tbuckley/cabot-search huggingface dataset:
Barriers to accessing healthcare services: A multidisciplinary approach towards improving pancreatic cancer survival in a Canadian province.
Authors: Elizabeth Faour, Bruce Colwell, Nathan William Dana Lamond, Stephanie Leann Snow, Alwin S. Jeyakumar, Nikhilesh Gajanan Patil, Andreu F. Costa, Mark Walsh, Boris Gala-Lopez, Scott M Livingstone, Kevork Peltekian, Ashley Stueck, Weei-Yuarn Huang, Thomas Arnason, Ravi Ramjeesingh
Journal: Journal of Clinical Oncology (2019)

e18018 Background: Pancreatic cancer (PC) is associated with the highest death rate among common malignancies and is the fourth leading cause of cancer-related death in North America. Despite similar access to treatment options across Canada, the province of Nova Scotia (NS) has the lowest 5-year survival rate for PC. To investigate reasons behind the poor PC outcomes in NS, a multidisciplinary team was created to investigate barriers to care and streamline patient flow. In 2016, initial data informed the reorganization of the hepatopancreaticobiliary (HPB) multidisciplinary team towards the goal of identifying and reducing barriers to care and, ultimately, improving survival. Methods: This quality improvement project included a retrospective chart review of PC patient data from a single institution (The NS Cancer Center), where over 80% of PC patients from this province are seen. A review of PC diagnosis, referrals patterns, and wait time data was undertaken. Results: Data was extracted on 365 patients with a diagnosis of PC between 2011 and 2014. During that period, only 40.4% of patients diagnosed with PC had a tissue diagnosis and just over 71% had a baseline CA19-9. Referral rate to Medical Oncology (MO) was 53%, mean wait time to see MO was 37.2 days and only 23% of patients received systemic treatment. Initiatives to improve access to care included standardization of diagnostic procedures, early triaging of referrals, transfer of port-a-cath (PAC) insertions from interventional radiology to the HPB surgeons, and the creation of provincial guidelines, which were implemented in 2016. Positive Improvements were observed in all identified barriers to care. Conclusions: Barriers to accessing care for PC patients in NS were identified, and a multidisciplinary team proposed provincial guidelines were implemented to expedite care. Preliminary results show improvement in all aspects of healthcare delivery. Survival data will be available in late 2019. [Table: see text]
PanCO: An open-label, single-arm pilot study of phosphorus-32 (P-32; Oncosil) microparticles in patients with unresectable locally advanced pancreatic adenocarcinoma (LAPC) in combination with FOLFIRINOX or gemcitabine + nab-paclitaxel (GNP) chemotherapies.
Authors: Paul J. Ross, Daniel Croagh, Morteza Aghmesheh, Adnan Nagrial, Nam Nguyen, Mehrdad Nikfarjam, Harpreet Singh Wasan, Thankamma V. Ajithkumar, Chinenye Iwuji, Alain Hendlisz, Thomas Maher, Anna Kraszewski, Marion Harris
Journal: Journal of Clinical Oncology (2019)

4125 Background: LAPC is associated with a poor prognosis. Current standard treatment is limited to chemotherapy or chemo-radiotherapy. P-32 Microparticles is a brachytherapy device that implants a predetermined dose of P-32 into pancreatic tumours via endoscopic ultrasound (EUS) guidance. This reports the initial results of a pilot study in combination with chemotherapy. Methods: Eligible patients were permitted to receive either GNP or FOLFIRINOX. P-32 was implanted at week 4 or 5. The dose of P-32 was calculated from tumour volume to deliver an absorbed dose of 100 Gy. Diffusion pattern of the P-32 suspension was assessed by EUS and bremsstrahlung SPECT/CT imaging. Safety data was graded using CTCAE v4.0 criteria. Response was assessed according to RECIST 1.1 with CT scans every 8 weeks and FDG-PET scans at baseline and week 12. Results: 50 patients were enrolled (Intent-to-Treat population (ITT)) of which 42 were implanted with the device (Per Protocol population (PP)). 