tbuckley/cabot-search huggingface dataset:
Observational analysis of patient trajectory in metastatic pancreatic cancer.
Authors: Stephanie McCutcheon, Nathan Bahary, Henry Q. Xiong, Peter G. Ellis, Hans Benson, Melinda Krebs
Journal: Journal of Clinical Oncology (2016)

e15707 Background: Metastatic pancreatic cancer is an aggressive disease. Given that data suggest limited benefit from second line therapy and the challenges associated with a rapid decline in performance status, it is reasonable to evaluate how many patients receive disease-directed therapy after first line failure. This observational analysis of UPMC CancerCenter (UPMC) data captured in the Via Portal (VP) examines the trajectory of care for patients with metastatic pancreatic cancer. Methods: UPMC providers utilize Via Pathways decision support algorithms in their daily practice through the web-based VP. We analyzed all new treatment starts for metastatic pancreatic patients captured in the VP from Jul 2009 to Dec 2014. Patients on therapy at the time of this analysis were excluded in entirety. Days on treatment was defined as time elapsed between patient visits in the VP, not actual treatment start/stop dates. Off treatment decisions (selected from a list) were reported for the last treatment received. We assumed patients were no longer on active treatment if 4 weeks elapsed without a visit. Off treatment decisions were not reported for these patients. Results: A total of 782 new treatment starts were captured. Of those, 534 had off treatment decisions captured for the following: End of Life Care (57%), Observation (18%), Referral to Other Provider (11%), Other Reason (6%), Poor PS (4%), Second Opinion (2%), Patient Refused (2%). Conclusions: The majority of patients did not receive second line therapy and only 13.4% went on to third line. The median number of days on treatment was consistent for the first three therapies received. End of Life Care was chosen most frequently when stopping therapy. Ongoing work includes promoting early incorporation of palliative and/or end of life care into the pathways. Additionally, more active chemotherapy combinations that became the standard of care near the end of the evaluated period may enable more patients to receive multiple lines of therapy. These data are being actively evaluated and will be updated at the time of the presentation. Line of Therapy n % of Total (n = 782) Days on Treatment Avg / Median / StDev 1 782 100.0 102 / 72 / 93 2 317 40.5 102 / 69 / 107 3 105 13.4 93 / 70 / 80 4 42 5.4 87 / 56 / 91 5 11 1.4 102 / 70 / 103 6 2 0.3
Determining optimal sequencing of anti-PD-1 and BRAF-targeted therapy: A phase II randomised study of neoadjuvant pembrolizumab with/without dabrafenib and trametinib (D+T) in BRAF V600 mutant resectable stage IIIb/c/d melanoma (NeoTrio trial).
Authors: Maria Gonzalez, Alexander M. Menzies, Robyn Saw, Andrew J. Spillane, Omgo E. Nieweg, Kerwin F. Shannon, John F. Thompson, Julie R. Howle, Sydney Ch'ng, Jonathan Stretch, Monica Osorio, Louise Emmett, Helen Rizos, Alexander David Guminski, Matteo S. Carlino, Richard A. Scolyer, Georgina V. Long
Journal: Journal of Clinical Oncology (2018)

