bluuebunny/crossref_metadata_2025_split huggingface dataset:
A large multicenter, randomized, double-blind, crossover study in healthy volunteers, comparing pharmacokinetics and pharmacodynamics of Sandoz proposed biosimilar pegfilgrastim with European and United States reference pegfilgrastim.
Authors: Otto Gordon P. , Nakov Roumen , Schussler Steven , Schier-Mumzhiu Stefanie , Schelcher Celine , Koch Sven D. , Skerjanec Andrej , Wang Jessie , Krendyukov Andriy , Bellon Anne 
Published: May 2019

e23118 Background: Similarity of the pharmacokinetic (PK)/pharmacodynamic (PD) profiles of Sandoz proposed biosimilar pegfilgrastim and EU-reference biologic was confirmed in a pivotal Phase I study. In order to confirm PK/PD similarity to the US reference biologic, and to bridge between the two references, a 3-way study was conducted. Methods: A randomized, double-blind, single-dose, 3-treatment, 6-sequence crossover Phase I study was performed in healthy volunteers (HVs) to demonstrate similarity in PK, PD, safety and immunogenicity between Sandoz proposed biosimilar, US reference, and EU reference pegfilgrastim administered subcutaneously (6 mg/0.6 mL) in each treatment period. The primary objective was to demonstrate PK (AUC0-inf, AUC0-last, Cmax) and PD similarity (ANC AUEC0-last, ANC Emax). The study was powered (90%) to achieve confidence intervals (CIs) within biosimilarity margins 0.8─1.25 in pairwise comparisons. Secondary objectives were additional PK/PD parameters, safety and immunogenicity. Results: The study included 577 male and female HVs. PK and PD similarity were demonstrated between Sandoz proposed biosimilar and US reference (Table), as well as EU reference and between both reference biologics since the 90% CIs of the geometric mean ratios were contained within the pre-defined margins of 0.80‒1.25. Safety, immunogenicity and secondary PK/PD parameters were also similar across treatment groups. Conclusions: This large randomized, double-blind, single-dose, 3-treatment, 6-sequence crossover study demonstrated PK and PD similarity between Sandoz proposed biosimilar, US reference and EU reference pegfilgrastim with similar safety, local tolerability and immunogenicity. Clinical trial information: 2016-003549-27. [Table: see text]
The effect of sukshma vyayama joint loosening yoga on aromatase inhibitor-induced arthralgia (AI) in breast cancer patients: A feasibility study conducted on Facebook.
Authors: Leibel L. Leigh , Metri Kashinath G. , Prasad Rajendra , Mears J. Gregory 
Published: May 2019

e23129 Background: AI therapy causes joint pain in up to half of women, and up to 20% become non-compliant with treatment due to pain and discomfort. This pilot study investigated the efficacy of sukshma vyayama in improving AI-induced joint pain and evaluated the feasibility of delivering the intervention on Facebook. Methods: Breast cancer patients undergoing treatment with AI's with self-reported arthralgia were recruited via an IRB-approved announcement posted in two closed breast cancer support groups on Facebook to participate in a yoga study delivered on Facebook. Participants completed BPI, DASH, PRAI and WOMAC questionnaires before and after the study. Intervention consisted of 12 joint loosening exercises performed in a chair, once daily for 12 minutes, Monday-Friday for 4 weeks. Asynchronous video demonstrations were available in a secret Facebook group and viewing confirmed by typing "done" (time-stamped) in comments. Results: 200 women responded. 38 met the inclusion criteria/consent, 26 completed the online consent, interventions and pre/post questionnaires. Paired simple t tests results showed significant (P < 0.05) improvement in all the pain measures and quality of life parameters after yoga intervention compared to baseline. Conclusions: This study provides the first evidence that it is feasible to teach sukshma vyayama to patients on Facebook and that the intervention significantly improves AI-induced arthralgia. Teaching yoga via social media may provide better access to this therapeutic modality to patients at all points in the cancer care continuum globally. [Table: see text]
Mortality results from an oral oncolytic symptom management trial.
Authors: Vachon Eric , Champion Victoria 
Published: May 2019

