tbuckley/cabot-search huggingface dataset:
481TiP Checkmate 722: A phase 3 trial of nivolumab with chemotherapy or ipilimumab vs chemotherapy in epidermal growth factor receptor (EGFR)-mutation, T790M-negative stage IV or recurrent non-small cell lung cancer (NSCLC) after EGFR tyrosine kinase inhibitor (TKI) therapy
Authors: K. Nakagawa, J.C.-H. Yang, K. Park, Y. Ohe, Y.-L. Wu, J. Gainor, A. Blackwood-Chirchir, R. Yang, I.-F. Chang, T. Mok
Journal: Annals of Oncology (2016)
ATIM-17. INVESTIGATION OF ANTI-TUMOR CELLULAR IMMUNE RESPONSE ELICITED BY TOCA 511 &amp; TOCA FC THERAPY IN A RECURRENT HGG PHASE 1 TRIAL
Authors: Derek Ostertag, Timothy Cloughesy, Steven Kalkanis, Tom Mikkelsen, Joseph Landolfi, Bob Carter, Clark Chen, Asha Das, Douglas Jolly, Harry Gruber, Michael Vogelbaum
Journal: Neuro-Oncology (2016)

A dose-escalation clinical study (NCT01470794) using a retroviral replicating vector (RRV), Toca 511, in combination with oral Toca FC (extended-release 5-fluorocytosine [5-FC]) is ongoing to evaluate safety and preliminary efficacy of this investigational therapy in patients with recurrent HGG. Toca 511 (vocimagene amiretrorepvec) encodes a yeast-derived, codon-optimized, heat-stabilized cytosine deaminase (CD) that converts 5-FC to the anti-cancer drug 5-FU in infected tumors. This virus replicates preferentially in malignant tissue and may have wide application in cancer therapies. When Toca FC is administered, the infected cells are killed by the 5-FU metabolized from 5-FC by the cytosine deaminase protein. In animal tumor models, as infected cancer cells are killed, the diffusible 5-FU also kills neighboring susceptible cells, including myeloid immune suppressor cells that the cancer has attracted to set up an immune-suppressed tumor microenvironment. The killed cancer cells release molecules, such as DAMPs, PAMPs and TLRs that activate antigen presenting cells against released tumor-specific antigens. These tumor antigens are presented to the otherwise intact immune system in the absence of local tumor immune suppression, leading to a robust anti-tumor immune response that targets tumor specific antigens. In the clinical study presented here, Toca 511 is injected into resection cavity walls at time of tumor resection, and followed with multiple courses of Toca FC. Temporal changes in PBMC populations during treatment were measured. Assays included: subtyping of effector, memory, Treg, and myeloid derived suppressor cell panels by flow cytometry; and specific antitumor activity by assays for tumor reactive peripheral blood monocyte (PBMC). Tumor and blood exome sequencing was performed to assess immunogenic potential of the tumor. Measurement of tumor infiltrating lymphocytes was also performed. A multivariate analysis using immune data and clinical factors will be presented. Clinical data are consistent with the induction of anti-tumor immune responses after Toca-FC administration.
AA Amyloidosis and IgG4-Related Disease
Authors: Faiz Karim, Marian Clahsen-van Groningen, Jan A M van Laar
Journal: New England Journal of Medicine (2017)

In a letter describing a patient with renal AA amyloidosis associated with IgG4-related disease, the correspondents report that the treatment of IgG4-related disease may modulate inflammatory effects that could lead to secondary amyloidosis.
Multimodal laser-based angioscopy for structural, chemical and biological imaging of atherosclerosis
Authors: Luis E. Savastano, Quan Zhou, Arlene Smith, Karla Vega, Carlos Murga-Zamalloa, David Gordon, Jon McHugh, Lili Zhao, Michael M. Wang, Aditya Pandey, B. Gregory Thompson, Jie Xu, Jifeng Zhang, Y. Eugene Chen, Eric J. Seibel, Thomas D. Wang
Journal: Nature Biomedical Engineering (2017)
Impact of statin therapy on PSA kinetics during active surveillance of prostate cancer.
Authors: William Rogers, Daniel Rothschild, Jason R. Bylund, Ramakrishna Venkatesh, Jon Demos, Stephen E. Strup, David Preston, Paul L. Crispen
Journal: Journal of Clinical Oncology (2012)

