tbuckley/cabot-search huggingface dataset:
ChemoPalRx: Development and implementation of a chemotherapy mobile provider order entry system in a safety net hospital.
Authors: Kin Wai (Tony) Hung, Natasha Banerjee
Journal: Journal of Clinical Oncology (2019)

e18071 Background: Computerized provider order entry (CPOE) systems have been shown to enhance the safety and efficiency of prescribing chemotherapy over the handwritten ordering process. However, many institutions lack the financial ability, technological capability, or operational flexibility to invest in and implement such a system. In particular, Olive View-UCLA Medical Center (OVMC), a Los Angeles County safety net hospital, is among these institutions with unique restrictions that preclude the use of chemotherapy CPOE and mandate handwritten orders. Methods: In an effort to bridge the gap for safe chemotherapy prescribing, we aimed to develop and implement an effective, scalable, and sustainable chemotherapy provider order entry solution that was operationally sensitive to institutions without a chemotherapy CPOE. The solution was designed as a mobile application using Xcode, the integrative development environment of Apple Inc., with the Swift programing language. Results: On September 5th, 2018, we launched a free, chemotherapy provider order entry solution on the worldwide Apple App Store – ChemoPalRx. Using ChemoPalRx, providers can search, customize, and print common chemotherapy regimens in prescription format. Along with a reference library of over 120 order set and 450 medications, ChemoPalRx is equipped with the functions to automate dosage calculation, suggest pre-medications and safety parameters, and trigger alerts for missing prescribing information. As a quality improvement initiative, we implemented ChemoPalRx at OVMC. Implementation stages include obtaining administrative buy-in, consulting with multidisciplinary staffs, investing $100 USD for a prescription printer, and encouraging providers to download ChemoPalRx on their own mobile devices. An ongoing prospective cohort study is being conducted to determine ChemoPalRx effectiveness in reducing errors compared to handwritten orders. Conclusions: ChemoPalRx is developed to enhance the safety and efficiency of chemotherapy prescribing. Implementation of this mobile application is feasible in the safety-net hospital setting and has the potential to transform oncology practices globally.
Mean nocturnal respiratory rate predicts cardiovascular and all-cause mortality in community-dwelling older men and women
Authors: Mathias Baumert, Dominik Linz, Katie Stone, R. Doug McEvoy, Steve Cummings, Susan Redline, Reena Mehra, Sarah Immanuel
Journal: European Respiratory Journal (2019)

Respiratory frequency ( f R ) predicts in-hospital and short-term mortality in patients with a variety of pathophysiological conditions, but its predictive value for long-term cardiovascular and all-cause mortality in the general population is unknown. Here, we investigated the relationship between mean nocturnal f R and mortality in community-dwelling older men and women. We measured mean nocturnal f R during sleep from overnight polysomnography in 2686 men participating in the Osteoporotic Fractures in Men Study (MrOS) Sleep study and 406 women participating in the Study of Osteoporotic Fractures (SOF) to investigate the relationship between mean nocturnal f R and long-term cardiovascular and all-cause mortality. 166 (6.1%) men in the MrOS cohort (8.9±2.6 years’ follow-up) and 46 (11.2%) women in the SOF cohort (6.4±1.6 years’ follow-up) died from cardiovascular disease. All-cause mortality was 51.2% and 26.1% during 13.7±3.7 and 6.4±1.6 years’ follow-up in the MrOS Sleep study and the SOF cohorts, respectively. Multivariable Cox regression analysis adjusted for significant covariates demonstrated that f R dichotomised at 16 breaths·min −1 was independently associated with cardiovascular mortality (MrOS: hazard ratio (HR) 1.57, 95% CI 1.14–2.15; p=0.005; SOF: HR 2.58, 95% CI 1.41–4.76; p=0.002) and all-cause mortality (MrOS: HR 1.18, 95% CI 1.04–1.32; p=0.007; SOF: HR 1.50, 95% CI 1.02–2.20; p=0.04). In community-dwelling older men and women, polysomnography-derived mean nocturnal f R ≥16 breaths·min −1 is an independent predictor of long-term cardiovascular and all-cause mortality. Whether nocturnal mean f R can be used as a risk marker warrants further prospective studies.
Circulating tumor DNA analysis of neuroendocrine tumors.
Authors: Jason Scott Starr, Kabir Mody, Ali Roberts, Pashtoon Murtaza Kasi
Journal: Journal of Clinical Oncology (2019)

