tbuckley/cabot-search huggingface dataset:
Increased incidence of non-melanomatous skin cancer in patients with chronic lymphocytic leukemia, an 11-year case-control study
Authors: M. W. Schoen, P. S. Gable, A. M. Reese
Journal: Journal of Clinical Oncology (2007)

19554 Background: Chronic Lymphocytic Leukemia (CLL) is a disease of B lymphocytes that affects immune tolerance and surveillance. Patients with CLL have an increased risk of basal and squamous cell skin carcinomas, which tend to be aggressive. We report the incidence of non-melanomatous (NM) in a &gt;80% Caucasian cohort of patients with CLL and compared them to normal controls who reside in Southern California. Methods: A retrospective review was conducted of all patients in the Naval Medical Center San Diego tumor registry with CLL diagnosed between Jan 1, 1995 and Dec 31, 2005. The electronic records of 74 CLL patients and 100 control patients from the internal medicine clinic were assessed for skin biopsies performed at our institution revealing NM skin malignancies. Results: Within our CLL population, the average age at diagnosis was 72.2 years. 34% (25/74) had NM skin cancer with an incidence of 11,457 NM skin cancers per 100,000 person-years. The average number of malignant lesions was 3.7 per patient with one patient receiving 17 biopsies. 27% (7/25) of CLL patients with NM skin cancer had only squamous cell carcinoma and 23% (6/25) had only basal cell carcinoma. 42% (11/25) of patients had both squamous and basal cell cancers and one had a Merkel cell carcinoma. In the control population, the average age at diagnosis was 76.4 years. 16% (16/100) had NM skin malignancies with an incidence of 5,333 NM skin cancers per 100,000 person-years. The average number of malignant lesions was 3.7 per patient with one patient receiving 28 biopsies. 63% (10/16) had basal cell carcinomas, only 25% (4/16) had squamous cell carcinomas and 13% (2/16) had both types of cancer. Conclusions: Patients with CLL are at increased risk of developing NM skin cancers, especially squamous cell carcinomas. Patients with CLL have a 2.1 times higher risk of developing NM skin cancer than our control population, who had an incredibly high rate of skin cancer compared to prior publications. CLL patients should be closely screened for cutaneous malignancies in order to excise them before they cause further morbidity. Increased surveillance is especially prudent for elderly patients with fair skin types who have been exposed to a large amount of UV-light. No significant financial relationships to disclose.
Induction chemotherapy followed by thoracic irradiation with or without concurrent chemotherapy in locally advanced inoperable NSCLC: A randomized phase III trial
Authors: A. Ardizzzoni, L. Boni, T. Scolaro, G. Selvaggi, F. De Marinis, L. Buffoni, F. Grossi, V. D'Alessandro, S. Barbera, C. Caroti
Journal: Journal of Clinical Oncology (2008)

7520 Background: The combination of chemotherapy (CT) and radiotherapy (RT) is standard of care in the treatment of inoperable stage III NSCLC. The aim of this trial was to assess whether the addition of concurrent CT to thoracic RT following induction CT was able to improve treatment outcome. Methods: Eligible patients were required to have inoperable stage III NSCLC, age < 70 years, PS < 1 and FEV1 > 1L. Planned accrual was 300 patients to detect a 30% mortality reduction with the addition of concurrent CT in the experimental arm (α=5%, β=20%). Control arm treatment consisted of 2 cycles of paclitaxel 200 mg/m2 combined with either carboplatin AUC 6 or cisplatin 80 mg/m2 followed by 60–61.2 Gy continuous RT (180–200 cGy/fraction for 5 days/week for 6–7 weeks). Experimental arm consisted of identical induction CT and RT with the addition of paclitaxel 60 mg/m2 weekly for 6–7 weeks concurrently to RT. Results: Due to slow recruitment, accrual was terminated early, at the time of the second planned interim analysis when 151 eligible patients had been randomized. Patients characteristics were well balanced in the two arms. Overall median age was 61 years; most patients were males (91%), 67% had stage IIIB, 60% had PS 0, 42% had squamous histology. Induction CT was well tolerated in both control and experimental arm. RT was completed as planned in 88% and 77% of patients, respectively, with a median total RT dose of 60 Gy in both arms. Nearly 80% of patients in experimental arm completed concurrent weekly paclitaxel. Treatment toxicity was manageable in both arms (G3–4 esophagitis 3 vs 8%) without statistically significant differences. One toxic death occurred in the concurrent CT-RT arm. Overall response rate and median progression-free survival did not differ according to treatment (54 vs 52% and 7.1 vs 8.4 months). With a median follow-up of 5 years, median survival was 13.1 vs 15.1 months with a 3-year survival rate of 21.2 vs 21.9% in the control and experimental arm, respectively (HR=0.99). Conclusions: Although the accrual was terminated early, the results of this study, by means of a “futility analysis”, seem to exclude a clinical meaningful benefit with the addition of concurrent weekly paclitaxel to sequential CT-RT. No significant financial relationships to disclose.
Phase II study of biweekly gemcitabine and docetaxel as first-line treatment for advanced disease in non-small cell lung cancer (NSCLC) patients with ECOG performance status 2.
Authors: V. Giner, O. Juan Vidal, J. Muñoz, G. Esquerdo, A. Sanchez-Hernandez, J. Gómez-Codina, F. Aparisi, S. Maciá, A. López Jiménez, S. Catot
Journal: Journal of Clinical Oncology (2010)

