CT scan screening for lung cancer: risk factors for nodules and malignancy in a high-risk urban cohort

Background

Low-dose computed tomography (CT) for lung cancer screening can reduce lung cancer mortality. The National Lung Screening Trial reported a 20% reduction in lung cancer mortality in high-risk smokers. However, CT scanning is extremely sensitive and detects non-calcified nodules (NCNs) in 24–50% of subjects, suggesting an unacceptably high false-positive rate. We hypothesized that by reviewing demographic, clinical and nodule characteristics, we could identify risk factors associated with the presence of nodules on screening CT, and with the probability that a NCN was malignant.

Methods

We performed a longitudinal lung cancer biomarker discovery trial (NYU LCBC) that included low-dose CT-screening of high-risk individuals over 50 years of age, with more than 20 pack-year smoking histories, living in an urban setting, and with a potential for asbestos exposure. We used case-control studies to identify risk factors associated with the presence of nodules (n = 625) versus no nodules (n = 557), and lung cancer patients (n = 30) versus benign nodules (n = 128).

Results

The NYU LCBC followed 1182 study subjects prospectively over a 10-year period. We found 52% to have NCNs >4 mm on their baseline screen. Most of the nodules were stable, and 9.7% of solid and 26.2% of sub-solid nodules resolved. We diagnosed 30 lung cancers, 26 stage I. Three patients had synchronous primary lung cancers or multifocal disease. Thus, there were 33 lung cancers: 10 incident, and 23 prevalent. A sub-group of the prevalent group were stable for a prolonged period prior to diagnosis. These were all stage I at diagnosis and 12/13 were adenocarcinomas.

Conclusions

NCNs are common among CT-screened high-risk subjects and can often be managed conservatively. Risk factors for malignancy included increasing age, size and number of nodules, reduced FEV1 and FVC, and increased pack-years smoking. A sub-group of screen-detected cancers are slow-growing and may contribute to over-diagnosis and lead-time biases.     

Cancer,coronary artery disease and smoking: a preliminary report on differences in incidence between Seventh-day Adventists and others

A study was made of the incidence of certain types of disease among Seventh-day Adventists, a religious group of special interest because they refrain from smoking and drinking. Epidermoid cancer of the lung, previously shown to be related to smoking, was 10 times less common among Seventh-day Adventists than among the general population, even among those Seventh-day Adventists living in the Los Angeles area where all are exposed to smog. Similarly, cancers of the mouth, larynx, and esophagus, previously shown to be related not only to smoking but also to heavy drinking, were at least 10 times less common among Seventh-day Adventist men than among men of the general population. All other types of cancer, with the exception of cancer of the bladder and cervix, occurred among Seventh-day Adventists with the same frequency as in the general population. The latter occurred slightly less than in the general population. Myocardial infarction in Seventh-day Adventist males was less frequent and occurred at a later age than among males in the general population; while the age distribution of the disease among the Seventh-day Adventist females was similar to that of females in the general population.     

CANCER,CORONARY ARTERY DISEASE AND SMOKING—A Preliminary Report on Differences in Incidence Between Seventh-day Adventists and Others

A study was made of the incidence of certain types of disease among Seventh-day Adventists, a religious group of special interest because they refrain from smoking and drinking.Epidermoid cancer of the lung, previously shown to be related to smoking, was 10 times less common among Seventh-day Adventists than among the general population, even among those Seventh-day Adventists living in the Los Angeles area where all are exposed to smog. Similarly, cancers of the mouth, larynx, and esophagus, previously shown to be related not only to smoking but also to heavy drinking, were at least 10 times less common among Seventh-day Adventist men than among men of the general population. All other types of cancer, with the exception of cancer of the bladder and cervix, occurred among Seventh-day Adventists with the same frequency as in the general population. The latter occurred slightly less than in the general population.Myocardial infarction in Seventh-day Adventist males was less frequent and occurred at a later age than among males in the general population; while the age distribution of the disease among the Seventh-day Adventist females was similar to that of females in the general population.     

