Lung cancer in Spanish women: The WORLD07 project.

The WORLD07 study was a female-specific database, to prospectively characterise the clinical, histological, molecular and treatment-related features in Spanish women with lung cancer. Data were collected from patients' medical records and patient interviews from October 2007 to December 2012. A total of 2,060 women were analysed: median age, 61.3 years; white, 98.6%; postmenopausal, 80.2%; and no smokers, 55% including never smokers and ex-smokers. A family history of cancer was found in 42.5% of patients, 12.0% of patients had had a previous history of cancer (breast cancer, 39.7%). Most patients (85.8%) were diagnosed of non-small-cell lung cancer (NSCLC), most commonly reported with adenocarcinoma (71.4%), which was stage IV at diagnosis in 57.6%. Median overall survival (OS) for the entire population was 24.0 months, with a 1- and 2-year survival rate of 70.7% and 50.0% respectively. Median OS in patients with small-cell lung cancer was 18.8 months versus 25.0 months in patients with NSCLC (p = 0.011). Lung cancer appears to be a biologically different disease in women. By collecting prospective information about characteristics of women with lung cancer attending university hospitals in Spain, we hope to highlight the need to develop strategies based on gender differences and influence future healthcare policy.

Tobacco smoking as a risk factor of bronchioloalveolar carcinoma of the lung: pooled analysis of seven case-control studies in the International Lung Cancer Consortium (ILCCO).

BACKGROUND: The International Lung Cancer Consortium (ILCCO) was established in 2004, based on the collaboration of research groups leading large molecular epidemiology studies of lung cancer that are ongoing or have been recently completed. This framework offered the opportunity to investigate the role of tobacco smoking in the development of bronchioloalveolar carcinoma (BAC), a rare form of lung cancer. METHODS: Our pooled data comprised seven case-control studies from the United States, with detailed information on tobacco smoking and histology, which contributed 799 cases of BAC and 15,859 controls. We estimated the odds ratio of BAC for tobacco smoking, using never smokers as a referent category, after adjustment for age, sex, race, and study center. RESULTS: The odds ratio of BAC for ever smoking was 2.47 (95% confidence interval [CI] 2.08, 2.93); the risk increased linearly with duration, amount, and cumulative cigarette smoking and persisted long after smoking cessation. The proportion of BAC cases attributable to smoking was 0.47 (95% CI 0.39, 0.54). CONCLUSIONS: This analysis provides a precise estimate of the risk of BAC for tobacco smoking.

Epidemiology of lung cancer in women: risk factors, survival, and screening.

OBJECTIVE: Lung cancer remains the leading cause of cancer mortality in both men and women. Tobacco use causes the vast majority of lung cancer in women but does not explain all cases, because about one in five women who develop lung cancer have never smoked. CONCLUSION: Environmental exposures, genetic predisposition, hormonal factors, and viral infection may all play a role in lung cancer in women. A better understanding may provide an avenue to more effective screening, diagnosis, and therapy.

Detection of Epidermal Growth Factor Receptor (EGFR) Gene Mutation in Formalin Fixed Paraffin Embedded Tissue by Polymerase Chain Reaction-Single Strand Conformational Polymorphism (PCR-SSCP) in Non-Small Cell Lung Cancer in the Northeastern Region of Thailand

Background: The use of targeted specific genes in therapeutic and treatment decisions has been considered for lung cancer. The epidermal growth factor receptor (EGFR) gene, which is over expressed in non-small cell lung cancer (NSCLC), was considered as one of the targeted specific genes. EGFR mutations in exons 18­21, which encode a portion of the EGFR kinase domain, were found in NSCLC patients and were associated with the response of EGFRtyrosine kinase inhibitors (EGFR-TKIs). Therefore, a molecular technique for EGFR mutation detection has important benefits for therapy in NSCLC patients. This study aims to determine the EGFR mutations in patients with NSCLC using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) in exons 18-21. Methods: DNA samples were extracted from formalin fixed paraffin embedded tissues of NSCLC patients who attended hospital. The extracted DNA was used as a template for the EGFR gene amplification. Results: Occurrence of EGFR mutations were found in 29 out of 50 cases (58%).The frequency of EGFR mutations by first PCR at exon 18, 19, 20 and 21 were 6 (12%), 19 (38%) 20 (40%) and at 21 (42%), respectively. By PCR-SSCP, the frequencies of EGFR mutations at exon 18, 19, 20 and 21 were 3(6%), 18(36%), 23(46%) and 13(26%), respectively. All of the mutations found were in agreement with DNA sequencings. Conclusion: The high frequency of EGFR mutations in NSCLC suggests that PCR-SSCP is a efficient screening method and useful for treatment plan.

Paired Phase II Studies of Erlotinib/Bevacizumab for Advanced Bronchioloalveolar Carcinoma or Never Smokers With Advanced Non-Small-cell Lung Cancer: SWOG S0635 and S0636 Trials.

