tbuckley/cabot-search huggingface dataset:
Updated results at 6 year of the GERCOR C96.1 phase III study comparing LV5FU2 to monthly 5FU-leucovorin (mFufol) as adjuvant treatment for Dukes B2 and C colon cancer patients
Authors: T. Andre, E. Quinaux, C. Louvet, E. Gamelin, O. Bouche, E. Achille, P. Piedbois, N. Tubiana-Mathieu, M. Buyse, A. de Gramont
Journal: Journal of Clinical Oncology (2005)

3522 Background: Results of the C96.1 study showed no difference in terms if 3-yr DFS between LV5FU2 and mFufol, nor in terms of treatment duration, while tolerance favoured LV5FU2 [J Clin Oncol 2003;21:2896–2903]. We report here the updated results for DFS and the OS data with 6 yr follow-up. LV5FU2 for 6 months was retained as the standard arm for the MOSAIC study [N Engl J Med 2004, 350;23:2343–51]. Methods: between 7/96 and 11/99, 905 patients (pts) with Dukes B2 (43%) and C (57%) colon cancer were enrolled. A 2x2 factorial design randomisation was used to allocate pts to either 24 or 36 weeks of either monthly 5FU-LV (d,L-LV 200 mg/sqm or L-LV 100 mgsq/m 15 min iv infusion followed by 5FU 400 mg/sqm 15 min iv infusion, d1–5 q4 wk) or LV5FU2. Results: with a median follow-up time of 5.9 yr, there were no statistically significant differences between mFufol and LV5FU2 in terms of DFS (149 vs 148 events, HR:1.015; 95%CI 0.809–1.274; p=NS) and OS (103 vs 99 events, HR:1.015; 95%CI 0.750–1.302; p=NS). DFS and OS at 5 years were respectively 67% and 80% in both schedule arm. No statistical difference was observed between 24 or 36 months of chemotherapy. For the whole population, 245 pts relapsed with distant metastasis, 10 presented local relapse alone and 5 second colon or rectal cancer alone. Median OS from metastatic relapse was 24 months. Characteristics of relapsing pts as well as further chemotherapies administered (mostly based on oxaliplatin-5FU and CPT11–5FU) will be detailed during the meeting. Conclusions: DFS and OS were not statistically different between treatment groups and treatment durations. These data confirm the value of LV5FU2 as reference treatment for the MOSAIC study. The 24 months median OS for patients with metastatic relapse, related to the use of new actives drugs, could impair a too early analysis of OS in adjuvant treatment of colon cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche, sanofi-aventis Lilly Oncology, sanofi-aventis
The Effects of Live Attenuated Influenza Vaccine on Nasopharyngeal Bacteria in Healthy 2 to 4 Year Olds. A Randomized Controlled Trial
Authors: Valtyr Thors, Hannah Christensen, Begonia Morales-Aza, Ian Vipond, Peter Muir, Adam Finn
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Viral infections of the upper respiratory tract may influence the commensal nasopharyngeal bacteria. Changes in the bacterial niche could affect transmission dynamics. Attenuated vaccine viruses can be used to investigate this empirically in humans.Objectives: To study the effects of mild viral upper respiratory infections on nasopharyngeal bacterial colonization using live attenuated influenza vaccine (LAIV) as a surrogate.Methods: We used trivalent LAIV to evaluate the effects of viral infection on bacterial carriage and density of Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, and Staphylococcus aureus. A total of 151 healthy children were randomized 1:1 to receive the vaccine starting either at recruitment (n = 74) or 28 days later (n = 77) in a stepped wedge fashion, allowing comparisons between recipients and nonrecipients as well as whole-group comparisons pre- and postvaccination. Bacterial carriage and density were determined using quantitative polymerase chain reaction assays.Measurements and Main Results: A total of 151 children were recruited, 77 in the LAIV group and 74 in the control group. LAIV recipients (n = 63 analyzed) showed an apparent transient increase in H. influenzae carriage but no further significant differences in carriage prevalence of the four bacterial species compared with controls (n = 72 analyzed). S. pneumoniae density was substantially higher in vaccine recipients (16,687 vs. 1935 gene copies per milliliter) 28 days after the first dose (P < 0.001). Whole-group multivariable analysis (prevaccine, after one dose, and after two doses) also showed increases in density of other species and H. influenzae carriage prevalence.Conclusions: In the absence of any safety signals despite widespread use of the vaccine, these findings suggest that bacterial density, and thus transmission rates among children and to people in other age groups, may rise following attenuated influenza infections without associated clinical disease. LAIV could therefore be used as an experimental tool to elucidate the dynamics of transmission of nasopharyngeal bacteria.