TPS9604 Background: BRAF targeted and CTLA-4/PD-1 immunotherapies have high response rates and improve survival for patients (pts) with metastatic melanoma, however, most still die of this disease. It is hypothesised the activated cytotoxic T cell infiltrate that occurs early during treatment with BRAF/MEK inhibitors is potentiated by adding checkpoint inhibitors, resulting in improved response and survival. While trials combining BRAF/MEK inhibitors and anti-PD-1/L1 antibodies are underway in the metastatic setting, the neo-adjuvant (neo-adj) setting provides an opportunity to test different treatment schedules in small cohorts of pts. Tissue and blood biomarkers can be drawn at several timepoints and correlated to clinical and pathological endpoints to explore mechanisms of response, biomarkers of efficacy, and to select the best schedules to take forward to larger-scale trials. Methods: Eligible pts with BRAF V600 mut, stage IIIB/C/D, resectable and measurable (RECIST 1.1) melanoma are evenly assigned to 3 cohorts (n = 60). All pts undergo complete macroscopic resection (RES) at wk 12 and receive neo-adj therapy for 12 wks preceding RES, followed by 40 wks of adjuvant (adj) therapy. Cohort 1 receive sequential therapy with D+T for 2 wks, then 4 pembrolizumab (pembro) doses until wk 12, and 3 wkly pembro after RES. Cohort 2 receive concurrent D+T and 3 wkly pembro before and after RES. Cohort 3 receive 3 wkly pembro for the entire treatment course. Pembro is given at a flat dose of 200mg. Ultrasound of known disease areas is undertaken during the neo-adj period. CT and FDG PET/CT are used to measure response and exclude progression in the neo-adj phase, and to monitor for recurrence during adj and post treatment phases. Blood and tumour samples are collected at baseline, wk 1, 4 and 12. The primary endpoint is the complete pathological response rate at RES following 12 wks of therapy. Secondary endpoints include RECIST response, metabolic response, OS, RFS, safety/tolerability, surgical outcomes, quality of life, and biomarker analysis. First patient enrolled 29Nov2017. Clinical trial information: NCT02858921.
Analysis of immune-related prognostic markers in colon cancer patients randomized to surgery or surgery and adjuvant cytostatic treatment.
Authors: Lisa Villabona, Giuseppe V. Masucci, Peter Ragnhammar
Journal: Journal of Clinical Oncology (2016)

e15102 Background: HLA-A*02, a common allele in the Scandinavian population, is a negative prognostic factor in epithelial ovarian cancer. It is a strong predictor of patient outcome, only inferior to clinical staging. This prognostic trait in epithelial ovarian cancer is stronger by the presence of the gene compared with the expression of its protein, MHC class I. HLA-G has also been shown to be a poor prognostic marker and believed to have an immune suppressive role. Our aim was to analyse the prognostic markers HLA-A*02 genotype, MHC class I and HLA-G expression on tumour cells and the CD8+ lymphocyte infiltration in colon cancer patients with randomized treatment. Methods: Clinical information and primary tumours were collected from 520 colon cancer patients and followed for overall survival for 120 months. Patients hade stage II and III coloncancer and were randomized to surgery alone or surgery and adjuvant chemotherapy. HLA-A*02 genotype was determined by conventional PCR. MHC class I and HLA-G expression and CD8+ lymphocyte infiltration were determined by immunohistochemistry. Results: Patients with a stage III tumour and HLA-A*02 genotype had a better outcome if they had received adjuvant chemotherapy instead of just surgery, whereas this was not the case for patients with other HLA-A genotypes. MHC class I expression did not act as a prognostic factor, however the presence of CD8+ lymphocytes in the invasive margin and inside the tumour was a positive prognostic factor for overall survival. Interestingly HLA-A*02 genotype was a superior negative prognostic factor but only in the female patients. In the male patients, however, the absence of CD8+ lymphocytes and HLA-G expression was a worse prognosis. Conclusions: When combining the different markers, two patterns emerge. Male patients have a better prognosis with a high infiltration of CD8+ lymphocytes independent to the status of their HLA-A genotype. The prognosis of the female patients on the other hand, is independent on the amount of CD8+ lymphocyte infiltration or HLA-G expression, but have a poorer prognosis when they carry the HLA-A*02 genotype, suggesting that there are two different mechanisms in play.
Abstract 17889: A Randomized Controlled Trial of Moderate Glucose Control After Complex Pediatric Cardiac Surgery
Authors: Xu Wang, Shoujun Li, Xia Li, Kai Ma, Juxian Yang, Min Zeng, Shengli Li, Leilei Duan
Journal: Circulation (2015)

