Tobacco Pack-years Research Articles

Abstract 1877: Lung cancer risk in painters: Results from the SYNERGY pooled analysis

Abstract “Occupational exposure as a painter” was classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) based on increased risks of cancers of the lung, bladder, and mesothelioma. Painters are exposed to a mixture of known and suspected lung carcinogens; thus it has been difficult to identify the specific agent(s) contributing to the elevated risk of lung cancer. Although the exposure to occupational carcinogens could differ according to the job duties of a painter, it is unknown whether the risk of lung cancer differs according to the painter type. Data from the SYNERGY study were used to evaluate the risk of lung cancer associated with ever working as a painter, duration of employment, and type of painter (classified according to ISCO and ISIC codes). SYNERGY is a pooled effort of 11 case-control studies in European countries and Canada that includes detailed individual data on smoking for 13389 lung cancer cases and 16384 age- and sex-matched controls. Among the cases and controls, there were 462 and 383 painters, respectively. Multivariable unconditional logistic regression models were adjusted for age, gender, centre, tobacco pack-years, and occupational exposures to asbestos, silica, polycyclic aromatic hydrocarbons, chromium VI and nickel as assessed by a job-exposure matrix. An odds ratio (OR) of 1.31 (95% CI, 1.12-1.45) was associated with ever working as painter and the risk of lung cancer increased with increasing years of employment (p-value for trend = 0.0004). A similar magnitude of effect and trend with duration of employment was observed in construction painters (ISCO 93120/ISIC 5000) but not in automobile painters (ISCO 93960/ISIC 3843,9513). Results were similar when restricted to men but uninformative for women only due to small numbers. There was no significant difference in risk when stratified by histological type and restricted to never smokers. Painters, particularly in the construction industry, are at an increased risk for lung cancer and this risk increases with duration of employment. These results will be further refined by specific type of painter and by including additional studies to increase the precision of the risk estimates. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1877. doi:10.1158/1538-7445.AM2011-1877

A Case of Mycobacterium Avium-Intracellulare Following Initiation of Infliximab Therapy

Purpose: Tumor necrosis factor (TNF)-α inhibitors have significantly impacted the treatment of inflammatory bowel disease and rheumatological disorders, but their use leaves patients susceptible to opportunistic infections. Mycobacterium avium-intracellulare (MAI) refers to two ubiquitous species, M. avium and M. intracellulare, collectively termed MAI. The mode of transmission is believed to be ingestion or inhalation. The bacterium is translocated across the epithelium of the gastrointestinal or respiratory tracts and infects resting macrophages. TNF-α is essential for macrophage activation, as well as granuloma formation and maintenance, all key components of host defense against intracellular pathogens. Thus, patients on TNF-α inhibitors are at increased risk of MAI infection, though exceedingly rare. Case Presentation: A 40 year-old Caucasian male recently diagnosed with ileocolonic Crohn's disease was started on infliximab after he failed to respond to 6-mercaptopurine, mesalamine, and prednisone. A negative PPD and chest x-ray were documented before initiating treatment. Six months later he presented with right-sided pleuritic chest pain and night sweats. He denied cough, sputum production, fevers or skin changes. He has a 13 pack-year tobacco history and is a truck driver with no international travel history. Examination was significant for fine crackles localized to the right upper lobe and was otherwise normal. CT-scan of the thorax revealed right upper lobe parenchymal destruction with cystic cavities. Bronchoscopy with bronchoalveolar lavage, performed to obtain a sputum specimen, was negative for acid-fast bacilli staining. Due to high clinical suspicion, infliximab was discontinued and four-drug tuberculosis therapy (isoniazid, pyrazinamide, ethambutol and rifampin) was initiated. Two weeks later, culture grew Mycobacterium avium-intracellulare with intermediate susceptibility to clarithromycin on testing. The patient remains off infliximab therapy and is completing a one-year course of ethambutol, rifampin and clarithromycin with repeat CT-scans every three months. Discussion: We report a rare case of Mycobacterium avium-intracellulare infection after initiation of TNF-α inhibitor therapy. Although it is uncommon, MAI must be in the differential diagnosis when a patient on anti-TNF-α therapy presents with new lung infiltrates.

