tbuckley/cabot-search huggingface dataset:
Effects of resistance training on fatigue and quality of life in breast cancer patients undergoing radiotherapy.
Authors: Karen Steindorf, Martina E Schmidt, Oliver Klassen, Cornelia M Ulrich, Jan Oelmann, Nina Habermann, Philipp Beckhove, Robert Owen, Juergen Debus, Joachim Wiskemann, Karin Potthoff
Journal: Journal of Clinical Oncology (2014)

9534 Background: Breast cancer patients during and after radiotherapy often suffer from cancer-related fatigue which frequently impairs quality of life (QoL). Exercise may decrease fatigue and improve emotional well-being. However, studies on resistance training for patients during radiotherapy are scarce. Thus, we assessed the effects of a 12-week supervised resistance training intervention on fatigue and QoL in breast cancer patients during adjuvant radiotherapy within a randomized controlled trial. Methods: 160 patients (80/arm) with breast cancer stage 0-III undergoing adjuvant radiotherapy were randomly assigned to 12-weeks of progressive resistance training (2x/week) or group-based relaxation training (2x/week). The primary endpoint fatigue was assessed with the 20-item FAQ (0-10 scale), quality of life with the EORTC-QLQ-C30 and BR23 (0-100 scale). Statistical analyses were based on analysis of covariance models for the individual changes from pre- to post-intervention. Results: In intention-to-treat analyses, significant between-group mean differences (MD) favoring the intervention group were found for general fatigue (MD=-0.51, 95% confidence interval (CI): -1.01, -0.01, p=.044, effect size (ES)=0.33) and the subscale physical fatigue (MD=-0.83 (-1.48, -0.18), p=.013, ES=0.40), but not for affective (p=.91) or cognitive fatigue (p=.65). For QoL, significantly larger improvements regarding role function (MD=8.5 (0.6, 16.3), p=.035, ES=0.35) and pain (MD=-7.4 (-14.4, -0.3), p=.040, ES=0.34) were seen among exercisers compared to controls. Future perspective improved significantly stronger in the relaxation group than in exercise group (MD=-8.4 (-16.6, -0.1), p=.047, ES=0.34). Conclusions: This large randomized exercise intervention trial indicates that a 12-week resistance training program is an effective strategy to improve fatigue and important components of QoL in breast cancer patients during adjuvant radiotherapy. Further, as group-based relaxation training was chosen as control group and not usual care, our results indicate that resistance training provides beneficial effects that may go beyond psychosocial effects induced by group-based programs. Clinical trial information: NCT01468766.
Investigation of a food-borne outbreak of gastroenteritis in a school canteen revealed a variant of sapovirus genogroup V not detected by standard PCR, Sollentuna, Sweden, 2016
Authors: Maria-Pia Hergens, Joanna Nederby Öhd, Erik Alm, Helena H Askling, Sofia Helgesson, Mona Insulander, Nina Lagerqvist, Bo Svenungsson, Malin Tihane, Thomas Tolfvenstam, Per Follin
Journal: Eurosurveillance (2017)

A food-borne outbreak of gastroenteritis with more than 650 suspected cases occurred in April 2016 in Sollentuna, Sweden. It originated in a school kitchen serving a total of 2,700 meals daily. Initial microbiological testing (for Campylobacter, Salmonella, Shigella, Yersinia, Giardia, Cryptosporidium, Entamoeba histolytica , adeno-, astro-, noro-, rota- and sapovirus) of stool samples from 15 symptomatic cases was negative, despite a clinical presentation suggestive of calicivirus. Analyses of the findings from both the Sollentuna municipality environmental team and a web-based questionnaire suggested that the source of the outbreak was the salad buffet served on 20 April, although no specific food item could be identified. Subsequent electron microscopic examination of stool samples followed by whole genome sequencing revealed a variant of sapovirus genogroup V. The virus was not detected using standard PCR screening. This paper describes the epidemiological outbreak investigation and findings leading to the discovery.
Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: Findings of a Phase III Clinical Trial
Authors: Nicola Dalbeth, Graeme Jones, Robert Terkeltaub, Dinesh Khanna, Jeff Kopicko, Nihar Bhakta, Scott Adler, Maple Fung, Chris Storgard, Scott Baumgartner, Fernando Perez‐Ruiz
Journal: Arthritis & Rheumatology (2017)

