tbuckley/cabot-search huggingface dataset:
Outcomes of in-hospital cardiopulmonary resuscitation in patients with metastatic cancer.
Authors: Touqir Zahra, Guibenson Hyppolite, Parijat Saurav Joy, Creticus Petrov Marak, Gagan Kumar, Achuta Kumar Guddati
Journal: Journal of Clinical Oncology (2014)

6636 Background: Patients with metastatic cancer are increasingly availing the use of palliative care services. However, most of them also enroll in clinical trials of novel chemotherapeutic agents. The occurrence of an episode of cardiopulmonary resuscitation (CPR) while these patients are hospitalized may significantly affect their performance status and subsequent treatment. The data with regards to outcome of CPR in patients with metastatic disease is very limited. Methods: Using the Healthcare Cost and Utilization Project – California State Inpatient database 2005-2011, patients undergoing in hospital CPR were identified using appropriate ICD-9-CM. Chi square test and Wilcoxon rank test were used to compare discrete and continuous variables respectively. Significance was defined as p value set at <0.05. Bonferroni’s correction was applied for multiple comparisons. Results: There were 110,581 patients who underwent CPR from 2005 to 2011. Of these 5828 (5.3%) had metastatic cancer. After adjusting for age, the odds of mortality were 3.64 times higher (95% confidence interval 1.99-6.67) when compared to those without any cancer. Age was not associated with better outcomes in those with metastatic cancer undergoing CPR. The outcomes of patients who underwent CPR are shown below (see Table). Conclusions: The resource utilization in patients who underwent CPR is similar regardless of metastatic disease. The mortality however, is significantly higher in those with metastatic disease. Patients with metastatic cancer may benefit from early palliative care services if they undergo CPR and their functional status significantly deteriorates during hospitalization. No cancer Solid organ cancer Metastatic solid organ cancer Mortality (%) 69.7 78.6* 85.7* Invasive mechanical ventilation (%) 68.6 61.9* 63.3* Tracheostomy (%) 6.0 6.0 5.4 Disposition of survivors Home 34.7 31.8* 29.6* Home healthcare 12.5 17.0* 20.5* Nursing home 50.7 49.3 46.4* Others 2.1 1.9 3.5 Median LOS in survivors, days(IQR) 11(5-23) 13(7-22)* 14(7-25)* Median time to death 4(1-10) 5(1-11)* 6(2-13)* Median hospital charges, USD 97,283 89,916* 95,633 * p<0.025 when compared with patients with no cancer.
Efficacy and Safety of Avelumab Treatment in Patients With Advanced Unresectable Mesothelioma
Authors: Raffit Hassan, Anish Thomas, John J. Nemunaitis, Manish R. Patel, Jaafar Bennouna, Franklin L. Chen, Jean-Pierre Delord, Afshin Dowlati, Samith T. Kochuparambil, Matthew H. Taylor, John D. Powderly, Ulka N. Vaishampayan, Claire Verschraegen, Hans Juergen Grote, Anja von Heydebreck, Kevin Chin, James L. Gulley
Journal: JAMA Oncology (2019)

