tbuckley/cabot-search huggingface dataset:
Pediatric oncology provider views on biopsying solid tumors in children with relapsed or refractory disease for the purpose of genomic profiling.
Authors: Barrie Cohen, Michael Roth, Jonathan Michael Marron, Stacy W. Gray, David Geller, Bang H Hoang, Richard Greg Gorlick, Katherine A. Janeway, Jonathan Benjamin Gill
Journal: Journal of Clinical Oncology (2016)

10566 Background: Patients with relapsed and refractory solid tumors have a poor prognosis. Recent advances in genomic technology have made it feasible to screen tumors for actionable mutations, with the anticipation of potential future benefit to patients. Methods: Pediatric oncologists, whose names obtained via hospital web sites and publications, were emailed an anonymous 34 question survey assessing their willingness to offer rebiopsy for patients with relapsed disease for the purpose of tumor genomic profiling. They were presented with two scenarios evaluating morbidity and invasiveness of the procedures using the clinical examples of medulloblastoma and Ewing sarcoma. Results: 195 pediatric oncologists (24%) responded to the questionnaire. Morbidity and invasiveness of the procedure demonstrated significant differences in provider willingness to refer their patients for rebiopsy: 61 versus 30% (p < 0.0001) for morbidity; and 74 versus 59% for invasiveness (p < 0.005). Respondents were more likely to offer rebiopsy if they are told there is a high likelihood the results will impact clinical management (high pre-test probability) than for histologic confirmation alone (89% vs. 56% p = 0.017). Compared to the rate of rebiopsy for histologic confirmation, significantly fewer providers are willing to offer rebiopsy if they are led to believe there is a low likelihood of finding an actionable mutation (mean 45% vs. 56%, p = 0.021). Conclusions: The scenario defined pre-test probability of finding an actionable mutation is influential in determining provider willingness to offer rebiopsy for the purpose of tumor genomic profiling. Further research is warranted to evaluate the benefit of tumor genomic profiling on patient outcomes to provide clinicians the necessary data to inform their decisions on whether they should refer their patients.
When more is less: End-of-life disparities among ovarian cancer patients.
Authors: Jolyn Sharpe Taylor, Ning Zhang, Larissa Meyer, Lois M. Ramondetta, Diane C. Bodurka, Suja Rajan, Sharon Hermes Giordano
Journal: Journal of Clinical Oncology (2016)

e21517 Background: Medical care at the end of life (EoL) is often aggressive late in life. We assessed racial disparities in EoL care among ovarian cancer (OC) patients. Methods: Using Texas Cancer Registry-Medicare data, we selected OC patients who died 2000-2012, had > = 30 days from diagnosis to death and > = 13 months of continuous Medicare coverage before death. Descriptive statistics and multivariate logistic regressions were conducted to evaluate predictors of EoL quality care, using metrics from the National Quality Forum and ASCO QOPI (chemotherapy in the last 14 days of life (DoL), any ICU admission, > 1 ER or hospital admission in the last 30 DoL). Results: A total of 4,003 patients were included with 3,009 (75%) white, 637 (16%) Hispanic, 307 (8%) black and 50 (1%) other. Median age at death was 76, 85% had advanced stage at diagnosis, 74% with Charlson Comorbidity Index (CCI) < 2 and 79% lived in urban settings. 2,869 (72%) enrolled in Hospice prior to death but only 2,543 (64%) died in hospice. The median time in hospice before death was 19 days. In the final 30 DoL, 427 (11%) had > 1 ER visit, 554 (14%) > 1 hospital admission, 647 (16%) ICU admission, 789 (20%) invasive care and 454 (11%) life-extending care. In the final 14 DoL, 389 (10%) received chemotherapy. After controlling for year, age, stage at diagnosis, CCI, location, education and poverty levels, several outcomes differed by race. Hispanic (OR 0.77 [0.62-0.97];p = 0.04) and black (OR 0.73 [0.55-0.98];p = 0.02) patients were less likely to enroll in hospice and die in hospice (Hispanic (OR 0.77 [0.63-0.94];p = 0.01); black (OR 0.65 [0.50-0.85];p = 0.001)). Hispanic (OR 1.39 [1.08-1.78]; p = 0.009) and black (OR 1.40 [1.02-1.92]; p = 0.03) patients were more likely to go to the ICU and have > 1ER visit (Hispanic (OR 1.42 [1.06-1.92];p = 0.02); black (OR 2.27 [1.63-3.22]; p < .001)). Black patients (OR 1.34 [1.003-1.79];p = 0.04) were more likely to have invasive care. Hispanic (OR 1.37 [1.02-1.84]; p = 0.03) and black (OR 2.12 [OR 1.52-2.95];p < 0.001) patients were more likely to receive life-extending care. Conclusions: Minorities were less likely to enroll and remain in hospice and more likely to receive invasive and intensive care. There is an opportunity for addressing disparities in EoL quality care.
Abstract 19553: Med12 is a Transcriptional “Mediator” of Cardiac Contractile Function
Authors: Kedryn K Baskin, Susan DeLeon, Catherine Makarewich, Rhonda Bassel-Duby, Eric N Olson
Journal: Circulation (2016)

