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      Development of comprehensive nomograms for evaluating overall and cancer-specific survival of laryngeal squamous cell carcinoma patients treated with neck dissection

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          Abstract

          Background

          Neck dissection for laryngeal squamous cell carcinoma (LSCC) patients could provide complementary prognostic information for AJCC N staging, like lymph node ratio (LNR). The aim of this study was to develop effective nomograms to better predict survival for LSCC patients treated with neck dissection.

          Results

          2752 patients were identified and randomly divided into training ( n = 2477) and validation ( n = 275) cohorts. The 3- and 5-year probabilities of cancer-specific mortality (CSM) were 30.1% and 37.2% while 3- and 5-year death resulting from other causes (DROC) rate were 6.2% and 11.3%, respectively. 13 significant prognostic factors including LNR for overall (OS) and 12 (except race) for CSS were enrolled in the nomograms. Concordance index as a commonly used indicator of predictive performance, showed the nomograms had superiority over the no-LNR models and TNM classification (Training-cohort: OS: 0.713 vs 0.703 vs 0.667, CSS: 0.725 vs 0.713 vs 0.688; Validation-cohort: OS: 0.704 vs 0.690 vs 0.658, cancer-specific survival (CSS): 0.709 vs 0.693 vs 0.672). All calibration plots revealed good agreement between nomogram prediction and actual survival.

          Materials and Methods

          We identified LSCC patients undergoing neck dissection diagnosed between 1988 and 2008 from Surveillance, Epidemiology, and End Results (SEER) database. Optimal cutoff points were determined by X-tile program. Cumulative incidence function was used to analyze cancer-specific mortality (CSM) and death resulting from other causes (DROC). Significant predictive factors were used to establish nomograms estimating overall (OS) and cancer-specific survival (CSS). The nomograms were bootstrapped validated both internally and externally.

          Conclusions

          Comprehensive nomograms were constructed to predict OS and CSS for LSCC patients treated with neck dissection more accurately.

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          Most cited references38

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          Marital status and survival in patients with cancer.

          To examine the impact of marital status on stage at diagnosis, use of definitive therapy, and cancer-specific mortality among each of the 10 leading causes of cancer-related death in the United States.
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            Nomograms for predicting local recurrence, distant metastases, and overall survival for patients with locally advanced rectal cancer on the basis of European randomized clinical trials.

            The purpose of this study was to develop accurate models and nomograms to predict local recurrence, distant metastases, and survival for patients with locally advanced rectal cancer treated with long-course chemoradiotherapy (CRT) followed by surgery and to allow for a selection of patients who may benefit most from postoperative adjuvant chemotherapy and close follow-up. All data (N = 2,795) from five major European clinical trials for rectal cancer were pooled and used to perform an extensive survival analysis and to develop multivariate nomograms based on Cox regression. Data from one trial was used as an external validation set. The variables used in the analysis were sex, age, clinical tumor stage stage, tumor location, radiotherapy dose, concurrent and adjuvant chemotherapy, surgery procedure, and pTNM stage. Model performance was evaluated by the concordance index (c-index). Risk group stratification was proposed for the nomograms. The nomograms are able to predict events with a c-index for external validation of local recurrence (LR; 0.68), distant metastases (DM; 0.73), and overall survival (OS; 0.70). Pathologic staging is essential for accurate prediction of long-term outcome. Both preoperative CRT and adjuvant chemotherapy have an added value when predicting LR, DM, and OS rates. The stratification in risk groups allows significant distinction between Kaplan-Meier curves for outcome. The easy-to-use nomograms can predict LR, DM, and OS over a 5-year period after surgery. They may be used as decision support tools in future trials by using the three defined risk groups to select patients for postoperative chemotherapy and close follow-up (http://www.predictcancer.org).
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              Current Cigarette Smoking Among Adults — United States, 2005–2013

