tbuckley/cabot-search huggingface dataset:
Does body mass index affect lymph node retrieval in colon resection for cancer?
Authors: J. M. Pimiento, M. A. Cristancho, K. Aboulhosn, T. Fancher, J. A. Palesty, S. J. Dudrick
Journal: Journal of Clinical Oncology (2006)

13571 Background: The management of colon cancer is a multidisciplinary effort that begins with adequate staging centered around the assessment of lymphatic spread. Multiple research groups have studied the number of lymph nodes retrieved and its relation with the outcome of patients with colon cancer, reporting better outcome in patients with a higher number of nodes retrieved. It has been well established that fatty tissue makes lymph node recovery difficult.Our objective was to evaluate if Body Mass Index (BMI) is associated with the number of lymph nodes retrieved, age, stage or location of the tumor. Methods: Retrospective chart review of patient who underwent colon resection for cancer between January 2001 to January 2005. Demographics, BMI and pathologic findings were recorded. Results: 395 patients had diagnosis of colon cancer, 140 underwent surgical procedures for these malignancies. Only 127 patients had complete records. The average age was 72 years. The average lymph node retrieval was 11.4. There was a significant relation between nodes harvested and specimen length (p 0.0028), age (p 0.0011), and stage IV cancer (p 0.002). There was no significant relationship between lymph node retrieval and BMI (p 0.1), location of the tumor (p 0.6) or stage I, II or III. Conclusion: We did not find any statistically significant correlation between BMI and lymph node retrieval, confirming reports that indicate the necessity of adequate lymph node harvest in patients with colon cancer for adequate staging and treatment. This may be because this study was done at a non-specialized center and because the operations were done by a number of different surgeons and the histopathology by numerous pathologists. The relation of improved lymph node harvest with greater specimen length supports other studies that point toward surgical and pathologic techniques as the most important factors in the appropriate staging of colon cancers. Hence, standardized surgical and histopathologic techniques need to be employed for harvesting adequate numbers of lymph nodes in resection specimens because number of nodes is critical to therapy, and an insufficient numbers of nodes may have a detrimental impact on colon cancer patient outcome. A prospective study should be performed in order to confirm the results of this study. No significant financial relationships to disclose.
Results of a phase I/II trial of carboplatin/gemcitabine plus celecoxib for first-line treatment of stage IIIB/IV non-small cell lung cancer (NSCLC)
Authors: J. D. Burton, D. El-Sayah, M. Cherry, M. Bhargava, T. Terjanian, M. Odaimi, M. Vesoniaraki, J. Lowry, F. Forte, P. Friscia
Journal: Journal of Clinical Oncology (2005)

7250
Abstract 14657: Regulation of Endothelial Nitric Oxide Synthase by NADPH Oxidase 4 Inhibition
Authors: Coy Brunssen, Claudia Eickholt, Heike Langbein, Melanie Brux, Anja Leuner, Claudia Goettsch, Winfried Goettsch, Henning Morawietz
Journal: Circulation (2012)

The NADPH oxidase isoform NOX4 mainly produces H2O2. Previously we could show, that NOX4 is the major endothelial NOX isoform and constitutively active. Regulation of NOX4 and formation of reactive...
Clinical response at 4 months to neoadjuvant letrozole predicts distant disease free survival in postmenopausal women with stage II-III ER/PgR-positive breast cancer
Authors: V. Guillem, A. Llombart-Cussac, J. Lopez Guerrero, A. Guerrero, C. Fuster, A. Ruiz, M. A. Climent, I. Tena, C. Vazquez, A. Llombart-Bosch
Journal: Journal of Clinical Oncology (2006)

