884 results on '"G. Pfister"'
Search Results
152. PD42-06 SALVAGE RADICAL PROSTATECTOMY (SRP) FOR RADIORESISTANT PROSTATE CANCER (PCA): OUTCOME ANALYSIS OF 2 TERTIARY REFERAL CENTRES
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Tobias Kohl, David G. Pfister, Axel Heidenreich, Matteo Soligo, Jeffrey Karnes, Markus Grabbert, and Alessandro Morlaco
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Oncology ,medicine.medical_specialty ,Prostate cancer ,business.industry ,Prostatectomy ,Urology ,Internal medicine ,Radioresistance ,medicine.medical_treatment ,medicine ,Outcome analysis ,medicine.disease ,business - Published
- 2018
153. MP16-03 ONCOLOGICAL AND FUNCTIONAL OUTCOME OF RADICAL SALVAGE PROSTATECTOMY IN A LARGE CONTEMPORARY SERIES
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Tobias Kohl, Axel Heidenreich, David G. Pfister, Matteo Soligo, A. Morlacco, Markus Grabbert, and Jeffrey Karnes
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medicine.medical_specialty ,Series (stratigraphy) ,business.industry ,Urology ,General surgery ,medicine ,business ,Outcome (game theory) ,Salvage prostatectomy - Published
- 2018
154. The CU mobile Solar Occultation Flux instrument: structure functions and emission rates of NH3, NO2 and C2H6
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N. Kille, S. Baidar, P. Handley, I. Ortega, R. Sinreich, O. R. Cooper, F. Hase, J. W. Hannigan, G. Pfister, and R. Volkamer
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lcsh:TA715-787 ,lcsh:Earthwork. Foundations ,lcsh:TA170-171 ,lcsh:Environmental engineering - Abstract
We describe the University of Colorado mobile Solar Occultation Flux instrument (CU mobile SOF). The instrument consists of a digital mobile solar tracker that is coupled to a Fourier transform spectrometer (FTS) of 0.5 cm−1 resolution and a UV–visible spectrometer (UV–vis) of 0.55 nm resolution. The instrument is used to simultaneously measure the absorption of ammonia (NH3), ethane (C2H6) and nitrogen dioxide (NO2) along the direct solar beam from a moving laboratory. These direct-sun observations provide high photon flux and enable measurements of vertical column densities (VCDs) with geometric air mass factors, high temporal resolution of 2 s and spatial resolution of 5–19 m. It is shown that the instrument line shape (ILS) of the FTS is independent of the azimuth and elevation angle pointing of the solar tracker. Further, collocated measurements next to a high-resolution FTS at the National Center for Atmospheric Research (HR-NCAR-FTS) show that the CU mobile SOF measurements of NH3 and C2H6 are precise and accurate; the VCD error at high signal to noise ratio is 2–7 %. During the Front Range Air Pollution and Photochemistry Experiment (FRAPPE) from 21 July to 3 September 2014 in Colorado, the CU mobile SOF instrument measured median (minimum, maximum) VCDs of 4.3 (0.5, 45) × 1016 molecules cm−2 NH3, 0.30 (0.06, 2.23) × 1016 molecules cm−2 NO2 and 3.5 (1.5, 7.7) × 1016 molecules cm−2 C2H6. All gases were detected in larger 95 % of the spectra recorded in urban, semi-polluted rural and remote rural areas of the Colorado Front Range. We calculate structure functions based on VCDs, which describe the variability of a gas column over distance, and find the largest variability for NH3. The structure functions suggest that currently available satellites resolve about 10 % of the observed NH3 and NO2 VCD variability in the study area. We further quantify the trace gas emission fluxes of NH3 and C2H6 and production rates of NO2 from concentrated animal feeding operations (CAFO) using the mass balance method, i.e., the closed-loop vector integral of the VCD times wind speed along the drive track. Excellent reproducibility is found for NH3 fluxes and also, to a lesser extent, NO2 production rates on 2 consecutive days; for C2H6 the fluxes are affected by variable upwind conditions. Average emission factors were 12.0 and 11.4 gNH3 h−1 head−1 at 30 °C for feedlots with a combined capacity for ∼ 54 000 cattle and a dairy farm of ∼ 7400 cattle; the pooled rate of 11.8 ± 2.0 gNH3 h−1 head−1 is compatible with the upper range of literature values. At this emission rate the NH3 source from cattle in Weld County, CO (535 766 cattle), could be underestimated by a factor of 2–10. CAFO soils are found to be a significant source of NOx. The NOx source accounts for ∼ 1.2 % of the N flux in NH3 and has the potential to add ∼ 10 % to the overall NOx emissions in Weld County and double the NOx source in remote areas. This potential of CAFO to influence ambient NOx concentrations on the regional scale is relevant because O3 formation is NOx sensitive in the Colorado Front Range. Emissions of NH3 and NOx are relevant for the photochemical O3 and secondary aerosol formation.
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- 2018
155. Websites on Bladder Cancer: an Appropriate Source of Patient Information?
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Johannes Salem, Hendrik Borgmann, David G. Pfister, Timur H. Kuru, Angelika Cebulla, Melanie von Brandenstein, Pia Paffenholz, Igor Tsaur, Christian Bolenz, Cheryl T. Lee, Axel Haferkamp, and Axel Heidenreich
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medicine.medical_specialty ,Internet ,Consumer Health Information ,business.industry ,Public Health, Environmental and Occupational Health ,Health literacy ,Guideline ,Certification ,Popularity ,Checklist ,Readability ,Health Literacy ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Urinary Bladder Neoplasms ,Interquartile range ,030220 oncology & carcinogenesis ,Family medicine ,Medicine ,Humans ,030212 general & internal medicine ,business ,Comprehension ,Patient education - Abstract
A growing number of patients search for health information online. An early investigation of websites about bladder cancer (BCa) revealed mostly incomplete and particularly inaccurate information. We analyzed the quality, readability, and popularity of the most frequented websites on BCa. An Internet search on www.google.com was performed for the term “bladder cancer.” After selecting the most frequented websites for patient information, HONcode quality certification, Alexa popularity rank, and readability scores (according to US grade levels) were investigated. A 36-point checklist was used to assess the content according to the EAU guidelines on BCa, which was categorized into seven topics. The popularity of the 49 websites analyzed was average, with a median Alexa popularity rank of 41,698 (interquartile range [IQR] 7–4,671,246). The readability was rated difficult with 11 years of school education needed to understand the information. Thirteen (27%) websites were HONcode certified. Out of 343 topics (seven EAU guideline topics each on 49 websites), 79% were mentioned on the websites. Of these, 10% contained incorrect information, mostly outdated or biased, and 34% contained incomplete information. Publically provided websites mentioned more topics per website (median [IQR] 7 [5.5–7] vs. 5.5 [3.3–7]; p = 0.022) and showed less incorrect information (median [IQR] 0 [0–1] vs. 1 [0–1]; p = 0.039) than physician-provided websites. Our study revealed mostly correct but partially incomplete information on BCa websites for patients. Physicians and public organizations should strive to keep their website information up-to-date and unbiased to optimize patients’ health literacy.
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- 2018
156. Use of Larynx-Preservation Strategies in the Treatment of Laryngeal Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update
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Avraham Eisbruch, Quynh-Thu Le, Randy Weber, Gail Fass, Arlene A. Forastiere, Susan G. Fisher, Snehal G. Patel, David J. Adelstein, Gregory S. Weinstein, Nofisat Ismaila, David G. Pfister, William M. Mendenhall, Anthony F. Provenzano, Jan S. Lewin, Gregory T. Wolf, Cherie-Ann Nathan, Scott A. Laurie, and Bernard O'Malley
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Cancer Research ,medicine.medical_specialty ,Consensus ,medicine.medical_treatment ,Clinical Decision-Making ,MEDLINE ,Laryngectomy ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Swallowing ,medicine ,Adjuvant therapy ,Humans ,030223 otorhinolaryngology ,Intensive care medicine ,Laryngeal Neoplasms ,Neoplasm Staging ,Evidence-Based Medicine ,medicine.diagnostic_test ,business.industry ,Patient Selection ,Cancer ,Guideline ,medicine.disease ,United States ,Treatment Outcome ,Oncology ,Positron emission tomography ,030220 oncology & carcinogenesis ,business ,Organ Sparing Treatments - Abstract
Purpose To update the guideline recommendations on the use of larynx-preservation strategies in the treatment of laryngeal cancer. Methods An Expert Panel updated the systematic review of the literature for the period from January 2005 to May 2017. Results The panel confirmed that the use of a larynx-preservation approach for appropriately selected patients does not compromise survival. No larynx-preservation approach offered a survival advantage compared with total laryngectomy and adjuvant therapy as indicated. Changes were supported for the use of endoscopic surgical resection in patients with limited disease (T1, T2) and for initial total laryngectomy in patients with T4a disease or with severe pretreatment laryngeal dysfunction. New recommendations for positron emission tomography imaging for the evaluation of regional nodes after treatment and best measures for evaluating voice and swallowing function were added. Recommendations Patients with T1, T2 laryngeal cancer should be treated initially with intent to preserve the larynx by using endoscopic resection or radiation therapy, with either leading to similar outcomes. For patients with locally advanced (T3, T4) disease, organ-preservation surgery, combined chemotherapy and radiation, or radiation alone offer the potential for larynx preservation without compromising overall survival. For selected patients with extensive T3 or large T4a lesions and/or poor pretreatment laryngeal function, better survival rates and quality of life may be achieved with total laryngectomy. Patients with clinically involved regional cervical nodes (N+) who have a complete clinical and radiologic imaging response after chemoradiation do not require elective neck dissection. All patients should undergo a pretreatment baseline assessment of voice and swallowing function and receive counseling with regard to the potential impact of treatment options on voice, swallowing, and quality of life. Additional information is available at www.asco.org/head-neck-cancer-guidelines and www.asco.org/guidelineswiki .
