tbuckley/cabot-search huggingface dataset:
Pemetrexed versus taxane-containing platinum doublet therapy for advanced non-squamous non-small cell lung cancer (NSCLC): A systematic analysis.
Authors: Madhusmita Behera, Rathi Narayana Pillai, Taofeek Kunle Owonikoko, Suchita Pakkala, Conor Ernst Steuer, Nabil F. Saba, Dong Moon Shin, Chandra Prakash Belani, Fadlo Raja Khuri, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2015)

e19046 Background: Pemetrexed (PEM) is superior to gemcitabine in patients (pts) with non-squamous (NS) histology, when given in combination with cisplatin. Comparative efficacy data of platinum doublet containing PEM vs. taxanes (TAX) in NS histology is limited. Methods: An extensive search of published trials was conducted from electronic databases (MEDLINE, EMBASE, Cochrane) and meeting proceedings. Phase 2 and randomized trials (RCTs) reporting on the efficacy of PEM or TAX combined with any platinum agent in stage IIIB/IV NS-NSCLC pts were included. Trials enrolling < 10 pts and squamous histology were excluded. A systematic analysis of data was performed using Comprehensive Meta Analysis (Version 2.2) under fixed and random effect models. Clinical outcomes were compared using weighted estimates of overall and progression free survival (OS, PFS) and objective response rate (RR). A meta-analysis was performed on RCTs that directly compared the 2 regimens. All comparisons used a two-tailed T-test with a significance level of 0.05. Results: Forty-five studies reported between 2004-2014 were eligible, 5 of which were RCTs that compared both groups. A total of 7157 pts were included: 2596 PEM and 4561 TAX. The groups had comparable baseline characteristics: males 56% vs. 60%, adenocarcinomas 86% vs. 86%, stage IV 89% vs.84%, smokers 81% vs. 78%, PS (0/1) 45/53% vs. 39/60%, median age 63 vs. 62 years in PEM and TAX groups respectively. The median OS in PEM and TAX groups were 13.7 m and 13.2 m (p = 0.15) respectively. The median PFS was 6.1 m and 5.8 m (p= 0.08) for PEM and TAX respectively. The RR was 39% with PEM and 30% with TAX (p= 0.2). From meta-analysis of RCTs for efficacy, no difference was found in PFS (HR 0.91 CI 0.81-1.02; p= 0.1) or in RR (OR 0.9 CI 0.7-1.3, p= 0.9). The overall toxicity profile was similar for both groups with 59% ≥ grade 3 events in PEM vs. 64% in TAX. However, TAX had higher incidence of hematologic toxicities with a significantly higher rate of neutropenia (36% vs. 18%, p= 0.002). Conclusions: PEM or TAX when given in combination with platinum for treatment of advanced NS NSCLC have comparable efficacy. Hematological toxicity was higher with TAX.
Management of radiation dermatitis.
Authors: Soham Chaudhari, Patricia Lucey, Loren Gorcey, Sravana Chennupati, Shalom Kalnicki, Beth McLellan
Journal: Journal of Clinical Oncology (2015)