e18083 Background: Standard treatment for patients with stage IIIB/IV NSCLC currently includes a two-drug platinum-based chemotherapy regimen, but its benefit seems limited to patients with a performance status ≤1. This study has been conducted to assess the efficacy and toxicity of biweekly gemcitabine (G) and docetaxel (D) in patients with NSCLC with PS=2. Methods: Patients ≥18 years old with cytological or histological confirmation of advanced (stage IIIB/IV) NSCLC, PS=2, measurable lesion according RECIST criteria, adequate bone marrow, renal and hepatic function, were included. Prior systemic therapies for NSCLC and/or symptomatic brain metastases were not allowed. Patients received biweekly D 50 mg/m2 iv, G 2,000 mg/m2 iv, days 1 and 14, during 24 weeks. Toxicity was evaluated according to CTCAE 3.0. Results: 35 patients of 75 enrolled were included in this interim analysis. Characteristics of patients are shown in the Table. Median number of lesions was 3. A total of 171 cycles (median 4, range 1-6) were administered. Median relative dose intensity was 100.0% for D and G. Over all 35 patients analyzed, 1 patient achieved PR (2.9%), 13 SD (37.1%), 8 PD (22.9%) and 13 (37.1%) were not evaluable (6 due to death, 1 to adverse event, 1 to withdrawal and 5 continued in treatment). Overall response rate was 2.9 (95CI%:0.0%-8.5%). Toxicities are shown in the Table. Conclusions: Docetaxel and gemcitabine administered every 14 days as first line-treatment for advanced disease in NSCLC PS2 patients seems to be a safe and active regimen. Patients' characteristics and toxicities Patients' characteristics Age (yr) Median 63.7 Range 44.1-84.6 Histology (%) Squamous 40.0 Adenocarcinoma 22.9 Most common sites of metastases (%) Liver 28.1 Adrenal gland 25.0 Lymph nodes 21.9 Pleura 18.8 Bones 18.8 Prior treatment (%) Radiotherapy 11.8 Current smokers (%) 51.4 Main comorbidities (%) COPD 47.1 Cardiovascular 27.3 Help for daily living activities (%) 94.1 Toxicities Grade IV (%) Neutropenia 2.9 Grade III nonhematological (%) Disnea 5.7 Rush 2.9 Diarrhea 2.9 Asthenia 2.9 Grade III hematological (%) Leucopenia 2.9 Neutropenia 2.9 No significant financial relationships to disclose.
Top-down control of arousal and sleep: Fundamentals and clinical implications
Authors: Lukas Krone, Lukas Frase, Hannah Piosczyk, Peter Selhausen, Sulamith Zittel, Friederike Jahn, Marion Kuhn, Bernd Feige, Florian Mainberger, Stefan Klöppel, Dieter Riemann, Kai Spiegelhalder, Chiara Baglioni, Annette Sterr, Christoph Nissen
Journal: Sleep Medicine Reviews (2016)
Differential hepatic gene expression profiles identify improvement in MELD score following decompensation in alcoholic liver disease
Authors: Nicolas Lanthier, Yves Chalandon, Laura Rubbia-Brandt, Vincent Kindler, Antoine Hadengue, Laurent Spahr
Journal: Hepatology (2012)

