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Introduction Adolescent vaping remains a problem in the United States, yet little is known about what health warning themes most discourage vaping among adolescents. We sought to identify the most compelling themes for vaping warnings for US adolescents. Methods Participants were a national probability sample of 623 US adolescents aged 13–17 years, recruited in the summer of 2020. Adolescents were randomized to one of the five warning message themes about the potential health effects of vaping: 1. chemical harms, 2. lung harms, 3. Coronavirus Disease 2019 (COVID-19) harms, 4. nicotine addiction, or 5. control (messages about vape litter). The primary outcome was perceived message effectiveness (PME; 3-item scale). Secondary outcomes were negative affect (fear), attention, anticipated social interactions, and message novelty. Results Adolescents rated the chemical, lung, and COVID-19 harms warning messages higher on PME than nicotine addiction and control (all p < .05), while nicotine addiction was rated higher than control (p < .05). The chemical, lung, and COVID-19 harms warning themes also elicited greater negative affect than nicotine addiction and control (all p < .05). For all other secondary outcomes, the COVID-19 harms warning message theme was rated higher than nicotine addiction and control (all p < .05). Conclusion Adolescents perceived warning message themes about lung, chemical and COVID-19 health effects of vaping as more effective than nicotine addiction. To discourage vaping, the FDA and others should communicate to youth about the health effects of vaping beyond nicotine addiction. Implications Adolescents rated warning message themes about the lung, chemical, and COVID-19 health effects of vaping as more effective than nicotine addiction, while nicotine addiction was rated as more effective than control themes about vaping litter. To discourage vaping among adolescents, health messaging should expand message themes to communicate about a broader set of health effects of vaping beyond nicotine addiction.

Supplementary Figures. Supplemental Figure S1: Representative sections showing changes in expression between baseline biopsy and post-treatment surgical specimens. Supplemental Figure S2: Correlogram showing the correlation between changes in protein expression immunoscore, metabolic activity on PET and tumor size by CT scan.

Purpose: The altered PI3K/mTOR pathway is implicated in lung cancer, but mTOR inhibitors have failed to demonstrate efficacy in advanced lung cancer. We studied the pharmacodynamic effects of everolimus in resectable non–small cell lung cancer (NSCLC) to inform further development of these agents in lung cancer.Experimental Design: We enrolled 33 patients and obtained baseline tumor biopsy and 2[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging followed by everolimus treatment (5 or 10 mg daily, up to 28 days), or without intervening treatment for controls. Target modulation by everolimus was quantified in vivo and ex vivo by comparing metabolic activity on paired PET scans and expression of active phosphorylated forms of mTOR, Akt, S6, eIF4e, p70S6K, 4EBP1, and total Bim protein between pretreatment and posttreatment tissue samples.Results: There were 23 patients on the treatment arm and 10 controls; median age 64 years; 22 tumors (67%) were adenocarcinomas. There was a dose-dependent reduction in metabolic activity (SUVmax: 29.0%, −21%, −24%; P = 0.014), tumor size (10.1%, 5.8%, −11.6%; P = 0.047), and modulation of S6 (−36.1, −13.7, −77.0; P = 0.071) and pS6 (−41.25, −61.57, −47.21; P = 0.063) in patients treated in the control, 5-mg, and 10-mg cohorts, respectively. Targeted DNA sequencing in all patients along with exome and whole transcriptome RNA-seq in an index patient with hypersensitive tumor was employed to further elucidate the mechanism of everolimus activity.Conclusions: This “window-of-opportunity” study demonstrated measurable, dose-dependent, biologic, metabolic, and antitumor activity of everolimus in early-stage NSCLC. Clin Cancer Res; 21(8); 1859–68. ©2015 AACR.

