tbuckley/cabot-search huggingface dataset:
A social ecological study of access to breast cancer survivorship services.
Authors: Deborah Lefkowitz
Journal: Journal of Clinical Oncology (2018)

31 Background: Survivorship research has largely focused on the survivorship care plan and the transition back to primary care. Long-term survivor service needs remain understudied, particularly in the fragmented healthcare systems where many Americans receive their care. While numerous services support breast cancer patients through treatment, there is a sharp drop-off once treatment has been completed. This study investigated survivors’ post-treatment service access and use in a geographically dispersed, medically underserved population. Methods: Using a social ecological framework to analyze the interplay of individuals, healthcare facilities, and community resources, this study combined in-depth, semi-structured interviews with survey data from 75 breast cancer survivors across 27 cities in a two-county Affordable Care Act rating area. Interviews focused on challenges of access, available resources, and how resources were used. Surveys recorded service use, referral sources, and unmet needs across 27 services (e.g., psychosocial, financial, lymphedema) and information sources (e.g., online, support group, print materials). Results: Survivors ranged in age from 25 to 87, and 0 years of survivorship (still in active treatment) to 41 years (54% at 5+ years, 27% at 10+ years, and 12% at 20+ years). Access to survivorship services was accomplished in community settings (e.g., breast cancer nonprofits) more often than in medical facilities. In-person support groups were the most widely used resource, even by long-term survivors (over 40% were survivors of 5+ years), and played a key role in providing access to other services and information (e.g., nutrition, yoga). Many survivors addressed the lack of services through resourceful do-it-yourself solutions. Nevertheless unmet needs remained across the service spectrum. Conclusions: Community-based resources were pivotal in enabling access for a dispersed, underserved population and may serve as high-leverage points for interventions in healthcare systems. Research was supported by the National Cancer Institute of the National Institutes of Health under Award # F31CA192478.
Phase ib study of trastuzumab emtansine (TDM1) in combination with lapatinib and nab-paclitaxel in metastatic HER2-neu overexpressed breast cancer patients: Stela results.
Authors: Tejal Amar Patel, Joe Ensor, Angel Augusto Rodriguez, Anna Belcheva, Jorge German Darcourt, Polly Ann Niravath, John G. Kuhn, Virginia G. Kaklamani, Xiaoxian Li, Toniva Boone, Jenny Chee Ning Chang
Journal: Journal of Clinical Oncology (2018)

1035 Background: Based on our preclinical data, we conducted a phase I study oftrastuzumab-emtansine (T-DM1) in combination with Lapatinib and Nab-paclitaxel in patients with HER2 over-expressed stage IV breast cancer. Methods: Phase Ib study was conducted using 3+3 dose de-escalation design, with TDM1 with Lapatinib and nab-paclitaxel administered for a total of 4 cycles. Primary purpose was to evaluate the maximum tolerated dose (MTD) of T-DM1 with Lapatinib and Nab-paclitaxel. Safety, tumor response and pharmacokinetics (PK) were also assessed. Dose limiting toxicities (DLTs) were defined as ≥ grade 3 non hematological toxicity attributed to the study drugs. Key inclusion criteria were stage IV HER2 positive breast cancer, LVEF ≥ 45%, and peripheral neuropathy < grade 2. Results: The MTD was T-DM1 3.0 mg/kg every 3 weeks along with Lapatinib 750mg oral daily and Nab-paclitaxel 80mg/m2 weekly. Twenty four patients, median age 50 (47.9-55.9) years were enrolled. The dose limiting toxicities were diarrhea and elevated liver function tests. At MTD, 42.9% (6/14) experienced grade 3 or higher toxicity. Fourteen patients with median of 1 (range 0-5) prior metastatic treatments were evaluable for response. 12 patients (85.7%) had an objective response including 6 CR and 2 PR. T-DM1 pharmacokinetics was unaffected by Lapatinib. Conclusions: T-DM1 with Lapatinib and Nab-paclitaxel therapy was relatively well tolerated with significant anti-tumor activity observed. Clinical trial information: NCT02073916.
Met is involved in TIGAR-regulated metastasis of non-small-cell lung cancer
Authors: Mengqin Shen, Xiaoping Zhao, Li Zhao, Liang Shi, Shuxian An, Gang Huang, Jianjun Liu
Journal: Molecular Cancer (2018)