Introduction: Infants and children after cardiac surgery may develop hyper- or hypoglycemia, associating with higher nosocomial infection or neurological morbidities. Hypothesis: The hypothesis of this perspective randomized control study is moderate glucose control may improve clinical outcomes. Methods: We randomly assigned children(≤3 years of age) who were admitted to the pediatric cardiac intensive care unit (PICU) after cardiopulmonary bypass surgery into either moderate glucose control group (target blood glucose: 110-143mg per deciliter) or conventional glucose control group (target level below 200mg per deciliter). The primary outcome was the rate of nosocomial infection in PICU. Second outcomes include hospital mortality, duration of mechanical ventilation and PICU stay, and a composite morbidity variable included events of requiring extracorporeal membrane oxygenation, delayed sternal closure, dialysis-dependent renal failure and hypoglycemia. Results: A total of 593 patients underwent randomization: 293 to moderate glucose control group and 300 to conventional glucose control group. The baseline data were balanced between these two groups. Mean 72 hours time-weighted blood glucose average was lower in the moderate control group than in the conventional group (129.9±22.1 mg per deciliter vs. 138.8±28.6 mg per deciliter, p&lt;0.001). Although no statistically significance reached, there is a trend that nosocomial infection occurred less in moderate glucose group (17 (5.80%) vs. 29 (9.67%), P=0.054). Duration of mechanical ventilation was shorter in the moderate control group (18 (range, 4-300) hours vs 22 (range 3-771) hours, p=0.046). Hypoglycaemia (blood glucose ≤65mg per deciliter) which occurred in 7(2.39%) patients in the moderate group versus 8 (2.67%) in the conventional group, was statistically similar between groups. Other secondary outcomes did not differ significantly between groups. Conclusions: With moderate glucose control, although the major clinical outcomes did not change, this randomized control study showed shorter ventilation time after pediatric cardiac surgery, substantially benefit for patients with complex congenital cardiac anomalies.
Clinical parameters predicting response and outcomes to immunotherapy in metastatic cancers.
Authors: Rohan Garje, Adithya Chennamadhavuni, Sarah Bell, Gerald H. Clamon
Journal: Journal of Clinical Oncology (2018)

e15084 Background: Checkpoint inhibitors are approved as effective therapy in a number of malignancies. The response rates range between 20-40% in various cancers. Predictive as well as prognostic clinical characteristics and bio-markers are needed to identify the population that benefits with immunotherapy. Prior studies suggested that the presence of hepatic metastases is a marker of poor prognosis. In this study of patients treated with checkpoint immunotherapy, we evaluated if it also predicts poor response to immunotherapy. Other clinical factors such as age, BMI, baseline LDH, albumin, lymphocyte count, neutrophil count and neutrophil lymphocyte ratio (NLR) were explored as predictive markers of response to checkpoint immunotherapy. Methods: In this retrospective analysis of 215 patients conducted at University of Iowa, we included patients with renal cancer (N = 23), cutaneous melanoma (N = 181), ocular melanoma (N = 9) and other (N = 1) who were treated with ipilimumab, nivolumab or pembrolizumab. Results: Hepatic metastases were significantly more common with a N/L ratio > 4, increased ALT, and with other sites of metastases including bone, lung and other visceral organs. Patients with hepatic metastases had a significantly lower response rate ( p = 0.05) , were more apt to be deceased ( p < .01) but age, BMI, and baseline LDH were not associated with hepatic metastases. Factors significantly associated with improved overall survival included BMI > 30 and having received prior therapy before immunotherapy ( p = .04) Metastases to bone, liver, brain, and other visceral organs were associated with poorer survival. Patient age, gender and type of immunotherapy agent were not associated with survival. Too few patients were treated with concurrent antacids or had antibiotics within 30 days of immunotherapy to know if these factors were significant. Conclusions: Presence of hepatic metastases is associated with poor response to immunotherapy. Interestingly, BMI > 30 is associated with improved survival in patients who receive immunotherapy. Baseline parameters total number of patients (N = 215) Age > 70 27.4% BMI > 30 34.6% LDH > 220 22.2% Albumin > 3.4 91.6% Neutrophil/Lymphocyte (N/L) ratio > 4 28.6% Hepatic metastases 22.8%
Impact on survival of catastrophic karyotype events in 101 consecutive acute myeloid leukemia (AML) patients: High risk karyotype and chromothripsis.
Authors: Maria Chiara Fontana, Giovanni Marconi, Cristina Papayannidis, Viviana Guadagnuolo, Silvia Lo Monaco, Anna Ferrari, Elena Tenti, Andrea Ghelli Luserna di Rorà, Giorgia Simonetti, Maria Chiara Abbenante, Sarah Parisi, Stefania Paolini, Chiara Sartor, Antonella Padella, Simona Soverini, Marco Manfrini, Nicoletta Testoni, Carmen Baldazzi, Giovanni Martinelli
Journal: Journal of Clinical Oncology (2016)