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- 2017
157. A Multi-Institutional Comparison of Carboplatin-Based Regimens Versus Cetuximab in Chemoradiation for p16(-) Head and Neck Cancer
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Alexander Yaney, Aashish D. Bhatt, Thomas H. Beckham, R. Rupert, Eric J. Sherman, J. Tan, C.J. Tsai, Sean McBride, C. Barney, E. Healy, Lara Dunn, Dukagjin Blakaj, David G. Pfister, A. Branstetter, Nancy Y. Lee, Nadeem Riaz, Marcelo Bonomi, Jessica Wobb, and D.L. Mitchell
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Oncology ,Cancer Research ,medicine.medical_specialty ,Radiation ,Cetuximab ,business.industry ,Head and neck cancer ,medicine.disease ,Carboplatin ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,business ,medicine.drug - Published
- 2018
158. Phase II trial of bevacizumab + cetuximab + cisplatin with concurrent intensity-modulated radiation therapy for patients with stage III/IVB head and neck squamous cell carcinoma
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Daphna Y. Gelblum, David G. Pfister, Nancy Y. Lee, R.M. Gewanter, Han Xiao, Brynna Lipson, Shrujal S. Baxi, Jatin P. Shah, Eric J. Sherman, Heiko Schöder, Lisa Cox, Nora Katabi, Stephanie Smith-Marrone, Rachel Kurtzman, Matthew G. Fury, Sofia Haque, and Karen D. Schupak
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Bevacizumab ,Cetuximab ,business.industry ,medicine.medical_treatment ,medicine.disease ,Head and neck squamous-cell carcinoma ,Loading dose ,Primary tumor ,Radiation therapy ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Otorhinolaryngology ,Tolerability ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Mucositis ,business ,medicine.drug - Abstract
Background The purpose of this study was to evaluate the efficacy and tolerability of the addition of 2 monoclonal antibodies, bevacizumab and cetuximab, to 2 cycles of high-dose cisplatin administered concurrently with intensity-modulated radiation therapy (IMRT) for head and neck squamous cell carcinoma (HNSCC). Methods Patients with newly diagnosed stage III/IVB (M0) HNSCC received cetuximab (400 mg/m2 loading dose, followed by 250 mg/m2 weekly), bevacizumab (15 mg/kg, days 1 and 22), and cisplatin (50 mg/m2, days 1, 2, 22, and 23) concurrently with IMRT (70 Gy). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety and tolerability. Results Among 30 patients enrolled in this study, the primary tumor site was the oropharynx in 24 patients (p16 immunohistochemistry was positive in 17, negative in 1, and not done in 6 of the oropharyngeal tumors). Median age was 57 years (range, 38–77 years) and 27 patients had clinical stage IVA disease. All patients completed the full planned dose of radiation therapy. The most common ≥ grade 3 adverse events were lymphopenia, mucositis (functional), and dysphagia. With a median follow-up of 33.8 months, 2-year PFS was 88.5% (95% confidence interval [CI] = 68.1–96.1) and 2-year OS was 92.8% (95% CI = 74.2–98.1). Conclusion The addition of bevacizumab and cetuximab to 2 cycles of cisplatin, given concurrently with IMRT, was well-tolerated and was associated with favorable efficacy outcomes in this patient population. © 2015 Wiley Periodicals, Inc. Head Neck, 2015
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- 2015
159. Head and Neck Cancers, Version 1.2015
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Jatin P. Shah, John A. Ridge, Cristina P. Rodriguez, Loren K. Mell, Sue S. Yom, Maura L. Gillison, Robert I. Haddad, Paul M. Busse, Randal S. Weber, Miranda Hughes, Thomas V. McCaffrey, Barbara Burtness, Ellie Maghami, William M. Lydiatt, Merrill S. Kies, Jill Gilbert, David M. Brizel, Wesley L. Hicks, Sandeep Samant, Gregory T. Wolf, Frank Worden, Nicole R. McMillian, Robert L. Foote, Frank Dunphy, Antonio Jimeno, Ying J. Hitchcock, Harlan A. Pinto, Bruce H. Haughey, Sharon A. Spencer, Jimmy J. Caudell, David G. Pfister, Bharat B. Mittal, A. Dimitrios Colevas, David W. Eisele, and Anthony J. Cmelak
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medicine.medical_specialty ,Oncology ,business.industry ,Medicine ,Medical physics ,business ,Head and neck ,Disease control ,Neutron therapy - Abstract
These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (HN the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.
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- 2015
160. Trends in chemoradiation use in elderly patients with head and neck cancer: Changing treatment patterns with cetuximab
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Eric J. Sherman, Caitriona B. O'Neill, Shrujal S. Baxi, Nancy Y. Lee, David G. Pfister, Coral L. Atoria, and Elena B. Elkin
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Oncology ,medicine.medical_specialty ,genetic structures ,Cetuximab ,business.industry ,medicine.medical_treatment ,Comorbidity score ,Head and neck cancer ,Locally advanced ,medicine.disease ,Head and neck squamous-cell carcinoma ,Radiation therapy ,03 medical and health sciences ,0302 clinical medicine ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Surveillance, Epidemiology, and End Results ,030212 general & internal medicine ,business ,Chemoradiotherapy ,medicine.drug - Abstract
Background Cetuximab was approved for use in chemoradiation therapy (CRT) for locally advanced head and neck squamous cell carcinoma (HNSCC) in 2006. Methods Among 3705 patients with locally advanced HNSCC identified in the linked Surveillance Epidemiology and End Results (SEER) Medicare database, we assessed treatment trends, including surgery, radiation therapy (RT), CRT, and specific agents used in CRT. We examined the influence of demographic and clinical characteristics on the likelihood of receiving CRT before and after 2006. Results Chemoradiation use increased from 29% of patients diagnosed in 2001 to 61% in 2009 (p
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- 2015
161. Treatment-related toxicities in older adults with head and neck cancer: A population-based analysis
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James P. O'Neill, Nancy Y. Lee, David G. Pfister, Shrujal S. Baxi, Martin Henman, Coral L. Atoria, Elena B. Elkin, Caitriona B. O'Neill, and Eric J. Sherman
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Cancer Research ,education.field_of_study ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Head and neck cancer ,Population ,Cancer ,medicine.disease ,Head and neck squamous-cell carcinoma ,Cancer registry ,Surgery ,Radiation therapy ,Oncology ,Internal medicine ,medicine ,education ,business ,Feeding tube ,Cohort study - Abstract
BACKGROUND Despite advantages in terms of cancer control and organ preservation, the benefits of chemotherapy and radiation therapy (CTRT) may be offset by potentially severe treatment-related toxicities, particularly in older patients. The objectives of this study were to assess the types and frequencies of toxicities in older adults with locally or regionally advanced head and neck squamous cell carcinoma (HNSCC) who were receiving either primary CTRT or radiation therapy (RT) alone. METHODS With Surveillance, Epidemiology, and End Results cancer registry data linked with Medicare claims, patients who were 66 years old or older with locally advanced HNSCC, were diagnosed from 2001 to 2009, and received CTRT or RT alone were identified. Differences in the frequency of toxicity-related hospital admissions and emergency room visits as well as feeding tube use were examined, and controlling for demographic and disease characteristics, this study estimated the impact of chemotherapy on the likelihood of toxicity. RESULTS Among patients who received CTRT (n = 1502), 62% had a treatment-related toxicity, whereas 46% of patients who received RT alone (n = 775) did. When the study controlled for demographic and disease characteristics, CTRT patients were twice as likely to experience an acute toxicity in comparison with their RT-only peers. Fifty-five percent of CTRT patients had a feeding tube placed during or after treatment, whereas 28% of the RT-only group did. CONCLUSIONS In this population-based cohort of older adults with HNSCC, the rates of acute toxicities and feeding tube use in patients receiving CTRT were considerable. It is possible that for certain older patients, the potential benefit of adding chemotherapy to RT does not outweigh the harms of this combined-modality therapy. Cancer 2015. © 2015 American Cancer Society. Cancer 2015;121:2083–2089. © 2015 American Cancer Society.
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- 2015
162. Editorial Board / Contents / Imprint / Guidelines for Authors
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Ruth Knüchel, Marcela V. Maus, Judd W. Moul, Jan Herden, Hocine Habchi, Nicolas Mottet, Robert Qi, Timur H. Kuru, Pia Paffenholz, Axel Heidenreich, Brian C. Miller, David G. Pfister, Julius van Essen, Isabell Heidegger, and Daniel Porres
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Cancer Research ,Oncology ,Library science ,Hematology ,Editorial board - Published
- 2015
163. Role of Focal Therapy with High-Intensity Focused Ultrasound in the Management of Clinically Localized Prostate Cancer
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T. Kuru, Julius van Essen, David G. Pfister, and Daniel Porres
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Male ,Cancer Research ,medicine.medical_specialty ,Pathology ,Evidence-Based Medicine ,business.industry ,medicine.medical_treatment ,Standard treatment ,Prostatic Neoplasms ,Salvage therapy ,Hematology ,medicine.disease ,High-intensity focused ultrasound ,Focused ultrasound ,Focal therapy ,Prostate cancer ,Treatment Outcome ,Oncology ,Hifu treatment ,medicine ,Collateral damage ,High-Intensity Focused Ultrasound Ablation ,Humans ,Radiology ,business - Abstract
Overtreatment of prostate cancer (PC) remains one of the main burdens in uro-oncology. Focal therapy may be a reasonable alternative with less side effects and morbidity. Application of high-intensity focused ultrasound (HIFU) induces immediate and irreversible coagulation. The treatment leads to consecutive necrosis with sharply delineated margins, making HIFU a promising tool for the focal therapy of localized PC. Unlike radiation, the treatment leaves no collateral damage outside of the heated tissue, allowing repeated use of HIFU, if necessary. In case of non-organ-confined relapse, additional radical salvage therapy can be performed. This review gives an overview of the existing evidence on focal HIFU. Today, 3 HIFU devices are approved for the treatment of localized PC: Sonablate™, Ablatherm™ and the FocalOne™ device. In summary, the first published results of focal HIFU are promising. The quality of life and potency of the patients are well preserved. Therefore, HIFU treatment, and especially focal ablation of tumor foci, seems to be a safe alternative to standard treatment, with low side effects. The oncologic results seem satisfactory but need further follow-up to validate this practice of PC control.
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- 2015
164. Use of passive samplers in pollution monitoring: A numerical approach for marinas
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Bernhard Henkelmann, Karl-Werner Schramm, Sevil D. Yakan, Atilla Yılmaz, Burak Karacik, Baris Barlas, Oya S. Okay, and G. Pfister
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Pollutant ,Pollution ,lcsh:GE1-350 ,media_common.quotation_subject ,Environmental engineering ,Organochlorine pesticide ,Contamination ,Pesticide ,Polychlorinated Biphenyls ,Pollution monitoring ,Environmental chemistry ,Hydrocarbons, Chlorinated ,Environmental science ,Seawater ,Pesticides ,Polycyclic Aromatic Hydrocarbons ,Environmental Pollution ,SPMD ,Ships ,Water Pollutants, Chemical ,lcsh:Environmental sciences ,General Environmental Science ,media_common ,Environmental Monitoring - Abstract
Triolein-containing semipermeable membrane devices (SPMDs) and butyl rubber (BR) based sorbents were employed as passive samplers in 14 coastal stations of Turkey including shipyards and marinas to characterize time-integrated levels of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) and their relationship to potential pollution sources. Passive samplers of SPMDs and BR sorbents were deployed for 30 days in the spring of 2012. The maximum concentrations of total PAH and PCB compounds sequestered by SPMDs were 3338 ng g−1 SPMD and 4247 pg g−1 SPMD. (END)-I and DDT-related compounds were dominant OCP compounds for most of the sites in passive samplers. Total PAH concentrations in SPMDs were found 1.2 to 8 times higher than the concentrations in BRs. However, BR sorbents were able to sample some PAHs which could not be sampled by SPMDs. The concentrations of PCBs and OCPs in BRs were similar or higher than SPMDs. SPMD-data were used to estimate the average ambient water concentrations of the contaminants. Two existing theoretical approaches have been used to derive the concentrations of hydrophobic pollutants in the ambient waters. The results were found very similar and range from 7318 to 183864 pg L−1 for PAHs, from 2 to 186 pg L−1 for PCBs, and from 98 to 848 pg L−1 for OCPs. Furthermore, a simple numerical model was designed to estimate the boat-related water concentrations in marinas by using the seawater data supplied by SPMDs. The model was mainly built on the water concentration and the capacities of a particular marina and then applied to two sites in the second marina. A good correlation was found between the model outputs and SPMD-water data. Keywords: Passive water sampling, PAH, POP, Shipyard, Marina, Pollution
