tbuckley/cabot-search huggingface dataset:
Assessing the feasibility of developing and implementing a web-based patient education application.
Authors: Kara Mosesso, Chasity Walters, Christianne Supan, Ann Alice Jakubowski
Journal: Journal of Clinical Oncology (2018)

101 Background: Metabolic Syndrome (MetS) is common following allogeneic stem cell transplant (allo-SCT). Lifestyle counseling in the early post-transplant period is crucial for reducing morbidity and mortality related to MetS. The purpose of this study is to assess the feasibility of developing and implementing a video web-based patient education application that educates patients about Metabolic Syndrome (MetS) and provides preventative lifestyle recommendations following allo-SCT. Methods: We created and animated four video storyboards using evidence based research and recommended guidelines (from nationally recognized organizations). There is one video for each component of MetS including abdominal obesity, hypertension, hyperglycemia and dyslipidemia. The videos and a printable PDF overview of MetS were launched on a landing page on our patient education website (available to MSKCC and non-MSKCC patients) in August 2017. MSKCC patients are introduced to the website ( https://www.mskcc.org/cancer-care/patient-education/managing-metabolic-syndrome-after-allogeneic-stem-cell-transplant ) by the nurse practitioner at their Survivorship Visit. After approximately 10 weeks live, feasibility was assessed according to measured MSKCC and non-MSKCC patient use of the education application. Results: To date there have been 121 pageviews on the landing page, 89 of which are unique IP addresses. Video use statistics are noted in the table below. Conclusions: Developing a video web-based patient application is a feasible adjunct to support and expand upon face-to-face education. Future directions include determining patient satisfaction, change in knowledge and behavior as a result of the videos and perceived usability of the web-based program by integrating a Likert-type patient self-report questionnaire into a module on the landing page. [Table: see text]
Natural Biomaterials for Corneal Tissue Engineering, Repair, and Regeneration
Authors: Rachelle N. Palchesko, Santiago D. Carrasquilla, Adam W. Feinberg
Journal: Advanced Healthcare Materials (2018)

Corneal blindness is a major cause of vision loss, estimated to affect over 10 million people worldwide. Once impaired through clouding or shape change, the best treatment option for restoring vision is corneal transplantation using full or partial thickness cadaveric grafts. However, donor corneas are globally limited and face rejection and graft failure, similar to other transplanted organs. Thus, there is a need for viable alternatives to donor corneas in order to increase supply, reduce rejection, and to minimize variability in tissue quality. To address this, researchers have developed new materials and strategies to tissue engineer full or partial thickness cornea grafts in order to repair, regenerate, or replace the diseased cornea. This progress report first reviews the anatomy and physiology of the cornea to frame the biological requirements and discuss the injuries and diseases that necessitate the need fortransplantation, as well as the requirements for a suitable donor tissue alternative. This is followed by recent progress using naturally derived biomaterials including silk, collagen, amniotic membranes, and decellularized corneas. Finally, remaining challenges in the field as they relate to the biomaterials discussed are identified, and the future research directions that should result in further advances in restoring corneal vision are highlighted.
Oncogenic Properties of NEAT1 in Prostate Cancer Cells Depend on the CDC5L–AGRN Transcriptional Regulation Circuit
Authors: Xin Li, Xianteng Wang, Wanlu Song, Hui Xu, Rongyao Huang, Yuting Wang, Wenwei Zhao, Zhengtao Xiao, Xuerui Yang
Journal: Cancer Research (2018)

Abstract The long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been shown to regulate multiple cancer-related cellular activities including cell proliferation, apoptosis, and migration. In this study, we confirm that repression of NEAT1 induces DNA damage, disturbs the cell cycle, and arrests the proliferation of prostate cancer cells. By taking advantage of the prostate cancer tumor transcriptome profiles from The Cancer Genome Atlas, our data-mining pipeline identified a series of transcription factors (TF) whose regulatory activities on target genes depended on the level of NEAT1. Among them was putative TF CDC5L, which bound directly to NEAT1. Silencing NEAT1 in prostate cancer cells repressed the transcriptional activity of CDC5L, and RNA-seq and ChIP-seq analyses further revealed a handful of potential targets of CDC5L regulated by NEAT1 expression. One target of CDC5L, ARGN, mediated the strong phenotypic consequences of NEAT1 reduction, including DNA damage, cell-cycle dysregulation, and proliferation arrest. In summary, we have established the requirement of the CDC5L–AGRN circuit for the essential oncogenic role of NEAT1 in prostate cancer cells. Significance: An integrative methodology uncovers CDC5L–AGRN signaling as critical to the tumor-promoting function of long noncoding RNA NEAT1 in prostate cancer cells. Cancer Res; 78(15); 4138–49. ©2018 AACR.
The impact of age in the quality of life of patients diagnosed with breast cancer after curative treatment.
Authors: Adriana Reis Brandao Matutino, Jacqueline E Lewis, Sunil Verma, Ardythe Taylor, Sylvia Huber, Guanmin Chen
Journal: Journal of Clinical Oncology (2018)