To investigate the efficacy and safety of lesinurad in combination with febuxostat in a 12-month phase III trial in patients with tophaceous gout.Patients with serum urate (UA) ≥8.0 mg/dl (≥6.0 mg/dl with urate-lowering therapy) and ≥1 measurable target tophus were given febuxostat 80 mg/day for 3 weeks before randomization to receive lesinurad (200 or 400 mg daily) or placebo in addition to the febuxostat. The primary end point was the proportion of patients achieving a serum UA level of <5.0 mg/dl (month 6). The key secondary end point was the proportion of patients with complete resolution of ≥1 target tophus (month 12). Other end points included the percentage change in total target tophi area. Safety assessments included adverse events and laboratory data.Patients (n = 324) were predominantly male, with a mean age of 54.1 years. Significantly more patients achieved the serum UA target by month 6 with the addition of lesinurad 400 mg (76.1%; P < 0.0001), but not 200 mg (56.6%; P = 0.13), to the febuxostat therapy as compared with febuxostat alone (46.8%). At all other time points, significantly more patients in the lesinurad 200 mg group achieved the serum UA target. The number of patients with complete tophus resolution was not different between groups. Treatment with lesinurad (200 mg and 400 mg) plus febuxostat reduced the total target tophi area as compared with febuxostat alone (50.1% and 52.9% versus 28.3%, respectively; P < 0.05). Safety was generally comparable with that of febuxostat alone, except for higher rates of predominantly reversible elevations in the serum creatinine level, particularly with lesinurad 400 mg.Treatment with lesinurad in combination with febuxostat demonstrated superior lowering of serum UA levels as compared with febuxostat alone, with clinically relevant added effects on tophi and an acceptable safety profile with lesinurad 200 mg in patients with tophaceous gout warranting additional therapy.
BRCAness and prognosis of triple-negative breast cancer patients treated with neoadjuvant chemotherapy.
Authors: Sadako Akashi-Tanaka, Yuichi Tanino, Yutaka Yamamoto, Hiroshi Nishimiya, Mutsuko Yamamoto-ibusuki, Hirotaka Iwase, Seigo Nakamura
Journal: Journal of Clinical Oncology (2017)

e12111 Background: Triple-negative breast cancers (TNBCs) consist of patients which are recalcitrant to chemotherapy. Dysfunction of BRCA, called “BRCAness” may be predictive of sensitivity to DNA repair inhibitors. However, adequate assay of “BRCAness” are still not confirmed. Multiplex ligation-dependent probe amplification (MLPA) with the Probemix P376-B2 BRCA1ness (MRC-Holland, The Netherlands) can be one method to determine BRCAness. We previously reported that “BRCAness” by MLPA predict resistance to taxane during neoadjuvant chemotherapy (NAC) and poor outcome. In the present study, we evaluated the clinical significance of BRCAness in a multicenter retrospective study. Methods: The data on 94 patients with TNBC treated with NAC were obtained from 3 hospitals in Japan. Most of them were treated by anthracyclines plus taxanes in 86 patients between 2005 and 2015. BRCAness was determined by core needle biopsy (CNB) specimens prior to NAC and surgical specimens. Genes from those specimens were amplified by MLPA, and the amplicons were scored. BRCA1-like type (BRCAness) was determined by tumors with greater than 0.5 Results: pCR (ypT0/Tis/N0) rate was 46%. Recurrence occurred in 22 patients, 11 of whom died from breast cancer. (1) BRCA1-like type accounted for 51 patients while the sporadic type in 43 patients in CNB specimens. No major differences in pCR rates and recurrence were observed between the BRCA1-like type and sporadic type (19/51 vs. 24/43), respectively. Patients with BRCA1-like tended to resist taxane than those with sporadic type when treated with taxane first. Among the 51 non-pCR patients, 19 were BRCA1-like type and 31 were sporadic type upon surgical specimens. Patients with a BRCA1-like tumors had more recurrences, than non-BRCA-1-like (13/19 vs. 9/31, respectively, P &lt; 0.01). Conclusions: Tumors with BRCA-1 like tended to resist taxane than sporadic type when treated by taxane first. Anthracycline first might mask the progression during taxane regimen. Patients with BRCA1-like after NAC had more recurrences than those with sporadic type. Further study is needed to evaluate the significance of BRCAness.
Global Health Effects of Overweight and Obesity
Authors: Edward W. Gregg, Jonathan E. Shaw
Journal: New England Journal of Medicine (2017)