Supplementary Table S1. Differentially expressed genes

BackgroundThe scientific term for the substance people inhale and exhale from a vaping device is ‘aerosol’, but whether the public uses this term is unclear. To inform tobacco control communication efforts, we sought to understand what tobacco users call e-cigarette aerosols.MethodsParticipants were a national convenience sample of 1628 US adults who used e-cigarettes, cigarettes or both (dual users). In an online survey, conducted in spring 2021, participants described what ‘people inhale and exhale when they vape’, using an open-ended and then a closed-ended response scale. Participants then evaluated warning statements, randomly assigned to contain the term ‘aerosol’ or ‘vapor‘ (eg, ‘E-cigarette aerosol/vapor contains nicotine, which can lead to seizures’).ResultsIn open-ended responses, tobacco users most commonly provided the terms ‘vapor’ (31%) and ‘smoke’ (23%) but rarely ‘aerosol’ (pp>0.05).ConclusionsThe public rarely uses the term ‘aerosol’ to describe e-cigarette output, potentially complicating educational efforts that use the term. Future studies should explore public knowledge and understanding of the terms ‘aerosol’ and the more popular ‘vapor’ to better inform vaping risk communication.

Introduction Little research has examined the spillover effects of tobacco communication campaigns, such as how anti-smoking ads affect vaping. Aims and Methods Participants were a national sample of 623 U.S. adolescents (ages 13–17 years) from a probability-based panel. In a between-subjects experiment, we randomly assigned adolescents to view one of four videos online: (1) a smoking prevention video ad from the Food and Drug Administration’s (FDA) The Real Cost campaign, (2) a neutral control video about smoking, (3) a vaping prevention video ad from The Real Cost campaign, or (4) a neutral control video about vaping. We present effect sizes as Cohen’s d, standardized mean differences, with 95% confidence intervals (CIs). Results Exposure to The Real Cost vaping prevention ads led to more negative attitudes toward vaping compared with control (d = 0.30, 95% CI: 0.07, 0.53), while exposure to The Real Cost smoking prevention ads did not affect smoking-related outcomes compared with control (p-values > .05). Turning to spillover effects, exposure to The Real Cost smoking prevention ads led to less susceptibility to vaping (d = −0.34, 95% CI: −0.56, −0.12), more negative attitudes toward vaping (d = 0.43, 95% CI: 0.20, 0.65) and higher perceived likelihood of harm from vaping (d = 0.26, 95% CI: 0.04, 0.48), compared with control. Exposure to The Real Cost vaping prevention ads did not affect smoking-related outcomes compared with control (p-values > .05). Conclusions This experiment found evidence of beneficial spillover effects of smoking prevention ads on vaping outcomes and found no detrimental effects of vaping prevention ads on smoking outcomes. Implications Little research has examined the spillover effects of tobacco communication campaigns, such as how anti-smoking ads affect vaping. Using a national sample of 623 U.S. adolescents, we found beneficial evidence of spillover effects of smoking prevention ads on vaping outcomes, which is promising since it suggests that smoking prevention campaigns may have the additional benefit of reducing both smoking and vaping among adolescents. Additionally, we found that vaping prevention campaigns did not elicit unintended consequences on smoking-related outcomes, an important finding given concerns that vaping prevention campaigns could drive youth to increase or switch to using combustible cigarettes instead of vaping.

OBJECTIVE: Tobacco butts are the most littered item worldwide and pose a critical environmental and public health hazard. Given the positive impact of required graphic warnings on smoking, we sought to assess the impact of a policy requiring cigarette pack anti-littering messages on smokers’ littering intentions. METHODS: We randomly assigned US adult smokers (n = 719) to receive labels on the side of their cigarette packs for three weeks: anti-littering messages or messages about chemicals in cigarette smoke. RESULTS: Anti-littering messages elicited higher intentions to refrain from littering in the next month compared to chemical messages (p < .05). Anti-littering messages also led to increased knowledge about cigarette butts being the most common form of litter, the number of conversations about littering, and thinking about the proper disposal of cigarettes (all p < .05). Finally, smoking from packs labeled with anti-littering messages led to fewer weeks littering from car windows compared to packs labeled with chemical messages (p < .05), but did not affect completely refraining from littering cigarette butts. Mediators of the messages’ impact on littering intentions were thinking about proper cigarette butt disposal and perceived message effectiveness (both p < .05). CONCLUSIONS: Policies requiring anti-littering messages on cigarette packs would raise awareness about the problem of cigarette butt litter and bolster intentions to not litter.

