tbuckley/cabot-search huggingface dataset:
Flow-volume loops in central airway obstruction
Authors: Liliana Raposo, Antόnio Bugalho, Maria João Gomes
Journal: European Respiratory Journal (2011)

Introduction:  Central airway obstruction (CAO) leads to significant morbidity and mortality. In the last 40 years flow-volume loops (FVL) have been used as a noninvasive method to evaluate this condition although bronchoscopy is the gold standard. Few studies were made to verify the sensitivity and specificity of FVL in detecting CAO, or to investigate the morphological and quantitative changes of the curve in relation to location, type and degree of obstruction.   Methods:  Patients with an indication to perform bronchoscopy were selected consecutively. Bronchoscopy and FVL were carried out with a maximum interval of 7 days. Four experts, blinded to the quantitative data, were used to assess the morphology of FVL (suggestive or non-suggestive of CAO) and an independent element established the quantitative and morphological criteria (intra, extrathoracic variables and fixed).   Results:  82 patients were studied, 36 (44%) with CAO. The sensitivities and specificities in detecting CAO were, respectively: 91.3% and 88.9% for the quantitative criteria of FVL; 93.5% and 30.6% concerning the morphological criteria; 95.7% and 86.1%.if there was an aggregation of quantitative and morphological criteria. In patients with CAO the most common quantitative criteria were FEF 50 /FIF 50 ≥1, (83%) and FEV 1 /PEF ≥ 8 (36%). They correlated with localization, degree and type of obstruction.   Conclusions:  The morphology of the FVL has a good sensitivity but low specificity in detecting CAO. Quantitative criteria of the FVL have a high sensitivity and specificity. In clinical practice one should always use an aggregation between the morphological and quantitative criteria, since it maintains sensitivity, improving specificity.
Effect of Ca/Mg on neurotoxicity and blood concentration of platinum in patients on mFOLFOX6 therapy: A prospective randomized study
Authors: K. Ishibashi, N. Okada, T. Ishiguro, M. Yokoyama, T. Miyazaki, M. Matsuki, M. Sano, H. Ishida
Journal: Journal of Clinical Oncology (2008)

20639 Background: It remains controversial whether or not administration of calcium (Ca) and magnesium (Mg) can reduce the neurotoxicity specific to FOLFOX therapy. In addition, little is known about the effect of Ca/Mg on the blood concentration of platinum. Methods: Patients on mFOLFOX6 therapy for unresectable colorectal cancer were randomized to receive Ca/Mg (Ca/Mg group, n=17) or placebo (Placebo group, n=16) before and after the administration of oxaliplatin (85 mg/m2). In the Ca/Mg group, calcium gluconate (CalcicolR, 10 ml) and magnesium sulfate (Conclyte MgR, 10 ml) were infused before and after oxaliplatin. In both groups, blood samples were collected to determine the total and ultrafiltrable levels of platinum in plasma before and after (5 min, 1 hr, 3 hr, one week, and two weeks) administration of oxaliplatin in the first and fifth cycles of mFOLFOX6 therapy. Results: The cumulative occurrence of neurotoxicity (≥grade 2) did not differ between the two groups (p=0.97). Blood concentrations of platinum at each time and the area under the curve (AUC) were also not significantly different between the two groups. Furthermore, the response rate (RR) and disease control rate (DCR) did not differ significantly between the two groups (Ca/Mg group: RR 36%, DCR 73%. placebo group: RR 40%, DCR 70%, p>0.99). Conclusions: Administration of calcium and magnesium may not have any effect on neurotoxicity, the blood concentration profile of platinum, or the response rate in patients receiving mFOLFOX6 therapy. No significant financial relationships to disclose.
Abstract IA16: Acquired resistance to targeted therapeutics in hematologic malignancies
Authors: Neil P. Shah
Journal: Clinical Cancer Research (2015)