10531 Background: Letrozole (L) is more active than tamoxifen in early stage ER[+] breast cancer both as adjuvant (BIG-98 trial) or neoadjuvant (LET-024) therapy. However, complete pathological remissions to neoadjuvant endocrine therapy are anecdotal (&lt;5%), there are no new prognostic indicators with clinical implications. Methods: We have review our series of postmenopausal patients with stage II-III breast cancer ER/PgR[+] breast cancer treated in our institution with L as neoadjuvant therapy. All patients had completed 4 months of therapy (in the absence of PD), and had measurable clinical (or radiological) disease. An independent statistical analysis was conducted for disease free (DFS) and distant disease free survival (DDFS). Results: From IV/99 to XII/04, 107 patients fulfill the criteria. Median age 76 years (range 64 to 92); median tumour size 35 mm (range 25 to 100); cT2 75 (70%), cT3/4 32 (30%); cN[-] 83 (78%). The ORR (PR + CR) at 4 months was 63% (7 CR and 60 PR), 4 patients had PD as best response (4%) and 36 a SD (34%). Surgery was done in 63 patients (59%), including all non-responders. Only 2 patients received adjuvant CT. With a median follow-up of 32 month (range 8 to 66), 12 patients had relapsed (9 distant). The 3 years DFS and DDFS were 84% and 90% respectively. In univaried analysis: cN (p &lt; 0.02), cT3/4 (p &lt; 0.02), and clinical response at 4 months (CR) (p = 0.003) were related to DFS; and HER2 (p &lt; 0.05), cN (p &lt; 0.003), and CR (p = 0.007) with DDFS. Other factors like cT, HR-levels, or surgery were not significant. Multivariate analysis showed that only OR and cN remained independently predictive both for DFS and DDFS. Conclusions: Clinical response to neoadjuvant letrozole therapy is an independent predictor of distant disease free survival and could be of value to recommend or deny more aggressive therapies in addition to endocrine therapy. [Table: see text] No significant financial relationships to disclose.
Phase I clinical trial of CX-3543, a protein-rDNA quadruplex inhibitor
Authors: K. P. Papadopoulos, D. W. Northfelt, D. M. Hufnagel, A. D. Ricart, P. P. Griffin, M. D. Oslund, D. D. Von Hoff, W. G. Rice, J. K. Lim, R. F. Marschke
Journal: Journal of Clinical Oncology (2007)

3585 Background: CX-3543 inhibits over-expressed ribosomal RNA synthesis in cancer cells by disrupting an essential protein-rDNA quadruplex complex, thereby inducing selective apoptosis. A phase I clinical trial for CX-3543 was undertaken to determine the dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and pharmacokinetics (PK) of this agent. Methods: Eligible patients with advanced solid tumors received CX-3543 in successive dose cohorts at: 10, 20, 40, 80, 160, 240, 360 and 480 mg/m 2 . Drug is administered by daily intravenous infusion on the first five consecutive days of a three week cycle, and the infusion duration has varied from one hour to six hours. Response by RECIST is determined after every 2 cycles. Results: Thirty-three patients (M/F:19/14; median age 69, range 44–83) with advanced solid tumors were treated with intravenous CX-3543. No drug related serious adverse events (SAEs) were encountered. DLTs of infusion-related cough and headache were identified at 480 mg/m 2 (The MTD was 360 mg/m 2 ). These adverse events were fully and rapidly reversible upon slowing or interrupting the infusion. Other drug-related adverse events were of mild to moderate intensity. Four patients had stable disease for longer than 4 months and one patient, with stable disease for over one year, currently continues on study. CX-3543 demonstrated an increasing plasma terminal half life at the higher dose levels due to a ‘reservoir‘ effect from CX-3543 reversibly binding to blood cells. Conclusions: CX-3543 administered as a 6 hour infusion for five consecutive days of a three week cycle is well tolerated and has stabilized disease in a number of patients enrolled in this phase I study. This trial is now in an expanded enrollment phase at 360 mg/m 2 and pharmacodynamic measures, specifically FDG-PET scans and circulating tumor cells, have been included to detect biological activity at this dose level. No significant financial relationships to disclose.
Efficacy and safety of denileukin diftitox (Dd) in cutaneous T-cell lymphoma (CTCL) patients: Integrated analysis of three large phase III trials
Authors: A. Negro-Vilar, H. M. Prince, M. Duvic, S. Richardson, Y. Sun, M. Acosta
Journal: Journal of Clinical Oncology (2008)

