tbuckley/cabot-search huggingface dataset:
Ability of disease-modifying antirheumatic drugs to prevent or delay rheumatoid arthritis onset: a systematic literature review and meta-analysis
Authors: Stéphane Hilliquin, Benjamin Hugues, Stéphane Mitrovic, Laure Gossec, Bruno Fautrel
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Recent advances in knowledge of the pathogenesis of rheumatoid arthritis (RA) has led to promoting very early intervention. <h3>Objectives</h3> To assess the efficacy of therapeutic interventions in preventing or delaying RA onset with a systematic literature review (SLR) and meta-analysis (MA). <h3>Methods</h3> The SLR aimed to include all reports of randomised controlled trials of disease-modifying antirheumatic drugs or glucocorticoids used in patients presenting genetic and/or environmental risk factors for RA and/or systemic autoimmunity associated with RA, and/or symptoms without clinical arthritis and/or unclassified arthritis and in patients with RA. We searched PubMed, EMBASE and Cochrane databases for English articles published from 2006 to 2016 using the keywords 'undifferentiated arthritis' or 'very early rheumatoid arthritis' with 'therapy' or 'treatment'. Main outcome was RA occurrence, defined as fulfilment of the 1987 ACR criteria. The MA was performed with RevMan with the Mantel-Haenszel method. <h3>Results</h3> Among 595 abstracts screened, 10 reports of trials were selected. The studies included 1156 patients, with mean symptom duration 16.2±12.6 weeks. The occurrence of RA was available for nine studies, assessing methylprednisolone, methotrexate, a tumour necrosis factor blocker, abatacept or rituximab. In the group arthralgia without arthritis (people at risk of RA), the MA of the two available studies did not show significant reduction in RA occurrence at week 52 or more (pooled OR 0.74, 95% CI 0.37 to 1.49). For people with undifferentiated arthritis, the MA of the seven available studies revealed significant risk reduction with OR 0.73(95% CI 0.56 to 0.97). <h3>Conclusions</h3> This MA demonstrates that early therapeutic intervention may significantly reduce the risk of RA onset in this very first phase of the disease.
Midostaurin in patients with indolent systemic mastocytosis: An open-label phase 2 trial
Authors: Bjorn van Anrooij, Joanne N.G. Oude Elberink, Lambert F.R. Span, Jan G.R. de Monchy, Stefano Rosati, André B. Mulder, Johanna C. Kluin-Nelemans
Journal: Journal of Allergy and Clinical Immunology (2018)
Prediction of pathologic complete response by image-guided biopsy before surgery in breast cancer with complete clinical response to neoadjuvant chemotherapy: A prospective feasibility trial.
Authors: Han-Byoel Lee, Soo-Yeon Kim, Kyung Eun Kim, Jung Hyun Park, Young Wook Ju, Eunshin Lee, Hee-Chul Shin, Hyeong-Gon Moon, Dong-Young Noh, In-Ae Park, Nariya Cho, Wonshik Han
Journal: Journal of Clinical Oncology (2018)

566 Background: Patients who attain a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) have a favorable long-term outcome. In patients with pCR, it is suggested that the role of surgical excision may be limited to pathological confirmation, and thus may be omitted when pCR can be correctly predicted. The purpose of this study was to evaluate how accurately pCR can be predicted using MRI and image-guided biopsy. Methods: We prospectively enrolled 40 patients (mean age 47.1) between September 2016 and January 2018 who were suggested to have pCR on preoperative MRI. Lesion size ≤0.5cm or lesion-to-background parenchymal signal enhancement (SER) ratio ≤1.6 on MRI was defined as complete clinical response. Multiple core needle biopsy(CNB) (14G) or vacuum-assisted biopsy(VAB) (10G) was alternatively performed for the tumor bed around a clip marker placed during the course of NAC. Standard surgical excision was performed after biopsy. Matched biopsy and surgical specimens were compared for pCR assessment. Results: Pathologic complete response was confirmed in 27 (67.5%) surgical specimens, including 14/19 (73.7%) of HR-/HER2- and 6/8 (75%) of HR-/HER2+ patients. Preoperative biopsy had an accuracy of 90% (95% CI: 76-97%), negative predictive value of 87.1% (95% CI: 75-94%), and a false-negative rate of 30.8% (95% CI: 14-70%). Among four patients whose biopsy was not accurate in predicting pCR, two tumors were predicted to be > 0.5cm on MRI and two had less than five cores biopsied. Obtaining at least five cores in patients with ≤0.5cm lesion on MRI resulted in an accuracy of 97.1% (33/34), negative predictive value of 96.2% (25/26), and a false negative rate of 10%. There was no difference in accuracy in between multiple CNB and VAB. Breast pCR did not correlate with nodal status in 11.1% (3/27). Conclusions: Image-guided CNB or VAB can accurately identify patients with breast pCR in selected patients using preoperative MRI findings. This information will be used in a prospective clinical trial evaluating clinical safety of omitting breast surgery in patients with a breast pCR as determined by image-guided biopsy. Clinical trial information: NCT03273426.
ERBB Signaling Interrupted: Targeting Ligand-Induced Pathway Activation
Authors: Frederick H. Wilson, Katerina Politi
Journal: Cancer Discovery (2018)