Introduction: The Mediator complex regulates gene transcription by linking the basal transcriptional machinery with DNA bound transcription factors. The activity of the Mediator complex is modulated by a kinase submodule comprised of 4 proteins, including MED12. Although ubiquitously expressed, studies suggest that these proteins differentially regulate gene expression in a tissue-specific manner. MED12 regulates development in a variety of cell types through the regulation of different gene programs. Consequently, MED12 null mice are embryonically lethal, however the function of MED12 in the heart is not yet known. Hypothesis: We tested the hypothesis that MED12 is required for normal cardiac function. Methods: Mice harboring conditional cardiac-specific deletion of MED12 (cKO) were generated. We performed serial echocardiography on male cKO mice and controls through 12 weeks of age. RNAseq was performed on P1 ventricles, and calcium transients were measured using fluo-4 AM in P1 cardiomyocytes (CM). Chr...
The effect of medical social rehabilitation on quality of life in children with brain tumors: Interim results of observational prospective study.
Authors: Grigory Ja. Tseitlin, Alexander G. Rumyantsev, Alexander F. Karelin, Marina J. Kokoreva, Irina D. Borodina, Tatiana P. Nikitina, Anna V. Zinkovskaya, Natalia M. Porfir’eva, Tatyana I. Ionova
Journal: Journal of Clinical Oncology (2018)

10562 Background: Medical social rehabilitation is promising to support cancer children with the re-entry into ‘normal’ life. We aimed to study quality of life (QoL) changes in children with brain tumors (BT) after rehabilitation and identify independent predictors of QoL changes. Methods: Children of 6–17 y.o. underwent 4-week medical social rehabilitation after the end of cancer treatment (EOT). Children filled out child form of PedsQL and parents – parent form of PedsQL before and after rehabilitation. Statistical analysis included Generalised Estimation Equations (GEE), univariate logistic regression and multiple linear regression. Results: In total 82 survivors and their parents (44.4±11.1 y.o., 85% mothers) were enrolled. Mean age of children – 11.8±3.1 y.o.; 57% boys; 19 (23%) pts have overweight/obesity and other 19 (23%) pts have underweight/depletion according to the Body Mass Index (BMI); median duration time after EOT – 26 mos (1–123). According to child-reports QoL increased mainly in terms of emotional and psychosocial functioning (p < 0.05); according to parent-reports social, school and psychosocial functioning of children improved (p < 0.05). In general, child QoL improvement was revealed with adjustment for age, gender, time after EOT and baseline QoL (GEE, p < 0.05). Meaningful QoL improvement (QoL total score change ≥4.4) was observed in 58% of survivors. In the final logistic regression model (χ2 = 6.9, p < 0.05), overweight/obesity was independently associated with negative QoL changes after rehabilitation (OR = 6.71, p = 0.008). In multiple regression analysis, overweight/obesity (β -5.52, p = 0.05) and long period (≥5 yrs) after EOT (β -9.56, p < 0.01) were associated with negative QoL changes after rehabilitation (R2= 0.32, p < 0.05). Conclusions: Medical social rehabilitation is accompanied with QoL improvement in surviving children with BT. Rehabilitation program is not effective in terms of QoL in survivors with overweight/obesity and in those having long period after EOT. It might be taken into account for optimizing rehabilitation in survivors with childhood BT.
TCT-720 Right ventricular function as a predictor for mortality in TAVI patients
Authors: Zisis Dimitriadis, Verena Brandt, Smita Scholtz, Alberto Polimeni, Werner Scholtz, Jochen Boergermann, Stephan Ensminger, Tommaso Gori, Cornelia Piper, Thomas Muenzel, Dieter Horstkotte, Lothar Faber
Journal: Journal of the American College of Cardiology (2018)
Post-treatment evaluation of head and neck cancer patients in the era of advanced imaging and value-based care.
Authors: Thomas Hirsch, Michael Stadler, Bruce Campbell, Selim Firat, Becky Massey, Christopher J. Schultz, Monica Shukla, Stuart J. Wong, Jared R. Robbins
Journal: Journal of Clinical Oncology (2018)