The Global Burden of Disease (GBD) study that is now reported in the Journal offers a discouraging reminder that the global obesity epidemic is worsening in most parts of the world and that its implications regarding both physical health and economic health remain ominous.1 The study, in which researchers assembled data from 195 countries to model trends in overweight and obesity and related morbidity and mortality, showed that the prevalence of obesity has more than doubled since 1980 and is now 5% in children and 12% in adults — findings that mirror similar global trends in type 2 diabetes. Apart . . .
Randomised controlled trial of long-term maintenance corticosteroid therapy in patients with autoimmune pancreatitis
Authors: Jatinder Goyal, Jodie A Barkin, Jamie S Barkin
Journal: Gut (2017)

We read with great interest the article by Masamune et al 1 regarding the role of long-term maintenance corticosteroids in patients with autoimmune pancreatitis (AIP).1 AIP is a steroid responsive disorder, which has two distinct entities with overlapping features, classified as type I and type II AIP. While type I AIP is a part of a spectrum of IgG4-related disease with extrapancreatic manifestations, type II is a pancreas-specific disease. The diagnostic criteria, treatment approach and prognosis are different between the …
Efficacy and Safety of Elbasvir/Grazoprevir in Treatment-Naive Subjects with Chronic HCV GT 1, GT 4 and GT 6 Infection (C-CORAL): A Phase III Randomized Multinational Clinical Trial
Authors: Jacob George, Eduard Z. Burnevich, I-Shyan Sheen, Jeong Heo, Kinh Nguyen Van, Tawesak Tanwandee, Pin-Nan Cheng, Do Young Kim, Won Young Tak, Svetlana N. Kizhlo, Li W. Liang, Pauline A. Lindore, Joy Ginanni, Bach-Yen T. Nguyen, Janice Wahl, Eliav Barr, Michael Robertson, Rohit Talwani
Journal: Hepatology (2016)
Recurrent Patterns of Protein Expression Signatures in Pediatric Acute Lymphoblastic Leukemia: Recognition and Therapeutic Guidance
Authors: Fieke W Hoff, Chenyue W Hu, Yihua Qiu, Suk-Young Yoo, Amina Qutub, Terzah M. Horton, Steven M. Kornblau
Journal: Blood (2016)
OlympiAD: Phase III trial of olaparib monotherapy versus chemotherapy for patients (pts) with HER2-negative metastatic breast cancer (mBC) and a germline <i>BRCA</i> mutation (gBRCAm).
Authors: Mark E. Robson, Seock-Ah Im, Elżbieta Senkus, Binghe Xu, Susan M. Domchek, Norikazu Masuda, Suzette Delaloge, Wei Li, Nadine M. Tung, Anne Armstrong, Wenting Wu, Carsten Dietrich Goessl, Sarah Runswick, Pier Franco Conte
Journal: Journal of Clinical Oncology (2017)

