tbuckley/cabot-search huggingface dataset:
A physician-led team approach to improve advance directive completion rates in an inpatient oncology unit.
Authors: Manojna Konda, Aneesha Ananthula, Alan Baltz, Yadav Pandey, Dinesh Atwal, Issam Makhoul, Heather C Moore
Journal: Journal of Clinical Oncology (2019)

e18271 Background: Advance care planning (ACP) ensures that patients receive care which is consistent with their beliefs and preferences. Advance directive (AD) completion is an important part of this process, but there is much room for improvement as the AD completion rates in oncology patients have been reported to be as low as 10%. We sought to improve the AD completion rates in the inpatient oncology unit in our institution by undertaking an 8-week quality improvement project. Methods: Using a Plan-Do-Study-Act (PDSA) methodology, a multidisciplinary team lead by residents was created to review the process. 2 cycles of PDSA were conducted over a period of 8 weeks. Electronic medical record (EMR) was reviewed each morning, new patients admitted to oncology unit were identified, and those without AD on file were educated by a designated resident about the importance of completing AD. Based on the patients’ willingness, the case manager was alerted with daily communication to follow-up, provide more information and assistance to file the AD. The AD completion rates were tracked daily and communicated to the team through an e-mail. Results: Only 8.3% of hospitalized oncology patients had completed AD prior to our intervention. PDSA cycle 1 resulted in improving the AD completion rates to 28.9%. Barriers were identified after cycle 1 and were overcome by clarifying the role of each team member, addressing inconsistencies in AD filing, uploading into EMR and making the scanned AD easily accessible. After implementation of the above measures, PDSA cycle 2 resulted in improving the AD completion rates to 40.9%. Conclusions: Designating a person to take lead of a multi-disciplinary team, addressing the inconsistencies in the process and keeping a daily track through EMR can lead to an improvement in AD completion rates. Sustainability of this projects remains to be tested. However, there is a room for further improvement.
Controlled-release neurotensin-loaded silk fibroin dressings improve wound healing in diabetic rat model
Authors: Jianghui Liu, Liwei Yan, Wei Yang, Yong Lan, Qiyu Zhu, Hongjie Xu, Canbin Zheng, Rui Guo
Journal: Bioactive Materials (2019)

Diabetic foot ulcers (DFU), which may lead to lower extremity amputation, is one of the severe and chronic complications of diabetic mellitus. This study aims to develop, and use dressings based on Silk fibroin (SF) as the scaffold material, gelatin microspheres (GMs) as the carrier for the neurotensin (NT), a neuropeptide that acts as an inflammatory modulator in wound healing and NT as accelerate wound healing drug to treat DFU. We evaluated the wound healing processes and neo-tissue formation in rat diabetic model by macroscopic observation, histological observation (H&E staining and Masson's trichrome staining) and immunofluorescence analysis at 3, 7, 14, 21 and 28 post-operation days. Our results show that the NT/GMs/SF group performance the best not only in macroscopic healing and less scars in 28 post-operation days, but also in fibroblast accumulation in tissue granulation, collagen expression and deposition at the wound site. From release profiles, we can know the GMs are a good carrier for control release drugs. The SEM results shows that the NT/GMs/SF dressings have an average pore size are 40-80 μm and a porosity of ∼85%, this pore size is suit for wound healing regeneration. These results suggest that the NT/GMs/SF dressings may work as an effective support for control release NT to promote DFU wound healing.
Final analysis of phase II trial of regorafenib (REG) in refractory advanced biliary cancers (BC).
Authors: Dae Won Kim, Hanna Kelly Sanoff, Andrew Stewart Poklepovic, Fatima Tariq, Andrew B. Nixon, Yingmiao Liu, Richard D. Kim
Journal: Journal of Clinical Oncology (2019)