Direct comparisons of peripheral T-cell lymphoma with diffuse B-cell lymphoma of comparable histological grades--should peripheral T-cell lymphoma be considered separately?
Authors: A L Cheng, Y C Chen, C H Wang, I J Su, H C Hsieh, J Y Chang, W S Hwang, W C Su, T W Liu, H F Tien
Journal: Journal of Clinical Oncology (1989)

Peripheral T-cell lymphoma (PTCL) forms a morphologically heterogeneous group of non-Hodgkin's lymphomas (NHL) with distinct immunophenotypes of mature T cells. Progress has been slow in defining specific clinicopathological entities to this particular group of NHL. In order to elucidate the specific characteristics of PTCL, a direct comparison of PTCL with a group of diffuse B-cell lymphomas (DBCL) was performed. Between June 1983 and December 1987, we studied 114 adults with NHL, using a battery of immunophenotyping markers. Adult T-cell leukemia/lymphoma, lymphoblastic lymphoma, mycosis fungoides/Sézary syndrome, follicular lymphoma, well-differentiated lymphocytic lymphoma, and true histiocytic lymphoma were excluded from this study since these are distinct clinicopathologic entities with well-recognized immunophenotypes. Of the remaining 75 patients, 70 who had adequate clinical information were analyzed, and of these, 34 were PTCL and 36 were DBCL. Classified according to the National Cancer Institute (NCI) Working Formulation (WF), 68% of PTCL and 31% of DBCL were high-grade lymphomas. Clinical and laboratory features were similar, except PTCL had a characteristic skin involvement and tended to present in more advanced stages with more constitutional symptoms. Induction chemotherapy was homogeneous in both groups, and complete remission rates were 62% for PTCL and 67% for DBCL. Patients with DBCL had a better overall survival than patients with PTCL, but the survival benefit disappeared after patients were stratified according to intermediate- or high-grade lymphoma. A subgroup of PTCL patients who had received less intensive induction chemotherapy was found to have a very unfavorable outcome. We conclude that (1) PTCL follows the general grading concept proposed in WF classification; (2) within a given intermediate or high grade, PTCL and DBCL respond comparably to treatment; (3) the intensity of induction chemotherapy has a crucial impact on the outcome of PTCL patients; and (4) with a few exceptions, the clinical and laboratory features of PTCL and DBCL are comparable.
Lapatinib or placebo plus letrozole as preoperative treatment of hormone receptor-positive HER2-negative operable breast cancer. Preliminary report of safety and activity of the double-blind randomized phase IIb LET-LOB study
Authors: A. Frassoldati, V. Guarneri, A. Bottini, K. Cagossi, L. Cavanna, G. Bisagni, G. Jovic, F. Piacentini, C. Oliva, P. F. Conte
Journal: Journal of Clinical Oncology (2008)

623 Background: Crosstalk between hormone- and EGFR-family pathways is a possible cause of resistance to aromatase inhibitors (AI), as suggested by the increased expression of HER2, EGFR and MAPK in long-term estrogen-deprived breast cancer (BC) cells. Lapatinib (Lap) is an orally active small molecule inhibitor of EGFR and HER2 tyrosine-kinases. Combination of an AI and Lap in ER+/HER2- tumors could avoid the onset of resistance due to early stimulation of EGFR and HER2 pathways. To evaluate these effects, we designed an international multicenter phase IIb double-blind randomized trial in ER+/HER2- BC pts candidates for hormone neoadjuvant therapy. Methods: Postmenopausal pts with stage II-IIIa, HR+/HER2- BC are randomized to letrozole (Let; 2.5 mg/d) plus lapatinib (Lap; 1,500 mg/d) or placebo (P), given continuously for 24 weeks before surgery. Activity (with ultrasonographyc, US) and cardiac safety (with echocardiogram) assessment are performed after 12 and 24 weeks. Tissue biomarkers of hormone and EGFR-family related pathways are analyzed before and after treatment. An initial sample size of 42 pts will be enrolled assuming a 50% chance of cOR with Let+P and a 40% increase in cOR with the Let+Lap (equal to 70% absolute cOR). Additional 48 pts will be treated in case we observe 20 cOR in the first cohort (Simon's design). Results: 19 Italian and European centers are participating in the study. From April 2007, 28 pts have been randomized, and 15 pts were treated for at least 3 months (mo). Six pts completed the six mo treatment, and 4 underwent surgery. At diagnosis, mean US tumor size was 2.87 cm (range 2–6 cm). All pts were ER+ (73% ER+/PR+) and HER2-. No significant decrease in mean LVEF was observed at the 3-mo evaluation (60.9%-61.5%). No grade 3–4 toxicities were reported. A 34% absolute reduction in median longest US tumor diameter has been observed after 3 mo (15 pts) and 65% reduction has been obtained at 6 mo (6 pts). Updated blinded safety and activity results will be presented. Conclusions: The combination of Lap or P with Let in ER+/HER2-operable breast cancer was safe, without any early cardiac toxicity, and induced clear tumor shrinkage. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
Abstract 12706: Exercise Physiology and Determinants of Exercise Capacity in Patients With Fontan Circulation
Authors: Kei Inai, Eriko Shimada, Mikiko Shimizu, Tetsuko Ishii, Hirohumi Tomimatsu, Tokuko Shinohara, Toshio Nakanishi
Journal: Circulation (2012)

BACKGROUND: Precise mechanisms of limitations of cardiac performance and exercise intolerance in patients with Fontan physiology are not fully understood. OBJECTIVES: We assessed hemodynamics durin...
