tbuckley/cabot-search huggingface dataset:
Association of body mass index and systemic inflammation index with survival in patients with renal cell cancer treated with nivolumab.
Authors: Ugo De Giorgi, Giuseppe Procopio, Roberto Sabbatini, Claudia Caserta, Manfred Mitterer, Cinzia Ortega, Alessandro Scoppola, Giuseppe Fornarini, Francesco Ferraú, Paolo Marchetti, Claudio Verusio, Enrico Mini, Paolo Bidoli, Sebastiano Buti, Lucio Crino, Umberto Basso, Antonio Frassoldati, Alessandra Bearz, Giacomo Carteni, Cora N. Sternberg
Journal: Journal of Clinical Oncology (2019)

e16077 Background: Body mass index (BMI) and inflammation indexes are easily evaluated, predict survival in many tumors, and are potentially modifiable. The "obesity paradox" of longer survival in cancer patients with high BMI has been explained by altered fatty acid pathways, which could have an impact in immune-inflammatory function, and leptin-driven increase in T cell aging resulting in higher PD-1 expression and dysfunction, which leaves tumors notably more sensitive to checkpoint blockade. We evaluated the potential association of inflammatory indexes and BMI with the clinical outcome of metastatic renal cell carcinoma (mRCC) undergoing immune checkpoint inhibitor therapy. Methods: A prospective cohort of patients with mRCC treated with nivolumab enrolled in the Italian Expanded Access Program (EAP) from July 2015 through April 2016 was examined. Reference measures of inflammation were identified for neutrophil to lymphocyte ratio (NLR) &lt; /≥3, systemic immune-inflammation index (SII) &lt; /≥3 and platelet to lymphocyte ratio (PLR) &lt; /≥232. Patients were classified as high BMI (≥25 kg/m 2 ) versus normal BMI ( &lt; 25 kg/m 2 ). Results: Among 313 evaluable patients, 289 (75.1%) were male, median age was 65 years (range, 40 to 84), with 105 (24.9%) ≥70 years. In univariate analysis, age ≥70 years, performance status, BMI, SII, NLR and PLR were able to predict outcome. In multivariate analyses, SII ≥1375, BMI &lt; 25 and age ≥70 years independently predicted OS (HR, 2.96; 95% CI, 2.05-4.27; HR, 1.59; 95% CI, 1.10-2.30 and HR, 1.65; 95% CI, 1.07-2.55, respectively). Under the model of independent effects, a patient with both SII ≥1375 and BMI &lt; 25 was estimated to have much worse OS (HR, 3.37; 95% CI, 2.29-4.95, p &lt; 0.0001) than a patient with neither or only one risk factor. SII changes at 3 months predicted OS (P &lt; 0.0001). Conclusions: BMI combined with inflammation tripled the risk of death, suggesting that these biomarkers are critical prognostic factors for OS in patients with mRCC treated with nivolumab.
Expression level of NRP1 and SMAD2 in correlation to mutational status of RAS (BRAF) in pancreatic cancer.
Authors: Libor Stanek, Petra Tesarova, Robert Gurlich
Journal: Journal of Clinical Oncology (2019)

