tbuckley/cabot-search huggingface dataset:
Abstract 18774: Increased Epicardial Fat After Fontan Palliation Associated With Decreased Cardiac Output
Authors: Adam M Lubert, Jimmy C Lu, Albert P Rocchini, Mark D Norris, Sunkyung Yu, Prachi P Agarwal, Maryam Ghadimi Mahani, Adam L Dorfman
Journal: Circulation (2015)

Introduction: Epicardial fat produces multiple proinflammatory and proatherogenic cytokines and is associated with adverse cardiovascular events. Inflammation and resultant endothelial dysfunction may play a role in progressive myocardial dysfunction among adults with single ventricle physiology status post Fontan, but the potential impact of epicardial fat volume (EFV) has not been studied. This study aimed to quantify EFV in Fontan patients compared to a control group of repaired tetralogy of Fallot patients (rTOF) and to evaluate its association with ventricular ejection fraction and cardiac index. Methods: We retrospectively measured EFV on all patients post Fontan, 15 years or older, with cardiac magnetic resonance performed at the University of Michigan from 2007-2014, and 1:1 age, sex, and body mass index (BMI) matched patients with rTOF. EFV was measured manually on cine, steady-state free precession, short-axis images and was indexed to body surface area (BSA). Cardiac index was calculated as the sum of flow in the superior vena cava and inferior vena cava, indexed to BSA. A random subset of studies was re-measured &gt;1 week after initial measurement to assess intraobserver variability. Results: Fontan patients (n=63, mean age 22.3±6.0, 52% male) had a larger indexed EFV compared to rTOF (mean age 22.2±5.8, 52% male) measuring 75.6±29.2 vs. 60.0±19.9 ml/m 2 (p= 0.0003). There was no difference in BMI between the two groups (24.2±5.2 vs 24.2±5.6, p= 0.81). In Fontan patients, indexed EFV was inversely correlated with ventricular ejection fraction (r = -0.26, p = 0.03) and cardiac index (r = -0.34, p = 0.01). Intraobserver variability of the indexed EFV measurements in both groups was excellent (intraclass correlation coefficient of 0.95 and 0.93 in the Fontan group and rTOF group, respectively). Conclusions: Indexed EFV is higher in individuals post Fontan compared to patients with rTOF and is associated with lower ventricular ejection fraction and cardiac index. Increased epicardial fat could play a role in progressive myocardial dysfunction in this population, but longitudinal studies are necessary to establish any causative role.
Dose dense paclitaxel in patients with advanced liposarcoma: Subgroup analysis from a phase II trial.
Authors: Fernando Aldaco, Eduardo Cardenas, Guadalupe Cervantes, Josue Mora Perez
Journal: Journal of Clinical Oncology (2018)

e23557 Background: We previously reported outcomes in a prospective phase II trial evaluating the efficacy of dose dense paclitaxel in patients with advanced or metastatic soft tissue sarcomas. Recruitment was stopped after the first interim analysis due to a lack of effectiveness (stable sisease: 33%, progression disease: 66%, progresion free survival: 2.1 months and overall survival: 7.1 months - ASCO 2016-) ; however, liposarcoma subgroup (3 patients) showed some level of activity. After recruitment stopped for non-adipocytic sarcoma, we expanded liposarcoma cohort up to 6 patients. Methods: Phase II trial, open label, single arm trial. Approved by local ethics committee and informed consent was obtained for all subjects. From Sep 2014 – Aug 2016 patients with liposarcoma, stage IV or III non-candidate for local treatment, ECOG 0-2, measurable lesion (first 3 months assessed every 4 weeks) and adequate organ function where treated with, Paclitaxel 175 mg/m2 d1, q2w (up to 10 cycles) plus filgrastim 300 mcg d2-5. Results: Six (6) patients with liposarcoma were included. Median age: 54y (44-67), female: 66%, stage IV: 33%, stage III: 66%, naïve chemotherapy: 50%, Pleomorphic liposarcoma: 50%, Myxoid liposarcoma: 33%, Dedifferentiated liposarcoma: 16%, Median number of paclitaxel cycles was 6.3 (4-8), median follow-up of 22 months (18-32.5). Sixty-six of patients (66%) had stable sisease and 33% progressed, with 0% overall response rate. A median progression free survival of 6.7m (2.4-24.3) and a median overall survival not yet reached (four patients still alive, two deaths at 19.8m and 24.1m respectively), 100% overall survival at 18 months. No patients presented toxicity above grade 2. Most frequent grade 1 toxicity was neuropathy in 5/6 patients. Conclusions: Dose dense paclitaxel is well tolerated and demonstrates an unexpected efficacy in patients with advanced liposarcoma. Interestingly, overall response rate (CR/PR) has not been a reliable predictor of overall survival and progression free survival.