119 Background: Statin therapy has been associated with decreased serum PSA levels in men undergoing prostate cancer screening, lower rate of adverse pathologic features in radical prostatectomy specimens and decreased risk of biochemical recurrence following prostatectomy. Here we evaluate the impact of statin therapy on PSA kinetics during active surveillance of prostate cancer. Methods: A retrospective review of patients diagnosed with prostate cancer at our institution between the years 2000 and 2009 was performed. Patients undergoing at least 12 months of active surveillance were identified. PSA velocity and percentage change in PSA per year were compared between patients receiving and not receiving statin therapy during active surveillance. Subgroup analysis was performed on low risk patients (prebiopsy PSA &lt;10, Gleason score &lt;6, &lt;cT2). Results: We identified 81 patients meeting our inclusion criteria, 43% (35/81) were on statin therapy during active surveillance. Prebiopsy PSA was significantly lower in patients receiving statin therapy (6.0 ng/ml) compared to controls (8.3 ng/ml), p = 0.005. There was no difference in duration of active surveillance, PSA velocity, and percentage change in PSA per year based on statin use in all patients. When evaluating the 41 low risk patients, 54% (22/41) were on statin therapy. Prebiopsy PSA was lower in low risk patients receiving statin therapy (4.9 ng/ml) compared to controls (6.4 ng/ml), p= 0.055. PSA velocity was significantly lower in low risk patients (0.02 ng/ml/year) compared to low risk controls (0.89 ng/ml/year), p=0.024. Percentage change in PSA per year was significantly lower in low risk patients receiving statin therapy (-1.7%/year) compared to low risk controls (11.6%/year), p=0.05. The percentage of low risk patients receiving definitive therapy following a period of active surveillance on statin therapy was 9% (2/22)compared to 26% (5/19) in controls, p = 0.14. Conclusions: PSA kinetics during active surveillance appear to be significantly altered by statin therapy in low risk patients. Further evaluation of the impact of statin therapy on PSA kinetics and clinical outcomes of men undergoing active surveillance for prostate cancer are warranted.
The Effects of Inhaled Fluticasone Propionate on Seasonal Exacerbations in Preschool-Aged Children at High Risk for Asthma
Authors: William C. Anderson, John T. Brinton, Lance Ford, Shelby Lineberry, Casey Sakamoto, Marie Tomisato, Robert S. Zeiger, Robert F. Lemanske, Fernando D. Martinez, Theresa W. Guilbert, Leonard B. Bacharier, David M. Mauger, Stanley J. Szefler
Journal: Journal of Allergy and Clinical Immunology (2017)
Swine influenza A (H1N1) virus (SIV) infection requiring extracorporeal life support in an immunocompetent adult patient with indirect exposure to pigs, Italy, October 2016
Authors: Francesca Rovida, Antonio Piralla, Federico Capra Marzani, Ana Moreno, Giulia Campanini, Francesco Mojoli, Marco Pozzi, Alessia Girello, Chiara Chiapponi, Fausto Vezzoli, Paola Prati, Elena Percivalle, Anna Pavan, Maria Gramegna, Giorgio Antonio Iotti, Fausto Baldanti
Journal: Eurosurveillance (2017)

We describe a case of severe swine influenza A(H1N1) virus infection in an immunocompetent middle-aged man in October 2016 in Italy who had only indirect exposure to pigs. The patient developed a severe acute distress respiratory syndrome which was successfully supported by extracorporeal membrane oxygenation and treated with antiviral therapy. The sole risk factor for influenza was a body mass index &gt; 30 kg/m 2 . After a month of hospitalisation, the patient was discharged in good health.
Effect of margin width on local recurrence (LR) in triple-negative (TN) breast cancer treated with breast-conserving therapy (BCT).
Authors: Melissa Louise Pilewskie, Alice Y. Ho, Emily Orell, Michelle Stempel, Yu Chen, Anne Eaton, Sujata Patil, Monica Morrow
Journal: Journal of Clinical Oncology (2013)