<b/> A patient with advanced lung adenocarcinoma harboring a CD74-NRG1 gene rearrangement, which promotes ERBB2-ERBB3 heterodimerization and activation of downstream signaling, had an exceptional therapeutic response to an experimental anti-ERBB3 antibody. This result illustrates how NRG1 rearrangements, which are observed at a low frequency in a variety of solid tumors, may represent tractable therapeutic targets. Cancer Discov; 8(6); 676-8. ©2018 AACR.See related article by Drilon et al., p. 686.
Beyond the “at risk mental state” concept: transitioning to transdiagnostic psychiatry
Authors: Patrick D. McGorry, Jessica A. Hartmann, Rachael Spooner, Barnaby Nelson
Journal: World Psychiatry (2018)

The “at risk mental state” for psychosis approach has been a catalytic, highly productive research paradigm over the last 25 years. In this paper we review that paradigm and summarize its key lessons, which include the valence of this phenotype for future psychosis outcomes, but also for comorbid, persistent or incident non‐psychotic disorders; and the evidence that onset of psychotic disorder can at least be delayed in ultra high risk (UHR) patients, and that some full‐threshold psychotic disorder may emerge from risk states not captured by UHR criteria. The paradigm has also illuminated risk factors and mechanisms involved in psychosis onset. However, findings from this and related paradigms indicate the need to develop new identification and diagnostic strategies. These findings include the high prevalence and impact of mental disorders in young people, the limitations of current diagnostic systems and risk identification approaches, the diffuse and unstable symptom patterns in early stages, and their pluripotent, transdiagnostic trajectories. The approach we have recently adopted has been guided by the clinical staging model and adapts the original “at risk mental state” approach to encompass a broader range of inputs and output target syndromes. This approach is supported by a number of novel modelling and prediction strategies that acknowledge and reflect the dynamic nature of psychopathology, such as dynamical systems theory, network theory, and joint modelling. Importantly, a broader transdiagnostic approach and enhancing specific prediction (profiling or increasing precision) can be achieved concurrently. A holistic strategy can be developed that applies these new prediction approaches, as well as machine learning and iterative probabilistic multimodal models, to a blend of subjective psychological data, physical disturbances (e.g., EEG measures) and biomarkers (e.g., neuroinflammation, neural network abnormalities) acquired through fine‐grained sequential or longitudinal assessments. This strategy could ultimately enhance our understanding and ability to predict the onset, early course and evolution of mental ill health, further opening pathways for preventive interventions.
Effect and moderators of exercise on fatigue in patients with cancer: Meta-analysis of individual patient data.
Authors: Jonna van Vulpen, Maike Sweegers, Petra H.M. Peeters, Robert Usher Newton, Neil K Aaronson, Kerry S. Courneya, Paul Jacobsen, Irma Verdonck-De Leeuw, Johannes Brug, Laurien Buffart, Anne Maria May
Journal: Journal of Clinical Oncology (2018)