e20652 Background: Acute radiation dermatitis (RD) is a potentially distressing adverse event resulting from radiation therapy. RD significantly impairs patient compliance and quality of life and can lead to interruption in treatment. While several topical agents and dressings are used to treat RD, there is great variation in management among practitioners due to limited evidence-based recommendations. We aim to define the complex prophylaxis and treatment patterns for acute RD in the United States (US) to recognize if these patterns are associated with evidence-based guidelines. Methods: A Patterns of Care Survey of the current management of radiation dermatitis was conducted from August 2014 to December 2014 across the United States. The results were compared with the Multinational Association for Supportive Care in Cancer (MASCC) guidelines. The questions were designed to evaluate demographics of responders, their training and comfort in the management radiation dermatitis, and their patterns of care regarding treatment. Results: The MASCC panel strongly recommends the prophylactic use of gentle washing with water which 53.29% of participants encouraged. However, practitioners also recommended the use of Aloe Vera prophylactically (53.97%) and for Grade 1 RD (47.26%), both strongly discouraged by the panel based on several trials demonstrating its lack of efficacy. While MASCC makes no recommendations for emollients, they are utilized to treat Grade 1 RD by 74.25% of practitioners. The prophylactic use of topical steroids is strongly recommended by the MASCC, although only 30.14% of surveyed practitioners utilize them for this purpose, while 30.41% using them to treat Grade 1. The panel makes a weak recommendation for the prophylactic use of silver sulfadiazine cream which is used by 72.35% of participants for Grade 2 and 3 RD. Conclusions: There is a wide disparity between evidenced-based guidelines for preventing and treating RD and its practice in the US. Better education of the oncology and dermatology community and adherence to evidence-based guidelines may improve patient compliance and quality of life.
PS-126-Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis
Authors: Sara Lemoinne, Astrid Kemgang, Karima Ben Belkacem, Marjolene Straube, Sarah Jegou, Christophe Corpechot, Olivier Chazouillères, Chantal Housset, Harry Sokol
Journal: Journal of Hepatology (2019)
Pattern of relapse in limb/girdle low-grade liposarcoma/atypical lipomatous tumor (ALT) during guidelines-suggested follow up (FU).
Authors: Raimondo Piana, Lorenzo D'Ambrosio, Elena Maldi, Antonella Boglione, Danilo Galizia, Michele Boffano, Enrico Bellato, Ugo Albertini, Paola Bergnolo, Paola Boccone, Erica Palesandro, Alessandra Linari, Alessandro Comandone
Journal: Journal of Clinical Oncology (2015)

10570 Background: In soft tissue sarcomas (STS) after complete (marginal/wide/radical margins) surgery, surveillance should be tailored to individual patient’s (pts) risk that depends on histotype, grading and site of origin. Unfortunately there is a substantial lack of evidence to personalize FU and most guidelines (GL) suggest both clinical (history and physical examination) and imaging procedures (X-rays, CT, US, MRI) taking into account two broad categories (low- and high-grade STS) but ignoring histotype heterogeneity. We reviewed our prospectively collected STS database to assess ALT pattern and risk of relapse in order to improve our future FU policy. Methods: In 2001 our regional-based health system adopted a STS GL (www.reteoncologica.it) suggesting the following FU: pts examination every 4-6 months in the first 3 years, every 6 months until the 5th year, then yearly. Pts underwent local and chest imaging (either CT or X-rays). Average cost and exposure to X-rays were computed for the entire FU. We searched for pts affected by ALT with complete clinical records (centrally reviewed histology, surgical record, and at least 3-year FU). ALT-specific overall survival (OS), relapse-free survival (RFS) and local-RFS (LRFS) were estimated according to Kaplan-Meier method. Results: Between 2001 and 2011 we took care of 163 patients affected by LGL. Complete records were available in 152 (93%) pts. Adherence to FU was considered adequate in 127 (78%) pts (median age 58, IQR 50-67; median size 14 cm, IQR 8-19). Median FU was 117 months (95% CI 95-140). Ten-year OS, RFS and LRFS were 100%, 74% and 74%, respectively. Among the 13 (10%) relapsed pts, we observed 13 local relapses and no distant metastases. All relapses were surgically amenable. Two pts died during their FU and none because of systemic progression. The chest X-rays estimated 10-year FU cost is 450 euros per pts with an average total exposure of 0.9 mSv. Conclusions: Until a hardly foreseeable randomized trial on FU will be performed, our study, though retrospective, does not support the systematic use of chest imaging in ALT FU that adds apparently needless costs and low, but not negligible, ionizing radiation risks.
Outcome of combined bevacizumab and irinotecan for patients with progressive brain metastases from non-small cell lung cancer (NSCLC).
Authors: Evelyn M Brosnan, Camilo E. Fadul, Konstantin H. Dragnev, Melissa C Davis, Khushboo A Shah, Clifford J Eskey
Journal: Journal of Clinical Oncology (2015)

