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BACKGROUND: The association between duration of smoking abstinence before non-small-cell lung cancer (NSCLC) diagnosis and subsequent survival can influence public health messaging delivered in lung-cancer screening. We aimed to assess whether the duration of smoking abstinence before diagnosis of NSCLC is associated with improved survival. METHODS: In this retrospective, pooled analysis of cohort studies, we used 26 cohorts participating in Clinical Outcomes Studies of the International Lung Cancer Consortium (COS-ILCCO) at 23 hospitals. 16 (62%) were from North America, six (23%) were from Europe, three (12%) were from Asia, and one (4%) was from South America. Patients enrolled were diagnosed between June 1, 1983, and Dec 31, 2019. Eligible patients had smoking data before NSCLC diagnosis, epidemiological data at diagnosis (obtained largely from patient questionnaires), and clinical information (retrieved from medical records). Kaplan-Meier curves and multivariable Cox models (ie, adjusted hazard ratios [aHRs]) were generated with individual, harmonised patient data from the consortium database. We estimated overall survival for all causes, measured in years from diagnosis date until the date of the last follow-up or death due to any cause and NSCLC-specific survival. FINDINGS: Of 42â087 patients with NSCLC in the COS-ILCCO database, 21â893 (52·0%) of whom were male and 20â194 (48·0%) of whom were female, we excluded 4474 (10·6%) with missing data. Compared with current smokers (15 036 [40·0%] of 37â613), patients with 1-3 years of smoking abstinence before NSCLC diagnosis (2890 [7·7%]) had an overall survival aHR of 0·92 (95% CI 0·87-0·97), patients with 3-5 years of smoking abstinence (1114 [3·0%]) had an overall survival aHR of 0·90 (0·83-0·97), and patients with more than 5 years of smoking abstinence (10â841 [28·8%]) had an overall survival aHR of 0·90 (0·87-0·93). Improved NSCLC-specific survival was observed in 4301 (44%) of 9727 patients who had quit cigarette smoking and was significant at abstinence durations of more than 5 years (aHR 0·87, 95% CI 0·81-0·93). Results were consistent across age, sex, histology, and disease-stage distributions. INTERPRETATION: In this large, pooled analysis of cohort studies across Asia, Europe, North America, and South America, overall survival was improved in patients with NSCLC whose duration of smoking abstinence before diagnosis was as short as 1 year. These findings suggest that quitting smoking can improve overall survival, even if NSCLC is diagnosed at a later lung-cancer screening visit. These findings also support the implementation of public health smoking cessation strategies at any time. FUNDING: The Alan B Brown Chair, The Posluns Family Fund, The Lusi Wong Fund, and the Princess Margaret Cancer Foundation.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Feminino , Masculino , Estudos Retrospectivos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Estudos de Coortes , Fumar/epidemiologiaRESUMO
Lung cancer causes more deaths globally than any other type of cancer. To determine the best treatment, detecting EGFR and KRAS mutations is of interest. However, non-invasive ways to obtain this information are not available. Furthermore, many times there is a lack of big enough relevant public datasets, so the performance of single classifiers is not outstanding. In this paper, an ensemble approach is applied to increase the performance of EGFR and KRAS mutation prediction using a small dataset. A new voting scheme, Selective Class Average Voting (SCAV), is proposed and its performance is assessed both for machine learning models and CNNs. For the EGFR mutation, in the machine learning approach, there was an increase in the sensitivity from 0.66 to 0.75, and an increase in AUC from 0.68 to 0.70. With the deep learning approach, an AUC of 0.846 was obtained, and with SCAV, the accuracy of the model was increased from 0.80 to 0.857. For the KRAS mutation, both in the machine learning models (0.65 to 0.71 AUC) and the deep learning models (0.739 to 0.778 AUC), a significant increase in performance was found. The results obtained in this work show how to effectively learn from small image datasets to predict EGFR and KRAS mutations, and that using ensembles with SCAV increases the performance of machine learning classifiers and CNNs. The results provide confidence that as large datasets become available, tools to augment clinical capabilities can be fielded.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