67 Background: Breast cancer is increasing incidence and decreasing in mortality, leading to a higher prevalence of survivors who face the consequences of the disease and its treatment. The needs of pts in different age groups may be unique. Methods: Retrospective cross-sectional analyses were performed on pts with stages 0-III breast cancer seen at Breast Cancer Supportive Care Foundation in Calgary, Canada, 2008-2016. Descriptive statistics summarized demographics. QoL data were collected using an adapted QoL Scale/Breast Cancer Patient questionnaire measuring physical, emotional, social and spiritual factors. ANOVA tested association between demographics and QoL scores. Results: 490 pts were included. Ages at diagnosis were &lt; 40y (14.9%), 40-49y (34.2%), 50-59y (34.2%) and ≥60y (16.7%). Most pts had invasive disease (89.4%). 60% had breast conserving surgery, 45.3% mastectomy, 65.1% chemotherapy, 58% radiation therapy, 72% anti-hormonal therapy and 13.8% trastuzumab. Physical well-being: &lt; 40y pts had less pain than others (p &lt; 0.049). Emotional well-being: ≥60y pts reported better coping despite disease (p &lt; 0.017), less ongoing anxiety (p &lt; 0.02) and less stress due to changes in appearance (p &lt; 0.006) or self-concept (p &lt; 0.007) than others; ≥60y expressed more control in their lives (p &lt; 0.03) than others; compared to ≥60y, &lt; 40y pts felt less satisfied in life (p &lt; 0.005), less supported (p &lt; 0.02), more fearful of recurrence (p &lt; 0.02) and second cancer (p &lt; 0.005), more depressed (p &lt; 0.02) and more distressed upon completion of curative treatment (p &lt; 0.0002). Social well-being: &lt; 49y pts had higher levels of employment interference than ≥50y pts (p &lt; 0.002); &lt; 40y pts felt more isolated than others (p &lt; 0.05); &lt; 49y pts had higher financial burden than ≥50y pts (p &lt; 0.02); ≥60y pts had less concerns with sexuality than others (p &lt; 0.004). Spiritual well-being: ≥60y pts participated more in religious activities (p &lt; 0.04) and felt more hopeful (p &lt; 0.02) than 50-59y pts. Conclusions: Different age groups have specific needs after breast cancer curative therapy. Ongoing research in survivorship care is essential to develop appropriate programs that promote comprehensive support for pts and families.
Abstract 15947: Machine Learning to Predict Rapid Progression of Carotid Atherosclerosis in Patients With Impaired Glucose Tolerance in the ACT NOW Study
Authors: Xia Hu, Ali Abbasi, Aramesh Saremi, Huan Liu, Peter Reaven, Raymond Q Migrino
Journal: Circulation (2015)