4083 Background: While gemcitabine plus cisplatin has demonstrated significant antitumor activity as 1 st line therapy of BC, there is no effective treatment after failure of gemcitabine-based therapy. REG is an oral multi-kinase inhibitor that targets angiogenesis, oncogenesis and cancer proliferation/metastasis. We evaluated the efficacy of REG in BC. Methods: Patients (pts) with histologically proven BC who progressed on at least one line of systemic therapy received REG 160 mg daily 21 days on 7 days off, in 28 day cycles. The primary endpoint was 6-month (mo) overall survival (OS) and the secondary endpoints were median OS, progression free survival (PFS) and response rates (RR). Pre and post-treatment plasma were collected for cytokine evaluation. Results: A total of 39 pts received at least 1 dose of REG; 32 pts were evaluable for efficacy. Median age was 62 (range: 27-88) years and the primary sites of tumor were intrahepatic cholangiocarcinoma (68.8%), extrahepatic (18.8%), and gallbladder (12.5%). Pts were considered evaluable for efficacy if patients received more than 1 cycle of REG. For 32 evaluable pts, 6 mo OS was 52% with median PFS of 2.8 mo (95% CI: 1.1-4.5) and median OS of 7.9 mo (95% CI: 0-18.7). Median PFS and OS of the pts (n=20) failed 1 line of therapy were 3.7 mo (95% CI: 3.2-4.1) and 13.8 mo (95% CI: 1.8-25.8), respectively. Median PFS and OS of the pts (n=12) failed 2 lines were 1.8 mo (95% CI: 1.63-1.97) and 4.5 mo (95% CI: 2.6-6.3), respectively. RR was 9.4% (2 PR and 1 unconfirmed PR) and DCR was 62.5%. Total 71.8% of grade 3/4 adverse events (AE) were observed, and the most common AE were fatigue (56.4%) and hypertension (53.8%). Dose modification was required in 49% of the pts. Among the 23 cytokines analyzed, elevated baseline VEGF-A was associated with good prognosis (HR 0.62, p=0.01). Elevated baseline TIMP-1 (HR 1.79, p=0.04) and IL-6 (HR 1.33, p=0.05) were associated with poor prognosis. REG treatment decreased BMP-9, GP130, VEGF-R2 and VEGF-R3 and increased IL-6, PIGF, TIMP-1, VCAM-1 and VEGF-A significantly. Conclusions: The primary endpoint was met in this study. VEGF-A may be further evaluated as a predictive biomarker for REG in BC. Further randomized trials are warranted to confirm the efficacy and the correlative data. Clinical trial information: NCT02115542.
Clinical outcomes according to PD-L1 status and age in the prospective international SAUL study of atezolizumab (atezo) for locally advanced or metastatic urothelial carcinoma (UC) or non-UC of the urinary tract.
Authors: Cora N. Sternberg, Axel Stuart Merseburger, Ernest Choy, Daniel E. Castellano, Fernando Lopez-Rios, Nicholas James, Giuseppe Luigi Banna, Ugo De Giorgi, Cristina Masini, Aristotelis Bamias, Xavier Garcia del Muro, Thomas Powles, Ignacio Duran, Craig Gedye, Marija Gamulin, Friedemann Zengerling, Lajos Geczi, Sabine de Ducla, Simon Fear, Yohann Loriot
Journal: Journal of Clinical Oncology (2019)