e15784 Background: Pancreatic cancer is the second leading cause of death in tumor diseases worldwide. Neuropilin-1 (NRP1) is overexpressed in many tumors including the pancreatic cancer. The main goal is to reveal the role of NRP1 in the process of tumorigenesis. The expression of NRP1 and the presence of KRAS point mutation lead to the cell survival by lowering the SMAD2 phosphorylation. On the other hand, the NRP1 inactivation and the wild-type KRAS in tumor cells lead to the tumor growth inhibition. Our aim is to prove correlation between NRP1 level, SMAD2 and the mutational status of KRAS, NRAS in prognosis of patients with pancreatic cancer. Methods: Retrospective study is based on analysis of 50 FFPE bioptical samples (40 resections, 8 punctures, 2 thin-needle biopsies); histology verified all as adenocarcinomas. The expression level of NRP1 and SMAD2 is measured by Imunohistochemistry by mice monoclonal antibodies Anti-Neuropilin 1 and Anti-SMAD2 (Abcan) on the device BenchMark ULTRA (Ventana Medical Systems), Roche. DNA isolation is executed by QIAamp DNA Mini Kit. We used Codon Specific Mutation Detection Kit (Diatech pharmacogenetics) for detection of somatic point mutations in codons 12, 13, 61 and 146 of KRAS and NRAS genes. BRAF mutational status was revealed by direct sequencing on ABI Prism 3130. We monitor the level of expression of NRP1 and SMAD2 and correlate it to the mutational status of RAS and BRAF, and disease prognosis. Results: NRP1 expression was detected in 24 out of 50 cases, SMAD2 expression was detected in 13 of 50 cases, other cases without expression. KRAS gene mutation was detected in 8 cases out of 60, other cases of WT. Mutation in the NRAS gene was detected in 3 of 50 cases. BRAF gene mutation was detected in 1 case out of 50, other WT. NRP1 expression correlated with KRAS gene mutation status in 9 cases and a strong correlation (p = &lt; 0.001) was recorded. One case of mutation in the BRAF gene correlated with KRAS mutation status and NRP1 expression. Due to the small number of samples tested, without statistical significance. Inactivation of NRP1 was detected in 15 cases and was confirmed by the WT status of the KRAS gene. Conclusions: Was demonstrated that causal relationship exists between inactive NRP1 and wild-type KRAS, and that these should cause decrease of the rate of tumor growth. These characteristics, which are achievable simultaneously during the histological verification, may serve as a potential prognostic marker for subsequent decision of how radical surgical resection should be.
Association of Serum Cholesterol Levels With Peripheral Nerve Damage in Patients With Type 2 Diabetes
Authors: Johann M. E. Jende, Jan B. Groener, Christian Rother, Zoltan Kender, Artur Hahn, Tim Hilgenfeld, Alexander Juerchott, Fabian Preisner, Sabine Heiland, Stefan Kopf, Mirko Pham, Peter Nawroth, Martin Bendszus, Felix T. Kurz
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Lowering serum cholesterol levels is a well-established treatment for dyslipidemia in patients with type 2 diabetes (T2D). However, nerve lesions in patients with T2D increase with lower serum cholesterol levels, suggesting that lowering serum cholesterol levels is associated with diabetic polyneuropathy (DPN) in patients with T2D. <h3>Objective</h3> To investigate whether there is an association between serum cholesterol levels and peripheral nerve lesions in patients with T2D with and without DPN. <h3>Design, Setting, and Participants</h3> This single-center, cross-sectional, prospective cohort study was performed from June 1, 2015, to March 31, 2018. Observers were blinded to clinical data. A total of 256 participants were approached, of whom 156 were excluded. A total of 100 participants consented to undergo magnetic resonance neurography of the right leg at the Department of Neuroradiology and clinical, serologic, and electrophysiologic assessment at the Department of Endocrinology, Heidelberg University Hospital, Heidelberg, Germany. <h3>Exposures</h3> Quantification of the nerve's diameter and lipid equivalent lesion (LEL) load with a subsequent analysis of all acquired clinical and serologic data with use of 3.0-T magnetic resonance neurography of the right leg with 3-dimensional reconstruction of the sciatic nerve. <h3>Main Outcomes and Measures</h3> The primary outcome was lesion load and extension. Secondary outcomes were clinical, serologic, and electrophysiologic findings. <h3>Results</h3> A total of 100 participants with T2D (mean [SD] age, 64.6 [0.9] years; 68 [68.0%] male) participated in the study. The LEL load correlated positively with the nerve's mean cross-sectional area (<i>r</i> = 0.44;<i>P</i> &lt; .001) and the maximum length of a lesion (<i>r</i> = 0.71;<i>P</i> &lt; .001). The LEL load was negatively associated with total serum cholesterol level (<i>r</i> = −0.41;<i>P</i> &lt; .001), high-density lipoprotein cholesterol level (<i>r</i> = −0.30;<i>P</i> = .006), low-density lipoprotein cholesterol level (<i>r</i> = −0.33;<i>P</i> = .003), nerve conduction velocities of the tibial (<i>r</i> = −0.33;<i>P</i> = .01) and peroneal (<i>r</i> = −0.51;<i>P</i> &lt; .001) nerves, and nerve conduction amplitudes of the tibial (<i>r</i> = −0.31;<i>P</i> = .02) and peroneal (<i>r</i> = −0.28;<i>P</i> = .03) nerves. <h3>Conclusions and Relevance</h3> The findings suggest that lowering serum cholesterol levels in patients with T2D and DPN is associated with a higher amount of nerve lesions and declining nerve conduction velocities and amplitudes. These findings may be relevant to emerging therapies that promote an aggressive lowering of serum cholesterol levels in patients with T2D.
Tracking circulating cell-free tumor DNA in gastric cancer to detect early disease recurrence.
Authors: Jian Yang, Yuhua Gong, Vincent K. Lam, Yan Shi, Yan-Fang Guan, Yanyan Zhang, Liyan Ji, Yongsheng Chen, Yongliang Zhao, Feng Qian, Jun Chen, Pingang Li, Fan Zhang, Jiayin Wang, Ling Yang, Andrew Futreal, Jianjun Zhang, Xin Yi, Xuefeng Xia, Peiwu Yu
Journal: Journal of Clinical Oncology (2019)