10 received FOLFIRINOX and 40 GNP. Median age was 65, 28 were male and all had a PS 0/1. 1070 adverse events (ITT) were reported; 153 (80% of patients) were ≥ Grade 3. The most common AEs of ≥ Grade 3 were haematological (39, 46%) and gastrointestinal disorders (30, 34%). No serious device- or radiation-related toxicities have been reported. PP Local Disease Control Rate at Week 16 was 90%; 95% CI: 77-97% and at Week 24 was 71%; 95% CI: 55-84%. Overall Response Rate (ORR) was 31%; 95% CI: 18-47%. Median change in tumour volume from Baseline to Week 16 and to Week 24 was -38% (range +89% to -90%) and -27.5% (range +139% to -79%). Ten (24%) patients underwent surgical resection following repeat staging. Eight patients had R0 margin. Conclusions: The use of EUS-guided implantation of P-32 is feasible, with an acceptable safety profile in combination with first-line chemotherapy for LAPC patients. Encouraging OR and DCR are observed. Further follow-up to inform results of local progression free survival and progression free survival is warranted. Acknowledgement: Nab-paclitaxel was supported by Specialised Therapeutics Australia Pty Ltd. Clinical trial information: NCT03003078.
Response to immune checkpoint inhibition and survival in <i>BRCA-</i>associated recurrent ovarian cancer.
Authors: Ying L Liu, Julia Lindsay Boland, Karen Anne Cadoo, Claire Frances Friedman, Jason A. Konner, Roisin Eilish O'Cearbhaill, Carol Aghajanian, Dmitriy Zamarin
Journal: Journal of Clinical Oncology (2019)

2615 Background: Alterations in the DNA mismatch repair pathway increase susceptibility to immune checkpoint inhibition (ICI). Tumors with BRCA-related DNA repair defects may have increased antigenicity, which could drive response to ICI. Responses to ICI in ovarian cancer (OC) have been modest. We seek to evaluate the association of BRCA mutations with response to ICI and survival in recurrent OC. Methods: A single-center, retrospective review identified 103 women with recurrent OC and known BRCA mutation status (90 germline and 33 somatic testing) who received ICI between 1/2013-7/2018 (98 on study). Clinical characteristics and duration of ICI (Long &gt; = 24 vs. Short &lt; 24 weeks) were compared by BRCA status. Kaplan Meier survival analysis was used to calculate progression-free (PFS) and overall survival (OS) from start of ICI, and CoxPH models/logrank test were used to assess survival differences by BRCA status. Results: Deleterious germline (g) or somatic (s) BRCA 1/2 mutations were present in 29 (28%) women (12 g BRCA1, 9 g BRCA2, 3 s BRCA1, 5 s BRCA2, 1 g BRCA1/s BRCA1, 3 g BRCA2/s BRCA2, and 1 g BRCA2/s BRCA1). Patients (pts) with BRCA mutations had more lines of treatment prior to ICI (median 5 vs. 4, p = 0.03) and a longer time from diagnosis to ICI (median 54 vs. 38.5 months (mo), p = 0.01), but there were no significant differences in other variables including histology (86% high grade serous), stage at diagnosis (96% Stage III/IV), and platinum status (83% resistant), p &gt; 0.05. Four pts (15%) with BRCA mutations had long duration of ICI as compared with 20 pts (27%) in those without mutations, p = 0.20. Median PFS was 2.2 mo (95% CI 1.7-2.7) in those with BRCA mutations and 3.4 mo (95% CI 2.1-4.0) in those without mutations, HR 1.22 (95% CI 0.78-1.91, p = 0.38). At a median follow-up of 23.3 mo, median OS was 21.3 mo (95% CI 13.7-31.8) in those with BRCA mutations and 19.8 mo (95% CI 13.8-25.3) in those without. This was not significantly different, HR 1.00 (95% CI 0.54-1.87, p = 0.99), after adjustment for prior lines and time from diagnosis to ICI. Conclusions: In our study of heavily pretreated OC pts receiving ICI, BRCA 1/2 mutations were not associated with improved response or survival. These findings should be validated in larger studies.