LBA4 Background: Olaparib is an oral PARP inhibitor with anti-tumor activity in HER2-negative mBC with a g BRCAm (NCT00494234). OlympiAD (NCT02000622) was a randomized, open-label, phase III study that assessed efficacy and safety of olaparib vs standard single agent chemotherapy treatment of physician’s choice (TPC) in pts with HER2-negative mBC and a g BRCAm. Methods: Pts aged ≥18 y with HER2-negative mBC (hormone receptor positive or triple negative [TN]) and a g BRCAm, who had received ≤2 chemotherapy lines for mBC, were randomized (2:1) to olaparib tablets (300 mg po bid) or TPC (21-day cycles of either capecitabine [2500 mg/m 2 po days 1–14], vinorelbine [30 mg/m 2 IV days 1 and 8] or eribulin [1.4 mg/m 2 IV days 1 and 8]). Treatment was continued until objective disease progression (RECIST v1.1) or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR). Results: 302 pts were randomized (median age 44 y; 50% TN; 71% prior chemotherapy for mBC; 28% prior platinum) of whom 205 received olaparib and 91 received TPC (6 TPC pts were not treated). At 77% data maturity, PFS by BICR was significantly longer in pts treated with olaparib vs TPC (HR 0.58; 95% CI 0.43, 0.80; P=0.0009; 7.0 vs 4.2 months, respectively). Time to second progression (investigator-assessed) was also longer in the olaparib arm (HR 0.57; 95% CI 0.40, 0.83). Objective response rate was 59.9 and 28.8% in olaparib and TPC arms, respectively. Grade ≥3 adverse events (AE) occurred in 36.6 and 50.5% of olaparib and TPC pts, with AEs leading to discontinuation in 4.9 and 7.7% of pts, respectively. Mean change from baseline in global health-related quality of life (HRQoL, EORTC-QLQ-C30) across all timepoints favored olaparib (difference vs TPC 7.5; 95% CI 2.48, 12.44; P=0.0035). Conclusions: Olaparib tablet monotherapy provided a statistically significant and clinically meaningful PFS benefit to HER2-negative mBC pts with a g BRCAm, compared to standard TPC. The safety profile of olaparib was consistent with prior studies. The efficacy benefit was seen beyond the first progression and HRQoL also improved. Clinical trial information: NCT02000622.
Adjuvant chemotherapy related toxicities and their impact on treatment cessation in elderly patients with breast cancer.
Authors: Muhammad Iqbal, Sukesh Manthri, Kathy Robinson, Robert S. Mocharnuk, Meghna R. Desai
Journal: Journal of Clinical Oncology (2017)