<h3>Importance</h3> Patients with malignant mesothelioma whose disease has progressed after platinum and pemetrexed treatment have limited options. Anti–programmed cell death 1 (PD-1) antibodies have antitumor activity in this disease, but little is known about the activity of anti–programmed cell death ligand 1 (PD-L1) antibodies in patients with mesothelioma. <h3>Objective</h3> To assess the efficacy and safety of avelumab in a cohort of patients with previously treated mesothelioma. <h3>Design, Setting, and Participants</h3> Phase 1b open-label study (JAVELIN Solid Tumor) in patients with unresectable mesothelioma that progressed after platinum and pemetrexed treatment, enrolled at 25 sites in 3 countries between September 9, 2014, and July 22, 2015. <h3>Interventions</h3> Participants received avelumab, 10 mg/kg, every 2 weeks until disease progression, unacceptable toxic effects, or withdrawal from the study. <h3>Main Outcomes and Measures</h3> Prespecified end points included confirmed best overall response based on Response Evaluation Criteria In Solid Tumors, version 1.1; duration of response; progression-free survival (PFS); overall survival (OS); PD-L1 expression–based analyses; and safety. <h3>Results</h3> Of 53 patients treated with avelumab, the median age was 67 (range, 32-84) years; 32 (60%) were male. As of December 31, 2016, median follow-up was 24.8 (range, 16.8-27.8) months. Twenty patients (38%) had 3 or more previous lines of therapy (median, 2; range, 1-8). The confirmed objective response rate (ORR) was 9% (5 patients; 95% CI, 3.1%-20.7%), with complete response in 1 patient and partial response in 4 patients. Responses were durable (median, 15.2 months; 95% CI, 11.1 to not estimable months) and occurred in patients with PD-L1–positive tumors (3 of 16; ORR, 19%; 95% CI, 4.0%-45.6%) and PD-L1–negative tumors (2 of 27; ORR, 7%; 95% CI, 0.9%-24.3%) based on a 5% or greater PD-L1 cutoff. Disease control rate was 58% (31 patients). Median PFS was 4.1 (95% CI, 1.4-6.2) months, and the 12-month PFS rate was 17.4% (95% CI, 7.7%-30.4%). Median OS was 10.7 (95% CI, 6.4-20.2) months, and the median 12-month OS rate was 43.8% (95% CI, 29.8%-57.0%). Five patients (9%) had a grade 3 or 4 treatment-related adverse event, and 3 (6%) had a grade 3 or 4 immune-related, treatment-related adverse event. There were no treatment-related deaths. <h3>Conclusions and Relevance</h3> Avelumab showed durable antitumor activity and disease control with an acceptable safety profile in a heavily pretreated cohort of patients with mesothelioma. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT01772004
Fluorescence-guided lymph node mapping with indocyanine green for endometrial cancer: A feasibility study.
Authors: Marcin Misiek, Jakub Krzysztof Rzepka, Kamil Zalewski, Janusz Kopczyński, Stanislaw Gozdz
Journal: Journal of Clinical Oncology (2014)

e16549 Background: Traditional techniques of sentinel lymph node (SLN) mapping for endometrial cancer present challenges which may be overcome with newer technologies such as near infrared (NIR) imaging of the fluorescent dye indocyanine green (ICG). We performed a feasibility to identify pelvic and para-aortic sentinel lymph nodes with NIR imaging after cervical injection. Methods: Thirty-one subjects with early stage endometrial cancer who were scheduled for pelvic lymphadenectomy were prospectively enrolled for SLN mapping. ICG was injected into the cervical stroma at 3 o'clock and 9 o'clock prior to surgery. Data was collected for the number of nodes identified, the location of SLN's, the duration of procedure and the pathology characteristics of the SLN's compared to the non-sentinel lymph nodes. Results: Thirty-one subjects received cervical injection with at least one SLN observed in 30 subjects. Thirty of the thirty-one subjects who received 0.2 ml of 5 mg/ml mg injections of ICG mapped a SLN for an observed detection rate of 96% A median of 2.7 SLN's was identified per patient. Three patients had lymphatic metastases, all of which had a positive SLN. No adverse events were identified. Conclusions: A preoperative cervical injection of ICG identified a SLN in 96% of patients. Fluorescence imaging is a feasible, safe, time efficient and reliable method for lymphatic mapping in early stage endometrial cancer.
Abstract 15152: Magnetic Resonance Adenosine Perfusion Imaging as Gatekeeper of Invasive Coronary Intervention - Results of the Randomized Controlled MAGNET Trial
Authors: Dominik Buckert, Carsten Hackenbroch, Wolfgang Rottbauer, Peter Bernhardt
Journal: Circulation (2017)