1021 Background: Positive lumpectomy margins are associated with increased rates of LR after BCT; however, the effect of increasing negative margin distance on LR is controversial. Rates of LR vary by breast cancer subtype, with the highest rates seen in TN cancers. The purpose of this study was to examine the rate of LR in relationship to margin width in TN breast cancers treated with BCT. Methods: All women with TN breast cancer who underwent BCT between 1999-2009 were identified from a prospectively maintained database. Margins were defined as positive (tumor on ink), close (≤2mm), or negative (&gt;2mm) for either invasive or in situ cancer. Patients with positive margins (n=46) were excluded. Statistical comparisons were by t tests, Fisher’s exact test, and Wilcoxon rank sum test. Cumulative incidence of LR was compared using competing-risks methodology. Results: Characteristics of the 535 cancers (in 534 patients) with close (n=71) and negative (n=464) margins are compared in the Table. At median follow-up of 84 months (range, 8-165 months) there were 37 local, 18 regional, and 77 distant recurrences or deaths as first events. 10 patients had LR prior to planned radiation therapy (RT). The cumulative incidence of LR at 60 months for patients with close margins was 7.3% (95% CI, 1.1-13.6), and 5.1% (3.0-7.2) for negative margins. After controlling for use of chemotherapy, there was no significant difference in LR between the entire close and negative margin groups (p=.07) or after exclusion of recurrences prior to RT (p=.06). A difference in the risk of distant recurrence or death was not observed (p=.60). Conclusions: Margin width greater than 2mm was not associated with a clinically meaningful reduction in LR risk. This, coupled with reports of similar LR in TN cancers treated with BCT or mastectomy, suggests that larger surgical procedures do not improve outcomes in this high-risk patient subset. [Table: see text]
NTOX-02. DEVELOPMENT OF CYSTIC MALACIA AFTER HIGH DOSE CRANIAL IRRADIATION OF PEDIATRIC CNS EMBRYONAL TUMORS IN LONG-TERM FOLLOW-UP
Authors: Fumiyuki Yamasaki, Manish Kolakshyapati, Takeshi Takayasu, Ryo Nosaka, Kazuhiko Sugiyama, Kaoru Kurisu
Journal: Neuro-Oncology (2016)

The purpose of this study is to investigate the incidence of cystic malacia (CM) in long-term survivors of pediatric CNS embryonal tumors treated with cranial irradiation. Between 1990 and 2015, we treated 34 pediatric patients (18 males, 16 females) of embryonal tumors (25 medulloblastomas, 6 PNET, 3 pineoblastomas) with craniospinal irradiation. Follow-up ranged from 8.0 to 308.5 months (medain 77.8 months), the irradiation dose to the whole neural axis ranged from 18 to 41.4 Gy, and the total local dose from 43.2 to 60 Gy. All patients underwent follow-up MRI studies at least once a year. Of the 34 patients, 28 were censored during their follow-up due to recurrence (n=7), detection of secondary leukemia (n=1) and secondary diffuse astrocytoma (n=1), or the absence of CM on the last follow-up MRI study (n=19). At the time of this writing, 25 were alive and free of the original disease, recurrence or the development of secondary neoplasms other than cavernous angioma; 7 died of recurrence, 1 died of secondary leukemia and 1 was alive with diffuse astrocytoma. Post-treatment, 8 patients developed CM during a median course of 39.9 months (range 16.6 to 114.2 months). The site of prediction for CM was white matter around trigone of lateral ventricles with the incidence of 50.0% (4 in 8). Patients with supratentorial embryonal tumors developed CM statistically earlier than the patients with medulloblastoma (P=0.0329, Gehan-Breslow-Wilcoxon test). Among the same patient group, incidence of post-RT cavernous angioma increased progressively, while the incidence of post-RT CM did not increase after 10 years. We attribute the high incidence of post-RT CM in our long-term follow-up study to the cranial irradiation for embryonal tumors, especially supratentorial brain tumors, and recommend regular, long-term follow-up of brain tumor patients treated with cranial irradiation.
Cerebral Cortical Microinfarcts on 3-T Magnetic Resonance Imaging
Authors: Robert J. Wityk
Journal: JAMA Neurology (2017)

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Steep rise in norovirus cases and emergence of a new recombinant strain GII.P16-GII.2, Germany, winter 2016
Authors: S Niendorf, S Jacobsen, M Faber, A M Eis-Hübinger, J Hofmann, O Zimmermann, M Höhne, C T Bock
Journal: Eurosurveillance (2017)

Since early November 2016, the number of laboratory-confirmed norovirus infections reported in Germany has been increasing steeply. Here, we report the detection and genetic characterisation of an emerging norovirus recombinant, GII.P16-GII.2. This strain was frequently identified as the cause of sporadic cases as well as outbreaks in nine federal states of Germany. Our findings suggest that the emergence of GII.P16-GII.2 contributed to rising case numbers of norovirus gastroenteritis in Germany.
Diagnosis and Treatment of Pituitary Adenomas
Authors: Mark E. Molitch
Journal: JAMA (2017)