e21527 Background: Data from the National Cancer Institute’s Surveillance Epidemiology and End Results program show that the incidence of breast cancer is 243.1 per 100,000 in women 65 years of age and older. Guidelines regarding the management of older breast cancer patients are lacking due to their underrepresentation in adjuvant therapy trials and conflicting evidence regarding the benefits of therapy. The objective of this study was to investigate the frequency of adjuvant chemotherapy related side effects and their correlation with early termination of therapy in elderly breast cancer. Methods: We collected retrospective data in patients with in situ or invasive breast cancer diagnosed after the age of 65.Docetaxel &amp; cyclophosphamide, doxorubicin &amp; cyclophosphamide, tratuzumab in combination and other regimens were studied. Fisher’s exact test was used to determine an association between grade 3 or 4 toxicities and therapy termination. Binary logistic regression was used to assess whether a specific toxic effect could predict for early discontinuation of therapy. Treatment termination was defined as inability to tolerate the proposed number of chemotherapy treatment cycles. Results: Among 269 eligible cases, 72 (26.76%) patients were offered adjuvant chemotherapy. Most patients (n = 58, 80.55%) accepted chemotherapy but 14 (19.44%) refused. Nausea (n = 16, 27.6%), vomiting (n = 8, 13.8%), diarrhea (n = 12, 20.7%), stomatitis (n = 3, 5.2%), hypersensitivity (n = 3, 5.2%), rash (n = 10, 17.2%), hepatotoxicity (n = 1, 1.7%), neuropathy (n = 12, 20.7%), cognitive changes (n = 3, 5.2%), bone pain (n = 5, 8.6%), anemia (n = 15, 25.9%), thrombocytopenia (n = 7, 12.1%), neutropenia (n = 16, 27.6%), cardiotoxicity (n = 1, 1.7%), hospitalization due to neutropenic fever (n = 5, 8.6%) and pneumonia (n = 2, 3.4%) were observed. Among 17 patients who discontinued chemotherapy, 23.5% reported bone pain (OR = 12, 95%CI:1.22-117.2, p = 0.024) and 47.1% developed neutropenia (OR = 3.55, 95%CI:1.04-12.13, p = 0.054). Other toxicities were not significantly associated with therapy discontinuation. Conclusions: The odds of terminating chemotherapy early increases for those who experience grade 3 or 4 bone pain and neutropenia.
Assessment of multiple endocrine therapies for metastatic breast cancer in a multicenter national observational study.
Authors: Olivia Le Saux, Audrey Lardy-Cleaud, Sophie Frank, Paul H. Cottu, Barbara Pistilli, Marc Debled, Laurence Vanlemmens, Marianne Leheurteur, Anne-Valérie Guizard, Lilian Laborde, Lionel Uwer, Veronique D'hondt, Delphine Berchery, Veronique Lorgis, Jean-Marc Ferrero, Genevieve Perrocheau, Coralie Courtinard, Sylvie Chabaud, Mathieu Robain, Thomas Denis Bachelot
Journal: Journal of Clinical Oncology (2017)

1052 Background: For HR+/HER2– metastatic breast cancer (mBC), International guidelines recommend multiple lines of endocrine therapy (ET) before starting chemotherapy. Few studies have assessed the efficacy of such strategy on large populations. Our objective was to evaluate multiple ET activity according to clinical and biological characteristics and type of ET. Methods: All patients (pts) who initiated treatment for a newly diagnosed mBC between January 2008 and December 2014 in all 18 French Comprehensive Cancer Centers were included in the real life ESME database. ESME collects retrospective data using a clinical trial-like methodology. Database lock was 8 Dec 2016. Primary endpoint of the current study was progression free survival (PFS) on successive ET lines. Only pts with ET alone were assessed (pts receiving ET after chemotherapy as maintenance therapy, or combined with targeted treatment were excluded). Results: 9921 pts out of 16703 in ESME, had HR+/HER2- mBC (median age 62.0 years[range 23-96]). 53.9% of pts had visceral and 80.1% non visceral disease at diagnosis. Median OS of HR+/HER2- pts was 42.15 months (95% CI, 40.93-43.27). As first-line therapy, 4123 pts (41.6%) received ET alone, while 2038 received chemotherapy alone (20.5%) and 3667 received both (37%). Median PFS for first-line ET (N=4123) was 11.3 months (95% CI, 10.6-11.9). Only 668 pts (16%) received subsequent lines of ET alone. Types of ET used are described in the table below. Successive PFS will be reported at the meeting. Conclusions: Those data show that ET is prescribed to less than 50% of patients with HR+/HER2- mBC in first line and only to a small minority in subsequent lines. This is not in line with existing guidelines (NCCN, ABC3). Real-life median PFS for first-line ET is consistent with median PFS reported in clinical trials (Nabholtz, 2000). [Table: see text]
Predictors of prolonged benefit from palbociclib (PAL) plus fulvestrant (F) in women with endocrine-resistant hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) advanced breast cancer (ABC) in PALOMA-3.
Authors: Massimo Cristofanilli, Angela DeMichele, Carla Giorgetti, Dennis J. Slamon, Seock-Ah Im, Norikazu Masuda, Shailendra Verma, Sherene Loi, Marco Colleoni, Kathy Puyana Theall, Xin Huang, Cynthia Huang Bartlett, Nicholas C. Turner
Journal: Journal of Clinical Oncology (2017)