The peritoneal fluid reflects the effect on pancreatic cancer by intraoperative radiation therapy (IORT).
Authors: Yun Sun Lee, Hyung Sun Kim, Joon Seong Park
Journal: Journal of Clinical Oncology (2019)

e15742 Background: Pancreatic cancer has high aggressive features. Intraoperative radiation therapy (IORT) has advantage to deliver the radiation to the restrictive tumor bed immediately. In breast cancer, a study analyzing the wound fluid in patients underwent IORT found that the curative effect was due to the influence to the remaining cancer cell and tumor microenvironment. However, there is a lack of mechanism study related to the effectiveness of IORT in pancreatic cancer. The aim of this study is to investigate whether IORT influenced the responses of pancreatic cancer with peritoneal fluid in vitro and to evaluate the effect and mechanism of the IORT on pancreatic cancer. Methods: Between Apr 2018 and Jan 2019, 28 patients underwent radical resection for pancreatic cancer at Gangnam Severance Hospital. Peritoneal Fluid were obtained 24 hours immediately after operation by surgical drains. And fluid were treated in the pancreatic cancer cell lines (Miapaca-2, PANC1, AsPC1, BxPC3) in total 28 patients (IORT n = 14, no IORT n = 14). Proliferation of cells were measured by WST-1 manner and matrigel coated chambers were used to analyses the invasiveness. Proteomic analysis of fluid was determined by human cytokine antibody array kit (84 targets). Results: When the fluid from each patient was treated to cells different concentrations, the two-dimensional proliferation was stimulated 48 hours later in common but different reactivity was observed for each cell. In invasion assay, cancer cell attracted more by fluid than FBS and decreased invasiveness of cells was observed when treated the fluid from patient underwent IORT. According to the cytokine array, fluid displayed altered expression of several cytokines in patients underwent IORT (Angiogenin, MCP-1, IL-8, IL-6,ENA-78, p &lt; 0.01). Conclusions: We demonstrated that IORT cause the proteomic difference, thereby inducing a change in the biologic activity to pancreatic cancer cell. These results will help us understand the mechanism related to local tumor control and establish the biological basis of IORT. Through the further analysis and long-term follow-up, it will be possible to establish IORT dependent new molecular therapeutic targets or new treatments.
Genetic testing for hereditary breast and ovarian cancer in Indian population: A single institutional study.
Authors: Veda Padma Priya Selvakumar, Shubha Garg, Jatinder Kaur, Geeta Kadayaprath, Nitesh Rohatgi, Meenu Walia, Ranga Rao Rangaraju, Pramod Kumar Julka, Harit Kumar Chaturvedi, Amit Verma
Journal: Journal of Clinical Oncology (2019)

e13153 Background: Women with Hereditary breast ovarian cancer have an increased lifetime risk of developing breast, ovarian and other second primary cancers . A number of genes including BRCA 1 &amp; 2 have been implicated in Hereditary Breast Ovarian Cancer. In this background we sought to analyze the genetic pattern of patients who underwent genetic testing as per the NCCN criteria for hereditary breast ovarian cancer syndrome. Methods: All consecutive patients who fit into the NCCN criteria for genetic testing for Hereditary Breast Ovarian Cancer from 2016 to 2018 were referred to our genetic clinic. The data of all the patients who underwent further genetic testing after counselling were collected and analyzed. Results: Out of 155 patients who underwent genetic testing ,131 patients were found eligible for the study.127 were female and 4 were male. There were 27 pathogenic mutations identified while 32 were variants of unknown significance . The remaining 72 were negative for any of the known mutations. 22 were pathogenic for BRCA 1 Mutation , two pathogenic for BRCA 2 and one for TP53 ,PALB2 and ATM each. Out of the 32 VUS, 9 were BRCA 2, 4 in CDH 1, 2 in BRCA1, CHEK2 ,MSH2 and BRIP1 and one each in MLH1, MLH3, ATM, APC, RAD51D, XRCC3, NBN, TP53.Three patients had double VUS reported. BRCA 1 is the most common pathogenic mutation ( 16.79% ) found while BRCA 2 is the most common VUS reported ( 28 %). Conclusions: 20.6 % of eligible patients had pathogenic mutations which is much higher than the western literature. However the VUS rates in Indian population are high 22% owing to a paucity of genetic data of Indian population. Multigene testing helps in identifying other genes asscociated with the Hereditary breast ovarian cancer criteria in addition to BRCA 1 &amp; 2.
