tbuckley/cabot-search huggingface dataset:
Effects of presurgical exercise training on exercise capacity in operable lung cancer: A pilot study
Authors: C. J. Peddle, N. D. Eves, K. S. Courneya, M. Haykowsky, J. R. Mackey, A. A. Joy, T. J. Reiman, T. W. Winton, L. W. Jones
Journal: Journal of Clinical Oncology (2006)

17047 Background: Exercise capacity is a strong independent predictor of surgical outcome in patients with operable NSCLC and thus an established clinical tool to assess preoperative eligibility. The purpose of this study was to determine the effects of preoperative exercise training on exercise capacity in operable lung cancer. Methods: Using a single-group design, participants with suspected operable lung cancer were screened for eligibility at the time of diagnosis. Twenty-six patients were recruited and offered exercise training until surgical resection. Exercise training consisted of 5 endurance cycle ergometry sessions per week at 60 to 100% of patient’s baseline exercise capacity. Patients underwent cardiopulmonary exercise testing (CPET) including peak oxygen consumption (VO 2peak ), six minute walk distance (6MWD), and a pulmonary function test at baseline, immediately prior and 30 days post surgical resection. Results: The mean time from diagnosis to resection was 67 ± 27 days. During this time, 6 patients were deemed ineligible and were removed from the analysis. Of the remaining 20 patients, 18 completed exercise training and 13 performed CPET post resection. The overall adherence rate was 72% (range 0%–100%) with patients completing a mean of 30 exercise sessions (range 0–75). Intention-to-treat analysis indicated that VO 2peak and 6MWD increased by 2.3 mL · kg −1 · min −1 [95% CI, 1.0 to 3.7; p = .002] and 40m [95% CI, 16 to 64; p=.003] respectively, from baseline to presurgery but decreased from pre to post resection [VO 2peak , −2.7 mL · kg −1 · min −1 , 95% CI, −3.9 to −1.6; p &lt; .001; 6 MWD, −44 m, 95% CI, −94 to 6.4; p = .082]. There were no differences between baseline and postsurgical exercise capacity. Per protocol analyses indicated that patients who achieved acceptable exercise adherence (≥80% of prescribed sessions, n = 12) increased VO 2peak and 6MWD by 3.2 mL · kg −1 · min −1 [95% CI, 1.1 to 5.4; p = .005] and 49 meters [95% CI, 12 to 85; p = .013], respectively. Conclusion: Preoperative exercise training is associated with improvements in exercise capacity in patients with operable NSCLC, particularly if acceptable adherence is achieved. This benefit may have important implications for surgical outcome and postsurgical recovery in this population. No significant financial relationships to disclose.
Abstract 18163: Clinical Cardiovascular Risk During Young Adulthood in Offspring of Hypertensive Pregnancies
Authors: Esther F Davis, Adam J Lewandowski, Christina Aye, Wilby Williamson, Henry Broadman, Rae-Chi Huang, Trevor A Mori, John Newnham, Lawrence Beilin, Paul Leeson
Journal: Circulation (2014)

Introduction:  Offspring of hypertensive pregnancies have increased cardiovascular risk factors during childhood. We studied whether pregnancy hypertension is associated with clinically relevant changes in the cardiovascular risk profile in adults at 20 years of age.   Methods:  We used data on 2868 offspring of women enrolled during pregnancy into the Western Australia Pregnancy Cohort (Raine) Study with detailed information on pregnancy as well as prospective measures into adult life of cardiovascular risk factors on 1151 subjects, including body size, blood pressure and fasting glucose, insulin and lipids.   Results:  Adult offspring of hypertensive pregnancies were 2.5 times (95% CI 1.32 to 4.56, p =0.004) more likely to have lifetime QRisk scores above the 75th centile with, on average, a 3.7+/-0.97 mmHg (p   Conclusions:  Maternal hypertension in pregnancy was associated with increased blood pressure such that 30% of adults aged 20 years with hypertensive blood pressures were born to a hypertensive mother. Incidence of hypertension was higher if their mother had a more complicated pregnancy history. Raised blood pressure and BMI were evident throughout childhood and early intervention may be of value to prevent adult hypertension.
Serum cyclophosphamide activity in patients treated for small cell carcinoma of the lung.
Authors: S C Sarpel, T Lad, R B Epstein
Journal: Journal of Clinical Oncology (1983)