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- 2014
165. Antiangiogenic therapies in urogenital malignancies: Fiction or fact?
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Friederike Haidl, David G. Pfister, Axel Heidenreich, and Isabel Heidegger
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Angiogenesis ,MEDLINE ,Review ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Testicular cancer ,Prostate ,Internal medicine ,medicine ,Urothelial cancer ,Penile cancer ,Genitourinary system ,business.industry ,Hematology ,Antiangiogenic therapeutics ,medicine.disease ,Review article ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,business - Abstract
Summary The use of antiangiogenic agents in cancer therapy has become an attractive target in oncological research. However, concerning the uro-oncological field, current guidelines only recommend the use of antiangiogenic agents in metastatic renal cell cancer. Yet in recent years, several approaches for sequential treatment with angiogenesis inhibitors in other urogenital malignancies apart from renal cell cancer are ongoing. Thus, the present review article aims to provide an overview about clinical studies with antiangiogenic agents in prostate-, bladder-, testicular-, as well as penile cancer patients. For this, a literature search was conducted using Medline; moreover we performed a systematic review of data presented at this year’s important urooncological meetings. Preliminary data revealed that there are several promising studies ongoing in prostate-, bladder-, testicular-, as well as penile cancer; however, larger studies should be conducted to optimize the use of antiangiogenic agents in clinical practice.
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- 2017
166. Tumor mutational load predicts survival after immunotherapy across multiple cancer types
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Christopher A. Klebanoff, Emmet Jordan, Rona Yaeger, Sviatoslav M. Kendall, Marc Ladanyi, Timothy A. Chan, José Baselga, Luc G. T. Morris, Jamie E. Chaft, Michael F. Berger, Alexander N. Shoushtari, Sandra P. D'Angelo, Gregory J. Riely, Ahmet Zehir, Nancy Y. Lee, Robert J. Motzer, A. Ari Hakimi, David G. Pfister, Cameron Brennan, Ronglai Shen, Charlotte E. Ariyan, Christopher A. Barker, Ingo K. Mellinghoff, William D. Tap, Martin H. Voss, Chung-Han Lee, Howard I. Scher, Paul Russo, Nadeem Riaz, David Barron, Antonio Omuro, Philip H. Gutin, Robert M. Samstein, Leonard B. Saltz, Lisa M. DeAngelis, Jedd D. Wolchok, Naiyer A. Rizvi, Zsofia K. Stadler, Dean F. Bajorin, Charles M. Rudin, Geoffrey Y. Ku, David B. Solit, Ronald P. DeMatteo, Matthew D. Hellmann, Bernard H. Bochner, Mrinal M. Gounder, Hikmat Al-Ahmadie, Pedram Razavi, Alan L. Ho, Gopa Iyer, Viviane Tabar, Shrujal S. Baxi, Jonathan E. Rosenberg, Thomas Kaley, Richard J. Wong, Yelena Y. Janjigian, and Neil H. Segal
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Oncology ,medicine.medical_specialty ,Immune checkpoint inhibitors ,medicine.medical_treatment ,Genomic data ,Antineoplastic Agents ,Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Internal medicine ,Neoplasms ,Genetics ,medicine ,Humans ,030304 developmental biology ,Predictive biomarker ,0303 health sciences ,Multiple cancer ,business.industry ,Cancer ,High-Throughput Nucleotide Sequencing ,Histology ,Immunotherapy ,medicine.disease ,Tumor Burden ,Mutation ,business ,030217 neurology & neurosurgery - Abstract
Immune checkpoint inhibitor (ICI) treatments benefit some patients with metastatic cancers, but predictive biomarkers are needed. Findings in select cancer types suggest that tumor mutational burden (TMB) may predict clinical response to ICI.To examine this association more broadly, we analyzed the clinical and genomic data of 1662 advanced cancer patients treated with ICI, and 5371 non-ICI treated patients, whose tumors underwent targeted next-generation sequencing (MSK-IMPACT). Among all patients, higher somatic TMB (highest 20% in each histology) was associated with better OS (HR 0.52; p=1.6 ×10(−6)). For most cancer histologies, an association between higher TMB and improved survival was observed. The TMB cutpoints associated with improved survival varied markedly between cancer types. These data indicate that TMB is associated with improved survival in patients receiving ICI across a wide variety of cancer types, but that there may not be one universal definition of high TMB.
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- 2017
167. Testicular Cancer on the Web-an Appropriate Source of Patient Information in Concordance with the European Association of Urology Guidelines?
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Hendrik Borgmann, Johannes Salem, Pia Paffenholz, Axel Haferkamp, Axel Heidenreich, Christian Ruf, Igor Tsaur, David G. Pfister, and Tim Nestler
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Adult ,Male ,medicine.medical_specialty ,Health Knowledge, Attitudes, Practice ,Concordance ,Urology ,030232 urology & nephrology ,Health literacy ,Guidelines as Topic ,03 medical and health sciences ,0302 clinical medicine ,Patient Education as Topic ,Testicular Neoplasms ,Germany ,Medicine ,Humans ,Disease management (health) ,Testicular cancer ,Internet ,Consumer Health Information ,business.industry ,Public Health, Environmental and Occupational Health ,Guideline ,medicine.disease ,Popularity ,Readability ,Health Literacy ,Oncology ,030220 oncology & carcinogenesis ,business ,Comprehension ,Patient education - Abstract
Despite the continuous growth of the internet, little is known about the quality of online information on testicular cancer, the most common solid malignancy in young men. In our study, we analysed the quality, readability and popularity of the most popular websites on testicular cancer. Therefore, we performed a web search for the term “testicular cancer” using www.google.com . Fifty-one websites were evaluated for HONcode quality certification, Alexa Popularity Rank and readability levels. Furthermore, the websites’ content on eight major topics of the current European Association of Urology Guidelines on testicular cancer was assessed. Fourteen (28%) had a HONcode quality certificate and the mean Alexa Popularity Rank of all 51 websites was 54,040 (interquartile range 6648–282,797). Websites were difficult to read requiring 9 years of US school education to properly understand the information. The websites mentioned 80% of the guideline topics on average, revealing “prognosis” (59%) and “follow-up” (57%) as underrepresented subtopics. Furthermore, 12% of all topics were displayed incorrectly, particularly due to wrong information concerning “aetiology” (42%). Sixty percent of the topics were mentioned in an incomplete fashion, with less than half of the websites displaying complete information on “staging” (47%), “diagnostic evaluation” (49%) or “disease management” (45%). In general, online health information concerning testicular cancer is mentioned correctly on most websites. However, improvement regarding readability and completeness of the given information is needed. Nevertheless, highly selected websites on testicular cancer can serve as an appropriate source of patient information.
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- 2017
168. MP68-01 EFFECTS AND OUTCOMES OF URETERAL STENTING PRIOR TO URETEROSCOPY VERSUS PRIMARY URETEROSCOPY IN URINARY STONE TREATMENT
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Melanie von Brandenstein, Ilgar Akbarov, David G. Pfister, Ali Tok, Mustafa Al-Mahmid, Axel Heidenreich, and Vahudin Zugor
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Urology ,Urinary stone ,Medicine ,Ureteroscopy ,business - Published
- 2017
169. MP53-20 RADIUM-223(RAD) IN MEN WITH SYMPTOMATIC CASTRATION-RESISTANT PROSTATE CANCER: GUIDELINE VERSUS CLINICAL REALITY
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Pia Paffenholz, David G. Pfister, Daniel Porres, Saskia Kanzelmeyer, Axel Heidenreich, and Isabel Heidegger
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Oncology ,Radium-223 ,medicine.medical_specialty ,business.industry ,Urology ,Guideline ,Castration resistant ,medicine.disease ,Clinical reality ,Prostate cancer ,Internal medicine ,medicine ,business ,medicine.drug - Published
- 2017
170. MP24-05 UPPER URINARY TRACT DECOMPRESSION USING ILEAL URETER REPLACEMENT IN COMPARISON TO ENDOURETERAL THERMOEXPANDABLE STENT [MEMOKATH 051]
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David G. Pfister, Axel Heidenreich, Mustafa Al-Mahmid, and Ilgar Akbarov
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medicine.medical_specialty ,Decompression ,business.industry ,030503 health policy & services ,Urology ,medicine.medical_treatment ,Stent ,Ileal ureter ,03 medical and health sciences ,0302 clinical medicine ,medicine ,030212 general & internal medicine ,0305 other medical science ,business ,Upper urinary tract - Published
- 2017
171. PD53-01 NON-GUIDELINE CONCORDANT TREATMENT OF TESTICULAR CANCER
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Axel Heidenreich, David G. Pfister, and Pia Paffenholz
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Oncology ,medicine.medical_specialty ,business.industry ,Guideline-concordant Treatment ,Urology ,Internal medicine ,medicine ,business ,medicine.disease ,Testicular cancer - Published
- 2017
172. MP80-03 DISTRESS SCREENING IN PATIENTS WITH UROGENITAL MALIGNANCIES
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David G. Pfister, Pia Paffenholz, Maria Angerer-Shpilenya, Axel Heidenreich, and Johannes Salem
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medicine.medical_specialty ,Genitourinary system ,business.industry ,Urology ,Internal medicine ,Medicine ,In patient ,Distress screening ,business - Published
- 2017
173. Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study
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David G. Pfister, Jonathan D. Cheng, Steven M. Powell, Jill Gilbert, Stephen V. Liu, Hyunseok Kang, Lori J. Wirth, Tanguy Y. Seiwert, Francis P. Worden, Erminia Massarelli, Nabil F. Saba, Robert I. Haddad, Michael K. Gibson, Ammar Sukari, Amy Meister, Xinxin Shu, Joshua Bauml, and Jared Weiss
- Subjects
0301 basic medicine ,Oncology ,Male ,Cancer Research ,Phases of clinical research ,Cetuximab ,Platinum Compounds ,Pembrolizumab ,B7-H1 Antigen ,0302 clinical medicine ,Monoclonal ,80 and over ,Medicine ,Humanized ,6.2 Cellular and gene therapies ,Cancer ,Aged, 80 and over ,education.field_of_study ,ORIGINAL REPORTS ,Middle Aged ,Survival Rate ,Infectious Diseases ,Local ,Response Evaluation Criteria in Solid Tumors ,Head and Neck Neoplasms ,6.1 Pharmaceuticals ,030220 oncology & carcinogenesis ,Retreatment ,Carcinoma, Squamous Cell ,Disease Progression ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Clinical Sciences ,Oncology and Carcinogenesis ,Population ,Antineoplastic Agents ,Antibodies, Monoclonal, Humanized ,Antibodies ,Disease-Free Survival ,03 medical and health sciences ,Rare Diseases ,Clinical Research ,Internal medicine ,Humans ,Oncology & Carcinogenesis ,Dental/Oral and Craniofacial Disease ,education ,Survival rate ,Aged ,business.industry ,Carcinoma ,Head and neck cancer ,Papillomavirus Infections ,Evaluation of treatments and therapeutic interventions ,medicine.disease ,Head and neck squamous-cell carcinoma ,Neoplasm Recurrence ,030104 developmental biology ,Squamous Cell ,Sexually Transmitted Infections ,Neoplasm Recurrence, Local ,business - Abstract
Purpose There are no approved treatments for recurrent/metastatic head and neck squamous cell carcinoma refractory to platinum and cetuximab. In the single-arm, phase II KEYNOTE-055 study, we evaluated pembrolizumab, an anti–programmed death 1 receptor antibody, in this platinum- and cetuximab-pretreated population with poor prognosis. Methods Eligibility stipulated disease progression within 6 months of platinum and cetuximab treatment. Patients received pembrolizumab 200 mg every 3 weeks. Imaging was performed every 6 to 9 weeks. Primary end points: overall response rate (Response Evaluation Criteria in Solid Tumors v1.1, central review) and safety. Efficacy was assessed in all dosed patients and in subgroups on the basis of programmed death ligand 1 (PD-L1) expression and human papillomavirus (HPV) status. Results Among 171 patients treated, 75% received two or more prior lines of therapy for metastatic disease, 82% were PD-L1 positive, and 22% were HPV positive. At the time of analysis, 109 patients (64%) experienced a treatment-related adverse event; 26 patients (15%) experienced a grade ≥ 3 event. Seven patients (4%) discontinued treatment, and one died of treatment-related adverse events. Overall response rate was 16% (95% CI, 11% to 23%), with a median duration of response of 8 months (range, 2+ to 12+ months); 75% of responses were ongoing at the time of analysis. Response rates were similar in all HPV and PD-L1 subgroups. Median progression-free survival was 2.1 months, and median overall survival was 8 months. Conclusion Pembrolizumab exhibited clinically meaningful antitumor activity and an acceptable safety profile in recurrent/metastatic head and neck squamous cell carcinoma previously treated with platinum and cetuximab.