Spirometry for detection of undiagnosed chronic obstructive pulmonary disease in primary care

Objective: The aim of this study was to assess the utility of family physicians’ office spirometry, to detect previously undiagnosed chronic obstructive pulmonary disease (COPD) in individuals who smoke. Furthermore, agreement between doctors with more or less experience in performing spirometry was assessed. Methods: Cross-sectional study. Smokers aged 40–69 years who attended a family practice centre were invited to participate. Variables considered were tobacco pack-years, time of tobacco use, smoking cessation, COPD symptoms, Medical Research Council Dyspnoea Scale values, pre- and post-bronchodilator spirometry data, and acceptability of spirometry curves. Results: 212 subjects underwent spirometry, and 179 yielded acceptable spirometry curves. Of these, 173 subjects underwent reversibility testing, of whom 39 (22.5%, 95% CI: 16.2–29.1%) were diagnosed as COPD. Of these, 48.7% were classified as COPD Stage I and 41.0% as Stage II following GOLD criteria. Age, gender, pack-years and cough were related to airflow obstruction levels. Symptom number was not related to presence of airflow obstruction. More than 80% of spirometry curves were acceptable. Agreement on curve acceptability between junior doctors and a family physician trainer was very good, but moderate between junior doctors and a pulmonologist.Conclusions: Forced spirometry data from smokers attending general practice doctors can be used to identify a significant number of previously undiagnosed COPD cases.

Analysis of the effect of p16 and tobacco pack-years (p-y) on overall (OS) and progression-free survival (PFS) for patients with oropharynx cancer (OPC) in Radiation Therapy Oncology Group (RTOG) protocol 9003.

5510 Background: Differences in OS and PFS were observed for HPV-positive (pos) and negative (neg) OPC patients (pts) treated with chemoradiation in RTOG 0129. We evaluated whether similar differences were observed when OPC pts were treated with radiotherapy alone in RTOG 9003. Methods: An unplanned, retrospective analysis was performed on archived tumor from OPC pts treated in RTOG 9003, a four-arm, phase III trial that compared standard-FX, to hyper-FX, accelerated (A)-FX with split or AFX with concomitant boost. Tumor HPV status for OPC pts was determined by a surrogate, p16 IHC (≥70% expression pos). Five-year OS and PFS were estimated (with 95% confidence intervals [CI]) by Kaplan- Meier method and compared by log-rank test. Hazard ratios (HR) for OS (death) and PFS (progression or death) were estimated by Cox models. Results: p16 was evaluable for29% (190/646) of OPC pts and only 39% were pos. OS/PFS outcomes were similar for pts with/without p16 data. p16-pos tumors were associated with better Zubrod PS, absent anemia, and T1 stage, but not assigned treatment. Overall median p-y of tobacco smoking was high (38 p-y), but was lower for the p16-pos group (29 vs. 45.9 p-y, p=0.016). At median f/u of 9.3 years, p16-pos OPC pts had better OS (5-year 49.0 vs. 19.6%, p<0.0001; HR 0.43, 95%CI 0.31-0.61) and PFS (5-year 43.6 vs.19.0%, p<0.0001; HR 0.45, 95% CI 0.32-0.63) than p16- neg pts. At 5-years, local-regional failure was lower for p16-pos OPC (30.5 vs. 54.9%, p<0.001) but distant metastases (11.1 vs. 13.0%, p=0.71) and second primary tumors (SPT, 13.8 vs. 11.4%, p=0.40) were not. The hazard of death (OS) or progression and death (PFS) significantly increased by 1% per p-y of tobacco smoking (for both, HR 1.01, 95% CI 1.00-1.01, p<0.002), after adjustment for Zubrod PS, T stage, N stage and p16. Conclusions: The relative hazard of death or progression for p16-pos vs. neg pts and for p-y of tobacco smoking appears independent of treatment by radiotherapy or chemoradiation. Absolute rates for OS, PFS, and SPT may be compromised in part by higher cumulative p-y of tobacco smoking in pts enrolled a decade before those in RTOG 0129. No significant financial relationships to disclose.

Relationships between hand‐rolled cigarettes and primary lung cancer: A Norwegian experience

Detailed smoking history of patients developing lung cancer is rarely known, especially not for users of hand-rolled cigarettes. In Norway, smoking hand-rolled tobacco is still popular, accounting for one-third of the total tobacco consume. A questionnaire-based study revealing detailed information about tobacco consume with consecutive inclusion of all persons developing lung cancer in Southern Norway 2002-2005. In this unselected population with 479 patients with newly diagnosed lung cancer, 95% had a smoking history and 88% of ever-smokers had smoked primarily hand-rolled cigarettes. The hand-rolled cigarette smokers had smoked fewer cigarettes daily (15) and less pack-years of tobacco (34) than fabricated cigarette smokers (20, P < 0.0001 and 42, P = 0.021, respectively). Smoking hand-rolled cigarettes was considerably more frequent than expected from official sales statistics. Hand-rolled cigarette smoking revealed an odds ratio of 13 for developing lung cancer compared with smoking fabricated cigarettes. In this unselected population with newly diagnosed lung cancer, nine out of 10 ever-smokers had smoked primarily hand-rolled cigarettes. Patients smoking hand-rolled cigarettes had a smoking history of fewer daily cigarettes and less pack-years tobacco consumed than fabricated cigarette smokers. In this study, hand-rolled cigarettes are more frequently used than shown in national statistics. Smokers of hand-rolled cigarettes may have a greatly increased risk for lung cancer compared with smokers of fabricated cigarettes.

