1,721,100 research outputs found
Targeted Agents: Management of Dermatologic Toxicities
No full textEpidermal growth factor receptor (EGFR) inhibitors are widely used in the treatment of many cancers, and the cutaneous toxicity profile associated with these agents has become prominent. In fact, dermatologic side effects have also been reported with other targeted agents, including both BRAF and mTOR inhibitors. During her presentation at the NCCN 19th Annual Conference, Dr. Barbara Burtness reviewed the array of skin complications caused by many targeted therapies, focusing on the more common culprits, the role of prophylactic versus reactive management strategies, the need to be attentive to potential infections, the importance of mastering local measures to improve quality of life and cosmetic issues, the therapeutic mainstays (oral and topical antibiotics and topical steroids), and the preference of improving these cutaneous complications over suspending anticancer treatment.</jats:p
Abstract IA17: Treatment de-intensification strategies for head and neck cancer
No full textAbstract
Oropharynx cancer (OPC) which is human papillomavirus (HPV)-related is more treatment-responsive and has a higher cure rate than tobacco-associated OPC. HPV-related cancers arise in patients who have a younger median age, lower comorbidity index, and lesser tobacco history than patients whose cancers are not HPV-related. Failure within the radiation field is relatively less common, while distant metastases account for a higher proportion of recurrences among patients with HPV-related cancers. Thus, treatment paradigms developed in an era when tobacco-associated head and neck cancer predominated focus on intense local therapy for a relatively treatment-resistant cancer among patients with many competing mortality risks, and may represent inappropriate treatment for patients with HPV-related cancers. Existing approaches based on high-dose cisplatin and 70 Gy of radiation in a primary treatment volume, as well as significant radiation to elective nodal areas, are not well supported by data from patients with HPV-related OPC and are of concern for a number of reasons. These include the possibility of increased noncancer mortality from concurrent cisplatin and full-dose radiation, as suggested by the long-term results of INT91-11; high rates of chronic radiation sequelae of swallowing impairment, chronic pain, lymphedema, hypothyroidism, osteonecrosis, dental loss, xerostomia, PTSD-like effects, and employment disability; inadequate systemic therapy in patients at increased risk for distant metastases; and cost.
These considerations have led to trials exploring a number of approaches to treatment deintensification. Trial designs have been challenging as normative data from patients with HPV-related OPC are scarce and event rates low. Numerous strategies have been envisioned to minimize toxicity, cost, or late sequelae, or do a better job of fitting treatment modality to failure pattern. When novel treatment schemes were initially proposed, there was concern that these would be a barrier to accrual, or that treating investigators would deviate from protocol because of skepticism about the novel approaches. In this context, initial trials either proposed very incremental changes, were conducted as single-arm studies, incorporated surgical staging after radiation, or utilized randomized phase II designs. The primary strategy to reduce late treatment sequelae of swallowing dysfunction has been reduction of radiation dose from 70Gy to 54-60Gy. Langdijk has demonstrated that a dose of &gt;56 Gy to pharyngeal constrictors predicts long-term swallowing dysfunction. As well, shortened radiation courses reduce acute toxicity because the highest grades of mucositis, dermatitis, and pain are documented at the highest cumulative radiation doses. Omission of chemotherapy, or substitution of cetuximab for cisplatin, is envisioned to reduce acute toxicity and chronic effects on hearing and renal function. Upfront transoral resection has been proposed to permit better staging, resulting in fewer patients being exposed to cisplatin, as well as potentially to permit reduced radiation dose.
The first trial specifically designed to enroll only HPV-related OPC and to test treatments which could minimize late sequelae was E1308. Patients with resectable p16 or HPV16 ISH + OPC were treated with induction cisplatin, paclitaxel, and cetuximab. This novel regimen was employed to build on prior ECOG experience with carboplatin, paclitaxel or carboplatin, paclitaxel and cetuximab induction therapy, both of which had demonstrated high response rates in HPV-related oropharynx cancer, including in the latter case biopsy-proven complete responses. Cisplatin was substituted for carboplatin to support accrual, given concerns from some investigators that carboplatin would be inadequate if followed by reduced radiation dose. Patients with clinical CR were treated with 54 Gy radiation and concurrent cetuximab. 2-year PFS and OS rates were 80% and 94% for patients with primary-site cCR treated with 54 Gy of radiation (n = 51); 96% and 96%, respectively, for patients with &lt; T4, &lt; N2c, and ≤ 10 pack-year smoking history who were treated with ≤ 54 Gy of radiation (n = 27). At 12 months, significantly fewer patients treated with ≤ 54 Gy had difficulty swallowing solids (40% v 89%; P = .011) or impaired nutrition (10% v 44%; P = .025).
Identical concerns about the impact of high-dose cisplatin and full-dose radiation on late function and noncancer mortality have also led to questions about the appropriateness of current standard of care in the postoperative setting. E3311 is a trial of transoral resection for T1-2 p16+ oropharynx cancer. Based on pathology, patients with N0 and N1 disease, without extranodal extension, are observed. Those with high node number, positive margins, or ENE receive postoperative radiation with cisplatin. Patients intermediate between those groups are randomized between 50 and 60 Gy. The study is anticipated to close to accrual in late 2017. A recent analysis of the National Cancer Database demonstrates that—despite single-institution retrospective data which had appeared to show that this was not the case— ENE is associated with inferior OS in patients with HPV-positive OPSCC, although both groups have 3-year OS of over 85%. Thus, elimination of cisplatin may be beneficial here as well, and ECOG has proposed a non-inferiority trial of postoperative radiation with cetuximab vs. the standard of radiation and cisplatin.
Current trials utilize T stage and smoking history to identify favorable-risk patients in whom treatment deintensification strategies will be important. Future studies may be able to utilize biomolecular characteristics such as TRAF3 mutation, mutational load, or inflamed phenotype to more precisely define favorable populations, as well as to aid in selection of cytotoxic vs. immunotherapy, or project rates of distant disease.
Citation Format: Barbara Burtness. Treatment de-intensification strategies for head and neck cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA17.</jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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