tbuckley/cabot-search huggingface dataset:
Investigating gender specific metabolic differences in non-small cell lung cancer by F-18 FDG PET
Authors: G. Howard, D. Zakalik, P. Vashist, C. O. Wong
Journal: Journal of Clinical Oncology (2007)

7663 Background: Lung cancer is the leading cause of cancer death in women, killing more women than breast, ovarian, and uterine cancers combined. Recent evidence suggests differences in lung cancer between the sexes. Women have better rates of survival, different histology, genetic, and molecular factors as compared to men. Metabolic characteristics of lung cancer have prognostic value. The use of F-18 FDG Positron Emission Tomography (PET) has been demonstrated in multiple studies to better determine outcome, improve diagnostic and staging techniques. Methods: 251 (M:F=101:150) patients with newly diagnosed biopsy proven NSCLC and evaluated by F-18 FDG PET(CT), without other malignancies, prior radiation or chemotherapy, were analyzed retrospectively from our institution. PET scans were obtained 1 hour after injection of 370 MBq F-18 FDG using a dedicated whole body PET-CT or PET scanner. The PET images were reconstructed with attenuation correction by either radioisotope or CT transmission scan. The SUV, defined as tumor activity divided by dose injected per lean body mass, from the PET cameras had been cross validated to produce the same value in a given phantom and patient. The maximum SUV was measured by searching the maximum value within a volume of known primary cancer. Results: The two groups were matched for age. Females had significantly less squamous cell carcinomas (18% vs. 29%, p=0.025) and more adenocarcinomas (41% vs. 30%, p=0.041) than males. Although there were no significant differences stage by stage between males and females, there was gradual transition or increment of SUV by stage in all female NSCLC with the SUV of stage I NSCLC being lower than that of cancers in stages II, III or IV (p=0.00022, 0.0088, and 0.0026 respectively). However, there were no such distinctions among male patients. There were no differences in SUV among various histological types of NSCLC between the sexes. Conclusions: The study suggests there are gender differences in the metabolic properties of NSCLC with distinctively more metabolically aggressive NSCLCs upon advancing stage in women but not in men. This gender specific metabolic difference is another discriminator besides other known gender factors and is potentially useful in the management of early stage NSCLC in women. No significant financial relationships to disclose.
Inhibiting Notch Activity in Breast Cancer Stem Cells by Glucose Functionalized Nanoparticles Carrying γ-secretase Inhibitors
Authors: Veronika Mamaeva, Rasmus Niemi, Michaela Beck, Ezgi Özliseli, Diti Desai, Sebastian Landor, Tove Gronroos, Pauliina Kronqvist, Ina K N Pettersen, Emmet McCormack, Jessica M Rosenholm, Mika Linden, Cecilia Sahlgren
Journal: Molecular Therapy (2016)

Cancer stem cells (CSCs) are a challenge in cancer treatment due to their therapy resistance. We demonstrated that enhanced Notch signaling in breast cancer promotes self-renewal of CSCs that display high glycolytic activity and aggressive hormone-independent tumor growth in vivo. We took advantage of the glycolytic phenotype and the dependence on Notch activity of the CSCs and designed nanoparticles to target the CSCs. Mesoporous silica nanoparticles were functionalized with glucose moieties and loaded with a γ-secretase inhibitor, a potent interceptor of Notch signaling. Cancer cells and CSCs in vitro and in vivo efficiently internalized these particles, and particle uptake correlated with the glycolytic profile of the cells. Nanoparticle treatment of breast cancer transplants on chick embryo chorioallantoic membranes efficiently reduced the cancer stem cell population of the tumor. Our data reveal that specific CSC characteristics can be utilized in nanoparticle design to improve CSC-targeted drug delivery and therapy.
Comprehensive Geriatric Assessment and Transitional Care in Acutely Hospitalized Patients
Authors: Bianca M. Buurman, Juliette L. Parlevliet, Heather G. Allore, Willem Blok, Bob A. J. van Deelen, Eric P. Moll van Charante, Rob J. de Haan, Sophia E. de Rooij
Journal: JAMA Internal Medicine (2016)