Abstract Targeted treatment approaches of hematologic malignancies provided many of the first inroads into the successful treatment of human malignancy with the emerging class of targeted therapeutics. Initial responsiveness to targeted therapy provides compelling evidence for the importance of specific targets for the maintenance of disease. Understanding mechanisms of acquired resistance further informs how malignant cells can circumvent target inhibition in patients, and in some instances, these insights have facilitated the successful development of next generation targeted therapeutics, best exemplified by BCR-ABL tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia (CML). As detailed genomic analyses are becoming more readily available, opportunities for developing and incorporating targeted therapeutics are expected to increase. It is becoming clear, however, that tumor heterogeneity in advanced hematologic malignancies can be substantial, and resistant subclones can compromise duration of response to targeted therapy. Several examples of acquired resistance to targeted therapeutics in human hematopoietic malignancies will be presented, as well as the implications of these molecular mechanisms toward future successful management of these diseases. Citation Format: Neil P. Shah. Acquired resistance to targeted therapeutics in hematologic malignancies. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr IA16.
Plasma EGFR and Her2 levels in non-small cell lung cancer patients treated with gefitinib
Authors: K. Kasahara, S. Tamori, A. Sakai, Y. Tambo, T. Araya, T. Sone, H. Kimura, M. Fujimura
Journal: Journal of Clinical Oncology (2008)

19007 Background: Although EGFR mutation is a strong predictive factor of EGFR-TKI, it is difficult to obtain tumor tissue which is suitable to examine EGFR mutations in patients (pts) with metastatic non-small cell lung cancer (NSCLC). The objectives of study are to evaluate roles of plasma EGFR and HER2 levels as a biomarker of gefitinib treatment. Methods: Patients: pts who histologically or cytologically proven NSCLC received 250 mg of gefitinib daily. Plasma EGFR levels were measured by ELISA kit (Oncogene Science, USA) as manufacture’s instruction. Tumor responses were evaluated by RECIST guidelines. Time to progression (TTP) and overall survival (OS) were calculated and evaluated by the Kaplan-Meier method. Groups were compared using the log-rank test. Risk factors associated with survival were evaluated using Cox proportional hazards regression modeling and multivariable analysis. Results: Of 93 patients (pts) enrolled in this investigation, 37 pts (40%) were female and 34 pts (37%) had never smoked. The most common histological subtype was adenocarcinoma (79%) and 66 pts (70%) had good PS 0–1. 22 patients (24%) achieved PR and 32 (33%) had SD as their overall response. Pretreatment levels of EGFR and HER2 were 40.0 and 8.8 ng/ml, respectively. There was no significant correlation between plasma EGFR or HER2 levels and patients’ characteristics. Plasma EGFR levels in patients who achieved PR or SD were significantly higher than that in patients with PD (42.81 ng/ml vs 36.02 ng/ml, p=0.049). High group (EGFR >40 ng/ml) had significantly longer OS (11.1 months in high group vs. 4.8 months in low group), and TTP (3.3 months in high group vs. 1.4 months in low group) than low group (EGFR <40 ng/ml). High EGFR associated with better OS in subgroup such as male (9.0 months in high group vs. 3.2 months in low group), non-adenocarcinoma (6.4 months in high group vs. 2.7 months in low group), EGFR mutation negative (7.6 months in high group vs. 4.6 months in low group). On multivariable analysis, high plasma EGFR levels remained significantly associated with improved TTP and OS. Plasma HER2 levels did not associate with responses to gefitinib, TTP, or OS. Conclusions: High levels of plasma EGFR may be a good predictor of clinical benefit of gefitinib. No significant financial relationships to disclose.
A phase I open-label study of escalating-dose oral cyclophosphamide (CTX), docetaxel (D), zoledronic acid (ZA), and high-dose calcitriol (HDC) for castration-resistant prostate cancer (CRPC).
Authors: C. E. Souza, D. A. Bastos, D. F. Jardim, S. C. Martins, R. Laporti, F. C. Maluf
Journal: Journal of Clinical Oncology (2010)