- Published
- 2017
174. Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas
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Snjezana, Dogan, Deborah J, Chute, Bin, Xu, Ryan N, Ptashkin, Raghu, Chandramohan, Jacklyn, Casanova-Murphy, Khedoudja, Nafa, Justin A, Bishop, Simion I, Chiosea, Edward B, Stelow, Ian, Ganly, David G, Pfister, Nora, Katabi, Ronald A, Ghossein, and Michael F, Berger
- Subjects
Adult ,Aged, 80 and over ,Male ,Maxillary Sinus Neoplasms ,Carcinoma ,DNA Mutational Analysis ,High-Throughput Nucleotide Sequencing ,SMARCB1 Protein ,Middle Aged ,Genes, p53 ,Isocitrate Dehydrogenase ,Article ,Carcinoma, Neuroendocrine ,Mutation ,Biomarkers, Tumor ,Humans ,Female ,Carcinoma, Small Cell ,Gene Deletion ,Aged - Abstract
Sinonasal undifferentiated carcinoma (SNUC) is a high-grade malignancy with limited treatment options and poor outcome. A morphologic spectrum of 47 sinonasal tumors including 17 (36.2%) SNUCs were analyzed at genomic level. Thirty carcinomas (Cohort 1) were subjected to a hybridization exon-capture next-generation sequencing assay (MSK-IMPACT™) to interrogate somatic variants in 279 or 410 cancer-related genes. Seventeen sinonasal tumors (Cohort 2) were examined only for presence of IDH1/2 exon 4 mutations by Sanger sequencing. IDH2 R172 single nucleotide variants were overall detected in 14 (82.4%) SNUCs, in 2 (20%) poorly-differentiated carcinomas with glandular/acinar differentiation, and in one of 2 high-grade neuroendocrine carcinomas, large cell type (HGNEC). No IDH2 mutation was detected in any of 5 olfactory neuroblastomas or in any of 5 SMARCB1–deficient carcinomas.
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- 2017
175. Performance of a Trigger Tool for Identifying Adverse Events in Oncology
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David G. Pfister, Christopher B. Anderson, David Classen, Aileen R. Killen, Elizabeth Fortier, Allison Lipitz-Snyderman, Andrew S. Epstein, Saul N. Weingart, and Coral L. Atoria
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,Original Contributions ,MEDLINE ,Medical Oncology ,Cohort Studies ,03 medical and health sciences ,Patient safety ,0302 clinical medicine ,Internal medicine ,Medicine ,Humans ,030212 general & internal medicine ,Longitudinal Studies ,Adverse effect ,Aged ,Retrospective Studies ,Aged, 80 and over ,Oncology (nursing) ,business.industry ,Health Policy ,Medical record ,Cancer ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Quality Improvement ,030220 oncology & carcinogenesis ,Cohort ,Female ,business ,Cohort study - Abstract
Purpose: Although patient safety is a priority in oncology, few tools measure adverse events (AEs) beyond treatment-related toxicities. The study objective was to assemble a set of clinical triggers in the medical record and assess the extent to which triggered events identified AEs. Methods: We performed a retrospective cohort study to assess the performance of an oncology medical record screening tool at a comprehensive cancer center. The study cohort included 400 patients age 18 years or older diagnosed with breast (n = 128), colorectal (n = 136), or lung cancer (n = 136), observed as in- and outpatients for up to 1 year. Results: We identified 790 triggers, or 1.98 triggers per patient (range, zero to 18 triggers). Three hundred four unique AEs were identified from medical record reviews and existing AE databases. The overall positive predictive value (PPV) of the original tool was 0.40 for total AEs and 0.15 for preventable or mitigable AEs. Examples of high-performing triggers included return to the operating room or interventional radiology within 30 days of surgery (PPV, 0.88 and 0.38 for total and preventable or mitigable AEs, respectively) and elevated blood glucose (> 250 mg/dL; PPV, 0.47 and 0.40 for total and preventable or mitigable AEs, respectively). The final modified tool included 49 triggers, with an overall PPV of 0.48 for total AEs and 0.18 for preventable or mitigable AEs. Conclusion: A valid medical record screening tool for AEs in oncology could offer a powerful new method for measuring and improving cancer care quality. Future improvements could optimize the tool’s efficiency and create automated electronic triggers for use in real-time AE detection and mitigation algorithms.
- Published
- 2017
176. Editorial Board / Imprint / Innentitel / Contents
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Julie Steinestel, Jürgen E. Gschwend, Martin Bögemann, Kurt Miller, Andreas Jan Schrader, David G. Pfister, Christof Bernemann, Druck, and Johannes M. Wolff
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Cancer Research ,Medical education ,Pathology ,medicine.medical_specialty ,Oncology ,business.industry ,medicine ,Hematology ,Editorial board ,business - Published
- 2017
177. New Chapter in Our Understanding of Human Papillomavirus-Related Head and Neck Cancer
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Matthew G. Fury and David G. Pfister
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Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Internal medicine ,Transoral robotic surgery ,medicine ,Humans ,Papillomaviridae ,Survival rate ,Cyclin-Dependent Kinase Inhibitor p16 ,Survival analysis ,business.industry ,Head and neck cancer ,HPV infection ,ORIGINAL REPORTS ,medicine.disease ,Neoplasm Proteins ,Radiation therapy ,Oropharyngeal Neoplasms ,Carcinoma, Squamous Cell ,Female ,business ,Progressive disease ,Chemoradiotherapy - Abstract
Our knowledge about the relationship between human papillomavirus (HPV) and squamous cell upper aerodigestive track cancers has advanced considerably over the last decade. We now know the oropharynx is the head and neck subsite particularly vulnerable to the development of tumors attributed to prior HPV infection. HPV 16 is the most common viral subtype, with implications regarding potential preventive measures. The incidence of HPV-related head and neck cancer is increasing, and the epidemiology of the disease and its risk factors are better understood. Patients with HPVpositive versus -negative disease differ. The former are younger and more likely to be white, a nonsmoker, have disease that is more responsive to therapy and overall have a better prognosis. Other factors such as prior tobacco use can still adversely affect the anticipated survival outcomes of patients with HPV-related head and neck cancer. Patients at the initial presentation of their locoregional disease have been the focus of the work to date that has generated these and other insights. The role of HPV tumor status in the recurrent or metastatic setting, however, has received far less attention. In this regard, the article by Fakhry et al that accompanies this editorial represents an important contribution to a new chapter in our understanding of HPV-related head and neck tumors. Specifically, how the HPV status of a recurrent or metastatic oropharynx cancers affects anticipated prognosis, and the related implications for disease management and the evaluation of new therapies. In their article, Fakhry et al present a comprehensive retrospective analysis of 181 patients who were enrolled on either Radiation Therapy Oncology Group (RT0G) 0129 or 0522 for their primary chemoradiotherapy treatment, subsequently experienced progressive disease, and in whom immunohistochemical p16 data were available as a surrogate marker for HPV status. With a median follow-up of 4 years after progression, time to progression (8.2 v 7.3 months, P .67, for p16-positive v –negative tumors) and patterns of disease progression did not differ significantly based on p16 status. The central finding was a dramatic difference in median overall survival after disease progression: 2.6 years for p16-positive cases versus 0.8 years for p16negative cases (P .001). This impact of tumor p16 status on overall survival after progression remained robust after multivariable analysis to address potential prognostic confounders and accounted for a 52% reduction in risk of death. Of note, the application of salvage surgery was associated with a reduction in mortality of similar magnitude. The observed difference in median overall survival between the p16-positive and -negative groups is not entirely unexpected. The molecular underpinnings of the inferior prognosis for p16-negative tumors in the locoregional disease setting after primary treatment would be expected to remain relevant at least in part in the recurrent/ metastatic setting. In addition, a similar analysis by Canadian investigators who analyzed a cohort of patients with oropharynx cancer with distant spread of disease after radiation or chemoradiotherapy, found that patients with an HPV-related cancer had a better survival rate at 2 years than patients with HPV-unrelated disease (11% v 4%, P .02). Based on their data, Fakhry et al understandably conclude that tumor HPV status should be a stratification factor in clinical trials studying patients with recurrent or metastatic oropharynx cancers. It has become commonplace for a number of cancers to design trials specifically for patients with tumors harboring predefined molecular characteristics. Stratification by p16 or HPV status is already occurring and expected in trials evaluating therapies for patients with previously untreated locally or regionally advanced head and neck cancers. Indeed, studies in this untreated population for which entry is limited to patients with HPV-related oropharynx cancer are in progress, evaluating, as examples, different chemoradiotherapy programs (RTOG 1016), different radiation doses after induction chemotherapy (Eastern Cooperative Oncology Group [ECOG] 1308) and primary management with transoral robotic surgery (ECOG 3311). Considering tumor HPV status and avoiding prognostic imbalance in treatment groups so as to avoid potentially misleading comparisons would seem particularly prudent when planning studies in the recurrent and metastatic setting, given that very modest improvements in survival, even in the 1to 2-month range, have provided the basis for the approval and licensing of often expensive drugs for the treatment of advanced, refractory cancer. It should be emphasized, however, that the anticipated survival differences by tumor p16 or HPV status will depend on what starting point for the survival analysis is chosen. The estimated difference in typical clinical trials evaluating drug therapies for patients with recurrent or metastatic head and neck cancer may be far less than the 1.8 year difference in medians reported by Fakhry et al, since attempts at salvage with surgery or radiation would have likely already occurred pre-enrollment. Thus patients with a better prognosis rendered disease free by these interventions are eliminated from the denominator. Available data from the EXTREME (Erbitux in First-Line Treatment of Recurrent or Metastatic Head and Neck Cancer) and SPECTRUM JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 32 NUMBER 30 OCTOBER 2
- Published
- 2014
178. Head and Neck Cancers, Version 2.2014
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Thomas V. McCaffrey, Maura L. Gillison, Anthony J. Cmelak, Ying J. Hitchcock, Jimmy J. Caudell, Gregory T. Wolf, Miranda Hughes, Ellie Maghami, Cristina P. Rodriguez, Harlan A. Pinto, Paul M. Busse, Bharat B. Mittal, David E. Schuller, John A. Ridge, Antonio Jimeno, David W. Eisele, Loren K. Mell, David G. Pfister, Sharon A. Spencer, David M. Brizel, Frank Dunphy, A. Dimitrios Colevas, Bruce H. Haughey, Merrill S. Kies, Jill Gilbert, William M. Lydiatt, Wesley L. Hicks, Nicole R. McMillian, Robert I. Haddad, Randal S. Weber, Barbara Burtness, Sandeep Samant, Frank Worden, Renato G. Martins, Sue S. Yom, and Jatin P. Shah
- Subjects
medicine.medical_specialty ,Glottis ,business.industry ,medicine.medical_treatment ,General surgery ,Cancer ,medicine.disease ,Radiation therapy ,medicine.anatomical_structure ,Oncology ,Quality of life ,DENTAL EVALUATION ,medicine ,Combined Modality Therapy ,Stage (cooking) ,business ,Head and neck - Abstract
Copyright © 2014 by the National Comprehensive Cancer Network. All rights reserved. This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers focuses on glottic laryngeal cancer, which is the most common type of laryngeal cancer and has an excellent cure rate. The lymphatic drainage of the glottis is sparse, and early stage primaries rarely spread to regional nodes. Because hoarseness is an early symptom, most glottic laryngeal cancer is early stage at diagnosis. Updates to these guidelines for 2014 include revisions to "Principles of Radiation Therapy" for each site and "Principles of Surgery," and the addition of a new section on "Principles of Dental Evaluation and Management."