Older adults acutely hospitalized are at risk of disability. Trials on comprehensive geriatric assessment (CGA) and transitional care present inconsistent results.To test whether an intervention of systematic CGA, followed by the transitional care bridge program, improved activities of daily living (ADLs) compared with systematic CGA alone.This study was a double-blind, multicenter, randomized clinical trial conducted at 3 hospitals with affiliated home care organizations in the Netherlands between September 1, 2010, and March 1, 2014. In total, 1070 consecutive patients were eligible, 674 (63.0%) of whom enrolled. They were 65 years or older, acutely hospitalized to a medical ward for at least 48 hours with an Identification of Seniors at Risk-Hospitalized Patients score of 2 or higher, and randomized using permuted blocks stratified by study site and Mini-Mental State Examination score (<24 vs ≥24). The dates of the analysis were June 1, 2014, to November 15, 2014.The transitional care bridge program intervention was started during hospitalization by a visit from a community care registered nurse (CCRN) and continued after discharge with home visits at 2 days and at 2, 6, 12, and 24 weeks. The CCRNs applied the CGA care and treatment plan.The main outcome was the Katz Index of ADL at 6 months compared with 2 weeks before admission. Secondary outcomes were mortality, cognitive functioning, time to hospital readmission, and the time to discharge from a nursing home.The study cohort comprised 674 participants. Their mean age was 80 years, 42.1% (n = 284) were male, and 39.2% (n = 264) were cognitively impaired at admission. Intent-to-treat analysis found no differences in the mean Katz Index of ADL at 6 months between the intervention arm (mean, 2.0; 95% CI, 1.8-2.2) and the CGA-only arm (mean, 1.9; 95% CI, 1.7-2.2). For secondary outcomes, there were 85 deaths (25.2%) in the intervention arm and 104 deaths (30.9%) in the CGA-only arm, resulting in a lower risk on the time to death within 6 months after hospital admission (hazard ratio, 0.75; 95% CI, 0.56-0.99; P = .045; number needed to treat to prevent 1 death, 16). No other secondary outcome was significant.A systematic CGA, followed by the transitional care bridge program, showed no effect on ADL functioning in acutely hospitalized older patients.Netherlands Trial Registry: NTR2384.
Gefitinib (G) plus interleukin-2 (IL-2) in previously treated patients with advanced non-small cell lung cancer (NSCLC)
Authors: G. Tomasello, S. Buti, G. Bosio, I. Stifani, M. Maestrelli, M. Brighenti, R. Porzio, S. Lazzarelli, F. Negri, R. Longarini, R. Passalacqua
Journal: Journal of Clinical Oncology (2007)