BACKGROUND: Lung cancer biomarker-driven therapies are the gold standard of treatment and recent studies suggest a higher prevalence of specific targetable biomarkers among Hispanic/Latinos (H/L) than Non-Hispanic Whites (NHW). The study aimed (1) to identify Florida (FL) and Puerto Rico (PR) physicians' knowledge and perceived value of newer genomic data regarding race/ethnicity in relation to optimal lung cancer treatment and survival; and (2) to identify modifiable practice barriers both across and within each location regarding biomarker testing in lung cancer. METHODS: A 25-item survey was administered to a stratified random sample of physicians in FL and PR (medical oncologists, radiation oncologists, pulmonologists, and pathologists). Questions targeted domains of biomarker knowledge, attitudes toward testing, barriers, and practice behaviors regarding lung cancer biomarker testing. RESULTS: The response rate was 45%. Participants identified guiding treatment decisions (82%) and personalizing treatments for patients (78%) as key benefits to mutation testing. PR physicians were more likely (p=0.022) to believe H/L had an elevated incidence of targetable epidermal growth factor receptor (EGFR) mutations compared to NHW. They also perceived lack of appropriate testing resources as a primary barrier compared to FL physicians (43.6% vs. 20.6%, p<0.001), whereas FL physicians identified mutation tests not conducted routinely as part of patient diagnosis as a primary barrier (43.1% vs 24.2%, p= 0.008). CONCLUSIONS: Practice behaviors differed by specialty and between locations, and differences were noted concerning physician's preferences for ordering mutation testing, indicating a clear need for education among physicians in both locations. IMPACT: Educating physicians regarding biomarker testing is imperative to improve patient care.
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At present it is unknown whether the higher prevalence of human papillomavirus (HPV) infection among smokers in men is attributed to a higher probability of acquiring an infection or because of longer infection persistence. Thus, we investigated the role of smoking on the incidence (acquisition) and clearance (persistence) of genital HPV infections among 4,026 men in the HPV in Men (HIM) Study, a multinational prospective study of the natural history of genital HPV infection in men. Genital HPV infections were grouped by any, oncogenic and nononcogenic HPV infections and smoking status was categorized as current, former and never smokers. The incidence of any, oncogenic and nononcogenic HPV infections was significantly higher among current smokers compared to former and never smokers (p < 0.01). In multivariable analyses adjusting for sexual behavior and potential confounders, when compared to never smokers, current smokers exhibited significantly higher probability of acquiring any [hazard ratio (HR) = 1.23; 95% confidence interval (CI) 1.02-1.50] and nononcogenic (HR = 1.21; 95% CI 1.00-1.45) infections and a borderline significant probability for oncogenic infections (HR = 1.18; 95% CI 0.98-1.41). Although the median duration of HPV infection was generally longer among current smokers, we found no statistically significant associations in the multivariable analyses. Overall, these results demonstrated that current smoking exhibited the highest incidence and highest probability of acquiring genital HPV infections.
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Doenças dos Genitais Masculinos/epidemiologia , Infecções por Papillomavirus/epidemiologia , Fumar/epidemiologia , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Feminino , Doenças dos Genitais Masculinos/virologia , Humanos , Incidência , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Análise Multivariada , Infecções por Papillomavirus/virologia , Prevalência , Estudos Prospectivos , Comportamento Sexual/estatística & dados numéricos , Parceiros Sexuais , Inquéritos e Questionários , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: This analysis assessed the acquisition (incidence) and persistence (clearance) of human papilloma virus (HPV) infection by self-reported race among men in The HPV in Men (HIM) Study, a multinational prospective study of the natural history of genital HPV infections. METHODS: Self-reported race was categorized as White, Black, Asian/Pacific Islander (PI), or multiple and mixed race. Genital samples were combined for HPV DNA testing and categorized by any, oncogenic, and non-oncogenic HPV infections. RESULTS: Asian/PI race had significantly the lowest incidence of any, oncogenic, and non-oncogenic HPV infection (P < 0.001). In multivariable analyses, Asian/PI race was associated with a lower probability of acquiring any [HR = 0.63; 95% confidence interval (CI), 0.42-0.95] and non-oncogenic HPV infection (HR = 0.61; 95% CI, 0.40-0.93) when compared to Whites. No significant associations were evident for Asian/PI race for clearance. Multiple and mixed race was significantly associated with lower probability of acquiring non-oncogenic HPV infection (HR = 0.83; 95% CI, 0.69-0.99) and borderline significant associations were observed for any HPV (HR = 0.91) and oncogenic infections (HR = 0.92). Multiple and mixed race was associated with a lower probability of clearing any (HR = 0.92; 95% CI, 0.84-1.00) and oncogenic HPV infections (HR = 0.85; 95% CI, 0.75-0.95). CONCLUSION: Asian/PI race had the lowest incidence of HPV and exhibited a lower probability of acquiring new HPV infections. Multiple and mixed race had the second lowest incidence of infection and was associated with a lower probability of acquiring and clearing an HPV infection. IMPACT: Race-specific differences in HPV infection could be due to behavior, innate genetic differences, or circulating intratypic HPV variants.
