tbuckley/cabot-search huggingface dataset:
How to Manage the Obese Patient With Cancer
Authors: Andrew G. Renehan, Michelle Harvie, Ramsey I. Cutress, Michael Leitzmann, Tobias Pischon, Sacha Howell, Anthony Howell
Journal: Journal of Clinical Oncology (2016)

Purpose Obesity (body mass index [BMI] ≥ 30 kg/m2) is common among patients with cancer. We reviewed management issues in the obese patient with cancer, focusing on how obesity influences treatment selection (including chemotherapy dosing), affects chemotherapy toxicity and surgical complications, and might be a treatment effect modifier. Methods The majority of evidence is drawn from observational studies and secondary analyses of trial data, typically analyzed in N × 3 BMI categories (normal weight, overweight, and obese) matrix structures. We propose a methodological framework for interpretation focusing on sample size and composition, nonlinearity, and unmeasured confounding. Results There is a common perception that obesity is associated with increased treatment-related toxicity. Accordingly, cytotoxic chemotherapy dose reduction is common in patients with elevated BMI. Contrary to this, there is some evidence that full dosing in obese patients does not result in increased toxicity. However, these data are from a limited number of regimens, and fail to fully capture cytotoxic drug pharmacodynamics and pharmacokinetic variability in obese patients. Among patients undergoing surgery, there is evidence that elevated BMI is associated with increased perioperative mortality and increased rates of infectious complications. A novel finding is that these relationships hold after surgery for malignancy, but not for benign indications. There are biologic plausibilities that obesity might be an effect modifier of treatment, but supporting evidence from clinical studies is inconsistent. Conclusion In line with the ASCO 2012 guidelines, chemotherapy dosing is probably best performed using actual body weight in obese patients. However, specific regimens known to be associated with increased toxicity in this group should be used with caution. There is no guidance on dose for obese patients treated with biologic agents. Currently, there are no specific recommendations for the surgical management of the obese patient with cancer.
Treatment and characteristics of patients treated for hepatocellular carcinoma (HCC) by physician types in the United States.
Authors: Brian S. Seal, Susan H Foltz Boklage, Carl V Asche
Journal: Journal of Clinical Oncology (2012)

375 Background: This study provides a description of the characteristics of patients treated for HCC and how they differ in terms of those treated by 1 type of physician vs. those treated by ≥ 2 physicians. Methods: This was a longitudinal, retrospective analysis of claims from the Thomson Reuters MarketScan database for patients treated for incident HCC. The patients were selected based upon those being treated for malignant neoplasm’s of the liver as their primary diagnosis (ICD-9 code 155.00) and they were required to have continuous eligibility around their initial liver cancer incidence data for 6 months prior and ≥ 12 months subsequent to treatment. Excluded were those having evidence of HCC and any other type of tumor in the prior 6 months. The study period was from 01/01/2006 until 06/30/2010. Descriptive analysis was used to draw comparisons between patients seen by 1 vs. ≥ 2 specialists. Results: 967 patients were analyzed, of whom 631were seen by 1 and 336 were seen by ≥2 physicians. The groups were similar except for age (75.8% of 1 physician were aged 45 to 64 years vs. 89.9% ≥ 2 physicians), gender (55.8% males for the 1 vs. 75.3% ≥2 physicians), not having Hepatitis C (75.4% in the 1 vs. 57.4% ≥2 physicians), not having Cirrhosis (70.4% in the 1 vs. 56.3% ≥2 physicians), not having other diseases of the liver (56.6% in the 1 vs. 47.6% ≥2 physicians), not having chemotherapy (92.6% in the 1 vs. 71.4% ≥2 physicians), not having TAE (86.2% in the 1 vs. 60.7% ≥2 physicians), not having ablation (95.3% in the 1 vs. 84.2% ≥2 physicians), and not having resection (93.3% in the 1 vs. 84.2% ≥2 physicians). The top physicians consulted were: Internal Medicine (16.3%); Medical Doctor (16.03%); Gastroenterology (14.37%); Multispecialty Physician Group (13.65%); Oncology/Hematology (13.35%); Family Practice (9.41%); and Surgeon (7.86%). Conclusions: It was found that the HCC patients treated by 1 vs. ≥ 2 physicians were younger, predominantly female [Odds Ratio (OR) of 1.977], less likely to have Hepatitis C (OR of 0.649], and less likely to have ≥ 1 selected treatment (OR of 0.224). The patients were seen by Internal Medicine, General Medical, Multispecialty Groups, and Family Practice more often than Oncologists.
Resolvin D1 and Resolvin D2 Protect Against Hypoxia/Reoxygenation Induced Lung and Kidney Damage in a Sickle Cell Mouse Model of Acute Vaso-Occlusive Crisis
Authors: Alessandro Mattè, Antonio Recchiuti, Charles Serhan, Angela Siciliano, Enrica Federti, Olga Weinberg, Brian Kalish, Carlo Brugnara, Lucia De Franceschi
Journal: Blood (2015)
Biorelevant test for supersaturable formulation
Authors: Enxian Lu, Shoufeng Li, Zhongqin Wang
Journal: Asian Journal of Pharmaceutical Sciences (2016)