7044 Background: Genomic alterations are proved to initiate cancer and related to prognosis in AML. We tested 101 consecutive AML patients (pts) at diagnosis to find prognostic implications of new genomic analysis techniques. Methods: We performed traditional cytogenetic and SNP 6.0 or Cytoscan HD Array (Affymetrix). SNP Array data were analyzed by a bio statistical tool (Nexus Copy Number v7.5). All the patients were tested for FLT3 and P53 mutational status. Survival analysis was performed with Kaplan-Meier method using Mantel-Cox test. Results: Outof 101 patients, 22 patients (21.8%) had a mutation of TP53, 27 patients had secondary AML. Seventy of 101 patients were treated with intensive chemotherapy, 13/101 were treated with 5-azacitidine, 3/101 were inserted in clinical trials, and 12/101 did not receive specific therapies. By karyotype analysis, 3/101 patients had t(8;21) or inv(16) (LR), 51/101 Normal Karyotype or other alterations (SR), and 47/101 had at least one alteration between -5, del(5q), -7, del(7q), t(6;9), t(9;22), abn(3q), (11q), (20q), (21q), (17p), or complex karyotype (HR). With SNP array 8/101 patients showed chromothripsis events involving different chromosomes. This group of patients had median age of 68.5 years (range 56-76), and all had complex karyotype. All these patients harbored TP53 mutation. TP53 is significantly more mutated in chromothripsis patients than in those with HR karyotype without chromothripsis (p < 0.001). In our set, chromothripsis defines a group of patients with poor prognosis compared with all other patients (p < 0.001), median survival 2.57 months vs 18.53 months. Chromothripsis define patients with worst prognosis even in HR group (p = 0.01). Moreover, we identified as abnormal several pathways regulating: cytoskeleton, histone acetyltransferase microtubules, telomere and positive regulation of cell cycle (p < 0.001). Conclusions: Our data suggest that chromothripsis independently defines a group of patients with poor prognosis. Chromotripsis is highly associated with TP53 mutation. Genomic characterization of those patients could reveal underlying mechanisms.
TCT-777 Guided De-Escalation of DAPT in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention with BVS implantation: A post-hoc Analysis from the Randomized TROPICAL-ACS Trial
Authors: Lukasz Koltowski, Mariusz Tomaniak, Bartosz Rymuza, Michal Kowara, Radoslaw Parma, Anna Komosa, Mariusz Klopotowski, Tommaso Gori, Daniel Aradi, Kurt Huber, Martin Hadamitzky, Steffen Massberg, Grzegorz Opolski, Dirk Sibbing, None Zenon Huczek
Journal: Journal of the American College of Cardiology (2018)
Abstract 2242: Very High Resolution Near Field Imaging of Ablation with a Newly-Developed Forward-Looking Catheter Mounted Microlinear Intracardiac Imaging Array
Authors: David J Sahn, K. Kirk Shung, Jonathan Cannata, Douglas N Stephens, Raymond Chia, Peter Chen, Kai Thomenius, Aaron Dentinger, Muhammad Ashraf, Matthew O’Donnell, Aman Mahajan, Kalyanam Shivkumar
Journal: Circulation (2007)

Background: We have developed the first forward-looking highly steerable intracardiac echo probe developed for ultrasound visualization of ablation. It is a 24-element forward-looking microlinear array on a 9 Fr catheter that has additional electrodes so it can be localized compared to separate ablation catheters through electrofield navigation by NavX. Methods: In 4 studies of closed-chest pigs, we have imaged ablation locations in the right atrium and the isthmus and on the right side of the septum and at the right ventricular apex, and also imaged across the septum at ablations in the left ventricle along the septum with this device. Results: Images at 150–170 frames/sec at 12–15 MHz give very high detail of the changes occurring during ablation, including liquefaction, heating changes, brightening and thickening of tissue, and thrombus formation in the adjacent region in unheparinized pigs. The devices are well enough shielded from RF energy that there is little interference, and yet an ablation is being performed. A catheter tip artifact makes it easy to see the actual location of the ablation catheter tip with the microlinear array. Tissue Doppler/strain rate imaging also yields the possibility of determining mechanical changes occurring in ablation where brightening of tissue associated with stiffening diminished mechanical strain deformations in ablated lesions, especially in the ventricles. Conclusions: This new technology provides a new method for guidance and, more importantly, a method for understanding the changes that occur with RF ablations in experimental animals and, eventually, in patients.
Chemotherapy-induced neutropenia risk models to guide the use of myeloid stimulating factors in intermediate risk chemotherapy: A cost and practicality analysis.
Authors: Chetan Jeurkar, Tiffany Pompa, Ho-man Yeung, Pamela A. Crilley, David Lane Topolsky, Michael Styler
Journal: Journal of Clinical Oncology (2017)