4519 Background: Atezo, a monoclonal antibody targeting PD-L1, is an approved therapy for locally advanced/metastatic UC based on IMvigor210 and IMvigor211 phase II and III trials. The single-arm SAUL study (NCT02928406) with a broader patient (pt) population demonstrated median overall survival (OS) of 8.7 months and a safety profile consistent with previous atezo trials. Methods: Pts with locally advanced/metastatic UC or non-UC of the urinary tract received atezo 1200 mg every 3 weeks until disease progression or unacceptable toxicity. Populations excluded from IMvigor211 (renal impairment, ECOG PS 2, treated asymptomatic CNS metastases, stable controlled autoimmune disease, concomitant steroids, HIV positive, non-UC) were eligible. The primary endpoint was safety; OS and overall response rate (ORR) were secondary endpoints. Predefined subgroup analyses included outcomes according to PD-L1 status (VENTANA SP142) and age in the overall population (and the IMvigor211-like subgroup for PD-L1). Results: Between Nov 2016 and Mar 2018, 1004 pts were enrolled; 997 received atezo. Efficacy is summarized below. Incidences of grade ≥3 treatment-related adverse events were similar irrespective of PD-L1 status (overall IC 0/1 vs 2/3: 11% vs 16%; IMvigor211-like IC 0/1 vs 2/3: 11% vs 15%) or age (≥65 y: 13%; ≥75 y: 12%; ≥80 y: 10%). Conclusions: OS and ORR appear more favorable in IC 2/3 vs IC 0/1 subgroups (overall and in the IMvigor211-like population). Atezo was effective and well tolerated across subgroups including elderly pts. Clinical trial information: NCT02928406. [Table: see text]
Impact of hormone-therapy used in CRPC patients: Evaluation of abiraterone acetate/prednisone or enzalutamide on activity and cognitive functions in aged castrated mice.
Authors: Hélène Castel, Tareq Al Sagheer, Martine Dubois, Cynthia Campart, Laurence Desrues, Marie Lange, Pierrick Gandolfo, Florence Joly
Journal: Journal of Clinical Oncology (2019)

e16526 Background: Prostate cancer (PC) is a major public health problem and represents the most frequent cancer in elderly male patients. Although most patients initially respond to androgen deprivation therapy (ADT) through inhibition of gonadal testosterone biosynthesis, the majority of these patients will progress to metastatic castration-resistant PC (mCRPC). Novel oral agents targeting androgen signaling axis, abiraterone acetate (AA)+prednisone (P) and enzalutamide (ENZ) are available and used in mCRPC patients in addition to ADT, but their impact on cognition is not well understood. Recently, the AQUARiUS study (Thiery-Vuillemin et al., ESMO Open, 2018) showed that after treatment, median Quality of life score improved with AAP. Additionally, results from a phase 2 trial showed that a worsening of depression symptoms were more often detected in ENZ- than in AAP-treated patients (Khalaf et al., Eur Urol, 2018). Methods: Here we developed a preclinical animal model to clarify the potential impact of AAP or ENZ on emotional reactivity and cognitive functions including spontaneous activity, anxiety-like and depression-like behaviors or spatial memory and learning. Results: In aged castrated mice receiving per os vehicle or AAP or ENZ, we showed that, in contrast to AAP, exposure to ENZ reduced spontaneous activity and increased depressive-like behaviors. AAP-treated mice displayed diminished self-grooming suggesting lower arousal in a novel environment. None of the treatments provoked anxiety-like behavior, learning and memory deficits. However, the swimming strategies (Morris-water maze) in AAP and ENZ groups were slightly altered. Analysis of plasma from treated mice revealed a detectable level of corticosterone only in AAP group. Conclusions: These data establish the impact of ENZ on emotional reactivity and of both ENZ and AAP on subtle cognitive functions in castrated aged male subjects. It paves the road for future effective research that could lead to better management of quality of life in mCRPC.
Comparison of definitive cervical cancer management with concurrent chemotherapy and radiation between two centers with variable resources and opportunities for improved treatment delivery.
Authors: Francis Adumata Asamoah, Pearl Aba Anoa Scott, Zhigang Yuan, Daniel Celestino Fernandez, Samuel Anoa Boateng, Michael E. Montejo, Mervin Anoa Agyeman, Charles Aidoo, Mian M. Shahzad, Jing-Yi Chern, Hye Sook Chon, Robert Michael Wenham, Verna D. Vanderpuye, Joel Yarney, Kosj Yamoah, Kamran A. Ahmed
Journal: Journal of Clinical Oncology (2019)