Oral health, mouthwashes and cancer – what is the story?

Two hospital-based case-control studies were conducted in central and eastern Europe and Latin America. CASE / CONTROL SELECTION: Cases and controls were recruited in Moscow (Russia), Bucharest (Romania) and Lodz and Warsaw (Poland) from 1998 to 2002, and from 1998 to 2003 in Buenos Aires (Argentina), La Habana (Cuba) and the Brazilian towns Rio de Janeiro, São Paulo, Pelotas, Porto Alegre and Goiânia. Incident cases of squamous cell carcinoma of the head and neck (oral cavity, pharynx, larynx) and oesophagus, as well as age- (in quinquennia) and sex frequency-matched controls, were enrolled from 1998 to 2003. Control subjects included residents of the study areas for at least 1 year who were admitted to the same hospitals as the cases or in a comparable catchment area (controls in São Paulo were not recruited from oncology hospitals, and population-based controls were enrolled in Warsaw). Controls were hospitalised for prespecified conditions thought to be unrelated to tobacco use or alcohol consumption. Both studies were coordinated by the International Agency for Research on Cancer according to an identical protocol for both case and control recruitment. Data from the central European and Latin American studies were analysed separately. Multivariable logistic regression models, including terms for oral health indicators, age, sex, education, country (central Europe) or centre (Latin America), tobacco pack-years and cumulative alcohol consumption, were used to obtain odds ratios (OR) and 95% confidence intervals (CI). All oral hygiene indicators and covariates were analysed as categorical variables, except for age, cumulative alcohol consumption, tobacco pack-years, and age when full-time education was completed, which were analysed as continuous variables. Case-control comparisons were made using t tests for continuous variables and chi-square tests for categorical variables; two-sided P values were obtained. Effect modification was assessed by stratifying on smoking (never/ former/ current) and drinking (never/ ever) habit. Heterogeneity between centres was tested. Risk factors for head and neck cancer, independent of tobacco use and alcohol consumption, were as follows: poor condition of the mouth [central Europe OR, 2.89 (95% CI, 1.74-4.81); Latin America OR, 1.89 (95% CI, 1.47-2.42)]; lack of toothbrush use [Latin America OR, 2.36 (95% CI, 1.28-4.36)], and daily mouthwash use [Latin America OR, 3.40 (95% CI,1.96-5.89]. Missing six to 15 teeth was an independent risk factor for oesophageal cancer [central Europe OR, 2.84 (95% CI, 1.26-6.41); Latin America OR, 2.18 (95% CI, 1.04-4.59)]. These results indicate that periodontal disease (as indicated by poor condition of the mouth and missing teeth) and daily mouthwash use may be independent causes of cancers of the head, neck and oesophagus.

Cannabis Smoking and Risk of Lung Cancer in Men: A Pooled Analysis of Three Studies in Maghreb

Cannabis is the most widely consumed illicit drug worldwide and the relation between cannabis smoking and lung cancer is suggestive, albeit inconclusive. We conducted three hospital based case-control studies in Tunisia, Morocco, and Algeria, three areas of high prevalence of cannabis consumption as well as production. This paper presents the pooled analysis of these three studies restricted to men with a total of 430 cases and 778 controls. Ninety-six percent of the cases and 67.8% of the controls were tobacco smokers and 15.3% of the cases and 5% of the controls were ever cannabis smokers. All cannabis smokers were tobacco users. Adjusting for country, age, tobacco smoking, and occupational exposure, the odds ratio (OR) for lung cancer was 2.4 (95% confidence interval [CI]: 1.6-3.8) for ever cannabis smoking. This association remained after adjustment for lifetime tobacco packyears as continuous variable, OR = 2.3 (95% CI: 1.5-3.6). The OR adjusted for intensity of tobacco smoking (cigarette/d) among current tobacco smokers and never cannabis smokers was 10.9 (95% CI: 6.0-19.7) and the OR among current tobacco users and ever cannabis smokers was 18.2 (95% CI: 8.0-41.0). The risk of lung cancer increased with increasing joint-years, but not with increasing dose or duration of cannabis smoking. Our results suggest that cannabis smoking may be a risk factor for lung cancer. However, residual confounding by tobacco smoking or other potential confounders may explain part of the increased risk.