e19059 Background: About 30-44% of patients with non-small cell lung cancer (NSCLC) will develop brain metastases, with a median survival if untreated of less than 3 months. Treatment options are limited to surgery, whole brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). As more effective treatments for systemic disease are available, the brain is a frequent site of progression that after radiation is especially difficult to treat. Brain re-irradiation for recurrent disease is associated with prohibitively high risks for complications. New treatment options are desperately needed. We report the results of combination therapy with bevacizumab and irinotecan in patients with NSCLC who have developed progressive brain metastases. Methods: This is a retrospective study between 2011 and 2014, of 8 patients with brain metastases from NSCLC who were treated with bevacizumab and irinotecan, after progression of disease in the brain despite WBRT or SRS radiation. Brain MRI was used to measure response after 2 to 4 doses of therapy. Adverse effects, number of cycles, progression free survival (PFS) and overall survival (OS) were recorded. Results: Median shrinkage of lesion size was 53% (range 22-100%) after a median of 2.5 doses. The PFS median from start of therapy was 4 months (range 1-14). The OS was 5.2 months (range 1-23). The regimen was well tolerated. None of the patients had intracranial or systemic bleeding and the most common side effects were fatigue, nausea and diarrhea. Conclusions: Combination therapy with bevacizumab plus irinotecan for progressive brain metastases after radiation results in more than 50% response rate and appear to extend survival in this small retrospective cohort, lending support for further exploration in a randomized clinical trial.
FRI-294-Mitochondrial GNMT-complex II is recovered by miR-873-5p targeting in NAFLD
Authors: David Fernández Ramos, Pablo Fernández Tussy, Fernando Lopitz Otsoa, Jorge Simón, Lucía Barbier Torres, Beatriz Gómez Santos, Maitane Núñez, Mikel Azkargorta, Virginia Gutiérrez de Juan, Marina Serrano-Macia, Rubén Rodríguez Agudo, Devin G. Champagne, Paula Iruzubieta, Juan Anguita, Mercedes Rincón, Felix Elortza, Arslanow Anita, Marcin Krawczyk, Frank Lammert, Melanie Kirchmeyer, Iris Behrmann, Rui E. Castro, Javier Crespo, Shelly C. Lu, Marta Varela-Rey, Patricia Aspichueta, Teresa Cardoso Delgado, José M. Mato, María Luz Martínez-Chantar
Journal: Journal of Hepatology (2019)
Patients' consent should have been sought
Authors: H. Goodare
Journal: BMJ (1996)

EDITOR,—It is ironic that a study in which informed consent was not sought1 should be published in the same issue as an editorial by Richard Smith calling for action on misconduct in research.2 The study falls well short of good clinical research practice, which is a requirement in trials sponsored by the pharmaceutical industry.3 The hospital ethics committee was surely at fault in allowing the research to proceed in contravention of the Nuremberg Code.

In her commentary Claire Foster addresses …
FLT-PET (Fluorothymidine) and Ki-67 to measure effects of a short course of aromatase inhibitor therapy in ER+ breast cancer patients.
Authors: Hannah M. Linden, Lanell Peterson, Brenda F. Kurland, Alena Novakova, Andrew Shields, Vijayakrishna K. Gadi, Jennifer M. Specht, Mark Muzi, Paul Kinahan, David A. Mankoff
Journal: Journal of Clinical Oncology (2015)