e14571 Background: Identifying locoregional gastric cancer patients who are at high risk for relapse after resection could facilitate early intervention. By detecting molecular residual disease (MRD), circulating tumor DNA (ctDNA) has been shown to predict post-operative relapse in several cancers. Here, we aim to evaluate MRD detection by ctDNA and its association with clinical outcome in resected gastric cancer. Methods: This prospective cohort study enrolled 46 patients with stage I-III gastric cancer that underwent resection with curative intent. Resected tumor samples and plasma samples were obtained for targeted deep sequencing and longitudinal ctDNA profiling. Results: ctDNA was detected in 45% of treatment-naïve plasma samples. T stage was independently associated with pre-operative ctDNA positivity (p = 0.006). All patients with detectable ctDNA in the immediate post-operative period eventually experienced recurrence. ctDNA positivity at any time during longitudinal post-operative follow-up was associated with worse DFS and OS (HR = 14.78, 955 CI, 7.991-61.29, p &lt; 0.0001 and HR = 7.664, 95% CI, 2.916-21.06, p = 0.002, respectively), and preceded radiographic recurrence by a median of 6 months. Conclusions: In locoregional gastric cancer patients treated with curative intent, these results indicate that ctDNA-detected MRD identifies patients at high risk for recurrence and can facilitate novel treatment intensification studies in the adjuvant setting to improve survival.
Circulating tumor DNA dynamics, serial testing and evolution on treatment in 322 colorectal cancer patients.
Authors: Pashtoon Murtaza Kasi, Saivaishnavi Kamatham, Dorin Colibaseanu, Amit Merchea, Faisal Shahjehan, Jason Scott Starr, Kabir Mody
Journal: Journal of Clinical Oncology (2019)

3566 Background: According to the American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) joint review on circulating tumor DNA (ctDNA) issued in March 2018, widespread use of ctDNA assays in most patients with advanced cancer is still an area of ongoing research. However, multiple studies thereafter published and/or presented support its use in patients with metastatic colorectal cancer (CRC). This has led to several institutions adopting it as ‘clinical practice’. The aim of this study is to report on our institution’s adoption of ctDNA testing for every patient at the time of diagnosis and/or time of progression. Methods: We report on results of 322 CRC patients with 607 ctDNA tests at our center from January 2017 to February 2019 using a commercially available platform (Guardant360). Results: Among 322 patients of our cohort, a total of 607 ctDNA tests were done (Table). 127 (39.4%) of these tests were serial analyses. In the CRC patients who had serial testing, at progression, mechanisms of resistance included acquisition of KRAS, NRAS, EGFR mutations; and HER2- and MET-amplifications. The subclonal mutations were noted to disappear when the selective inhibition was stopped. This was seen in patients on targeted therapies/biologics rather than chemotherapy. This was of value in treatment modification, clinical trial selection and/or monitoring of disease progression in these patients. Conclusions: While ctDNA testing may not be ready for primetime in all advanced cancers, it is increasingly being adopted in practice for especially metastatic CRC. Of particular value is the serial ctDNA testing in the RAS/RAF wildtype subset and now BRAF V600E mutant CRC on anti-EGFR based therapies. [Table: see text]
Carbon ion reirradiaton for patients with malignant gliomas: Toxicity and first results of the prospective dose-escalation phase I/II CINDERELLA trial.
Authors: Stephanie E Combs, Denise Bernhardt, Sebastian Adeberg, Klaus K Herfarth, Andreas Unterberg, Wolfgang Wick, Juergen Debus, Stefan Rieken
Journal: Journal of Clinical Oncology (2019)

