tbuckley/cabot-search huggingface dataset:
Risk factors for a low FVC in the BOLD project
Authors: Bernet Kato, Peter Burney
Journal: European Respiratory Journal (2014)

Introduction : A low forced vital capacity (FVC) is associated with a poor prognosis regardless of the presence of airflow limitation or diagnosed restrictive disease. FVC varies markedly across different BOLD sites and is known to be associated with birth weight, poverty and ethnicity. Very little else is known about its determinants.   Methods : We have analysed the prevalence of a low FVC, defined by the NHANES Caucasian reference equations, in relation to risk factors measured in the BOLD study and have examined the geographical distribution before and after adjusting for these risk factors.   Results : A low FVC was associated with pack years of smoking (OR (95%CI) /20 pack years: 1.28 (1.17, 1.4), a BMI that was underweight (2.9 (1.9, 4.4)), overweight (1.3 (1.14, 1.5)) or obese (2.5 (2.0, 3.1)), education /completed educational level (university, secondary, primary, none) (1.11 (1.01, 1.22)), hospitalisation for breathing problems before the age of 10 years (1.88 (1.36, 2.62))and a history of TB (1.8 (1.3, 2.5)). The effect of adjusting for these factors varied from increasing the prevalence by 26% in men in Pune to reducing it by 17% in men and women in Lexington. After adjusting for all risk factors the prevalence of a low FVC (male; female) was highest in Pune (89;92%), Ife (81;78%), Mumbai (69;75%), Nampicuan (66;70%), Manila (60;65%), Cape Town (55;36%), Srinagar (34;32%), Guangzhou (25;23%), Sousse (12;13%) and London (11;8%) and lowest in Hannover (2;3%).   Conclusions : Smoking, BMI, education and a history of TB are associated with a low FVC but do not explain the geographic variation. This is also not simply a reflection of ethnicity. We remain ignorant of the origins of one of the most powerful predictors of mortality.
Breast cancer risk assessment: How risk models can “overdiagnose” risk.
Authors: Elissa Ozanne, Brian Drohan, Kevin S. Hughes
Journal: Journal of Clinical Oncology (2013)

184 Background: Overdiagnosis is commonly defined as a diagnosis of "disease" which will never cause symptoms or death during a patient's lifetime. Similarly, overdiagnosis can also happen when individuals are given the diagnosis of being at risk for a disease, such as being at high-risk for developing breast cancer. Women can be given such a diagnosis by meeting a set of risk assessment criteria, which are often accompanied by recommended management strategies. We sought to identify the extent and consequences of overdiagnosis for individuals being at high risk for breast cancer using the American Cancer Society (ACS) guidelines for the appropriate use of Magnetic Resonance Imaging (MRI). Methods: We identified women who fit the ACS criteria in a population based sample at a community hospital. The ACS criteria mentions three risk assessment models for determining a woman’s risk, and these criteria were reviewed to determine the extent of possible overdiagnosis in this population. The expected resource utilization resulting from this overdiagnosis, and the impact on patient quality of life are extrapolated. Results: 5,894 women who received mammography screening at the study site were included. 342 (5.8%) of the women were diagnosed as high risk by at least one model. However, only 0.2% of the total study population were diagnosed as high risk by all three models. One model identified 330 (5.6%) to be at high risk, while the other two models identified many fewer eligible women (25, 0.4% and 54, 0.9% respectively). Conclusions: Using different models to evaluation the ACS criteria identifies very different populations, implying a large potential for overdiagnosis. Further, this overdiagnosis is likely to result in the outcome of screening too many women, incurring false positives and unnecessary resource utilization.
Abstract 12500: Attenuated Basal Left Ventricular Wall Contraction in Patients With Mitral Valve Prolapse Can be Secondary to Annular Dilatation With Augmented Closing Force: Pre- and Post-Operative Speckle Tracking Echocardiographic Study
Authors: Shota Fukuda, Jae-Kwan Song, Hiroshi Kuwaki, Jeong-Yoon Jang, Masaaki Takeuchi, Byung-Joo Sun, Yun-Jeong Kim, Mai Iwataki, Kyoko Otani, Masataka Eto, Hidetoshi Yoshitani, Masahito Tamura, Haruhiko Abe, Yosuke Nishimura, Robert A Levine, Yutaka Otsuji
Journal: Circulation (2014)