Impaired glucose tolerance (IGT) is associated with increased cardiovascular disease. Identifying IGT patients with rapid atherosclerosis progression will help in early risk-stratification. Machine learning (ML) involves algorithms that can learn complex relationships from data to make accurate predictions. Unlike traditional low-dimensional statistical approaches, ML can handle high dimensional datasets to make accurate predictions. Aim: To test the performance of ML in identifying IGT patients who will develop rapid carotid plaque progression. Methods: In the ACT NOW study (IGT patients were randomized to receive either pioglitazone or placebo), 382 subjects had carotid intima-media thickness (IMT) measured at baseline and at 15-18 months. Patients with IMT change in the top 10 percentile (n=39) were classified as rapid progressors (RP) and the rest (n=343) considered non-rapid progressors (NRP). ML using Naïve Bayes model was performed using 115 clinical/laboratory variables to develop a model to fit the true value of the class label (RP, NRP). Experiments were conducted with 10-fold cross validation in training/validation sets. Class prediction was also performed using traditional logistic regression model using 5 variables found different between RP and NRP by univariate analyses. Model performance was assessed using area under receiver operating characteristic curve. Results: Mean±SD IMT change was 0.011±0.026 mm overall; 0.058±0.018 for RP and 0.006±0.02 for NRP. Area under the curve (AUC) for ML (0.855) was higher versus traditional logistic regression model (0.73) (Fig.). ML correctly classified 78% of instances with κ statistic of 0.32. Conclusions: ML using naïve Bayes method provided good predictive ability in identifying IGT patients who had the most rapid plaque progression. ML may improve clinical prediction over traditional low-dimensional biostatistical approaches.
Effects of a lymphedema prevention intervention on range of motion among women receiving lymph node dissection for breast cancer treatment (Alliance) CALGB 70305.
Authors: Electra D. Paskett, Heshan Liu, Jill Oliveri, Drew K. Seisler, Michael A Schwartz, Jennifer Le-Rademacher, Jeff A. Sloan, Jane M. Armer
Journal: Journal of Clinical Oncology (2018)

123 Background: Lymph node dissection, axillary or sentinel, often results in restrictions of arm movement, including range of motion (ROM), either temporarily or permanently. The objective of this secondary analysis was to determine if a lymphedema (LE) prevention program would also impact ROM in both the affected arm as well as the unaffected arm. Methods: As part of the Lymphedema Education and Prevention study (CALGB 70305), women from participating sites (N=41) were randomized to either the “education only” (n=253) arm (information about LE signs and symptoms and risk reduction strategies) or “education + exercise” (n=315) arm (education plus arm stretching and breathing exercises and a visit with a physical therapist). Self-administered surveys asking for how high the patient can reach with each arm at pre-surgery, 12 and 18 months after surgery were used to assess self-reports of ROM for each arm (5 categories in total: very little, about half, nearly full, overhead, and full). Differences in ROM between study groups for each arm were compared using chi-square tests before surgery, and 12 and 18 months after surgery. Results: Before surgery, women in the “education + exercise” group were less likely to report full ROM for both arms (left: 58% vs 75%; right: 57% vs 76%; p=0.0004 for both arms) compared to women in the “education only” group, while at 12 months, women in the “education + exercise” group reported greater ROM (left: 91% vs 84% p=0.16; right: 90% vs 83%; p=0.02) compared to women in the “education only” group. By 18 months, both groups approached 93% with full ROM for both arms. Conclusions: Women who participated in a LE prevention intervention that included exercise and a visit to a physical therapist regained full ROM in both arms sooner than women who did not receive the exercise intervention. All women receiving lymph node dissection should receive physical therapy to regain ROM quickly after surgery and to help maintain physical functioning. Support: UG1CA189823, UG1CA189817, UG1CA189819, U10CA180790, U10CA180836, U10CA180850, and UL1TR001409; Clinical trial information: NCT00376597.
Estimation of historical control rate for a single arm de-escalation study: Application to the POSITIVE trial.
Authors: Zhuoxin Sun, Olivia Pagani, Ann H. Partridge, Hatem A. Azim, Fedro Peccatori, Monica Ruggeri, Marco Colleoni, Richard D. Gelber, Meredith M. Regan
Journal: Journal of Clinical Oncology (2018)

