (2013)

Coronary vasospastic angina (VSA) plays an important role in the pathogenesis of ischemic heart disease (IHD). It is reported that patients with VSA have better prognosis than those with obstructiv...