e22161 Background: The purpose of this study was to evaluate the change in FLT-PET measures observed following a short course of Aromatase Inhibitor (AI) and to explore associations between FLT-PET changes and post-therapy Ki-67. Methods: Twenty-three female patients with ER+ breast cancer (AJCC stage 0-IIIA) underwent paired FLT-PET scans. The first scan occurred prior to the start of endocrine therapy and the second prior to surgery. After baseline imaging (and then ovarian suppression in premenopausal patients), AI was initiated, in the preoperative window until curative surgery (9-69 days). Tissue samples were taken from diagnostic biopsy and at the time of surgery for Ki-67 assessment. FLT uptake was measured using standardized uptake value (SUVmax) and the model parameter Ki(flux). Results: SUVmax ranged from 1.1 to 8.1 (median = 2.5) for the first scan and 0.8 to 3.7 (median = 1.8) for the second scan, with a median percent change of -27% (range 1-80% decrease). The median Ki was 0.025 mL/min/g (range = 0.001-.0.082) and 0.018 (range 0.001-0.078) for scan 1 and scan 2 respectively. The median Ki-67 was 12% (range 6-54) at biopsy and 3% (range 0-41) at surgery (2-36 percentage point decrease, median 9). Rank-order concordance between Ki-67 and FLT-PET measures was good, but the measures did not agree for response to therapy. Of the 9/22 evaluable biopsy samples with Ki-67 > 20%, 4 had Ki-67 ≤ 5% at surgery (-28%, -34%, -36%, -70% SUVmax); 2 were 5-20% at surgery (-10% and -80% SUVmax), and 3 were still > 20% (-27%, -32%, and -46% SUVmax). Trends in imaging parameters of response between (6) premenopausal vs (17) postmenopaual patients, and in (17) ductal vs (6) lobular patients were similar. Conclusions: FLT PET measured endocrine treatment induced metabolic changes in the preoperative window setting. Many of these early stage tumors had low baseline proliferation (13/22 Ki-67 ≤ 20% with median SUVmax 2.2). In tumors with high pre-therapy cell proliferation by Ki-67 or FLT-PET SUVmax, response was non-uniform and did not agree between tissue and imaging measures. Further study is necessary to examine the implications of these findings in early-stage, untreated disease.
Genome–Epigenome–Senescence: Is TET1 a Caretaker of p53-Injured Lung Cancer Cells?
Authors: Yutaka Kondo
Journal: Cancer Research (2019)

Abstract The study by Filipczak and colleagues identified the interplay between mutant p53 proteins and methylcytosine dioxygenase ten-eleven translocation 1 (TET1) in lung cancers. p53 transversion mutations were closely associated with high TET1 expression, which prevented genomic instability–associated cellular senescence. Depletion of TET1 was synergistic with classical antitumor drugs, such as cisplatin or doxorubicin, providing an attractive rationale for targeted therapies against TET1 combined with antitumor drugs in patients with p53-mutant lung cancer. See related article by Filipczak et al., p. 1758
SAT-247-The evaluation of the inhibitory effect of oral anti-hepatitis C virus agents on carcinogenesis
Authors: Seiichi Mawatari, Akihiro Moriuchi, Shuzo Tashima, Ai Kasai, Sho Ijuin, Kazuaki Tabu, Kohei Oda, Akio Ido
Journal: Journal of Hepatology (2019)
Abstract 210: Kawasaki Disease in Patients Older Than 10-years Old in a Children’s Hospital In Mexico City
Authors: ITZEL E RIOS-OLIVARES, LUIS M GARRIDO-GARCIA
Journal: Circulation (2015)

Background: Kawasaki Disease (KD) is an acute febrile illness characterized by systemic vasculitis of unknown etiology. Cardiac sequelae, such as coronary artery aneurysms (CAA), are one of the most important aspects of this disease. Actually KD is most frequently presented in children younger than 5-years old. Objective: To describe the clinical and laboratory features, cardiac sequelae and outcome in children older than 10-years old with KD who were attended at the Instituto Nacional de Pediatría in Mexico City. Methods: An observational, descriptive, retrospective and transversal case study. We reviewed the medical records of patients older than 10-years diagnosed with KD from August 1995 to May 2014, and analyzed gender, age, clinical manifestations, hemoglobin, leucocyte count, platelet count, ESR, CRP, albumin, sodium, potassium, AST, ASL, time from the onset of the symptoms to diagnosis, treatment used, the development of CAA and outcome in the acute phase of the disease. Results: We studied 18 cases of KD in patients older than 10-years old, 72.2% (13 of 18) were male with a mean age of 154 months (range 120 to 200). The time from the onset of the fever to diagnosis was 10.6 ± 5.8 days, (range 3 to 21 days). Skin lesions were the most common manifestation of KD and cervical lymphadenopathy was the least common clinical feature. 2 patients presented with KD shock syndrome. Complete KD was diagnosed in only 50% (9 of 18) of our cases. 16 patients received IVGG, 2 patients required a second GGIV dose and 10 patients also received steroids. 6 of 18 patients (30%) developed CAA. There were no deaths in our group. Conclusions: KD in patients older than 10-years old represent a clinical challenge because in the majority of the cases they presented with an atypical clinical picture which contribute to a delayed diagnosis. Also there is an increased risk of developing cardiac complications and CAA in this group of patients.
Therapeutic Delivery of miR-29b Enhances Radiosensitivity in Cervical Cancer
Authors: Tingting Zhang, Xiang Xue, Huixia Peng
Journal: Molecular Therapy (2019)