Supersaturable formulation can generate supersaturation after dissolution, providing kinetic advantage in vivo. However, the supersaturation may precipitate before being absorbed, which makes it difficult to ensure and predict its in vivo performance. The traditional USP method is typically for Quality Control (QC) purpose and cannot be used to predict the formulation in vivo performance. Therefore, there is generally a lack of a predictive biorelevant testing method. In this review, different types of supersaturable formulations are described, including amorphous dispersions, polymorphs, salts/co-crystals, weak base and supersaturable solubilized formulations. Different kinds of in vitro dissolution methods for supersaturable formulations are also reviewed and discussed. Most of the methods take the physiology of gastrointestinal (GI) track into consideration, allowing reasonable prediction of the in vivo performance of supersaturable formulation. However, absorbing drug from GI track into blood stream is a complicate process, which can be affected by different in vivo processes such as transporter and metabolism. These factors cannot be captured by the in vitro testing. Thus, combining in vitro biorelevant dissolution methods with physiology-based pharmacokinetic modeling is a better way for the product development of supersaturable formulation.
Effects of Recipients’ Body Weight and Total Nucleated Cell Dose on Outcomes of Unrelated Bone Marrow Transplantation: Analysis of Clinical Data of 3,114 Leukemia Patients from the Database of the Japan Marrow Donor Program
Authors: Takuya Yamashita, Hideki Akiyama, Kazuteru Ohashi, Makoto Onizuka, Shin-ichiro Mori, Hiroshi Sao, Koichi Miyamura, Hisashi Sakamaki
Journal: Blood (2008)
Expression of Nuclear Factor-kappa B Pathway Genes and Their Correlation with Clinical Features in Multiple Myeloma.
Authors: Manuella S.S. Almeida, Andre L. Vettore, Roberta S. Felix, Valeria C.C. Andrade, Fabricio Carvalho, Mihoko Yamamoto, Maria de Lourdes L.F. Chauffaille, Marco Antonio Zago, Gisele W.B. Colleoni
Journal: Blood (2007)
Trends in metastatic bladder cancer incidence and prognosis by histologic subtypes.
Authors: Thuy Koll, Xiang Fang, Shanmuga Subbiah
Journal: Journal of Clinical Oncology (2012)

322 Background: Approximately 5% of patients present with metastatic bladder cancer (MBC) at diagnosis.We aim to assess the trends of MBC at presentation over the last two decades using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Retrospective analysis of MBC patients at presentation was done using data from SEER for 1988-2003. Age, Sex, Histology, Race, use of palliative surgery and survival data was extracted. Results: 9357 patients with MBC were identified. Incidence of MBC remained same in the last 2 decades (6.05% vs 6.34%). The most common histology was (TCC) transitional cell with least common being Signet cell. Squamous cell carcinoma (SCC) was common in African Americans and in females. Common grade at presentation was poorly differentiated. Palliative surgery was done in 18.15% patients with radical cystectomy being the common type of surgery. Median survival was better in TCC with the worst outcomes in patients with SCC (Table). Conclusions: Incidence of MBC at presentation hasn’t changed over the last two decades with TCC being the most common type. Clinical trials integrating targeted therpy with chemotherapy is needed to improve outcomes of MBC patients. [Table: see text]
Evaluation of immune activation following neoadjuvant sipuleucel-T in subjects with localized prostate cancer.
Authors: Nadeem A. Sheikh, Johnna D. Wesley, Nikole Perdue, Frances P. Stewart, Lawrence Fong
Journal: Journal of Clinical Oncology (2012)