- Published
- 2014
179. Blickdiagnose bei der transurethralen Resektion von Harnblasentumoren
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A.S. Merseburger, David G. Pfister, Walter F. Thon, S. Ising, N. Riechert-Mühe, Markus A. Kuczyk, Andres J. Schrader, H. Eggers, Axel Heidenreich, S. Steffens, R. Lehmann, and A. Leitenberger
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,Urology ,medicine ,Clinical competence ,business ,Observer variation - Abstract
Goldstandard zur Diagnosestellung und Therapie eines Harnblasentumors ist die transurethrale Resektion (TURB) mit konsekutiver histopathologischer Begutachtung. Ziel der Studie war es zu uberprufen, inwieweit der operierende Urologe den Befund bzgl. Dignitat und Stadium per Blickdiagnose richtig pradizieren kann. Dies ist u. a. entscheidend fur die mogliche Indikation einer Mitomycin-Fruhinstillationstherapie. Im Rahmen dieser prospektiven Untersuchung haben Urologen aus 5 deutschen Kliniken ihre Einschatzung zur Dignitat, dem Tumorstadium und der Tumordifferenzierung in 311 Fallen unmittelbar nach der TURB anhand eines einheitlichen Fragebogens dokumentiert. Die Sensitivitat der Einschatzung, dass es sich bei dem resezierten Befund um ein Malignom handelte, betrug 97 %, wohingegen die Spezifitat nur bei 41 % lag. Der positive (PPV) bzw. negative Vorhersagewert (NPV) betrugen 76 bzw. 88 %. Es wurden ebenfalls haufiger muskelinvasive Tumoren vermutet als histopathologisch bestatigt (PPV 52 %). Wurde eine Muskelinvasivitat nach makroskopischem Eindruck ausgeschlossen, so stimmte dies in der uberwiegenden Mehrzahl der Falle (NPV 95 %). Das Ausbildungsstadium der Operateure wirkte sich interessanterweise nicht auf den Vorhersagewert der Blickdiagnose aus. Insgesamt wird deutlich, dass makroskopisch im Rahmen einer TURB tumorsuspekte Urothelveranderungen durch den operierenden Urologen, unabhangig von seinem Ausbildungsstand, nicht sicher beurteilt werden konnen. Der Urologe bleibt zur weiteren Therapieplanung auf das sichere Urteil des Uropathologen angewiesen.
- Published
- 2014
180. Metastasiertes kastrationsresistentes Prostatakarzinom
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Christian Schwentner, F. König, S. Zastrow, Kurt Miller, Henrik Suttmann, R. Eichenauer, M-O. Grimm, P. Albers, G. Geiges, David G. Pfister, and G. Mickisch
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Urology ,Treatment options ,Disease ,Castration resistant ,medicine.disease ,Prostate cancer ,Stable Disease ,Quality of life ,Internal medicine ,Medicine ,Position paper ,Therapy monitoring ,business - Abstract
This position paper is intended to help to structure and to standardize therapy monitoring in patients with metastatic castration-resistant prostate cancer (mCRPC). With the treatment options available today, patients with metastatic disease can often maintain good quality of life and stable disease for several years. It is crucial that once a therapy becomes insufficiently effective that it be replaced in a timely manner by a new treatment option. From a prognostic point of view, it is important that patients receive as many as possible and in the ideal case all currently available treatment options.
- Published
- 2014
181. Impact of obesity on the survival of patients with early-stage squamous cell carcinoma of the oral tongue
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Snehal G. Patel, Matthew G. Fury, R. A. Ghossein, David G. Pfister, Andrew J. Dannenberg, Luc G. T. Morris, Jay O. Boyle, Xi Kathy Zhou, Patrick G. Morris, Neil M. Iyengar, Clifford A. Hudis, Amit Kochhar, and Alejandro Pino
- Subjects
Cancer Research ,medicine.medical_specialty ,Prognostic variable ,Proportional hazards model ,business.industry ,Hazard ratio ,Overweight ,medicine.disease ,Obesity ,Gastroenterology ,Surgery ,Oncology ,Weight loss ,Internal medicine ,medicine ,medicine.symptom ,business ,Body mass index ,Cohort study - Abstract
BACKGROUND Although obesity increases risk and negatively affects survival for many malignancies, the prognostic implications in squamous cell carcinoma (SCC) of the oral tongue, a disease often associated with prediagnosis weight loss, are unknown. METHODS Patients with T1-T2 oral tongue SCC underwent curative-intent resection in this single-institution study. All patients underwent nutritional assessment prior to surgery. Body mass index (BMI) was calculated from measured height and weight and categorized as obese (≥ 30 kg/m2), overweight (25-29.9 kg/m2), or normal (18.5-24.9 kg/m2). Clinical outcomes, including disease-specific survival, recurrence-free survival, and overall survival, were compared by BMI group using Cox regression. RESULTS From 2000 to 2009, 155 patients (90 men, 65 women) of median age 57 years (range, 18-86 years) were included. Baseline characteristics were similar by BMI group. Obesity was significantly associated with adverse disease-specific survival compared with normal weight in univariable (hazard ratio [HR] = 2.65, 95% confidence interval [CI] = 1.07-6.59; P = .04) and multivariable analyses (HR = 5.01; 95% CI = 1.69-14.81; P = .004). A consistent association was seen between obesity and worse recurrence-free survival (HR = 1.87; 95% CI = 0.90-3.88) and between obesity and worse overall survival (HR = 2.03; 95% CI = 0.88-4.65) though without reaching statistical significance (P = .09 and P = .10, respectively) in multivariable analyses. CONCLUSIONS In this retrospective study, obesity was an adverse independent prognostic variable. This association may not have been previously appreciated due to confounding by multiple factors including prediagnosis weight loss. Cancer 2014;120:983–991. © 2013 American Cancer Society.
- Published
- 2014
182. Phase I study of induction chemotherapy with afatinib, ribavirin, and weekly carboplatin and paclitaxel for stage IVA/IVB human papillomavirus-associated oropharyngeal squamous cell cancer
- Author
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David G. Pfister, Nora Katabi, Lara Dunn, Alan A. Ho, Eric J. Sherman, Matthew G. Fury, and Sofia Haque
- Subjects
0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,Paclitaxel ,Afatinib ,Antiviral Agents ,Article ,Carboplatin ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,ErbB ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Ribavirin ,Medicine ,Humans ,Survival rate ,Papillomaviridae ,Aged ,Neoplasm Staging ,Dose-Response Relationship, Drug ,business.industry ,Papillomavirus Infections ,Induction chemotherapy ,Induction Chemotherapy ,Middle Aged ,Progression-Free Survival ,Regimen ,Oropharyngeal Neoplasms ,030104 developmental biology ,Otorhinolaryngology ,chemistry ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,business ,medicine.drug - Abstract
Background The human papillomavirus (HPV) E6 oncoprotein enhances the oncogenic potential of ErbB proteins in HPV-related malignancies. This phase I study evaluates the addition of afatinib, an ErbB family inhibitor, and ribavirin to paclitaxel and carboplatin induction chemotherapy in HPV-associated, locally advanced oropharyngeal squamous cell carcinoma (SCC). Methods This dose escalation study included 2 doses of oral afatinib: 30 and 40 mg daily. Ribavirin dosing was weight based. Paclitaxel (80 mg/m2) and carboplatin (area under the curve [AUC] 1.5) were administered on days 1 and 8 of each 21-day cycle. After 3 cycles, patients were removed from protocol to receive definitive treatment. Results Among 10 patients, there were no dose-limiting toxicities. Six patients (67%) had unconfirmed objective partial responses. The 2-year progression-free survival rate was 75%. Conclusion Afatinib, ribavirin, paclitaxel, and carboplatin induction chemotherapy is safe and well tolerated. The phase II recommended dose of afatinib is 40 mg oral daily in this combination regimen.