104 Background: Fatigue is a common and disabling complaint in patients with cancer and can be reduced by exercise. To further personalize exercise prescriptions, moderators of exercise effects on fatigue should be investigated. However, most randomized controlled trials (RCTs) are not adequately powered to identify heterogeneity in responses to exercise. Therefore, we conducted a meta-analysis using individual patient data (IPD) of exercise RCTs to investigate the effect and moderators of exercise on cancer-related fatigue. Methods: Within the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium, principal investigators of 34 exercise RCTs worldwide have shared their IPD, including in total 4366 cancer patients. A 1-step IPD meta-analysis, using a linear mixed-effect model with a random intercept on study was undertaken to investigate effect on fatigue. The result, a between-group difference in standardized z-scores, corresponds to a Cohen’s d effect size. An interaction term was included in the model to assess potential moderators including demographic (sex, age, marital status, education), clinical (body mass index, distant metastasis), intervention-related (timing, delivery mode, duration) and exercise-related (type, frequency, intensity, duration) characteristics. Results: Exercise significantly reduced fatigue (β = -0.17, 95% CI -0.22;-0.12). The effect was not moderated by demographic, clinical or exercise-related characteristics. Supervised exercise had significantly larger effects on fatigue than unsupervised exercise (β difference = -0.18, 95%CI -0.28;-0.08). Compared to the control group, supervised exercise significantly improved fatigue (β = -0.23, 95%CI = -0.29;-0.17), while unsupervised exercise did not (β = -0.04, 95%CI = -0.13;0.04). Conclusions: Exercise significantly reduces cancer-related fatigue across subgroups formed on the basis of demographic and clinical characteristics. The effect of exercise is significantly larger when performed under supervision. Hence, exercise, and preferably supervised exercise, represents a viable intervention for the prevention and treatment of fatigue among patients with cancer.
Phase Ib study of gedatolisib in combination with palbociclib and endocrine therapy (ET) in women with estrogen receptor (ER) positive (+) metastatic breast cancer (MBC) (B2151009).
Authors: Andres Forero-Torres, Heather Han, Elizabeth Claire Dees, Robert Wesolowski, Aditya Bardia, Peter Kabos, Rachel M. Layman, Janice M. Lu, Kenneth Alan Kern, Rachelle Perea, Kristen J. Pierce, Brett Houk, Nuzhat Pathan, Hope S. Rugo
Journal: Journal of Clinical Oncology (2018)

1040 Background: The majority of women with ER+ MBC develop resistance to ET. ET plus a CDK4/6 inhibitor (CDKi 4/6) demonstrate improved progression-free survival (PFS) in first/later line MBC. Preclinical evidence in PI3K mutant cell-line xenografts (PIK3CA) supported developing a triplet combination of gedatolisib (G), a dual inhibitor of PI3K/mammalian target of rapamycin (mTOR), with CDKi 4/6 palbociclib (P)+letrozole (L) or fulvestrant (F) for patients (pts) with ER+/HER2- MBC. Methods: This ongoing dose escalation/expansion study in pts with ER+/HER2- MBC, in first/later line MBC, evaluates dose-limiting toxicities/recommended phase 2 dose (DLTs/RP2D) for triplet regimens of G+P+L or G+P+F. A 3-arm expansion investigates objective response rate (ORR) compared to historical controls of Arm A) G+P+L in first-line, B) G+P+F in pts with no prior CDKi 4/6 in second-line and C) G+P+F in pts with prior CDKi 4/6. Pts receive G (180 mg IV/week) combined with P+L or P+F at standard of care doses. Secondary endpoints include safety, ORR, PFS, and pharmacokinetics (PK); exploratory endpoints include genomic analysis of PI3K/mTOR pathway. Results: 35 pts received G at RP2D of 180 mg with P+L (n = 15) or P+F (n = 20). Median numbers of prior therapies: G+P+L: 2 (range: 1-2); G+P+F: 1 (range 1-3). Most common (≥50%), drug-related adverse events (%): G+P+L: nausea (80), stomatitis (73), fatigue (60), neutropenia (60), dysgeusia (53); G+P+F: stomatitis (70), fatigue (70), neutropenia (60), nausea (60), dysgeusia (55). Cycle 1 DLTs: G+P+L: grade (gr) 3 neutropenia (n = 2), gr 3 stomatitis (n = 1), gr 3 febrile neutropenia (n = 1); G+P+F: gr 3 stomatitis (n = 2), gr 3 mucositis (n = 1), gr 3 abdominal pain (n = 1). Preliminary stable disease/partial response: G+P+L: 53%/33%; G+P+F: 55%/20%. No PK interactions were observed. PIK3CA and ER mutation status from circulating free deoxyribonucleic acid and duration of response will be reported. Genomic analysis of tumor tissue is underway. Conclusions: G can be combined with P+L or P+F with manageable toxicity and promising preliminary antitumor activity. Dose escalation is completed and expansion is ongoing. Clinical trial information: NCT02684032.
EGFR, MUC-1 and PD-L1 expressions in cases with triple negative breast cancer (TNBC).
Authors: Semra Paydas, Cem Mirili, Emine Bagir, Gulsah Seydaoglu, Ali Oğul, Mahmut Büyüksimsek, Abdullah Evren Yetisir, Bilgin Karaalioglu, Mert Tohumcuoglu
Journal: Journal of Clinical Oncology (2018)