178 Background: Sipuleucel-T is an FDA-approved autologous cellular therapy that has been demonstrated to prolong overall survival in subjects with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC). Methods: Subjects with localized prostate cancer were enrolled in an open-label, Phase 2 study (P07-1; NCT00715104 ) in which they received 3 infusions of sipuleucel-T at approximately 2-week intervals, beginning 6–7 weeks prior to radical prostatectomy. All samples were evaluated for cellular composition and antigen presenting cell (APC) activation pre- and post-culture with PA2024, a fusion protein comprising prostatic acid phosphatase and granulocyte macrophage-colony stimulating factor. Additionally, cytokines within the culture supernatant were assessed, and T and B cell activation were evaluated pre- and post-culture using flow cytometry. Results: Of the 42 enrolled subjects (median age: 61 years; 98% Caucasian), 38 received all 3 infusions of sipuleucel-T. Consistent with previous trials in mCRPC, CD54 upregulation (APC activation) was greater at the second and third infusions relative to the first. While the percent of CD4 + and CD8 + T cells was unchanged with treatment, the expression of early T cell activation markers (CD134, CD137, CD278 and CD279) was increased in pre-culture cells obtained after the first infusion, and further increased post-culture. Similarly, while the percent of B cells was unchanged, there was a progressive increase in memory B cells (CD20 + CD27 + IgD − CD86 + ; pre- and post-culture) and activated mature B cells (CD20 + CD27 + IgD + CD86 + ; post-culture) following the first infusion. Activated T cell-associated cytokines were significantly elevated (TNF-α, P &lt; 0.001; IFN-γ, P &lt; 0.001; and IL-2, P &lt; 0.001) in the second and third products. Conclusions: Neoadjuvant sipuleucel-T resulted in robust immune system activation that included APCs, memory and activated mature B cells, and both CD4 + and CD8 + T cells. The patterns observed at the second and third infusions, relative to the first, are consistent with an immunological prime-boost profile.
The Degree of Telomere Loss in Hematopoietic Cells Correlates with the Risk of Secondary Myelodysplasia/Acute Leukemia Development Following Autologous Stem Cell Transplantation.
Authors: Irene Ricca, Alberto Rocci, Marco Ruella, Manuela Zanni, Daniele Caracciolo, Marco Ladetto, Mario Boccadoro, Dario Ferrero, Corrado Tarella
Journal: Blood (2007)
Current Therapy 1982. Latest Approved Methods of Treatment for the Practicing Physician.
Journal: Annals of Internal Medicine (1982)

This book represents an attempt to provide for the practitioner the latest method of treatment for a variety of diseases. A board of twelve consulting editors and over two hundred physicians have contributed to the book. The contents are divided into fourteen sections: Infectious diseases, diseases of the digestive system, diseases of metabolism and nutrition, diseases of the endocrine system, diseases of the urogenital tract, venereal diseases, diseases of allergy, diseases of the skin, diseases of the respiratory system, diseases of the cardiovascular system, diseases of the blood and spleen, diseases of the nervous system, obstetric and gynecologic diseases and diseases due to physical and chemical agents. The discussions are brief, with a minimum of wasted words. However, the essentials of the method of treatment proposed by the contributors are sufficiently complete for the reader to obtain a clear understanding of the therapeutic problem. This book does not present a
The relationship of HIF2 and the progression of PTEN-deficient mouse prostate tumors.
Authors: W. Y. Kim, B. Zhou, G. Thomas
Journal: Journal of Clinical Oncology (2011)

30 Background: The hypoxia-inducible factor (HIF) transcription factor has already cemented its oncogenic role in the development of renal cell carcinoma (RCC). However, its role in the tumorigenesis of other solid tumors remains unspecificed. Our studies focus on a novel link between HIF and prostate carcinogenesis. Methods: Using both in vitro cell culture studies as well as in vivo studies (orthotopic xenograft and genetically engineered mouse models) we investigate the role of HIF in prostate cancer cell proliferation, invasion, and progression. Results: Both HIF1 and HIF2 appear to be necessary for the proliferation and invasion of prostate cancer cell lines in vitro. Preliminary analysis of a PTEN deficient mouse model of prostate cancer suggests that expression of a stabilized form of HIF2 promotes the development of a larger prostate tumor burden and a more aggressive histology (high grade prostate intraepithelial neoplasia [PIN] at earlier stages). Moreover, PTEN-deficient prostate tumors producing HIF2 are more proliferative and vascular and express increased levels of genes associated with epithelial to mesenchymal transition (EMT). Conclusions: There has been much interest in the role of angiogenesis and hypoxia in prostate cancer progression. Our preliminary data suggest that HIF2 is able to promote PTEN-deficient prostate cancer progression in mice by increasing proliferation, angiogenesis, and EMT. No significant financial relationships to disclose.
Reversible posterior leukoencephalopathy syndrome during R-ICE therapy for malignant lymphoma
Authors: Aya Ouchi, Koji Sano, Susumu Tanoue, Tomohito Machishima, Mitsuji Katori, Shuichi Masuoka, Kaichi Nishiwaki, Noriko Usui, Keisuke Aiba
Journal: Annals of Oncology (2015)
Soluble IL-2 Receptor α Is a More Sensitive Diagnostic Biomarker Than β2 Microglobulin and Predicts Survival in Follicular Lymphoma: Retrospective Analysis of 305 Cases
Authors: Akihiko Yokohama, Yoko Hashimoto, Shimizu Hiroaki, Akio Saito, Yuri Miyazawa, Hirono Iriujijima, Kotaro Toyama, Takuma Ishizaki, Takeki Mitsui, Hiromi Koiso, Makiko Takizawa, Takayuki Saito, Hiroshi Handa, Kayoko Murayama, Morio Matsumoto, Morio Sawamura, Hirokazu Murakami, Yoshihisa Nojima, Junko Hirato, Masaru Kojima, Norifumi Tsukamoto
Journal: Blood (2014)
The Impact of Radiological Response to Peptide Receptor Radionuclide Therapy on Overall Survival in Patients With Metastatic Midgut Neuroendocrine Tumors
Authors: Mehmet Yalchin, Amelia Oliveira, Eleni Theocharidou, Deborah Pencharz, Shaunak Navalkissoor, Ann-Marie Quigley, Martin Walker, Martyn Caplin, Christos Toumpanakis
Journal: Clinical Nuclear Medicine (2016)