6079 Background: Current guidelines recommend imaging (CT and/or PET) to evaluate treatment response and detect residual disease after nonsurgical management of head and neck cancers squamous cell cancers (HNSCC). To objectively evaluate the utility of these diagnostic tests, we reviewed our institutional cohort to better understand the value of these interventions compared to routine history and physical examination (PE). Methods: After IRB approval, we retrospectively reviewed an institutional cohort of 160 HNC patients who underwent definitive radiation +/- chemotherapy from 2003 - 2014. All patients had post-treatment history, PE, and imaging data, including a 4-month PET scan. The sensitivity, specificity, negative-predictive and positive-predictive values were calculated, along with Kaplan-Meier survival analyses for each symptom, PE, and imaging finding. Results: PE and symptoms had higher specificity than imaging but had lower sensitivity (see table). While imaging had good sensitivity and NPV, excess false positives led to poor specificity and PPV. When PE and symptoms were evaluated together, performance was similar to CT and PET. On KM analysis, all PE/symptom factors and PET response correlated with outcome, while baseline CT did not. There were no early interventions resulting from baseline CT scans. Conclusions: In an era of value-based care, a renewed emphasis on patient symptoms and PE findings may allow for improved resource utilization and cost of care. These are strong predictors of residual disease in the immediate post-treatment setting, suggesting a need to reevaluate current imaging paradigms, particularly the utility of post-treatment CT scans. Palpable nodes Persistent Primary Pain Odynophagia Dysphagia Post- Treatment CT 4-month PET Combination symptoms and PE Locoregional Control Sensitivity 0.17 0.27 0.53 0.17 0.42 0.61 0.81 0.67 Specificity 0.98 0.92 0.74 0.92 0.70 0.58 0.61 0.54 NPV 0.80 0.86 0.84 0.79 0.80 0.87 0.92 0.85 PPV 0.67 0.41 0.37 0.38 0.29 0.25 0.38 0.30 Death from Disease Sensitivity 0.18 0.20 0.53 0.20 0.53 0.52 0.80 0.80 Specificity 0.99 0.93 0.76 0.94 0.76 0.57 0.64 0.60 NPV 0.75 0.74 0.80 0.74 0.80 0.75 0.89 0.88 PPV 0.89 0.53 0.47 0.56 0.47 0.32 0.47 0.43
Co-expression patterns of immune checkpoint molecules in relation to <i>PD-L1</i> expression.
Authors: Sumanta K. Pal, Ari M. Vanderwalde, Christopher Szeto, Stephen Charles Benz, John Zachary Sanborn, Charles Joseph Vaske, Sandeep K. Reddy, Omid Hamid
Journal: Journal of Clinical Oncology (2018)

