tbuckley/cabot-search huggingface dataset:
Cervical cancer in young patients: Experience from the Peruvian National Cancer Institute.
Authors: Rossana Esther Ruiz Mendoza, Mariana Serrano Cardoso, Raul Mantilla, Natalia Valdiviezo, Mivael Olivera, Luis Mas, Henry Leonidas Gomez
Journal: Journal of Clinical Oncology (2016)

e17008 Background: In a third of the world, cervical cancer (CC) is the most common neoplasia and the first cause of cancer-related death in women younger than 40 years-old. Epidemiological studies report that CC incidence is rising among the young. Information on this topic is scarce and controversial. The aim of this study was to determine the clinicopathologic features, survival outcomes and prognostic factors of CC in young patients. Methods: Retrospective analysis of patients 35 years-old or younger diagnosed with CC between 2008 and 2012 at Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru. Results: During the study period, 449 patients with CC were admitted. The histologic types found were squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma in 86.4%, 11.3% and 2.4% of the cases, respectively. Mean tumor size was 4.98 cm (0.5 - 11 cm). Anemia, increased creatinine values and hydronephrosis were found in 55.7%, 21.2% and 13.8% of cases, respectively. Most of the patients (82.3%) presented with locally advanced disease. FIGO stages IIB (47.4%) and IIIB (25.8%) were the most frequent. With a median follow-up time of 45 months, the median survival time has not yet been reached. Five-year overall survival (OS) was 59.5%. Five-year OS within each FIGO stage was as follows: I, 90.9%; II, 57.5%; III, 42.7% and IV, 13.3%. In the univariate analysis; increased creatinine, anemia, tumor size, parametrial involvement, and hydronephrosis; were factors that affected survival. No significate association was found with the histological type. In the multivariate analysis, pre-treatment anemia (HR, 2.505; 95% CI, 1.594-3.938), parametrial involvement (HR, 2.622; 95% CI, 1.296-5.303) and hydronephrosis (HR, 1.618; 95% CI, 1.021-2.566) were significantly and independently related to survival. Conclusions: Despite being a preventable disease, CC in young Peruvian patients is diagnosed at advanced stages. OS within FIGO stages is similar to that reported for older patients. The relevance of conventional prognostic factors has been confirmed. The presence of anemia, emerged as a powerful independent prognostic factor that warrants further exploration.
Reasons for admission in patients with cancer, leukemia, lymphoma, and multiple myeloma (RAP-CALM) at Moi Teaching and Referral Hospital: Eldoret, Kenya—A pilot study.
Authors: Antoine Saliba, Christopher Mwaniki Wanjiku, Evangeline Wawira Njiru, Carole Jestang, Nicholas Kisilu, Peace Mbengei
Journal: Journal of Clinical Oncology (2018)