e15079 Background: HDC is a biological agent with activity either alone or in combination in CRPC. Preclinical studies have demonstrated that HDC is synergistic with other cytototoxic agents such as D and oral CTX. Methods: Eligible patients (pts) had progressive, metastatic, chemo-naive CRPC with ECOG 0 or 1. Three pts were treated in each cohort, expanded by 3 pts if a dose-limiting toxicity (DLT) was observed in one pt. If no DLT occurred after all pts completed 1 cycle in a cohort, pts were enrolled at the next dose level. If a DLT was seen in 2 pts, the dose level was closed. D was given I.V. on day 1 with ZA 4mg I.V. at the dose of 60 mg/m2 in the first cycle and escalated to 70 mg/m2 for the next cycles if no DLT occurred. HDC was given P.O. at a fixed dose of 50mcg divided in 4 doses on day 0. Oral CTX was given on days D1-10 and dose levels were: cohort 1 50mg/d; cohort 2 100mg/d and cohort 3 150mg/d. Cycles were given every three weeks. Efficacy was explored as: maximal confirmed PSA decline; partial or complete response (PR+CR) by RECIST criteria and/or changes in bone scan. Results: Fourteen pts were enrolled to complete the dose-finding phase. Characteristics included median age of 68 yrs (range 55-81) and median baseline PSA of 74.6 ng/mL (range 11-571). DLTs by dose level are summarized as: cohort 1, DLT in 1 of 6 pts (febrile neutropenia (Gr) 4); cohort 2, DLT in 1 of 4 pts (neutropenia (Gr) 4); and no DLT in cohort 3. A pt in cohort 3 had acute myocardial infarction probably not related to therapy. Preliminary measures of efficacy by method of assessment and cohort assignment are summarized (Table). Conclusions: We conclude that the D 70 mg/m2, HDC 50 mcg, ZA 4mg every three weeks in combination with oral CTX 50mg (cohort 1) and 100mg (cohort 2) on days1-10 is safe and demonstrates anticancer efficacy. Cohort 1 Cohort 2 Cohort 3 Median # cycles (range) 5.5 (2-10) 5.5 (1-8) 4 (2-7) PSA decline > 30% 3/6 3/4 3/4 > 50% 3/6 2/4 3/4 RECIST PR+CR 2/4 2/4 2/4 Bone Stable 6/6 4/4 4/4 No significant financial relationships to disclose.
FMNL1 Is Downregulated In Myelodysplastic Syndromes and Is Involved In Megakaryocytic Differentiation
Authors: Matheus Rodrigues Lopes, João Agostinho Machado-Neto, Fabiola Traina, João Kleber Novais Pereira, Irene Lorand-Metze, Fernando Ferreira Costa, Sara Teresinha Olalla Saad, Patricia Favaro
Journal: Blood (2013)
Abstract 146: Public Cardiopulmonary Resuscitation (CPR) Training - Are All Lay Providers the Same?
Authors: Shir Lynn Lim, Tracy Lian, Pei Ting Tan, Yiong Huak Chan, Benjamin Leong
Journal: Circulation (2013)

Background: Discordance exists in the prevalence of life-saving skills and bystander CPR rates. Public CPR training, while increasing the number of people trained, may not be training those most li...
Phase 2 Study of Ponatinib in Patients (Pts) with Advanced Gastrointestinal Stromal Tumors (Gist) After Failure of Tyrosine Kinase Inhibitor (Tki) Therapy: Early Results
Authors: M.C. Heinrich, M. von Mehren, G.D. Demetri, J. Fletcher, J. Sun, J.G. Hodgson, V.M. Rivera, C.D. Turner, S. George
Journal: Annals of Oncology (2014)
Metronomic chemotherapy plus/minus antiinflammatory treatment in far-advanced melanoma: A randomized multi-institutional phase II trial
Authors: A. Reichle, T. Vogt, B. Coras, K. Bross, P. Terhheyden, K. Neuber, U. Trefzer, E. Schultz, L. Fischer von Weikersthal, R. Andreesen
Journal: Journal of Clinical Oncology (2005)