Introduction Perceived message effectiveness (PME) is a common metric to understand receptivity to tobacco prevention messages, yet most measures have been developed with adults. We examined adolescents’ interpretation of language within candidate items for a new youth-targeted PME measure using cognitive interviewing. We sought to understand the meaning adolescents assigned to our candidate PME items to improve item wording. Aims and Methods Participants were 20 adolescents, ages 13–17 years from the United States. Cognitive interviews used a structured guide to elicit feedback on comprehension, answer retrieval, and language regarding a set of Reasoned Action Approach-based survey items that assessed the PME of smoking and vaping prevention ads. We employed thematic analysis to synthesize findings from the interviews. Results Interviews identified three main issues related to survey items: ambiguity of language, word choice (risk and other terminology), and survey item phrasing. Adolescents preferred direct, definitive language over more ambiguous phrasing which they saw as less serious (eg, “will” instead of “could”). For risk terminology, they preferred terms such as “harmful” and “dangerous” over “risky,” which was viewed as easy to discount. The term “negative effects” was interpreted as encompassing a broader set of tobacco harms than “health effects.” Adolescents said that the term “vape” was preferable to “e-cigarette,” and identified ways to simplify item wording for greater clarity. Conclusions Tobacco risk terms that appear similar differ in meaning to adolescents, and more direct and unambiguous language is preferred. Our findings informed changes to the PME scale items to improve clarity and reduce measurement error. Implications This study adds to the literature on how adolescents interpret tobacco prevention language. Adolescents may interpret terminology differently than adults, which could lead to ambiguity in meaning and thus measurement error. Through cognitive interviewing, we identified and improved the language in a youth-focused PME measure for tobacco and vaping prevention.

IntroductionThe pace and scale of the COVID-19 pandemic, coupled with ongoing efforts by health agencies to communicate harms, have created a pressing need for data to inform messaging about smoking, vaping, and COVID-19. We examined reactions to COVID-19 and traditional health harms messages discouraging smoking and vaping.MethodsParticipants were a national convenience sample of 810 US adults recruited online in May 2020. All participated in a smoking message experiment and a vaping message experiment, presented in a random order. In each experiment, participants viewed one message formatted as a Twitter post. The experiments adopted a 3 (traditional health harms of smoking or vaping: three harms, one harm, absent) × 2 (COVID-19 harms: one harm, absent) between-subjects design. Outcomes included perceived message effectiveness (primary) and constructs from the Tobacco Warnings Model (secondary: attention, negative affect, cognitive elaboration, social interactions).ResultsSmoking messages with traditional or COVID-19 harms elicited higher perceived effectiveness for discouraging smoking than control messages without these harms (all p vaping elicited higher perceived effectiveness for discouraging vaping (p ConclusionsMessages linking smoking with COVID-19 may hold promise for discouraging smoking and may have the added benefit of also discouraging vaping.

Evidence about the health problems associated with sugary drink consumption is well-established. However, little is known about which sugary drink health harms are most effective at changing consumers' behavior. We aimed to identify which harms people were aware of and most discouraged them from wanting to buy sugary drinks. Participants were a national convenience sample of diverse parents (n = 1,058), oversampled for Latino parents (48%). Participants rated a list of sugary drink-related health harms occurring in children (7 harms) and in adults (15 harms). Outcomes were awareness of each harm and how much each harm discouraged parents from wanting to purchase sugary drinks. Most participants were aware that sugary drinks contribute to tooth decay in children (75%) and weight gain in both children (73%) and adults (69%). Few participants were aware that sugary drinks contribute to adult infertility (16%), arthritis (18%), and gout (18%). All health harms were rated highly in terms of discouraging parents from wanting to buy sugary drinks (range: 3.59-4.11 on a 1-5 scale), with obesity, pre-diabetes, and tooth decay eliciting the highest discouragement ratings. Harm-induced discouragement was higher for participants who were aware of more health harms (B = 0.05, p 0.0001), identified as female (B = 0.15 compared to male, p = 0.02), or had an annual household income of $50,000 or more (B = 0.16 compared to less than $50,000, p = 0.03). These findings suggest health messages focused on a variety of health harms could raise awareness and discourage sugary drink purchases.