              Tobacco use is the leading cause of preventable disease and death in the United States, resulting in more than 480,000 premature deaths and $289 billion in direct health care expenditures and productivity losses each year (1). Despite progress over the past several decades, millions of adults still smoke cigarettes, the most commonly used tobacco product in the United States (2). To assess progress made toward the Healthy People 2020 target of reducing the proportion of U.S. adults who smoke cigarettes to ≤12.0% (objective TU-1.1),* CDC used data from the 2013 National Health Interview Survey (NHIS) to provide updated national estimates of cigarette smoking prevalence among adults aged ≥18 years. Additionally, for the first time, estimates of cigarette smoking prevalence were assessed among lesbian, gay, or bisexual persons (LGB) using NHIS data. The proportion of U.S. adults who smoke cigarettes declined from 20.9% in 2005 to 17.8% in 2013, and the proportion of daily smokers declined from 16.9% to 13.7%. Among daily cigarette smokers, the proportion who smoked 20–29 cigarettes per day (CPD) declined from 34.9% to 29.3%, and the proportion who smoked ≥30 CPD declined from 12.7% to 7.1%. However, cigarette smoking remains particularly high among certain groups, including adults who are male, younger, multiracial or American Indian/Alaska Native, have less education, live below the federal poverty level, live in the South or Midwest, have a disability/limitation, or who are LGB. Proven population-based interventions, including tobacco price increases, comprehensive smoke-free policies in worksites and public places, high-impact anti-tobacco mass media campaigns, and easy access to smoking cessation assistance, are critical to reducing cigarette smoking and smoking-related disease and death among U.S. adults, particularly among subpopulations with the greatest burden (3). NHIS is an annual, nationally representative, in-person survey of the noninstitutionalized U.S. civilian population. The NHIS core questionnaire is administered to a randomly selected adult in each sampled household. The 2013 NHIS included 34,557 respondents aged ≥18 years; the response rate was 61.2%. Current cigarette smokers were respondents who reported smoking ≥100 cigarettes during their lifetime and, at the time of interview, reported smoking every day or some days. The mean number of cigarettes smoked per day was calculated among daily smokers. Data were adjusted for nonresponse and weighted to provide nationally representative estimates. Current cigarette smoking was assessed overall and by sex, age, race/ethnicity, education, poverty status,† U.S. Census region,§ and disability/limitation status.¶ Current smoking was also assessed by sexual orientation**; starting in 2013, sexual orientation questions were added to NHIS for the first time. Differences between groups were assessed using the chi-square test. Logistic regression was used to analyze trends during 2005–2013, and the Wald test was used to determine statistical significance (p<0.05). Current cigarette smoking among U.S. adults declined from 20.9% (an estimated 45.1 million persons) in 2005 to 17.8% (42.1 million) in 2013 (p<0.05 for trend) (Table). In 2013, current cigarette smoking prevalence was higher among males (20.5%) than females (15.3%). Prevalence was highest among adults aged 25–44 years (20.1%) and lowest among those aged ≥65 years (8.8%). By race/ethnicity, prevalence was highest among adults reporting multiple races (26.8%) and among American Indians/Alaska Natives (26.1%), and lowest among non-Hispanic Asians (9.6%). By education (among adults aged ≥25 years), prevalence was highest among persons with a General Education Development (GED) certificate (41.4%) and lowest among those with a graduate degree (5.6%). Among groups by family income, prevalence was higher among persons living below the poverty level (29.2%) than those at or above this level (16.2%). By region, prevalence was highest in the Midwest (20.5%) and lowest in the West (13.6%). Adults who reported having a disability/limitation had a higher prevalence (23.0%) than those reporting no disability/limitation (17.0%). Cigarette smoking prevalence was higher among LGB adults (26.6%) than straight adults (17.6%). Among straight adults, males (20.3%) had a higher smoking prevalence than females (15.0%); however, among LGB adults, prevalence did not differ by sex (Figure 1). Among all U.S. adults, the proportion of daily smokers declined from 16.9% to 13.7% during 2005–2013. Among current cigarette smokers, every day smoking decreased from 80.8% (36.5 million persons) in 2005 to 76.9% (32.4 million) in 2013 (p<0.05 for trend), and some day smoking increased from 19.2% (8.7 million) in 2005 to 23.1% (9.7 million) in 2013 (p<0.05 for trend). Among daily smokers, mean CPD declined from 16.7 in 2005 to 14.2 in 2013 (p<0.05 for trend). During 2005–2013, increases occurred in the proportion of daily smokers who smoked 1–9 CPD (16.4% to 23.3%) or 10–19 CPD (36.0% to 40.3%), whereas declines occurred among those who smoked 20–29 CPD (34.9% to 29.3%) or ≥30 CPD (12.7% to 7.1%) (p<0.05 for trend) (Figure 2). Discussion During 2005–2013, declines occurred in the prevalence of cigarette smoking among U.S. adults and the proportion of daily smokers who smoked the heaviest (i.e., ≥30 CPD). Cigarette smoking prevalence was higher among certain subpopulations, including adults who are male, younger, multiracial or American Indian/Alaska Native, have less education, live below the federal poverty level, live in the South or Midwest, have a disability/limitation, or are LGB. What is already known on this topic? Tobacco use is the leading cause of preventable disease and death in the United States, resulting in more than 480,000 premature deaths and $289 billion in direct health care expenditures and productivity losses each year. Despite progress over the past several decades, millions of adults still smoke cigarettes, the most commonly used tobacco product in the United States. What is added by this report? Cigarette smoking among U.S. adults declined from 20.9% in 2005 (an estimated 45.1 million persons) to 17.8% in 2013 (42.1 million). Among smokers who smoke daily, the average number of cigarettes smoked per day declined from 16.7 in 2005 to 14.2 in 2013, and the proportions of daily smokers who smoked 20–29 or ≥30 cigarettes per day also declined. In 2013, cigarette smoking prevalence was higher among lesbian, gay, or bisexual adults (26.6%) than straight