e18676 Background: In this study, we describe the distribution of hospital admissions for patients with cancer, including malignant solid tumors, leukemia, and lymphoma, in a tertiary referral center in Eldoret, Kenya. A consultation to Hematology/Oncology is placed for patients with an active diagnosis of cancer who are admitted to MTRH. Methods: We followed patients with an active diagnosis of cancer (solid malignant tumor, multiple myeloma, leukemia, or lymphoma) who were admitted to MTRH over the five months extending between September 2017 and January 2018. Medical information was extracted from the weekly inpatient consult service summaries. Results: Table 1 shows the patient characteristics. Median length of stay was 17 days (range: 1 – 439 days) for our 157 patients. Females had a significantly longer length of stay when compared to males (38 versus 18 days, p = 0.043). 24.3% of patients died during the hospital stay. Four patients were readmitted during the study interval. 80.5% of patients with solid tumors had stage IV disease. Most patients (13.1%) were admitted to the hospital with symptomatic anemia requiring transfusion therapy. Other reasons for admission are detailed in Table 1. Conclusions: Despite recent advances, length of hospital stays, cancer stage at the time of presentation, and inpatient mortality rates remain high. Table 1. Characteristics of patients admitted to Moi Teaching and Referral Hospital in Eldoret, Kenya Sex, % female 90 (57.3%) Age, median in years (range) 48 years (14 – 48 years) Cancer diagnosis, % Breast 36 (22.9%) Sarcoma (angiosarcoma, rhabdomyosarcoma, synovial sarcoma, osteosarcoma) 10 (6.4%) Multiple myeloma 9 (5.7%) Acute myeloid leukemia 9 (5.7%) Colorectal 9 (5.7%) Non-Hodgkin’s lymphoma 9 (5.7%) Chronic myelogenous leukemia 8 (5.1%) Hepatocellular carcinoma 7 (4.5%) Reasons for admission Anemia requiring transfusion therapy 21 (13.1%) Respiratory failure 20 (12.5%) Breast infection 14 (8.8%) Refractory pain 10 (6.3%) Poor feeding, vomiting, hypovolemia 9 (5.6%) Stage of cancer for solid malignant tumors, % Stage I 0 Stage II 2 (1.6%) Stage III 22 (17.9%) Stage IV 99 (80.5%)
A toll-like receptor agonist to drive melanoma regression as a vaccination adjuvant or by direct tumor application.
Authors: Richard Eldon Royal, Luis M Vence, Tara Wray, Janice N. Cormier, Jeffrey Edwin Lee, Jeffrey E. Gershenwald, Merrick I. Ross, Jennifer Ann Wargo, Rodabe Navroze Amaria, Michael A. Davies, Adi Diab, Isabella Claudia Glitza, Wen-Jen Hwu, Sapna Pradyuman Patel, Scott Eric Woodman, Willem W Overwijk, Patrick Hwu
Journal: Journal of Clinical Oncology (2017)

9582 Background: Toll like receptor (TLR) agonists may enhance vaccination or direct immune activation at the tumor microenvironment. This trial evaluates the biologic and clinical effects of Resiquimod, a TLR 7/8 agonist that can activate both myeloid (mDC, TLR 8) and plasmacytoid (pDC, TLR 7) dendritic cells, in patients with advanced stage melanoma. Methods: Class I HLA-A0201+ subjects with in-transit melanoma metastases or high risk for recurrence were vaccinated weekly with peptide vaccination (class I restricted peptide GP100 209-2m and, if HLA-DP4+, also with class II restricted peptide MAGE-3 243-258 ). Subjects were randomized 1:1 to receive Resiquimod as an adjuvant applied to the GP100 vaccination site. Subjects with in-transit disease were thereafter treated with resiquimod topically on half of the target lesions. Results: All patients (n = 47) underwent GP100 209-2m vaccination, a majority (39) also received the MAGE-3 243-258 peptide. The type I interferon-inducible genes (Mx A and IRF7), IFNg, and IP-10 RNA expression were up-regulated only in vaccination sites treated with Resiquimod (each p &lt; 0.01) , demonstrating pDC activation (Type I interferon) and possibly T and NK cell activation (IFNg and IP-10). Nineteen subjects had in-transit disease at entry into the trial. In response to peptide vaccination alone, tumor regression was more likely in patients who received Resiquimod at the vaccination site (group A) compared to those who did not (group B). (4/9 vs 0/10, p = 0.033). In group A, 5 patients continued treatment with Resiquimod topically on the tumors, and all had tumor response (4PR, 1CR). In group B, 5 continued to tumoral resiquimod and 3 had regression (3 PR). Conclusions: Resiquimod increases Type I interferon and IFNg at the peptide vaccination site by activation of pDC/mDC and increases the antitumor response sufficiently to mediate regression of in-transit melanoma metastasis. Resiquimod on in-transit melanoma, in vaccinated hosts, drives regression of metastases, regardless of previous exposure at vaccination. Clinical trial information: NCT00960752.
Nodal involvement and survival in synovial, clear cell, angio, rhabdo, and epithelioid sarcoma.
Authors: Haotong Wang, Ruoyu Miao, Alex Jacobson, Graham Boyd, Saveli Goldberg, Deverati Mitra, Gregory Michael Cote, Edwin Choy, Francis J Hornicek, Kevin Raskin, Thomas F. DeLaney, Yen-Lin Chen
Journal: Journal of Clinical Oncology (2018)