TIGAR is a p53 target gene that is known to protect cells from ROS-induced apoptosis by promoting the pentose phosphate pathway. The role of TIGAR in tumor cell invasion and metastasis remains elusive. Here we found that downregulation of TIGAR reduced the invasion and metastasis of NSCLC cells in vitro and in vivo. Immunohistochemical analysis of 72 NSCLC patients showed that TIGAR and Met protein expression was positively correlated with late stages of lung cancer. Besides, patients with high co-expression of TIGAR and Met presented a significantly worse survival. In addition, we found that Met signaling pathway is involved in TIGAR-induced invasion and metastasis. Our study indicates that TIGAR/Met pathway may be a novel target for NSCLC therapy. It is necessary to evaluate the expression of TIGAR before Met inhibitors are used for NSCLC treatment.
Long-term benefit from tamoxifen therapy for patients with Luminal A and Luminal B breast cancer: Retrospective analysis of the STO-3 trial.
Authors: Linda Lindström, Nancy Yu, Adina Iftimi, Christina Yau, Laura van 't Veer, Bo Nordenskjöld, Christopher Benz, Tommy Fornander, Olle Stål, Kamila Czene, Laura Esserman
Journal: Journal of Clinical Oncology (2018)

541 Background: Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer spanning more than 20 years, but the biological factors influencing this risk are unknown. Here we aimed to investigate the long-term survival and benefit from tamoxifen therapy for patients with Luminal A and Luminal B subtype tumors. Methods: The Stockholm Tamoxifen (STO-3) trial enrolled 1780 postmenopausal patients from 1976 until 1990 with lymph node-negative breast cancers and tumors less than or equal to 30 mm in diameter, randomly assigned to at least two years of adjuvant tamoxifen (40 mg daily) vs no adjuvant treatment. All patients had a complete long-term follow-up until December 31, 2012, and detailed patient and clinical information. Gene expression data was generated using custom designed Agilent arrays from FFPE breast cancer tumor tissue and was used to define Luminal A and Luminal B subtype tumors. ER, PR, HER2 and Ki-67 were also reassessed in 2014. Long-term breast cancer-specific survival was performed using Kaplan-Meier analysis and flexible parametric survival models were used to estimate the time-varying hazard ratios (HRs) adjusting for patient and tumor characteristics. Results: A statistically significant difference in long-term survival (25 years) by Luminal subtype and trial arm was seen (Log Rank, P < 0.0001). For Luminal A and Luminal B patients, the 25 year survival was 88% versus 69% for treated patients and 73% versus 58% for untreated patients. Luminal A patients in the tamoxifen treated arm had a significantly reduced long-term risk of fatal breast cancer up to 20 years after breast cancer diagnosis (HR at 15-years: 0.59; 95% CI, 0.35-0.98; and HR at 20-years: 0.65; 95% CI, 0.32-1.30) as compared to the untreated arm. However for patients with Luminal B tumors, a significantly reduced long-term risk was only seen up to 10 years after diagnosis (HR at 5-years: 0.37; 95% CI, 0.18-0.73; and HR at 10-years: 0.68; 95% CI, 0.31-1.47). Conclusions: Patients with Luminal A subtype tumors have a long-term benefit from tamoxifen therapy, whereas the benefit for patients with Luminal B tumors is up to ten years after diagnosis. Clinical trial information: STO-3 trial from 1976 no registration# at the time.