Introduction: Mitral annulus (MA) is generally enlarged in patients with mitral valve prolapse (MVP), which may raise MV closing force acting to shift the MV and its adjacent basal left ventricular (LV) wall toward left atrium. Hypothesis: MA dilatation with augmented MV closing force may disturb basal LV wall systolic contraction in patients with MVP. Methods: In 11 healthy controls and 34 patients with MVP, 3 apical views were obtained to assess longitudinal strain of basal- and mid-LV segments by speckle tracking analysis. The ratio of basal- to mid-LV strain value was then calculated. MA area was calculated by annulus diameters in apical 4- and 2- chamber views. MV closing force was calculated as MA area х (systolic blood pressure - 10). Results: Patients with MVP showed significantly larger MA area (5.3±1.0 vs 3.8±0.7 cm2/m2) and MV closing force (638±192 vs 431±66 mmHg•cm2/m2), and reduced basal-LV strain (-18±3 vs -21±2%) than controls (all p&lt;0.005), whereas mid-LV strain was similar between the 2 groups (-22±4 vs -22±3%, p=0.4). Consequently, significantly lower basal/middle ratio was observed in patients with MVP compared to controls (0.86±0.11 vs 0.95±0.08, p=0.004). By multivariate analysis, reduced basal/middle strain ratio was associated with augmented MV closing force (β=0.45, p=0.005) (Figure A), independent from the severity of mitral regurgitation (p=0.7). The basal/middle strain ratio significantly increased to 1.07±0.10 after annular size reduction in 5 patients with surgical MV plasty (p=0.04) (Figures B and C). Conclusions: In patients with MVP, an increase in MV closing force corresponding to MA dilatation, as opposed to the severity of mitral regurgitation, was related to attenuated basal LV wall contraction, which can be restored by MV plasty with annular size reduction.
Cytogenetic abnormalities in mesenchymal stem cells in chronic lymphocytic leukemia (CLL) patients and normal subjects
Authors: W. Ding, T. R. Knox, S. A. Smoley, D. L. Van Dyke, N. E. Kay
Journal: Journal of Clinical Oncology (2009)

e22002 Background: Mesenchymal stem cells (MSC) residing in the marrow support hematopoiesis and protect cancer cells from undergoing cell death induced by chemotherapy. Recent reports have described clonal cytogenetic abnormalities in the MSC of acute myeloid leukemia and myelodysplastic syndrome patients. To determine if cytogenetic abnormalities are present in MSC from CLL patients, we analyzed karyotypes of MSC from 13 CLL patients and 5 normal subjects. Methods: Stromal cells from marrow core biopsies of 13 CLL patients and 5 normal control subjects were isolated, cultured and confirmed as MSC based on their immunophenotype and capacity to differentiate into three lineages. After 3–4 non-stimulated cell culture passages, the karyotype was analyzed in 5–40 metaphase cells from each subject Abnormalities were considered clonal using the accepted convention of the same chromosomal gain or rearrangement in 2 or more cells or loss in at least 3 cells. For each CLL patient, interphase FISH analysis to detect the common CLL-associated abnormalities was performed on freshly isolated peripheral blood mononuclear cells (PBMC). Results: Clonal cytogenetic abnormalities of the cultured MSC were observed in 6 of 13 CLL patients (46%) and 3 of 5 control subjects (60%). The 6 CLL MSC had different clonal abnormalities than the PBMC CLL FISH studies. One CLL MSC exhibited trisomy 5, one exhibited trisomy 8, and one had monosomy X clone. One MSC had a balanced t(1;16). One MSC had a balanced t(3;12) and a del(3p), and one had a complex karyotype with 4 unbalanced rearrangements. The clonal aberrations observed in the 3 controls included a del(3p) in two cases, and in one case an inv(5) and a del(10q). There was no correlation of the chromosomal abnormalities in CLL MSC with clinical stage. Conclusions: Marrow MSC derived from CLL patients and normal subjects do show an array of cytogenetic abnormalities including clonal chromosomal abnormalities. However the genetic abnormalities found in both CLL and normal MSC could represent acquired genomic instability associated with advanced age, rather than oncogenesis associated with CLL. [Table: see text]
The prognostic relevance of response evaluation to chemotherapy by FDG-PET/CT in patients with metastatic non-small cell lung cancer.
Authors: C. Ordu, N. Alan Selcuk, C. Akosman, B. Oyan
Journal: Journal of Clinical Oncology (2011)