2059 Background: The prospective phase I/II CINDERELLA trial investigates toxicity and effectiveness of a dose escalated reirradiation with carbon ions in patients with recurrent gliomas. Methods: Following a dose escalating protocol, 52 patients with WHO°II-IV gliomas were irradiated with carbon ions with doses of 3 Gy (RBE) in 10 – 16 fractions in 7 dose leels. Median age was 42 years (range: 28 - 69) with 19 female and 33 male participants. Forty-one patients were diagnosed with WHO°III/IV gliomas and 11 patients with WHO°II gliomas. At the time of reirradiation, all patients showed contrast-enhancing recurrences. MRI-based treatment planning encompassed the contrast enhancing lesion (GTV) with additional safety margins of 5 mm (CTV) and 3 mm (PTV). Clinical follow-up visits including contrast-enhanced MRI were scheduled every two months. We used RANO-criteria for diagnosis of progression. Survival rates were analyzed with Kaplan-Meier estimator. Relevant prognostic factors were determined with log rank-test, and toxicity was classified according to CTCAE v4.0. Results: Median time between first irradiation and reirradiation was 9 months (range: 7 – 228). PTV size was 12 – 310 ml. During follow-up ≥°3 toxicities were not observed. Follow-up MRI suggested radiation necrosis in 4 patients. Median overall survival was 352 days and was not influenced by age, gender or radiation dose. A significant trend for improved survival rates was seen in patients with small target volumes (480 days [PTV &lt; 75ml] vs. 322 days [PTV &gt; 75ml], p = 0.06) and initial low grade histology (497 days [WHO °II] vs. 322 days [WHO°III/IV], p = 0.069). During follow-up, 45 patients had local progression, while clinical deterioration was not seen. Median local progression-free survival was 138 days. Twenty-eight patients received chemo-/immunotherapy after reirradiation. Of those, 14 patients were treated with bevacizumab. Progression after reirradiation did not influence overall survival significantly. Conclusions: Carbon ion re-irradiation with 10-16 fractions of 3 Gy for patients with recurrent gliomas is safe; no dose limiting toxicities were observed. Median overall survival with approximately one year is high in comparison to other treatment options. It remains unclear if RANO-criteria is securing the diagnosis of therapy failure after carbon ion reirradiation. Further randomized controlled trials must be awaited to evaluate the effectiveness of reirradiation of carbon ions compared to other treatment options. Clinical trial information: NCT01166308.
Abstract P315: Is Self-rated Health Associated With Ideal Cardiovascular Health? The Multi-Ethnic Study of Atherosclerosis
Authors: Olatokunbo I Osibogun, Oluseye Ogunmoroti, Erica S Spatz, Gregory L Burke, Erin D Michos
Journal: Circulation (2018)

Introduction: Self-rated health (SRH) is a commonly used indicator of health status. It has been identified as a determinant of health-promoting behaviors and a predictor of morbidity and mortality. However, little is known about the association between SRH and ideal cardiovascular health (CVH) as measured by the American Heart Association Life’s Simple 7 (LS7) criteria. We examined whether SRH was associated with ideal CVH, for the overall cohort and by sex and race/ethnicity. Methods: We conducted a cross-sectional analysis of 6457 men and women of 4 race/ethnicities, aged 45 to 84 years, who participated in the Multi-Ethnic Study of Atherosclerosis. SRH was measured on a 5-point Likert scale (excellent, very good, good, fair and poor). CVH was determined using the LS7 score with each of the 7 metrics scored from 0-2, and a total score ranging from 0-14. Scores of 0-8 indicate an inadequate score, 9-10, average and 11-14, optimal. Odds ratios (OR) and 95% confidence intervals were calculated for the associations between SRH and LS7 score categories using multinomial logistic regression, adjusted for age, sex, race/ethnicity, education, income, marital status, health insurance status and chronic diseases Results: The mean age (SD) of participants was 62 (10) years; 53% were women. Approximately, 16% of participants rated their health as excellent, 33% very good, 41% good and 9% poor-fair. In this population, 47% had inadequate LS7 scores, 33%, average and 20% optimal. The odds of having a higher LS7 score increased as SRH improved. Using participants who rated their health as poor-fair as the reference group, the adjusted OR for having an optimal LS7 score in the overall cohort was: excellent 3.0 (2.1-4.3); very good 1.6 (1.1-2.1); good 1.2 (0.9-1.7). A similar trend was observed in the stratified analyses by sex and race/ethnicity ( Table ) Conclusion: A more favorable SRH was associated with better CVH irrespective of sex or race/ethnicity. Further research could explore whether optimization of SRH predicts cardiovascular outcomes.
Prophylactic gabapentin decreases fatigue and swallowing difficulty in patients undergoing concurrent chemo-radiation (CCR) for head and neck cancer (HNC): Interim results from a randomized controlled trial.
Authors: Barbara A. Murphy, Michael Ghiam, Kenneth J. Niermann, Anthony Cmelak, Michael K. Gibson, Jill Gilbert, Derek Smith
Journal: Journal of Clinical Oncology (2019)