Long-term follow-up of brentuximab vedotin ± dacarbazine as first line therapy in elderly patients with Hodgkin lymphoma.
Authors: Jonathan W. Friedberg, Andres Forero-Torres, Beata Holkova, Jerome H. Goldschmidt, Ralph V. Boccia, Rodolfo Bordoni, Vivian Jean M. Cline, Dipti Patel-Donnelly, Patrick J. Flynn, Gregg A. Olsen, Robert W. Chen, Faith Galderisi, Yinghui Wang, Jeff Porter Sharman, Christopher A. Yasenchak
Journal: Journal of Clinical Oncology (2018)

7542 Background: Elderly patients (pts) with Hodgkin lymphoma (HL) have few treatment (tx) options and poor outcomes compared to younger pts. This phase 2, frontline, open-label trial studied brentuximab vedotin monotherapy (BV; ADCETRIS) and BV+dacarbazine (DTIC) in these pts (NCT01716806). We previously reported high response rates (92% and 100%, respectively) and complete remission rates (73% and 62%, respectively) as well as manageable safety profiles (Forero-Torres 2015, Friedberg 2017). Methods: Twenty-seven pts ≥ age 60 with classical HL not eligible for standard tx received 1.8 mg/kg BV; then 22 others received 1.8 mg/kg BV+375 mg/m2 DTIC (12 cycles), then BV. Radiographic scans were done at Cycles 2, 4, 8, 12, 16 (for continued BV), end of tx, then per standard of care. Follow-up visits were every 3 months (mos). Results: Survival and peripheral neuropathy (PN) results are presented below. BV+DTIC resulted in 3-year (yr) PFS and OS rates of 52% and 90%, respectively, while BV alone rates were 34% and 71%. Most pts had tx-emergent PN and had either complete resolution or some resolution/improvement. Nearly all ongoing PN was Grade 1/2; 1 pt had ongoing Grade 3 PN. Conclusions: BV alone and BV+DTIC appear to induce long-term remissions for a subset of elderly HL pts. The addition of DTIC appears to increase durability of response and survival although not statistically assessed. PN resolution/improvement was observed for the majority of pts. These durable responses suggest that BV+DTIC may be an induction option for frail, elderly pts ineligible for standard tx. Clinical trial information: NCT01716806. BV (N = 27) BV+DTIC (N = 22) Median observation time from first dosea, mos (range) 42.6 (4.6, 56.3) 37.8 (14.8, 44.8) Median PFSa, mos (range) 10.5 (2.6+, 52.2+) NR (4.2+, 39.6+) 3-yr PFS ratea (95% CI) 34% (16%, 53%) 52% (26%, 73%) Median OS, mos (range) NR (4.6+, 56.3+) NR (6.7+, 44.8+) 3-yr OS rate (95% CI) 71% (49%, 85%) 90% (65%, 97%) Tx-emergent PN, n (%) 24 (89%) 19 (86%) Complete resolution, n/N (%) 9/24 (38%) 5/19 (26%) Some resolution/improvementb, n/N (%) 9/24 (38%) 8/19 (42%) Median time to resolution/improvement, weeks 12.6 4.9 Ongoing Grade 1/2, n/N (%) 14/15 (93%) 14/14 (100%)
Examining the relationship between cost of novel oncology drugs and their clinical benefit over time.