Cyclophosphamide requires in vivo activation for its cytotoxicity. A bioassay of serum cyclophosphamide activity based on inhibition of normal peripheral blood CFU-C by serum from cyclophosphamide-treated patients was developed. Seventeen patients with small cell cancer of the lung were studied before and after cyclophosphamide administration in an attempt to correlate serum cytotoxicity in vitro with clinical response to chemotherapy. A correlation (r = 0.61, p less than 0.01) was discovered between serum cytotoxicity in vitro and subsequent leukopenia in vivo. However, a dose-response relationship was not found between serum cytotoxicity and response to chemotherapy. Besides drug dosage and blood level, other factors govern the sensitivity of small cell lung cancer to chemotherapy.
Metastatic renal cell carcinoma (mRCC) patients (pts) with sarcomatoid features treated with VEGF-targeted therapy
Authors: A. R. Golshayan, S. George, D. Y. Heng, P. Elson, L. Wood, J. A. Garcia, H. Aydin, M. Zhou, R. M. Bukowski, B. I. Rini
Journal: Journal of Clinical Oncology (2008)

5102 Background: Sarcomatoid differentiation is an aggressive RCC variant associated with poor outcomes. There is limited data regarding the use of VEGF-targeted therapy in these pts. Methods: Pts with mRCC with sarcomatoid features treated with VEGF- targeted therapy were identified. Tissue nephrectomy samples were reviewed by a single pathologist and the percentage of sarcomatoid elements were estimated. Objective response, tumor burden shrinkage, progression-free (PFS) and overall survival (OS) were determined. A comparison group of 29 pts with clear cell RCC without sarcomatoid components (NS) also treated with anti-VEGF therapy and matched for gender, risk factors and treatment received were also evaluated. Results: Sarcomatoid differentiation was found in 43 pts: 33 clear cell, 1 papillary, 1 chromophobe, 1 mixed and 7 unclassified RCC subtypes. The median percentage of sarcomatoid elements was 20% (range, 5–80%). Pts received sunitinib (49%), sorafenib (28%), bevacizumab (19%) or sunitinib + bevacizumab (5%). All pts had prior nephrectomy and 44% had 1 prior systemic therapy. Tumor shrinkage was documented in 47% of pts, and median shrinkage was 2% (range, -85% to +127%). Eight pts (19%) achieved partial responses (PR), 21 (49%) stable disease (SD) and 14 pts (33%) had progressive disease (PD) as their best response. Median PFS and OS were 5.3 months and 11.8 months respectively. The NS group had greater tumor shrinkage (29% vs. 5%, p=0.01) and median PFS (13.2 vs. 5.5 months, p=0.05) than the sarcomatoid group. There was no significant difference in median PFS based upon treatment given. Pts with <20% sarcomatoid elements appeared to have better responses to VEGF-targeted therapy (Table). Conclusions: Pts with mRCC with sarcomatoid differentiation demonstrate objective responses and tumor shrinkage with anti-VEGF therapy, particularly with <20% sarcomatoid elements. Clinical Outcome Based on Percentage of Sarcomatoid Components Sarcomatoid Percentage PR SD PD Tumor Shrinkage (median, range) Median PFS (months) Median OS (months) < 20% 33% 40% 17% -6.5% (-58.0, 53.0) 7.9 16.4 ≥20% 0 30% 69% +23.0% (-19.1, 47.0) 3.1 6.4 p-value 0.006 0.05 0.49 0.16 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Antigenics, Bayer, Genentech™ BioOncology, Novartis, Onyx, Pfizer Oncology, Wyeth Bayer, Genentech™ BioOncology, Novartis, Onyx, Pfizer Oncology, Wyeth Bayer, Genentech™ BioOncology, Pfizer Oncology, Wyeth
Abstract 18117: Trends in the Utilization and Outcomes of Medicare Beneficiaries Undergoing Catheter Ablation for Ventricular Tachycardia
Authors: Omair Yousuf, Robbert Zusterzeel, WIlliam Sanders, Carmen Dekmezian, Henry Silverman, Thomas MaCurdy, Saman Nazarian, Ronald Berger, Danica Marinac-Dabic, Daniel Caños, David Strauss
Journal: Circulation (2014)