6059 Background: Preliminary data suggest that gabapentin (G) administered during HNC radiation may decrease treatment associated pain. To confirm this, we undertook a prospective, randomized trial in HNC patients undergoing CCR. Primary outcomes: pain severity (scale of 0-10) and opioid use. Exploratory outcomes: local and systemic symptoms measured by the Vanderbilt Head and Neck Symptom Survey version 2 plus the general symptom survey (VHNSSv2/GSS). We report results of the exploratory endpoints from the interim analysis. Methods: Measures: VHNSSv2 - 50 items, demonstrated reliability/validated, captures acute/chronic local HNC specific symptoms; GSS – 11 item checklist, demonstrated content validity, captures acute/chronic systemic symptoms. Population: HNC patients (≥ stage 2) undergoing primary or adjuvant CCR. Procedures: Randomized to standard pain management (SPM) or SPM + G dose escalated to 900mg tid. VHNSSv2/GSS completed weekly during treatment beginning week 1 and ending the last week of radiation therapy. Results were analyzed using a mixed-effects regression analysis adjusting for baseline levels of each symptom. Results: 71 patients completed a mean of 5.5 surveys. Patients on G experienced a reduction in overall systemic symptoms as measured by the GSS (11-items, p = 0.0073), fatigue (two-items, p = 0.013 ) sleep disturbance (five items, p &lt; 0.0001) , neurosensory eating (3 items, p = 0.026), phlegm-related symptoms (4 items, p = 0.004), and trend to better smell (2 items, p = 0.055). No impact on swallow, xerostomia, voice, dental or musculoskeletal symptoms was noted. Conclusions: This exploratory analysis suggests that G may moderate neurological and neuropsychiatric toxicities in HNC patients undergoing CCR. Further studies are warranted.
Abstract 14983: Platelet Drop After Implantation of the CoreValve Prothesis is Comparable to the Edwards Sapien Valve
Authors: Suzanne Fateh-Moghadam, Karin Mueller, Sebastian Werner, Patrik Htun, Martin Steeg, Beqir Sutaj, Rezo Jorbenadze, Meinrad Gawaz, Wolfgang Bocksch
Journal: Circulation (2013)

Background: After CoreValve (CoV) implantation a significant platelet drop is observed which might be due to the large cage of the prosthesis and to platelet consumption. Patients (pts) are treated...
Predictors of post-operative mortality following pancreatectomy: A contemporary nationwide analysis.
Authors: Shaakir Hasan, Stephen Abel, Vivek Verma, Suzanne Schiffman, Shyam Thakkar, Abhijit Kulkarni, Harry Kenneth Williams, Dulabh Monga, Gene Grant Finley, Alexander Kirichenko, Zachary D. Horne, Rodney E Wegner
Journal: Journal of Clinical Oncology (2019)

e15706 Background: To date, the only curative option for pancreatic cancer is surgical resection, which only 15-20% of patients are eligible for at diagnosis. The conventional operation is a pancreaticoduodenectomy which carries a mortality risk of 3-7%. We used the National Cancer Database (NCDB) to examine surgical outcomes following pancreatectomy. Methods: We queried the NCDB from 2004-2015 for patients with stage I-III adenocarcinoma of the pancreas treated surgically. Outcomes reported were 30 and 90 day mortality, readmission within 30 days, and prolonged hospital stay. Prolonged hospital stay was defined as 17 days and 8 cases per year was used to define high volume centers. Multivariable logistic regression was used to identify predictors of all outcomes. Propensity matching was conducted to account for indication bias. Results: We identified 24,798 patients meeting eligibility criteria. The median patient age was 66 (40-90). The majority of patients were stage T3 (47%) N0 (65%) with pancreatic head lesions (83%). Fifty-seven percent of patients were treated with a Whipple procedure. Most patients (83%) were treated with surgery up front. Overall unadjusted risk of 30 day and 90 mortality ranged from 1.32-2.54% and 4.1-7.12%, respectively, depending on extent of surgery. On multivariable analysis predictors of 30 day mortality included preoperative therapy, increased age, higher comorbidity score, lower income, type of surgery, and treatment at a low volume center. Ninety day mortality was associated with preoperative therapy, increased age, increased comorbidity score, higher T stage, more extensive surgery, and treatment at a low volume center. Multivariable analysis revealed increased comorbidity score, treatment at an academic facility, and non-partial pancreatectomy as predictive of readmission. Prolonged hospital stay was associated with increasing age, decreased education, lower income, non-Caucasian race, more extensive surgery, and more remote year of treatment. Propensity matched Kaplan-Meier analysis showed improved survival with treatment at high volume centers, median survival of 23 months compared to 21 months (p = 0.0026). Conclusions: In the largest population based series to date, the 30 day mortality rates remain acceptably low with an increase seen at 90 days. The predictors of post-operative mortality seen here (age, comorbidity score, extent of surgery, and center volume) highlight the need for appropriate patient selection and physician experience to help achieve the best possible perioperative outcomes.