Authors: Ronak Saluja, Erica McDonald, Vanessa Sarah Arciero, Sierra Cheng, Matthew C. Cheung, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2017)

6598 Background: The average launch price of oncology drugs has increased by 10% annually from 1995 to 2013. The purpose of this study was to determine if the clinical benefit of novel oncology drugs has increased proportionally over time and is correlated with launch price. Methods: Novel oncology drugs fromrandomized controlled trials (RCTs) cited for clinical efficacy evidence in drug approvals between January 2006 and August 2015 were identified. For each drug, only the first FDA approved indication was included. To determine clinical benefit, all included RCTs were scored using the ASCO Value Framework and the ESMO Magnitude of Clinical Benefit Scale. The launch price for the FDA approval year of each drug was extracted from RedBook. Each drug’s 28-day cost was determined using the dosage schedule outlined in the respective RCT and was adjusted to 2015 USD using the consumer price index. The relationships between 28-day drug cost and FDA approval year, and between incremental drug cost (difference in total drug cost between experimental and control arms accounting for treatment duration) and FDA approval year were examined using generalized linear regression models (gamma distribution and log link). Ordinary least square models were used to evaluate the relationship between ASCO/ESMO scores and FDA approval year. Spearman’s correlation coefficients between 28-day/incremental drug costs and ASCO/ESMO scores were also calculated. Results: Forty RCTs were included in this analysis. The 28-day drug cost was significantly associated with FDA approval year (p = 0.04), with an average increase of 8.5% per year. Incremental drug cost was also significantly associated with FDA approval year (p &lt; 0.001) with an increase of 28.6% per year. The mean ASCO and ESMO scores were 26 and 3, respectively. Both scores were not statistically associated with FDA approval year (p = 0.73 and p = 0.86, respectively) and were also not correlated with 28-day or incremental drug costs (all rho &lt; = 0.2). Conclusions: Novel oncology drugs are not priced according to their clinical benefit. The rising cost of novel oncology drugs over time is not associated with an increase in their clinical benefit, suggesting a decrease in their value over time.
Three-fold overestimation of tumor mutation burden using 248 gene panel versus whole exome.
Authors: Andrew Nguyen, Chad Garner, Sandeep K. Reddy, John Z Sanborn, Stephen Charles Benz, Tara Elisabeth Seery, Shahrooz Rabizadeh
Journal: Journal of Clinical Oncology (2018)

12117 Background: Next generation sequencing (NGS) Gene panel testing is used to imputed tumor mutational burden (iTMB) and has shown rough correlation with TMB derived from whole exome sequencing (WES). TMB is used to estimate immune checkpoint inhibitor (ICT) response based on potential neoantigen load. We hypothesized that actual TMB (aTMB), consisting of mutations across the exome, and expressed TMB (eTMB), consisting of expressed genes, would differ substantially from iTMB. Methods: Retrospective analysis of a database from a commercial DNA tumor:normal and RNAseq platform was carried out. We analyzed 890 clinical samples composing of both primary and metastatic disease by whole genome sequencing (WGS) or WES and RNA sequencing (RNA-Seq), and compared true tumor mutational burden to a predicted tumor mutational burden from a list of 248 genes thought to drive cancer. (COSMICv76) Results: Estimated tumor mutational burden based only on the list of 248 genes had an average of 15.79 mutations per megabase (14.16--17.43, 95% CI) whereas WGS/WES derived TMB had an average of 5.09 mutations per megabase of coding DNA (4.22--5.96). The relationship between gene panel size, aTMB and eTMB will be presented. Conclusions: In this retrospective analysis using a 248 gene list as a panel to impute TMB, we observed a roughly 3-fold over-estimate of TMB. This may impact ICT prescription and expectation of clinical benefit.
Impact of Medicare coverage on the characteristics of lung cancer screening participants and their outcomes.