Cancer mortality 1981–2016 and contribution of specific cancers to current socioeconomic inequalities in all cancer mortality: A population-based study

BackgroundIn many high-income countries cancer mortality rates have declined, however, socioeconomic inequalities in cancer mortality have widened over time with those in the most deprived areas bearing the greatest burden. Less is known about the contribution of specific cancers to inequalities in total cancer mortality.MethodsUsing high-quality routinely collected population and mortality records we examine long-term trends in cancer mortality rates in Scotland by age group, sex, and area deprivation. We use the decomposed slope and relative indices of inequality to identify the specific cancers that contribute most to absolute and relative inequalities, respectively, in total cancer mortality.ResultsCancer mortality rates fell by 24 % for males and 10 % for females over the last 35 years; declining across all age groups except females aged 75+ where rates rose by 14 %. Lung cancer remains the most common cause of cancer death. Mortality rates of lung cancer have more than halved for males since 1981, while rates among females have almost doubled over the same period.ConclusionCurrent relative inequalities in total cancer mortality are dominated by inequalities in lung cancer mortality, but with contributions from other cancer sites including liver, and head and neck (males); and breast (females), stomach and cervical (younger females). An understanding of which cancer sites contribute most to inequalities in total cancer mortality is crucial for improving cancer health and care, and for reducing preventable cancer deaths.     

Genetic susceptibility for lung cancer: interactions with gender and smoking history and impact on early detection policies

OBJECTIVES: To identify a subgroup of former, current and never smokers (males and females) at high risk for developing lung cancer, based on their genetic susceptibility profiles, to estimate their lifetime probabilities of the disease, and to assess the potential mortality reduction that could be achieved by screening the high-risk group. METHODS: Case-control data (764 cases and 677 matched controls), on two assays of DNA damage and repair (mutagen susceptibility and DNA repair capacity, DRC) in different smoking categories were used to obtain estimates of susceptibility using the formula of total probability. The estimates were inserted into a model of lung cancer natural history and detection by screening to assess mortality reduction due to screening of high-risk individuals. RESULTS: The high-risk group was defined as that 12.5% of the population who were above the third quartile for bleomycin sensitivity and below the median for DRC. High-risk male current, former, and never smokers had lifetime probabilities for developing lung cancer of 38, 21, and 5%, respectively. Females had lower probabilities to develop lung cancer: 15, 8, and 1.5% for high-risk current, former, and never smokers, respectively. Screening of high-risk smokers (12.5% of all smokers) reduced overall mortality by 7% compared to 30% reduction if all smokers were screened. Analogous results were obtained for former and never smokers. CONCLUSIONS: Genetic susceptibility constitutes an important factor in the selection of a high-risk group for early lung cancer detection.     

Profile of cancer in the Eastern Mediterranean region: The need for action

BackgroundMany countries in the Eastern Mediterranean region (EMR) are undergoing marked demographic and socioeconomic transitions that are increasing the cancer burden in region. We sought to examine the national cancer incidence and mortality profiles as a support to regional cancer control planning in the EMR.MethodsGLOBOCAN 2012 data were used to estimate cancer incidence and mortality by country, cancer type, sex and age in 22 EMR countries. We calculated age-standardized incidence and mortality rates (per 100,000) using direct method of standardization.ResultsThe cancer incidence and mortality rates vary considerably between countries in the EMR. Incidence rates were highest in Lebanon (204 and 193 per 100,000 in males and females, respectively). Mortality rates were highest in Lebanon (119) and Egypt (121) among males and in Somalia (117) among females. The profile of common cancers differs substantially by sex. For females, breast cancer is the most common cancer in all 22 countries, followed by cervical cancer, which ranks high only in the lower-income countries in the region. For males, lung, prostate, and colorectal cancer in combination represent almost 30% of the cancer burden in countries that have attained very high levels of human development.ConclusionsThe most common cancers are largely amenable to preventive strategies by primary and/or secondary prevention, hence a need for effective interventions tackling lifestyle risk factors and infections. The high mortality observed from breast and cervical cancer highlights the need to break the stigmas and improve awareness surrounding these cancers.     