12113 Background: Targeting immune checkpoints has led to clinical benefit across a variety of tumor types, and employing combinations has enhanced response rates even further. We hypothesize that profiling the tumor and associated microenvironment can help tailor rational combinations of immunotherapeutic strategies. Methods: Whole transcriptomic sequencing (RNA-Seq; ∼200x106 reads per tumor) of 1,880 unselected clinical cases was performed (NantHealth; Culver City, CA). Cases reflected 38 distinct histologies including but not limited to breast (17.8%), colon (9.5%), lung (7.9%), pancreatic (6.5%), ovarian (5.4%), brain (4.9%) and prostate cancer (2.7%). Cases were categorized as PD-L1-low, PD-L1-normal and PD-L1-high by cutoffs defined in TCGA expression profiles. Expression and co-expression of 6 checkpoint markers (PD-L1, PD-L2, CTLA4, IDO1, LAG3 and TIM3) were analyzed for tissue-specific enrichment and within PD-L1-defined categories. Immune-cell infiltration was estimated using RNA deconvolution based on known immune cell marker genes (Bindea et al 2013). Results: Checkpoint expression did not cluster in a tissue-dependent manner. PD-L1 shows no significant co-expression pattern with any of the analyzed checkpoint markers aside from its ortholog PD-L2 (R = 0.77; P = 1.9x10-285). Within the PD-L1-low category, IDO1 and TIM3 had relatively high expression and were highly correlated with each other (R = 0. 81; P = 4.6x10-17). The PD-L1-low category was especially deprived of memory T cells and eosinophils. Within the PD-L1-high category, overall expression of all checkpoint markers was higher. Amongst PD-L1 high patients, CTLA4 expression was highly variable (mean 2.5±1.1; log2[TPM+1]) and lacked correlation with PD-L1 (R = -0.09). In contrast, while LAG3 also had variable expression in the PD-L1-high setting, it was strongly correlated with CTLA4 (R = 0.79, P = 7.4x10-14). The PD-L1-high category was especially enriched for Th1, NK CD56dim, and CD8 T-cells. Conclusions: High and low PD-L1 expression in the tumor and adjacent microenvironment are associated with variations in key checkpoint molecules. Low expression of PD-L1 may be an ideal setting for use of IDO- or TIM3-directed therapies.
Achieving pain control with patient-reported personalized pain goals among patients with cancer in the inpatient setting.
Authors: Maria Alma Rodriguez, Shalini Dalal, Lee Cheng, Alma Yvette DeJesus, Carin Hagberg
Journal: Journal of Clinical Oncology (2018)

e18534 Background: Cancer pain is highly prevalent in patients with cancer. Personalized pain goal (PPG) is a patient-reported outcome of a pain management goal that allows the patient to achieve comfort with pain. Increasing the number of patients who meet their PPG, as well as decreasing their overall pain levels are continued goals for managing patients with pain. We aimed to describe the percentage of hospital inpatient admissions with documented pain intensity scale (PIS) achieving PPG at MD Anderson Cancer Center. Methods: The study has been approved by the Institutional Quality Improvement Assessment Board. We searched our electronic health records for cancer patients aged ≥ 18 years, who had been admitted to our hospital between January 1, 2017, and December 31, 2017. Both patient-reported PPG and PIS are described on a 0-10 scale (0, no pain; 10, worst pain). Baseline PPG value was defined as initial average PPG score within 24-hours follow-up time when the first PPG was reported. PIS was defined as average PIS score between times of the first PPG and hospital discharge. The achievement of PPG was defined as average PIS ≤ initial average PPG+1. Results: Of total 27,876 inpatient admissions, we identified 27,354 (98.1%) admissions who had reported PPGs, which involved with 15,696 unique patients (median age 61.8, female 46.9%). The initial average PPG score was 1.32 (median 0.73), with distribution of 92.9%, 7.0%, and 0.1% for mild (0-3), moderate (4-6), and severe pain (7-10), respectively. Judged by initial average PPG score for mild, moderate, and severe, the proportions of patient admissions, who had achieved or exceeded their PPGs were 67.8%, 91.3%, and 100.0%, respectively, during their entire hospital stay. Conclusions: Our findings suggest the importance of documenting patient-reported PPG for enhancing pain management among patients with cancer. To improve care delivery in an environment of patient-centeredness, holistic measurements are needed to help in the assessment of how well patients’ needs for safe and quality delivery of compassionate pain care.
Phase 1b trial of nintedanib in combination with bevacizumab in patients with advanced solid tumors.
Authors: Ravi Kumar Paluri, Peng Li, Benjamin Scott Jones, Ankit Madan, Mary Jerome, Debi Miley, Jennifer Keef, Francisco Robert
Journal: Journal of Clinical Oncology (2018)