Radioresistant cervical cancer is likely to give rise to local recurrence, distant metastatic relapse, and decreased survival rates. Recent studies revealed microRNA mediated regulation of tumor aggressiveness and metastasis; however, whether specific microRNAs regulate tumor radioresistance and can be exploited as radiosensitizing agents remains unclear. Here, we find that miR-29b could promote radiosensitivity in radioresistant subpopulations of cervical cancer cells. Notably, therapeutic delivery of miR-29b mimics via R11-SSPEI nanoparticle, whose specificity has been proved by our previous studies, can sensitize the tumor to radiation in a xenograft model. Mechanistically, we reveal a novel function of miR-29b in regulating intracellular reactive oxygen species signaling and explore a potential application for its use in combination with therapies known to increase oxidative stress such as radiation. Moreover, miR-29b inhibits DNA damage repair by targeting phosphate and tension homology deleted on chromsome ten (PTEN), and overexpression of PTEN could partially rescue miR-29b-mediated homologous recombination (HR)-DNA damage repair and increase radiosensitivity. These findings identify miR-29b as a radiosensitizing microRNA and reveal a new therapeutic strategy for radioresistant tumors.
Core-shell metal-organic frameworks with fluorescence switch to trigger an enhanced photodynamic therapy
Authors: Yuan Liu, Christina S. Gong, Lisen Lin, Zijian Zhou, Yijing Liu, Zhen Yang, Zheyu Shen, Guocan Yu, Zhantong Wang, Sheng Wang, Ying Ma, Wenpei Fan, Liangcan He, Gang Niu, Yunlu Dai, Xiaoyuan Chen
Journal: Theranostics (2019)

The design of hybrid metal-organic framework (MOF) nanomaterials by integrating inorganic nanoparticle into MOF (NP@MOF) has demonstrated outstanding potential for obtaining enhanced, collective, and extended novel physiochemical properties. However, the reverse structure of MOF-integrated inorganic nanoparticle (MOF@NP) with multifunction has rarely been reported.
Abstract 17169: Computationally-Engineered Analog of Stromal Cell-Derived Factor 1α Preserves the Mechanical Properties of Infarcted Myocardium Under Planar Biaxial Tension
Authors: Hanjay Wang, Andrew Wisneski, Michael J Paulsen, Zhongjie Wang, Hector Lopez Hernandez, Yue Xuan, Daniel von Bornstaedt, Amanda N Steele, Lyndsay M Stapleton, Haley J Lucian, Anahita Eskandari, Akshara D Thakore, Justin M Farry, Camille E Hironaka, Kiah M Williams, Matthew Wu, John W MacArthur, Y. Joseph Woo
Journal: Circulation (2018)