8551 Background: ONTAK (Dd), a fusion protein targeting IL-2 receptor in malignant cells, is approved for the treatment of persistent/recurrent CTCL expressing CD25. Dd has been studied in 307 early or advanced stage CTCL patients in three large Phase III trials, Studies #10, #11, #14, the last two recently completed. Integrated efficacy and safety analysis of the trials is presented. Methods: Dd doses were 9 or 18 μg/kg IV, daily for 5 days, repeating every 21 days, up to 8 courses. Patients in Study #10 and #11 were CD25(+) (ie. had CD25 immunostaining in > 20% of malignant cells); Study 14 also included CD25(-) patients. Response confirmation required 3 consecutive courses and was adjudicated by an independent Data Endpoint Review Committee in each trial, using a weighted severity skin, blood and lymph node count. Primary endpoint: Overall Response (ORR, including complete [CR], clinical complete [CCR], or partial [PR] response). Key secondary endpoint: Progression-Free Survival (PFS). Results: Demographics: similar across trials and between arms on each study. Integrated efficacy results are shown in the Table below. Placebo data provides the first detailed measure of spontaneous responses in CTCL patients. Both Dd doses showed significantly better ORR and PFS and lower rates of PD than placebo. Both CD25(+) and CD25(-) patients responded to Dd. Retreated patients also showed significant benefit. Many (70%) Dd responses were confirmed at Course 5 or later. Most AEs were mild or moderate. Grade 3/4 AEs (Dd 74%, Placebo 36%), and SAEs (Dd 41%, Placebo 20%) decreased to placebo levels after course 2 or 3. Conclusions: This analysis represents the largest investigation of a single agent for treatment of CTCL with a placebo arm. The data provide evidence of efficacy and clinical benefit for Dd in all patients with CTCL, regardless of CD25 status. Integrated Efficacy Results Efficacy Endpoint Placebo (N=44) All Dd-treated (N=263) Dd HD CD25(+) (N=118) Dd HD CD25(-) (N=36) Dd Retreated* (N=29) ORR (%) 15.9 38.0** 47.5** 30.6 27.6 CR/CCR 2.3 9.1 11.0 8.3 6.9 PR 13.6 28.9 36.4 22.2 20.7 PD 52.3 17.5 11.0 25.0 34.5 PFS (median days) 124 794** 870** >487** 205** * Patients who responded to Dd on Study 10 or 11, then relapsed and were retreated on Study 14. ** P<0.02 or better compared with Placebo. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eisai Eisai Eisai Ligand
Phase II study of S-1 in patients with gemcitabine resistant advanced pancreatic carcinoma
Authors: K. Sudo, T. Yamaguchi, T. Ishihara, K. Nakamura, H. Saisho
Journal: Journal of Clinical Oncology (2006)

14070 Background: S-1 is an oral fluoropyrimidine derivative with reported response rate of 21.1∼37.5% for advanced pancreatic carcinoma (Ueno, Oncology 2005; Furuse, ASCO 2005). The primary objective of this study was to assess the efficacy and safety of S-1 in patients with gemcitabine resistant advanced pancreatic carcinoma. Methods: Patients with histologically or cytologically proven, metastatic pancreatic carcinoma who had failed prior chemotherapy with gemcitabine were eligible for this study. Other eligibility criteria included an ECOG performance status (PS) of 2 or less; an age of at least 20 years; adequate organ function; and written informed consent. S-1 was administered orally at a dose of 40 mg/m2 twice daily for 28 days, followed by a 14-day rest period. Treatment was repeated every 6 weeks until disease progression. Results: Seventeen patients were enrolled with the following characteristics: median age 67 (range 40–75); male/female = 9/8; ECOG PS 0/1/2 = 1/8/8. All patients were included in analysis. Treatment was generally well tolerated and no life threatening toxicity was observed. Grade 3–4 toxicities were anorexia (17.6%) and fatigue (5.9%). Common grade 1–2 toxicities were anorexia (35.3%), anemia (35.3%), leukocytopenia (29.4%) and diarrhea (23.5%). Three patients were discontinued S-1 because of toxicities. Out of the 17 eligible patients, 3 patients (17.6%) achieved a partial response and 5 patients (29.4%) had stable disease. A marked decrease (≥50%) in tumor markers was observed in 5 (29.4%) of the patients. (CA 19–9 in 3 patients, CEA in 1 patient, DUPAN-2 in 1 patient) The median progression-free survival and the median survival time from the date of initiation of S-1 were 4.1 months (95% CI, 2.0 to 6.2 months) and 5.7 months (95% CI, 2.6 to 8.7 months), respectively. Conclusions: S-1 is well tolerated and active in patients with gemcitabine resistant advanced pancreatic carcinoma. Further investigation of this treatment appears warranted. No significant financial relationships to disclose.
Detection of tumor progression via cell-free DNA (cfDNA) in patients with colorectal cancer.
Authors: Marika Mende, Christian Thiede, Caroline Schuster, Daniela Ellen Aust, Gunnar Folprecht
Journal: Journal of Clinical Oncology (2015)