Calculation of the 1995 lung cancer incidence in the Netherlands and Sweden caused by smoking and radon: risk implications for radon

A two-mutation carcinogenesis model was used to calculate the expected lung cancer incidence caused by both smoking and exposure to radon in two populations, i.e. those of the Netherlands and Sweden. The model parameters were taken from a previous analysis of lung cancer in smokers and uranium miners and the model was applied to the two populations taking into account the smoking habits and exposure to radon. For both countries, the smoking histories and indoor radon exposure data for the period 1910-1995 were reconstructed and used in the calculations. Compared with the number of lung cancer cases observed in 1995 among both males and females in the two countries, the calculations show that between 72% and 94% of the registered lung cancer cases may be attributable to the combined effects of radon and smoking. In the Netherlands, a portion of about 4% and in Sweden, a portion of about 20% of the lung cancer cases (at ages 0-80 years) may be attributable to radon exposure, the numbers for males being slightly lower than for females. In the Netherlands, the proportions of lung cancers attributable to smoking are 91% for males and 71% for females; in Sweden, the figures are 70% and 56%, respectively. The risk from radon exposure is dependent on gender and cigarette smoking: the excess absolute risk for continuous exposure to 100 Bq m-3 ranges between 0.003 and 0.006 and compares well with current estimates, e.g. 0.0043 of the International Commission on Radiological Protection (ICRP). The excess relative risk for continuous exposure to 100 Bq m-3 shows a larger variation, ranging generally between 0.1 for smokers and 1.0 for non-smokers. The results support the assumption that exposure to (indoor) radon, even at a level as low as background radiation, causes lung cancer proportional to the dose and is consistent with risk factors derived from the miners data.     

Lung and breast cancer mortality among women in France: Future trends

Estimates of mortality in future years are crucial for communication, prevention and anticipation related to the burden of diseases and for developing scenarios studying the effects of reducing environmental exposure. The aim of this study is to project observed trends of mortality in France for lung and breast cancer among females to 2021. Projections of mortality rates are based on a Bayesian age-period-cohort model and a Poisson distribution. We used cancer mortality data from the French mortality register (period 1977–2006) and population data from population registers (estimated for 1977–2006 and projected for period 2007–2021 using five scenarios: largest, smallest, youngest, older, average population). Alternative models were tested (generalized additive model, negative binomial distribution).For the average population scenario, lung and breast cancer mortality rates age-standardized to the world population, are respectively: 11.5 per 10⁵ women (Credibility interval: 10.3–12.8) and 15.9 (14.4–17.6) in 2007–2011, 14.6 (11.7–18.1) and 14.5 (11.6–18.0) in 2012–2016, 18.2 (12.6–26.0) and 13.3 (9.1–18.9) in 2017–2021.Projections show an ongoing increase for lung cancer and decrease for breast cancer mortality rates, which are expected to be equal in 2012–2016. Compared projections of these two cancers using a similar method had not been done before. Aggressive prevention strategies targeting smoking among women are needed to control this fast growing epidemic of avoidable cancer. Planning of health care capacity for diagnosis and treatment of cancer among females is also necessary.     

Characteristics of Malignant Tumors in 230 Husband–Wife Pairs

The aim of this study is to obtain a reference point for early detection of tumors in individuals whose spouses were diagnosed with malignant tumors. Data from 230 husband and wife pairs with malignant tumors were collected and analyzed from the family history records of 15,000 people who came to the Department of Cancer Prevention, Cancer Institute/Hospital, Chinese Academy of Medical Sciences for cancer screening between January 2009 and May 2012. The median diagnosis age was 67 years for husbands and 65 years for wives. A total of 214 cases (46.5 %) had digestive system malignancies. Respiratory system cancers were diagnosed in 64 husbands, of whom 20 (31.3 %) had spouses also with respiratory system cancer. Lung cancer ranked first for the females. The total number of lung cancer and commonly seen female-specific cancers (breast, ovarian, uterine, and cervical) was 127 (55.2 %). The difference in age at diagnosis between spouses was less than 10 years in 134 couples (58.3 %), while 77 (33.5 %) couples had an age difference less than 5 years. A family history of malignant tumors in first-degree relatives was documented in 48.3 % of the husbands and 48.7 % of the wives. The occurrence of cancer in both spouses of the couples studied resulted from an interaction between genetic and environmental factors. Nonhereditary factors such as diet, smoking, passive smoking, and air pollution also contributed to the development of cancers. It is recommended that when husband is diagnosed with cancer, the wife should be screened focusing on lung, breast, and gynecological cancers. If the wife was diagnosed with malignant disease, then screening for lung and digestive system cancers should be emphasized in the husband.     