e18055 Background: The aim of this retrospective study was to explore the prognostic role of metabolic response to chemotherapy, determined by 18-fluorodeoxyglucose positron emission tomography (FDG-PET), in pts with metastatic non-small-cell lung cancer (NSCLC). Methods: In this study, 30 pts with metastatic NSCLC were retrospectively analyzed for the prognostic factors of survival. Disease evaluation was done with FDG-PET/CT before, 2-3 cycles after and at the end of the chemotherapy. Anatomical response was evaluated according to Response Evaluation Criteria In Solid Tumors (RECIST 1.1) and metabolic response was evaluated according to ‘PET Response Criteria in Solid Tumors (PERCIST 1.0)’. Results: During the mean follow-up of 12.2 months, 23 (77%) pts died and 7 (23%) pts are still alive. The median overall survival (OS) and progression free survival were 10.2 months (3.5-51.3) and 6 months (2.1-18), respectively. At the end of first-line chemotherapy, 10 pts (33%) achieved metabolic and anatomic response (complete or partial response). Of the 19 pts who had an interim response analysis after 2-3 cycles of chemotherapy, 3 (16%) achieved an anatomic response, while 9 (47%) achieved a metabolic response. In univariate analyses, favorable prognostic factors for OS were number of cycles of first-line chemotherapy (>4 vs. ≤4 cycles), achieving a response to chemotherapy at completion of therapy according to the PERCIST 1.0 and RECIST 1.1. Median OS was longer in pts achieving an anatomical response (11.5 mo vs. 9.6 mo, p=0.038) and metabolic response (16.6 mo vs. 7.3 mo, p=0.009) at the completion of first line therapy when compared to non-responding pts. The OS of pts with metabolic response after 2-3 cycles of chemotherapy also extended (17.2 mo vs. 6.1 mo, p=0.047). Anatomic response at interim analysis did not predict OS, probably due to few pts with anatomic response. In multivariate analyses, metabolic response after completion of therapy was the independent factor for OS. Conclusions: Metabolic response to first line chemotherapy is at least as effective as anatomic response in predicting survival. It may be an earlier prognostic factor for survival in pts with metastatic NSCLC.
Biomarkers of survival statistics (boss) analytical platform
Authors: Michael McNamara, Ian Hilgart, William Redmond
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Immunotherapy is transforming how cancer is treated, and the Providence Portland Cancer Center has played an important role in this progress through clinical trials and pre-clinical research. However, even the most efficacious of these therapies only benefit a subset of patients
Warning Symptoms Are Associated With Survival From Sudden Cardiac Arrest
Authors: Eloi Marijon, Audrey Uy-Evanado, Florence Dumas, Nicole Karam, Kyndaron Reinier, Carmen Teodorescu, Kumar Narayanan, Karen Gunson, Jonathan Jui, Xavier Jouven, Sumeet S. Chugh
Journal: Annals of Internal Medicine (2015)

Background: Survival after sudden cardiac arrest (SCA) remains low, and tools for improved prediction of patients at long-term risk for SCA are lacking. Alternative short-term approaches aimed at preemptive risk stratification and prevention are needed. Objective: To assess characteristics of symptoms in the 4 weeks before SCA and whether response to these symptoms is associated with better outcomes. Design: Ongoing prospective population-based study. Setting: Northwestern United States (2002 to 2012). Patients: Residents aged 35 to 65 years with SCA. Measurement: Assessment of symptoms in the 4 weeks preceding SCA and association with survival to hospital discharge. Results: Of 839 patients with SCA and comprehensive assessment of symptoms (mean age, 52.6 years [SD, 8]; 75% men), 430 (51%) had warning symptoms (50% of men vs. 53% of women; P = 0.59), mainly chest pain and dyspnea. In most symptomatic patients (93%), symptoms recurred within the 24 hours preceding SCA. Only 81 patients (19%) called emergency medical services (911) to report symptoms before SCA; these persons were more likely to be patients with a history of heart disease (P < 0.001) or continuous chest pain (P < 0.001). Survival when 911 was called in response to symptoms was 32.1% (95% CI, 21.8% to 42.4%) compared with 6.0% (CI, 3.5% to 8.5%) in those who did not call (P < 0.001). Limitation: Potential for recall and response bias, symptom assessment not available in 24% of patients, and missing data for some patients and SCA characteristics. Conclusion: Warning symptoms frequently occur before SCA, but most are ignored. Emergent medical care was associated with survival in patients with symptoms, so new approaches are needed for short-term prevention of SCA. Primary Funding Source: National Heart, Lung, and Blood Institute.
Does nutritional status affect treatment tolerability and efficacy in metastatic colorectal cancer (mCRC) patients? Results of a prospective multicenter study.
Authors: M. Barret, D. Malka, T. Aparicio, F. Bonnetain, C. Dalban, C. Locher, J. Sabate, S. Louafi, T. Mansourbakht, A. Attar, J. Taïeb
Journal: Journal of Clinical Oncology (2011)