Background: Sustained ventricular tachycardia (VT) is a significant cause of sudden death, progressive ventricular dysfunction, and heart failure hospitalizations. Radiofrequency catheter ablation is used to control incessant VT and prevent or reduce the frequency of VT episodes. However, data regarding mortality and complication rates with VT ablation are limited. Objective: To measure the incidence of procedural complications, repeat ablations, hospitalization for heart failure and ventricular tachycardia, and short and long term mortality in patients undergoing VT ablation. Methods: We conducted a population-based, retrospective cohort study of all fee-for-service Medicare beneficiaries who underwent catheter ablation for VT between 2000 and 2012. The main outcome measures were major complications within 30 days and 1-year rates of death, repeat ablation and heart failure and VT hospitalization. Results: There were 21,073 patients that received a VT ablation during the study period (mean age 70 years; 77% were men; 90% were white). The ablation frequency increased from 647 in 2000 to 2,760 in 2012. The 30-day incidence of pericardial complications was 2.3%, vascular complications 6.8%, stroke or transient ischemic attack 1.5%, need for mechanical circulatory support 2.3%, and death 4.2%. The 1-year incidence per 1,000 person-years for repeat ablation was 81, death 176, and hospitalization for heart failure and VT 156 and 272, respectively (Figure). Conclusions: Utilization of catheter ablation for VT has increased over the past 12 years. Major complications after VT ablation are relatively infrequent, but not trivial. These findings should inform discussion of potential procedural complications and long term prognosis and may have considerable implications when discussing treatment options for patients with VT.
Measures of aggressive care in advanced non-small cell lung cancer (NSCLC) patients
Authors: J. McCannon, V. A. Jackson, J. A. Billings, W. F. Pirl, J. Greer, T. J. Lynch, J. S. Temel
Journal: Journal of Clinical Oncology (2007)

9063 Background: Data suggests that cancer care has become more aggressive over the last decade. Patients with advanced NSCLC have a short life expectancy and achieve only a modest survival benefit from chemotherapy. Investigating the aggressiveness of care during and at the end of life (EOL) is a key first step to better understanding quality of care in this patient population. Methods: This exploratory study uses previously defined measures of aggressive care (Earle, JCO 22(2), 2004) to evaluate a small cohort of patients with advanced NSCLC. We performed a pilot study of integrated palliative care in good performance status (PS) patients with newly diagnosed advanced NSCLC, which has been previously reported. This is a retrospective chart review of patients accrued at Massachusetts General Hospital (MGH) using the electronic medical record and case report forms for data collection. Results: 46 patients were enrolled from 10/03 to 6/05 (median age 65.5, 28 female). 43 (93%) patients had stage IV disease and the remainder had stage IIIB with effusions. 45 (98%) of patients had PS 0–1. 39 (85%) patients died at the time of chart review with a median follow up of 29.3 months. Using Earle's data as a benchmark more patients in this study received and began new chemotherapy at the EOL. Patients were also more likely to present to the emergency room (ER) and be admitted to the hospital. While more patients were admitted to hospice before death, the length of stay (LOS) in hospice was shorter and many patients still died in acute care hospitals. Conclusions: This study supports the finding that current cancer care is aggressive with many patients receiving chemotherapy at the EOL and having a short LOS in hospice. [Table: see text] No significant financial relationships to disclose.
High rate of complete pathologic response using neoadjuvant trastuzumab in women with human epidermal growth factor 2 positive stage III breast cancer
Authors: M. A. Alrefae, D. Roberge, L. Panasci
Journal: Journal of Clinical Oncology (2008)

11575 Background: Neoadjuvant treatment of women with local-regional advanced human epidermal growth factor 2 (HER2) positive breast cancer presents a challenge because of the paucity of data supporting the use of trastuzumab in this setting. We reviewed clinical and pathologic response rates in women treated at our institution with neoadjuvant trastuzumab containing chemotherapy regimens. Methods: Oncology charts of 2006–2007 were reviewed to identify women treated for stage III breast cancer with neoadjuvant trastuzumab. The primary endpoints recorded were the occurrence of complete clinical and pathologic response. The later was defined as complete absence of viable invasive tumor cells on pathologic examination. Results: A total of 10 patients were identified with median age of 54 years. All patients had biopsy confirmed HER2 positive stage III breast adenocarcinoma by IHC. HER 2 overexpression was confirmed in 8 patients with FISH. Five patients (50%) had inflammatory tumors and 7 patients (78%) were clinically node positive. The mean tumor size was 8.5 cm (range 0–15 cm). A metastatic work up was negative in all cases. Trastuzumab was not administered simultaneously with anthracyclines. A mean of 8.2 chemotherapy cycles was delivered prior to surgery. Trastuzumab was given weekly in 6 patients, and every 3 weeks in 4 patients. Objective clinical response was documented in all patients, seven (78%) achieved complete clinical response. All underwent modified radical mastectomy including axillary lymph node dissection. Complete pathologic response in the breast and axillary lymph nodes was confirmed in 4 patients (40%). Treatment was well tolerated with 1 of the epirubicin treated patients developing significant decline in her ejection fraction after 10 months of trastuzumab. Conclusions: Neoadjuvant treatment of local-regional advanced HER2 breast cancer with a variety of trastuzumab- containing chemotherapy regimens yielded a high rate of complete clinical and pathologic responses. Despite the lack of high-level evidence, trastuzumab should be considered in women undergoing neoadjuvant chemotherapy for local-regional advanced HER2 positive breast cancer. No significant financial relationships to disclose.
Evaluation of multidisciplinary (MultiD) care in thoracic oncology.
Authors: G. L. Phelps, O. O. Bankole, S. Sarwar, J. J. McFarlane, R. U. Osarogiagbon
Journal: Journal of Clinical Oncology (2010)