Summary of a Canadian Study of Smoking and Health

The object of this study was to investigate the relationship between residence, occupation and smoking habits, and mortality from chronic diseases, particularly lung cancer. It was a prospective study, initiated by a questionnaire sent to Canadian veteran pension recipients. The study was based on the replies of 78,000 males and 14,000 females, together with data on the deaths occurring among these respondents over a six-year follow-up period—July 1, 1956 to January 30, 1962.The outstanding finding of this study was that cigarette smokers compared to non-smokers had excessive mortality, particularly from heart and circulatory diseases, lung cancer, and bronchitis and emphysema. The mortality ratios for heart and circulatory diseases were elevated even for those who smoked cigarettes less than five years, and remained relatively constant as the duration of smoking increased. The mortality ratios for lung cancer increased markedly as the duration of smoking increased. A small excess in mortality was noted among urban residents. An association between cause of death and occupation was not evident in this study.Findings based on the data on smoking collected in this study were incorporated into the Report of the U.S. Surgeon-General''s Advisory Committee on Smoking and Health.     

Association between lung cancer screening and smoking cessation

IntroductionAdults with high-risk smoking histories benefit from annual lung cancer screening. It is unclear if there is an association between lung cancer screening and smoking cessation among U.S. adults who receive screening.MethodsWe performed this population-based cross-sectional study using data from the Behavioral Risk Factor Surveillance System (2017–2020). We defined individuals eligible for lung cancer screening as adults 55–80 years old with ≥ 30 pack-year smoking history who were currently smoking or quit within the last 15 years. We assessed the association between lung cancer screening and current smoking status.ResultsBetween 2017 and 2020, 12,382 participants met screening criteria. Current smoking was reported by 5685 (45.9 %) participants, of whom 40.4 % (2298) reported a cessation attempt in the prior year. Lung cancer screening was reported by only 2022 (16.3 %) eligible participants. Lung cancer screening was associated with lower likelihood of currently smoking (odds ratio [OR] 0.705, 95 % CI 0.626–0.793) compared to individuals who did not receive screening. Screening was also associated with higher likelihood of reporting a cessation attempt in the prior year (OR 1.562, 95 % CI 1.345–1.815) compared to individuals who did not receive screening.ConclusionsReceipt of lung cancer screening was associated with lower smoking rates and more frequent cessation attempts among U.S. adults. Better implementation of lung cancer screening programs is critical and may profoundly increase smoking cessation in this population at risk of developing lung cancer.     

Cancer incidence and mortality in people aged less than 75 years: Changes in Australia over the period 1987–2007

BackgroundAustralia has one of the highest rates of cancer incidence worldwide and, despite improving survival, cancer continues to be a major public health problem. Our aim was to provide simple summary measures of changes in cancer mortality and incidence in Australia so that progress and areas for improvement in cancer control can be identified.MethodsWe used national data on cancer deaths and newly registered cancer cases and compared expected and observed numbers of deaths and cases diagnosed in 2007. The expected numbers were obtained by applying 1987 age–sex specific rates (average of 1986–1988) directly to the 2007 population. The observed numbers of deaths and incident cases were calculated for 2007 (average of 2006–2008). We limited the analyses to people aged less than 75 years.ResultsThere was a 28% fall in cancer mortality (7827 fewer deaths in 2007 vs. 1987) and a 21% increase in new cancer diagnoses (13,012 more diagnosed cases in 2007). The greatest reductions in deaths were for cancers of the lung in males (?2259), bowel (?1797), breast (?773) and stomach (?577). Other notable falls were for cancers of the prostate (?295), cervix (?242) and non-Hodgkin lymphoma (?240). Only small or no changes occurred in mortality for cancers of the lung (female only), pancreas, brain and related, oesophagus and thyroid, with an increase in liver cancer (267). Cancer types that showed the greatest increase in incident cases were cancers of the prostate (10,245), breast (2736), other cancers (1353), melanoma (1138) and thyroid (1107), while falls were seen for cancers of the lung (?1705), bladder (?1110) and unknown primary (?904).ConclusionsThe reduction in mortality indicates that prevention strategies, improvements in cancer treatment, and screening programmes have made significant contributions to cancer control in Australia since 1987. The rise in incidence is partly due to diagnoses being brought forward by technological improvements and increased coverage of screening and early diagnostic testing.     