PurposeTobacco prevention media campaigns are an important tool to address youth tobacco use. We developed a theory-based perceived message effectiveness (PME) Scale to use when vetting messages for campaigns.MethodsParticipants were a national sample of N=623 US adolescents (ages 13–17 years) recruited from a national probability-based panel. In an online experiment, we randomised adolescents to view tobacco prevention ads. All participants viewed an ad on smoking or vaping from the US Food and Drug Administration’sThe Real Costcampaign and a control video, in a random order. After ad exposure, we assessed PME using nine candidate items and constructs for convergent and criterion validity analyses. We used confirmatory factor analysis and examined information curves to select the scale items.ResultsA brief PME scale with three items (α=0.95) worked equally well for demographically diverse adolescents with different patterns of tobacco use.The Real Costads generated higher PME scores than the control videos for both vaping and smoking (convergent validity; pConclusionsThe University of North Carolina PME Scale for Youth is a reliable and valid measure of the potential effectiveness of vaping and smoking prevention ads. Employing PME scales during message development and selection may help youth tobacco prevention campaigns deploy more effective ads.

Purpose: The altered PI3K/mTOR pathway is implicated in lung cancer, but mTOR inhibitors have failed to demonstrate efficacy in advanced lung cancer. We studied the pharmacodynamic effects of everolimus in resectable non–small cell lung cancer (NSCLC) to inform further development of these agents in lung cancer. Experimental Design: We enrolled 33 patients and obtained baseline tumor biopsy and 2[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging followed by everolimus treatment (5 or 10 mg daily, up to 28 days), or without intervening treatment for controls. Target modulation by everolimus was quantified in vivo and ex vivo by comparing metabolic activity on paired PET scans and expression of active phosphorylated forms of mTOR, Akt, S6, eIF4e, p70S6K, 4EBP1, and total Bim protein between pretreatment and posttreatment tissue samples. Results: There were 23 patients on the treatment arm and 10 controls; median age 64 years; 22 tumors (67%) were adenocarcinomas. There was a dose-dependent reduction in metabolic activity (SUVmax: 29.0%, −21%, −24%; P = 0.014), tumor size (10.1%, 5.8%, −11.6%; P = 0.047), and modulation of S6 (−36.1, −13.7, −77.0; P = 0.071) and pS6 (−41.25, −61.57, −47.21; P = 0.063) in patients treated in the control, 5-mg, and 10-mg cohorts, respectively. Targeted DNA sequencing in all patients along with exome and whole transcriptome RNA-seq in an index patient with hypersensitive tumor was employed to further elucidate the mechanism of everolimus activity. Conclusions: This “window-of-opportunity” study demonstrated measurable, dose-dependent, biologic, metabolic, and antitumor activity of everolimus in early-stage NSCLC. Clin Cancer Res; 21(8); 1859–68. ©2015 AACR.

To examine use of and interest in cessation strategies among nondaily and daily college student smokers.800 undergraduate student smokers aged 18 to 25.The authors examined nondaily versus daily smoking in relation to use of and interest in cessation strategies using an online survey.Nondaily (65.8%) versus daily smokers (34.3%) were more likely to have made a quit attempt (p = .01) but less likely to have used any assistance (p.001). Nondaily smokers were less interested in pharmacotherapy and traditional behavioral interventions; however, there was no difference in interest in technology-based interventions among nondaily versus daily smokers. Controlling for covariates, there were no significant differences in interest in traditional or technology-based behavioral interventions. Higher motivation, lower confidence, and depressive symptomatology were related to interest in each intervention. Smoking for social reasons was related to interest in technology-based interventions.Different intervention strategies may be appropriate for nondaily and daily smokers.

