tbuckley/cabot-search huggingface dataset:
A randomized trial of gemcitabine (G) versus G plus cisplatin in chemotherapy-naive advanced pancreatic adenocarcinoma: The GIP-1 <i>(Gruppo Italiano Pancreas— GOIM/GISCAD/GOIRC)</i> study
Authors: G. Colucci, R. Labianca, F. Di Costanzo, V. Gebbia, G. Cartenì, B. Massidda, L. Frontini, M. Falconi, C. Gallo, M. Di Maio
Journal: Journal of Clinical Oncology (2009)

4504 Background: Single-agent gemcitabine (G) remains standard treatment for advanced pancreatic adenocarcinoma (APC). The GIP-1 randomized phase III trial (clinicaltrials.gov ID NCT00813696 ) was performed to compare the combination of cisplatin (P) and G vs. G alone as 1st-line treatment. Methods: Patients (pts) with locally advanced and/or metastatic pancreatic adenocarcinoma, age 18–75, Karnofsky Performance Status (KPS) ≥50, were randomized to receive G (arm A) or G+P (arm B). In arm A, G was administered at 1000 mg/m2 weekly for 7 consecutive wks, and, after a 2-week rest, on day 1, 8, 15 every 4 wks. In Arm B, P 25 mg/m2 weekly (with the exception of day 22) was added to G, same dose used in Arm A (Colucci et al, Cancer 2002; 94:902–10). No maximum number of cycles was planned. Primary endpoint was overall survival (OS). Clinical benefit (CB), objective response rate (ORR), progression-free survival (PFS), toxicity and quality of life were secondary endpoints. To have 80% power of detecting a 0.74 Hazard Ratio (HR) of death (corresponding to increase in median OS from 4.8 to 6.5 months, with bilateral alpha=0.05, 400 pts were planned and 355 deaths were required for final analysis. Results: From April 2002 to April 2007, 400 pts were enrolled (A:199, B; 201) in 46 Italian Institutions. Median age was 63 yrs (range 35–75), 59% were males, 84% stage IV, 83% KPS≥80. After a median follow-up of 38.2 months and 357 deaths, median OS was 8.3 vs 7.2 months in arm A and B, respectively (HR 1.10, 95% CI 0.89–1.35, p=0.38). Median PFS was 3.9 vs 3.8 months in arm A and B, respectively (HR 0.97, 95% CI 0.80–1.19, p=0.80). ORR was 10.1% in arm A and 12.9% in B (p=0.37). CB response was experienced by 23.0% and 15.1% (Arm A vs B, p=0.057). Patients assigned to combination arm experienced more anaemia (all grades: 50% vs 39%, G3: 5% vs 1%), more neutropenia (all grades: 44% vs 36%, G3&amp;4: 25% vs 14%) and more thrombocytopenia (all grades: 57% vs 29%, G3&amp;4: 16% vs 5%). No relevant differences were seen in non-haematological toxicity. Conclusions: Weekly combination of P and G, compared to single-agent G as 1st-line treatment of APC, failed to demonstrate any improvement in OS, PFS, ORR and clinical benefit. No significant financial relationships to disclose.
Quantification of Lipid-Rich Core in Carotid Atherosclerosis Using Magnetic Resonance T2 Mapping
Authors: Joshua T. Chai, Luca Biasiolli, Linqing Li, Mohammad Alkhalil, Francesca Galassi, Chris Darby, Alison W. Halliday, Linda Hands, Timothy Magee, Jeremy Perkins, Ed Sideso, Ashok Handa, Peter Jezzard, Matthew D. Robson, Robin P. Choudhury
Journal: JACC. Cardiovascular imaging (2016)