- Published
- 2016
183. HIV-Associated Urogenital Malignancies
- Author
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Marcus Hentrich and David G. Pfister
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Antineoplastic Agents ,HIV Infections ,Medical Oncology ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Pharmacotherapy ,Acquired immunodeficiency syndrome (AIDS) ,Internal medicine ,Epidemiology of cancer ,medicine ,Humans ,030212 general & internal medicine ,Chemotherapy ,Bladder cancer ,Evidence-Based Medicine ,Genitourinary system ,business.industry ,virus diseases ,Cancer ,Hematology ,medicine.disease ,Treatment Outcome ,Anti-Retroviral Agents ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Drug Therapy, Combination ,business ,Urogenital Neoplasms - Abstract
Non-AIDS-defining malignancies (NADM) are a leading cause of morbidity and mortality for HIV-infected subjects. The risk of testicular germ cell cancer (GCC) and renal cell cancer is slightly increased in the setting of HIV, whereas there is a slightly decreased risk of prostate cancer and bladder cancer. As in industrialized countries the majority of people living with HIV are men, and people aged 55 and older now account for more than a quarter of persons living with HIV, both testis and prostate cancer are assumed to occur with increased frequency in HIV-infected subjects. Overall, treatments should be the same as in HIV-negative patients with urogenital malignancies. Since the introduction of combination antiretroviral therapy (cART) the outcome appears to have improved due to a decrease in HIV-related deaths. HIV-infected men who are treated with standard therapies for GCC now have a similar cancer-free survival compared with their HIV-negative counterparts. Screening and treatment for prostate cancer should follow recommendations established for HIV-negative men. During radio- or chemotherapy patients should receive concurrent cART but the drug-drug interaction potential must be taken into account.
- Published
- 2016
184. Challenges and Opportunities for Developing New Therapeutics for Salivary Gland Cancers
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David G. Pfister and Alan L. Ho
- Subjects
0301 basic medicine ,Clinical Trials as Topic ,Salivary gland ,Oncology (nursing) ,business.industry ,Health Policy ,Disease Management ,Salivary Gland Neoplasms ,Bioinformatics ,Combined Modality Therapy ,03 medical and health sciences ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,medicine ,Humans ,business - Published
- 2018
185. A Pilot Study of Stereotactic Body Radiotherapy (SBRT) Combined with a PD-L1 Antibody Durvalumab (D) and a CTLA-4 antibody Tremelimumab (T) To Treat Metastatic Anaplastic Thyroid Cancer (ATC)
- Author
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Wanqing Iris Zhi, David G. Pfister, C.J. Tsai, V. Wu, A.Y. Ho, T. Brinkman, Eric J. Sherman, Nancy Y. Lee, James Vincent Fetten, and Nadeem Riaz
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Radiation ,Durvalumab ,biology ,business.industry ,medicine.disease ,CTLA-4 ,Internal medicine ,PD-L1 ,medicine ,biology.protein ,Radiology, Nuclear Medicine and imaging ,Antibody ,Anaplastic thyroid cancer ,business ,Stereotactic body radiotherapy ,Tremelimumab ,medicine.drug - Published
- 2019
186. Last-line Treatment with the Quad Shot Regimen for Previously Irradiated Head and Neck Cancers
- Author
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Jay O. Boyle, D. Fan, Luc T. Morris, Nancy Y. Lee, Loren S. Michel, Eric J. Sherman, Ming Fan, J.J. Kang, James Vincent Fetten, B. Singh, Boris Mueller, R.J. Wong, C.J. Tsai, Jennifer R. Cracchiolo, Marc Cohen, Jatin P. Shah, Yao Yu, A. Shaha, Nadeem Riaz, M.B. Bernstein, Hao Wang, Anna Lee, Lara Dunn, Sean McBride, A.Y. Ho, David G. Pfister, Ian Ganly, Snehal G. Patel, Benjamin R. Roman, Li-Tzong Chen, and Daphna Y. Gelblum
- Subjects
Cancer Research ,Regimen ,Radiation ,Oncology ,business.industry ,Shot (pellet) ,Medicine ,Radiology, Nuclear Medicine and imaging ,Line (text file) ,business ,Head and neck ,Nuclear medicine - Published
- 2019
187. Erratum zu: Therapiesituation beim metastasierten kastrationsnaiven Prostatakarzinom (mCNPC) und die Auswirkungen im klinischen Alltag
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G. von Amsberg, Martin Bögemann, Martin Schostak, P. J. Goebell, Peter Hammerer, Christian Wülfing, David G. Pfister, Thomas Steuber, Stefan Machtens, and Christian Schwentner
- Subjects
Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,0302 clinical medicine ,Geriatric care ,business.industry ,030220 oncology & carcinogenesis ,Urology ,medicine ,030212 general & internal medicine ,business - Abstract
Die Behandlung des metastasierten Prostatakarzinoms (mPC) erlebt derzeit einen Paradigmenwechsel. Verschiedene randomisierte Phase-III-Studien konnten zeigen, dass die Chemotherapie mit Taxanen das Uberleben der Patienten mit mPC signifikant verlangert. Das gilt sowohl fur die metastasierte Erkrankung in der Kastrationsresistenz (metastasiertes kastrationsresistentes Prostatakarzinom [mCRPC]), als auch im hormonnaiven Stadium der Erkrankung (metastasiertes kastrationsnaives Prostatakarzinom [mCNPC]). Beim mCNPC verlangerte Docetaxel in Kombination mit der Androgendeprivationstherapie (ADT) die mediane Gesamtuberlebenszeit der Patienten gegenuber der alleinigen ADT um 15 Monate. Vergleichbare Ergebnisse erreichte die endokrine Kombinationstherapie mit ADT/Abirateron. Vor dem Hintergrund der aktuellen Datenlage erscheint es sinnvoll, den Stellenwert der fruhen Kombinationstherapie mit ADT/Docetaxel bzw. ADT/Abirateron sowie deren Auswirkungen auf die Folgetherapien beim mCRPC zu diskutieren und Hinweise fur den klinischen Alltag zu formulieren.
- Published
- 2019
188. Biomarker predictors of outcome from a randomized trial of nivolumab +/- stereotactic body radiotherapy (SBRT) in metastatic (M1) head and neck squamous cell carcinoma (HNSCC)
- Author
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Daniel C. McFarland, Wanqing Iris Zhi, C. Jillian Tsai, Nadeem Riaz, Jahan Aghalar, Sean McBride, David G. Pfister, Lara Dunn, Loren S. Michel, Alan Loh Ho, Eric J. Sherman, Nancy Y. Lee, and Juliana Eng
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.drug_class ,Monoclonal antibody ,medicine.disease ,Head and neck squamous-cell carcinoma ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,Biomarker (medicine) ,Nivolumab ,business ,Stereotactic body radiotherapy ,030215 immunology - Abstract
6063 Background: A minority of patients with M1 HNSCC respond to the anti-programmed death (PD-1) monoclonal antibody, Nivolumab (Nivo). We sought to determine biomarker predictors of outcome to Nivo in M1 HNSCC. Methods: Patients with M1 HNSCC were randomized (n = 60) with stratification by virus status (EBV/HPV+ vs not) to either Nivo alone or Nivo+SBRT to a single lesion. The primary end-point was objective response rate (ORR) in non-irradiated lesions with overall survival (OS) as a secondary end-point. PD-L1 staining in ≥ 1% of tumor cells was regarded as positive. Tumor mutation burden (TMB) was determined using a next generation sequencing assay (MSK IMPACT). Predictive model selection was done to minimize the Akaike Information Criterion (AIC). Results: There was no difference in ORR comparing the two treatment arms (p = 0.86). On univariate analysis, virus status trended towards predicting both ORR (Positive 41.9% vs Negative 20.7%, (p = 0.14)) and OS (1-yr OS for Positive, 65.9% vs 1-yr OS for Negative 40.6%, p = 0.08). In the sub-group of patients for whom PDL1 staining was available (n = 56), there was a trend towards association with ORR: PDL1+ 50% vs PDL1- 23.5% (p = 0.08). PDL1+ patients demonstrated significantly longer OS (1-yr OS 63% vs 47%, p = 0.02). There was no association between virus status and PDL1 staining. IMPACT data was available in 46 patients. TMB was significantly higher in virus negative (mean 8.1 mut/mB) vs. virus positive (mean 4.6 mut/mB) (p = 0.01); TMB was similar comparing PDL1+ to PDL1- (p = 0.47). TMB was higher in responders than non-responders (p = 0.02); TMB was significantly higher in virus positive responders (p = 0.01) and trended towards being higher in virus negative responders (p = 0.10). A model to predict ORR that included PDL1, virus status, and TMB minimized AIC with a C-index of 0.72. A model to predict OS that included PDL1 and virus status minimized AIC with a C-index of 0.62. Conclusions: A multi-variate model including viral status, PDL1 status, and TMB predicts well response to Nivolumab in M1 HNSCC. A model containing PDL1 and virus had moderate predictive value for OS. Clinical trial information: NCT02684253.
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- 2019
189. Analysis of three models to predict pathohistology in patients undergoing postchemotherapy RPLND for (pcRPLND) advanced nonseminomatous germ cell tumors (NSGCT)
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Alessandro Nini, Martin Hellmich, Axel Heidenreich, Peter Albers, David G. Pfister, Andreas Hiester, Tim Nestler, and Pia Paffenholz
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Oncology ,Cancer Research ,medicine.medical_specialty ,Radiomics ,business.industry ,Internal medicine ,medicine ,In patient ,Germ cell tumors ,medicine.disease ,business - Abstract
e16053 Background: We aim to validate the two best performing prediction models (Vergouwe and Leao) for final pathohistology in NSGCT patients undergoing pcRPLND and we introduce a new radiomics approach. Methods: A cohort of 496 patients treated between 2008 and 2018 was used to validate the 2 prediction modelsusing published formulas and thresholds.For group comparisons, we used t-test or chi-square test. ROC were plotted (sensitivity against 1-specificity) and AUC was calculated. We determined the optimal cut point and used bootstrapping (1,000 replications) to estimate its variability. A p-value of < 0.05 was considered statistically significant. For radiomics, lymph nodes identified on CT images, were semiautomatically segmented with 93 radiographic features (pyRadiomics package). A linear support vector machine algorithm was applied to analyze reproducible radiomics features. A continuous reduction of features analyzed was performed using Random Forest algorithms and ROC analysis. Results: The Vergouwe model had a significantly better AUC compared to Leao model (0.749 [CI 0.706-0.792] vs. 0.689 [0.642-0.736], p = 0.004) to predict benign histology. At a threshold of > 70% for the probability of benign disease, the Leao model would have avoided RLND in 8.6% with benign disease with an error rate of 5.6% for viable tumor. The Vergouwe model would avoid pcRPLND in 23.4% with benign disease with an error rate of 12.7% for viable tumor/teratoma. Of the 93 radiomic features analyzed, 51 features were reproducible. Applying the trained algorithm resulted in a AUC of 82% with a diagnostic sensitivity of 81% and a specificity of 83%. Conclusions: The discriminatory accuracy of both models is not sufficient to safely select patients for surveillance strategy instead of pcRPLND. The radiomics model is promising but needs prospective validation. Further studies including new biomarkers are needed to optimize the accuracy of potential prediction models.
