Purpose-To prospectively identify markers of response to therapy and outcome in an organsparing trial for advanced oropharyngeal cancer.Patients and Methods-Pretreatment biopsies were examined for expression of epidermal growth factor receptor (EGFR), p16, Bcl-xL, and p53 as well as for p53 mutation. These markers Authors' Disclosures of Potential Conflicts of Interest:Although all authors completed the disclosure declaration, the following author (s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure were assessed for association with high-risk human papillomavirus (HPV), response to therapy, and survival. Patient variables included smoking history, sex, age, primary site, tumor stage, and nodal status.Results-EGFR expression was inversely associated with response to induction chemotherapy (IC) (P = .01), chemotherapy/radiotherapy (CRT; P = .055), overall survival (OS; P = .001), and diseasespecific survival (DSS; P = .002) and was directly associated with current smoking (P = .04), female sex (P = .053), and lower HPV titer (P = .03). HPV titer was significantly associated with p16 expression (P < .0001); p16 was significantly associated with response to IC (P = .008), CRT (P = . 009), OS (P = .001), and DSS (P = .003). As combined markers, lower HPV titer and high EGFR expression were associated with worse OS (ρ EGFR = 0.008; ρ HPV = 0.03) and DSS (ρ EGFR = 0.01; ρ HPV = 0.016). In 36 of 42 biopsies, p53 was wild-type, and only one HPV-positive tumor had mutant p53. The combination of low p53 and high Bcl-xL expression was associated with poor OS (P = . 005) and DSS (P = .002).Conclusion-Low EGFR and high p16 (or higher HPV titer) expression are markers of good response to organ-sparing therapy and outcome, whereas high EGFR expression, combined low p53/ high Bcl-xL expression, female sex, and smoking are associated with a poor outcome. Smoking cessation and strategies to target EGFR and Bcl-xL are important adjuncts to the treatment of oropharyngeal cancer.
IntroductionAppropriate treatment of advanced oral/oropharyngeal squamous cell carcinoma is a difficult challenge. Less than 50% of patients survive more than 5 years 1 . Surgery affects visible structures important for eating, swallowing, speaking, and human interaction. Organ sparing treatments can save important structures and can lead to improved outcome in patients who respond to such therapy. Induction chemotherapy followed by concurrent chemoradiation has shown efficacy both for organ sparing and survival in laryngeal cancer with 3 yr survival rates of 86% 1, 2 . For oral cancer and oropharyngeal cancer this treatment is less effective with 3 yr survival rates of 47% and 67% respectively 3 .Corresponding Author: Dr. Carey, 1301 East Ann St., Ann Arbor, MI 48109-0506. Conflict of Interest: Dr. Kurnit has interest in a company (SensiGen LLC) that is developing the HPV detection method.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Thus, it is important to understand the factors that determine which tumors respond well and which tumors fail to respond so that new targeted therapeutic approaches can be developed to overcome resistance and improve outcome. We have previously demonstrated that p53 status and BclxL are important determinants of response to cisplatin in HNSCC in vitro 4 . Furthermore, high and low Bcl-xL expression in pretreatment tumor biopsies containing wild type p53 identifies those oropharynx cancer patients with the worst and best survival respectively. In this report, we extend our analysis of predictive markers in oropharynx cancer. NIH Public AccessCarcinoma of the head and neck is the 6 th most common malignancy worldwide. Smoking remains the number one risk factor for head and neck cancer and may also influence response to therapy. Despite declining smoking rates in the United States, incidence of oropharyngeal and oral cavity tumors is increasing in young adults. HPV-16 infection is associated with a significant proportion of squamous cell carcinomas of the oropharynx particularly for those lacking other risk factors 5-8 . Epidermal growth factor receptor is overexpressed in up to 90% of HNSCC. High expression of EGFR has been linked to local recurrence after radiation in HNSCC 9 . The purpose of this study was to determine if HPV, EGFR, and smoking are determinants of outcome in patients with advanced oropharyngeal cancer treated on an organ sparing protocol. MethodsPretreatment biopsies were used to prospectively assess predictive biomarkers. A quantitative method that combines PCR and mass spectroscopy to identify HPV type and copy number 1...
Introduction: Despite the prevalence of intimate partner violence (IPV), there is a paucity of research exploring the role that physicians might play in intervening with IPV perpetrators.Methods: A qualitative study explored interactions between family medicine physicians and male perpetrators of IPV. Fifteen physicians were purposefully sampled from 1 hospital system. The physicians were individually interviewed using a semistructured interview guide, and interview transcripts were analyzed using techniques from grounded theory.Results: Three main themes relating to physicians' experiences were identified: (1) how physicians learned of or identified IPV perpetration by men (usually disclosure by the victim, but perpetrators also disclosed it); (2) how physicians assessed for comorbidities or responded to IPV perpetration by men; and (
Background:In studies involving nonpharmacological complementary and alternative medicine interventions, participant blinding is very difficult. Participant expectations may affect perceived benefit of therapy. In studies of yoga as treatment for chronic low back pain, little is known about the relationship between patient expectations and preferences on outcomes. This study was designed to identify baseline predictors of preference and to determine if expectations and preferences for different doses of yoga affect back-related function and low back pain intensity.Methods:This was a secondary data analysis of a 12-week randomized controlled trial comparing once-weekly vs twice-weekly yoga for treatment of chronic low back pain in 93 adults from a predominantly low-income minority population. At baseline, participants were asked about back function, back pain, treatment expectations, and treatment preferences. We created a variable “concordance” to describe the matching of participant preference to randomized treatment. Our outcome variables were change in back function and pain intensity after 12 weeks of yoga instruction. We performed logistic regression to identify predictors of preference for once- or twice-weekly yoga instruction. We created linear regression models to identify independent associations between expectations, preference, concordance, and outcomes.Results:Worse back function at baseline was associated with 20% higher odds of preferring twice-weekly yoga (OR 1.2, CI 1.1, 1.3). Individuals with higher expectation scores for twice-weekly yoga had 90% higher odds of preferring twice-weekly vs once-weekly yoga (OR 1.9, CI 1.3, 2.7). Individuals with higher expectation scores for once-weekly yoga had 40% less odds of preferring twice-weekly yoga (OR 0.6, CI 0.5, 0.9). After controlling for baseline characteristics, we found no statistically significant relationship between treatment outcomes, preference, expectation scores, or concordance.Conclusion:In a population of predominantly low-income minority participants with chronic low back pain, worse back function was associated with preference for more frequent yoga classes. Those who preferred more yoga classes had higher expectations for those classes. Twelve-week change in back pain intensity and back function were not affected by dosing preference, expectation score, or concordance. More research is needed to better measure and quantify preference, expectations, and their relationship to outcomes in yoga research.
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