The aim of this study was to: 1) provide tissue validation of quantitative T2 mapping to measure plaque lipid content; and 2) investigate whether this technique could discern differences in plaque characteristics between symptom-related and non–symptom-related carotid plaques. Noninvasive plaque lipid quantification is appealing both for stratification in treatment selection and as a possible predictor of future plaque rupture. However, current cardiovascular magnetic resonance (CMR) methods are insensitive, require a coalesced mass of lipid core, and rely on multicontrast acquisition with contrast media and extensive post-processing. Patients scheduled for carotid endarterectomy were recruited for 3-T carotid CMR before surgery. Lipid area was derived from segmented T2 maps and compared directly to plaque lipid defined by histology. Lipid area (%) on T2 mapping and histology showed excellent correlation, both by individual slices (R = 0.85, p < 0.001) and plaque average (R = 0.83, p < 0.001). Lipid area (%) on T2 maps was significantly higher in symptomatic compared with asymptomatic plaques (31.5 ± 3.7% vs. 15.8 ± 3.1%; p = 0.005) despite similar degrees of carotid stenosis and only modest difference in plaque volume (128.0 ± 6.0 mm3 symptomatic vs. 105.6 ± 9.4 mm3 asymptomatic; p = 0.04). Receiver-operating characteristic analysis showed that T2 mapping has a good ability to discriminate between symptomatic and asymptomatic plaques with 67% sensitivity and 91% specificity (area under the curve: 0.79; p = 0.012). CMR T2 mapping distinguishes different plaque components and accurately quantifies plaque lipid content noninvasively. Compared with asymptomatic plaques, greater lipid content was found in symptomatic plaques despite similar degree of luminal stenosis and only modest difference in plaque volumes. This new technique may find a role in determining optimum treatment (e.g., providing an indication for intensive lipid lowering or by informing decisions of stents vs. surgery).
Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia and Granulomatous Inflammation Mimicking High-Grade Malignancy on FDG-PET/CT
Authors: Joyce Hsu, Leo Jia, Darko Pucar, Hadyn Williams, Jayanth Keshavamurthy
Journal: Clinical Nuclear Medicine (2016)

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare form of preinvasive lung lesion associated with indolent carcinoid tumor formation. This disease is characterized by multiple small pulmonary nodules with low SUVmax on F-FDG PET. Biopsy and immunohistochemical staining for neuroendocrine markers confirm diagnosis. There is no consensus for treatment, which typically involves surgical excision or management of symptoms with steroid-based therapies. We report an unusual case of DIPNECH colocalizing with necrotizing granulomatous inflammation mimicking high-grade aggressive malignancy on FDG-PET and a typical case of DIPNECH for comparison with low FDG avidity.
HIV-Related Myocardial Vulnerability to Infarction and Coronary Artery Disease
Authors: Matthew J. Feinstein, Sumeet S. Mitter, Ajay Yadlapati, Chad J. Achenbach, Frank J. Palella, Pedro Engel Gonzalez, Sheridan Meyers, Jeremy D. Collins, Sanjiv J. Shah, Donald M. Lloyd-Jones
Journal: Journal of the American College of Cardiology (2016)
Electrochemoterapy (ECT) for the treatment of superficial tumor localizations
Authors: M. Guida, G. Porcelli, E. Ruggieri, A. Zito, V. Mattioli, S. Montemurro, G. Colucci
Journal: Journal of Clinical Oncology (2009)