18042 Background: Previous studies in patients with NSCLC treated with IL-2 reported relatively long survival (Cancer 1994;73:1353–60) and a recent study indicated that lymphocytes are activated by G treatment (J Cancer Res Clin Oncol. 2006;132:719- 725.). In this study we explored the possible synergism between IL-2 and G in terms of response rate, survival and toxicity. Methods: From September 2003 to November 2006, 70 consecutive chemotherapy treated patients with advanced, progressive NSCLC received oral G 250 mg daily in a compassionate use program at a single institution. The first 39 patients included in the study received only G, the others 31 also received subcutaneous IL-2: 1 MUI/m 2 twice a day on day 1 and 2, once a day on day 3, 4, 5 every week for 4 consecutive weeks with 4 week rest period. This is a phase II trial combined with a cohort design each having a different outcome event. All the evaluations were made using Recist criteria and according to the intention to treat principle. Results: The main patients characteristics and results are showed in the table below. Fifty-one (73%) patients received one prior chemotherapy regimen, while 17 (24%) received = two prior lines of treatment. *Median, months ±95% CI. §p value&lt;0.05 Cox’s regression analysis, including PS, gender, smoke, skin toxicity, histology and use of IL-2, revealed that only skin toxicity [p&lt;0.001; HR 0.29;CI 95% 0.16–0.54] and use of IL-2 [p&lt;0.001; HR 0.33;CI 95% 0.18–0.60] were significantly associated with improvement in OS. Patients treated with IL-2 also showed grade 2–3 fever in 46%, fatigue in 21%, arthralgias in 13%, besides the known G- related toxicity. Conclusions: In this consecutive, non-randomized, series of patients, the use of IL-2 seems to increase the efficacy of G. Further randomized studies of TK inhibitors with IL-2 are warranted. [Table: see text] No significant financial relationships to disclose.
Use of radium-223 in heavily pretreated metastatic castrate resistant prostate cancer (mCRPC) patients.
Authors: Dipenkumar Modi, SeongHo Kim, Hirva Mansurali Mamdani, Clara Hwang, Hersham Gayar, Ulka N. Vaishampayan, Richard Joyrich, Elisabeth I. Heath
Journal: Journal of Clinical Oncology (2015)

275 Background: Ra 223 has been shown to improve overall survival in mCRPC patients with symptomatic bone metastases. Little is known about the utility of following PSA during Ra 223 therapy in heavily pretreated patients. Here we report our experience with Ra 223 in such a setting. Methods: We reviewed 26 heavily pretreated mCRPC patients who received Ra 223 at 3 institutions and evaluated the trend of PSA during treatment, the association of various demographic, clinical and biochemical variables with PSA trend, and the correlation of PSA trend with clinical outcomes. Patients received IV Ra 223 every 4 weeks with a planned total of 6 cycles. Results: Twenty six patients were treated between August 2013 and August 2014. Median age was 70 years (range 49-80); 77% (N=20) were European American (EA), 19% (N=5) were African Americans (AA), unknown for 1 patient. Prior therapy included docetaxel in 77% (N=20) of patients, cabazitaxel in 19% (N=5), enzalutamide in 65% (N=17), and abiraterone in 54% (N=14). 62% (N=16) received at least 3 prior therapies.35% (N=9) received all 6 cycles of Ra 223, while 18% (N=4) received only 1 cycle. Median alkaline phosphatase level increased from 126.0 U/L (54.0, 514.0) to 332.0 U/L (136.0, 566.0) at the end of Ra 223 therapy. Median pre-therapy PSA was 100.3 and median post-therapy PSA was 429.5. 54% (N=14) patients had &gt;50% rise in PSA. Higher pre-therapy PSA was strongly associated with higher post-therapy PSA (Pearson’s correlation coefficient = 0.84, p &lt;0.0001). Faster rate of rise in PSA was observed in patients with higher number of bone metastasis and those who have had prior therapy with docetaxel. The patients with &gt;50% PSA rise had reported overall higher pain scores by visual assessment scale. Ra 223 was discontinued in 15% (N=4) patients due to myelosuppression and in 8% (N=2) due to side effects. Conclusions: All heavily pretreated patients receiving Ra 223 therapy for mCRPC showed PSA progression and reasonable tolerability. Only 35% of patients were able to receive all 6 cycles of Ra 223.
Abstract 17969: Percutaneous Coronary Intervention for Acute Spontaneous Coronary Artery Dissection is Associated with Reduced Rates of Technical Success
Authors: Marysia Tweet, Sharonne Hayes, Amir Lerman, Charanjit Rihal, Rajiv Gulati
Journal: Circulation (2012)

Background: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic acute coronary syndrome (ACS). Acute outcomes with percutaneous coronary intervention (PCI) in this patient group r...
In acute low back pain, adding oxycodone/acetaminophen or cyclobenzaprine to naproxen did not improve pain or function
Authors: Christopher R. Carpenter
Journal: Annals of Internal Medicine (2016)