552 Background: A randomized, controlled clinical trial is the optimal method to evaluate the effect of an experimental therapy. However a single arm trial can be used when randomization is infeasible or unethical. POSITIVE is a prospective, single arm, international study aimed at young (age 18-42) women with endocrine responsive (ER+) breast cancer (BC) who desire pregnancy. It will assess whether temporary interruption of adjuvant endocrine therapy (for up to 2 yrs) after 18-30 months of use is safe in terms of risk of recurrence. We describe methods to estimate a historical control rate for POSITIVE using data from the SOFT/TEXT Phase 3 trials. Methods: The primary endpoint of POSITIVE is breast cancer recurrence (BCR) at 3 yrs. In this analysis, we first identified a cohort of SOFT/TEXT pts meeting POSITIVE eligibility criteria. Method I uses the SOFT/TEXT cohort to calculate 3 yr annualized hazard rates by a piecewise exponential model and 3 yr BCR rate by Kaplan-Meier (KM) estimate. Method II uses the SOFT/TEXT cohort to group-match SOFT/TEXT pts to POSITIVE pts; sample sets of SOFT/TEXT pts were randomly drawn with replacement 5000 times to obtain sets having baseline characteristics well-balanced with POSITIVE pts. The mean 3 yr annualized hazard rates and 3 yr KM BCR rates, and their 2.5th and 97.5th percentiles, were estimates (95% CI) for the control group. Results: 149 POSITIVE pts were included; 1499 SOFT/TEXT pts met the eligibility criteria. POSITIVE pts were younger, had fewer positive nodes, and fewer received chemotherapy. Method II refines Method I to adjust for the imbalanced characteristics and provides more precise estimates of the annualized BCR hazard rates and 3 yr BCR rates (Table). Clinical trial information: NCT02308085. Conclusions: The methods used only baseline characteristics of the POSITIVE study and in addition to final analysis interpretation, have a potential role for trial monitoring. The methods should, and will, be applied using data from other sources (e.g. ABCSG-12, ASCO CancerLinQ) to assure a consistent, robust estimate of an historical control rate across different cohorts. Annualized BCR hazard rate 95% CI 3 yr BCR rate 95% CI Method I 3.4% 2.8%, 4.0% 9.5% 7.9%, 11.1% Method II 3.1% 2.6%, 3.7% 8.7% 7.2%, 10.3%
Precision-guided long-acting analgesia by hydrogel-immobilized bupivacaine-loaded microsphere
Authors: Wenjing Zhang, Cong Ning, Weiguo Xu, Hanze Hu, Mingqiang Li, Guoqing Zhao, Jianxun Ding, Xuesi Chen
Journal: Theranostics (2018)

Peripheral nerve blockade (PNB) is a conventional strategy for the management of acute postoperative pain. However, the short duration of the associated analgesia and the potential systemic toxicity due to the low molecular weights of local anesthetics limit their application. Methods: An in situ forming injectable Gel-microsphere (Gel-MS) system consisting of PLGA-PEG-PLGA Gel (Gel) and Gel-immobilized bupivacaine-loaded microsphere (MS/BUP) was prepared for precision-guided long-acting analgesia. A series of in vitro characterizations, such as scanning electron microscopy, rheology analysis, confocal laser scanning microscopy, drug release, and erosion and degradation, were carried out. After that, the in vivo analgesia effect of the Gel-MS system, the immobilization effect of Gel on the MS, and biocompatibility of the system were evaluated using a sciatic nerve block model. Results: The BUP release from the Gel-MS system was regulated by both the inner MS and the outer Gel matrix, demonstrating sustained BUP release in vitro for several days without an initial burst release. More importantly, incorporation of the Gel immobilized the MS and hindered the diffusion of MS from the injection site because of its in situ property, which contributed to a high local drug concentration and prevented systemic side effects. In vivo, a single injection of Gel-MS/BUP allowed rats to maintain sensory and motor blockade significantly longer than treatment with MS/BUP (P < 0.01) or BUP-loaded Gel (Gel-BUP, P < 0.01). Histopathological results demonstrated the excellent biodegradability and biocompatibility of the Gel-MS system without neurotoxicity. Conclusion: This precision-guided long-acting analgesia, which provides an in situ and sustained release of BUP, is a promising strategy for long-acting analgesia, and could represent a potential alternative for clinical pain management.
Association of Plane of Total Mesorectal Excision With Prognosis of Rectal Cancer
Authors: Julia Kitz, Emmanouil Fokas, Tim Beissbarth, Philipp Ströbel, Christian Wittekind, Arndt Hartmann, Josef Rüschoff, Thomas Papadopoulos, Elisabeth Rösler, Peter Ortloff-Kittredge, Ulrich Kania, Hans Schlitt, Karl-Heinrich Link, Wolf Bechstein, Hans-Rudolf Raab, Ludger Staib, Christoph-Thomas Germer, Torsten Liersch, Rolf Sauer, Claus Rödel, Michael Ghadimi, Werner Hohenberger
Journal: JAMA Surgery (2018)