e15698 Background: Neuroendocrine tumors (NETs) and carcinomas (NECs) are a diverse group of tumors with an equally diverse biology and clinical behavior. Data on tissue-based genomic profiling of NETs exists, however, there is limited data using circulating tumor DNA (ctDNA) technology. We sought out to characterize NETs via ctDNA to identify genomic alterations. Methods: 27 patients with metastatic NET/NEC with 32 total plasma samples were analyzed using Guardant360 ctDNA assay. Breakdown of NET/NEC by location: 14 pancreatic NET (pNET), 11 NEC, 1 small bowel NET, 1 lung NET. The ctDNA test detects single nucleotide variants in 54-73 genes, copy number amplifications, fusions, and indels in selected genes. Results: Of the 27 patients, 19 (70%) had a detectable genomic alteration. The detectable (non-synonymous) alterations are as follows: TP53 (n = 14, 70%), NF1 (n = 8, 40%), EGFR (n = 5, 25%), BRCA2 (n = 4, 20%), KRAS (n = 4, 20%), ARID1A (n = 3, 15%), CDK6 (n = 3, 15%), ALK (n = 3, 15%), MET (n = 2, 10%), PTEN (n = 2, 10%), BRAF (n = 2, 10%), MTOR (n = 2, 10%) AKT1 (n = 1), BRCA1 (n = 1), CCND2 (n = 1), CCNE1 (n = 1), CTNNB1 (n = 1), ESR1 (n = 1), FGFR2 (n = 1), HRAS (n = 1), IDH1 (n = 1), KIT (n = 1), MYC (n = 1), NOTCH1 (n = 1), NRAS (n = 1), PDGFRA (n = 1), RAF1 (n = 1), RB1 (n = 1), SMAD4 (n = 1), STK11 (n = 1), TSC1 (n = 1), ERBB2 (n = 1), PIK3CA (n = 1). Conclusions: This experience highlights the feasibility of ctDNA to help identify genomic alterations in this patient population. Further studies incorporating ctDNA testing in this patient population are warranted.
Bovine milk-derived exosomes mediated delivery of resibufogenin and its effect on platinum-resistant ovarian carcinoma.
Authors: Guannan Zhou, Jingxin Ding
Journal: Journal of Clinical Oncology (2019)

e17065 Background: Platinum-resistant ovarian carcinoma presents poor prognosis owing to its chemotherapeutic resistance. Resibufogenin is a kind of traditional Chinese medicine with potential anti-cancer ability. Exosomes are naturally occurring membrane particles that mediate intercellular communication by delivering molecular information between cells. The purpose of the current study was to evaluate the effect of bovine-milk-derived exosomes as carriers of resibufogenin to Platinum-resistant ovarian carcinoma and investigate the mechanism. Methods: Exosomes were isolated from bovine-milk using differential centrifugation and characterized by electron microscopy, nanoparticle tracking analysis, and western blot. Drug screening among 172 traditional Chinese medicines to find out resibufogenin. The exosomes were loaded with resibufogenin and the effectiveness of exosome-mediated drug was assessed with viability assay, transwell assay and flow cytometry assay. The distribution of exosome-delivered resibufogenin in cells was inspected by confocal microscopy. Xenograft mouse models were constructed to clarify the treatment response in vivo. mRNA sequencing assay, qPCR assay, immunohistochemistry assay and western blotting assay were used to detect and verify the targeted pathways. Results: Our main finding that resibufogenin inhibits the proliferation, migration and invasion in platinum-resistant ovarian carcinoma. Bovine-milk-derived exosomes delivered resibufogenin into platinum-resistant ovarian carcinoma and enhanced the cytotoxicity of resibufogenin. In vivo experiment demonstrated that resibufogenin suppressed the growth of xenograft tumors, with lower ki-67 expression and higher tunel expression. The mRNA sequencing assay, qPCR assay, immunohistochemistry assay and western blotting assay showed that the PI3K/AKT and Regulation of actin cytoskeleton signaling pathways account for the results above. Conclusions: Bovine-milk-derived exosomes can be used as effective carriers of resibufogenin to platinum-resistant ovarian carcinoma. Bovine-milk-derived exosomes-loading resibufogenin inhibits platinum-resistant ovarian carcinoma growth and migration in vitro and in vivo through PI3K/AKT and Regulation of actin cytoskeleton signaling pathway.
Effect of montelukast and rupatadine on rituximab infusion time, rate, severity of reactions, and cost of administration.
Authors: Rouslan Kotchetkov, Jesse McLean, Lauren Gerard, Derek Nay, Sean P. Hopkins
Journal: Journal of Clinical Oncology (2019)