e13526 Background: ECT is an effective local treatment for palliation on inoperable superficial neoplastic lesions from any type of tumour. It combines chemotherapy and electric pulses that permeabilize the cell membrane in a transient and reversible manner, allowing low-perrneant drugs to enter the cell, thus magnifying their cytotoxicity. Recent1y, a new device (Clinoporetor, IGEA-Srl, Italy) has been developed to supply electric pulses with appropriate parameters permitting the clinical use of ECT. Methods: We treated 26 pts, M/F 12/14; median age 61 yrs, range 38–87: 7 breast cancer with nodular or infiltrating lesions in thoracic or abdominal wall; 12 melanoma (2 wide infiltration of thoracic wall, 10 in transit metastases or loco-regional recurrences); 2 head-neck cancer with a wide neck-scalp infiltration; 3 lymphomas with cutaneous lesions, 1 soft tissue sarcoma with a subcutaneous recurrence, 1 gastric cancer with 2 cutaneous localizations. The areas treated ranged from 1 to 30 cm on diameter. 12 pts requested a prior surgery debulking and 3 pts received ECT in pre-irradiated area. Intravenous bleomycin (15 mg/m 2 ) were used in all patient; electric pulses were than applied to the tumor areas by needle electrodes in a time window of 20 minutes. In total 32 procedures were performed, 6 as out-patient in local anaesthesia and 26 in general anaesthesia; 6 pts requested a second application. Results: Treatment was safe and well tolerated, particularly when general anaesthesia was used. At the second/third week, all pts showed a regression of almost all lesions with a necrotic, fibro-sclerotic evolution. After 1–2 months from ECT, we obtained a 70% CR and a 10%PR of the lesions. Some pts showed a response after the second procedure. About 50% of lesions remained in remission for a long period (median 8 months, range 1–23+); 11 of 12 pts previously undergone surgical debulking never relapsed in the treated area. Concomitant systemic treatment, no rapid spreading of the disease and surgical debulking were related to a better local control and survival. Conclusions: ECT is a promising and safe treatment for superficial lesions from different malignancies. General anaesthesia and surgical debulking permit to treat very large and deeper lesion with a very good local control. No significant financial relationships to disclose.
Phase II trial of bevacizumab (B) plus everolimus (E) for refractory metastatic colorectal cancer (mCRC).
Authors: I. Altomare, K. B. Russell, H. E. Uronis, M. Morse, S. D. Hsu, Y. Zafar, J. C. Bendell, A. Starodub, W. Honeycutt, H. Hurwitz
Journal: Journal of Clinical Oncology (2010)

3535 Background: For patients (pts) with mCRC, treatment options are absent after progression on 5-FU, oxaliplatin, irinotecan, bevacizumab, and cetuximab/panitumumab. Preclinical data demonstrate combined VEGF and mTOR inhibition has greater antiangiogenic and antitumor activity than either monotherapy, and phase I data demonstrated that the combination of B + E is safe and generally well tolerated. This phase II trial evaluates efficacy and tolerability of B+E in mCRC patients who have progressed on standard therapies. Methods: 50 pts with refractory mCRC were treated with B 10 mg/kg q2 wks and E 10 mg PO QD until progression. Blood, skin, and tumor biopsies pre- and on-treatment were collected for markers of response and resistance. Results: 47 of 50 pts had prior B exposure; 42 pts had previously progressed on B. Median number of prior regimens was 4. Although no complete or partial responses were seen, 46% of pts achieved disease control for a median duration of 6.1 months (mos) (range 2.3-12.6): 8 pts had minor responses (median duration of response 4.1 mos, range 2.3-11.9+) and an additional 15 patients had SD (median duration of response 6.7 mos, range 3.2-12.6+). Three patients with prolonged stable disease have been on treatment > 1 year. There was one grade (Gr) 4 adverse event (AE) of hypokalemia. Noteworthy grade 3 AEs related to treatment were hypertension (n = 7), mucositis/proctitis (n = 3), fistula/abcess (n = 3), bowel perforation (n = 1), azotemia/proteinuria (n = 2), fatigue (n = 2), thrombocytopenia (n = 2), hyperglycemia (n = 6), hypokalemia (n = 6), hypophosphatemia (n = 2), hyperlipidemia (n = 3) and hyperbilirubinemia (n = 2). There was one Gr 3 event each of rhabdomyolysis, neuropathy, volume depletion, prolonged QT interval, GI hemorrhage and neutropenia. Other events of interest were: Gr 1-2 mucositis (68%, n = 34), Gr 1-2 hyperlipidemia (64%, n = 32). Biomarker data is pending. Conclusions: B + E has promising activity in refractory mCRC (even in pts who have progressed on a B-based regimen) with a disease control rate of 46%, suggesting B + E may overcome resistance to B. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Novartis, Roche Genentech, Novartis, Roche Genentech, Novartis
High efficiency transduction of chronic lymphocytic leukemia with adenovirus type 35
Authors: F. Hedjran, D. Whitacre, T. Kipps, T. R. Reid
Journal: Journal of Clinical Oncology (2006)