adults (17.6%). What are the implications for public health practice? These findings underscore the importance of continued implementation of effective public health interventions that can reduce smoking-related disparities and accelerate progress toward meeting the Healthy People 2020 target to reduce the proportion of U.S. adults who smoke cigarettes to ≤12.0%. These evidence-based interventions include increasing the price of tobacco products, implementing and enforcing comprehensive smoke-free laws, warning about the dangers of tobacco use with high-impact antismoking media campaigns, and increasing access to help with quitting. Observed disparities in smoking prevalence are consistent with previous studies (2). Differences by race/ethnicity might be partly explained by sociocultural influences and practices related to the acceptability of tobacco use (4). Differences by education might be partly attributable to variations in exposure and understanding of information about the health hazards of smoking (5). Responses to newly added questions on sexual orientation in the 2013 NHIS questionnaire†† revealed that LGB adults have higher cigarette smoking prevalence than their straight counterparts, which might be attributed to multiple factors, including, for example, greater stress due to social stigma and discrimination, and targeted marketing toward this population by the tobacco industry (6). These disparities underscore the importance of enhancing the implementation and reach of proven strategies to prevent and reduce tobacco use among these groups, as well as expanding questions on surveillance tools to better capture data on subpopulations with the greatest burden of tobacco use. The 50th anniversary Surgeon General’s report on the health consequences of smoking concluded that disease and death from tobacco use are overwhelmingly caused by cigarettes and other combusted products, and that rapid elimination of their use will dramatically reduce this burden (1). Although the decline in overall cigarette smoking prevalence during 2005–2013 from 20.9% to 17.8% is encouraging, approximately 42.1 million adults still smoke cigarettes; this underscores the need for continued implementation of evidence-based interventions outlined in the World Health Organization MPOWER package.§§ These interventions include increasing the price of tobacco products, implementing and enforcing comprehensive smoke-free laws, warning about the dangers of tobacco use with high-impact antismoking media campaigns, and increasing access to help with quitting. Such population-based interventions have been shown to reduce population smoking prevalence (3). For example, in 2013, CDC’s national tobacco education campaign, Tips from Former Smokers (TIPS),¶¶ resulted in a 75% increase in average weekly calls to the national telephone quitline portal 1-800-QUIT-NOW, and the number of unique visitors to the Tips website ( http://www.cdc.gov/tips ) increased nearly 38-fold compared with the 4 weeks before the campaign (7). Additionally, the Surgeon General recently called for consideration of further strategies that could significantly accelerate the decline in smoking, including the reduction of nicotine content in cigarettes to nonaddictive levels and greater restrictions on sales, particularly at the local level, including bans on entire categories of tobacco products (1). The findings in this report are subject to at least six limitations. First, cigarette smoking status was self-reported and not validated by biochemical testing; however, self-reported smoking status correlates highly with serum cotinine levels (8). Second, because NHIS does not include institutionalized populations and persons in the military, results are not generalizable to these groups. Third, the NHIS response rate of 61.2% might have resulted in nonresponse bias. Fourth, the questionnaire did not assess gender identity; the inclusion of transgender persons in addition to LGB persons would be expected to yield higher estimates of use among sexual minorities. Fifth, this report does not include estimates of cigar or other combustible tobacco use, which have generally not declined in recent years, and have even increased in some populations (1). Finally, these estimates might differ from those from other surveillance systems. These differences can be partially explained by varying survey methodologies, types of surveys administered, and definitions of current smoking; however, trends in prevalence are comparable across surveys (1). Sustained, comprehensive state tobacco control programs funded at CDC-recommended levels accelerate progress towards reducing the health and economic burden of tobacco-related diseases in the United States (3). However, in 2014, despite combined revenue of more than $25 billion from settlement payments and tobacco excise taxes for all states, states will spend only $481.2 million (1.9%) on comprehensive tobacco control programs,*** representing <15% of the CDC-recommended level of funding for all states combined (3). Moreover, only two states (Alaska and North Dakota) currently fund tobacco control programs at CDC-recommended levels. Implementation of comprehensive tobacco control policies and programs can result in substantial reductions in tobacco-related morbidity and mortality and billions of dollars in savings from averted medical costs (3).
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                2 May 2017
                16 February 2017
                : 8
                : 18
                : 29722-29740
                Affiliations
                1 Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
                2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
                3 Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
                Author notes
                Correspondence to: Qing-hai Ji, jiqinghai@ 123456shca.org.cn
                Article
                15414
                10.18632/oncotarget.15414
                5444698
                28430613
                0e88c855-779e-4cc7-add3-eff843bc73e8
                Copyright: © 2017 Shi et al.

                This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 30 November 2016
                : 1 February 2017
                Categories
                Research Paper

                Oncology & Radiotherapy
                laryngeal squamous cell carcinoma,nomogram,overall survival,cancer-specific survival,lymph node ratio

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