11567 Background: Synovial, Clear cell, Angiosarcoma, adult Rhabdomyosarcoma and Epithelioid sarcoma is often referred to by the mnemonic SCARE as soft tissue sarcoma subtypes with higher risk of lymph node involvement(LNI). This study is to identify the incidence of LNI, prognosis and predictors of LNI, treatment and patterns of failure. Methods: We identified 829 patients with the diagnosis of the above 5 histologies who were treated in our institution and retrospectively reviewed 343 patients who were diagnosed from 2000 to 2017. Statistical significance was assessed with Chi-square and Wald tests. Kaplan-Meier analysis was used to analyze survival outcomes. Results: Primary SCARE sarcoma sites include head and neck(71, 21%), upper extremity(57, 17%), lower extremity(90, 26%), thorax, abdomen and pelvis(47, 14%), trunk and retroperitoneum(44, 13%), GU, GYN and other(34, 10%). 152 present with Stage 2 and 109 with Stage 3 disease (AJCC7). Primary tumor size was = < 5 cm in 123, 5-10 cm in 77 and > 10 cm in 57. LNI was found in 54(16%) patients, of whom 48 were positive at diagnosis and 6 were found during follow up. LNI rates differed significantly (table 1). Tumor size(p = 0.05), histology(p < 0.001), metastasis(p < 0.001) were found as predictors of LNI. 282(82%) patients underwent resection with R0 in 177 patients. Sentinel lymph node biopsy was performed in a limited number of patients. 171(50%) patients received chemotherapy. 247(72%) patients received radiation therapy. Median follow up is 26.5 months. 5-year overall survival(OS) in SCARE histology is 72.7, 41.3, 34.5, 30.8, 45.4% respectively. Synovial sarcoma(SS) has better survival compared to others(p < 0.001). LNI was associated with worse OS (p = 0.001) and DFS(p = 0.001). Multivariate analysis identified LNI(HR = 1.89, p = 0.005), large tumor size(HR = 1.05 per cm, p = 0.003), metastasis(HR = 3.31, p < 0.001) as significant factors affecting OS. Conclusions: LNI is significantly higher in clear cell, angiosarcoma, rhabdomyosarcoma and epithelioid sarcoma than SS, is predicted by larger tumor size, and has poorer prognosis. Synovial Clear cell Angiosarcoma Rhabdomyosarcoma Epitheloid Sarcoma Overall: 343 125 18 78 73 49 LNI (p = 0.0015) 6% 28% 15% 21% 29% M+ at presentation (N.S.) 10% 3% 23% 27% 24%
EGFR/CD16A tetravalent bispecific antibody AFM24 to engage NK-cells to kill EGFR expressing tumor cells and safety results in cynomolgus monkey studies.
Authors: Anne Kerber, Michael Kluge, Uwe Reusch, Kristina Ellwanger, Ivica Fucek, Michael Weichel, Torsten Haneke, Stefan Knackmuss, Erich Rajkovic, Martin Treder
Journal: Journal of Clinical Oncology (2017)

e14001 Background: The epidermal growth factor receptor is a target for the treatment of solid tumors, like CRC, HNSCC and NSCLC. Therapeutic success of EGFR-targeting agents depends on mutations defining resistance to these agents, thus an effective EGFR-targeting therapy overcoming resistance would offer an attractive new treatment option. Natural killer (NK-) cells play a central role in the innate immune system and can destroy cancer cells. NK-cell-engaging bispecific antibodies may offer a safe and effective therapy to target EGFR-expressing tumor cells irrespective of their mutational status. Methods: AFM24 was generated using proprietary human anti-EGFR and anti-CD16A variable domains and characterized for binding, stability, manufacturability, efficacy and safety in biophysical and functional assays in vitro and in vivo. Assays for binding to target/effector cells and cytotoxicity were performed in the presence of physiologically relevant IgG levels using EGFR + tumor cell lines with and without RAS. The safety profile of AFM24 was investigated in vitro for off-target activity and in vivo in cynomolgus monkeys. Results: AFM24 showed excellent biophysical properties and picomolar EC 50 values in cytotoxicity assays. It was more potent than cetuximab, or an antibody with cetuximab-derived anti-EGFR variable domain. Importantly, AFM24 was less prone to IgG interference and eliminated cell lines harboring negative predictive biomarkers in in vitro cytotoxicity assays, even in the presence of relevant serum IgG levels. AFM24 demonstrated in vivo efficacy in a humanized hu-NOG mouse model. Furthermore, AFM24 exhibited a favorable safety profile in cynomolgus monkeys. It was well tolerated up to 94 mg/kg in a single dose, maximum tolerated dose study (MTD) when administered as a 2 hour infusion. Conclusions: Our data suggest that AFM24 is a highly potent and potentially safer drug candidate suitable for the treatment of EGFR-expressing cancers with the potential to overcome resistance to other EGFR-targeting agents and to avoid toxic side effects seen with other anti-EGFR therapeutics.
Gemcitabine and metabolite pharmacokinetics in advanced NSCLC patients after bronchial artery and intravenous infusion.
Authors: Abeer F Alharbi, Robert Arthur Kratzke, Mark N. Kirstein
Journal: Journal of Clinical Oncology (2018)