Purpose of the Report Peptide receptor radionuclide therapy (PRRT) is an effective treatment for advanced neuroendocrine tumors (NET); however, long-term survival data are scarce. The aim of this study is to determine long-term survival in patients with metastatic midgut NET, according to response to PRRT. Patients and Methods One hundred thirty-three consecutive patients with progressive metastatic midgut NET underwent PRRT. Response at 1 year post PRRT was classified as partial response, stable disease, disease progression, or death. Survival was assessed according to response to PRRT, and predictors of overall survival (OS) and progression-free survival (PFS) were identified. Results At 1 year post PRRT, 9% had partial response, 50.4% stable disease, 10.5% disease progression, and 30.1% were dead. The OS was 33.5, and PFS was 28.5 months. Predictors of disease progression/death were chromogranin A greater than 10 ULN (OR, 4.6; P = 0.007) and hepatic tumor load greater than 50% (OR, 5; P = 0.004). There was no difference in OS between patients with partial response and those with stable disease post PRRT. In multivariate Cox regression, predictors of OS were number of PRRT cycles (HR, 0.33; P < 0.0005), hepatic tumor load greater than 50% (HR, 3.46; P = 0.01), and outcome at 1 year post PRRT (HR, 21.37; P < 0.0005). Predictors of PFS were number of PRRT cycles (HR, 0.39; P < 0.0005), previous resection of liver metastases (HR, 3.56; P = 0,023), and hepatic tumor load greater than 50% (HR, 3.06; P < 0.0005). Conclusions Patients with progressive metastatic midgut NET who achieved stable disease at 1 year post PRRT had similar OS with those with partial response. Hepatic tumor burden was a strong predictor of response to PRRT, PFS, and OS.
Validation of MSKCC-criteria in metastatic renal cancer patients treated with sorafenib or sunitinib.
Authors: I. Hoffmeister, L. Riesenbeck, S. Bierer, T. Koepke, L. Hertle, B. Thielen, E. Herrmann
Journal: Journal of Clinical Oncology (2011)