e12584 Background: Immune checkpoint ligand PD-L1 and transmembrane oncogenic protein MUC-1 are upragulated in TNBC and contribute aggressive behavior of this disease. It has been shown that pharmacologic targeting of MUC-1 suppress the PD-L1 expression in cell lines. The aim of this study is to explore the association between MUC-1, PD-L1 and EGFR expressions in tumor samples and to compare them with survival times and also possible role of therapeutic targeting of these molecules Methods: MUC-1, EGFR and PD-L1 expressions were detected by immunohistochemistry in cases with TNBC. Clinical and prognostic parameters were compared with MUC-1, EGFR and PD-L1 expressions Results: 97 cases with TNBC were evaluated; 17 of them had stage I, 47 had stage II, 27 had stage III and 6 had stage IV disease. All of the cases had been treated by anthracycline and taxane containing regimens. MUC-1, EGFR and PD-L1 were detected in 34, 61 and 17 cases, respectively. PFS and OS were found to be longer in cases with EGFR expression and MUC-1 and EGFR double expressors for MUC-1 and EGFR. Table 1 shows PFS and OS times according to the EGFR, MUC-1 and PDL-1 expressions. EGFR was found to be significant in Cox regression analysis. Conclusions: EGFR was found to be the most important prognostic indicator in patients with TNBC. Table 1. Progression free survival (PFS) and overall survival (OS) according to MUC-1, EGFR and PD-L1 expression in TNBC. Total(n) PFS OS Total(%) Event (n) Mean p* Mean p MUC1 negative 63 64,9 23 96,499 ,176 112,039 0.202 positive 34 35,1 8 122,744 132,350 EGFR negative 36 37,1 17 84,714 ,050* 92,889 0,013* positive 61 62,9 14 120,362 133,890 PD-L1-tumor negative 80 82,5 28 105,687 0,207 116,125 ,121 positive 17 17,5 3 125,889 135,182 PD-L1-microenvironment negative 77 79,4 27 103,807 0,118 117,411 ,199 positive 20 20,6 4 127,930 133,500 MUC1-EGFR Both (-) 24 24,7 14 69,750 77,458 Both (+) 22 22,8 5 119,773 0,045* 131,136 ,025* MUC1-PD-L1 Both (-) 55 56,7 22 106,964 Both (+) 10 10,3 2 130,400 ,250
Sustaining Health-Protective Behaviors Such as Physical Activity and Healthy Eating
Authors: Genevieve F. Dunton
Journal: JAMA (2018)

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Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update
Authors: Antonio C. Wolff, M. Elizabeth Hale Hammond, Kimberly H. Allison, Brittany E. Harvey, Pamela B. Mangu, John M.S. Bartlett, Michael Bilous, Ian O. Ellis, Patrick Fitzgibbons, Wedad Hanna, Robert B. Jenkins, Michael F. Press, Patricia A. Spears, Gail H. Vance, Giuseppe Viale, Lisa M. McShane, Mitchell Dowsett
Journal: Journal of Clinical Oncology (2018)

Purpose To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline. Methods Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations. Recommendations Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in > 10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not "must") be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended work-up for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 ( HER2/chromosome enumeration probe 17 [CEP17] ratio ≥ 2.0; average HER2 copy number < 4.0 signals per cell), ISH group 3 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 6.0 signals per cell), and ISH group 4 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 4.0 and < 6.0 signals per cell). The diagnostic approach includes more rigorous interpretation criteria for ISH and requires concomitant IHC review for dual-probe ISH groups 2 to 4 to arrive at the most accurate HER2 status designation (positive or negative) based on combined interpretation of the ISH and IHC assays. The Expert Panel recommends that laboratories using single-probe ISH assays include concomitant IHC review as part of the interpretation of all single-probe ISH assay results. Find additional information at www.asco.org/breast-cancer-guidelines .
Hematopoietically Active Adrenal Myelolipoma Mimicking Breast Cancer Metastasis
Authors: John J. Manov, Alexander Diaz-Bode, Russ Kuker
Journal: Clinical Nuclear Medicine (2018)