5534 Background: Cervical cancer remains a global health challenge particularly in low to middle income countries with under resourced healthcare systems. We present the experiences of two centers practicing in variable resource environments to determine predictors of improved radiochemotherapy outcomes. Methods: This retrospective review describes baseline demographic and clinicopathologic characteristics of cervical cancer patients treated with concurrent chemotherapy and radiation between 2014 and 2017 at the National Radiotherapy Oncology and Nuclear Medicine Center (NRONMC) in Korle Bu Teaching Hospital, Accra, Ghana and Moffitt Cancer Center, Tampa, Florida, USA. Results: Ghanaian patients presented at an older median age (56 vs. 49 years, p &lt; 0.001), with predominantly stage IIIB disease (43% vs. 16%, p &lt; 0.001) and squamous cell histology (89% vs. 79%, p &lt; 0.001). Median treatment duration was longer for Ghanaian patients (58 vs. 52 days, p &lt; 0.001). Ghanaian patients were less likely to receive concurrent chemotherapy (68% vs. 100%, p &lt; 0.001) and interstitial brachytherapy implants (0 vs 19%, p &lt; 0.001). No Ghanaian patients received a radiation boost to pelvic or paraortic lymph nodes (p &lt; 0.001). Ghanaian patients had lower local control (64% vs. 93%, p &lt; 0.001) and overall survival (82% vs. 95%, p = 0.02) at 24 months, respectively. For stages IB, IIA, IIB, IIIB, 24 month local control rates for NRONMC vs. Moffitt patients were (60% vs. 93%; p = 0.05), (89% vs. 100%; p = 0.35), (91% vs. 91%; p = 0.89), (53% vs. 91%; p = 0.02) and 24 month OS rates were (85% vs. 100%; p = 0.06), (100% vs. 100%; p = 0.48), (85% vs. 96%; p = 0.2), (73% vs. 91%; p = 0.24), respectively. Treatment duration &gt; 55 days predicted poorer overall survival on multivariable analysis (MVA). Stage ≥III disease predicted poorer local control on MVA. Conclusions: Significant differences were noted in treatment and disease characteristics between the two centers. Feasible improvements for patients treated at NRONMC include removing financial barriers to chemotherapy access, improving radiotherapy delivery capacity to reduce treatment delays, and screening programs to reduce advanced disease presentation.
Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update—Integration of Results From TAILORx
Authors: Fabrice Andre, Nofisat Ismaila, N. Lynn Henry, Mark R. Somerfield, Robert C. Bast, William Barlow, Deborah E. Collyar, M. Elizabeth Hammond, Nicole M. Kuderer, Minetta C. Liu, Catherine Van Poznak, Antonio C. Wolff, Vered Stearns
Journal: Journal of Clinical Oncology (2019)

This focused update addresses the use of Oncotype DX in guiding decisions on the use of adjuvant systemic therapy.ASCO uses a signals approach to facilitate guideline updating. For this focused update, the publication of the Trial Assigning Individualized Options for Treatment (TAILORx) evaluating noninferiority of endocrine therapy alone versus chemoendocrine therapy for invasive disease-free survival in women with Oncotype DX scores provided a signal. An expert panel reviewed the results of TAILORx along with other published literature on the Oncotype DX assay to assess for evidence of clinical utility.For patients with hormone receptor-positive, axillary node-negative breast cancer whose tumors have Oncotype DX recurrence scores of less than 26, there is little to no benefit from chemotherapy, especially for patients older than age 50 years. Clinicians may recommend endocrine therapy alone for women older than age 50 years. For patients 50 years of age or younger with recurrence scores of 16 to 25, clinicians may offer chemoendocrine therapy. Patients with recurrence scores greater than 30 should be considered candidates for chemoendocrine therapy. Based on informal consensus, the panel recommends that oncologists may offer chemoendocrine therapy to these patients with recurrence scores of 26 to 30. Additional information can be found at www.asco.org/breast-cancer-guidelines.
Cumulative odds of increased comorbid score in head and neck cancer.
Authors: Katherine M. Polednik, Aleksandr R Bukatko, Matthew Gaubatz, Matthew C Simpson, Eric Adjei Boakye, Kahee A Mohammed, Nosayaba Osazuwa-Peters
Journal: Journal of Clinical Oncology (2019)