6093 Background: MultiD decision making is advocated in thoracic oncology because of the range of management options. This approach is difficult to implement, its benefits are empirical and likely dependent on compliance with recommendations. We evaluated outcomes after MultiD Thoracic Oncology Conference (MDTOC) discussion. Methods: Review of all cases presented at a weekly MDTOC from 1/1/07 to 9/30/09. Categorical variables compared by chi-squared and Fisher's exact tests, survival estimated by the Kaplan-Meier method, survival curves by log-rank test and Cox-proportional hazards for multiple regression analysis of survival. Results: See Table. Conclusions: A third of all MDTOC recommendations, 40% of recommendations for invasive procedures, were not implemented. Physician decision accounts for most discordance. Race and insurance status were associated with discordance. Patients with discordant care had poorer survival. MultiD planning improves the outcome of thoracic oncology care. Focus on causes of discordant care is warranted. Total N (%) Concordant % Discordant % P Median age (years) 158(42) 59 59 0.6 Gender Female 217(58) 63 37 0.9 Male 212(58) 63 37 <0.04 Race Black 152(42) 58 42 <0.001 White 103(28) 69 31 0.3 Insurance Commercial 207(55) 73 27 Government 64(17) 64 36 None 352(94) 42 58 Performance status 0-1 24(6) 63 37 2-4 58 42 Reason for discussion Diagnosis 142(38) 61 39 0.3 Staging 47(13) 72 28 1st Rx 113(30) 57 43 >1st Rx 51(14) 65 35 Adjuvant Rx 17(5) 76 24 Histology NSCLC 180(59) 62 38 0.4 SCLC 14(5) 71 29 Nonlung 88(29) 67 33 Other 24(8) 79 21 Recommendations All 77(20) 79 21 <0.001 X-ray 111(30) 50 50 <0.02 Biopsy 44(12) 50 50 Combined modality 53(14) 60 40 Chemotherapy 5(1) 80 20 Radiotherapy 70(19) 71 29 Resection 16(4) 69 31 Other 35(18) 49 51 Invasive procedures 34(17) 56 44 Endoscopy 29(15) 48 52 Percutaneous biopsy 88(44) 68 32 Mediastinoscopy 10(5) 20 80 Surgery Other Reasons for discordance % Clinician decision 61 Loss to follow-up 19 Patient refusal 15 Survival (years) OS 2.0 2.1 1.3 0.004 PFS 1.1 1.3 0.8 0.02 Hazard ratio Unadjusted OS 1.8 0.004 PFS 1.5 0.02 Stage-adjusted OS 1.7 0.02 PFS 1.4 0.04 No significant financial relationships to disclose.
In vivo platform for translational drug development and biomarker discovery in pancreatic cancer
Authors: M. Hidalgo, B. Rubio-Viqueira, C. Weekes, D. Song, P. Shah, W. Messersmith, W. Messersmith, S. Altiok, P. Kulesza, A. Maitra, A. Jimeno
Journal: Journal of Clinical Oncology (2006)

4000 While there are many new agents entering clinical development, there is very little data to prioritize which agents should be explored in pancreas cancer. Furthermore, often there is no information on biomarkers that may predict the activity of these drugs in pancreas cancer. In this project, we have generated a cohort of 30 pancreatic cancer xenografts by implanting in nude mice tumor materials from surgical specimens. Molecular studies show that a) these tumors maintain the genetic features of the originator cancer such as KRAS, p53 and DPC4 gene status; b) tumors represent the heterogeneity of pancreatic cancer well (there is not selection of any genotype in the xenograft ) and c) features do not changed over time. We have used this platform to explore the activity of a battery with a total of 10 new anticancer agents including inhibitors of MAPK, EGFR, mTOR, src kinase, Ras oncogene, mitosis regulators, angiogenesis, heat shock protein and hedgehog pathway inhibitors using a methodology similar to a two stage phase II clinical trial. All agents are tested against 10 xenografts. Those inactive are not explored anymore. Active agents are tested against the full set of tumors. Thus far we have shown that inhibitors of mTOR and MAPK have substantial activity in this model while Ras interacting agents and EGFR targeted drugs have no single agent activity. For active agents, we have characterized the tumors for potential strategies and biormarkers that may predict activity using both a target-focus approach as well as general profiling approach. Signaling inhibitors are more active in tumors with evidence of activation of the targeted pathway. In addition, ex vivo assays indicate that the ability to inhibit the targeted pathway is associated with agent activity. This information may help to prioritize agents for clinical development in pancreatic cancer. [Table: see text]
P362Pathological cardiac remodeling caused by cardiomyocyte/vascular smooth muscle glucocorticoid receptor deficiency
Authors: RV Richardson, EA Rog-Zielinska, AJW Thomson, CM Moran, CJ Kenyon, GA Gray, KE Chapman
Journal: Cardiovascular Research (2014)