Metastatic cancers promote cachexia through ZIP14 upregulation in skeletal muscle
Authors: Gang Wang, Anup K. Biswas, Wanchao Ma, Manoj Kandpal, Courtney Coker, Paul M. Grandgenett, Michael A. Hollingsworth, Rinku Jain, Kurenai Tanji, Sara Lόpez-Pintado, Alain Borczuk, Doreen Hebert, Supak Jenkitkasemwong, Shintaro Hojyo, Ramana V. Davuluri, Mitchell D. Knutson, Toshiyuki Fukada, Swarnali Acharyya
Journal: Nature Medicine (2018)
Changes in Influenza Vaccination Requirements for Health Care Personnel in US Hospitals
Authors: M. Todd Greene, Karen E. Fowler, David Ratz, Sarah L. Krein, Suzanne F. Bradley, Sanjay Saint
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Annual influenza vaccinations are currently recommended for all health care personnel (HCP) to limit the spread of influenza to those at high risk of developing serious complications from the virus. Vaccination coverage has been shown to be significantly greater among employers requiring and encouraging HCP to receive the annual influenza vaccination. <h3>Objectives</h3> To compare the proportion of respondent hospitals requiring HCP to receive annual influenza vaccination between 2013 and 2017 and to assess the degree to which these proportions differed between Veterans Affairs (VA) and non-VA hospitals. <h3>Design, Setting, and Participants</h3> This national survey study included responses from 1062 infection preventionists between 2013 and 2017 from nationally representative samples of all VA and non-VA hospitals in the United States. Data analysis was conducted from November 17, 2017, to March 26, 2018. <h3>Main Outcomes and Measures</h3> Survey response indicating hospital requirement for annual influenza vaccination of HCP. <h3>Results</h3> The overall response rate for the 2013 survey was 69.3% (non-VA, 70.6% [403 of 571]; VA, 63.5% [80 of 126]) and in 2017 was 59.1% (non-VA, 59.1% [530 of 897]; VA, 58.9% [73 of 124]). Among all responding hospitals, mandatory influenza vaccination requirements for HCP increased from 37.1% in 2013 to 61.4% in 2017 (difference, 24.3%; 95% CI, 18.4%-30.2%;<i>P</i> &lt; .001). This change was driven by non-VA hospitals, as requirement policies increased from 44.3% (171 of 386) in 2013 to 69.4% (365 of 526) in 2017 (difference, 25.1%; 95% CI, 18.8%-31.4%;<i>P</i> &lt; .001). Conversely, there was no significant change during this period in the proportion of VA hospitals that required influenza vaccinations for HCP (1.3% [1 of 77] to 4.1% [3 of 73]; difference, 2.8%; 95% CI, −2.4% to 8.0%;<i>P</i> = .29). <h3>Conclusions and Relevance</h3> Despite a substantial increase in mandates among non-VA hospitals, we found that many non-VA hospitals and nearly all VA hospitals are still not currently mandating influenza vaccinations for HCP. In addition to implementing other well-described strategies to increase vaccination rates, health care organizations should consider mandating influenza vaccinations while appropriately weighing and managing the moral, ethical, and legal implications.
Pre‐Metastatic Niche: Biomaterial Scaffolds as Pre‐metastatic Niche Mimics Systemically Alter the Primary Tumor and Tumor Microenvironment (Adv. Healthcare Mater. 10/2018)
Authors: Brian A. Aguado, Rachel M. Hartfield, Grace G. Bushnell, Joseph T. Decker, Samira M. Azarin, Dhaval Nanavati, Matthew J. Schipma, Shreyas S. Rao, Robert S. Oakes, Yining Zhang, Jacqueline S. Jeruss, Lonnie D. Shea
Journal: Advanced Healthcare Materials (2018)