Economic impact of the 31-gene expression profile test in the Medicare-eligible population with cutaneous melanoma.
Authors: Federico A. Monzon, Sarah Kurley, Lauren Perry, Lesly Ann Dossett, John T. Vetto, Charles Mathews
Journal: Journal of Clinical Oncology (2019)

6630 Background: Sentinel lymph node biopsy (SLNB) is recommended as a staging procedure for patients with cutaneous melanoma (CM), but SLNB is associated with additional surgical risks and costs. The SLN positivity rate is approximately 12-16% overall and varies by age. Older patients have lower SLN positivity rates despite a higher metastatic rate. A 31-gene expression profile (31-GEP) test classifies 5-year metastatic risk (Classes 1A [lowest risk], 1B, 2A, and 2B [highest risk]), including SLN metastasis. As previously demonstrated using a large multicenter database, patients with Class 1A, T1-T2 (≤2.0 mm thickness) CM have an overall SLN positivity likelihood &lt; 5%, below the NCCN guideline threshold for SLNB. The aim of this study was to determine the relative cost impact of patient management via traditional care versus using the 31-GEP test to guide SLNB and surveillance plans for 16,572 patients ≥65 years (Medicare-eligible) with T1-T2 CM who are SLNB-eligible. Methods: Decision tree models were used to compare management strategies (surveillance, SLNB) according to traditional care based on SLNB staging and with 31-GEP test utilization. Models used T category from AJCC TNM staging guidelines and SEER data for incidence estimations. Model outcomes included total Medicare costs of melanoma treatment and patient management. Cost impact of the 31-GEP test was calculated based on the difference in Medicare costs between the traditional care and 31-GEP test paradigms. Results: Under the paradigm in which the 31-GEP guided SLNB and surveillance in patients ≥65 years with T1-T2 CM who are eligible for SLNB, 11,157 fewer SLNBs would be performed per year, a 67% reduction in SLNB procedures in this population. This would result in a net annual cost savings of $68M, a 31% reduction in total costs. Use of the 31-GEP testing to guide surveillance in patients ≥65 with T3-T4 melanoma, in addition to T1-T2 melanoma, were also analyzed and also demonstrated a reduction in costs. Conclusions: Results from this study suggest that using the 31-GEP test to guide SLNB and surveillance offers substantial cost savings compared to traditional care for Medicare-eligible patients.