6612 Background: Adenovirus (Ad) vectors have been used extensively in genetic manipulation of cultured cells and gene therapy, with the group C Ad serotypes 2 and 5 being most widely used. The group C viruses have been shown to infect target cells in a two-step process. There is an initial high-affinity step in which Ad fiber protein binds to the the coxsackie/adenovirus receptor (CAR), increasing the local concentration of the virus at the cell surface. In the second step, the Ad penton base protein binds to integrins on the target cell surface and the virus is internalized. CLL cells to not express CAR and so require a very high concentration of Ad5 for transduction. Group B adenoviruses differ from other groups, having been shown to require CD46 (the measles virus receptor) to infect target cells. We are investigating Ad35 for use as a gene therapy vector and a laboratory tool for manipulating CLL cells ex vivo. Methods: We used a modified viral vector (Shayakhmetov et al., 2000 J Virol (74) pp 2567–83) with first 64 amino acids from the Ad5 fiber fused to the last 279 amino acids from the Ad35 fiber substituted into the Ad5 fiber ORF. This vector was used to assess the relative efficiency of the chimeric Ad5/35 vector compared to wild-type Ad5. Results: Primary CLL cells were transduced by the standard Ad5 and chimeric Ad5F35 vectors. Ad5F35 vector is about 100-fold more potent at transducing CLL cells compared to an Ad5 vector. Twelve CLL, PBMC and HeLa samples were tested for CD46 expression by flow cytometry. Each CLL population was 90–99% bright for CD46. Primary CLL cells and normal PBMCs were transduced by Ad5F35-GFP at an MOI of 10. The CLL cells are more transducible than normal PBMCs (p&lt;0.05). This difference in transducibility is not a result of low CD46 expression. Conclusions: Adenovirus Type 35 is a promising vector for use in delivering gene therapy agents to CLL cells at significantly lower viral doses and more favorable therapeutic index compared with traditional Ad5 vectors. No significant financial relationships to disclose.
Action is urged to improve physical health in severe mental illness
Authors: Anne Gulland
Journal: BMJ (2016)

Doctors and other health professionals have come together to urge greater action to tackle poor physical health in people with severe mental illness.

A report published by organisations including the Royal College of Psychiatrists, the Academy of Medical Royal Colleges, and the Royal College of General Practitioners makes a number of recommendations to ensure that people with severe mental illness receive the same standards of physical healthcare as the general population and to reduce their risk of premature death.1

The authors note that nearly half (46%) of people with a severe mental illness have …
Abstract PR13: Understanding the systemic interactions between primary tumors and disseminated tumor initiating cells
Authors: Zafira Castano, Christine L. Chaffer, Asaf Spiegel, Ayush Pant, Andrea L. Richardson, Ferenc Reinhardt, Timothy Marsh, Susanne Janssen, Ann M. Gifford, Robert A. Weinberg, Sandra S. McAllister
Journal: Cancer Research (2016)