Introduction: Current guidelines support non-invasive detection of inducible myocardial ischemia in the work-up of patients with stable coronary artery disease (CAD). Nevertheless, coronary x-ray angiography (CXA) remains the most often performed diagnostic test in this setting, with more than one-half of elective percutaneous coronary interventions done without previous stress-testing. Hypothesis: In this prospective and randomized trial we aimed to prove non-inferiority of a cardiac magnetic resonance (CMR) vs. a CXA driven CAD management approach regarding cardiac events and quality of life in patients with intermediate to high CAD probability. Methods: Patients with intermediate to high CAD probability were prospectively enrolled into the study. On a 1:1 randomization basis either CXA (Group I) or contrast-enhanced (Dotarem, Guerbet, France) adenosine-perfusion CMR at 3 Tesla (Group II) was performed. Indication for revascularization was given according to results of the index procedure. Primary endpo...
Prognostic significance of the novel IASLC classification in resected pN0 lung adenocarcinomas.
Authors: Emanuela Vattemi, Andrea Ambrosini-Spaltro, Antonio Ruiu, Christine Seebacher, Birgit Feil, Francesco Zaraca, Reinhold Perkmann, Rodolfo Carella, Claudio Graiff
Journal: Journal of Clinical Oncology (2014)

e22113 Background: The aim of this study is to validate impact of tumor architecture defined according to the novel IASLC/ATS/ERS classification on patient overall survival (OS) in resected pN0 invasive pulmonary adenocarcinomas. Methods: We identified patients who underwent resection of pN0 adenocarcinoma from 1998 to 2008 in our institution. Two pathologists, blinded to patient outcome, independently performed histopathologic subtyping according to IASLC/ATS/ERS classification. Histomorphologic data were correlated with patient outcome. Kaplan-Meier curves were used to calculate 5-year survival. Univariate and multivariate analysis were undertaken to control prognostic factors. The following variables were included in the univariate analysis: Sica grade and patterns, pathological 7th edition TNM stage, pleural invasion, lymphatic invasion, vascular invasion, peritumoral lymphocytic infiltrate, -cell type and tumor diameter. Multivariate analysis was used for variables that were found to be significant in the univariate analysis. Results: Sixty-six patients were studied; median age 65 ys (48-84), 71% male. 29 patients (43%) were staged as I, 25 (37%) as II and 12 (18%) as IIIA. Median follow up was 53 months (range: 3-146). Five mutually exclusive tumor histology pattern groups were identified: solid (30,3%), papillary (18,18%), lepidic (3,03%), acinar (43,9%) and mucinous (4,55%). Solid pattern tumors were associated with a lower OS (median: 21 months) than nonsolid pattern tumors(median: 66 months). At univariate analysis, UICC stage (p < 0.001), T (p<0.001), Sica score (p=0.042), Sica primary pattern (0.030) and lymphocytic infiltrate (p=0.001) were related to shorter OS. The predominant growth pattern (p= 0.051), the cell type (p= 0.134) and the other variables were not associated with OS. Multivariate analysis confirmed Sica patterns as an independent prognostic marker of shorter OS (p = 0.044), together with stage and T. Conclusions: Our data confirm the role of known prognostic factors, such as UICC stage and T, as predictor of survival in pN0 patients and suggest the relevance of architectural pattern according to Sica as an efficient new prognostic factor.
Challenging the dogma that first remission is the longest in patients (pts) with advanced ovarian cancer (AOC).
Authors: Sarah Benafif, Thomas Carter, Gordon J. S. Rustin, Marcia Hall
Journal: Journal of Clinical Oncology (2014)