Cancer patterns in Canada.

Cancer is diagnosed in about 70 000 Canadians each year and is the leading cause of the loss of potential years of life before age 75 among women. Life-threatening forms of cancer will develop in at least one of every three Canadian newborns during their lifetimes if current cancer risks are not reduced. Lung and breast cancers are, respectively, the leading causes of premature death due to cancer among men and women. Compared with other countries Canada has low death rates for stomach cancer but high rates for certain smoking-related cancers (those of the lung and of the mouth and throat), leukemia and cancers of the colon, breast and lymphatic tissues. Newfoundland has the highest rates of death from stomach cancer and the lowest rates of death from prostatic cancer, whereas the western provinces have the opposite pattern. The rates of death from lung cancer among men are highest in Quebec, the province with the highest prevalence of smoking. In Canada the overall rates of death from cancer increased by 32% among men from 1951 to 1983. However, among women they declined by 12% from 1951 to 1976 and increased from 1976 to 1983, particularly among those aged 55 to 74. The rising rates of death due to lung cancer were primarily responsible for these increases. Lung cancer will likely displace breast cancer as the leading cancer killer of Canadian women by 1990. Given the relatively low survival rates for cancers caused by smoking and the lack of substantial improvement in rates for the most frequent types of cancer, preventive strategies that include effective measures to reduce tobacco consumption are urgently required.     

Gender-specific trends in cigarette smoking and lung cancer incidence: A two-stage age-stratified Bayesian joinpoint model

BackgroundPrevious studies have explored population-level smoking trends and the incidence of lung cancer, but none has jointly modeled them. This study modeled the relationship between smoking rate and incidence of lung cancer, by gender, in the U.S. adult population and estimated the lag time between changes in smoking trend and changes in incidence trends.MethodsThe annual total numbers of smokers, by gender, were obtained from the database of the National Health Interview Survey (NHIS) program of the Centers for Disease Control and Prevention (CDC) for the years 1976 through 2018. The population-level incidence data for lung and bronchus cancers, by gender and five-year age group, were obtained for the same years from the Surveillance, Epidemiology, and End Results (SEER) program database of the National Cancer Institute. A Bayesian joinpoint statistical model, assuming Poisson errors, was developed to explore the relationship between smoking and lung cancer incidence in the time trend.ResultsThe model estimates and predicts the rate of change of incidence in the time trend, adjusting for expected smoking rate in the population, age, and gender. It shows that smoking trend is a strong predictor of incidence trend and predicts that rates will be roughly equal for males and females in the year 2023, then the incidence rate for females will exceed that of males. In addition, the model estimates the lag time between smoking and incidence to be 8.079 years.ConclusionsBecause there is a three-year delay in reporting smoking related data and a four-year delay for incidence data, this model provides valuable predictions of smoking rate and associated lung cancer incidence before the data are available. By recognizing differing trends by gender, the model will inform gender specific aspects of public health policy related to tobacco use and its impact on lung cancer incidence.     

Cancer Incidence among Adolescents and Young Adults in Urban Shanghai, 1973-2005

Background

Lack of cancer incidence information for adolescents and young adults led us to describe incidence trends within the young population of 15 to 49 year-olds in urban Shanghai between 1973 and 2005.

Methods

During 1973 to 2005, data on 43,009 (45.8%) male and 50,828 (54.2%) female cancer cases aged 15–49 years from the Shanghai Cancer Registry were analyzed. Five-year age-specific rates, world age-standardized rates, percent change (PC), and annual percent change (APC) were calculated using annual data on population size and its estimated age structure.

Results

During the 33-year study period, overall cancer incidence of adolescents and young adults among males marginally decreased by 0.5% per year (P<0.05). However, overall cancer incidence for females slightly increased by 0.8% per year (P<0.05). The leading cancer for males in rank were liver, stomach, lung, colorectal, and nasopharyngeal cancers and for females were breast, stomach, colorectal, thyroid, and ovarian cancers. Among specific sites, incidence rates significantly decreased for cancers of the esophagus, stomach, and liver in both sexes. In contrast, incidence rates significantly increased for kidney cancers, non-Hodgkin lymphoma, and brain and nervous system tumors in both sexes and increased for breast and ovarian cancers among females.