598 Background: Individualized therapy based on molecular stratification has become an integrative part in modern targeted treatment approaches. Here, we aimed to assess whether repeated measurements of cfDNA in patients' plasma could indicate tumor progression. Methods: We prospectively collected and stored serum from patients with colorectal cancer presenting for treatment or follow-up. KRAS and NRAS mutations were determined in the formalin fixed, paraffin embedded initial tumor material. A group of patients with confirmed KRAS or NRAS mutation, radiologically proven tumor progression and subsequent change of therapy was selected. cfDNA was extracted from samples taken at time of progression, as well as day -30 and day -60. Mutations were analyzed using a highly sensitive method based on ultradeep Next Generation Sequencing on a semiconductor-based NGS system (IonTorrent PGM), with a lower limit of detection down to 0.01% for selected mutations. Results: Twenty patients were identified to meet the inclusion criteria; 17 were KRAS mutated, three were NRAS mutated within the initial tumor material. In three patients (15%), RAS-mutation was not detectable at time of progression. While in two of them RAS-mutation had been measurable in prior samples, in one case the mutation was not detectable in cfDNA at any time. In 11 (65%) of the remaining 17 patients, RAS variant allele frequency (VAF) in the cfDNA was increased at time of progression compared to measurements at days -30 and/or -60. The median slope of increase was 3.5 (range 0.12 to 15.13). In six patients, there was no correlation between tumor progression and cfDNA; The amount of cfDNA decreased in comparison to prior measurements, either at 30 days prior to or at progression. Conclusions: In almost all cases cfDNA could be detected in the blood of patients with RAS-mutated tumors which demonstrates the high sensitivity of the method. Data suggest a trend toward an increase of cfDNA during tumor progression. However, it is not clear why deviations, especially a decrease of VAF in cfDNA occurred in some patients prior to or at tumor progression. Currently unknown tumor-biological or therapy-associated factors might contribute to this finding. Further investigation is planned.
Poor oral health including active caries in 187 UK professional male football players: clinical dental examination performed by dentists
Authors: Ian Needleman, Paul Ashley, Lyndon Meehan, Aviva Petrie, Richard Weiler, Steve McNally, Chris Ayer, Rob Hanna, Ian Hunt, Steven Kell, Paul Ridgewell, Russell Taylor
Journal: British Journal of Sports Medicine (2015)

Background The few studies that have assessed oral health in professional/elite football suggest poor oral health with minimal data on impact on performance. The aim of this research was to determine oral health in a representative sample of professional footballers in the UK and investigate possible determinants of oral health and self-reported impact on well-being, training and performance. Methods Clinical oral health examination of senior squad players using standard methods and outcomes carried out at club training facilities. Questionnaire data were also collected. 8 teams were included, 5 Premier League, 2 Championship and 1 League One. Results 6 dentists examined 187 players who represented &gt;90% of each senior squad. Oral health was poor: 37% players had active dental caries, 53% dental erosion and 5% moderate-severe irreversible periodontal disease. 45% were bothered by their oral health, 20% reported an impact on their quality of life and 7% on training or performance. Despite attendance for dental check-ups, oral health deteriorated with age. Conclusions This is the first large, representative sample study in professional football. Oral health of professional footballers is poor, and this impacts on well-being and performance. Successful strategies to promote oral health within professional football are urgently needed, and research should investigate models based on best evidence for behaviour change and implementation science. Furthermore, this study provides strong evidence to support oral health screening within professional football.
Multicenter Web-based phase III study to test the survival equivalence of non-platinum-based (NPB) vs platinum-based (PB) therapy for advanced non-small cell lung cancer (NSCLC): The Dartmouth NPB Chemotherapy Trial (D0112)
Authors: J. R. Rigas, M. Carey, B. Cole, A. Evans, R. Page, F. Yunus, M. Ruben, H. Ghazal, K. Dragnev
Journal: Journal of Clinical Oncology (2004)