6500 Background: Rituximab is associated with frequent infusion reactions which carry significant burden to patients and health care practitioners. Standard pre-medications (SP) do not prevent reactions sufficiently. Rupatidine (R) and Montelukast (M) are used for symptomatic treatment of urticaria and allergic rhinitis. We assessed addition of R, M and their combination on Rituximab infusion, rate, severity of reactions and cost of administration. Methods: Adult patients with lymphoproliferative disorders treated at our cancer center between Jan 2018 to Jan 2019 were evaluated with Rituximab-containing regiments. Since the majority of reactions occur during the first infusion, our study was limited to the initial Rituximab treatment. Patients received either SP with diphenhydramine/acetaminophen and additional R, M or R+M combination. Comparative analysis of infusion time/rate, severity of infusion reactions, number of rescue medications and cost of Rituximab infusions among groups was performed using one-way ANOVA with Tukey post-hoc or chi-square. The study was approved by our institutional IRB. Results: Patients received either: 1) SP; 2) SP + Rupatadine (R) 10 mg; 3) SP + Montelukast (M) 10 mg; or 4) both (SP+R+M). Patient demographics are shown in the table. Compared to SP, the R, M and R+M groups had greater improvement in Rituximab delivery. Mean infusion time was 306 [range 235-441] min. in SP, 254 [105-390] in M, 265 [193-350] in R and 248 [196-342] in R+M groups, (p=0.0001). Infusion reactions occurred in 92% in SP vs. 38, 45, 33% in M, R and R+M groups (p=0.0001). Median reaction grade was 2 in SP, 1 (M), 0 (R and R+M). Median number of rescue medications was 3 [0-10] in SP vs 0 [0-7] in M, R and R+M groups. Cost of rescue medications (US$) was 38 [0-63] (SP), 11 [0-50] (M), 17 [0-63] (R), 12 [0-58] (R+M) groups (p&lt;0.0001). Mean nursing cost (US$) per patient infusion was calculated as 269 [207-388] in SP vs 222 [92-343] (M), 233 [170-308] (R), 218 [174-301] (R+M) group. Conclusions: Addition of R, M and particularly R+M significantly improved Rituximab delivery, lowered the rate and severity of infusion reactions, and lowered the cost of Rituximab administration. [Table: see text]
A phase II, open label, randomized controlled trial of nivolumab plus ipilimumab with stereotactic radiotherapy versus ipilimumab plus nivolumab alone in patients with melanoma brain metastases (ABC-X Trial).
Authors: Maria Gonzalez, Angela M. Hong, Matteo S. Carlino, Victoria Atkinson, Wei Wang, Serigne Lo, Michael Paul Brown, Matthew C. Foote, Mark B. Pinkham, Hien Le, Daniel E. Roos, Monica Osorio, Neda Haghighi, David Kok, Michael A. Postow, Grant A. McArthur, Alexander M. Menzies, Georgina V. Long
Journal: Journal of Clinical Oncology (2019)