e21195 Background: We investigated the efficacy, safety, and pharmacokinetics of gemcitabine administered via bronchial artery infusion (BAI) and IV infusion in advanced NSCLC patients. Methods: Patients were eligible if they had received at least two prior cytotoxic chemotherapy regimens. Gemcitabine was administered via BAI as 600 mg/m2 on day 1 of cycle 1, followed by IV as 1000 mg/m2 on day 8 of cycle 1, and IV on days 1 and 8 of all subsequent cycles. Pharmacokinetics for gemcitabine and dFdU metabolite in plasma, and dFdCTP active metabolite in peripheral blood mononuclear cells (PBMC) were evaluated following BAI and IV administration in cycle 1. Plasma and PBMC specimens were collected prior to the dose, and then at 10 time points to 72 hours post dose. Data regarding the post-treatment response, overall survival (OS), and toxicities were collected. Results: Three male patients (age range 59-68 years) were evaluated. All patients responded with stable disease or better. One PR was observed after cycle 3, and the remaining had SD. Cmax (Mean±SD) following BAI for gemcitabine, dFdCTP and dFdU were 7.71±0.13, 66.5±40.6 and 38±6.27 μM and following IV infusion, 17±2.36, 50.8±3.61 and 83.2±12.3 μM, respectively. The AUCinf (Mean±SD) following BAI for gemcitabine, dFdCTP and dFdU were 6.89±1.2, 791.1±551.2 and 829.9±217.8 μM* hr and following IV infusion, 12.5±3.13, 584±86.6 and 1394.64±682.2 μM* hr, respectively. The AUC and Cmax of dFdCTP after BAI were higher than IV. The median OS was 6.27 months. No grade 3 or 4 toxicity observed. The most common side effects were all grade ≤ two involving nausea, vomiting, rigor, thrombocytopenia and anemia. Conclusions: Gemcitabine administered by BAI is safe and well tolerated. Systemic exposure to dFdCTP was higher after lower dose BAI than IV in two out of three patients. Clinical trial information: NCT00619021.
Cognitive computing in oncology: A qualitative assessment of IBM Watson for Oncology in Mexico.
Authors: Catherine Sarre-Lazcano, Alejandra Armengol Alonso, Fidel David Huitzil Melendez, Oscar Arrieta, Andrew D Norden, Alexandra Urman, Mariana Perroni, Alice Landis-Mcgrath, Heriberto Medina-Franco
Journal: Journal of Clinical Oncology (2017)