Introduction: Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) results in abnormal tissue biomechanics and impaired cardiac function, ultimately leading to heart failure. We hypothesized that intramyocardial delivery of engineered stromal cell-derived factor 1α analog (ESA), our previously-developed supra-efficient pro-angiogenic chemokine, preserves biaxial LV mechanical properties after MI. Methods: Male Wistar rats (n=46) underwent sham surgery (n=15) or permanent left anterior descending coronary artery ligation (n=31). Rats sustaining MI were randomized for intramyocardial injections of either saline (100 μL, n=15) or ESA (6 μg/kg, n=16), delivered at standardized peri-infarct sites. After 4 weeks, echocardiography was performed, and the hearts were explanted. Biaxial tensile testing of the anterior LV wall was performed using a strain-controlled biaxial load frame (Fig. 1A), producing up to physiologic circumferential and longitudinal strains (ε=20%, each). The modulus was determined along each axis, and maximum shear stress was calculated as a composite metric of the tissue’s response to physiologic strains. Data are expressed as mean±SEM. Results: At 4 weeks post-MI, ESA-treated hearts had smaller end-diastolic LV internal dimension (6.89±0.27 cm vs 7.69±0.22 cm, p=0.03) and improved ejection fraction (63.7±2.9% vs 49.4±4.4%, p=0.01) compared to saline-injected controls. Hearts treated with ESA exhibited lower moduli than saline controls in both the circumferential (269.4±33.2 kPa vs 431.5±55.6 kPa, p=0.02) and longitudinal axes (182.4±25.0 kPa vs 332.3±51.2 kPa, p=0.02, Fig. 1B). The maximum shear stress for ESA-treated hearts was significantly reduced compared to that for saline controls (5.8±0.8 kPa vs 9.0±1.2 kPa, p=0.03) and was similar to that for sham controls (Fig. 1C). Conclusion: Intramyocardial ESA injection mitigates post-MI tissue stiffening and preserves biaxial LV mechanical properties.
Pediatric diffuse intrinsic gliomas in a single center.
Authors: Rejin Kebudi, Fatma Betul Cakir, Sema Buyukkapu Bay, Omer Gorgun, Fulya Yaman Agaoglu, M. Emin Darendeliler
Journal: Journal of Clinical Oncology (2015)

e21014 Background: Prognosis of diffuse intrinsic pontine gliomas (DIPG) is dismal. We previously published results of our center 1990-2012. Patients recieving temozolamide or other chemotherapy as adjuvant to radiotherapy (RT) had a better survival than the historical group recieving RT alone (Kebudi R, Childs Nervous System, 2013). Since May 2010, patients with progressive disease and newly diagnosed patients recieved chemotherapy and nimotuzumab as adjuvant treatment. Nimotuzumab is an IgG1 antibody that targets epidermal growth factor receptor (EGFR). Overexpression of EGFR is reported in some pediatric DIPGs. In this study the treatment outcome of these patients was assessed. Methods: Since 2004, TMZ was used during RT, followed by TMZ after RT for 12 courses. Patients with progressive disease (PD) received Nimotuzumab (150 mg/m2) weekly for 11 weeks, followed by every other week, combined with carboplatin or vinorelbine. After May 2010, children with primary diagnosis received TMZ during RT, and Nimotuzumab and TMZ after RT; and Nimotuzumab+Vinorelbine if progressive disease. Results: As of January 2015, Nimotuzumab was used in 21 children with DIPG patients: 8 with PD, 13 primary diagnosis. Among PD patients, 5 had clinical improvement/stable disease for 18, +30, +18, 8 and 6 months; 2 are alive with disease (AWD) at 53 months and 25 months from initial diagnosis, 3 died of disease (DOD) at 24, 14 and 13 months from diagnosis. Two had a biopsy: pilocytic astrocytoma (+53mo.) and high grade glioma (+24 mo). The other 3 had stable disease for 5, 4, and 1 month but progressed and died. 10/13 new patients had clinical improvement after RT, 3 deteriorated during RT (2 DOD,, 1 AWD) . Four had clinical improvement for a duration of 19, +24, 14, and 11 months; 1 is AWD, 3 are DOD. The other 6 were stable for 5, 6, 6, +7 and +9 months:3 are DOD and 2 are AWD at +9 and +10 months Nimotuzumab was well tolerated with no major adverse effect. The median survival is 14 months for PD patients and 9 months for primary disease. Conclusions: The prognosis of children with DIPG is dismal. Nimotuzumab was well tolerated with TMZ or vinorelbine. Our results show that nimotuzumab containing regimens might be promising in patients with progressive disease.