Authors: Tawee Tanvetyanon, Donald L. Klippenstein, Matthew B. Schabath, Kacie Gebhardt, Christie Pratt Pozo, Scott Joseph Antonia
Journal: Journal of Clinical Oncology (2016)

e18017 Background: Lung cancer screening with low-dose CT (LDCT) reduces lung cancer mortality when performed among high-risk individuals. Screening of lower risk individuals is discouraged as it may not be efficacious. In February 2015, Medicare and other health insurance plans began covering LDCT among high-risk individuals. We sought to compare the high-risk characteristics, according to NCCN guideline, among LDCT participants at our institution, before and after this change. Methods: Data based on self-reported characteristics and outcomes of lung cancer screening participants were prospectively collected. LDCT was available as fee-for-service prior to Medicare coverage since Aug 2011. Chi-square or one-way ANOVA test was used to compare groups. Multivariable logistic regression analysis was performed to identify predictor of positive screening. Results: In pre-Medicare period (Aug 2011 -Jan 2015) and in post-Medicare period (Feb 2015 -Jan 2016), 173 and 64 participants underwent LDCT respectively, corresponding to a rate of 4.3 vs. 6.4 new participants screened per month. In pre- and post-Medicare periods, smoking greater than 30 pack-years was observed in 61.8% vs. 79.7% of participants (p= 0.015); age between 55-80 years was observed in 90.8% vs. 93.8%; and, for those who quit smoking, quit within the past 15 years was observed in 72.7% vs. 76.8%. Overall, the proportions of participants who met all high-risk criteria for screening increased from 46.5% to 62.5% (p= 0.045). Positive screening, defined as Lung-RADS category 3 or 4, occurred in 15.0% vs. 28.1% (p= 0.021) of patients across the periods. There were 5 patients subsequently diagnosed with lung cancer, all with a positive screening. Multivariable model including demographic and high-risk characteristics indicated that meeting of all high-risk criteria was the only significant predictor of positive screening with odds ratio 3.53 (95% CI: 1.59, 7.77; p= 0.002). Conclusions: In this study, Medicare coverage of lung cancer screening was significantly associated with an increase in the proportion of participants who met all high-risk criteria for screening. Meeting of the criteria independently predicted a positive screening result.
Primary pulmonary sarcomas: The results of surgical treatment.
Authors: Janusz Golota, Monika Rucinska, Karolina Osowiecka, Tadeusz Orlowski
Journal: Journal of Clinical Oncology (2017)

e22540 Background: Primary pulmonary sarcomas (PPS) are the very rare cancer type (0.01% - 0.4% of all malignant tumours of the lung). PPS can derive from stromal elements of the bronchial wall, blood vessels and connective tissue steep of lung parenchyma. The aim of the study was evaluation of PPS patients’ outcome. Methods: The analysis included 23 patients (11 males, 12 females) age 28-70 years (median 49.6 years) with PPS treated surgically in the Department of Surgery, Institute of Lung Diseases and Tuberculosis in Warsaw from 1994 to 2009. Results: There were 3 leiomyosarcomas (13%), 3 hemangiopericitomas (13%), 3 MFH (13%), 3 malignant peripheral nerve sheath tumours (13%), 3 PNET (13%), 2 fibrosarcomas (8.8%), 2 liposarcomas (8.8%), 2 sarcomas synoviale (8.8%), 1 angiosarcomas (4.3%), 1 chondrosarcomas (4.3%) (according to the 3rd edition of the WHO Classification of Tumours of Soft Tissue and Bones). There were performed 5 pneumonectomies (21.7%), 5 lobectomys (21.7%), 5 wedge resection (21.7%), 6 exploratory thoracotomys (26.1%), 2 stent inserts (8.8%). In the case of 15 patients (65%) were performed operation R0. Adjuvant therapy was used in 7 patients (30%), 3 patients (13%) received chemotherapy, 2 patients (13%) radiotherapy and 1 patient (4%) chemo-radiotherapy. Palliative chemotherapy and or radiotherapy were given to 6 patients (26%). Median overall survival (OS) was 22 months (5- and 10-years OS was 26% and 17%, respectively) and depended on sex (p = 0.006), tumor size (p = 0.02), operation R0 (p = 0.07). Conclusions: Surgery, especially operation R0, is the most effective treatment method of PPS. Subsequent studies on larger groups are necessary.
Tumor expression of cyclooxygenese-2 (COX-2) and vascular expression growth factor (VEGF) expression to predict survival outcome in locally advanced cervical cancer.