e14018 Background: Malnutrition (MN) could reduce survival, tolerance and response to treatment, as well as quality of life of patients (pts) in numerous cancers. Data involving mCRC are scarce and often outdated. The purpose of this study was to evaluate, in mCRC pts, the effect of MN on survival and tolerance to modern chemotherapeutic regimens, and to identify a suitable measurement method to assess their nutritional status. Methods: In this prospective, multicentric study, demographic, oncologic and nutritional data, including various nutritional indexes already used in cancerology (Nutritional Risk Index [NRI], Prognostic Inflammatory and Nutritional Index [PINI], nutritional evaluation according to the French National Accreditation and Evaluation in Health Agency [ANAES] and weight loss during the past six months [Δ weight]) were prospectively collected in all mCRC consecutive pts for 15 days in 8 hospitals in France. Chemotherapy related toxicities were graded according to the NCI-CTC, V3.0. Survivals were calculated (Kaplan Meier) and compared (log Rank). Cox univariate models were used to study and compare the prognostic significance of the indexes. Results: 114 mCRC pts (median age: 65 [22; 92] years) participated to the study. Malnutrition occurred in 32 to 65% of pts, and severe malnutrition in 15 to 19%, depending on the score used to assess it. Severe malnutrition, as defined by a Δ weight >15% during the last 6 months, was, above all other indexes, strongly correlated to survival. It was associated with a decreased median overall survival (16.8 months [IC95% : 7.2-37.2] vs 37.2 months [30-42] in non-malnourished patients, HR= 2.03, [IC95%: 1.04-3.99], p=0.04) and to an increased rate of grade ≥2 toxicities (88% vs 56%, p=0.03) in the two months following this nutritional assessment. Conclusions: In mCRC pts, malnutrition seems to be relatively frequent and associated with reduced overall survival and increased chemotherapy-induced toxicities. Δ weight appears as a simple and reliable nutritional tool to detect and evaluate malnutrition in daily practice in this population.
Caspase activation: Stepping on the gas or releasing the brakes?
Authors: Guy Salvesen
Journal: Cancer Research (2005)

SY30-3   Apoptosis is initiated by activation of caspase-8 (death receptor pathways), or caspase-9 (some developmental, stress and genomic damage pathways). The initiators converge on the direct activation of executioner caspases-3 and 7 by limited proteolysis. Thus, a minimal two step activation cascade is at the heart of apoptosis. Despite the differing triggering events of initiator and executioner caspase activation, we hypothesize a conserved zymogen activation mechanism. This pathway is regulated by endogenous caspase inhibitors: members of the IAP family of zinc finger proteins. These proteins operate as direct fast binding active site directed inhibitors of caspases 3, 7 and 9. We hypothesize that the IAPs regulate cell death by providing a catastrophic threshold that must be exceeded for apoptosis to occur. This talk will consider the extent to which zymogen activation (stepping on the gas) and derepression of IAPs (releasing the breaks) contribute to execution of the apoptotic program.
Identification of Novel Recurrent Copy Number Variations and Regions of Copy-Neutral Loss of Heterozygosity by High Resolution Genomic Array in Pre-Treatment and Relapsed B-CLL.
Authors: Samantha JL Knight, Elham Sadighi Akha, Adele Timbs, Tariq Enver, Andrew R Pettitt, Jenny Taylor, Chris S Hatton, Anna Schuh
Journal: Blood (2009)
Induction carboplatin/paclitaxel/gemcitabine (CPG) followed by concurrent weekly carboplatin/paclitaxel (CP) and radiation therapy in unresectable stage III non small cell lung cancer (NSCLC)
Authors: F. Oniga, A. Paccagnella, S. Fasan, S. Ardit, C. Gatti, R. Biason, M. Medici, P. D'Amanzo, M. G. Ghi, O. Nascimben
Journal: Journal of Clinical Oncology (2004)