Abstract The causes for breast cancer recurrence in the form of metastatic disease and the reasons why less than 1% of disseminated tumor cells form metastases are unknown. A number of studies have demonstrated that the aggressive cancer cell population capable of driving metastasis feature properties of the epithelial-mesenchymal transition (EMT) and tumor initiation (TI). We previously reported novel mechanisms by which systemic and microenvironmental factors enrich tumors for EMT and TI genes and demonstrated that recurrence rates are not strictly due to tumor cell intrinsic properties (Castano et al., Cancer Discovery 2013). Using a preclinical model of breast cancer during the early phases of metastatic disease, when patients harbor disseminated tumor initiating cells (TICs) in the periphery at the time of their primary diagnosis (McAllister SS et al., Cell 2008), we recently made a surprising, and seemingly contrasting discovery. Specifically, we found that certain primary tumors can inhibit progression of disseminated TICs into overt tumors, maintaining them in the TI state and slowing their proliferation and differentiation to form tumor tissue mass. We established that the primary tumor induce mobilization of IL1beta-expressing monocytes that are recruited to sites where TICs reside. At those sites, signaling via the IL1 receptor maintains the EMT/TI state of the disseminated cells, thus promoting disease indolence. Importantly, surgical removal of the primary tumor enables TICs at the secondary sites to exit the EMT/TI state and to produce robustly growing tumors. Confirming our xenograft results, we established that stromal expression of IL1β in patient tumors is associated with poor outcome. Collectively, these data highlight the profound impact a primary tumor can exert on metastasizing cells - in this case, by altering the systemic environment to the detriment of secondary tumor growth. Moreover, our data highlight a central role for IL1β in modulating tumor cell plasticity and suggest it may provide a novel avenue for targeting recurrent disease. Citation Format: Zafira Castano, Christine L. Chaffer, Asaf Spiegel, Ayush Pant, Andrea L. Richardson, Ferenc Reinhardt, Timothy Marsh, Susanne Janssen, Ann M. Gifford, Robert A. Weinberg, Sandra S. McAllister. Understanding the systemic interactions between primary tumors and disseminated tumor initiating cells. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr PR13.
Identifying Causes for Excess Mortality in Patients With Diabetes: Closer but Not There Yet
Authors: Oriana Hoi Yun Yu, Samy Suissa
Journal: Diabetes Care (2016)

Diabetes is a chronic disease associated with increased morbidity and mortality (1), mainly from cardiovascular disease (2–6). Treatment of diabetes includes normalizing hyperglycemia to attain glycemic targets and treatment of cardiovascular risk factors such as hypertension and dyslipidemia. This multifactorial intervention strategy has been shown to decrease cardiovascular and all-cause mortality among patients with type 2 diabetes (7). Nevertheless, mortality in diabetes remains elevated (2,5).

A number of epidemiological studies have quantified the risk of death among patients with diabetes and assessed the causes of death (2–6), with highly varying results (Table 1). The South Tees Diabetes Mortality Study (2) found an over threefold increase in all-cause mortality, mainly attributed to increased cardiovascular deaths, but found no increased risk of cancer mortality. The Australian Diabetes, Obesity and Lifestyle Study (AusDiab) (3) of over 10,000 individuals reported a little over twofold increase in the risk of all-cause mortality, with the majority due to cardiovascular causes. The Emerging Risk Factors Collaboration (ERFC) study (6), involving over 800,000 individuals, reported a little under twofold increase in the risk of all-cause mortality associated with diabetes. It also found that diabetes was associated with an increased risk of death from cancer (hazard ratio [HR] 1.25 [95% CI 1.19–1.31]), from vascular disease (HR 2.32 [95% CI 2.11–2.56]), and from nonvascular and noncancer etiologies (HR 1.73 [95% CI 1.62–1.85]). More recently, a study using the Swedish National Diabetes Register (5) on over 400,000 patients with type 2 diabetes matched to more than 2 million subjects …
ULTRASOUND MEASUREMENT OF CHEST WALL THICKNESS IN ELITE RUGBY PLAYERS; A COMPARISON BETWEEN THE NEEDLE THORACOCENTESIS SITES
Authors: C Jones, A Adejuwon
Journal: British Journal of Sports Medicine (2016)