Authors: Jiraporn Setakornnukul, Kullathorn Thephamongkhol, Tuenjai Chuangsuwanich, Kanchana Amornpichetkul, Nantakan Apiwarodom
Journal: Journal of Clinical Oncology (2016)

e17021 Background: Standard practice of locally advanced cervical cancer is concurrent chemo-radiotherapy (CCRT); however even patients in the same stage have large different survival outcome. VEGF and COX-2 are markers for angiogenesis pathway and therefore as potential predictors for spreading outside primary organ and cancer related death. Methods: All consecutive stage IB-IIIB cervical cancer patients (pts) underwent CCRT with available paraffin box at our institute from 2002 to 2007 were analyzed. The estimated study size was 50 pts to detect the different survival 94% vs 56% in COX-2 and 89% vs 47% in VEGF under 0.05 of α error and 80% of power. Immunohistochemistry (IHC) of COX-2 was positively defined as more than 50% of tumor cells contain with intense strain. Positive IHC of VEGF was the score from multiply intensity and quantity score more than 4. Results: Median F/U time was 75 months. 16 pts (33%) had positive COX-2 and/or VEGF, 4 (8%) for positive VEGF only, 9 (19%) for positive COX-2 only, and 3 (6%) for positive COX-2/VEGF. 5-yr unadjusted overall survival in both negative COX-2/VEGF was 79% (95% CI: 61%-89%), 50% (95% CI: 6%-84%) for positive VEGF only, 33% (95% CI: 8%-62%) for positive COX-2 only, and 0% for both positive COX-2/VEGF. There was clinically significant synergistic effect between COX-2/VEGF on overall survival by Cox proportional hazards model, HR 17.7; 2.5-123.9, p=0.004 (Table). Conclusions: COX-2 and VEGF expression in stage IB-IIIB cervical cancer were important poor prognostic factors for survival. This result established their clinically synergistic effect. Univariable and Multivariable analysis for overall survival. HR;95%CI, p value Univariable analysis Multivariable analysis VEGF negative (n=42) 1 1 positive (n=7) 3.7; 1.3-10.3, 0.013 6.7; 1.6-27.5, 0.008 COX-2 negative (n=37) 1 1 positive (n=12) 3.4; 1.4-8.4, 0.007 5.4; 1.9-15.9, 0.002 COX-2/ VEGF negative COX-2/VEGF (n=33) 1 1 positive VEGF only (n=4) 3.1; 0.7-14.7, 0.149 5.3; 0.7-43.9,0.120 positive COX-2 only (n=9) 3.1; 1.1-8.8, 0.033 5.0; 1.3-18.4, 0.016 positive COX-2/VEGF (n=3) 9.3; 2.4-36.7, 0.001 17.7; 2.5-123.9, 0.004
Surgeon and hospital variation in adjuvant chemotherapy delivery to patients with stage III colon cancer.
