tbuckley/cabot-search huggingface dataset:
Surgical resection for multifocal (T4 or M1) non-small cell lung cancer (NSCLC): Are the T4 and M1 designations valid?
Authors: J. L. Port, D. Becker, R. J. Korst, P. Lee, N. K. Altorki
Journal: Journal of Clinical Oncology (2005)

7219 Background: The international staging system for lung cancer designates intralobar satellites as IIIB disease and single extralobar satellites as M1 disease. We sought to determine the impact of multifocality of NSCLC on survival and its relevance to stage designation. Methods: A retrospective review of the thoracic cancer registry between 1990–2004 was performed. Patients with resected lung cancer with intralobar or extralobar satellites identified either preoperatively or in the resected specimen were included. Patients with multicentric bronchioloalveolar cancer were excluded. All patients had a lobectomy with a mediastinal node dissection. Extralobar lesions had a wedge resection or segmentectomy. Median follow-up for the entire group was 19.2 months and 21.8 months for surviving patients. Survival was calculated by the Kaplan-Meier method. A Cox proportional hazards regression model was performed to identify relevant factors only in the T4 patients, given the small numbers in the M1 group. Results: 39 patients had T4 disease (median age 67) and 16 had M1 disease (median age 71). Only six patients in each group were clinically suspected to have multifocal disease. In the T4 group 12/39 patients and in the M1 group 5/16 patients had more than 1 satellite lesion. Overall 5-year survival was 44% for patients with T4 primaries and 48% for patients with M1 disease. Patients without nodal metastases had an improved survival (T4N0, 53%, M1N0, 56%). For T4 primaries the Cox regression identified male gender (adjusted HR 3.8, 95% CI,1.2–12.3; p<0.05) as an important negative prognostic variable with a trend towards significance for nodal status (adjusted HR 1.9, 95% CI, 0.9–1.6; p=0.3). Conclusions: Patients with intralobar multifocal non-small cell lung cancer detected in the resected specimen have a more favorable prognosis after surgical resection than might be predicted by their stage IIIB designation. Five year survival rates, especially in T4N0 patients more closely approximate those with stage II NSCLC. Furthermore, a select group of patients with extralobar satellites may benefit from surgical resection. No significant financial relationships to disclose.
Single nucleotide polymorphisms and expression/amplification of HER2 in patients with breast cancer.
Authors: A. V. Boddy, N. Cresti, D. Jamieson, M. Pinkilgton, M. W. Verrill
Journal: Journal of Clinical Oncology (2011)

1523 Background: Human Epithelial growth factor Receptor 2 (HER2) gene is amplified and/or over-expressed in about 20% of breast cancers. Two high-frequency, coding, non-synonymous Single Nucleotide Polymorphisms (SNPs) have been described in the HER2 gene. The first (Ile655Val) is related to a residue in the trans-membrane domain, the second (Ala1170Pro) induces an amino acid change in the intra-cellular carboxyl-terminal tail. We aimed to investigate the potential influence of these SNPs on the amplification/over-expression of HER2 in breast tumours. Methods: Breast cancer patients with known HER2 status in tumours were selected in an outpatient clinic. HER2 status (positive or negative) was assessed according to international standard criteria using Immuno-Histo-Chemistry and/or Fluorescent In Situ Hybridization. Germ-line DNA was extracted from peripheral nucleated blood cells and genotyping of the two SNPs was performed by fluorogenic 5' nuclease assay using the endogenous 5' nuclease activity of AmpliTaq Gold DNA polymerase. Results: Two hundred and ninety three patients were recruited in the study. Forty seven per cent of tumours were HER2-positive and 53% were HER2-negative. The genotypes were in Hardy-Weinberg equilibrium and minor allele frequency for Ile655Val and Ala1170Pro were respectively 21% and 29%. There was no correlation between Ile655Val genotype and HER2 status (proportions of HER2-positive tumours among Ile homozygous patients and carriers of the Val allele were respectively 46% and 48%, p=0.705). However, when the Ala1170Pro SNP was considered, the proportion of HER2-positive tumours was significantly higher among carriers of the Pro allele than it was among Ala homozygous patients (56% vs 38%, p=0.002). Conclusions: Our preliminary results suggest that the Ala1170Pro SNP in the HER2 gene may have a role in the development of HER2-positive breast tumours. Validation of this finding in a different population of patients, along with evaluation of allele-specific amplification in tumour samples is warranted.