Biomaterial implants that mimic the premetastatic niche are shown to redirect immune and tumor cell populations in vivo. However, the systemic effects of premetastatic niche mimics on metastasis progression have yet to be characterized. In article 1700903 by Lonnie D. Shea and co-workers, synthetic biomaterial implants are shown to systemically alter the primary tumor and the tumor microenvironment to promote an invasion-suppressive phenotype. Cover art designed and produced by Stephen Alvey, University of Michigan, Department of Engineering.
Phase II study of Ra-223 combined with hormonal therapy and denosumab for treatment of hormone receptor-positive breast cancer with bone-dominant metastasis.
Authors: Naoto T. Ueno, Rie K. Tahara, Babita Saigal, Takeo Fujii, James M. Reuben, Hui Gao, Anthony Lucci, Nuhad K. Ibrahim, Senthil Damodaran, Yu Shen, Diane D. Liu, Gabriel N. Hortobagyi, Debu Tripathy, Bora Lim, Beth A. Chasen
Journal: Journal of Clinical Oncology (2018)

1065 Background: Radium-223 dichloride (Ra-223) is a targeted alpha therapy that induces a localized cytotoxic effect on bone metastases. We evaluated the efficacy of combined Ra-223, hormonal therapy, and denosumab in patients with hormone receptor (HR)-positive, bone-dominant metastatic breast cancer. Methods: In this single-center phase II study (NCT02366130), patients received Ra-223 (55 kBq/kg intravenously) on day 1 and then every 4 weeks for 6 cycles. Patients also received a hormonal agent (i.e., tamoxifen, aromatase inhibitor, or fulvestrant) at standard dosage and denosumab (120 mg) every 4 weeks. One non-bone metastatic site was allowed. There was no limit on the number of prior hormonal therapies, and one prior chemotherapy was allowed for metastasis. Response was evaluated by PERCIST on FDG PET-CT at baseline, 6 and 9 months (mo). Primary objective was disease control rate at 9 mo. Secondary objectives were tumor response rate at 6 mo and safety. Results: After patient accrual (n = 36), the first 30 patients who had 6 mo follow-up or progression prior to 6 mo were analyzed. The median number of prior therapies for metastasis was 1 (range, 0-4). Five patients (16%) received chemotherapy and 7 (23%) a CDK4/6 inhibitor. The median follow-up time was 12.2 mo (95% confidence interval [CI], 9.6–31.7). The disease control rates were 60% at 6 mo and 48% at 9 mo (5 patients had complete response). The median progression-free survival (PFS) was 7.4 mo (95% CI, 4.8–not reached [NR]). The bone-PFS was 15.9 mo (95% CI, 7.4–NR). The median PFS was significantly superior in patients with bone only metastasis than bone with other metastatic site at baseline (NR vs 4.4 mo; p < 0.0001). There were no grade 3 or 4 adverse events (AEs). The hematologic AEs were neutropenia (23%), anemia (20%), and thrombocytopenia (13%). Conclusions: Our results suggest that addition of Ra-223 to a hormonal agent and denosumab is a potentially effective approach in patients with HR-positive breast cancer with bone metastasis, with no major toxic effects. The impact of metastatic site outside of the bone at baseline must be factored into future clinical trial designs. We will report the updated result. Clinical trial information: NCT02366130.
Itraconazole targets cell cycle heterogeneity in colorectal cancer
Authors: Simon J.A. Buczacki, Semiramis Popova, Emma Biggs, Chrysa Koukorava, Jon Buzzelli, Louis Vermeulen, Lee Hazelwood, Hayley Francies, Mathew J. Garnett, Douglas J. Winton
Journal: The Journal of Experimental Medicine (2018)

Cellular dormancy and heterogeneity in cell cycle length provide important explanations for treatment failure after adjuvant therapy with S-phase cytotoxics in colorectal cancer (CRC), yet the molecular control of the dormant versus cycling state remains unknown. We sought to understand the molecular features of dormant CRC cells to facilitate rationale identification of compounds to target both dormant and cycling tumor cells. Unexpectedly, we demonstrate that dormant CRC cells are differentiated, yet retain clonogenic capacity. Mouse organoid drug screening identifies that itraconazole generates spheroid collapse and loss of dormancy. Human CRC cell dormancy and tumor growth can also be perturbed by itraconazole, which is found to inhibit Wnt signaling through noncanonical hedgehog signaling. Preclinical validation shows itraconazole to be effective in multiple assays through Wnt inhibition, causing both cycling and dormant cells to switch to global senescence. These data provide preclinical evidence to support an early phase trial of itraconazole in CRC.
EGFR L792H and G796R: Two Novel Mutations Mediating Resistance to the Third-Generation EGFR Tyrosine Kinase Inhibitor Osimertinib
Authors: Qi Zhang, Xu-Chao Zhang, Jin-Ji Yang, Zhen-Fan Yang, Yu Bai, Jian Su, Zheng Wang, Zhou Zhang, Yang Shao, Qing Zhou, Jin Kang, E-E Ke, Yi-Chen Zhang, Zhong-Yi Dong, Zhi-Hong Chen, Hai-Yan Tu, Wen-Zhao Zhong, Xue-Ning Yang, Yi-Long Wu
Journal: Journal of Thoracic Oncology (2018)
Effect of physical activity trackers and daily text messages on quality-of-life in colorectal survivors (Smart Pace): A pilot randomized controlled trial.
Authors: Hilary Chan, Katherine Van Loon, Stacey A. Kenfield, June M. Chan, Emily Mitchell, Li Zhang, Alan Paciorek, Galen Joseph, Angela Laffan, Yoshimi Fukuoka, Christine Miaskowski, Jeffrey A. Meyerhardt, Alan P. Venook, Erin Van Blarigan
Journal: Journal of Clinical Oncology (2018)