A 66-year old woman had a left breast mass. Biopsy showed invasive ductal carcinoma. A PET/CT scan demonstrated hypermetabolism in the left breast and atypical heterogeneously increased uptake throughout the skeleton as well as a minimally FDG-avid right adrenal myelolipoma. PET/CT 4 months later after 6 cycles of neoadjuvant chemotherapy demonstrated increased size and FDG avidity of this adrenal mass concerning for metastasis and uniformly increased skeletal FDG avidity. Biopsy demonstrated adrenal myelolipoma. The growth and increased FDG avidity of the adrenal myelolipoma were due to the action of colony-stimulating factors on the tumor's hematopoietic component.
The Use of Carbamazepine to Expedite Metabolism of Risperidone Long-Acting Injection Through Induction of CYP3A4 in a Patient With Extrapyramidal Symptoms
Authors: Paul A. Fuchs, Lindsey Miller, Max Schiff
Journal: American Journal of Psychiatry (2018)

Aggression ratings were lower by a mean of 1.5 points (SD56.2) in children whose mothers had phosphatidylcholine supplementation compared with placebo, but there was no similar effect of phosphatidylcholine supplementation compared with placebo for children whose mothers were abusing drugs and alcohol (20.4,SD55.7).These differences are not significant, and the number of children studied limits the certainty of any conclusions.As Wakschlag et al. note in their reply to Bell and Ajula, other risk factors may also affect these children.However, it would seem that public health efforts should encourage both prenatal drug and alcohol abstinence and phosphatidylcholine supplementation, now recommend by the American Medical Association (3), along with other elements of good maternal care, at the time of conception or as early in gestation as possible.
Efficacy of chemotherapy or chemo‐anti‐PD‐1 combination after failed anti‐PD‐1 therapy for relapsed and refractory hodgkin lymphoma: A series from lysa centers
Authors: Cédric Rossi, Julia Gilhodes, Marie Maerevoet, Charles Herbaux, Franck Morschhauser, Pauline Brice, Sylvain Garciaz, Cécile Borel, Loïc Ysebaert, Lucie Obéric, Julien Lazarovici, Bénédicte Deau, Jehan Dupuis, Adrien Chauchet, Julie Abraham, Fontanet Bijou, Aspasia Stamatoullas‐Bastard, Jean‐Valère Malfuson, Camille Golfier, Camille Laurent, Sarah Pericart, Alexandra Traverse‐Glehen, Salim Kanoun, Thomas Filleron, René‐Olivier Casasnovas, Hervé Ghesquières
Journal: American Journal of Hematology (2018)

Abstract Anti‐PD‐1 therapy provides high response rates in Hodgkin lymphoma (HL) patients who have relapsed or are refractory (R/R) to autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV), but median progression free survival (PFS) is only one year. The efficacy of treatment following anti‐PD‐1 is not well known. We retrospectively investigated the efficacy of salvage therapies for unsatisfactory response to anti‐PD‐1 therapy, assessed by PET‐CT according to the Lugano criteria, in 30 R/R HL patients. Patients were highly pretreated before anti‐PD‐1 (70% received ASCT and 93% BV). Unsatisfactory responses to anti‐PD1 therapy were progressive disease (PD) ( n = 24) and partial response (PR) ( n = 6). For the 24 PD patients, median anti‐PD‐1 related PFS was 7.5 months (95%CI, 5.7‐11.6); 17 received subsequent CT alone (Group 1) and 7 received CT in addition to anti‐PD‐1 (Group 2). 16/24 patients (67%) obtained an objective response. In the 15 patients treated with the same CT, twelve obtained PR or complete response (CR). In Group 1, there were 7 CR (41%), 3 PR (18%), and 7 PD (41%). In Group 2, there were 4 CR (57%), 2 PR (29%), and 1 SD (14%). No unexpected toxicity was observed. Six patients who achieved response proceeded to allogeneic SCT. With a median follow‐up of 12.1 months (7‐14.7), the median PFS following the initiation of CT was 11 months (95% CI 6.3‐not reached) and the median of overall survival was not reached. These observations in highly pretreated HL patients suggest that anti‐PD‐1 therapy might re‐sensitize tumor cells to CT.