Source Citation Friedman BW, Dym AA, Davitt M, et al. Naproxen with cyclobenzaprine, oxycodone/acetaminophen, or placebo for treating acute low back pain: a randomized clinical trial. JAMA. 2015;314:1572-80. 26501533
BI 836826, a Novel Fc-Engineered Antibody in Combination with Phosphoinositide-3-Kinase Inhibitor for Treatment of High Risk Chronic Lymphocytic Leukemia
Authors: Deborah M Stephens, Kyle A Beckwith, Carolyn Cheney, Xiaokui Mo, Joseph M Flynn, Jeffrey A. Jones, Kami J. Maddocks, Karl-Heinz Heider, Natarajan Muthusamy, John C. Byrd
Journal: Blood (2014)
Outcomes of gastrointestinal stromal tumors (GIST) and other intra-abdominal sarcomas (IAS) in the era of imatinib therapy
Authors: D. M. Steinert, L. J. Blakely, S. R. Patel, M. A. Burgess, L. L. Chen, J. C. Trent, A. K. Raymond, R. S. Benjamin
Journal: Journal of Clinical Oncology (2004)

9047 Background: IASs are undergoing a diagnostic evolution. In the era of kit immunohistochemistry and imatinib mesylate therapy the outcome of IASs is unknown. Methods: We analyzed 268 consecutive patients who were referred to our institution for evaluation of the diagnosis of GIST from 12/15/00 to 9/1/01. Patients diagnosed with GIST were treated with imatinib mesylate, and patients diagnosed with other IAS were treated with standard sarcoma chemotherapy. A single sarcoma pathologist reviewed all patients' tumor blocks. Descriptive statistics were performed from the data obtained and comparisons were made using log rank testing. Results: Of 268 patients, 4 patients were excluded because of diagnoses other than sarcoma. Another 46 patients were excluded because no data were available at the time of this abstract. Of the remaining 218 patients, 159 (72.9%) were GIST and 59 (27.1%) were IAS specifically: 31 leiomyosarcoma, 10 spindle cell tumors, 4 unclassified sarcomas, and 14 other types of sarcoma. The median age of patients diagnosed with GIST was 54 (25 -90) and was 52 (20 –87) for patients diagnosed with other IAS. The most common primary tumor sites for patients with GIST were stomach (37.1%), small bowel (34%), and colon (6.3%); whereas, patients with other intra-abdominal sarcomas occurred in the retroperitoneum (25.4%), abdominal viscera (18.6%), and pelvis (11.9%). The most common metastatic sites seen in patients with GIST were liver (68.6%) and peritoneum (51.6%); whereas other IASs metastasized to the liver (39%) and peritoneum (30.5%). While median survival from the time of diagnosis has not been reached in patients with GIST, in other IAS median survival is 63.8 months. Time to progression in patients with GIST was 16.4 months after imatinib and 5.1 months in patients with IAS treated with standard sarcoma chemotherapy. The 5 year survival rate for GIST is 0.80 (95%CI 0.74,0.86), while for other IAS it is 0.53 (95% CI 0.41,0.67). Conclusions: Survival and time to progression are worse for IAS compared to GISTs. New therapies for these tumors are needed. No significant financial relationships to disclose.
Abstract 2092: Heart Failure Patients with Diabetes Have More Comorbidities and Self Care Problems
Authors: Sandra B Dunbar, Seongkum Heo, Susan J Pressler, Eun K Song, Debra K Moser, Terry A Lennie
Journal: Circulation (2008)