Sequential cisplatin/VM-26 and vincristine/cyclophosphamide/doxorubicin in metastatic neuroblastoma: an effective alternating non-cross-resistant regimen?
Authors: J L Bernard, T Philip, J M Zucker, D Frappaz, A Robert, G Margueritte, A Boilletot, N Philippe, P Lutz, H Roche
Journal: Journal of Clinical Oncology (1987)

We report the results of a French multicentric pilot study of remission induction therapy in metastatic neuroblastoma. Thirty-five successive unselected patients entered the study over 1 year and were treated by alternating sequences of cisplatin/VM-26 (PE) and vincristine/cyclophosphamide/doxorubicin (CADO). Three courses of each sequence were delivered. Disease reevaluation was extensive, with special focus on bone marrow status. Using strict criteria, 24 patients (68%) achieved a good partial response (GPR), which comprised normalization of bone marrow, and ten (28%) achieved a partial response (PR), and one progressed. The overall response rate was 96%. Thirty-two patients underwent surgery, and complete macroscopic removal of the primary was achieved in 21 (65%). After completion of induction and surgery, six patients (17%) were in complete remission (CRm), without evidence of any residual disease; nine (26%) were in very good partial remission (VGPRm; same as CRm except persistence of nonpathologically evaluable improved bone scan), and 19 (51%) were in partial remission (PRm). Toxicity was acceptable, and no treatment-related deaths occurred. These results show no substantial improvement compared with those previously reported with similar but nonalternating regimens. We advocate a two-category concept (response, remission) to describe initial therapy results in metastatic neuroblastoma and emphasize the need to assess bone marrow by an extensive evaluation.
A comparison of ECOG PS assigned and objectively measured physical activity.
Authors: J. M. Walsh, J. M. Hussey, M. J. Kennedy, D. M. O' Donnell
Journal: Journal of Clinical Oncology (2010)

e19526 Background: The ECOG PS scale is a widely used measure of functional status in oncology and is a good predictor of prognosis and treatment benefit. However, the relationship between the physical endpoints of this scale and objective measures of physical activity has not been formally investigated. Methods: Eighty-nine patients (10 male) with a median age of 56 (range 36-81years) and diagnosis of breast (59), thoracic (7), colorectal (12), gynaecological (9) and prostate (2) cancers consented to participate. Institutional ethics approval was obtained. Accelerometer data (RT3), self-report physical activity data (International Physical Activity Questionnaire-IPAQ) and fatigue data (Brief Fatigue Inventory-BFI) were collected for an average of 6 days in the home before pretreatment assessment. RT3, (IPAQ) and BFI values were compared to the ECOG PS score assigned by the treating oncologist. Results: A large proportion of time was spent sedentary regardless of ECOG PS level assigned (Table). Significant inverse correlations were found between percentage time “up and about” (RT3) and ECOG PS score assigned (Spearman's ρ = −0.33, p = 0.002) and between ECOG PS and self-report level of activity (IPAQ) (ρ = −0.33, p = 0.003). A significant positive correlation between estimated fatigue levels (BFI) and ECOG PS (ρ = 0.38, p = 0.001) was found. Conclusions: Although significant associations were found between ECOG PS assigned and objectively measured physical activity, self-report activity and fatigue levels, patients and physicians overestimated physical activity. Patients in all groups were sedentary, spending less than 50% of waking hrs “up and about”—usually used as the cutoff between ECOG 2 and 3. Objective measures of physical activity may add to the assessment for treatment and clinical trial inclusion. ECOG PS assigned and mean (SD) percentage time in spent sedentary hours as a percentage of waking hours ECOG score and definition Number of patients Mean (SD) percentage time of waking hours spent sedentary 0 Unrestricted in physical activity (n = 25) 54.4 (18.4) 1 Strenuous activity restricted, able light work (n = 53) 63.1 (16.4) 2 Up and about > 50% waking hrs (n = 6) 70.1 (16.9) 3 Confined to bed or chair > 50% waking hrs (n = 5) 76.1 (7.3) No significant financial relationships to disclose.