401 Background: To validate the Memorial Sloan-Kettering Cancer Center (MSKCC) criteria as a prognostic factor in patients with metastatic renal cell carcinoma (mRCC) treated with the tyrosine kinase inhibitors (TKIs) sorafenib (So) or sunitinib (Su). Methods: Clinical and laboratory parameters from 83 patients with mRCC were investigated. All patients were treated at our institution between 2006 and 2009. Specifically, the MSKCC criteria (Karnofsky performance status &lt;80%, time between diagnosis and treatment &lt; 1 year, baseline anemia, elevated LDH &gt; 1.5 times upper limit of normal, and elevated serum calcium) were evaluated as surrogate parameters for progression-free survival (PFS). Results: 34 (41.0%) patients were treated as first-line, and 49 (59.0%) patients were treated as second-line treatments, respectively. In univariate analyses, a poor ECOG status was associated with an unfavorable progression-free survival (p&lt;0.0001); similarly high risk MSKCC criteria correlated with a worse PFS (p=0.003). Furthermore, response to therapy was a surrogate parameter (p&lt;0.0001). Albeit statistically not significant, prior nephrectomy (p=0.056), histologic subtype (p=0.052) as well as baseline anemia (p=0.079) tended to be associated with PFS. In multivariate analyses, only the ECOG status (ECOG 0/1 vs. ECOG 2, p=0.001) and best treatment response (p&lt;0.001) were independent prognostic markers, but not MSKCC criteria. Conclusions: In this patient cohort, MSKCC criteria did not show prognostic relevance in terms of PFS. The role of risk group stratification according to MSKCC in patients with mRCC and treatment with TKIs must be questioned. No significant financial relationships to disclose.
Retrospective Analysis of 59 Cases FLT3-ITD Mutation Positive Acute Myeloid Leukemia
Authors: Jie Sun, Juan Hu, Shuangwei Ying, Zhen Cai, Jingsong He, Weiyan Zheng, Yi Luo, Guoqing Wei, Jie Zhang, Xiujin Ye, Wanzhuo Xie, He Huang
Journal: Blood (2014)
Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study
Authors: Matthew D Hellmann, Naiyer A Rizvi, Jonathan W Goldman, Scott N Gettinger, Hossein Borghaei, Julie R Brahmer, Neal E Ready, David E Gerber, Laura Q Chow, Rosalyn A Juergens, Frances A Shepherd, Scott A Laurie, William J Geese, Shruti Agrawal, Tina C Young, Xuemei Li, Scott J Antonia
Journal: The Lancet Oncology (2016)
BALB/3T3 fibroblast-conditioned medium attracts cultured mast cells derived from W/W but not from mi/mi mutant mice, both of which are deficient in mast cells
Authors: T Jippo-Kanemoto, S Adachi, Y Ebi, H Matsuda, T Kasugai, S Nishikawa, Y Kitamura
Journal: Blood (1992)
The Prostate Cancer Clinical Trials Consortium (PCCTC) bone scan data capture tool for clinical trials using Prostate Cancer Working Group 2 (PCWG2) criteria: Effect on data accuracy and workload.
Authors: M. J. Morris, J. S. Farrelly, J. J. Fox, E. R. Dennis, L. H. Schwartz, H. Schöder
Journal: Journal of Clinical Oncology (2011)

121 Background: PCWG2 Concensus Criteria proposed time-to-event endpoints in early phase clinical trials. Chief among these was time to radiographic progression for bone scintigraphy (BS), based on a standardized definition with additional rulesets to account for early flare. The PCCTC created a tool to operationalize these definitions in clinical trials. We tested the impact of the tool on clinical trial workload and data adequacy. Methods: The BS capture tool was vetted and amended through nine versions by a multidisciplinary group from PCCTC participating institutions. Accruals at Memorial Sloan-Kettering Cancer Center on two phase III trials using the same drug, contracting research organization (CRO), and electronic data capture system were analyzed. The first trial did not use the PCCTC tool. The second incorporated the tool in its data collection plan and case report form. Workload and data capture adequacy for each trial were determine by examining the total number of imaging queries from the database query reports obtained from the CRO as a function of the total number of scans and patients. Results: Data from this analysis are found in the table . The relative number of queries per scan was reduced by 85.33% by use of the tool. The queries:scan ratios were 0.82 versus 0.12 before and after the use of the tool respectively; likewise, the ratios of queries: patient were 2.81 vs. 0.44. Conclusions: Using the PCCTC BS tool to standardize data capture and operationalize PCWG2 radiographic progression criteria, imaging data are more completely reported and workload for study research staff decreased. The reproducibility and feasibility of the BS tool is further being tested in two ongoing phase III studies in which PCWG2 criteria are being clinically qualified. These efforts to quantitate, standardize, and qualify imaging data advance the goal of developing an imaging biomarker in metastatic prostate cancer. [Table: see text] No significant financial relationships to disclose.
Studies of the Proteasome Inhibitor Sensitivity Modulator Tight Junction Protein 1 Highlight a Role for Signaling through the Epidermal Growth Factor Receptor in Determining Proteasome Capacity
Authors: Xing-Ding Zhang, Veerabhadran Baladandayuthapani, Heather Yan Lin, George Mulligan, Bin Li, Dixie-Lee Esseltine, Lin Qi, Jian-Liang Xu, Walter Hunziker, Bart Barlogie, Saad Z. Usmani, Qing Zhang, John Crowley, Antje Hoering, Bing-Zong Li, Huihan Wang, Jiexin Zhang, Isere Kuiatse, Jin-Le Tang, Jin He, Jing Yang, Richard Eric Davis, Wencai Ma, Zhiqiang Wang, Lin Yang, Robert Z. Orlowski
Journal: Blood (2014)