Phase II trial of irinotecan plus cisplatin with concurrent thoracic radiotherapy (TRT) in patients with previously untreated locally advanced non-small cell lung cancer (NSCLC)
Authors: M. Fukuda, H. Soda, Y. Nakamura, M. Fukuda, A. Kinoshita, S. Nagashima, H. Nakano, H. Yamaguchi, S. Kohno, M. Oka
Journal: Journal of Clinical Oncology (2007)

18071 Background: The combined modality of the third generation new agent plus cisplatin with concurrent TRT is considered ideal for locally advanced non-small cell lung cancer. However, it is difficult to conduct because of severe toxicities. Methods: Patients fulfilling the following eligibility criteria were enrolled: previously untreated, good performance status (PS 0–2), age &lt;75, stage III, and adequate organ function. The patients received irinotecan 60 mg/m 2 i.v. on days 1, 8 and 15, and cisplatin 80 mg/m 2 i.v. on day 1 in the first group. The doses were reduced to 50 and 60 mg/m 2 in the second group, respectively. Two cycles of chemotherapy were repeated every 4 weeks. Thoracic radiotherapy of 2 Gy/day commenced on day 2 of each chemotherapy cycle, with 28 and 32 Gy administered in the first and second cycles, respectively. Primary endpoint and objective sample size were response rate and 45 patients, respectively. Results: Fifty patients were eligible and 48 (16 in the 1st, 32 in the 2nd group) patients were assessable for response, toxicity and survival. The overall response (OS) was 83% (95% confidence interval (CI), 70–93%). Grade 4 leukopenia, neutropenia, grade 3 or 4 diarrhea, pneumonitis, esophagitis and fatigue occurred in 21%, 48%, 19%, 10% and 19%, respectively. The median time to progression was 8.2 months. The median overall survival time (MST), and the 2- and 5-year survival rates were 20.1 months, 47.1% and 17.1%, respectively. In subgroup analysis, the OS of 1st and 2nd groups were 75% and 88% (not significant), respectively. The MST of 1st and 2nd groups were 13.1 and 33.4 months, respectively, and significant favor with 2nd group (p=0.011). The execution rates of irinotecan on day 15 were significant higher in 2nd (22% vs. 48%) groups (p=0.032), and the survival separated by execution times on day 15 were significantly favor with higher execution time group (p=0.026). Conclusions: This therapy is active and further investigations are warranted at the 2nd group dose level. High execution of chemotherapy on day 15 may be important for the achievement of concurrent chemoradiotherapy. No significant financial relationships to disclose.
Oncolytic edmonston-strain measles virus as a novel therapeutic agent for non-small cell lung cancer.