Case 17-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely
Journal: New England Journal of Medicine (1985)

Case Records of the Massachusetts General Hospital from The New England Journal of Medicine — Case 17-1985 — A 13-Year-Old Boy with Aniridia and Proteinuria 11 Years after Nephrectomy for a Wilms' Tumor
SAT0542 DETECTION OF SUBCLINICAL LV MYOCARDIAL DYSFUNCTION IN RHEUMATOID ARTHRITIS PATIENTS BY SPECKLE TRACKING
Authors: yasser gazar, Mohammed Nawar, Abdelhamid Ismail
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) have shorter life expectancy and their risk of cardiovascular (CV) death is more than 50% higher than the rest of the population. Early myocardial dysfunction may be detectable more precisely and sooner using speckle tracking echocardiography. <h3>Objectives</h3> This study was designed to assess myocardial (LV) systolic function by STE (speckletracking Echocardiography) strain imaging in patients with RA without known CVD and to correlate the findings with characters of the disease. <h3>Methods</h3> Cross-sectional observational study enrolled 60 patients with RA (mean age 46.22 ± 8.14 years) without known CVD, and 20 healthy controls. All subjects underwent a standard echocardiographic examination as well as the speckle tracking assessment of left ventricle strains. <h3>Results</h3> Speckle-tracking assessment of LV systolic function revealed decreased GLS among the patients group (-16.80% vs. -22.35%, P&lt;0.001). There was a negative correlation between the duration of RA and the GLS (r = - 0.301). Receiver operating characteristics (ROC) curve was used to define the best cut off value of GLS which was -20, with sensitivity of 76.7%, specificity of 80%, positive predictive value of 92%, negative predictive value of 63% with diagnostic accuracy of 83.9%. <h3>Conclusion</h3> The speckletracking method for myocardial strain analysis showed unambiguously systolic impairment of longitudinal strain parameters. So, patients with RA should undergo a full comprehensive echocardiographic study for assessment of LV systolic function. <h3>References</h3> [1] SHARMA A, KAUSHIK R, KAUSHIK RM, KAKKAR R: Echocardiographic evaluation of diastolic dysfunction in rheumatoid arthritis– a case–control study. Mod Rheumatol 25: 552- 557, 2015. [2] KARPOUZAS GA, MALPESO J, CHOI TY, LI D, MUNOZ S, et al.: Prevalence, extent and composition of coronary plaque in patients with rheumatoid arthritis without symptoms or prior diagnosis of coronary artery disease. Ann Rheum Dis 73: 1797-1804, 2014. <h3>Disclosure of Interests</h3> None declared
AIE-based theranostic systems for detection and killing of pathogens
Authors: Xuewen He, Ling-Hong Xiong, Zheng Zhao, Zaiyu Wang, Liang Luo, Jacky Wing Yip Lam, Ryan Tsz Kin Kwok, Ben Zhong Tang
Journal: Theranostics (2019)

Pathogenic bacteria, fungi and viruses pose serious threats to the human health under appropriate conditions. There are many rapid and sensitive approaches have been developed for identification and quantification of specific pathogens, but many challenges still exist. Culture/colony counting and polymerase chain reaction are the classical methods used for pathogen detection, but their operations are time-consuming and laborious. On the other hand, the emergence and rapid spread of multidrug-resistant pathogens is another global threat. It is thus of utmost urgency to develop new therapeutic agents or strategies. Luminogens with aggregation-induced emission (AIEgens) and their derived supramolecular systems with unique optical properties have been developed as fluorescent probes for turn-on sensing of pathogens with high sensitivity and specificity. In addition, AIE-based supramolecular nanostructures exhibit excellent photodynamic inactivation (PDI) activity in aggregate, offering great potential for not only light-up diagnosis of pathogen, but also image-guided PDI therapy for pathogenic infection.
Quantifying febrile neutropenia rates using electronic medical records in a large integrated delivery network.