Expression of <i>BAG-1</i> in Invasive Breast Carcinomas
Authors: Shou-Ching Tang, Nadine Shaheta, Garry Chernenko, Mohmoud Khalifa, Xikui Wang
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The purpose of this study was to retrospectively evaluate the expression of BAG-1 in invasive breast carcinomas. The intensity and subcellular distribution of BAG-1 expression was correlated with conventional prognostic factors and with disease-free and overall survival. PATIENTS AND METHODS: One hundred forty patients diagnosed with invasive breast cancer in St. John's, Newfoundland, between 1986 and 1996 were included in the study. The median follow-up of the study was 8 years. Expression of BAG-1 was determined by immunohistochemical staining of paraffin-embedded breast tumor tissues. RESULTS: Of the 140 breast carcinomas examined, 77.1% were positive for BAG-1 expression. Except for differentiation, no correlation was observed between BAG-1 expression and conventional prognostic factors such as age, histology, stage, and estrogen and progesterone receptor status. In multivariate analysis, BAG-1 expression was significantly associated with shorter disease-free (P = .0052) and overall survival (P = .0033). Patients whose tumors expressed nuclear BAG-1 tended to have a shorter disease-free (63 v 84 months; P = 0.4493) and overall (69 v 99 months, P = .1009) survival. CONCLUSION: BAG-1 is overexpressed in the majority of invasive breast carcinomas. Although BAG-1 did not correlate with conventional prognostic factors, its overexpression, especially the nuclear expression, may be associated with a shorter disease-free and overall survival. Our preliminary data strongly indicate that further investigation is warranted to define the role of BAG-1 as an independent prognostic factor in patients with newly diagnosed breast cancer.
Phase II trial of vinblastine plus nifedipine (VN) in patients with advanced renal cell carcinoma (RCC)
Authors: G. Schwartsmann, F. Medina da Cunha, L.A. Silveira, G. Salgado, M.S. Thereza, J. Vinholes, P. Preger, F. Segal
Journal: Annals of Oncology (1991)
&lt;italic&gt;In Vitro&lt;/italic&gt; Growth of Normal and Leukemic Human Bone Marrow
Authors: Clarence H. Brown, III, M.D., Paul P. Carbone, M.D.
Journal: JNCI Journal of the National Cancer Institute (1971)

Human bone marrow grown in an enriched methylcellulose culture medium and stimulated in vitro by the supernatant from a monolayer culture of human embryo kidney cells produced granulocytic, mononuclear, and mixed cell colonies. Bone marrow from normal individuals regularly formed from 8–48 colonies per 2 × 105 marrow nucleated cells (immature nucleated cells), whereas marrow from patients with acute leukemia (myelocytic and lymphocytic) in relapse did not grow to form colonies. Marrow from patients with acute leukemia in remission and from patients with chronic myelocytic leukemia formed normal numbers of granulocytic and mononuclear cell colonies. Two patients with acute myelocytic leukemia in remission, but with granulocytic hyperplasia in the marrow, exhibited excessive colony production. This technique may help assess the status of disease in patients with acute leukemia.
NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung
Authors: Ismini Lasithiotaki, Ioannis Giannarakis, Eliza Tsitoura, Katerina D. Samara, George A. Margaritopoulos, Christiana Choulaki, Eirini Vasarmidi, Nikolaos Tzanakis, Argyro Voloudaki, Prodromos Sidiropoulos, Nikolaos M. Siafakas, Katerina M. Antoniou
Journal: European Respiratory Journal (2016)

In this study we investigated the implication of NLRP3 inflammasomes in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis–usual interstitial pneumonia (RA-UIP). NLRP3 inflammasome activation at baseline and following stimulation with lipopolysaccharide/ATP was evaluated by measuring interleukin (IL)-1β and IL-18 levels released in the bronchoalveolar lavage fluid (BALF) fluid and by cultures of BALF cells. IL-1β and IL-18 levels were significantly elevated in the BALF and BALF macrophage cultures from RA-UIP patients, consistent with pre-existing inflammasome activation in these patients. In contrast, in IPF, BALF levels of IL-1β were significantly less elevated relative to RA-UIP and IL-18 was lower than controls. Furthermore, upon inflammasome stimulation, IPF BALF macrophage cultures failed to upregulate IL-1β and partly IL-18 secretion, in contrast to controls, which showed robust IL-1β and IL-18 upregulation. Interestingly, RA-UIP BALF cell cultures treated with lipopolysaccharide/ATP showed a potent stimulation of IL-18 secretion but not IL-1β, the latter being already elevated in the unstimulated cultures, while examination of the intracellular IL-1β levels in RA-UIP BALF cells upon NLRP3 inflammasome stimulation showed a significant upregulation of IL-1β suggesting the NLRP3 pathway could be further activated. Taken together, our results suggest distinct inflammasome activation profiles between autoimmune and idiopathic lung fibrosis.
Ras Analysis of the Planet Study: Phase Ii Trial of Panitumumab (P) Plus Folfox4 or Folfiri in Subjects with Wild-Type (Wt) Kras Colorectal Cancer (Crc) and Liver-Limited Disease (Lld)
Authors: A. Abad, B. Massuti Sureda, C. Grávalos, P. Escudero, C. Guillen-Ponce, A. Gómez, M.J. Safont, J. Gallego Plazas, J. Sastre, C. Pericay, R. Dueñas, C. López, F. Losa, M. Valladares-Ayerbes, E. González Flores, L. Robles Díaz, L. Layos, A. Carrato, E. Aranda
Journal: Annals of Oncology (2014)
Anti-proliferative activity of CC-5013 in 5q- myelodysplastic syndrome (MDS) and acute lymphocytic leukemia (ALL) cell lines
Authors: A. K. Gandhi, S. Naziruddin, D. Verhelle, H. Brady, P. Schafer, D. Stirling
Journal: Journal of Clinical Oncology (2004)

6618 Background: Phase I/II studies of CC-5013 (Revimid™) in MDS have shown erythropoietic and cytogenetic responses, especially among 5q- patients. The 5q deletion is a primary chromosomal change among various hematological malignancies including MDS, and it affects expression of genes on the locus including the tumor suppressor interferon regulatory factor- 1 (IRF-1). The activity of CC-5013 was tested in various 5q mutant MDS, AML, and ALL cell lines to assess associations between CC-5013 efficacy and genetic alterations. Methods: The MDS cell line MUTZ-1, AML cell lines KG-1 and UT-7, and ALL cell line Loucy, along with control cell lines Jurkat and MUTZ-5 were tested for sensitivity to CC-5013 using 3H-thymidine incorporation, annexinV and propidium iodide (PI) staining. IRF-1 expression and CD19 or EPO receptor-induced Akt phosphorylation were analyzed by western blot. Gene expression was analyzed using the Affymetrix U133 GeneChip. Results: The cell proliferation IC50 values for MUTZ-1, KG-1, and Loucy cells are 2.5, 66 and 100 μM respectively. The MUTZ-5, UT-7 and Jurkat cell line IC50s were well above 100 μM. Cell cycle analysis indicates CC-5013 causes G0/G1 arrest in the sensitive cell lines. In MUTZ-1 cells, there is a 3–8% increase in apoptosis with CC-5013. MUTZ-1 and KG-1 cells express less IRF-1 protein than UT-7 cells, consistent with their 5q status. CC-5013 inhibited Akt phosphosphorylation in response to CD19 or EPO stimulation of MUTZ-1 cells. Genes regulated by CC-5013 in MUTZ-1 cells include genes involved in cell adhesion and a metalloprotease. Conclusions: CC-5013 has preferential anti-proliferative activity against 5q mutant cell lines. This inhibition appears to be due to G0/G1 arrest with a small apoptotic component, and correlates with IRF-1 expression. In MUTZ-1 cells, CC-5013 interferes with growth signals via Akt and increases expression of genes found at the 5q locus. These molecular events may explain the sensitivity of 5q mutant hematopoietic tumor clones to CC-5013-induced toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene Corp. Celgene Corp. Celgene Corp.