Authors: M. Patel, B. A. Jacobson, A. A. Sadiq, A. Raza, S. J. Russell, R. A. Kratzke
Journal: Journal of Clinical Oncology (2010)

e13536 Background: Oncolytic viruses are emerging as a novel therapy for many tumors. Attenuated measles virus (MV) is particularly promising due to its broad antitumor efficacy and track record of safe use in humans as a vaccine. Non-small cell lung cancers (NSCLC) overexpress the measles receptor, CD46, and therefore, we hypothesized that MV could be an effective therapy for NSCLC. Methods: H2009, H520, H522, H2030, A549, and H460 NSCLC cell lines and immortalized human bronchial epithelial cells (HBEC) were used for all experiments. Measles virus expressing GFP (MV-GFP) was used for all experiments. Proliferation assays were done by treating cells with MV-GFP or control at the desired multiplicity of infection (MOI) with and without 25nM gemcitabine for 72 hours. Cell number was assessed by counting viable cells using Trypan Blue exclusion method. Cells were assayed for the induction of apoptosis using poly(ADP) ribose polymerase (PARP) cleavage assay and Annexin V staining using the Guava-Nexin Assay. The role of 5'-mRNA cap dependent translation in NSCLC susceptibility to MV infection was assessed using 5' 7mGTP Sepharose pulldown assay. Results: For all the NSCLC cell lines tested, MV-GFP treatment resulted in cytopathic effect within 24 hrs. All cell lines demonstrated a dose-dependent decrease in proliferation with MV treatment. 4/6 cell lines demonstrated an IC50 of MOI <0.1 while for HBEC cells, the IC50 was >0.5 MOI (p value <0.05 HBEC v. NSCLC cells for all MOI). Furthermore, cell death was mediated by apoptosis induction as indicated by both PARP cleavage assay as well as Annexin V staining in all cell lines tested. Combination therapy of MV-GFP with gemcitabine resulted in greater cell kill than with either alone in H2009 and H522 cells (p<0.05). Finally, MV-GFP treatment resulted in inhibition of binding to the 5'mRNA cap 48 to 72 hours after infection for all cell lines tested. Conclusions: MV has potent antiproliferative activity against NSCLC cells and sensitizes them to the effect of gemcitabine. One possible mechanism of its cytotoxicity is inhibition of cap-depedent protein translation. MV should be developed further as a novel therapeutic agent for NSCLC. No significant financial relationships to disclose.
A1.11 Anti-type II collagen immune complex-induced granulocyte reactivity is associated with joint erosions in ra patients with anti-collagen antibodies
Authors: Vivek Anand Manivel, Azita Sohrabian, Marius C Wick, L Håkansson, Amir Elshafie, Johan Rönnelid
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> RA patients with anti-collagen antibodies (anti-CII) are characterised by acute RA onset (Mullazehi et al, ARD 2007) and early joint erosions (Mullazehi et al ART 2012), as well as increased production of TNF by peripheral blood mononuclear cells from anti-CII immune complexes (IC) in vitro (Mullazehi et al A&amp;R 2006). We have previously (abstract EWRR 2012) shown that polymorphonuclear neutrophil granulocytes (PMN) react towards anti-CII IC. The aim was to investigate whether functional PMN responses are associated with the clinical acute onset RA phenotype. <h3>Methods</h3> A set of 72 baseline patient sera (24 anti-CII positive, 24 anti-CII negative/RF positive and 24 anti-CII negative/RF negative) was chosen from a clinically well-characterised RA cohort with 2-year radiological follow-up (Larsen score). PMN and PBMC isolated from healthy donors were stimulated with anti-CII IC prepared with sera from the patients. PMN expression of CD16 and CD66b were measured by flow cytometry, and PMN production of myeloperoxidase (MPO) and IL-17, and PBMC production of TNF was measured with ELISA. <h3>Results</h3> CD66b, MPO, and TNF were significantly up-regulated and CD16 was significantly down-regulated by IC made with anti-CII positive sera. Even anti-CII low positive sera were able to impact the expression of CD16, CD66b and TNF. There was linear correlation to CD16, CD66b, MPO and TNF production in relation to anti-CII levels (r = -0.3152, 0.6755, 0.2532 and 0.5846, respectively). CD16 correlated with early joint erosion (p = 0.024, 0.034, 0.046 at baseline, one and two years) and CD66b was associated with changes in joint erosion (p = 0.017 and 0.016, at one and two years compared to baseline, respectively). CD66b was associated with baseline CRP and PBMC production of TNF was associated with baseline ESR, in accordance to our earlier findings. No correlations were observed with IL-17. <h3>Conclusion</h3> We have earlier shown that PBMC anti-CII IC-induced production of TNF was associated with CRP and ESR in newly diagnosed RA patients. Here we show that PMN reactivity against anti-CII IC is uniquely associated with joint destruction. PMN reactivity towards anti-CII IC in cartilage of patients can contribute to joint destruction in newly diagnosed RA patients.