Authors: Holly Budlong, Chia-Wei Lin, Joanie Aasen, Darcy Malard Johnson, Elyssa Mason, John Caloyeras, Erin Conley, Rajesh Belani, Arpit Rao
Journal: Journal of Clinical Oncology (2019)

e18298 Background: Febrile neutropenia (FN) is a key driver of morbidity and mortality in oncology patients receiving myelotoxic chemotherapy. Identification and prophylaxis per guidelines can result in a substantial reduction of FN risk and is a key oncology quality of care measure. This project evaluated the feasibility of using electronic medical records (EMR) to quantify FN rates and characterize patients at risk for FN. Methods: Search algorithm was used in EMR to identify patients initiating oncologic care between 1/1/2016 and 12/1/2017 at the Masonic Cancer Clinic, University of Minnesota—Fairview Health System, for a lymphoid, gastrointestinal, breast, female genital, or thoracic malignancy. FN event was identified using a diagnosis of neutropenia (ICD-10: D70.x) with associated fever (ICD-10: R50.2-R50.9) or infection (ICD-10: A40.x, A41.x, B95.0-B95.8, B96.0-B96.8, T80.21-T80.29) during the myelotoxic chemotherapy course. FN rates were evaluated overall and by cancer type, disease status, prior chemotherapy use, select comorbidities, age, curative or palliative intent, and treatment plan FN risk. Results: A total of 1,123 patients receiving 1,663 myelotoxic chemotherapy plans were identified. Patients were predominately female (60%) with a mean age of 61 years (SD: 14.1). A total of 66 patients experienced 79 FN events. Of these events, 70 (88.6%) resulted in a hospitalization. The FN rate during the study period was 5.9% (95% CI: 2.3%-10.2%). Factors associated with the highest FN rates were: lymphoid malignancy (9.9%), non-metastatic disease (7.2%), no prior chemotherapy (6.5%), ≥ 3 comorbidities. Conclusions: Our findings indicate it is feasible to estimate FN rates using a search algorithm with a known FN definition in the EMR of a large integrated delivery network. While additional analyses are planned to account for concomitant patient characteristics to fully understand the occurrence of FN, the current project nevertheless demonstrates the ability of estimating FN rates to both measure care quality and allow pursuing quality improvement (QI) initiatives for appropriate FN prophylaxis. The results also have the potential to serve as a benchmark for similar QI projects in other large healthcare systems.
Chemotherapy-related outcomes in triple-negative breast cancer.
Authors: Rebecca M. Wellmann, Sanaz N. Ghafouri, Nicholas Patrick McAndrew, Sara A. Hurvitz
Journal: Journal of Clinical Oncology (2019)

e12049 Background: Triple-negative breast cancer (TNBC) is associated with a poor prognosis when compared to hormone receptor positive breast cancers. Anthracycline-based regimens (ABRs) are mainstays of treatment for non-metastatic TNBC. However, anthracyclines are associated with an increased risk of potentially life-threatening adverse effects. We sought to compare survival outcomes in patients with early TNBC treated with ABRs versus those treated with anthracycline-sparing regimens (ASRs). Methods: All patients treated for stage I-III TNBC who had undergone curative-intent surgery at a large academic medical center between January 2013-May 2018 were included in the study. Event-free survival (EFS) and disease-free survival (DFS) were the primary endpoints, with overall survival (OS) as a secondary endpoint and were defined as per standardized STEEP criteria. Kaplan-Meier, multivariable Cox regression, and log-rank tests were used to define key survival and treatment related differences between subjects treated with ABRs vs ASRs. Results: 137 patients met inclusion criteria with a median follow-up of 39 months. 21 patients (15%) recurred and 16 (12%) died. Patients treated with ABRs (n = 26, 19%) compared with ASRs (n = 111, 81%) had significantly shorter median EFS (38 months vs not-yet-reached, NYR, p &lt; 0.001), DFS (37 months vs NYR, p &lt; 0.001), and OS (50 months vs NYR, p &lt; 0.001). Though patients in the ABR vs the ASR group were more likely to be node-positive (Odds Radio 3.46, p = 0.006), shorter survival estimates in the ABR group were observed after adjusting for nodal status. 27% of patients (7/26) had an anthracycline added after suboptimal response to an ASR. After adjusting for these patients, the survival findings were similar. 43 patients (31%) received a platinum containing ASR. In the platinum subgroup, ASRs were associated with longer EFS and DFS compared to ABRs, but this effect was not statistically significant in the node-positive group. No cardiac or secondary leukemic events were observed in either group. Conclusions: ABRs were associated with shorter EFS, DFS and OS, even after adjusting for certain high-risk clinical features. Larger studies are needed to identify the role of platinum containing ASRs in patients with early TNBC.