e23139 Background: Although mortality rates have declined, cancer remains the second leading cause of death in the United States. There has been an increase in prescriptions of oral oncolytic agents (OOA), which are typically prescribed to late stage patients as third or fourth line therapy. Because of this, death rates are higher among these patients and may impact attrition rates in OOA intervention trials. For researchers working with late stage patients, attrition by mortality should be considered when determining sample size. The purpose of this report is to identify the mortality incidence and its related factors in a symptom management randomized controlled trial (RCT). Methods: A total of 272 cancer patients newly prescribed OOAs (136 males, 136 females) were entered into the 12-week, multi-site RCT after signing written consent. Hospice patients were ineligible. Patients were randomized to experimental (n = 137) and control (n = 135) groups, with experimental group receiving an automated phone adherence intervention and a Symptom Management Toolkit (SMT). Data were gathered through recruitment site screening, patient interviews, medical record audits (MRA), and obituary searches at 6 months post-enrollment. A multiple logistic regression model was used to test the effect of concurrent intravenous chemotherapy, age, sex, intervention group, OOA class, comorbidities, and emergency room and hospital visits on death. Hematologic patients (n = 26) were excluded as none died, resulting in multicollinearity. Results: Fifteen patients (6%) died during the 12 week study period, while 34 (14%) died during the 6 months after enrollment. ER visits ( p .02), cardiovascular disease ( p.05), and depression ( p .01) were significantly associated with death 6 months from enrollment. Fifty-seven (23%) patients reported visiting the ER and 68 (28%) patients had a hospital stay during the study period. Conclusions: As would be hypothesized, adverse events and comorbidities were associated with death in this RCT. Mortality was similar by intervention group. Behavioral trials, even those lasting six months, should estimate attrition rates considering death and/or entry into hospice. Adequate planning in sampling will be critical for success in these types of trials. Clinical trial information: NCT02043184.
Effect of free amino acids mix with medium triglycerides and Withania somnifera on cancer cachexia.
Authors: Gaddam Kalyan R , Shambaugh Shawn C. , Kanamori David E. , Rustagi Pradip K. , Ng Richard Kim-Thean , Bell Susana , Desai Ajay , Gorla Giridhar R. , Cartmell Alan D. , Patel Rishi 
Published: May 2019

e23140 Background: Cancer cachexia is a multifactorial syndrome involving systemic inflammation, negative protein and energy balance, and involuntary loss of lean muscle mass. It not only adversely affects quality of life but also leads to poor responses to chemotherapy and reduced survival rates. Conventional nutritional support has not been successful in cancer cachexia and most commercially available formulas have shown little to no effect on cancer cachexia. This study assessed nutritional benefits of E2 Energy, an amino acid (AA) supplement powder enriched with branched-chain AAs, medium-chain triglycerides, and Withania somnifera, on body weight, lean muscle mass, and cancer-related piper fatigue score. Methods: This prospective, open-label preliminary feasibility study was conducted in patients receiving active treatment for cancer (e.g. chemotherapy, radiation, targeted therapy, or hormone therapy) with documented evidence of significant weight loss. Patients were evaluated at baseline and at the end of treatment (12 weeks) for lean muscle mass as measured by bioimpedance analysis, body weight, C-reactive protein (CRP), serum albumin, fatigue as measured by Piper Fatigue Scale (PFS), and proinflammatory cytokines (IL-1, IL-2, IL-6, and TNF-α). Being a pilot study, enrollment was restricted to approximately 30 patients with focus on descriptive statistics rather than formal tests of hypotheses. Results: We analyzed data of 15 patients who completed at least 6 weeks of treatment. Treatment with AA powder increased lean muscle mass in 12 (80%) patients. Similarly, PFS scores improved in 14 (93.33%) patients. Overall, in 6 patients (40%), body weight either remained stable or increased from baseline values. Six patients presented abnormal cytokine levels at baseline; however, their results at follow-up were unavailable, thus making interpretation inconclusive. Conclusions: Treatment with AA powder supplement may prevent loss in lean muscle mass, reduce fatigue, and curtail weightloss. However, these results must be substantiated in large well-designed (randomized) studies.
An observational study to evaluate the potential of Onlife to improve chemotherapy-induced peripheral neuropathy: Final results of the STEFANO trial.
Authors: Zaiss Matthias R. , Uhlig Jens , Zahn Mark-Oliver , Decker Thomas , Lehmann Helmar C. , Harde Johanna , Vannier Corinne , Hogrefe Cathrin , Marschner Norbert 
Published: May 2019