e16528 Background: In the management of AOC, it is traditionally thought that the longest treatment free interval (TFI) is seen after 1st line treatment. In 2011, of 908 AOC pts at MVCC, we showed 1/3 had a longer TFI with a later line of treatment. We have now reviewed records to identify factors that may contribute to longer TFI with a later line of treatment Methods: Of 233 patients where TFI was longer at a later line of treatment, those with the most lines of treatment were examined. 25 pts treated between 1988-2010 had 4 - 12 treatments. Family history of breast/ovarian cancer (FH), use of non-cytotoxic therapies, amongst other parameters were examined specifically in relation to TFI. Results: Six of 25 records studied (24%) pts had a FH and had a median 7 (6-12) treatment lines. Of the 25 records examined, 8 (32%) had a longer TFI after 2nd line treatment, 4 more had a 3rd TFI longer than that after 1st line treatment. Overall, TFI was longer than the preceding interval in 60% (15/25) of pts receiving 3rd line, in 46% (11/24) with 4th line and 32% (6/19) with 5th line treatment. Radiotherapy (RT) was used in 6 cases, 3 of which were given as a standalone treatment for relapsed disease. In all 6 pts, the TFI associated with RT was longer than the preceding TFI. Single agent hormonal treatment was used in 13 pts to treat relapsed disease (8 third line, 2 fourth line, 1 fifth line). In these pts the relevant TFI (chemotherapy) was 43-800 days (Median 329). In 20 pts who received RT or hormonal treatment, further responses to platinum were seen in 50%. Conclusions: Time to first relapse is not always indicative of a pt’s subsequent TFI. Indicators of possible BRCA mutation (Pts with FH) accounted for ¼ of this group confirming its’ association with longer TFIs. In this highly selected group (25/233), the prevalence of non-cytotoxic treatment strategies such as RT and hormones may also have contributed to increase the TFI. It is essential that the remainder of this cohort of 233 patients are examined in the same way and patients receiving newer non-cytotoxic agents such as VEGF inhibitors, tyrosine kinase inhibitors and PARP inhibitors, to test this hypothesis further.
Early outcomes in patients with locally advanced rectal cancer following total neoadjuvant therapy.
Authors: Tyler Friedrich, Karyn A. Goodman, Stephen Leong, Whitney Herter, Sarah Lindsey Davis, Jon Vogel, Ana Gleisner, Cheryl Lauren Meguid, William T. Purcell, Martin McCarter, Michelle Cowan, Tracey E. Schefter, Wells A. Messersmith, Christopher Hanyoung Lieu
Journal: Journal of Clinical Oncology (2018)

848 Background: The current standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiation followed by surgery, and then adjuvant chemotherapy. An alternative approach currently being offered to patients at University of Colorado is total neoadjuvant therapy (TNT), in which patients receive all of their planned treatment, including systemic chemotherapy, preoperatively. Methods: Records of patients from the University of Colorado multidisciplinary colorectal clinic between 2/2015 and 5/2017 were retrospectively reviewed. Treatment plans for included patients involved 8 cycles of preoperative chemotherapy with FOLFOX (5-fluoruracil, oxaliplatin, leucovorin), followed by chemoradiation with concurrent capecitabine, and then resection. Patient data collected includes demographic information, initial staging, chemotherapy and radiation received, adverse effects, surgical outcomes, and clinical and pathological response to treatment. Results: At the time of our analysis, 14 patients have completed TNT and undergone surgical resection, with either abdominoperineal resection or low anterior resection (LAR), at the University of Colorado. Patients ranged in age from 39 to 74 years (mean age 56) with 8 patients (57%) female sex. All 14 patients received 5-fluorouracil with all 8 cycles, though 4 (29%) required omission of oxaliplatin by cycle 8. Toxicities from preoperative treatment were as expected, without significant delays in surgery. Of the 14 patients, 4 (29%) showed a pathologic complete response (grade 0, no residual tumor) on their surgical pathology, with 8 (57%) having either grade 0 or 1 (minimal residual tumor) response. Of the 5 patients who underwent LAR with diverting loop ileostomies, mean time to ostomy reversal was 53.6 days (range 49-61). No patients developed clinically-apparent metastatic disease during preoperative therapy. Conclusions: The use of preoperative chemotherapy in addition to standard chemoradiation for locally advanced rectal cancer is well-tolerated, results in a high rate of pathologic complete response, and allows for early reversal of diverting ileostomies.
Epidemiologic and phylogenetic analysis of the 2018 West Nile virus (WNV) outbreak in Israel demonstrates human infection of WNV lineage I
Authors: Yaniv Lustig, Ruslan Gosinov, Neta Zuckerman, Yael Glazer, Laor Orshan, Danit Sofer, Eli Schwartz, Gili Schvartz, Yigal Farnoushi, Avishai Lublin, Oran Erster, Uri Shalom, Tamar Yeger, Orna Mor, Emilia Anis, Ella Mendelson
Journal: Eurosurveillance (2019)