e17555 Background: Survival of head and neck cancer is impacted by known clinical factors, including anatomic subsite, stage of presentation, and treatment modality. An important clinical factor less explored is comorbidity burden. While it is known that a greater comorbidity burden is prognostic for poorer outcomes, it is unclear how the odds of presenting with increased comorbidity score is associated with head and neck cancer anatomic subsite. This study aimed at estimating the cumulative odds of increased comorbidity in head and neck cancer based on anatomic subsites. Methods: Data queried from National Cancer Database (2004-2015). Study sample (N = 328,504) consisted of Stage I-IV, Head and neck Squamous Cell Carcinoma (HNSCC) patients, with no missing demographic variables (age, sex, race, insurance status, local income, local population density). Multivariable cumulative logit model was used to estimate outcome of interest: odds of higher Charlson-Deyo comorbid condition score(CDCC) at HNSCC diagnosis. Results: Compared to patients diagnosed with oropharyngeal cancer (mostly HPV-related HNSCC), patients diagnosed with more tobacco-related HNSCC, such as laryngeal cancer (aOR: 1.69, 95% CI: 1.65-1.73), hypopharyngeal cancer (aOR: 1.33, 95% CI: 1.28-1.38), oral cavity (aOR: 1.26, 95% CI: 1.23-1.29), and sinonasal cancer (aOR: 1.12, 95% CI: 1.06-1.19) had greater odds of presenting with a higher CDCC. Patients with nasopharyngeal cancer did not statistically differ from oropharyngeal patients in odds of higher CDCC presentation. Conclusions: Patients diagnosed with cancers of larynx, hypopharynx and oral cavity (typically associated with tobacco and alcohol use) present with greater comorbid burden compared to patients diagnosed with oropharyngeal cancer (typically associated with HPV). It is important that the role of comorbidity burden be recognized in head and neck cancer prognostication.
Meta-analysis of effect of hormone therapies on lipid levels in breast cancer patients.
Authors: Hsin-Hui Huang, Marnie Bertolet, Emma Barinas-Mitchell, Brenda Diergaarde, Chung-Chou Chang
Journal: Journal of Clinical Oncology (2019)

e18243 Background: Breast cancer (BC) patients with hormone-sensitive tumors often receive adjuvant hormone therapy for an extended period. How this affects lipid levels is not known. This study evaluated the relationship between dyslipidemia, a cardiovascular disease risk factor, and use of adjuvant hormone therapy among breast cancer patients. Methods: Randomized clinical trials for adjuvant hormone treatment in post-menopausal BC patients without residual cancer after primary treatment that reported lipid levels were identified in PubMed and EMBASE (N = 13). Bayesian network meta-analysis for longitudinal data was used to evaluate each drug’s effect on the mean changes in lipid levels from baseline. Key covariates were examined to determine heterogeneity of treatment effects; consistency of estimates was assessed using the arm-based method. Results: Toremifene improved all lipids more than any other hormone drug studied (see Table). Most aromatase inhibitors (AIs) did not significantly impact lipids. Age, baseline lipid value, and prior usage of Tamoxifen modified the drug effects on most lipids. However, these modifications do not change the overall conclusion. Conclusions: Selective estrogen receptor modulators (SERMs) are beneficial to most lipid profiles, but AIs do not have consistent impacts on lipids. Tailoring hormone drug prescriptions based on medical conditions of BC patients is recommended. [Table: see text]
Brain metastases as a first site of recurrence in patients on chemotherapy with controlled systemic cancers: An increasingly urgent clinical scenario.
Authors: Kaelin O'Connell, Carlos G Romo, Stuart A. Grossman
Journal: Journal of Clinical Oncology (2019)