e23143 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, long-term side effect of many antineoplastic agents and has a detrimental impact on patients (pts)’ quality of life and functional activities of daily living. Currently, preventive measures and treatment options for CIPN are quite limited. OnLife is a dietary supplement that contains a patented mixture of fatty acids with anti-inflammatory, neuroprotective and antinociceptive properties. Methods: The STEFANO study – an observational, prospective, two-cohort, multicenter study of dietary supplementation – was designed to evaluate the potential of OnLife to improve CIPN in adult pts with completed neo-/adjuvant chemotherapy and manifest CIPN (grade 1-3) (Cohort A: colon cancer, oxaliplatin-containing therapy; cohort B: breast cancer, paclitaxel therapy). Pts received OnLife for 3 months. The primary objective – assessment of changes in CIPN – was evaluated by comparing the severity of sensory and motor CIPN according to CTCAE v4.03 before, during and after treatment with OnLife. Secondary endpoints included patient-reported experience of symptoms and functional limitations related to CIPN. Descriptive statistics were used to analyze data. Results: In total, 75 breast cancer pts with paclitaxel-induced and 71 colon cancer pts with oxaliplatin-induced peripheral neuropathy, respectively, received OnLife. Based on physician-rated CTCAE grades, 21.3% of breast cancer pts and 12.7% of colon cancer pts had a sustained improvement of sensory CIPN after OnLife treatment. Concerning motor CIPN, the proportions were 12.0% and 9.9%, respectively. According to patient-reported outcomes, 45.3% of breast cancer pts and 23.9% of colon cancer pts had less symptoms and functional limitations related to sensory CIPN after OnLife treatment. Concerning motor CIPN, the proportions were 32.0% and 22.5%, respectively. Conclusions: STEFANO provides indications of the potential of OnLife to reduce severity of objective and subjective CIPN-related symptoms. Therefore, it is a promising agent to meet the unmet medical need of management options for patients with established CIPN. Clinical trial information: NCT03065478.
Physical activity platform to improve bone health in cancer survivors.
Authors: Skinner Cathy 
Published: May 2019

TPS11632 Background: Cancer treatment-induced bone loss and the subsequent risk of fractures in both men and women is a significant burden on national health care. US cancer survivors will reach 18 million by 2022 and by 2025 and the projected burden of osteoporosis is $25.3B. Cancer patients treated with medications that lower hormone levels face an increased risk of fractures. Clinical studies report that moderate-intensity resistance exercises prevent a decline in bone health in female cancer survivors, and that strength training may reduce complications such as fatigue, muscle wasting, and bone loss. Unfortunately, only a small percentage of female cancer survivors engage in and adhere to a strength training exercise routine. Several factors account for this low level of engagement such as poor awareness of the benefits of exercise, lack of motivation, and the lack of affordable and easily accessible exercise programs designed for cancer survivors. Internet-based self-managed programs of exercises and guidance can potentially address these problems, and can be scaled for broader dissemination. Methods: The Thrivors platform seeks to shift the current paradigm of poor adherence to exercise by providing an affordable and accessible means of improving outcomes for cancer survivors. Thrivors plus Bone Health (Thrivors+BH), will be a first-of-its-kind offering of clinically validated bone health exercises that can be customized to a cancer survivor's pain and energy levels, with several novel interactive feedback features. The product has supportive modules for connecting with a community of other users, mindfulness training, nutritional advice and educational information. The Thrivors platform is scalable, device-agnostic, and allows analysis of de-identified usage data. The two versions of the platform will be deployed in a 20-week, two-arm randomized controlled trial of 50 breast cancer survivors. Adherence to exercise sessions (primary outcome) and platform usage will be measured by platform software, while user engagement (secondary outcomes) will be assessed by surveys. Differences between primary and secondary outcomes for the control and intervention groups will be evaluated. Usage statistics, motivational responses and user feedback will be used to further refine platform features and content. Clinical trial information: NCT03651037.
Prospective study of germline and somatic alterations for early onset lung cancer patients (EOLUNG MASTER protocol).
Authors: Jove Maria , Gausachs Mireia , Bosch-Barrera Joaquim , Carcereny Costa Enric , Teule Alex , Izquierdo Angel , Navarro Matilde , Palmero Ramon , Vilariño Noelia , Ruffinelli Jose Carlos , Sais Elia , Moran Teresa , Estival Anna , Fina Claudia , Brunet Joan , Capella Gabriel , Lazaro Conxi , Nadal Ernest 
Published: May 2019