e18166 Background: Watson for Oncology (WFO) is a Memorial Sloan Kettering trained cognitive computing system designed to extract structured and unstructured data from medical records; ingest a large body of published evidence and guidelines; and provide evidence-based treatment options tailored to an individual patient. In Mexico, 160,000 new cases of cancer are diagnosed per year, causing almost 80,000 deaths. 70% of cases are diagnosed at a late stage (Secretariat of Health, 2016). Given the burden of cancer on morbidity and mortality in Mexico, WFO was evaluated as a potential tool to help oncologists select treatment options for their patients. Our objective was to gain feedback on the experience of using WFO in a Mexican population by a panel of local oncology experts, retrospectively comparing their treatment recommendations to the options provided by WFO. Methods: Patient cases with lung, breast, gastric, colon and rectal cancer diagnosed within the last 5 years were included. Physician users were asked to describe the perceived utility of WFO and to compare the treatment options proposed by WFO with local treatment decisions and guidelines. Results: A total of 100 cases were processed using WFO. Oncologists found WFO to be very useful. They felt that it would be particularly beneficial in clinics that lack subspecialist expertise, and for training medical students and residents. Differences between WFO recommendations and those of the Mexican oncologists were attributed primarily to limited access to high-cost therapies in Mexico and differences between U.S. and Mexican cancer treatment guidelines. Conclusions: WFO is a cognitive computing tool that has the potential to improve the consistency, efficiency, and overall quality of cancer care in Mexico. By surfacing relevant literature and evidence, WFO may provide support for coverage of effective yet high-cost therapies.
Carfilzomib weekly 20/56mg/m², lenalidomide and dexamethasone for early relapsed refractory multiple myeloma.
Authors: Valentine Richez, Stephanie Guidez, Isabelle Azais, Geraldine Durand, Vincent Javaugue, Antoine Brigaud, Antoine Machet, Niels Moya, Cecile Gruchet, Arthur Bobin, Anthony Levy, Florence Sabirou, Celine Dieval, Emmanuel Fleck, Isabelle Princet, Delphine Bauwens, Guillemette Fouquet, Frank Bridoux, Herve Avet-Loiseau, Xavier Leleu
Journal: Journal of Clinical Oncology (2018)

8017 Background: Triplet-based lenalidomide plus dexamethasone (Rd) combinations have become the new standard of care for early relapse and refractory multiple myeloma (RRMM), including carfilzomib plus lenalidomide/dexamethasone (KRd) based on ASPIRE phase 3 data. In ASPIRE, K is given twice a week at 20/27mg/m² on days 1, 2, 8, 9, 15, 16 of a 28 days based cycle. In ENDEAVOR, a second Kd phase 3 study validated that K 20/56mg/m² twice weekly was safe in early RRMM. We hypothesized that KRd on a weekly basis was far less inconvenient to patients (pts). The aim of this study was to evaluate efficacy and toxicity of KRd weekly regimen in pts treated for early RRMM. Methods: 28 pts received KRd in 28-day cycles until disease progression or until occurrence of unacceptable toxic effects. K was administered as a 30-minute infusion on days 1,8,15 (starting dose, 20mg/m2 on day 1 of cycle 1; target dose, 56mg/m2). R (25mg) was given on days 1 to 21. D (40mg) was administered weekly. Results: The median age was 64 years (45 - 80) with 14% older than 70 years, sex ratio M/F 1.3 and ISS disease stage 2 or 3 in 39%. Pts had received a median of 1 (1 - 3) previous lines of therapy including proteasome inhibitors (100%) and immunomodulatory drugs (43%). With a median follow up of 8 months, 3 pts (11%) relapsed, and one patient died. The median number of KRd cycles administered was 6.5 (1 – 12). Overall response rate was 93%, with 89% ≥VGPR and 61% ≥CR. The mean time to a response was 1.6 months. The median TTP and OS at 12 months were 89% and 95%, respectively. 29% of pts have discontinued treatment, with solely 50% due to adverse events (AEs). Hematologic AEs ≥ grade 3 were reported in 57% and non hematologic AEs ≥ grade 3 in 36%. No pts died related to AEs. Overall AEs ≥ grade 3 seen in ≥10% of pts was neutropenia, thrombocytopenia, vomiting and pyrexia. No pts experienced any severe cardiovascular AEs, including cardiac failure or any severe cardiac issues or thromboembolic events. Conclusions: KRd weekly at 20/56mg/m2 is effective and safe to early RRMM pts. Further studies are warranted to confirm this data on a larger MM population. Furthermore, analysis of long-term outcome is needed on our studied population.
TCT-23 Derivation and Validation of Temperature Recovery Time as an Invasive Predictor of Microvascular Obstruction and Prognosis After ST-Segment Elevation Myocardial Infarction.
Authors: Annette Maznyczka, David Carrick, Alex Payne, Greg James-Rae, Jaclyn Carberry, Margaret McEntegart, Mark Petrie, Hany Eteiba, Mitchell Lindsay, Staurt Hood, Stuart Watkins, Ahmed Mahrous, Alex McConnachie, Keith Oldroyd, Colin Berry
Journal: Journal of the American College of Cardiology (2018)
Nephrotoxicity testing in vitro--what we know and what we need to know.
Authors: W Pfaller, G Gstraunthaler
Journal: Environmental Health Perspectives (1998)