e13590 Background: As the treatment of non-central nervous system (CNS) malignancies improves, brain metastases (BM) are occurring more often in patients with controlled primary disease. In a retrospective analysis of 1953 patients with BM, 44.7% had a controlled primary tumor at the time of BM diagnosis. Given that prognosis after BM remains dismal, it is necessary to identify groups who might benefit from improved delivery of initial systemic therapy across the blood brain barrier (BBB). Methods: A retrospective literature review was conducted to estimate the proportion of patients with non-small cell lung cancer (NSCLC), breast cancer, and melanoma treated with chemotherapy in whom BM was the initial site of recurrence. Only studies explicitly reporting CNS metastasis with controlled extra-cranial (EC) disease on chemotherapy or reporting the first site of recurrence after chemotherapy were included. Results: Four studies of advanced NSCLC reported an average of 23% of patients who developed BM as an initial site of recurrence. Breast cancer cases varied by subtype with a range of 4 - 19%. In four papers reporting HER-2 status, an average of 14% of patients treated with traztuzumab had CNS metastasis with controlled EC disease. In three papers assessing patients with metastatic melanoma on chemotherapy, 4 – 25% initially progressed in the CNS. Conclusions: Of the 1024 patients treated with chemotherapy and achieving controlled systemic disease in this retrospective review, first recurrence in the brain was common: 23% in NSCLC, 12% in breast cancer, and 12% in melanoma. While chemotherapy controlled non-CNS disease, concentrations of these drugs were clearly subtherapeutic in the CNS. Preventing BM in patients with NSCLC, breast cancer, and melanoma will require novel therapeutic approaches designed to facilitate drug entry through an intact BBB early in the treatment of the primary tumor. [Table: see text]
Prevalence of targetable mutations in black patients with lung cancer: A systematic review and meta-analysis.
Authors: Yonette Paul, Sunil G Iyer, Leonardo Tamariz, Zsuzsanna Nemeth, Gilberto Lopes
Journal: Journal of Clinical Oncology (2019)

e13105 Background: Although poorer outcomes of lung cancer in Blacks compared to other racial groups has been strongly linked to socio-economic factors, it is important to investigate whether lower prevalence of targetable mutations limit treatment options, thereby also contributing to worse outcomes. This study examines the prevalence of EGFR, ALK, ROS-1 and BRAF lung cancer mutations in Blacks compared to other races. Methods: We conducted a meta- analysis compliant with PRISMA guidelines. Searched databases included PubMed/MEDLINE, Cochrane CENTRAL, EMBASE, Google Scholar and clinicaltrials.gov. Publication bias was mitigated by searching clinicaltrials.gov for unpublished studies. Searches were run to 11/19/2018. Two rounds of screening were performed based on title and then abstract by two independent reviewers. For the purposes of this study we defined racial groups as Black, Asian, Hispanic, and White/Caucasian. We selected studies of lung cancer patients (any stage or type) where the prevalence of at least one mutation was reported in Blacks. We calculated the pooled prevalence of mutations by racial group using fixed effects, exact binomial distributions and Freeman-Turkey double arcsine transformation to stabilize the variances. Results: Prevalence % of mutations by race reported with 95% Confidence Interval in parentheses N = number of tests performed We included 20 studies which totaled 11,867 lung cancer patients. Each mutation tested on a tissue sample was considered an event, for a total of 15,306 events. EGFR was the most prevalent mutation in Blacks (6%). Compared to other races Blacks had the lowest prevalence of all four mutations. Conclusions: In the era of targeted therapy, outcomes for metastatic lung have improved significantly. Of concern, our results show that Blacks are disproportionately ineligible for these therapies due to lower prevalence of targetable mutations. More research is needed to evaluate the unique tumor characteristics and therapeutic strategies in this sub group of patients, in the hope of achieving better disease outcomes.[Table: see text]