- Published
- 2019
190. Tabelecleucel in combination with pembrolizumab (Pembro) in platinum-pretreated, recurrent/metastatic Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (EBV+NPC)
- Author
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Yang Zhang, Lillian L. Siu, Joshua Bauml, David G. Pfister, Missak Haigentz, Douglas Adkins, Jennifer Hsing Choe, Cesar A. Perez, Wen Shi, Willis H. Navarro, Guilherme Rabinowits, and A. Dimitrios Colevas
- Subjects
Cancer Research ,Poor prognosis ,business.industry ,Pembrolizumab ,Disease ,medicine.disease_cause ,medicine.disease ,Epstein–Barr virus ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,EBV Positive ,Cancer research ,Overall survival ,Medicine ,business ,030215 immunology - Abstract
TPS6092 Background: Approximately 25% of patients (pts) with NPC develop RM disease, which has a poor prognosis (median overall survival [mOS]: 12–16 mo), despite standard treatments with radiation and/or chemotherapy. NPC is an EBV-associated cancer in which programmed cell death ligand 1 (PD-L1) expression is upregulated upon EBV activation. Pembro showed antitumor activity in a phase 1b study of pts with RM-NPC (objective response rate [ORR]: 26%; mOS: 16.5 mo) (Hsu, J Clin Oncol 2017;35:4050-56). Targeting RM EBV+ NPC with tab-cel immunotherapy (off-the-shelf, allogeneic EBV-specific T cells) in pts has also shown promise, with 2-yr OS rates of 84% (Prockop, ASCO 2016;34:3012). The favorable safety profile of tab-cel offers the opportunity for combination immunotherapy with pembro for increased efficacy. Methods: This multicenter, open-label, single-arm phase 1b/2 study evaluates safety and efficacy of tab-cel in combination with pembro. Study participants are ≥12 yrs of age with incurable, locally recurrent or metastatic EBV+ NPC previously treated with platinum-containing therapy. Pts are checkpoint-inhibitor naïve (phase 1b/2) or refractory to anti-PD-1 or anti-PD-L1 therapy (phase 1b). Tab-cel is selected from a bank based on matching ≥2 HLA alleles, including ≥1 restricting HLA allele, between pts and donors. Tab-cel will be administered intravenously (IV) on days 1, 8, and 15 of a 21-day cycle. Initial tab-cel dose is 2x106 cells/kg and the de-escalated tab-cel dose (if needed) is 1x106 cells/kg. Pembro is administered at 200 mg IV Q3W in adults and 2 mg/kg IV Q3W in pts aged 12 to 17 yrs. Primary outcomes of phase 1b are to characterize dose-limiting toxicities, identify the maximum tolerated dose (MTD) or in the absence of MTD, the recommended phase 2 dose, and assess safety. Primary outcomes for phase 2 are ORR and safety. Secondary endpoints include progression-free survival, OS, and duration of response. Enrollment is ongoing for 12-24 participants in the phase 1b portion of the study with a 6+6 design. Phase 2 is expected to enroll 36 pts. Clinical trial information: NCT03769467.
- Published
- 2019
191. Pilot study combining PD-L1 antibody durvalumab (D) with CTLA-4 antibody tremelimumab (T) and stereotactic body radiotherapy (SBRT) to treat metastatic anaplastic thyroid cancer (ATC)
- Author
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Alan Loh Ho, Nadeem Riaz, Vanessa Wu, Eric J. Sherman, Nancy Y. Lee, David G. Pfister, Wanqing Iris Zhi, James Vincent Fetten, and C. Jillian Tsai
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Oncology ,Cancer Research ,medicine.medical_specialty ,Durvalumab ,biology ,business.industry ,Thyroid ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,CTLA-4 ,030220 oncology & carcinogenesis ,Internal medicine ,PD-L1 ,biology.protein ,Medicine ,Antibody ,Anaplastic thyroid cancer ,business ,Stereotactic body radiotherapy ,Tremelimumab ,030215 immunology ,medicine.drug - Abstract
6088 Background: ATC is a rare and aggressive cancer with very limited treatment options. The thyroid is one of the most immunogenic organs in the body and PD-L1 is commonly expressed on ATC tumor cells and PD-1 in the inflammatory cells in the ATC microenvironment. However, antibodies to PD-1 as single agents have a poor record in this disease. Methods: This study evaluated the addition of T (75 mg every 4 weeks up to 4 doses) to D (1500 mg every 4 weeks). SBRT 9Gy x 3 fractions was given within the first 2 weeks of treatment to produce an “abscopal” effect. Major inclusion criteria: Metastatic ATC; ECOG PS 0-2; No prior immunotherapy; Last anti-cancer treatment > 7 days prior to starting study. Primary objective 1-year overall survival with target of ≥ 2 out of 12 patients. Results: 12 patients were accrued. Male – 50%; Median PS 1; Median Age – 71 (49-82); Prior radiation to neck (75%); Prior chemotherapy (75%). MSI-High was noted in 2/11 subjects. BRAFV600E mutation in 3/12 subjects. There were 0 confirmed responses and only 1 subject with SD for 4 cycles or longer. Median time on treatment was 11 weeks (1-28+ weeks). MSI status did not affect treatment response. MSI-High patients were on treatment before progression for 8-14 weeks. Median overall survival was 14.5 weeks with only one person alive past 1 year. Neither the presence of a BRAF or p53 mutation appeared to affect either outcome. Conclusions: T/D with SBRT was not active in metastatic ATC. Future studies looking at other novel immunotherapy combinations in ATC should be evaluated. Biopsies done on study are being analyzed. Clinical trial information: NCT03122496.
- Published
- 2019
192. A retrospective analysis of cisplatin dosing strategies when used with radiation on outcomes in head and neck squamous cell carcinoma of the oropharynx
- Author
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Nancy Y. Lee, Eric J. Sherman, Zhigang Zhang, Alan Loh Ho, Vatche Tchekmedyian, James Vincent Fetten, Yao Yu, J.J. Kang, David G. Pfister, Nadeem Riaz, Sean McBride, Stephanie Lobaugh, Linda Chen, C. Jillian Tsai, and Lara Dunn
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Cisplatin ,Oncology ,Cancer Research ,medicine.medical_specialty ,Radiosensitizer ,business.industry ,Head and neck cancer ,Gold standard (test) ,medicine.disease ,Head and neck squamous-cell carcinoma ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Retrospective analysis ,Dosing ,business ,030215 immunology ,medicine.drug - Abstract
6079 Background: Cis is the gold standard radiosensitizer for CRT to treat head and neck cancer. Prospective trials have required that cis be administered early in the week (Mon/Tues) to optimize radiosensitization without evidence to support this practice. This retrospective analysis considers the impact of cis day of week (DOW) administration and other variables on OPSCC pt outcomes. Methods: We reviewed OPSCC cases treated with primary CRT at our center. Pts treated with non-cis or induction chemotherapy were excluded. Data collected includes age, DOW (Mon/Tues vs Wed/Thurs/Fri), smoking status, total dose (TD) of cis (≤200mg/m2 vs > 200mg/m2), single dose (SiD) [100mg/m2 x1 day] vs split dose (SpD) [50mg/m2 x2 days] administration, T stage (0-2b vs 2c-3), N stage (0-2b vs 2c-3), overall survival (OS) (from start of RT), local/regional/distant failure, KPS and HPV/p16 status. Univariate Cox proportional hazards regression was used to analyze OS and multivariate Cox proportional hazard model investigated the relationships between OS and cis dosing variables while controlling for other factors. Results: 745 pts with OPSCC were treated with CRT from 7/31/2001-2/7/2014. 459 used cis based regimens and were included. Median age at start of RT was 55. 311 pts (67.8%) received SpD, 124 (27%) received SiD, 8 (1.7%) received weekly cis and 16 (3.5) received mixed cycles. 269 (58.6%) received ≤200mg/m2. 232 (50.5%) were HPV/p16 positive, 40 (8.7%) were negative and 187 (40.7%) were unknown. Median f/u was 7.9yrs (1.8m -18.9yrs). There were 92 (20%) deaths, and 75 (16.4%) recurrences (local/regional and distant) with 44 (9.6%) competing events. In univariate analysis, age, N stage, T stage, KPS and HPV/p16 status were significantly associated with OS, while DOW, TD, and SiD/SpD were not. In multivariate analysis (MVA), none of the associations between cis dosing and OS were significant (although MVA was limited by low number of events and total variables included). Conclusions: This retrospective analysis suggests that the DOW cis is given has no impact upon CRT outcomes for OPSCC pts. SpD cis represents an alternative administration approach.
- Published
- 2019
193. A phase II trial cohort of nivolumab plus ipilimumab in patients (Pts) with recurrent/metastatic adenoid cystic carcinoma (R/M ACC)
- Author
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Crystal Tran, Sofia Haque, Loren S. Michel, Eric J. Sherman, Alan Loh Ho, Julian Azar, Vatche Tchekmedyian, Lara Dunn, Anuja Kriplani, Irina Ostrovnaya, James Vincent Fetten, Luc G. T. Morris, Nora Katabi, and David G. Pfister
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Salivary gland ,business.industry ,Adenoid cystic carcinoma ,Standard treatment ,Ipilimumab ,Meth ,medicine.disease ,Blockade ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Internal medicine ,Cohort ,medicine ,Nivolumab ,business ,030215 immunology ,medicine.drug - Abstract
6084 Background: R/M ACC is a malignant neoplasm most commonly of salivary gland origin with no standard treatment. The impact of combined PD-1/CTLA-4 checkpoint blockade in R/M ACC is unknown. Methods: In a two-stage minimax phase II trial, pts with progressive R/M ACC (non-salivary primaries allowed) were enrolled and treated with nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (1 cycle = 6 weeks). Imaging, using RECIST v1.1 response assessment, was scheduled to be performed approximately every 12 weeks. The primary endpoint was overall response rate (ORR = complete response [CR]+partial response [PR]) per RECIST v1.1. To detect a difference between an unacceptable ORR of 5% and a desirable ORR of 20% (one-sided type I error of 10%, power of 90%), at least 1 in the first 18 pts required an observed response. At least 4 responses of 32 total pts were needed to meet the primary endpoint. Treatment beyond progression of disease (PD) was allowed at the discretion of the investigator. A second cohort of pts with non-ACC salivary cancer is still accruing for separate analysis. Results: From 6/12/2017-6/20/2018, 32 pts were enrolled and evaluable for the primary endpoint. There was 1 confirmed PR in the first 18 pts, therefore enrollment of the second stage continued. ORR was 6% (2/32). One additional pt had an unconfirmed PR (-31% regression before CNS PD). For best overall response, there were 2 PRs, 15 SD, and 11 PD. Four pts never reached a first disease assessment: 3 due to death from clinical PD and 1 was removed for toxicity. Six pts discontinued the trial for toxicities (Grade 4 (G4) neutropenia/sepsis and G3 adrenal insufficiency (1), G2 hypophysitis (2), G3 arthritis > 7 days (1), G3 colitis (1), and G3 hepatitis/G4 creatinine kinase (CK) elevation (1)). The 2 confirmed PRs consisted of -73.1% and -58.4% regressions, with a duration of therapy of 18.4 and 7.8 months, respectively (treatment ongoing for both). Conclusions: The study did not meet its primary endpoint, though the responses observed were dramatic. Paired biopsy and peripheral blood samples will be analyzed to elucidate insights into mechanisms of response and resistance to dual checkpoint blockade. Clinical trial information: NCT03172624.