1050 Background: PAL+F improved progression-free survival (PFS) over F + placebo (P) in patients (pts) with endocrine-resistant HR+/HER2– ABC. We examined factors predictive of long-term benefit on PAL+F. Methods: Pre/postmenopausal pts with HR+/HER2– ABC that progressed on prior endocrine therapy (ET) were randomized 2:1 to PAL (125 mg/d oral [3 wk on, 1 wk off]) + F (500 mg) or P+F. Characteristics of pts with prolonged benefit (treatment [tx] duration ≥18 mo for PAL+F; ≥12 mo for P+F based on median PFS and tx duration) were compared with the intent-to-treat (ITT) population. Results: PAL+F improved PFS vs P+F (11.2 vs 4.6 mo; hazard ratio, 0.50). By Aug 2016, 138 pts had long-term benefit: 100/347 (29%) pts on PAL+F received tx for ≥18 mo, including 70 (20%) who received &gt; 2 y (26–39 cycles). In contrast, 38/174 (22%) pts on P+F received ≥12 mo of tx; only 16 (9%) received &gt; 2 y (27–38 cycles). No apparent differences in baseline characteristics of pts with long-term benefit were observed between groups except that a greater proportion of those on P+F had a single site of disease involvement (40% PAL+F vs 63% P+F). Pts with long-term benefit on PAL+F had lower rates of visceral disease (42% vs 60%), liver metastases (18% vs 40%), and ≥3 disease sites (27% vs 39%) at baseline vs the ITT population; no difference in sensitivity to prior ET was observed (84% vs 79%). Objective response rate (ORR) was higher among pts with prolonged benefit on PAL+F vs ITT (36% vs 26%). Conclusions: PAL+F is associated with prolonged benefit in about a third of pts treated with the combination in PALOMA-3. These pts achieve higher ORR compared to other study pts and the benefit is independent of baseline site and number of metastatic recurrences and prior endocrine sensitivity. Benefit from F alone is less prolonged and appears limited to those with 1 site of disease involvement. The analysis confirms the efficacy of PAL+F in HR+ ABC with visceral recurrence. Biomarker analyses are ongoing in pts with long-term benefit to understand molecular features predictive of tx sensitivity. Funding: Pfizer. Clinical trial information: NCT01942135.
Exosome-Derived miR-25-3p and miR-92a-3p Stimulate Liposarcoma Progression
Authors: Lucia Casadei, Federica Calore, Chad J. Creighton, Michele Guescini, Kara Batte, O. Hans Iwenofu, Abeba Zewdu, Danielle A. Braggio, Kate Lynn Bill, Paolo Fadda, Francesca Lovat, Gonzalo Lopez, Pierluigi Gasparini, James L. Chen, Raleigh D. Kladney, Gustavo Leone, Dina Lev, Carlo M. Croce, Raphael E. Pollock
Journal: Cancer Research (2017)

Despite the development of combined modality treatments against liposarcoma in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25-3p and miR-92a-3p are secreted by liposarcoma cells through extracellular vesicles and may be useful as potential biomarkers of disease. Both miR-25-3p and miR-92a-3p stimulated secretion of proinflammatory cytokine IL6 from tumor-associated macrophages in a TLR7/8-dependent manner, which in turn promoted liposarcoma cell proliferation, invasion, and metastasis via this interaction with the surrounding microenvironment. Our findings provide novel and previously unreported insight into liposarcoma progression, identifying communication between liposarcoma cells and their microenvironment as a process critically involved in liposarcoma progression. This study establishes the possibility that the pattern of circulating miRNAs may identify recurrence prior to radiological detectability while providing insight into disease outcome and as a possible approach to monitor treatment efficacy. Cancer Res; 77(14); 3846-56. ©2017 AACR.