Authors: Zhaomin Xu, Carla Francesca Justiniano, Adan Z Becerra, Christopher Thomas Aquina, Francis P. Boscoe, Maria J. Schymura, Larissa K. F. Temple, Fergal J. Fleming
Journal: Journal of Clinical Oncology (2017)

3596 Background: It is well established that age and comorbidities have significant impact on adjuvant chemotherapy delivery to stage III colon cancer patients. This study examines differences in the hospital and surgeon-specific probabilities of adjuvant therapy delivery to stage III colon cancer patients by comorbidity burden and age. Methods: Patients who underwent surgery for stage III colon cancer from 2004-2013 were included from the New York State Cancer Registry and the Statewide Planning and Research Cooperative System. Comorbidity burden was defined with the Charlson Comorbidity Index (CCI). Multilevel logistic regressions characterized variation in adjuvant chemotherapy delivery among individual hospitals and surgeons by CCI and age. Results: 11575 patients met inclusion criteria, of which 59% received adjuvant therapy. Younger age, lower CCI, and high volume surgeons/hospitals were associated with delivery of adjuvant therapy (p &lt; 0.01). Median time to chemotherapy was 43 days among CCI = 0 vs 48 among CCI≥2. The risk adjusted hospital and surgeon-specific probabilities of adjuvant delivery decreased with increasing CCI and age. The proportion of variation attributable to surgeons, vs hospitals, increased with CCI and age. Hospital variation between the highest and lowest hospitals increased from a 6-fold difference among CCI = 0 to an 11 fold difference among CCI≥2. Surgeon variation increased from a 14-fold difference among CCI = 0 to a 40 fold difference among CCI≥2. Conclusions: Variation in adjuvant chemotherapy delivery to stage III colon cancer patients increased with higher comorbidity burden and age. While a larger proportion of variation is attributable to surgeons among patients with the highest CCI and the most elderly, the vast majority of the variation is related to hospital factors. Even taking into account that some patients may be unfit for adjuvant therapy, this variation in treatment is alarmingly high. [Table: see text]
Bioimaging predictors of rilpivirine biodistribution and antiretroviral activities
Authors: Brendan M. Ottemann, Austin J. Helmink, Wenting Zhang, Insiya Mukadam, Christopher Woldstad, James R. Hilaire, Yutong Liu, JoEllyn M. McMillan, Benson J. Edagwa, R. Lee Mosley, Jered C. Garrison, Bhavesh D. Kevadiya, Howard E. Gendelman
Journal: Biomaterials (2018)
Molecular and neuro-radiological characteristics of diffuse grade II and III gliomas involving the insula.
Authors: Emeline Tabouret, Paloma Compes, Amandine Etcheverry, Carole Colin, Romain Appay, Nicolas Cordier, Olivier L. Chinot, Hervé Delinguette, Nadine Girard, Henry Dufour, Philippe Metellus, Dominique Figarella-Branger
Journal: Journal of Clinical Oncology (2018)

e14050 Background: we previously reported the occurrence of IDH wild-type (IDHwt) low grade glioma (LGG) involving the insula that carried a poor prognosis. Our objective was to characterize the molecular and neuro-radiological features of adult insula LGG. Methods: we retrospectively included all patients (Pt) who underwent a surgical resection for LGG with insular involvement. The clinical, pathological, molecular and neuro-radiological characteristics were recorded. Results: We included 43 Pt from 1993 to 2013 with a median age of 44.4 years (range 23.8-71.1). According to the two main genetic alterations, we recorded 6 grade II and 2 grade III IDH mutated (IDHmut) 1p/19q-codeleted oligodendrogliomas, 22 grade II and 6 grade III IDHmut astrocytomas and 7 grade II IDHwtastrocytomas (A-wt). These molecular groups significantly differed in median age at inclusion, ATRX, TP53 and pTERT mutations, EGFR amplification and 7p gain and 10q loss. Vimentin staining was exclusively recorded in tumor cells from A-wt which had a lower expression of Nkx2.2 (p = 0.001). Methylome unsupervised analysis clustered Pt similarly to molecular groups. No difference was observed for the ADC values. Mean cerebral blood volume (CBV) (p= 0.018), maximal value of CBV (p= 0.017), ratio of the corrected CBV (p= 0.022) and temporal maximum intensity projection (p= 0.048) were lower for A-wt: no Pt with A-wt presented with angiogenesis. Volumetric segmentation of ADC allowed the identification of the tumor cores, which were smaller in A-wt (p < 0.001). The tumor occurrences (cores) were exclusively located into the temporo-insular region for the A-wt, preferentially in the right hemisphere. Median progression-free survival (PFS) and overall survival (OS) were 50.9 months (95%CI: 26.7-75.0) and 80.9 months (60.1-101.6). By multivariate analysis (adjusted by the extent of surgery), IDHwt (p= 0.009), A-wt (p= 0.009), 7p gain and 10q loss (p= 0.009) and vimentin positive staining (p= 0.011) were associated with poor PFS. 7p gain and 10q loss (p= 0.016) and vimentin positive staining (p= 0.029) were associated with poor OS. Conclusions: Insular A-wt presented with poor prognosis despite a smaller tumor core and no angiogenesis on neuro-imaging.