Occupation and risk of lung cancer in Central and Eastern Europe: the IARC multi-center case–control study

We sought to evaluate the role of occupation and industry in lung carcinogenesis in six countries in Central and Eastern Europe. This multi-center case-control study included 2,056 male and 576 female lung cancer incidence cases diagnosed from 1998 to 2001 and 2,144 male and 727 female controls frequency-matched for sex and age. Unconditional regression models were applied to calculate the odds ratios after controlling for potential confounders including age (5-year groups), study center (15 centers), and tobacco pack-years. Elevated odds ratios (ORs) were found for men employed as production workers (OR 1.45, 95% CI 1.22-1.72), bookkeepers and cashiers (1.81, 1.03-3.24), general farmers (1.67, 1.08-2.60), livestock workers (2.54, 1.09-5.88), miners (2.17, 1.47-3.23), toolmakers and metal patternmakers (2.56, 1.34-4.94), glass formers (2.55, 1.18-5.50), dockworkers, and freight handlers (1.49, 1.04-2.12). Industries with elevated risk among men included mining (1.75, 1.20-2.57), manufacture of cement, lime, or plaster (3.62, 1.11-12.00), casting of metals (2.00, 1.17-3.45), manufacture of electric motors (2.18, 1.24-3.86). For women, elevated ORs were found for medical, dental, veterinary doctors (2.54, 1.01-6.31), librarians and curators (7.03, 1.80-27.80), sewers 3.63 (1.12-10.23). This study identifies new areas for further, explanatory analyses, especially in production work, and indicates new possible sources of exposure to cancer risk for women.

High prevalence of occult endobronchial malignancy in high risk patients with moderate sputum atypia

Early stage radiographically occult lung cancer has a high cure rate, but comprises a small fraction of all lung cancer. Abnormal sputum cytology is one indication for bronchoscopy in patients with chest imaging that is not suspicious for lung cancer. While there is good evidence that sputum cytologic findings of carcinoma, carcinoma in situ or severe atypia predict high rates of diagnosis of lung cancer, less is known of the frequency in which lung cancer is diagnosed in bronchoscopies carried out for the indication of moderate sputum atypia. One small series, published in abstract form only, reported an 8% rate of diagnosis of lung cancer in subjects bronchoscoped for moderate atypia. We tested the hypothesis that moderate sputum atypia is an indicator of occult central airway cancer in a retrospective analysis of a group of high risk subjects, defined as current or former smokers with >30 pack-years tobacco smoking and airflow obstruction with moderate atypia sputum cytology. Seventy-nine such subjects with no evidence of malignancy on chest radiograph at the time bronchoscopy was scheduled underwent white light and autofluorescence bronchoscopy. Lung cancer was found in five subjects; three had invasive squamous cell carcinomas and two had carcinoma in situ. Seven additional subjects had severe dysplasia found on endobronchial biopsy. Moderate sputum atypia may be an important marker of risk for occult endobronchial malignancy in high risk subjects.

Comorbidity and KPS are independent prognostic factors in stage I non-small-cell lung cancer

Purpose: To determine the prognostic role of comorbidity in Stage I non-small-cell lung cancer (NSCLC) treated with surgery or radiotherapy (RT).Methods and Materials: One hundred sixty-three patients with clinical Stage I NSCLC were analyzed for overall survival (OS) and comorbidity. One hundred thirteen patients underwent surgery (surgical group) and 50 patients received definitive radiotherapy (RT group). Ninety-six percent of the surgical group had lobectomy or pneumonectomy, and negative margins were achieved in 96% of the patients. The median dose to the tumor for the RT group was 61.2 Gy (range 30.8–77.4). The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and the Charlson scale were used to rate comorbidity. Karnofsky performance scores (KPS) were available in 42 patients; the rest of the scores were determined retrospectively by two physicians independently, with 97% agreement.Results: The OS was 44% for the surgical group and 5% for the RT group at 5 years. Noncancer-related mortality was observed in 31% and 62% of the surgical and RT patients, respectively. On univariate analysis, performed on all patients (n = 163), squamous cell histologic type (p <0.001), clinical Stage T2 (p = 0.062), tumor size >4 cm (p = 0.065), >40 pack-year tobacco use (p <0.001), presence of a CIRS-G score of 4 (extremely severe, CIRS-G4: [+]) (p <0.001), severity index of >2 (p <0.001), Charlson score >2 (p = 0.004), KPS <70 (p <0.001), and treatment with RT (p <0.001) were associated with a statistically significant inferior OS. Multivariate analysis with histologic features, clinical T stage, age, tobacco use, KPS, comorbidity [CIRS-G(4)] and treatment group on all patients showed that squamous cell histology, >40 pack-year tobacco use, KPS <70, and presence of CIRS-G(4) were independently associated with an inferior OS. Treatment modality, T stage, and age did not have any statistically significant effect on OS. Statistically significant differences were found between the surgical and RT groups in Charlson score (p = 0.001), CIRS-G total score (p = 0.004), severity index (p = 0.006), CIRS-G4(+) (p <0.001), KPS (p <0.001), amount of tobacco use (p = 0.002), clinical tumor size (p <0.001), clinical T stage (p = 0.01), forced expiratory volume in 1 s (p = 0.001), and age (p = 0.008), in favor of the surgical group.Conclusion: The presence of significant comorbidity and KPS of <70 are both important prognostic factors, but were found to be independent of each other in Stage I NSCLC. Therefore, comorbidity and KPS assessment are recommended when analyzing the prognostic effects of tumor or treatment-related factors on OS.