Previous retrospective studies have shown that surgical quality affects local control in rectal cancer..In this secondary end point analysis, we evaluated the prognostic effect of the total mesorectal excision (TME) plane in the CAO/ARO/AIO-04 phase 3 randomized clinical trial.The CAO/ARO/AIO-04 trial enrolled 1236 patients with cT3-4 and/or node-positive rectal adenocarcinoma from 88 centers in Germany between July 25, 2006, and February 26, 2010.Patients were randomized to receive treatment with standard fluorouracil-based preoperative chemoradiotherapy (CRT) alone (control arm) or oxaliplatin (experimental arm) followed by TME and adjuvant chemotherapy.The TME quality (mesorectal, intramesorectal, and muscularis propria plane) was prospectively assessed in 1152 operation specimens. An assessment was performed independently by pathologists and surgeons. The results were correlated with clinicopathologic data and the clinical outcome was tested, including multivariable analysis with the Cox regression model.Of 1152 German Caucasian participants, 332 (28.8) were women and the mean age was 63 years. The plane of TME was mesorectal in 930 patients (80.7%), intramesorectal in 169 (14.7%), and muscularis propria in 53 (4.6%). In a univariable analysis, the TME plane was significantly associated with 3-year disease-free survival (mesorectal vs intramesorectal vs muscularis propria, 95% CI, 73.1-78.8 vs 61.6-76.0 vs 55.6-81.3, respectively; P = .01), cumulative incidence of local and distant recurrences (mesorectal vs intramesorectal vs muscularis propria, 95% CI, 2.0-4.5 vs 1.2-8.1 vs 2.5-20.5, respectively; P < .001; and mesorectal vs intramesorectal vs muscularis propria, 95% CI, 17.0-22.4 vs 18.3-32.0 vs 14.2-39.0, respectively; P = .03, respectively), and overall survival (mesorectal vs intramesorectal vs muscularis propria, 95% CI, 88.3-92.3 vs 79.7-91.0 vs 81.6-98.7, respectively; P = .02). In contrast to the pathologist-based evaluation, the assessment of TME plane by the operating surgeon failed to demonstrate prognostic significance for any of these clinical end points. In a multivariable analysis, the plane of surgery (mesorectal vs muscularis propria TME) constituted an independent factor for local recurrence (P = .002).This phase 3 randomized clinical trial confirms the long-term clinical effect of TME plane quality on local recurrence, as initially reported in the MRC CR07 study. The data highlight the key role of pathologists and surgeons in the multidisciplinary management of rectal cancer.ClinicalTrials.gov Identifier: NCT00349076.
Adjuvant tamoxifen adherence in men with early stage breast cancer.
Authors: Oluchi Oke, Jiangong Niu, Mariana Chavez-MacGregor, Hui Zhao, Sharon Hermes Giordano
Journal: Journal of Clinical Oncology (2018)

550 Background: Most male breast cancers (MBC) are hormone-receptor positive, part of the standard treatment of these patients includes adjuvant tamoxifen. Prior small, single-institution studies have suggested that men may have high rates of discontinuing adjuvant endocrine treatment. We examined rates of tamoxifen discontinuation and medication adherence in a large population-based cohort of MBC patients. Methods: In the SEER-Medicare database male patients with non-metastatic MBC, diagnosed between 2007-2013, age 65 and older, with Part D coverage, and with tamoxifen prescriptions within one year of diagnosis were identified. The cumulative incidence of drug discontinuation was calculated for each year after diagnosis. Adherence was defined as a medication possession ratio (MPR) of > -80% among those patients who were filling tamoxifen prescriptions. A logistic regression model was used to assess predictors of tamoxifen adherence. Results: We identified 451 patients who met eligibility criteria. Median age at diagnosis was 75 years. Median follow-up was 32.5months. 34% of patients had Stage I breast cancer, 48% Stage II, and 18% Stage III. Among those with known hormone receptor status, 99% had hormone receptor positive cancer. Rates of tamoxifen discontinuation were 19.8%, 30.7%, 39.6%, 46.8% and 61.4% at 1, 2, 3, 4, and 5 years after diagnosis, respectively. Among the men who were still taking tamoxifen, the corresponding adherence rates were 77.4%, 75.2%, 71.4%, 67.9%, and 63.5%. In the adjusted model, significant predictors of lower adherence included residing in a high poverty area (OR 0.26, 95% CI 0.08-0.86) and Charlson comorbidity score of ≥2 (OR 0.46, CI 0.21-1.00). Conclusions: Older men with breast cancer have high rates of tamoxifen discontinuation, with 61% of patients discontinuing tamoxifen before the end of year 5. In addition, even among those patients continuing tamoxifen, a substantial number of patients are non-adherent. Further research should evaluate potentially modifiable reasons for treatment discontinuation and lack of adherence to tamoxifen.