TPS9600 Background: Nivolumab combined with ipilimumab is active in melanoma brain metastases, with intracranial response rates &gt; 55% and durable survival in treatment naïve patients (pts) (Long GV et al Lancet Onc 2018; Tawbi H et al NEJM 2018). We seek to determine if the addition of stereotactic radiotherapy (SRS) results in improved intracranial outcomes. Methods: This is a multisite, open-label, phase 2 trial in systemic treatment-naïve pts with melanoma brain metastases. Pts must have ≥1 asymptomatic brain metastases that are ≥5mm and ≤40mm as per modified RECIST 1.1, on gadolinium-enhanced MRI, and no history of previous treatment with SRS. Eligible pts are randomly assigned to either receive nivolumab plus ipilimumab with SRS or nivolumab plus ipilimumab alone. Nivolumab (1mg/kg) and ipilimumab (3mg/kg) are given every 3 weeks for 4 doses. Following induction, 480mg nivolumab is given every 4 weeks until progression, unacceptable toxicity, or a maximum of 2 years. SRS is administered as single fraction of 16-22Gy, or hypofractionated for larger lesions (24-27Gy in 3 fractions), within 7 days of immunotherapy commencement. Pts will be evaluated for intracranial and extracranial tumour response, and overall response, every 6 weeks to week 24 and 12 weekly thereafter until overall disease progression or death. The primary endpoint is neurologic specific survival (NSS) at 12 months. Secondary endpoints include intracranial response rate, intracranial PFS, overall PFS, overall progression free survival, overall survival, neurocognitive function and incidence of radiation necrosis. 109 patients in each cohort (218 total) will achieve &gt; 80% power at the significance level (alpha) of 0.10 to detect a minimum absolute increase of 9% in the NSS rate at 12 months. Clinical trial information: NCT03340129.
A phase II study of autologous tumor infiltrating lymphocytes (TIL, LN-144/LN-145) in patients with solid tumors.
Authors: Jason Alan Chesney, Jose Lutzky, Sajeve Samuel Thomas, Jorge J. Nieva, Eva Munoz Couselo, Juan Martin-Liberal, Juan Francisco Rodriguez-Moreno, Alex Cacovean, Huiling Li, Maria Fardis, Scott N. Gettinger
Journal: Journal of Clinical Oncology (2019)

TPS2648 Background: Adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has demonstrated durable complete responses in immunogenic tumors with high mutational burden in metastatic melanoma patients who had not received prior immune checkpoint inhibitors (ICI); CR rate 24%. Pembrolizumab is an approved agent for the treatment of metastatic melanoma and head &amp; neck cancers, among others. Further, ICI have been reported to potentially enhance the efficacy of TIL therapy. One aim of this study is to improve the efficacy response for early line patients by combining TIL with anti-PD-1 in ICI-naïve patients with metastatic melanoma (Cohort 1) and head &amp; neck cancers (Cohorts 2). In Cohort 3, TIL therapy alone is offered to NSCLC patients who have received prior systemic therapy, including ICI. Methods: IOV-COM-202 is a prospective, Phase 2 multicenter, open-label study in which 36 patients (12 per cohort) are to be enrolled in one of three cohorts; Cohorts 1 and 2: TIL therapy in combination with pembrolizumab, or Cohort 3: TIL therapy alone. Patients will have tumors resected at local centers and shipped to a central GMP facility to undergo a 22-day manufacturing process that yields cryopreserved infusion product (LN-144/LN-145) that is shipped back to treating center. All patients receive TIL therapy consisting of 1 week of preconditioning cyclophosphamide/fludarabine, followed by a single infusion of LN-144/LN-145 (Day 0) and up to 6 doses of IL-2 (600,000 IU/kg). Patients in Cohorts 1 and 2 also receive pembrolizumab on Day -1 and then Q3W for up to 2 years or until disease progression or acceptable toxicity. Co-primary endpoints for each cohort are objective response rate (ORR) per RECIST 1.1, and safety (grade ≥ 3 TEAE). Eligibility criteria: Cohorts 1 (melanoma) and 2 (head &amp; neck): patients must not have received prior ICI (eg, anti-PD-1, anti-CTLA-4) and may have received up to 3 lines of prior systemic therapy, Cohort 3 (NSCLC): patients must have received 1-3 prior lines of systemic therapy including ICI. After tumor resection for TIL manufacturing, patients must have additional measurable disease for assessment per RECIST 1.1. Adequate bone marrow/organ function and ECOG PS of 0 or 1 is required. Clinical trial information: NCT03645928.
Non-inferiority of a new advanced dry plasma thawing system compared to leading standard method: Preservation of coagulation and anticoagulation proteins necessary for use in the clinic.
Authors: Farideh Z. Bischoff, Will Davey, Brian Read, Tess Deleon, Rebequec Laba, Fred Thacher, Moni Shavit
Journal: Journal of Clinical Oncology (2019)