TPS9122 Background: Lung cancer (LC) is a rare disease among young adults. Polymorphisms in genes involved in carcinogenic metabolism of tobacco and/or xenobiotic metabolism have been identified in those patients. The growing use of next generation sequencing (NGS) unravelled germline mutations in genes associated with hereditary cancer in patients with LC. However, germline DNA mutations have not been systematically studied in young adults with LC. Early onset LC patients are likely to harbor actionable somatic mutations. Broad hybrid NGS can identify actionable genomic alterations in LC patients deemed driver negative by routine molecular analysis. Trial Design: This is a multicentre, prospective, single-cohort study to determine whether young patients with LC harbor germline mutations and to evaluate the impact of NGS using Foundation One platform on the therapeutic options and overall survival for this specific patient population. Major inclusion criteria: 1) patients already or newly diagnosed of non-small cell lung cancer at any stage at age < 51; 2) to have sufficient tumor sample to perform standard molecular diagnosis ( EGFR/ALK/ROS1/BRAF); 3) to provide written informed consent for the study. Methods: After signing the informed consent form, family history of cancer and smoking history will be collected and a peripheral blood sample will be obtained. Germline targeted sequencing will be carried out in our centre using a customized hereditary cancer panel (I2HCP) of 136 genes designed to cover the coding exons and intron-exon boundaries of genes associated with moderate or high risk of hereditary cancer. Patients with clinical criteria for hereditary cancer or harboring pathogenic or probably pathogenic germline alteration will be referred to the genetic counselling unit. Patients will follow the usual clinical pathway for biomarker analysis and in case of remaining tumour material it will be used for conducting comprehensive genomic profiling through Foundation One platform. When tumour material available will not be sufficient to perform NGS, a tumour re-biopsy will be considered. Enrolment begun on June 2018 and, to date, a total of 41 patients have been included in the study.
MS201944-0170: A phase IIa study to investigate the clinical activity and safety of avelumab in combination with cetuximab plus gemcitabine and cisplatin in patients with advanced squamous NSCLC.
Authors: Ciardiello Fortunato , Dols Manuel Cobo , Juan Vidal Oscar , Paz-Ares Luis G. , de Castro Carpeño Javier , Felip Enriqueta , Campelo Rosario Garcia , Losonczy Gyorgy , Szalai Zsuzsanna , Vicente David , Schröder Andreas , Beier Frank , Bhandge Prasad , Galffy Gabriella 
Published: May 2019

TPS9123 Background: Preclinical studies have demonstrated that cetuximab plus chemotherapy results in immunogenic cell death and an increase in CD8+ T cells in the tumor microenvironment. Avelumab (an anti–PD-L1 antibody) has previously shown antitumor activity in NSCLC. We hypothesize that the combination of cetuximab with platinum-based chemotherapy and avelumab may have synergistic antitumor activity. Methods: This phase IIa, single-arm, multicenter study is investigating the clinical activity and safety of avelumab in combination with cetuximab plus gemcitabine and cisplatin in patients with advanced squamous NSCLC who are treatment naive in the advanced setting (NCT03717155). Eligibility criteria include histologically confirmed stage IV, metastatic or recurrent NSCLC with squamous histology, with no prior systemic therapy for metastatic NSCLC, no prior therapy with any antibody/drug targeting T-cell coregulatory proteins, and ECOG PS of 0 to 1. Patients with a tumor harboring an activating EGFR mutation or ALK rearrangement are excluded. Patients will receive doublet chemotherapy (cisplatin 75 mg/m2 on day 1, gemcitabine 1250 mg/m2 on days 1 and 8), cetuximab on days 1 (250 mg/m2) and 8 (500 mg/m2), and avelumab 800 mg on days 1 and 8 for a total of four 3-week cycles. Thereafter, avelumab (800 mg) and cetuximab (500 mg/m2) will be administered as maintenance treatment Q2W until disease progression, unacceptable toxicity, or withdrawal. Enrollment in a safety run-in, which will evaluate the safety and tolerability of avelumab in combination with cetuximab plus gemcitabine and cisplatin, is planned for the first 6 patients. Enrollment began on October 30, 2018. Study enrollment will continue until approximately 40 evaluable patients have been recruited. The primary endpoint is confirmed best overall response per RECIST 1.1 by investigator assessment. Secondary endpoints include safety (NCI CTCAE v5.0) and tolerability of the combination, duration of response, survival, and tumor biomarkers. The study is ongoing at sites in Hungary and Spain. Clinical trial information: NCT03717155.
CLARITY-BPA: Bisphenol A or Propylthiouracil on Thyroid Function and Effects in the Developing Male and Female Rat Brain
Authors: Bansal Ruby , Zoeller R Thomas 
Published: May 2019