The kidney is affected by many chemicals. Some of the chemicals may even contribute to end-stage renal disease and thus contribute considerably to health care costs. Because of the large functional reserve of the kidney, which masks signs of dysfunction, early diagnosis of renal disease is often difficult. Although numerous studies aimed at understanding the mechanisms underlying chemicals and drugs that target various renal cell types have delivered enough understanding for a reasonable risk assessment, there is still an urgent need to better understand the mechanisms leading to renal cell injury and organ dysfunction. The increasing use of in vitro techniques using isolated renal cells, nephron fragments, or cell cultures derived from specific renal cell types has improved our insight into the molecular mechanisms involved in nephrotoxicity. A short overview is given on the various in vitro systems currently used to clarify mechanistic aspects leading to sublethal or lethal injury of the functionally most important nephron epithelial cells derived from various species. Whereas freshly isolated cells and nephron fragments appear to represent a sufficient basis to study acute effects (hours) of nephrotoxins, e.g., on cell metabolism, primary cultures of these cells are more appropriate to study long-term effects. In contrast to isolated cells and fragments, however, primary cultures tend to first lose several of their in vivo metabolic properties during culture, and second to have only a limited life span (days to weeks). Moreover, establishing such primary cultures is a time-consuming and laborious procedure. For that reason many studies have been carried out on renal cell lines, which are easy to cultivate in large quantities and which have an unlimited life span. Unfortunately, none of the lines display a state of differentiation comparable to that of freshly isolated cells or their primary cultures. Most often they lack expression of key functions (e.g., gluconeogenesis or organic anion transport) of their in vivo correspondents. Therefore, the use of cell lines for assessment of nephrotoxic mechanisms will be limited to those functions the lines express. Upcoming molecular biology approaches such as the transduction of immortalizing genes into primary cultures and the utilization of cells from transgenic animals may in the near future result in the availability of highly differentiated renal cells with markedly extended life spans and near in vivo characteristics that may facilitate the use of renal cell culture for routine screening of nephrotoxins.
Updated safety and long term clinical outcomes in TRANSCEND NHL 001, pivotal trial of lisocabtagene maraleucel (JCAR017) in R/R aggressive NHL.
Authors: Jeremy S. Abramson, Leo I. Gordon, Maria Lia Palomba, Matthew Alexander Lunning, Jon E. Arnason, Andres Forero-Torres, Michael Wang, David G. Maloney, Alison Sehgal, Charalambos Andreadis, Enkhtsetseg Purev, Scott R. Solomon, Nilanjan Ghosh, Tina M. Albertson, Benhuai Xie, Jacob Garcia, Tanya Siddiqi
Journal: Journal of Clinical Oncology (2018)

7505Background: Lisocabtagene maraleucel (liso-cel; JCAR017) is a CD19-directed 4-1BB CAR T cell product administered in defined composition at a precise dose of CD8 and CD4 CAR T cells. A multicen...
Abstract 15073: High Sensitivity C Reactive Protein is Associated With Carotid Intoma Media Thickness in White but Not Black Individuals. The Brazilian Longitudinal Study of Adult Health (ELSA Brasil)
Authors: Paulo H Harada, Itamar S Santos, Tatjana Rundek, Isabela M Benseñor, Paulo A Lotufo
Journal: Circulation (2016)

Introduction: Carotid intima media thickness (cIMT) differences across races are insufficiently explained by traditional cardiovascular risk factors distribution Hypothesis: hsCRP association with ...