3139 Background: Recently we have shown that control of tumor-associated inflammatory processes may result in improved progression-free (PFS) and overall survival (OS) independent of tumor type. Methods: A randomized multi-institutional phase II trial was designed to select metronomic chemotherapy (Arm A: trofosfamide 50 mg po three times daily, day 1+) or combined antiinflammatory/metronomic treatment (Arm B: trofosfamide as abovementioned plus rofecoxib 25 mg po, day 1+, and pioglitazone 60 mg po, day 1+) for further evaluation in a phase III trial. Following disease progression cross-over from Arm A to B was allowed. Assuming 33 eligible patients in each arm, the study had 0.80 power to detect a difference in PFS at 3 months of more than 30%. All p-values reported are two-sided. Results: Patient characteristics: Eligible patients (pts) Arm A: 32, Arm B 35. Treatment characteristics were equally balanced for age, AJCC stage, performance status, number of prior chemotherapies (A: 62%, B: 60% of pts), and C-reactive protein (CRP). The mean number of metastatic sites was A: 2.1 (range 1 to 3), B: 3.0 (range 1 to 5). Response, PFS and OS: Two pts achieved objective response (Arm A: 1 PR, Arm B: 1 CR). Median PFS of pts in Arm A was 1.2 months (0.9 to 1.5), in Arm B 2.0 mos (1.2 to 2.8), p = 0.002, median PFS at 3 mos 14% vs 49% in Arm B. Median PFS and OS for CRP responders (CRP decline within the first month on treatment: Arm A 6%, Arm B 69% of pts) was 2.0 vs 1.4 mos, p = 0.0098, and 18.8 months vs 5.3 months, p = 0.0092, respectively. The median OS of pts in Arm A was 8.2 mos (range 6.6 to 9.8), in Arm B 18.5 mos (5.9 to 31.1), p = 0.16. Toxicities: WHO Grade 3 (no Grade 4) toxicities were reported in 6 patients (19%) in Arm A and 10 patients (28%) in Arm B, due to higher rates of edema. Conclusions: The current phase II trial has shown for the first time that control of tumor-associated inflammatory processes may improve PFS beyond that achieved with metronomic chemotherapy, and that CRP response is a valid indicator for favorable PFS and OS. No significant financial relationships to disclose.
Tumor MGMT promoter hypermethylation changes over time limit temozolomide efficacy in a phase II trial for metastatic colorectal cancer
Authors: A. Amatu, L. Barault, C. Moutinho, A. Cassingena, K. Bencardino, S. Ghezzi, L. Palmeri, E. Bonazzina, F. Tosi, R. Ricotta, T. Cipani, P. Crivori, R. Gatto, G. Chirico, G. Marrapese, M. Truini, A. Bardelli, M. Esteller, F. Di Nicolantonio, A. Sartore-Bianchi, S. Siena
Journal: Annals of Oncology (2016)
Concomitant chemoradiotherapy: rationale and clinical experience in patients with solid tumors.
Authors: E E Vokes, R R Weichselbaum
Journal: Journal of Clinical Oncology (1990)

Concomitant chemoradiotherapy can be used in order to increase both the local and systemic control of solid tumors. The rationale for its use and experimental data for selected chemotherapy drugs are reviewed. Clinical trials have focused on increasing complete response (CR) and survival rates; in addition, improved quality of life by decreasing the use of conventional surgical procedures is being pursued. Both of these goals may have been achieved for some tumors, most notably for anal cell carcinoma. Improved survival with concomitant chemoradiotherapy has also been shown for patients treated on randomized studies for pancreatic, colorectal, small-cell lung, head and neck, and cervical cancer. These results call for the continued investigation of this approach in the laboratory and in the clinic.
Molecular subgroup of high-grade serous ovarian cancer (HGSOC) as a predictor of outcome following bevacizumab.
Authors: Charlie Gourley, Andrena McCavigan, Timothy Perren, James Paul, Caroline Ogilvie Michie, Michael Churchman, Alistair Williams, W. Glenn McCluggage, Mahesh Parmar, Richard S. Kaplan, Laura A. Hill, Iris A Halfpenny, Eamonn J. O'Brien, Olaide Raji, Steve Deharo, Timothy Davison, Patrick Johnston, Katherine E. Keating, D. Paul Harkin, Richard D. Kennedy
Journal: Journal of Clinical Oncology (2014)

5502 Background: HGSOC is a histopathological diagnosis and may represent multiple diseases at a molecular level. We investigated whether distinct molecular subgroups may influence treatment choice. Methods: mRNA was extracted from 265 macrodissected formalin fixed paraffin embedded HGSOCs from Scottish patients (pts) treated with primary debulking then platinum based chemotherapy. Transcriptional analysis was performed using the Ovarian DSA microarray. This was repeated using 283 UK samples from the ICON7 study [first line paclitaxel/carboplatin +/- concomitant and maintenance bevacizumab (bev) for 12 months]. Results: Unsupervised hierarchical clustering (Scottish tumours) identified three major subgroups, two with angiogenic gene upregulation and one with angiogenic gene repression and immune gene upregulation. This latter 'immune' subgroup had a superior overall survival (OS) compared to the other two subgroups combined [HR = 0.66 (0.46-0.94)]. A 63-gene expression signature to prospectively identify this subgroup was generated and validated as prognostic for OS in an independent dataset [HR = 0.32 (0.19-0.54)]. As the immune subgroup had repressed angiogenesis-related gene expression we hypothesised that these pts would benefit less from bev [power to detect interaction > 2 in predicted direction for progression free survival (PFS) in ICON7 was 88% (α=0.1, one-tail)]. In ICON7 the gene signature showed a difference in impact of bev on PFS between the immune and proangiogenic subgroups (1-sided test for interaction, p=0.016). For the immune group (41% of cases), the addition of bev conferred a worse PFS [HR = 1.73 (1.12-2.68)] and OS [HR = 2.00 (1.11-3.61)] compared to chemotherapy alone. In the proangiogenic group there was a non-significant trend to improved PFS for the addition of bev (median 17.4 vs 12.3 months in controls). Conclusions: An immune molecular subgroup of HGSOC has superior survival to other HGSOC. The addition of bev appears to significantly reduce PFS and OS in this subgroup. Patients in the proangiogenic subgroups have a trend towards a PFS benefit from bev. These data suggest a mechanism for stratification of bev therapy and should be validated in additional datasets.
Ultrastructure of Endocrine Cells and Argyrophil Carcinoids of the Stomach of Praomys (Mastomys) natalensis 2
Authors: Carlo Capella, Enrico Solcia, Katharine C. Snell
Journal: JNCI Journal of the National Cancer Institute (1973)