Aims There are no known published studies to support current pitch side guidelines for the management of a tension pneumothorax in a sporting population (1). Temporary management of this condition involves needle thoracocentesis (NT) at the 2nd intercostal space mid clavicular line (2MCL). The 5th intercostal space anterior axillary line (5AAL) has been suggested as an alternative site.1 The aim of the study was to compare chest wall thickness (CWT) at the 2MCL and the 5AAL of an elite rugby union team. The secondary aim was to calculate potential NT failure between player positions; Forwards and Backs. Methods Potential failure was calculated by comparing CWT in relation to both a standard cannula length of 4.5 cm and the advised needle length of 5.0 cm. Ultrasound recorded three measurements of CWT at the 2MCL and 5AAL on both sides of the thorax. Results Forty-three male players with a mean age of 25.7 years participated. Forwards demonstrated a thicker CWT than Backs at both sites. The mean CWT at 2MCL was 3.78 cm in Forwards and 3.30 cm in Backs. The mean CWT at the 5AAL site was uniformly thinner and measured 3.16 cm in Forwards and 2.40 cm in Backs. 22.2% (n=6) of Forwards had a CWT greater then 4.5 cm. 11.1% (n=3) of Forwards had a CWT greater then 5.0 cm at 2MCL. For all player positions the CWT at the 5AAL was less than 5.0 cm. Conclusions Forward position rugby players had a greater CWT than Back players. One in ten Forward players had the potential to fail NT in accordance to suggested guidelines. CWT at the 5AAL was significantly thinner (p&lt;0.05) than at the 2MCL for all players and may be a more suitable NT site for Forward players.
Predictive role of <sup>18</sup>F-FDG-PET/CT 1 month before and after hypofractionated stereotactic body radiation therapy for stage I non-small cell lung cancer
Authors: S. Song, J. Ryu, S. Lee, S. Ahn, J. Kim, J. Lee, C. Park, E. Choi
Journal: Journal of Clinical Oncology (2009)

7569 Background: To know the predictive role of 18 F-FDG-PET/CT 1month before and after stereotactic body radiation therapy (SBRT) to stage I non-small cell lung cancer (NSCLC). Methods: Between 2004 and 2007, 20 patients received SBRT with 48 Gy for 4 consecutive days and checked two times of FDG- PET/CT and chest CT with contrast-enhancement at 1 month before and after SBRT. Change of maximal SUV (SUV max ) on FDG-PET/CT and the longest tumor diameter on chest CT before and after SBRT was measured. Patients only with high FDG uptake, SUV max 3.0 or above, on FDG-PET/CT before SBRT and tumor diameter below 5 cm were analyzed in this study. Change of tumor diameter was classified to PR (partial response), SD (stable disease), and DP (disease progression) as RECIST criteria and change of SUV max was described as % change. Chest CT was checked at every 3 or 6 months during follow-up. Results: Mean time intervals from SBRT to FDG-PET/CT and chest CT were 32 and 30 days respectively. Mean longest tumor diameter was changed from 2.59 cm (1.36–3.93) to 2.17 cm (1.18–3.41), and its reduction rate was -16.2%. By RECIST criteria, 4 patients showed PR, 15 patients showed SD, and other 1 patient showed DP. Mean decrease rate of SUV max on FDG-PET/CT was -52.1% and its mean value was changed from 7.1 (3.2–13.1) to 3.4 (0.3–9.8). Median follow-up time was 16 months. Local tumor progression developed in 2 (10%) patients and time to progression was 3.4, 6.1 months. Tumor responses on post-SBRT chest CT were PR in 1 and SD in the other 1 patient, and SUV max changes were -31.9%, -25.5% in each. Most of patients showing no response, SD or DP, didn't recur after SBRT, and so chest CT at 1 month could not predict actuarial tumor response. On the contrary to chest CT, no patients showing SUV max decreases over 40% experienced tumor progression after SBRT. High decrease rate of SUV max over 40% decrease on FDG-PET/CT 1 month after SBRT could warrant good actuarial local tumor control earlier. Conclusions: Change of SUV max on FDG-PET/CT 1 month before and after SBRT could predict actuarial local tumor control of stage I NSCLC earlier and 1 month after SBRT was adequate timing for the earlier evaluation of tumor response. No significant financial relationships to disclose.
A Different Ontogenesis for CLL Cases Carrying Stereotyped Antigen Receptors: Molecular and Computational Evidence
Authors: Nikos Darzentas, Anastasia Hadzidimitriou, Fiona Murray, Katerina Hatzi, Par Josefsson, Nikolaos Laoutaris, Carol Moreno, Achilles Anagnostopoulos, Jesper Jurlander, Athanasios Tsaftaris, Nicholas Chiorazzi, Chrysoula Belessi, Paolo Ghia, Richard Rosenquist, Frederic Davi, Kostas Stamatopoulos
Journal: Blood (2008)