We aimed to study the hepatic differentially expressed genes associated with 1) bone marrow stem cell therapy (BMST) and 2) the evolution of liver function during follow-up in a well-characterized patients’ population of acutely decompensated alcoholic liver disease (ALD). Methods: This study derives from the material and bio-clinical data issued from a trial of autologous bone marrow stem cell transplantation in patients with ALD (Hepatology 2011, A62), for which an informed consent was obtained in all cases. Transcriptome profiling was performed on snap liver frozen samples with Affymetrix GeneChip Human arrays containing 43134 transcripts. Differential gene expression was analyzed on liver tissue obtained at the 4-week follow-up visit after BMST (n=12) or after standard medical therapy alone (n=12). We also compared differentially expressed transcripts on baseline biopsy performed early after admission, according to the evolution of liver insufficiency at 3 months, irrespective of treatment allocation. We defined patients with a ≥ 3 points decrease in MELD compared to baseline value as “improvers” (n=17), and those with less than 3 points decrease in MELD as “non improvers” (n=13). Serum soluble receptor of TNF (STNF) and hepatocyte growth factor (HGF) were measured. Results: 1) Autologous BMST did not provide any clinical, biological or histological benefits compared to standard medical therapy (Hepatology 2011, A62). However, in stem cell treated patients, at a 5% false discovery rate, gene expression changes at 4 weeks of follow-up were predominantly associated with inflammation and immune chemotaxis (SAA, CXCL6, CXCL13, CCL19), as well as in hematopoietic cell protein (CD45), compared to patients with standard therapy alone. 2) Differentially expressed genes in baseline biopsy characterized the “improvers” and the “non-improvers”. Genes involved in cell cycle mitosis (cyclin A and B, CDK1, CDC20) were upregulated in improvers compared to non-improvers, as well as genes involved in monocyte attraction, cytoskeleton motility and Wnt signaling (CXCL14, actin, collagen, CD68, Wnt11). Both serum STNF and HGF were also higher in improvers compared to non-improvers. Conclusion: In patients with decompensated ALD, the effect of BMST on liver tissue at 4 weeks of follow-up is limited to changes in genes linked with lympho-monocyte chemotaxis and one hematopoietic cell surface protein. The differentially expressed genes involved in cell proliferation at admission are associated with the clinical outcome, supporting the role of liver cell regeneration in the improvement of liver function.
Patient (pt) evaluation of the Oncology Pt Emergency Network (OPEN): Implications for oncology practices
Authors: C. A. Presant, S. Hartono, M. Ampudia, F. Howard
Journal: Journal of Clinical Oncology (2008)

6545 Background: Pt emergency preparedness is important in disasters (Katrina, Los Angeles fires 2007). MOASC developed a preparedness program OPEN (www.open-central.com; Proc ASCO 2007 abstract 17003, 2006 abstract 6142). This study determined pt satisfaction with OPEN. Methods: Pts were given wallet cards with emergency information (diagnosis, stage, treatment, doses), and a copy of their EMR history. Pts completed a survey and a semistructured interview to validate results. Results: Of 190 consecutive pts, 28% were male, 86% had cancer. Pts uniformly ranked importance of this program high (1.22/ scale of 1 best-3 worst). Pts felt they were able to keep their medical records up to date, and by themselves (1.22–1.33/3), and said all pts should participate (1.20/3). Although designed for disasters, pts also wanted OPEN records for reviewing themselves (94%), taking to other doctors (97%), using at emergency rooms (99%), and when traveling (99%). 96% wanted paper copies, significantly more than e-mail (48%, p < 0.001), or fax (18%, p < 0.001). 63% wanted records available on the doctor website for remote access by the pt or other physicians, still less than by paper (p < 0.001). 21% also wanted it on a portable drive, but only 14% wanted it on a national password protected website (less than doctor website p < 0.0001). EMR usage by physician was ranked high (1.51/5). Pts preferred physicians to use EMR to monitor compliance of care with national guidelines (1.56/5). Pts did not want to pay extra for EMR services (2.40/3). Pts more commonly wanted copies of their medical records kept by a son or daughter (55%) compared to other family (2%-12%) or friend (2%, p<0.0001). 90% said they would recommend OPEN to family members. Interviews documented increased trust in the physician for participating in OPEN. Conclusions: OPEN, the first tested patient emergency preparedness program, is highly rated by pts and can be used for free by all oncologists. Pts desire physicians to use EMR and monitor guideline compliance. Many pts want electronic access to medical records through the physician's office, but do not desire national database storage of their records. OPEN enhances the physician-pt relationship and is highly recommended. Supported by grants from ASCO and Astra-Zeneca. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Medical Oncology Association of Southern California
Evaluation of the Effect of Interleukin 18 Associated Genetic Polymorphisms on Risk of Cardiovascular Events in Patients With Acute Coronary Syndrome
Authors: Agneta Siegbahn, Åsa Johansson, Niclas Eriksson, Emil Hagström, Christoph Varenhorst, Axel Åkerblom, Maria Bertilsson, Tomas Axelsson, Bryan J. Barratt, Richard C. Becker, Anders Himmelmann, Stefan K. James, Hugo A. Katus, Philippe G. Steg, Robert F. Storey, Ann-Christine Syvanen, Lars Wallentin
Journal: Circulation (2013)