2591 Background: Vascular endothelial growth factor (VEGF) inhibitors have produced demonstrable but limited clinical benefit for various cancers. One mechanism of resistance includes revascularization secondary to up-regulation of alternative pro-angiogenic signals such as platelet derived growth factor receptor (PDGFR) and fibroblast growth factor receptor (FGFR) pathway. Nintedanib (Nin) is an oral triple kinase inhibitor that blocks the VEGFR, PDGFR and FGFR pathways and may improve antitumor activity by overcoming resistance to anti-VEGF therapies. This study evaluated the safety & tolerability (primary objective) of Nin in combination with bevacizumab (Bev). Methods: Patients (pts) were treated with escalating doses of Nin (150mg or 200mg oral twice daily) and Bev (15 mg/kg once intravenously every 3 weeks) until disease progression or unacceptable toxicity using standard 3 + 3 phase1 design. The plasma levels of angiogenic biomarkers were correlated with clinical outcomes. Results: Eighteen pts with advanced tumors [lung (9), colon (8) and cervical (1)] pretreated with at least two lines of chemo were enrolled. Fifty percent (9 patients) were pretreated with bev. The final dose of Nin is 200mg twice a day with no observed dose limiting toxicities (DLT). The common adverse events were fatigue (grade 1-3); nausea & diarrhea (grade 1-2). Two pts came off study due to grade 3 fatigue. The disease control rate (DCR) was 72% (1 CR,1 PR & 11 SD).The median progression free survival (PFS) was 4 months (m), and median overall survival (OS) was 14m. The PFS rate at 6, 12, and 18m was 22%, 11%, and 11% and the OS rate at 6, 12, and 18 m was 83%, 70% and 28% respectively. Durable clinical response was observed in pre-Bev treated pts (1CR, 4 SD). The median OS for colon (n = 8) not reachable with 57% alive at 18m; median OS for lung (n = 9) was 13m with 13% alive at 18m. Better DCR was correlated with lower baseline PIGF levels as well as increased level from baseline. Longer PFS was associated with higher than the median baseline values for VEFGR2, E-selectin and lower SDF-1α. Conclusions: Nin was well tolerated with Bev with no DLT’s. Significant clinical activity was observed in Bev pretreated patients suggesting Nin can overcome Bev resistance. Clinical trial information: NCT02835833.
Combination of metformin plus TKI vs. TKI alone in EGFR(+) LUNG adenocarcinoma: A randomized phase II study.
Authors: Oscar Gerardo Arrieta Rodriguez, Feliciano Barron Barron, Miguel-Ángel Salinas Padilla, Laura Alejandra Ramirez-Tirado, Diana Flores-Estrada, Graciela Cruz-Rico, Manuel Jesús Arguelles Jiménez, Andres Felipe Cardona Zorrilla
Journal: Journal of Clinical Oncology (2018)

9013 Background: Metformin has been shown to have antitumor activity by increasing AMPK through different mechanisms involving tumor suppressor gene, LKB1. LKB1 inactivation is common in Non-small cell lung cancer (NSCLC) and is associated with a more aggressive clinical phenotype. Retrospective studies have shown that metformin could effectively increase the sensitivity to TKIs in NSCLC, thus improving Progression Free Survival (PFS) and potentially impacting Overall Survival (OS) in these patients. We compared the effect of metformin in combination with EGFR-TKI versus TKIs alone on the clinical prognosis of adenocarcinoma patients with EGFR mutations. Methods: In this phase 2 clinical trial (NCT03071705) we randomly assigned 116 patients with stage IV EGFR-mutated lung adenocarcinoma to receive therapy with metformin + EGFR-TKI (M+TKI) (n = 49) or EGFR-TKI (TKI) alone (n = 67). TKI was chosen upon clinician´s discretion. Patients were excluded if they had a history of diabetes or had received therapy with metformin or TKIs ( > 2 cycles) previous to enrollment. The primary endpoint was PFS, secondary endpoints included objective response rate (ORR), disease control rate (DCR) and OS. Results: Baseline characteristics were well balanced between treatment arms. Mean patient follow up was 12.9 (±10.9) months. Median PFS was significantly longer for patients receiving M+TKI compared to those who received TKI (14.0 months vs. 10.0 months; p = 0.017) . ORR was higher in the experimental arm of the trial, compared to the control group (67.4% vs. 47.5%; p = 0.044), although, the DCR was similar in the two groups (97% vs. 88.5%; p = 0.085). Median OS was 24.8 months. Patients receiving M+TKI had a longer OS compared to those receiving TKI (27.2 months vs. 19.0 months, p = 0.015). Multivariate analysis showed that, among others, the therapeutic arm (M+TKI vs. TKI) is an independently associated factor for both PFS and OS. Conclusions: Our study strongly suggests that the addition of Metformin to standard EGFR-TKI therapy has a significant effect in PFS, ORR and OS of patients with EGFR-mutated NSCLC. Metformin use is a safe and efficacious addition to the therapeutic scheme of EGFR+ NSCLC. Clinical trial information: NCT03071705.