Platinum-based therapy combined with cetuximab is standard first-line therapy for recurrent or metastatic squamous cell carcinoma of the head and neck (RMSCCHN). Preclinical studies have suggested that mammalian target of rapamycin inhibitors may overcome resistance to epidermal growth factor receptor blockers and may augment cetuximab antitumor activity. We conducted a phase 1b trial of carboplatin, cetuximab, and everolimus for untreated RMSCCHN.Patients received carboplatin (area under the curve = 2 mg/ml/min; 3 weeks on, 1 week off), cetuximab (with a loading dose of 400 mg/m(2) and then 250 mg/m(2) weekly), and dose-escalating everolimus (2.5, 5.0, 7.5, and 10 mg/day) with a 3+3 design. After 4 cycles, patients without progression continued cetuximab/everolimus until progression or intolerable toxicity. Patients (age ≥ 18 years) had previously untreated, unresectable RMSCCHN not amenable to radiotherapy and an Eastern Cooperative Oncology Group performance status of 0 to 2.The study enrolled 20 patients (male/female = 18/2) with RMSCCHN; the median age was 65 years (44-75 years). Thirteen patients received everolimus (male/female = 92%). Two of 6 patients receiving 2.5 mg/day experienced dose-limiting toxicity (DLT) with grade 3 hyponatremia and nausea. In 7 patients receiving de-escalated everolimus (2.5 mg every other day), grade 3 hyperglycemia produced DLT in 1 of 6 patients. The objective response rate (RR) was 61.5% (all partial responses). Progression-free survival (PFS) was 8.15 months. The pharmacokinetics of everolimus was described with a 2-compartment mixed-effects model. There was a significant correlation between tumor p-p44/42 staining and response (P = .044) and a marginally significant correlation between phosphorylated mammalian target of rapamycin and overall survival.The maximum tolerated dose of everolimus with cetuximab and carboplatin was 2.5 mg every other day. The regimen was associated with an encouraging RR and PFS, and this suggested possible clinical efficacy in a select group of patients with squamous cell carcinoma of the head and neck.

To examine predictors of smoking in young adulthood among (1) adolescent nonsmokers and (2) adolescent smokers.Data were analyzed from a longitudinal study of adolescents to young adulthood in 1988-1998.Predictors of smoking in young adulthood among adolescent nonsmokers included less education, being unmarried in adulthood, lower family social support, non-smoking parents, and increased alcohol use over time. Predictors of smoking in young adulthood among adolescent smokers included lower family social support, more adolescent friends who used drugs, and slower decreases in depressive symptoms over time.Distinct factors predict smoking initiation versus maintenance among young adults.

6083 Background: Platinum-based therapy in combination with Cet is the standard first line systemic therapy in RMSCCHN. Preclinical studies suggest that mTOR inhibitors may restore sensitivity to EGFR inhibitors in resistant cell lines, and that in combination with Cet may augment anti-tumor activity. We conducted a phase Ib trial of C, Cet and E for untreated RMSCCHN. Methods: Patients received C at AUC=2 on a 3 weeks on 1 off schedule with Cet weekly at a fixed dose and E at escalating dose levels of 2.5, 5.0, 7.5 and 10 mg daily using a 3+3 design. After 4 cycles of therapy patients without disease progression continued on maintenance Cet and E until disease progression or intolerable toxicity. Patients had previously untreated RMSCCHN not amenable to surgery or radiotherapy, age ≥ 18 years and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2. Results: After IRB approval, the study enrolled 18 patients with RMSCCHN between February 8, 2011 and Jan 25 2013. One patient was a screen failure. Four had an anaphylactic reaction to Cet and were excluded from the analysis. A total of 13 patients received E (M/F: 92%); median age 65 (44-75yrs). Two of six patients treated at dose level 1 (E-2.5 mg/day) experienced dose limiting toxicity (DLT) with grade 3 hyponatremia and nausea. Additional 7 patients were treated with de-escalated dose of E (2.5 mg QOD). No DLTs were observed at this dose level. Salient clinically relevant Grade >2 toxicities included: leukopenia (23%), neutropenia (15%) hyponatremia (18%), hyperglycemia, nausea, rash, hypokalemia, urinary infection, bacteremia, (each 8%). Dose reductions of C were necessary for a total of 18/61 delivered cycles of therapy. A response rate (RR) of 62.5% with all responders having partial responses (PR) was observed. The PFS was 7.8 months. Conclusions: The MTD of E in combination with Cet and C is estimated at 2.5 mg QOD. Though this is less than the commonly utilized dose of E, the regimen was associated with encouraging response rate and PFS Clinical trial information: NCT01283334.