e14675 Background: Cancer can affect the bone marrow, cause anemia and internal or excess bleeding, requiring blood or plasma transfusion. Fresh frozen plasma (FFP) should be thawed before transfusing to patients but it must be monitored closely to avoid contamination, uncontrolled or prolonged thawing which may subsequently lead to plasma protein denaturation. In this study, we compared and evaluated the effect of two different thawing methods on clotting factor activities as well as factors such as throughput and turnaround time. Methods: Over a period of approximately one month, November 6 to December 3, 2018, our testing laboratory at the UCSD School of Medicine received three sets of samples for a total of 197 freshly collected (pre-freeze) or freshly thawed plasma samples (standard commercial thawing device and the new dry ZipThaw device) that had been collected and processed in accordance with a San Diego Blood Bank protocol described elsewhere. The Lab conducted over 1,782 tests on these plasma for the following factors: Prothrombin time (PT), International Normalized Ratios (INR), Activated Partial Thromboplastin time (aPTT) Factor VIII activity, Factor V activity, Protein C activity, Protein S antigen, Von Willebrand activity and Thrombin Antithrombin Complex (TAT) concentration. The assays were carried out on an ACL TOP 700 Hemostasis Analyzer (Instrumentation Laboratory, Bedford, MA, USA) using manufacturer’s reagents and automated protocols. The ACL TOP 700 has validated precision CV of 5- 10%. All assays were completed within 4 hours of collection or, if frozen, within 4 hours of thawing. The statistical analysis method employed is two-tailed, student t-test. Results: We observed 100% concordance with no statistically significant differences between the pre-freeze group and the two different post thaw groups, except for a slight increase in the mean TAT complex concentration. Overall, the means of all three groups were well within the normal range defined by the assay kits (1-10 ng/ml). Further, the increased mean TAT is more notable with standard method (33%, p = 0.004) than with the ZipThaw (18%, p = 0.054). Conclusions: We report for the first time non-inferiority between the new ZipThaw device and the leading commercial predicate in plasma thawing while preserving coagulation and anticoagulation proteins and minimizing activation of clotting cascade. The results provide support for the use of ZipThaw device in clinical settings.
Despite Policies to Improve Faculty Diversity, Disparities Persist at Public Health Schools
Authors: Rita Rubin
Journal: JAMA (2019)

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Comprehensive germline multigene panel testing changes clinical care for patients with breast cancer: Untapped clinical utility and PARP inhibitor trial eligibility.
Authors: Peter D. Beitsch, Pat W. Whitworth, Kevin S. Hughes, Rakesh Patel, Paul Baron, Barry Rosen, Ian Grady, Dennis Holmes, Rache M. Simmons, Linda Ann Smith, Gia Compagnoni, Cynara L. Coomer, Eric Allen Brown, Karen Barbosa, Patricia Clark, Linsey P. Gold, Lee B. Riley, Edward D. Esplin, Shan Yang, Robert L. Nussbaum
Journal: Journal of Clinical Oncology (2019)

1583 Background: HBOC testing guidelines were established to identify patients with clinically actionable variants and limit economic burden. We report the impact of germline results on health outcome based on clinical decision making and treatment interventions, regardless of guidelines, in a multi-center registry. Methods: 20 community-based and academic participated in an IRB approved registry. Patients with breast cancer were tested with an 80-gene panel; clinical information was collected. Results: Data on 912 patients has been analyzed to date. 50.5% met NCCN criteria; 49.5% did not. Pathogenic/likely pathogenic (P/LP) germline mutations were found in 8.65% of patients. Of all patients with P/LP findings, 85% had variants in cancer-risk genes with established management recommendations and 80% had germline variants conferring eligibility for clinical trials and precision medicine-based cancer treatments, such as PARP inhibitors. For 62% of patients with P/LP germline mutations, clinicians reported results impacted patients’ health outcome. And for 69%, results impacted the health outcome of patients’ relatives. There was no significant association between BRCAPRO scores and patients having a P/LP finding, whether in BRCA1/2 alone (p = 0.42) or for any cancer gene (p = 0.57). Physician reported impact on patient outcome associated significantly with the presence of P/LP germline findings (p &lt; 0.00001). There was no significant difference in the clinician reported clinical utility of variants of uncertain significance (VUS) compared to negative results (p = 0.467). Conclusions: Comprehensive panel testing of breast cancer patients impacts physician assessed patient outcomes and informs changes in surgical treatment strategy, medical therapies and proactive screening. The data suggest that BRCAPRO calculators are poor predictors of germline presence of P/LP findings. Physicians in this study demonstrate the ability to discern the clinically actionable value of P/LP mutations from non-actionable VUS. Multigene panels impact breast cancer patient care by identifying precision medicine treatment interventions, and guiding long-term medical management and preventive surveillance for patients and family members.