Background : Approximately 30 – 47% of heart failure (HF) patients have diabetes mellitus (DM) which is associated with increased risk for rehospitalization and death. Little data exist on psychological factors, physical symptoms, and comorbidities that could affect self care and outcomes in this population. Purpose : To compare HF patients with and without diabetes on demographic, clinical and psychosocial factors associated with self-care and outcomes. Methods : Participants (N = 212, 61 ±11 years old, 62% male, 25% African-American, 62% NYHA functional class III/IV, 37% with DM) from a larger study on nutrition and Body Mass Index (BMI) in HF completed clinical assessments, interviews and questionnaires. Variables and measures were: comorbidities; psychosocial factors of anxiety (Brief Symptom Inventory), depressive symptoms (Beck Depression Inventory-II), and social support (Perceived Social Support Scale); frequency and severity of HF symptoms (Symptom Status Questionnaire); and outcomes of functional status (Duke Activity Status Index; DASI ) and quality of life (MLHFQ). Hospitalizations after 12 months were obtained from medical record review and patient/family interview in a subset. Data were analyzed by t-tests, Chi-Square and nonparametric statistics. Results : Patients with DM were older (63 ± 9 vs 60±12 years, p=.02), had higher BMI (32 ± 6.4 vs 29.4 ± 6.7 kg/m 2 , p=.003), and a greater proportion had coronary artery disease, stroke, and renal dysfunction (p=.01) than those without DM. Thirty-seven percent were receiving insulin therapy. Although no differences in psychosocial factors were found, those with DM reported greater symptom severity (13.7 ±6.7 vs 10.7 ± 6.9 p=.003), and exhibited lower DASI scores (11.4 ± 10.8 vs 15.8 ± 13, p=.001), and MLHFQ scores (45.1 ± 22 vs 38.5 ± 23, p=.04) as well as more total hospitalizations at 12 months (1.5 ± 2.8 vs .55 ± 1.1 p=.04, n=122) than those without DM. Conclusion : HF patients with concomitant DM are at risk for more complex self care regimens due to increased comorbidities and symptom severity, and reduced functional status and quality of life with increased hospitalizations. These data may be useful in designing a comorbidity model of self management interventions to improve outcomes.
Role of Adjuvant Therapy in a Population-Based Cohort of Patients With Early-Stage Small-Cell Lung Cancer
Authors: Chi-Fu Jeffrey Yang, Derek Y. Chan, Paul J. Speicher, Brian C. Gulack, Xiaofei Wang, Matthew G. Hartwig, Mark W. Onaitis, Betty C. Tong, Thomas A. D’Amico, Mark F. Berry, David H. Harpole
Journal: Journal of Clinical Oncology (2016)

Purpose Data on optimal adjuvant therapy after complete resection of small-cell lung cancer (SCLC) are limited, and in particular, there have been no studies evaluating the role of adjuvant chemotherapy, with or without prophylactic cranial irradiation, relative to no adjuvant therapy for stage T1-2N0M0 SCLC. This National Cancer Data Base analysis was performed to determine the potential benefits of adjuvant chemotherapy with and without prophylactic cranial irradiation in patients who undergo complete resection for early-stage small-cell lung cancer. Patients and Methods Overall survival of patients with pathologic T1-2N0M0 SCLC who underwent complete resection in the National Cancer Data Base from 2003 to 2011, stratified by adjuvant therapy regimen, was evaluated using Kaplan-Meier and Cox proportional hazards analysis. Patients treated with induction therapy and those who died within 30 days of surgery were excluded from analysis. Results Of 1,574 patients who had pT1-2N0M0 SCLC during the study period, 954 patients (61%) underwent complete R0 resection with a 5-year survival of 47%. Adjuvant therapy was administered to 59% of patients (n = 566), including chemotherapy alone (n = 354), chemoradiation (n = 190, including 99 patients who underwent cranial irradiation), and radiation alone (n = 22). Compared with surgery alone, adjuvant chemotherapy with or without radiation was associated with significantly improved survival. In addition, multivariable Cox modeling demonstrated that treatment with adjuvant chemotherapy (hazard ratio [HR], 0.78; 95% CI, 0.63 to 0.95) or chemotherapy with radiation directed at the brain (HR, 0.52; 95% CI, 0.36 to 0.75) was associated with improved survival when compared with no adjuvant therapy. Conclusion Patients with pT1-2N0M0 SCLC treated with surgical resection alone have worse outcomes than those who undergo resection with adjuvant chemotherapy alone or chemotherapy with cranial irradiation.
Conditional Survival of Patients With Metastatic Testicular Germ Cell Tumors Treated With First-Line Curative Therapy
Authors: Jenny J. Ko, Brandon Bernard, Ben Tran, Haocheng Li, Tehmina Asif, Igor Stukalin, Margaret Lee, Daphne Day, Nimira Alimohamed, Christopher J. Sweeney, Philippe L. Bedard, Daniel Y.C. Heng
Journal: Journal of Clinical Oncology (2016)