As at 12 November 2018, an outbreak of West Nile virus (WNV) was responsible for 139 WNV infection cases in Israel. Here, we characterise the epidemiology of the outbreak and demonstrate that only WNV lineage I was circulating in mosquitoes and responsible for WNV infection in humans. This suggests that the concurrence of the outbreak in Israel with WNV outbreaks in several European countries is not due to a common, more virulent WNV genotype.
Prognostic implications of residual disease tumor-infiltrating lymphocytes and residual cancer burden in triple-negative breast cancer patients after neoadjuvant chemotherapy
Authors: S.J. Luen, R. Salgado, M.V. Dieci, A. Vingiani, G. Curigliano, R.E. Gould, C. Castaneda, T. D’Alfonso, J. Sanchez, E. Cheng, E. Andreopoulou, M. Castillo, S. Adams, S. Demaria, W.F. Symmans, S. Michiels, S. Loi
Journal: Annals of Oncology (2018)

For primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), higher pretreatment tumor-infiltrating lymphocytes (TILs) correlates with increased pathologic complete response (pCR) rates, and improved survival. We evaluated the added prognostic value of residual disease (RD) TILs to residual cancer burden (RCB) in predicting survival post-NAC.
Dimethyl Oxalyl Glycine a Prolyl Hydroxylase Inhibitor Decreases Early Gastrointestinal Gvhd Via Two Independent Pathways of Apoptosis after Allogeneic Hematopoietic Cell Transplantation
Authors: Reena Kumari, Senthilnathan Palaniyandi, Ethan Strattan, Sabarinath Venniyil Radhakrishnan, Gerhard Carl Hildebrandt
Journal: Blood (2018)
Inhibition of MEK1 increases carboplatin sensitivity in ovarian cancer.
Authors: Balazs Gyorffy, Andras Lanczky, Imre Pete, Carsten Denkert, Tibor Krenacs, Nora Meggyeshazi, Zsófia Pénzváltó
Journal: Journal of Clinical Oncology (2014)