Randomized trial of standard dose to a higher dose prophylactic cranial irradiation (PCI) in limited-stage small cell cancer (SCLC) complete responders (CR): Primary endpoint analysis (PCI99–01, IFCT 99–01, EORTC 22003–08004, RTOG 0212)
Authors: C. Le Pechoux, M. Hatton, A. Kobierska, F. Guichard, A. Dunant, S. Senan, R. Jones, R. Arriagada, A. Wolfson
Journal: Journal of Clinical Oncology (2008)

LBA7514 Background: Use of PCI improves survival in patients (pts) with SCLC. The optimal PCI dose for limited-stage SCLC is not known but a meta-analysis suggested that the incidence of brain metastases (BM) might be reduced at higher PCI doses. This trial compared the effect of standard versus higher PCI doses on BM incidence. Methods: Pts with limited-stage SCLC in CR were randomised to standard (25 Gy/10 fractions/12 days) or higher PCI dose (36 Gy) delivered using either conventional (18 fractions/24 days) or accelerated hyperfractionated radiotherapy (24 twice-daily fractions/16 days). The main endpoint was BM incidence. Secondary end- points were survival, quality of life (QoL) and late sequelae assessed yearly. 700 pts were required to show an absolute decrease of 15% BM incidence at 2 years (power 90%, type I error 5%, 2-sided logrank test). Results: Between September 1999 to December 2005, 720 pts (360 in each arm) were randomised. Median age: 60 years. Males: 64% pts. At baseline, all had brain imaging and 93% neurological and QoL evaluation. 94% pts received the allocated PCI dose. No differences in toxicity were observed (Le Pechoux et al. J Thor Onc 2007). Median follow-up: 38 months. 2-year rates and hazard ratios (HR) (95% confidence interval) are given below. The results do not change with sensitivity and competing risk analyses. Conclusion: This study shows a non-significant lower incidence of brain metastases after higher-dose PCI. Besides the hypothesis of a false positive result, the increased chest relapse and mortality rates in the higher PCI dose arm are so far biologically unexplained. PCI with a total dose of 25 Gy remains the standard of care in limited-stage SCLC. Supported by Association pour la Recherche sur le Cancer, Programme Hospitalier de Recherche Clinique Events Standard dose Higher dose HR p Brain metastasis 30% (25%-36%) 24% (18%-30%) 0.77 (0.55-1.08) 0.13 Other metastases 41% (35%-47%) 42% (37%-48%) 1.19 (0.93-1.52) 0.16 Chest relapse 40% (34%-46%) 48% (42%-54%) 1.32 (1.04-1.69) 0.02 Overall survival 42% (37%-48%) 37% (32%-42%) 1.22 (1.02-1.47) 0.03 No significant financial relationships to disclose.