Purpose The International Germ Cell Cancer Collaborative Group (IGCCCG) criteria prognosticate survival outcomes in metastatic testicular germ cell tumor (MT-GCT), but how the initial risk changes over time for those who survived since curative treatment is unknown. Patients and Methods We assessed patients eligible for first-line therapy for MT-GCT at five tertiary cancer centers from 1990 to 2012 for 2-year conditional overall survival (COS) and conditional disease-free survival (CDFS), defined as the probability of surviving, or surviving and being disease free, respectively, for an additional 2 years at a given time point since the initial diagnosis. Results For all patients (N = 942), 2-year COS increased from 92% (95% CI, 91% to 94%) at 0 months to 98% (95% CI, 97% to 99%), and 2-year CDFS increased from 83% (95% CI, 81% to 86%) at baseline to 98% (95% CI, 97% to 99%) at 24 months after diagnosis. Two-year COS improved by 2% (97% at 0 months, 99% at 24 months) in the IGCCCG favorable-risk group, by 5% (94% at 0 months, 99% at 24 months) in the intermediate-risk group, and by 22% (71% at 0 months to 93% at 24 months) in the poor-risk group. Two-year CDFS improved significantly at 12 months for each risk group (favorable, 91% baseline v 95% at 12 months; intermediate, 84% v 95%; poor, 55% v 85%). Baseline IGCCCG risk stratification was not associated with long-term COS or CDFS for patients who survived to greater than 2 years post therapy. No significant differences in COS and CDFS were noted between seminoma and nonseminoma; patients ≥ 40 years old had inferior 2-year COS from 0 to 12 months, but no differences were noted at 18 months. Conclusion Our data suggest that the concept of conditional survival applies to patients with MT-GCT treated with curative therapy. Patients with MT-GCT who survived and remained disease free more than 2 years after the diagnosis had an excellent chance of staying alive and disease free in additional subsequent years, regardless of the initial IGCCCG risk stratification.
Epidemiology of Bone Cancer in Children
Authors: Andrew G. Glass, M.D., Joseph F. Fraumeni, Jr., M.D.
Journal: JNCI Journal of the National Cancer Institute (1970)

In a search for etiologic clues to primary bone cancer in childhood, we examined 1,532 death certificates of all children in the United States dying from these neoplasms, 1960–66, and 396 hospital charts from 12 institutions. Mortality from osteogenic sarcoma did not differ by race, whereas mortality from Ewing's sarcoma was virtually absent among nonwhite children. Bone tumors increased progressively with age through childhood and adolescence. Girls had slightly higher rates at the start of adolescence, but much lower rates after 15 years. There were no time-space variations to suggest environmental factors, such as infectious agents or radioactive materials resulting from the testing of nuclear weapons. Bone cancer seemed related to a variety of antecedent skeletal defects, but not to nonskeletal anomalies. Retinoblastoma occurred in 2 children with osteogenic sarcoma, and neoplasms of bone and brain seemed unduly frequent among close relatives. Thus the pathogenesis of bone cancer in children is influenced by race, sex- and age-associated factors correlated with skeletal growth, preexisting bone defects, and genetic and/or environmental influences underlying family aggregates.