Evaluation of the Effect of Interleukin 18 Associated Genetic Polymorphisms on Risk of Cardiovascular Events in Patients With Acute Coronary Syndrome
Phase II trial of thalidomide (TD), tamoxifen (TX), and temozolomide (T) for patients with advanced malignant gliomas (MG)
Authors: T. Ahmed, B. Chen, G. Rabbani, M. N. Wallam, D. Benzil
Journal: Journal of Clinical Oncology (2005)

1575 Background: Patients with MG have a poor survival despite surgery, radiation therapy (RT). Chemotherapy (CTX) is often used but the overall impact on survival is poor. Methods: We studied the combination of TD, TX and T in a phase II trial for patients with MG. Standard response criteria and NCI toxicity criteria were used. We also assessed quality-of-life (QoL). Eligibility criteria included histologic confirmation of Glioblastoma (GBM) or Anaplastic astrocytoma (AA), no chemo or RT for 3 weeks and ECOG PS of ≤ 2. 20 patients entered the trial: 8 were female; median age 51 years (r 24–84); 17 had GBM and 3 had AA. 9 patients had prior RT and 5 prior CTX. 28-day treatment cycles consisted of daily TD 100 mg PO and TX 100 mg PO for the full duration of each cycle and T 75 mg/m2 PO) for the first 21 days of each cycle. Treatment continued until disease progression. Primary outcomes measures were patient survival, response, toxicity and changes in QoL. Results: 6 patients discontinued therapy prior to response evaluation. 9 of 14 patients had disease stabilization and response (64%, 95% CI, 39%–89%), lasting 8–135 weeks (median 12 weeks) documented by MRI scan. No CR was seen. One patient remained progression free for 2 years. By Kaplan Meier analysis, mean survival was 75 ± 18 weeks (95% CI, 41–110 weeks) with a median time to progression of 47 weeks (95% CI, 15–79 weeks). One patient had a sustained decrease in WBC and T was held. Mean WBC was 9.4 x10e3/ul, which fell to a mean of 5.58 x 10e3/ul. Hgb and platelets were not significantly affected. 4 patients developed deep vein thrombosis (DVT): subsequent patients were given prophylactic warfarin. 2 patients had pulmonary embolism. No other grade 3 or 4 toxicities were noted. Changes in QoL scores during treatment did not significantly correlate with disease progression. Conclusions: Outpatient therapy with temozolomide, thalidomide, and tamoxifen is well tolerated and results in stabilization/response in 64% of patients. Prophylaxis with warfarin may prevent DVT in patients on tamoxifen. The overall impact on survival will require further study. Supported by the ZA Arlin Cancer Research Institute, Schering-Plough Corp. and Celgene Corp Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, Schering-Plough
A phase I study of bevacizumab (BV) plus ABT-510 in patients with advanced solid tumors
Authors: H. E. Uronis, J. Bendell, G. Blobe, M. Morse, D. Geier, A. Nixon, L. Howard, D. Evans, H. Li, H. Hurwitz
Journal: Journal of Clinical Oncology (2007)