Endocrine cells of the gastric mucosa and gastric argyrophil carcinoids of Praomys (Mastomys) natalensis were compared. Based on their ultrastructural and staining patterns, 5 types of endocrine cells were identified in nontumorous gastric mucosa: the 5-hydroxytryptamine-(5HT)-storing argentaffin or enterochromaffin (EC) cell, primarily of the pyloric mucosa; the gastrin (G) cell, restricted to the pyloric glands; the D cell, resembling D cells of the pancreatic islets and found in both pyloric and oxyntic mucosa; and 2 types of argyrophil cells peculiar to the oxyntic glands—the ECL cell and a round-granule "A" cell differing ultrastructurally from glucagon-producing A cell of Mastomys' pancreas. The anaplastic cells of Mastomys' carcinoids partially reproduced the ultrastructural and staining patterns of Eel and round granule cells, to which they should be genetically related. EC, G, and D cells seemed unrelated to tumor cells. In tumor-bearing animals EC and mucous cells showed signs of functional stimulation, whereas G cells seemed dormant; these findings may be related to the histamine-dependent hyperchlorhydria of such animals.
Beliefs and concerns African American (AA) and white (W) patients (pts) with breast, lung, and colon cancer bring to bear on the decision to undergo chemotherapy
Authors: D. Smith, B. N. Polite, F. Hlubocky, S. Gehlert, C. K. Daugherty
Journal: Journal of Clinical Oncology (2007)

9076 Background: AA have poorer stage-specific survival for breast, colon and lung cancer than whites and are also less likely to receive therapy for these cancers. This study seeks to explore the set of beliefs and concerns patients with primarily resected breast, lung, and colon cancer bring to bear on the decision to receive chemotherapy. Methods: Semi-structured interviews were conducted and recorded by a non-physician, African-American interviewer on patients with colon, breast, and lung cancer referred to medical oncology for chemotherapy. Grounded theory methods were used to analyze and code the interview transcripts. Results: A total of 27 interviews were conducted (17AA, 10W) including pts with breast (5), colon (6) and lung cancer (16). All but 7 of the pts were referred for adjuvant therapy. Three major themes emerged: (1) Patient versus physician control in decision making; (2) Absolute trust in one's physician versus qualified trust; (3) Major role of God in the decision making process versus a partnership or minimal role of God. In terms of decision-making, roughly equal portions of AA and W (53% vs 54%) expressed a patient centered locus of control. In the area of trust, AA were less likely to express an absolute trust in their physicians (59% vs. 80%). Finally, with respect to the role of God, AA were more likely to express a major role of God for their cancer and treatment (41% vs. 7%). Very few pts viewed the opinion or advice of family or friends as important and while many expressed concerns about the side-effects of therapy, very few identified that as being an important factor in their decision to undergo therapy. Conclusions: Issues of locus of control, physician trust and the role of God were areas identified as important in the chemotherapy decision-making process and for which variability existed among the pts interviewed. Analysis of these interviews informed the incorporation of validated measures of decision-making, physician trust, and the role of God as a locus of control in an ongoing close-coded survey of a similar cancer population. No significant financial relationships to disclose.
Abstract 14146: Systolic Anterior Motion of the Mitral Valve Alters Three Dimensional Hemodynamics in the Ascending Aorta in Hypertrophic Cardiomyopathy
Authors: Bradley D. Allen, Lubna Choudhury, Alex J. Barker, Pim von Ooij, Jeremy D. Collins, James C. Carr, Robert O. Bonow, Michael Markl
Journal: Circulation (2013)

Bradley D. Allen, 2013 Finalist and Presenting Author