Variation in the human glucocorticoid receptor (GR) gene associates with relative glucocorticoid resistance, hypertension and increased cardiovascular disease risk. Here, the contribution of cardiovascular GR to disease risk was assessed in male and female "SMGRKO" mice with cardiomyocyte and vascular smooth muscle deletion of GR. SMGRKO mice, generated by crossing GR "floxed" mice (congenic on C57BL/6J) with SM22α-Cre mice, have reduced cardiac GR protein and mRNA levels (by 52% and 57%, respectively), compared to Cre-negative littermate controls. Loss of cardiovascular GR impairs viability. There are fewer SMGKRO mice than controls at weaning with a greater effect in females [SMGRKO:Control; females 27:79(25% vs expected 50%); males 37:68(35%) p<0.0001]. Doppler measurements (Visualsonics Vevo770 ultrasound) of blood flow within the left ventricle show a detrimental increase in the myocardial performance index, which measures combined systolic and diastolic function, in both sexes of adult SMGRKO mice. This is primarily due to prolonged isovolumetric contraction time (p<0.05) indicating impairment of the initial left ventricular contractile phase. In male SMGRKO mice (but not female) heart weight (% body weight) was increased (Control:0.50±0.02%; SMGRKO:0.55±0.01%, p<0.05) as was cardiomyocyte cross sectional area (Control:180±4μm2; SMGRKO:194±4μm2, p<0.01). Furthermore, cardiac levels of mRNA encoding myosin heavy chain-β, a marker of pathological cardiac hypertrophy, were elevated in male SMGRKO mice only (p<0.05). Both sexes showed left ventricular fibrosis (histopathology) and elevated levels of cardiac mRNA encoding pro-fibrotic factors. Thus, cardiomyocyte/smooth muscle GR-deficiency causes the same functional impairment of isovolumetric contraction but differential pathological changes in the left ventricle of surviving male and female mice. Whether pathology is worse in neonatal or fetal SMGRKO females is under investigation. These findings support a role for cardiovascular GR in determination of cardiovascular disease risk, though without overt signs of cardiac hypertrophy in females.
Surface modification of a POSS-nanocomposite material to enhance cellular integration of a synthetic bioscaffold
Authors: Claire Crowley, Poramate Klanrit, Colin R. Butler, Aikaterini Varanou, Manuela Platé, Robert E. Hynds, Rachel C. Chambers, Alexander M. Seifalian, Martin A. Birchall, Sam M. Janes
Journal: Biomaterials (2016)

Polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) is a versatile nanocomposite biomaterial with growing applications as a bioscaffold for tissue engineering. Integration of synthetic implants with host tissue can be problematic but could be improved by topographical modifications. We describe optimization of POSS-PCU by dispersion of porogens (sodium bicarbonate (NaHCO3), sodium chloride (NaCl) and sucrose) onto the material surface, with the principle aim of increasing surface porosity, thus providing additional opportunities for improved cellular and vascular ingrowth. We assess the effect of the porogens on the material's mechanical strength, surface chemistry, wettability and cytocompatibilty. Surface porosity was characterized by scanning electron microscopy (SEM). There was no alteration in surface chemistry and wettability and only modest changes in mechanical properties were detected. The size of porogens correlated well with the porosity of the construct produced and larger porogens improved interconnectivity of spaces within constructs. Using primary human bronchial epithelial cells (HBECs) we demonstrate moderate in vitro cytocompatibility for all surface modifications; however, larger pores resulted in cellular aggregation. These cells were able to differentiate on POSS-PCU scaffolds. Implantation of the scaffold in vivo demonstrated that larger pore sizes favor cellular integration and vascular ingrowth. These experiments demonstrate that surface modification with large porogens can improve POSS-PCU nanocomposite scaffold integration and suggest the need to strike a balance between the non-porous surfaces required for epithelial coverage and the porous structure required for integration and vascularization of synthetic scaffolds in future construct design.