Conclusions

Overall cancer incidence rates of adolescents and young adults decreased in males whereas they increased in females. Our findings suggest the importance of further epidemiology and etiologic studies to further elucidate factors contributing to the cancer incidence trends of adolescents and young adults in China.     

Opportunities with W.H.O

Available statistics were studied to define the extent of the lung cancer problem in Canada. Because of the low overall survival in treated and untreated cases at one year, mortality figures provide a rough index of morbidity from this disease.Male lung cancer death rates rose steadily from 3.0 to 24.6, and female rates from 1.6 to 4.0 per 100,000 population between 1931 and 1961. In males, the greatest increase occurred in the 70-74 year age group (eighteen-fold) and in females in the 80-84 year age group (seven-fold).Lung cancer caused 2774 deaths in Canada in 1961, and was the leading cause of cancer deaths for males in all age groups from 40 to 79 years. It accounted for approximately 1 in 5 of all cancer deaths in males and 1 in 26 in females.Lung cancer mortality in Canada has not increased to the same extent as in certain other countries, but to counter the rising trend, changes in the smoking habits of the population are required as well as community and industrial control of atmospheric carcinogens.     

Lung Cancer Screening with Computer Aided Detection Chest Radiography: Design and Results of a Randomized,Controlled Trial

Introduction

The sensitivity of CT based lung cancer screening for the detection of early lung cancer is balanced by the high number of benign lung nodules identified, the unknown consequences of radiation from the test, and the potential costs of a CT based screening program. CAD chest radiography may improve the sensitivity of standard chest radiography while minimizing the risks of CT based screening.

Methods

Study subjects were age 40–75 years with 10+ pack-years of smoking and/or an additional risk for developing lung cancer. Subjects were randomized to receive a PA view chest radiograph or placebo control (went through the process of being imaged but were not imaged). Images were reviewed first without then with the assistance of CAD. Actionable nodules were reported and additional evaluation was tracked. The primary outcome was the rate of developing symptomatic advanced stage lung cancer.

Results

1,424 subjects were enrolled. 710 received a CAD chest radiograph, 29 of whom were found to have an actionable lung nodule on prevalence screening. Of the 15 subjects who had a chest CT performed for additional evaluation, a lung nodule was confirmed in 4, 2 of which represented lung cancer. Both of the cancers were seen by the radiologist unaided and were identified by the CAD chest radiograph. The cumulative incidence of symptomatic advanced lung cancer was 0.42 cases per 100 person-years in the control arm; there were no events in the screening arm.

Conclusions

Further evaluation is necessary to determine if CAD chest radiography has a role as a lung cancer screening tool.ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01663155","term_id":"NCT01663155"}}NCT01663155     

Effectiveness of the public health policy for breast cancer screening in Finland: population based cohort study.

OBJECTIVE: To evaluate the effectiveness of screening for breast cancer as a public health policy. DESIGN: Follow up in 1987-92 of Finnish women invited to join the screening programme in 1987-9 and of the control women (balanced by age and matched by municipality of residence), who were not invited to the service screening. SETTING: Finland. SUBJECTS: Of the Finnish women born in 1927-39, 89893 women invited for screening and 68862 controls were followed; 1584 breast cancers were diagnosed. MAIN OUTCOME MEASURES: Rate ratio of deaths from breast cancer among the women invited for screening to deaths among those not invited. RESULTS: There were 385 deaths from breast cancer, of which 127 were among the 1584 incident cases in 1987-92. The rate ratio of death was 0.76 (95% confidence interval 0.53 to 1.09). The effect was larger and significant (0.56; 0.33 to 0.95) among women aged under 56 years at entry. 20 cancers were prevented (one death prevented per 10000 screens). CONCLUSIONS: A breast screening programme can achieve a similar effect on mortality as achieved by the trials for breast cancer screening. However, it may be difficult to justify a screening programme as a public health policy on the basis of the mortality reduction only. Whether to run a screening programme as a public health policy also depends on its effects on the quality of life of the target population and what the resources would be used for if screening was not done. Given all the different dimensions in the effect, mammography based breast screening is probably justifiable as a public health policy.