3541 Background: BV is a potent inhibitor of vascular endothelial growth factor (VEGF) with broad clinical activity both alone and in combination. ABT-510 is a 9 amino acid synthetic analog of the N-terminal region of thrombospondin (TSP-1), an endogenous inhibitor of angiogenesis. ABT-510 exhibits anti-angiogenic effects in preclinical models and has been well-tolerated as a single agent in previous Phase I &amp; 2 studies. As a combination anti-angiogenesis therapy, we evaluated BV + ABT-510 in a phase I biomarker study. Methods: In cohorts of 3–6 patients, BV and ABT-510 were evaluated. BV was dosed in mg/kg IV q2weeks and ABT-510 was given daily in mg SC BID; cycle length was 28 days. Dose levels were as follows: (1) BV 5/ ABT-510 50; (2) BV 10/ ABT-510 50; (3) BV 10/ ABT-510 100. At the recommended phase II dose, 20 patients are being enrolled for detailed biomarker studies. DLT was defined as any hematological toxicity = grade 4 or grade = 3 non- hematological event in Cycle 1 related to treatment, with the exception of grade 3 hypertension adequately controlled by medication. Eligible patients had advanced solid tumors, adequate organ and marrow function, and no co-morbidities suggesting increased risk for class-related toxicities. Dermal wound angiogenesis assays were analyzed for visualization as well as phospho-VEGFR2, TGFβ, phospho-AKT, and thrombospondin-1 and -2, both pre- and on-treatment. Plasma was assayed for multiple angiogenic factors. Results: 22 patients have been enrolled; 17 are currently evaluable for toxicity and 14 for efficacy. No DLT were seen in any cohort. Possible treatment related adverse events occurring in later cycles included: gr3 GI bleed (n=1) and gr3 headache (n=1). 7 patients had stable disease as best response (range 8- 64+ weeks); 2 remain on therapy, one at 64+ weeks and one at 24+ weeks. Conclusions: BV + ABT-510 is well-tolerated and has hints of activity in refractory tumors. The recommended phase II dose is BV 10mg/kg IV q14d and ABT-510 100mg SC BID. Updated clinical and biomarker data will be presented. No significant financial relationships to disclose.
The results of immunotherapy of community acquired pneumonia
Authors: Usman Farkhutdinov, Albert Mirchaidarov, Rafagat Farkhutdinov
Journal: European Respiratory Journal (2013)

Disorders in free radical processes and immune system play an important role in inflammatory formation in patients with community acquired pneumonia (CAP ) .  The aim was to study the production of active oxygen forms (AOF) and inflammatory mediator cytokine TNF-a in patients with CAP and the efficacy of i.v. immunoglobulin immunovenin (IMV) in their treatment.   Methods:  The study included 37 patients with CAP. The production of AOF in the blood of patients was studied by registration of luminol dependent chemiluminescence (ChL). In addition the level of TNF-a was determined in the patients blood. 19 patients with CAP received standard therapy. In 18 patients with CAP IMV was added to conventional treatment.   Results:  In comparison with normal findings ChL intensity of blood in patients with CAP was higher by 2.8 times. It indicated increased production of AOF by blood cells. The level of TNF-a in patients blood has been found to be increased by 2.5 times. Administration of IMV decreased generation of AOF in blood, reduced the level of TNF-a by 1.9 times, produced positive effect on the course of the inflammation. In patients who received standard therapy high ChL intensity of blood and increased level of TNF-a were maintained, symptoms of inflammation have been observed for a long time.   Conclusion:  In patients with CAP IMV administration decreased AOF production and the level of TNF-a in blood, improved the results of the treatment.
Diverse cancer prevention needs in a population seeking risk assessment for gastrointestinal (GI) cancers
Authors: M. J. Hall, C. Rybak, C. Mazar, A. Balsham, S. L. Manne, E. Slater, D. S. Weinberg, N. J. Meropol
Journal: Journal of Clinical Oncology (2009)

1539 Background: Demand for hereditary cancer risk assessment has increased dramatically in the past decade. However, the population seeking risk assessment for GI cancers is heterogeneous, requiring primary (PP), secondary (SP), and tertiary (TP) prevention strategies. In an effort to improve targeting of prevention resources, we examined clinical cancer prevention needs as well as 1) estimates of personal risk, 2) risk beliefs 3) interest in genetic testing (GT) among individuals seeking GI risk evaluation. Methods: The Gastrointestinal Tumor Risk Assessment Program (GI-TRAP) offers risk assessment to persons seeking evaluation for a risk of a GI or related cancer. Following informed consent, participants complete a health history questionnaire prior to counseling, education, and genetic services. Results: In total, 398 individuals from 278 families were evaluated (1999–2008)( Table 1 ). Moderate-to-high risk persons with SP needs (i.e. intensive screening, chemoprevention, and genetic testing), dominated the population (281/398, 70.6%), mainly due to significant family history (FHx) of GI-related cancer (236/281, 84.0%) and/or personal history (PHx) of colorectal polyps (128/281, 45.6%). Individuals at high-risk due to a PHx of cancer were infrequent (68/398, 17.1%); here, TP needs focused on GT were common, as interest was highest in this group (p&lt;0.01). A low-risk group (49/411, 11.9%) with minimal PHx or FHx, had mainly PP needs (i.e. risk factor management, education related to appropriate screening). Nonetheless, prior to counseling, the magnitude of personal estimated risk in this group paralleled that of the higher risk groups. Conclusions: Perceived cancer risks and beliefs may not reflect true prevention needs. Risk stratification strategies are critical for targeting education, risk counseling, and/or GT resources while maximizing current prevention goals. [Table: see text] No significant financial relationships to disclose.