Risk of pulmonary tuberculosis relative to silicosis and exposure to silica dust in South African gold miners.

OBJECTIVES: To investigate the following questions. (1) Is silica dust on its own, without the presence of silicosis, associated with an increased risk of pulmonary tuberculosis (PTB) in workers exposed...

Do overall treatment time, field size, and treatment energy influence local control of T1–T2 squamous cell carcinomas of the glottic larynx?

To evaluate treatment and patient related prognostic factors that may influence local control in the treatment of T1-T2 squamous cell carcinoma of the glottic larynx. One hundred nine patients with invasive, previously untreated T1-T2 squamous cell carcinoma of the glottic larynx were treated with curative intent with radiotherapy at the Fox Chase Cancer Center between June 1980 and November 1991. Follow-up ranged from 26-165 months (mean 83 months). The 2-year local control rates for patients with T1 and T2 lesions were 89% and 80%, respectively. The 2-year local control rate for patients whose overall treatment time was < 50 days was 92% vs. 82% for patients whose overall treatment time was > 50 days (p = 0.07). The 2-year local control rate for patients treated with an irradiated area < 36 cm(2) was 90% compared to 86% in patients who were treated to an area > or = 36 cm(2). The 2-year local control rate for patients treated with 60Co was 83% vs. 92% for patients treated with 6 MV x-ray. Cox proportional hazards regression analysis was performed using the following variables: treatment energy, irradiated area, gender, tobacco pack years, tumor differentiation, overall treatment time, total dose, dose per fraction, and T stage. Overall treatment time (p = 0.05) was the only variable that significantly influenced local control. Extending the overall treatment time was found to adversely influence local control. Neither the irradiated area nor treatment energy was found to influence local control in early stage vocal cord carcinoma.

Survival pattern and cause of death in patients with multiple sclerosis: results from an epidemiological survey in north east Scotland.

The mean survival period in a series of 216 multiple sclerosis deaths, which formed part of a large prevalence sample observed in the Grampian region of Scotland, was 24.5 years, with an insignificant difference between females (25.7 years) and males (23.5 years). A third of the patients survived for over 30 years after onset. The age at death ranged between 25-80 years, with majority of the deaths occurring in the seventh decade (37%). On comparing life expectancy with the Scottish general population using life tables, only a slight reduction in the short-term (less than 10 years from onset) survival was noted in all age groups, with the exception of those with onset over the age of 50 years. The long-term life expectancy was however markedly reduced in all age groups compared with the controls. The survival period could be accurately predicted from the degree of disability at a point in time, and could be correlated with a number of clinical features, the most important of which was the age at onset. Eighty five per cent of those with onset of multiple sclerosis over the age of 50 years died within 20 years. Patients with a cerebellar disturbance at onset survived the shortest, and those with a brainstem lesion or retrobulbar neuritis the longest; those with a pyramidal dysfunction had an intermediate prognosis. Other parameters which could be correlated with the survival were: the timing and frequency of occurrence of psychiatric and urinary symptoms, interval between onset and first relapse and the course of the disease. As expected, most patients (89%) were significantly disabled (unable to walk) prior to death, only a minority, however, had become so within 10 years of the onset (10%). Sixty two per cent of the patients died of complications of multiple sclerosis. No unusual excess of any disease was noted amongst other causes. As expected, the majority of patients (55%) had bronchopneumonia as the terminal event, 11% had septicaemia, 15% had myocardial infarction and 4% had documented pulmonary embolism. This is the largest series of its kind where prognosis, judged by survival period, has been assessed amongst all multiple sclerosis patients derived from a prevalence sample and observed till death.