Pituitary adenomas may hypersecrete hormones or cause mass effects. Therefore, early diagnosis and treatment are important.Prevalence of pituitary adenomas ranges from 1 in 865 adults to 1 in 2688 adults. Approximately 50% are microadenomas (<10 mm); the remainder are macroadenomas (≥10 mm). Mass effects cause headache, hypopituitarism, and visual field defects. Treatments include transsphenoidal surgery, medical therapies, and radiotherapy. Prolactinomas account for 32% to 66% of adenomas and present with amenorrhea, loss of libido, galactorrhea, and infertility in women and loss of libido, erectile dysfunction, and infertility in men; they are generally treated with the dopamine agonists cabergoline and bromocriptine. Growth hormone-secreting tumors account for 8% to 16% of tumors and usually present with enlargement of the lips, tongue, nose, hands, and feet and are diagnosed by elevated insulin-like growth factor 1 levels and growth hormone levels; initial treatment is surgical. Medical therapy with somatostatin analogues, cabergoline, and pegvisomant is often also needed. Adrenocorticotropic hormone (ACTH)-secreting tumors account for 2% to 6% of adenomas and are associated with obesity, hypertension, diabetes, and other morbidity. Measurement of a late-night salivary cortisol level is the best screening test but petrosal sinus sampling for ACTH may be necessary to distinguish a pituitary from an ectopic source. The primary treatment of Cushing disease (hypercortisolism due to ACTH-producing adenomas, which is the cause in approximately 65% of the cases of hypercortisolism) is adenoma resection and medical therapies including ketoconazole, mifepristone, and pasireotide. Hyperthyroidism due to thyroid-stimulating hormone-secreting tumors accounts for 1% of tumors and is treated with surgery and somatostatin analogues if not surgically cured. Clinically nonfunctioning adenomas account for 15% to 54% of adenomas and present with mass effects; surgery is generally required, although incidentally found tumors can be followed if they are asymptomatic.Patients with pituitary adenomas should be identified at an early stage so that effective treatment can be implemented. For prolactinomas, initial therapy is generally dopamine agonists. For all other pituitary adenomas, initial therapy is generally transsphenoidal surgery with medical therapy being reserved for those not cured by surgery.
Deletions of Chromosome 13q in Myeloproliferative Neoplasms: Mapping, Relation to the JAK2-V617F Mutation and Evaluation of Potential Tumor Suppressor Candidates
Authors: Damla Olcaydu, Tiina Berg, Bettina Gisslinger, Heinz Gisslinger, Robert Kralovics
Journal: Blood (2008)
Pembrolizumab after progression on platinum and cetuximab in head and neck squamous cell carcinoma (HNSCC): results from KEYNOTE-055
Authors: R. Haddad, T. Seiwert, D.G. Pfister, F. Worden, S.V. Liu, J. Gilbert, N.F. Saba, J. Weiss, L.J. Wirth, A. Sukari, H. Kang, M.K. Gibson, E. Massarelli, S. Powell, A. Meister, X. Shu, J. Cheng, J. Bauml
Journal: Annals of Oncology (2016)
Vγ9Vδ2 T (γδ) lymphocytes: a promising approach for immunotherapy of solid tumors
Authors: P. J. Squiban, E. Bompas, J. Bennouna, V. Levy, H. Sicard, S. Lafaye de Micheaux, E. Viey, S. Salot, J. Tiollier, F. Calvo
Journal: Journal of Clinical Oncology (2007)