A clinical trial simulation study of a new pediatric phase I trial methodology: The rolling six design
Authors: J. Skolnik, B. Jayaraman, D. Patel, E. O'Connor, J. S. Barrett, P. C. Adamson
Journal: Journal of Clinical Oncology (2007)

9564 Background: Phase I cancer trials have traditionally used the 3+3 study design in which cohorts of three patients at a time are enrolled. The study is suspended to accrual with every 3rd patient, and again suspended to replace inevaluable patients. As the pediatric phase I starting dose is based on adult phase I safety data, we hypothesized that pediatric study timelines could be shortened without increasing risk using a novel rolling six design, in which up to 6 patients are concurrently enrolled per dose level. Methods: A trial simulation approach comparing the standard 3+3 design to the rolling six design was performed. Discrete time events (accrual/enrollment, evaluation and/or time to dose limiting toxicity (DLT) or inevaluability) with outcome probabilities (DLT/inevaluability) assigned to each subject based on historical data from phase I pediatric oncology trials. The probability of DLT was a function of dose level and varied distributions were used to assign discrete time elements. Metrics for study efficiency (time to complete study, total number of patients required) were determined for each design. Simulated trials and decision rule logic were coded using PC/Windows SAS v9.1. Results: The rolling six design outperformed the 3+3 design for the most relevant metrics. Average (±SD) time to study completion was 373±90 days vs. 431±98 days and the total number of patients required was 20±5 vs. 17±4 for the rolling six vs. 3+3 designs, respectively. There was no difference in the number of DLTs per study (3±1) between designs. Conclusions: The rolling six design is predicted to shorten pediatric phase 1 study timelines and will be tested prospectively in upcoming COG phase I trials. No significant financial relationships to disclose.
Abstract P374: Short-term Weight Loss Patterns and Physical and Psychological Predictors within a Randomized Trial
Authors: Veronica Yank, Lan Xiao, Lisa Goldman Rosas, Randall S Stafford, Sandra Wilson, Qiwen Huang, Jun Ma
Journal: Circulation (2012)

Objective To examine weight loss patterns and their baseline predictors among participants in a Diabetes Prevention Program-based group lifestyle intervention. Methods Overweight/obese participants in the intensive intervention arm (n=72) of an ongoing 3-arm randomized weight loss trial were weighed at each of 12 weekly classes. Cluster analysis grouped participants with similar patterns of 12-week weight loss. Bivariate analysis identified candidate baseline predictor variables (P&lt;0.1), which were then entered into a stepwise multinomial logistic regression analysis to identify variables significantly associated with greater weight loss patterns. Results Participants had a mean age of 55.0 yrs (SD 10.8); 49% were female, 79% Non-Hispanic White, and 97% college educated; and 58% earned &gt;$125,000/yr. Mean Body Mass Index was 31.9 kg/m 2 (SD 5.2), 56% had pre-diabetes, and 90% had metabolic syndrome. Cluster analysis identified three weight loss patterns (Figure): modest &amp; delayed (G1: n=15; 21%); moderate &amp; steady (G2: 43; 60%); and substantial &amp; early (G3: 14; 19%). Only participants in G2 and G3 had significant weight loss. Candidate predictor variables included sex, physical activity, physical function, family/friend encouragement for dietary change, obesity-related problems, depression symptoms, and body image dissatisfaction. On stepwise logistic analysis comparing G2 and G3 vs. G1, greater weight loss patterns were associated with higher physical activity (standardized β=0.62 (95% CI 0.09, 1.14), P=0.01) and physical function (0.47 (-0.04, 0.99), P=0.05), fewer obesity-related problems (-0.48 (-1.03, 0.07), P=0.09), and less friend encouragement for dietary change (-0.79 (-1.37, -0.22), P=0.003). Conclusion We identified 12-week weight loss patterns and baseline variables that may be important predictors of response to an evidence-based group lifestyle intervention. Friend encouragement for dietary change may have a more complex relationship to weight loss than suggested by prior research. Funding(This research has received full or partial funding support from the American Heart Association, National Center)