7071 Background: For patients (pts) with advanced disease and a good performance status (PS) PB therapy is recommended. To date, the survival benefit of a NPB remains unanswered. This trial is designed to compare the overall survival (OS) of NPB vs PB therapy for advanced NSCLC testing for equivalence. Methods: Pt eligibility: pathological stage IIIB/IV NSCLC, PS 0–2, and no prior chemotherapy. Randomized pts were stratified by stage and PS to arm A: carboplatin AUC = 6 + docetaxel 75 mg/m2 every 3 wks (PB) or arm B: gemcitabine 1 gm/m2 + docetaxel 40 mg/m2 days 1 and 8 every 3 wks (NPB). The primary endpoint is OS. Relative risk (RR) and log-rank will be used to establish therapeutic equivalence (RR 0.8–1.2). Planned sample size 928 pts. This trial is monitored by an independent SDMC and source documentation (SD) for all web-based entries is sought. Results: As of December 2003, 732 pts (367 pts arm A vs 365 pts arm B) are enrolled at 87 sites. Pt characteristics are balanced for gender (38% female), age (median 65, range 36–90), PS (14% PS2), stage (76% stage IV) and histology (51% adenocarcinoma, 20% squamous cell). Arm A received 1,538 cycles and 1,335 cycles in arm B. Serious adverse events (SAEs) occurred 135 pts in arm A and 184 in arm B. Only 30% of all SAEs are attributed to therapy. There were 2 treatment-related deaths, one on each arm. In July 2003 at a predefined interim analysis with 97% of the data SD, 250 deaths occurred among 620 randomized pts. The OS yielded p = 0.38. The 1-year survival rate was 45% for PB and 42% for NPB. The pre-specified stopping rule for superiority was p = 0.01. The SDMC recommended continuation. We anticipate completion by May 2004 and presentation of the final data sets in June 2004. Conclusions: At the predefined interim analysis, there appears to be no statistical survival advantage for platinum or non-platinum-based therapy. At present, there appear to be qualitative and quantitative differences in SAEs. Upon completion, we will definitively comment on the equivalence of a non-platinum-based treatment for this disease. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis Abbott; Amgen; Aventis; Bristol-Myers Squibb; Genentech; GlaxoSmithKline; Ortho Biotech; Ligand; Merck; Pfizer; OSI; Roche
Relapse After Allogeneic Hematopoietic Stem Cell Transplantation (HCT) For Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) Following Intravenous Busulfan/Fludarabine Based Conditioning: Outcomes and Monocyte Chemo-Attractant Protein -1( MCP-1) As a Predictive Marker Of Relapse
Authors: Abraham Matar, Melhem M. Solh, Alicja J Copik, Sally Litherland, Alvin oliverasAlmodovar, Kristin Rathmann, Yasser Khaled
Journal: Blood (2013)
Radiological morphology of low-grade primary central nervous system lymphoma in immunocompetent patients
Authors: E. Thiel, K. Jahnke, A. Schilling, L. Fischer, J. Heidenreich, H. Stein, A. Korfel
Journal: Journal of Clinical Oncology (2005)

1536 Background: Primary central nervous system lymphomas (PCNSL) are usually high-grade and very rarely low-grade non-Hodgkin’s lymphomas. They are typically contrast-enhancing lesions in contact with the subarachnoid space and without necrosis. The purpose of this study was to evaluate the radiological morphology and clinical characteristics of low-grade PCNSL. Methods: Records were reviewed from 332 patients screened for inclusion in 3 multicenter prospective trials. Ten patients (3%) with low-grade PCNSL (7 men, 3 women, median age 59 years, range 19–61 years) were identified. The pathological diagnosis of low-grade PCNSL was confirmed by a consultant hematopathologist in all patients. Brain magnetic resonance imaging (MRI) scans were obtained from all patients and centrally reviewed by two consultant neuroradiologists. Results: MRI scans were abnormal in all patients. There were 4 patients with one PCNSL manifestation, 2 with 2, and 4 with multiple manifestations. The lesions were found in the hemispheres (n = 8), basal ganglia (n = 2), corpus callosum (n = 1), and spinal cord (n = 1). Necrosis was diagnosed in only one patient. The ventricular ependyma was involved in 5 patients, one of whom had lymphoma cells in the cerebrospinal fluid. On T2-weighted images, the lesions were hyperintense in 9 patients and isointense in one patient. Nearly all lesions showed enhancement, strong in 5 and only mild to moderate in 4 patients. It was homogeneous in 4 and heterogeneous in 5 patients. Edema was moderate in 5 and marked in 4 patients. Altogether, 8 patients had a radiological morphology atypical of classical high-grade PCNSL with a subsequent false or delayed diagnosis. Conclusions: Low-grade PCNSL may have a variable and atypical radiological morphology compared to high-grade PCNSL and thus carries the risk of false or delayed diagnosis. Thus, all cases require neuropathological confirmation. No significant financial relationships to disclose.