5557 Background: Primary systemic treatments for ovarian cancer are paclitaxel and carboplatin chemotherapy. Platinum resistant cancers progress/recur in approximately 25% of cases within six months. We aimed to identify clinically useful biomarkers of platinum resistance. Methods: A database of ovarian cancer transcriptomic datasets including treatment and response data was set up by mining the GEO and TCGA repositories. Receiver operator characteristics (ROC) analysis was performed in R for each gene and these were then ranked using their achieved area under the curve (AUC) values. The most significant candidates were selected and in vitrofunctionally evaluated using RNA interference, qRT-PCR, MTT tests and FACS in four epithelial ovarian cancer cell lines (SKOV-3-, CAOV-3, ES-2, OVCAR-3). We collected 94 tumor samples and the strongest candidate was validated by IHC and qRT-PCR in these. Results: All together 1,152 eligible patients were identified, the median relapse-free survival was 24.8 months with 731 progressions. Based on the ROC analysis the eight most significant genes were JRK, CNOT8, RTF1, CCT3, NFAT2CIP, MEK1, FUBP1 and CSDE1. The silencing of MEK1, CSDE1, CNOT8, RTF1 and FUBP1, and the pharmacological inhibition of MEK1caused significant sensitization in the cell lines. Of the eight genes, JRK (p=3.2E-05), MEK1 (p=0.0078), FUBP1 (p=0.014), CNOT8 (p=0.00022) also correlated to progression free survival. The correlation between the best biomarker candidate MEK1 and survival was validated in two independent cohorts by qRT-PCR (n=35, HR=5.8, p=0.003) and IHC (n=59, HR=4.3, p=0.033). Conclusions: We identified MEK1 as a promising biomarker candidate of response to platinum based chemotherapy in ovarian cancer.
Safety and immunologic efficacy of personalized multiple HLA class I-restricted peptide vaccines for breast cancer patients in the adjuvant setting.
Authors: Uhi Toh, Nobutaka Iwakuma, Mai Mishima, Miki Takenaka, Ryuji Takahashi, Mina Furukawa, Teruhiko Fujii, Etsuyo Ogo, Shino Nakagawa, Maki Tanaka, Tetsuro Sasada, Kyogo Itoh, Yoshito Akagi
Journal: Journal of Clinical Oncology (2014)

TPS3130 Background: Despite several attempts to introduce immunotherapy in cancer treatments have been carried out mostly without achieving significant clinical effects for refractory cancer, HER-2+ breast cancer(BC) patients (pts) who received adjuvant trastuzumab(Tz) followed by vaccination with peptide vaccines(PVs) have a lower recurrence rate than adjuvant Tz therapy alone and suggested new adjuvant that can increase the efficacy of the novel immunotherapic strategies.(Sears AK, J Clin Oncol 29: 2011) We previously demonstrated safety, high immunogenicity and clinical benefit for pts with metastatic BC using selected personalized PVs (Toh U, 2013 SABCS), we further conducted a Phase II trial evaluating selected multiple PVs in the adjuvant setting to prevent BC recurrence. The primary endpoint of the study is to evaluate the safety and immunological response to selected multiple peptides vaccination carried out in pts who are in clinical disease free and have completed standard adjuvant chemotherapy, the secondary endpoints were recurrence free survival and overall survival. Methods: This single arm, multicentrePhase II trial enrolled each of HLA-A2, A24, A26 or A3 superfamily molecule postoperative BC patients. Pre-vaccination plasma was measured for their IgG levels reactive to each of the previously reported 31 candidate peptides followed by administration subcutaneously of the four peptides at maximum showing higher levels of IgG. Total sixteen vaccinations were given as weekly for initial eight administrations and as biweekly for further eight inoculations. The concurrent adjuvant endocrine therapy was available during vaccinations. Currently 22 pts have been accrued and 17 pts have completed treatment. Follow-up will be carried out for 24 months to register adverse events and to evaluate the immunological effects. Levels of IgG reactive to each peptide in the pre- and post-treatment plasma were measured using LUMNEX system as well as specific T-cell cytotoxicity assessed by Elispot in the pre- and post-treatment peripheral blood lymphocytes at every 6 times of vaccination. Correlation between survival and the immune activity was investigated. Clinical trial information: 000003081.
Preclinical and Nonclinical Characterization of HPN217: A Tri-Specific T Cell Activating Construct (TriTAC) Targeting B Cell Maturation Antigen (BCMA) for the Treatment of Multiple Myeloma
Authors: Che-Leung Law, Wade Aaron, Rick Austin, Manasi Barath, Evan Callihan, Thomas Evans, Maria Gamez Guerrero, Golzar Hemmati, Adrie Jones, Kathryn Kwant, Llewelyn Lao, Bryan Lemon, Katrine Moldt, Purbasa Patnaik, Kenneth Sexton, Holger Wesche, Yinghua Xiao, Stephen Yu, Tim Yu
Journal: Blood (2018)