A comparison of quality of life in colon cancer patients receiving adjuvant uracil/ftorafur + leucovorin versus 5-fluorouracil + leucovorin in NSABP C-06
Authors: G. Yothers, J. A. Kopec, P. A. Ganz, H. S. Wieand, B. Lembersky, N. Wolmark
Journal: Journal of Clinical Oncology (2005)

8080 Background: The NSABP C-06 trial demonstrated that adjuvant therapy with oral uracil/ftorafur (UFT) + leucovorin (LV) is equivalent to standard intravenous regimen of 5-fluorouracil (5-FU) + LV in terms of disease-free survival and overall survival in patients with stage II and III carcinoma of the colon. This study compared health-related quality of life (HRQL), convenience of care (COC) and symptoms in the two arms of NSABP C-06. Methods: HRQL was measured with the Functional Assessment of Cancer Therapy, Colon (FACT-C) questionnaire, plus the SF-36 Vitality Scale and overall 0–10 rating of HRQL. These instruments were administered at baseline, during chemotherapy (week 15–16), and at 1 year. COC was measured with a modified ECOG Burden of Care scale and symptoms were evaluated using the Symptom Distress Scale (SDS) and Treatment-Specific Symptom Checklist (SCL). The COC scale, SDS and SLC were administered at baseline, day 1 of each treatment cycle and 1 year. Statistical comparisons used repeated measures analyses controlling for demographic variables and baseline scores. Results: NSABP C-06 accrued 1608 patients, 803 to the 5-FU arm and 805 to the UFT arm. Participation rates in the HRQOL study were >90% at baseline and >60% at 1 year. There were no differences between the two arms in overall FACT-C scores, domain-specific FACT-C scores, or overall ratings of HRQL. Patients in the UFT arm reported a significantly higher COC (9 points on 0–100 scale, p<0.0001). Statistically significant but extremely small differences (<3 points on 0–100 scale) were observed for SF-36 Vitality Scale (favoring 5-FU), SDS (favoring UFT) and SCL (favoring UFT). Abdominal pain and diarrhea were more common in the UFT arm whereas skin and respiratory problems were more common in the 5-FU arm. In both arms, overall HRQL ratings improved slightly over time. Conclusions: Oral treatment with UFT + LV is perceived by patients as more convenient than standard intravenous 5-FU + LV. While the pattern of symptoms associated with each regimen is different, the impact on HRQL in general, and within the categories of colon-specific, physical, emotional, social, and functional health, is similar. No significant financial relationships to disclose.
Acquisition of breast tissue in a biomarker modulation study using bexarotene in women at high risk of breast cancer
Authors: B. Arun, S. Mohsin, A. Miller, C. Isaacs, K. Saxton, S. Hilsenbeck, W. Lamph, K. Johnson, P. Brown, R. Elledge
Journal: Journal of Clinical Oncology (2005)

1002 Background: Bexarotene is a synthetic retinoid analogue that binds to members of the RXR subclass of receptors. We have previously demonstrated that this RXR-selective retinoid prevents ER-negative breast cancer in preclinical animal models. We are now testing this agent in a randomized, placebo-controlled Phase II cancer prevention trial in women at high risk of breast cancer. The primary endpoint of this trial is change in breast epithelial cell proliferation measured by Ki67 immunohistochemical staining after drug treatment. Secondary endpoints are measurement of other retinoid-regulated biomarkers (apoptosis, ER, PR, retinoid regulated genes). Methods: Women at high risk of breast cancer (defined by having ≥ 10% chance of a BRCA1 or 2 mutation) were enrolled in this multi-institutional trial. Women received study drug (placebo or bexarotene at 200mg/m2) for 28 days. Non-directed breast core needle biopsies were taken before and after the study medication. Biomarker analysis will be performed using these samples. Results: 47 of planned 100 subjects have been enrolled; 37 have taken the study drug or placebo. Median age: 42 years (range: 20–82). Median risk of carrying a BRCA1/2 mutation: 30% (range: 11–100%) by the BRCAPro, Couch, or Myriad models. Genetic testing for BRCA1 or 2 mutations was done for all subjects. Seven subjects (16.6%) were found to have a mutation in either BRCA1 or BRCA 2. 37 women had baseline breast biopsies. Of 69 samples, 52 (75%) were satisfactory for biomarker analysis (defined by the presence of epithelial cells on H&E). Epithelial cell adequacy rates increased over time. 30 patients had pre- and post-treatment biopsies. 23/30 (77%) of the day 1 and 23/30 (77%) of the day 28 biopsies were satisfactory; 19 of 30 (63%) of the paired samples are satisfactory and available for analysis. Conclusions: Current results from this study demonstrate that accrual of high-risk women to biomarker modulation trials of novel agents is feasible. Adequate tissue for analysis of many biomarkers has been obtained using core needle biopsy. Once accrual is complete we will determine whether bexarotene suppresses breast epithelial cell growth in high-risk women. Supported by NIH grant U19CA086809. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ligand NCI, NIH
Fludarabine and cladribine in relapsed/refractory low-grade non-Hodgkin's lymphoma: A phase II randomized study
Authors: C. Tondini, M. Balzarotti, I. Rampinelli, P. Valagussa, M. Luoni, A. De Paoli, A. Santoro, G. Bonadonna
Journal: Annals of Oncology (2000)