- Published
- 2019
194. Muskelinvasives Harnblasenkarzinom nach radikaler Zystektomie
- Author
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A. Thissen, Axel Heidenreich, and David G. Pfister
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Gynecology ,medicine.medical_specialty ,Neoplasm Invasiveness ,business.industry ,Urology ,Treatment outcome ,Medicine ,business - Abstract
Hintergrund Die Indikation zur Einleitung einer adjuvanten Chemotherapie beim Urothelkarzinom der Harnblase nach radikaler Zystektomie wird entsprechend der verschiedenen internationalen Leitlinien aufgrund der suboptimalen Evidenz zunehmend kritisch beurteilt. Die adjuvante Therapie sollte aufgrund der ungunstigen Evidenzsituation vornehmlich klinischen Studien vorbehalten werden. Unter klinischen Bedingungen konnte die adjuvante Chemotherapie bei Patienten mit ausgedehnten lymphknotenpositiven Befunden eingesetzt werden. Klinische, pathohistologische und molekulare Risikofaktoren, die mit einem gunstigen bzw. ungunstigen Ansprechen auf die adjuvante Therapie verbunden sind, werden in der Literatur nur sparlich beschrieben.
- Published
- 2013
195. Evaluation of Romidepsin for Clinical Activity and Radioactive Iodine Reuptake in Radioactive Iodine–Refractory Thyroid Carcinoma
- Author
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Ronald Ghossein, R. Michael Tuttle, Eric J. Sherman, David G. Pfister, Heiko Schöder, Ashok R. Shaha, Ashima Lyall, Donna Lisa, Matthew G. Fury, Sofia Haque, and Y. B. Su
- Subjects
Adult ,Male ,Sodium-iodide symporter ,Oncology ,medicine.medical_specialty ,Pathology ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Thyroid Gland ,chemistry.chemical_element ,Iodine ,Radiation Tolerance ,Romidepsin ,Iodine Radioisotopes ,Thyroid carcinoma ,Endocrinology ,Depsipeptides ,Internal medicine ,medicine ,Adenoma, Oxyphilic ,Humans ,Whole Body Imaging ,Thyroid Neoplasms ,Radionuclide Imaging ,Thyroid cancer ,Aged ,Antibiotics, Antineoplastic ,business.industry ,Carcinoma ,Thyroid ,Thyroid Cancer and Nodules ,Middle Aged ,medicine.disease ,Survival Analysis ,Carcinoma, Papillary ,Histone Deacetylase Inhibitors ,medicine.anatomical_structure ,chemistry ,Thyroid Cancer, Papillary ,Response Evaluation Criteria in Solid Tumors ,Female ,Thyroglobulin ,Radiopharmaceuticals ,business ,Follow-Up Studies ,medicine.drug - Abstract
Historically, systemic therapy for radioactive iodine (RAI)-refractory thyroid cancer has been understudied. Available drugs have modest efficacy. Romidepsin is a histone deacetylase inhibitor with potent antitumor effects both in vitro and in vivo. In thyroid cancer cell lines, romidepsin increases expression of both thyroglobulin and the sodium iodide symporter messenger RNAs, suggesting the possibility of improved iodine concentrating ability of RAI-resistant tumors.This was a single-institution Simon 2-stage phase II clinical study. Eligible patients had progressive, RAI-refractory, recurrent/metastatic, nonmedullary, nonanaplastic thyroid cancer. Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 measurable disease and adequate organ/marrow function were required. Romidepsin 13 mg/m² was administered intravenously on days 1, 8, and 15, in cycles of 28 days. The primary endpoint was the response rate by RECIST; change in RAI avidity was a secondary endpoint. The study closed after the first stage due to the lack of response.Twenty patients were enrolled: female, 50%; median age, 64 years; histology, 8 papillary/1 follicular/11 Hürthle. Grade 4-5 adverse events (AEs) possibly related to the drug: grade 5, 1 sudden death; grade 4, 1 pulmonary embolus. Twelve of 20 subjects had a reported adverse event. No RECIST major responses have been seen. Response per protocol: stable disease, 13; disease progression, 7. Restoration of RAI avidity was documented in two patients. Median overall survival and time on study was 33.2 (1-71+) and 1.7 (0.46-12) months, respectively.We observed preliminary signs of in vivo reversal of RAI resistance after treatment with romidepsin. However, no major responses were observed and accrual was poor after the grade 5 AE.
- Published
- 2013
196. Water concentrations of PAH, PCB and OCP by using semipermeable membrane devices and sediments
- Author
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Karl-Werner Schramm, Burak Karacik, Oya S. Okay, G. Pfister, and Bernhard Henkelmann
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Pollutant ,Geologic Sediments ,Chemistry ,Organochlorine pesticide ,Sediment ,Membranes, Artificial ,Aquatic Science ,Oceanography ,Polychlorinated Biphenyls ,Pollution ,Calculation methods ,Semipermeable membrane devices ,Environmental chemistry ,Hydrocarbons, Chlorinated ,Pesticides ,Polycyclic Aromatic Hydrocarbons ,Water Pollutants, Chemical ,Environmental Monitoring - Abstract
Water concentrations of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) were estimated from semipermeable membrane devices (SPMDs) and from sediment pollutant concentrations. SPMDs were deployed in the Istanbul Strait and Marmara Sea and retrieved after 7 and 21 days. Performance reference compounds (PRCs) were used to determine the site-specific sampling rates of the compounds. Water concentrations (C-w) of the analyzed compounds estimated by using two different calculation methods for SPMDs were found similar. C-w of total PAHs estimated from SPMDs (Cw-spmd) were found between 13 and 79 ng L-1 and between 7.0 and 68 ng L-1 for 7 and 21 days of deployments respectively. Water concentrations of PCBs using sediment data was found as between 0.001 and 11.0 ng L-1. The highest value of Cw-spmd for two deployments were 2.8 ng L-1 for OCPs. C-w estimated from sediment concentrations were generally higher than those estimated from SPMDs. (C) 2013 Elsevier Ltd. All rights reserved.
- Published
- 2013
197. Long-term regional control in the observed neck following definitive chemoradiation for node-positive oropharyngeal squamous cell cancer
- Author
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Nisha Ohri, Heiko Schöder, Richard J. Wong, Ian Ganly, Shyam Rao, Luc G. T. Morris, Jeremy Setton, Michael J. Zelefsky, Nancy Y. Lee, David G. Pfister, Jatin P. Shah, Dennis H. Kraus, Anuj Goenka, Suzanne L. Wolden, Borys Mychalczak, Benjamin H. Lok, and Nadeem Riaz
- Subjects
Cancer Research ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Radiography ,Neck dissection ,Physical examination ,Radiation therapy ,Oropharyngeal Neoplasm ,Oncology ,Positron emission tomography ,Cohort ,medicine ,Radiology ,business ,Chemoradiotherapy - Abstract
Traditionally, patients treated with chemoradiotherapy for node-positive oropharyngeal squamous cell carcinoma (N+ OPSCC) have undergone a planned neck dissection (ND) after treatment. Recently, negative post-treatment positron-emission tomography (PET)/computed tomography (CT) imaging has been found to have a high negative predictive value for the presence of residual disease in the neck. Here, we present the first comprehensive analysis of a large, uniform cohort of N+ OPSCC patients achieving a PET/CT-based complete response (CR) after chemoradiotherapy, and undergoing observation, rather than ND. From 2002 to 2009, 302 patients with N+ OPSCC treated with 70 Gy intensity-modulated radiation therapy and concurrent chemotherapy underwent post-treatment clinical assessment including PET/CT. CR was defined as no evidence of disease on clinical examination and post-treatment PET/CT. ND was reserved for patients with
- Published
- 2013
198. Application of satellite observations for identifying regions of dominant sources of nitrogen oxides over the Indian Subcontinent
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Sachin D. Ghude, Santosh H. Kulkarni, Chinmay Jena, Gabriele G. Pfister, G. Beig, S. Fadnavis, and R. J. van der A
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Atmospheric Science ,business.industry ,Flux ,SCIAMACHY ,Troposphere ,Geophysics ,Space and Planetary Science ,Climatology ,Earth and Planetary Sciences (miscellaneous) ,Environmental science ,Coal ,Satellite ,Emission inventory ,business ,Biomass burning ,NOx - Abstract
[1] We used SCIAMACHY (10:00 LT) and OMI (13:30 LT) tropospheric NO2 columns to study diurnal and seasonal patterns in NO2 concentrations over India. Using characteristics of seasonal variability in tropospheric NO2 columns, we present a simple methodology to identify the dominant NOx source category for specific regions in India. Regions where the dominant source category is classified as biomass burning are found generally to agree with the ATSR fire count distribution. Relating OMI NO2 columns to surface NOx emission, we find that biomass burning emission account for an average flux of 1.55 × 1011 molecules cm−2 s−1 during the peak burning period. Furthermore, extrapolating this estimated flux to the total burned area for the year 2005, biomass burning is estimated to account for 72 Gg of N emissions. Additional analysis of fire events in Northeast India shows a marked increase in TES retrieved O3 concentrations, suggesting significant photochemical ozone formation during the peak biomass burning period. Regions where the dominant source type was categorized as anthropogenic are in good agreement with the distribution of major industrial regions and urban centers in India. Tropospheric NO2 columns over these anthropogenic source regions increased by 3.8% per year between 2003 and 2011, which is consistent with the growth in oil and coal consumption in India. The OMI-derived surface NO2 mixing ratios are indirectly validated with the surface in situ measurements (correlation r = 0.85, n = 88) obtained from the air quality monitoring network in Delhi during August 2010 to January 2011. Most of the OMI-derived surface NO2 values agree with surface-based measurements, supporting the direct utility of OMI observation for emission estimates. Finally, we use OMI NO2 columns to estimate NOx emissions for selected large cites and major thermal power plants in India and compare these estimates with the INTEX-B and EDGAR emission inventory. We find that, for a few locations, OMI-derived emission show fair agreement; however, for many locations, NOx emissions differ from INTEX-B and EDGAR inventories.
- Published
- 2013
199. A VLSI FSM design system.
- Author
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M. J. Meyer, Prathima Agrawal, and R. G. Pfister
- Published
- 1984
200. Sharing a diagnosis of HPV-related head and neck cancer: The emotions, the confusion, and what patients want to know
- Author
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Andrew G. Shuman, David G. Pfister, Geoffrey W. Corner, Elyse Shuk, Jennifer L. Hay, Shrujal S. Baxi, Elena B. Elkin, and Eric J. Sherman
- Subjects
Gynecology ,medicine.medical_specialty ,Pediatrics ,business.industry ,Head and neck cancer ,virus diseases ,medicine.disease ,Oropharyngeal Neoplasm ,Otorhinolaryngology ,medicine ,Patient communication ,Neoplasm staging ,Human papillomavirus ,medicine.symptom ,business ,Oropharyngeal Cancers ,Confusion ,Patient education - Abstract
BACKGROUND Oropharyngeal cancers are increasingly associated with human papillomavirus (HPV). Little is known about the experience of patients receiving this diagnosis.
- Published
- 2012
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