10086 Background: The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) have published guidelines for use of prophylactic colony stimulating factors (CSF) for patients at risk for chemotherapy induced neutropenia (CIN). Both recommend CSF if the chemotherapy regimen has a &gt;20% febrile neutropenia (FN) risk. If the regimen is of intermediate CIN risk, the guidelines are less definitive. In this study, we looked at lung cancer patients receiving intermediate CIN risk chemotherapy and applied two risk models developed by Hosmer et al and Bozcuk et al to see if they have adjunct value to the NCCN and ASCO guidelines to more accurately predict CIN. Methods: This was a retrospective study of 43 patients with a diagnosis of lung cancer who were treated with chemotherapy at Drexel University from 2005-2016. Risk models developed by Hosmer et al and Bozcuk et al along with the NCCN and ASCO guidelines were applied to the cohort of patients. Results: The Hosmer calculator recommended giving CSF to 26 patients, the Bozuk calculator for 22 patients, the NCCN guidelines for 25 patients and the ASCO guidelines for 38 patients. Sensitivities, specificities, and pricing information for one course of filgrastim are listed for each risk model in the Table. Conclusions: In lung cancer patients receiving intermediate CIN risk chemotherapy, the Hosmer calculator had the best combination of sensitivity, specificity, and ease of use. The Bozcuk calculator, while accurate, was more difficult to use. The NCCN guidelines missed more patients with severe CIN while the ASCO guidelines gave CSF to the greatest number of patients. The cost for using CSF would have been highest using the ASCO guidelines. Therefore, we recommend the Hosmer calculator for lung cancer patients receiving intermediate risk CIN chemotherapy as it lends to accurate but judicious use of CSF. [Table: see text]
Tumor vascular normalization monitor by non-contrast intravoxel incoherent motion diffusion-weighted MRI.
Authors: Yunlong Pan, Pan Jinghua, Xiaoxu Zhao, Hui Ding, Jinlian Huang, Shengbin Zhu
Journal: Journal of Clinical Oncology (2018)

e15707 Background: Tumor vascular normalization has been proposed as a new concept for anti-tumor angiogenesis, and the normalization time window had been considered as an opportunity to improve drug delivery. However, there is still lack of a noninvasive method to monitor the process of tumor vascular normalization.we aim to investigate whether the non-contrast intravoxel incoherent motion (IVIM) diffusion-weighted MRI can monitor the process of tumor vascular normalization. Methods: This study included 35 BALB/C mice in the Endostar group and the control group. The tumor xenograft model was established using the CT26 cells. The Endostar group group was treated with recombinant human endostatin 5mg/kg per day. The control group was treated with 0.9% normal saline. The IVIM-MRI was utilized to detect the perfusion of xenograft tumors in 0d, 2d, 4d, 6d, 8d, 10d and 12d, each day with 5 mice in the two group. We detected the vessel density (CD31) and pericyte coverage (αSMA/CD31) of xenograft tumors via under the immunofluorescence. Correlations of D slow ADC (D), D*-fast ADC (D*) and F-Faction ADC (F) with pericyte coverage were analysed. Results: The value of D in the two groups had no significant difference. The D*-fast ADC after treatment for 0d and 2d had no significant difference, however, D* values of the Endostar group were increasing after treatment for 4d, 6d and 8d, and were higher than that of the control group in 4d, 6d, 8d and 10d. In 12d, D* values had no significant difference in the two groups. The F value of Endostar group was significantly lower than the control group in 2d, and higher than the control group in 6d and 8d. The vessel density in Endostar group was significantly lower than that of the control group in 4d, 6d, 8d and 10d, and the pericyte coverage in Endostar group was higher than the control group in 6d, 8d and 10d. There were significant correlations between pericyte coverage with D* and F value. Conclusions: The IVIM-MRI can monitor the effects of anti-tumor angiogenesis in colorectal cancer xenograft mice model. The D* and F value of IVIM-MRI can be considered as effective and noninvasive indicators for detecting the tumor vascular normalization in anti-angiogenesis treatment.