Background: We conducted this ‘window- of-opportunity’ study to characterize the biologic activity of everolimus, an allosteric inhibitor of mTOR pathway, in patients with surgically resectable NSCLC. Methods: Patients with surgically resectable NSCLC (Stage I-III) underwent baseline tumor biopsy and FDG PET/CT scan followed by treatment with everolimus (5 or 10mg daily for up to 28 days). A repeat PET/CT scan was obtained 24 hours prior to surgery. Blood samples for pharmacokinetic (PK) assay for drug levels were collected at 0.5, 1, 2, 5, 8 and 24 hours post drug ingestion on Days 1, 8 and 21. Control patients not treated with everolimus also had paired FDG PET/CT scans prior to surgery. Target modulation by everolimus was assessed in vivo by PET and ex vivo by immunohistochemical detection of total and phosphorylated mTOR, Akt, S6, eIF4e and 4EBP1 in pretreatment and posttreatment tissue samples. Alterations in common driver mutations in NSCLC were assessed using SnapShot minisequencing technique. Results: We enrolled 33 patients; 23 on everolimus and 10 on the control arm. Median age: 64 yrs (range 36-77), gender: (14/19 -M/F), stage (I - 14; II - 13; IIIA - 6); histology (adenocarcinoma - 22; squamous - 7; others - 4). Treatment was tolerated well with mostly grade 1/2 toxicities (hyperglycemia, hypertriglyceridemia, anemia and fatigue) and 32 of 33 patients proceeded with surgery on schedule. Compared to controls, there was significant reduction in SUVmax and median anatomic tumor size in a dose-dependent manner in everolimus-treated patients (15.38 vs. -21.74 vs. -23.23; p=0.012 and 4.39 vs. 0 vs.-13.33; p=0.039 in the control, 5mg and 10mg cohorts respectively). There was a similar trend in reduced metabolic activity in Ras mutant tumors treated with 10mg everolimus compared to control (88% vs. -28%). Comparison of baseline biopsy samples and resected tumor specimens in control and everolimus-treated patients showed reduction of S6 (-27.38 vs. 0 vs. -78.95; p=0.0536), pS6 (-20 vs. -29.17 vs. -57.14; p=0.0233) and p4EBP1 (-45.83 vs. 0 vs. -75; p=0.057) with greatest reduction observed in patients treated with higher dose of everolimus. Conclusions: Everolimus exerts a measurable, dose-dependent biologic activity in NSCLC tumors. ‘Window of opportunity’ studies in early stage NSCLC provide strong mechanistic insights and guide development of novel targeted agents. Acknowledgements: This study was supported by NCI grant P01 CA116676. Everolimus was provided by Novartis Oncology. TKO, GS, SS, SSR and FRK are Georgia Cancer Coalition Distinguished Cancer Scholars. Citation Format: Taofeek Kunle Owonikoko, Daniel L. Miller, Seth Force, Gabriel Sica, Scott Kono, Madhusmita Behera, Jennifer Mendel, Zhengjia Chen, Allan Pickens, Robert W. Fu, William F. Auffermann, Jaqueline Rogerio, William E. Torres, Haian Fu, John Hohneker, Shi-Yong Sun, Anthony A. Gal, Suresh S. Ramalingam, Fadlo R. Khuri. Window of opportunity preoperative interrogation of mTOR pathway in patients with resectable non-small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-194. doi:10.1158/1538-7445.AM2013-LB-194