AbstractThe CLARITY-BPA experiment, a large collaboration between the National Institute of Environmental Health Sciences, the National Toxicology Program, and the US Food and Drug Administration, is designed to test the effects of bisphenol A (BPA) on a variety of endocrine systems and end points. The specific aim of this subproject was to test the effect of BPA exposure on thyroid functions and thyroid hormone action in the developing brain. Timed-pregnant National Center for Toxicological Research Sprague-Dawley rats (strain code 23) were dosed by gavage with vehicle control (0.3% carboxymethylcellulose) or one of five doses of BPA [2.5, 25, 250, 2500, or 25,000 µg/kg body weight (bw) per day] or ethinyl estradiol (EE) at 0.05 or 0.50 µg/kg bw/d (n = 8 for each group) beginning on gestational day 6. Beginning on postnatal day (PND) 1 (day of birth is PND 0), the pups were directly gavaged with the same dose of vehicle, BPA, or EE. We also obtained a group of animals treated with 3 ppm propylthiouracil in the drinking water and an equal number of concordant controls. Neither BPA nor EE affected serum thyroid hormones or thyroid hormone‒sensitive end points in the developing brain at PND 15. In contrast, propylthiouracil (PTU) reduced serum T4 to the expected degree (80% reduction) and elevated serum TSH. Few effects of PTU were observed in the male brain and none in the female brain. As a result, it is difficult to interpret the negative effects of BPA on the thyroid in this rat strain because the thyroid system appears to respond differently from that of other rat strains.
The Low-Dose ACTH Test: Usefulness of Combined Analysis of Serum and Salivary Maximum Cortisol Response in Pediatrics
Authors: Vaiani Elisa , Lazzati Juan Manuel , Ramirez Pablo , Costanzo Mariana , Gil Silvia , Dratler Gustavo , Zaidman Veronica , Chaler Eduardo , Belgorosky Alicia 
Published: May 2019

AbstractContextThe low-dose (1 µg) ACTH test (LDT) is widely used to assess central adrenal insufficiency (CAI); however, the serum cortisol cutoff value is controversial. Salivary cortisol (SC) may be a more accurate measurement for CAI.ObjectiveTo assess a new maximum cutoff value of serum cortisol after LDT in pediatric patients, taking into account serum and SC measurements.Design and SettingProspective study in a pediatric tertiary referral center.Working HypothesisThe combined analysis of serum and SC response to LDT might improve LDT for CAI diagnosis.Participant and Outcome MeasurementA total of 145 pediatric patients underwent LDT. Serum and SC levels were measured. A central adrenal sufficient (CAS) response was established according to the reference serum cortisol cutoff value of ≥497 nmol/L.ResultsThe LDT study showed central adrenal sufficiency in 72 patients and CAI in 73 patients. Considering the lower quartile of maximum SC value (21 nmol/L) in the CAS group, an intermediate CAI (InCAI) group and a real CAI (RCAI) group were defined. Regarding the median maximum value of serum cortisol levels in the InCAI group, a new serum cortisol cutoff value of 450 nmol/L was established. Furthermore, 91% of the patients in the RCAI group were below this cutoff value.ConclusionThe combined evaluation of maximum serum and SC levels to LDT might be useful to define an InCAI group and to avoid unnecessary hormone replacement therapy. However, rigorous patient follow-up is required