7351 Background: Preliminary results from a phase III trial in advanced NSCLC comparing CP vs CPG suggest an advantage in RR and TTP with a superior but acceptable toxicity for CPG. We used CPG as induction regimen in stage III pts. Eligibility Criteria: ECOG 0–1, unresectable stage III, measurable disease, no prior chemotherapy, informed consent. Treatment: induction CT: 2 cycles of Carboplatin AUC6, Paclitaxel 200mg/m2 day 1, and Gemcitabine 1000mg/m2days 1–8 q 21 days. Concurrent CT: Carboplatin AUC 2 and Paclitaxel 45 mg/m2 weekly with concomitant RT (60 Gy). After 40 Gy pts were revaluated for surgery, if inoperable they received definitive CT/RT. Results: From April 1998 to November 2002, 41 consecutive patients entered. Patient characteristics were: ECOG PS 0/1: 27/14(66/34%); stage IIIA/IIIB: 18/23(44/56%); median age 62 (41–77); male/female 34/7(83/17%); histology: 26(63.5%) squamous cell carcinoma, 8(19,5%) adeno, 3(7.3%) large cell and 4(9,7%) undifferentiated. The induction treatment was well tolerated with 15%/25% G3/4 neutropenia and 15%/5% G3/4 thrombocytopenia and 2 cases of febrile neutropenia. The most severe toxicities occurred in the last part of concurrent treatment: 27% grade 3 esophagitis that required dose reduction and 1 treatment interruption were observed. 2 patients had reversible grade 3 neuropathy and 1 patient died with pneumonitis 2 months after the end of the treatment. 38 pts were evaluable for response. RR to induction CPG was 47.4% (5.3% cRC). After induction CT 4 pts developed distant metastases, one suffered rapid deterioration of PS and another underwent surgery. These six pts were not submitted to the subsequent CT/RT. Overall, 31 pts. completed the planned treatment. The RR at the end was 23/38, 60.5% (95% CI, 43,3% to 75.9%), with 16.2% cRC. Median survival was 18,6 mo (95% CI, 6.88 to 30.38), with 1-, 2- and 3-yr survival of 67.7%, 47.1% and 12.6% respectively. Median TTP was 13 mo, with 1,2, and 3-yr PFS of 50.8%, 36.3% and 12.0% respectively. Conclusion: This treatment is feasible in an outpatient setting with promising survival. No significant financial relationships to disclose.
A phase II-III study comparing concomitant chemoradiotherapy (CRT) versus cetuximab/RT (CET/RT) with or without induction docetaxel/cisplatin/5-fluorouracil (TPF) in locally advanced head and neck squamous cell carcinoma (LASCCHN): Efficacy results (NCT01086826).
Authors: Maria Grazia Ghi, Adriano Paccagnella, Daris Ferrari, Paolo Foa, Maria Cossu Rocca, Elena Verri, Evaristo Maiello, Giuseppe Azzarello, Consuelo D'Ambrosio, Claudia Casanova, Monica Guaraldi, Giovanni Mantovani, Ciro Rossetto, Andrea Bonetti, Tiziana Cipani, Lucio Crino, Haralabos Koussis, Gabriella Pieri, Alessandro Gava, Irene Floriani
Journal: Journal of Clinical Oncology (2013)

6003 Background: This is the first phase III study directly comparing CRT vs CET/RT in LASCCHN. Primary endpoints of this study were to compare: 1) overall survival (OS) of induction vs. no induction arms; 2) Grade 3-4 in-field toxicity of CRT vs. CET/RT. Preliminary toxicity results of concomitant treatments (primary endpoint for this comparison) were reported at the 2012 ASCO meeting. Here we present response rate and survival data for the two concomitant treatments (CRT vs. CET/RT), irrespective of induction chemotherapy. Methods: Untreated patients with unresectable LASCCHN, stage III-IV, ECOG PS 0–1 were randomized to a 2x2 factorial design: Arm A1: CRT (2 cycles of cisplatin/5fluorouracil concomitant to RT); Arm A2: CET/RT; Arm B1: 3 cycles of TPF followed by the same CRT; Arm B2:3 cycles of TPF followed by CET/RT. Results: A total of421 patients were randomized: 261 received CRT (131 Arm A1+ 130 Arm B1) and 160 received CET/RT (80 Arm A2+ 80 Arm B2). 82% were male; median age was 60y; PS of 0 (79%) or 1 (21%). Stage was III (32%) or IV (68%). Sites of disease were: oral cavity 20%, oropharynx 57%, hypopharynx: 23%. No significant differences were observed in patients’ characteristics distribution. At a median follow-up of 32.9 months, a total of 174 deaths occurred (204 required for final OS analysis). Data on activity and efficacy of CRT and CET/RT are shown in the Table. Conclusions: No significant differences were observed in response rate, progression free survival and OS between CRT and CET/RT. Pts are still being followed-up to assess OS of induction vs. no induction arms. Clinical trial information: NCT01086826. [Table: see text]