559 Background: There are over 1.3 million colorectal cancer (CRC) survivors in the United States, and many of whom suffer from lower health-related quality-of-life (HRQoL) years after diagnosis and treatment. Physical activity may improve survival outcomes and HRQoL for CRC survivors. Feasible interventions to support physical activity after CRC diagnosis are needed. Methods: We conducted a two-arm randomized controlled trial of 41 men and women who had completed treatment for CRC. Participants in the intervention arm were given a Fitbit Flex™ and received daily text messages for 12 weeks. HRQoL was assessed in both arms at baseline and 12 weeks using the RAND Short Form Survey (SF-36) and the Functional Assessment of Cancer Therapy – Colorectal (FACT-C). Survey score changes from baseline to 12 weeks were compared between the two arms using independent t-tests, and scores at baseline and 12 weeks were compared using paired t-tests. SAS was used for analysis, and statistical significance was declared at p &lt; 0.05. Results: We observed a statistically significant increase in the FACT-C functional well-being sub-scale in individuals in the intervention arm pre- and post- intervention (mean ∆ 1.81 ± 2.76; p: 0.02). There was no change in functional well-being in the control arm (mean ∆ -0.35 ± 4.12; p: 0.71). The between-arm comparison of change from baseline to 12 weeks was not statistically significantly ( p: 0.08). There was a statistically significant increase in the FACT-C emotional well-being sub-scale in the control arm (mean ∆ 1.20 ± 2.48; p: 0.04) and in the SF-36 role physical sub-scale in the control arm (mean ∆ 22.5 ± 38.8; p: 0.02). No other measures of HRQoL were statistically significantly different within groups, across time points, or between groups. Conclusions: A 12-week physical activity intervention using a Fitbit Flex™ and daily text messages may improve functional well-being among CRC survivors. Larger randomized studies are needed to definitively determine if a digital physical activity intervention improves functional well-being among CRC survivors, and if the improvement can be sustained over time. Clinical trial information: NCT02966054.
Bioglass Activated Albumin Hydrogels for Wound Healing
Authors: Yanling Zhou, Long Gao, Jinliang Peng, Min Xing, Yan Han, Xiaoya Wang, Yuhong Xu, Jiang Chang
Journal: Advanced Healthcare Materials (2018)

Abstract In this study, a novel Bioglass/albumin composite hydrogel with controllable injectability, good adhesiveness, and bioactivity, is developed by utilizing dual‐functional bioactive ions released from Bioglass, which on one side controls the gelling time by creating an alkaline environment to regulate the cross‐linking reaction between human serum albumin and succinimidyl succinate modified poly(ethylene glycol), and on the other side stimulates wound healing. The composite hydrogel exhibits adhesive property that is superior to clinically used fibrin and cyanoacrylate glues. The gelation time of the composite hydrogel could be regulated via changing the amounts of Bioglass which endows the hydrogel with good injectability. The in vivo experiment confirms that this composite hydrogel has good bioactivity to stimulate angiogenesis and enhance chronic wound healing. Moreover, for the first time, the concentrations of the bioactive ions released from the composite hydrogel in situ are quantified during wound healing using a microdialysis technique, and a correlation of the in vitro and in vivo concentration of ions released from the hydrogel is determined, which is extremely important for understanding the bioactivity mechanisms of Bioglass/bioceramic‐based biomaterials and designing biomaterials for tissue regeneration.
Ectopic Salivary Gland in a Patient With Prostate Cancer at 18F-Choline PET/CT
Authors: Lea Cuppari, Laura Evangelista
Journal: Clinical Nuclear Medicine (2018)

Abstract A 65-year-old man with prostate cancer surgically treated in June 2016 underwent 18 F-choline PET/CT in April 2017 for a biochemical recurrence of disease. PET/CT revealed a high tracer uptake in a solid nodulation near the left masseter muscle with a high SUVmax. The patient underwent both ultrasonography examination and fine needle aspiration cytology that confirmed the presence of an ectopic salivary gland. This case highlights that, in patients undergoing choline PET/CT, a careful analysis of the physiological biodistribution should be made by considering also the presence of accessory salivary glands.
Benefit of haemostatic spray in variceal bleeding: early application of spray or early application of guidelines?
Authors: Jonathan Mitchell, James O’Beirne
Journal: Gut (2018)

We read with considerable interest the recent report by Ibrahim et al 1 on the use of haemostatic powder in addition to standard of care management for oesophageal variceal bleeding. The authors have performed a randomised controlled trial of early (<2 hours) application of haemostatic powder compared with ‘early’ elective endoscopy (performed at 12–24 hours) and found a significant improvement in the primary outcome, which was clinical haemostasis in the first 24 hours and endoscopic haemostasis at early elective endoscopy. The authors suggest that this very early control of bleeding could translate into improved survival, which was significantly better in the powder group although the trial was not powered for this outcome. The authors highlight that despite guidelines …