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Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/etnologia , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Florida/epidemiologia , Doenças dos Genitais Masculinos/epidemiologia , Doenças dos Genitais Masculinos/etnologia , Doenças dos Genitais Masculinos/virologia , Genótipo , Humanos , Incidência , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
This study was conducted to assess the association between prior history of respiratory disease and lung cancer among Mexican Americans using data from a multi-racial/ethnic lung cancer case-control study. Cases (n = 204) were patients with previously untreated lung cancer. Healthy control participants (n = 325) were recruited from a large physician group practice. Demographics, cigarette use, and history of respiratory disease were collected. Multivariable logistic regression models were used to estimate relative risk. Prior history of COPD (OR = 2.0; 95 % CI 1.2-3.3) and pneumonia (OR = 2.2; 95 % CI 1.3-3.6) were associated with an increased risk of lung cancer. These findings illustrate that prior COPD and pneumonia are associated with an increased risk of lung cancer among Mexican Americans. To our knowledge, this is one of largest case-control analyses assessing the role of respiratory disease and lung cancer risk specifically among Mexican-Americans.
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Carcinoma Pulmonar de Células não Pequenas/etiologia , Pneumopatias/complicações , Neoplasias Pulmonares/etiologia , Americanos Mexicanos , Idoso , Estudos de Casos e Controles , Intervalos de Confiança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pneumonia/complicações , Doença Pulmonar Obstrutiva Crônica/complicações , Rinite Alérgica Sazonal/complicações , Fatores de Risco , Autorrelato , Fumar/efeitos adversos , Texas/epidemiologiaRESUMO
Human papillomavirus (HPV) causes anal, penile and oropharyngeal cancers in men. Genital HPV prevalence in men appears to vary by world region with men residing in Asia having among the lowest prevalence. Unfortunately, there is little information on prevalence of HPV infection in men by race. The purpose of this study was to examine HPV prevalence by race across three countries. 3,909 men ages 18-70 years enrolled in an ongoing prospective cohort study of the natural history of HPV in men (The HIM Study) were included in the analysis. Participants completed risk factor questionnaires and samples were taken from the penile epithelium and scrotum for HPV detection. HPV testing of the combined DNA extract was conducted using PCR and genotyping. Asian/Pacific Islanders had the lowest HPV prevalence of 42.2% compared to Blacks (66.2%), and Whites (71.5%). The Asian/Pacific Islander race was strongly protective in univariate analysis (prevalence ratio (PR) = 0.59; 95% confidence interval (CI): 0.48-0.74) and multivariate analysis for any HPV infection (PR = 0.65; 95% CI: 0.52-0.8). Stratified analysis by lifetime number of female partners also showed strong inverse associations with the Asian/Pacific Islander race. We consistently observed the lowest prevalence of HPV infection among Asian/Pacific Islanders with moderate inverse associations even after various adjustments for potential confounding factors. Unmeasured behavioral factors, sexual mixing with low risk women, and/or race-specific differences in the frequency of germline variations among immune regulating genes may underlie these associations. Further studies among Asian populations that incorporate measures of immuno-genetics are needed to understand this phenomenon.