3064 Background: The Vγ9Vd2 T (γd) blood lymphocyte subset has a strong cytotoxic potential and can be selectively activated with chemically-synthesized, structural analogues of non-conventional antigens like BrHPP (IPH1101). Their proliferation requires low dose of Interleukin-2 (IL-2). Methods: We developed several in vitro and in vivo models to assess the immunotherapeutic potential of IPH1101-activated γd cells: - Direct cytotoxicity assays on patient-derived primary tumor cell lines - Extensive pharmacodynamics in the non human primate (NHP) - Small scale in vitro amplification assays for IPH1101-sensitive patient pre-selection Then, two Phase I clinical trials were performed in solid tumor patients: - Autologous cell therapy with ex vivo IPH1101- expanded γd cells (1, 4 or 8.10 9 cells) - Direct administration of IPH1101 (200 to 1800 mg/m 2 i.v.) and low dose IL-2 (10 6 U/m 2 s.c.). Results: In NHP, IPH1101 and low dose IL-2 induce early pro-inflammatory cytokine release and dose-dependent γd cell amplification in peripheral blood. In vitro, mRCC tumor cells are efficiently and selectively killed by autologous γd cells. In Phase I clinical trials, both ex vivo expanded γd cells and IPH1101 were well tolerated. - Cell therapy-related AEs included mainly gastrointestinal disorders, flu-like symptoms and hypotension. Six patients showed stabilized disease. Median duration of stabilization was 25.7 weeks. 2 pts treated with 4.10 9 or 8.10 9 cells showed substantial tumor shrinkage at the 14-week evaluation (-22% and -48%, respectively). - When IPH1101 was administered with low dose of IL-2, a significant increase of blood γd T cells was observed (up to 240 times the basal values) and in terms of clinical activity assessment, among the evaluable mRCC population (n=15), 8 patients presented disease stabilization for more than 35 weeks, including 6 for more than 51 weeks. Conclusions: For the first time, a specific γd immunotherapy was fully developed and led to Phase I clinical trials. It has been found well tolerated. Encouraging signs of disease stabilisation in mRCC patients suggest that γd may have a role in the treatment of cancers resistant to conventional therapies. A phase 2 is ongoing in mRCC patients. No significant financial relationships to disclose.
Inflammatory Signaling Regulates Embryonic Hematopoietic Stem and Lymphoid Progenitor Cell Formation
Authors: Yan Li, Virginie Esain, Li Teng, Jian Xu, Isaura Frost, Wanda Kwan, Amanda D Yzaguirre, Marijke W Maijenberg, Stuart H. Orkin, Kai Tan, Trista E North, Nancy A. Speck
Journal: Blood (2014)
Leg Ulcers in Sickle Cell Anemia Are Associated with Laboratory Markers of Hemolysis and SNPs in KL and Genes of the TGF-β/BMP Pathway.
Authors: Vikki G. Nolan, Adeboye H. Adewoye, Clinton T. Baldwin, Qian-Li Ma, Diego F. Wyszynski, John J. Farrell, Alice Bisbee, Matt Fourcade, Lindsay A. Farrer, Martin H. Steinberg
Journal: Blood (2005)
Early detection and curative treatment of hepatocellular carcinoma: A cost‐effectiveness analysis in France and in the United States
Authors: Benjamin Cadier, Julie Bulsei, Pierre Nahon, Olivier Seror, Alexis Laurent, Isabelle Rosa, Richard Layese, Charlotte Costentin, Carole Cagnot, Isabelle Durand‐Zaleski, Karine Chevreul
Journal: Hepatology (2017)

Hepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis. Patients outside clinical trials seldom benefit from evidence‐based monitoring. The objective of this study was to estimate the cost‐effectiveness of complying with HCC screening guidelines. The economic evaluation compared surveillance of patients with cirrhosis as recommended by the guidelines (“gold‐standard monitoring”) to “real‐life monitoring” from the health care system perspective. A Markov model described the history of the disease and treatment course including current first‐line curative treatment: liver resection, radiofrequency ablation (RFA), and liver transplantation. Transition probabilities were derived mainly from two French cohorts, CIRVIR and CHANGH. Costs were computed using French and U.S. tariffs. Effectiveness was measured in life years gained (LYG). An incremental cost‐effectiveness ratio (ICER) was calculated for a 10‐year horizon and tested with one‐way and probabilistic sensitivity analyses. The cost difference between the two groups was $648 ($87,476 in the gold‐standard monitoring group vs. $86,829 in the real‐life monitoring group) in France and $11,965 ($93,795 vs. $81,829) in the United States. Survival increased by 0.37 years (7.18 vs. 6.81 years). The ICER was $1,754 per LYG in France and $32,415 per LYG in the United States. The health gain resulted from earlier diagnosis and access to first‐line curative treatments, among which RFA provided the best value for money. Conclusion : Our results indicate that gold‐standard monitoring for patients with cirrhosis is cost‐effective, attributed to a higher probability of benefiting from a curative treatment and so a higher survival probability. (H epatology 2017;65:1237‐1248)
Phase I Study of Clofarabine (JC0707) in Adult Japanese Patients with Acute Myeloid Leukemia (AML)
Authors: Takahiro Yamauchi, Tatsuya Suzuki, Kiyoshi Ando, Tadashi Nagai, Kazuhiko Kakihana, Yasuhiko Miyata, Reginald Ewesuedo, Yasuhiro Tabata, Michinori Ogura
Journal: Blood (2011)