BACKGROUND: Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636). MATERIALS AND METHODS: Eligible patients with BAC or adenocarcinoma with BAC features (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636) received erlotinib 150 mg/day with bevacizumab 15 mg/kg until progression or prohibitive toxicity. Never smokers with BAC were preferentially enrolled to SWOG S0636. The primary endpoint for both trials was overall survival. RESULTS: A total of 84 patients were enrolled in the SWOG S0635 trial and 85 in the SWOG S0636 trial. The objective response rate was 22% (3% complete response) in the SWOG S0635 trial and 50% (38% confirmed; 3% complete response) in the SWOG S0636 trial. The median progression-free survival was 5 and 7.4 months in the S0635 and S0636 trials, respectively. The median overall survival was 21 and 29.8 months, respectively. Toxicity consisted mainly of rash and diarrhea in both trials. CONCLUSION: Although the field has moved toward molecular, rather than clinical, selection of patients as optimal candidates for EGFR TKI therapy, these results support the hypothesis that a subset of patients in whom erlotinib is particularly active could receive an incremental benefit from the addition of bevacizumab.

Epidemiology of bronchioloalveolar carcinoma: improvement in survival after release of the 1999 WHO classification of lung tumors.

PURPOSE: Classification changes for bronchioloalveolar carcinoma (BAC) by the WHO in May 1999 narrowed its definition. This study was undertaken in an attempt to characterize the impact of these changes on the epidemiology of BAC. PATIENTS AND METHODS: This retrospective study involves data analysis from the population-based Cancer Surveillance Programs of three Southern California counties from 1995 to 2003. BAC cases diagnosed after May 1999 are compared with BAC cases before that time by clinicopathologic variables including survival. RESULTS: Incident cases (11,969) of non-small-cell lung cancer (NSCLC) were analyzed, including 626 cases of BAC (5.2%). Median overall survival (OS) for BAC patients diagnosed after May 1999 (> 53 months) was significantly improved over median OS for BAC patients before May 1999 (32 months; P = .012). This survival benefit remained after adjustment for sex, smoking status, and stage at presentation (hazard ratio for time of diagnosis before May 1999 compared with a diagnosis after May 1999 = 1.43; P = .015). Median OS for non-BAC NSCLC patients diagnosed before May 1999 (9 months) did not differ from the median OS of such patients afterwards (10 months; P = .09). CONCLUSION: This epidemiologic study is the first to demonstrate a survival advantage for BAC patients diagnosed after May 1999 compared with BAC patients diagnosed before this time-a finding that persists after adjustment for sex, smoking status, and stage at presentation. We believe that this observed survival benefit likely reflects changes in the revised 1999 WHO classification.

Bronchioloalveolar carcinoma.

PURPOSE: To review bronchioloalveolar carcinoma (BAC). MATERIALS AND METHODS: English language articles were identified through a Melvyl Medline Search (1966 to 1995) and through the bibliographies of selected articles. RESULTS: An increase in BAC appears to be responsible for the observed rise in the incidence of adenocarcinoma of the lung. Patients with BAC tend to be younger at diagnosis, are more likely to be female, and less likely to be cigarette smokers when compared with other patients with non-small-cell lung cancer (NSCLC). The etiology of this disease is unclear, but multiple environmental insults have been implicated. There are three subtypes of BAC and the symptoms and prognosis of the disease depend on the subtype and extent of disease, but are generally similar to other histologic types of NSCLC. The radiographic differential diagnosis is broad and includes both benign and malignant diseases. The treatment approach to patients with BAC is similar to those with other types of NSCLC. CONCLUSION: BAC appears to be increasing in incidence, especially in young, nonsmoking females. Three subtypes of the disease exist and are responsible for the variable clinical presentations. Further epidemiologic investigation is needed to elucidate the etiology and pathogenesis of this unique disease.

Redefining bronchioloalveolar carcinoma.

Bronchioloalveolar carcinoma (BAC) is a subtype of non-small cell lung cancer (NSCLC) with distinct clinical and pathologic features. Although BAC appears to be on a pathologic continuum with adenocarcinoma, the most recent World Health Organization (WHO) classification system has set stringent criteria for the diagnosis. Though malignant, these cancers tend to be peripheral and grow in a lepedic fashion along the alveolar septae without parenchymal invasion. This clear distinction based on histopathology allows for a more definite separation of the natural history and behavior of BAC in clinical studies. Recent clinical trials of molecular targeted anticancer therapies have led to a deeper understanding of the unique features of this cancer and suggest that BAC may require a different therapeutic paradigm from other NSCLCs.

Pathology of human bronchioloalveolar carcinoma and its relationship to the ovine disease.

Lung cancer is a leading cause of cancer with a poor prognosis. Bronchioloalveolar carcinoma (BAC) is a rare tumor that has always intrigued physicians. Since the last World Health Organization classification the pathology has been clarified; BAC per se is an adenocarcinoma with a pure bronchioloalveolar growth pattern and appears as an in situ alveolar adenocarcinoma. More usually BAC is a clinically recognizable entity presenting as multi-focal nodules evolving towards pneumonia associated with pulmonary shunting. Pathology is that of a multifocal mixed adenocarcinoma: bronchioloalveolar and papillar. Whatever the stage, survival is better than in other forms of non-small cell lung cancer (NSCLC). The true frequency of BAC is unknown, although it is a rare form of lung cancer; smoking cannot be excluded as a risk factor. It appears that p53 and ras genes are less often mutated than in other lung adenocarcinomas, suggesting that the cellular mechanisms involved are different. Ovine pulmonary adenocarcinoma (OPA) presents with the same symptoms as BAC in humans and is caused by a betaretrovirus Jaagsiekte sheep retrovirus. Very early on, clinical and histological similarities with human BAC were stressed. A recent series of OPA described, according to the third edition of the WHO classification for human lung cancer, mixed adenocarcinoma, BAC and papillary and/or acinar carcinoma. An immunohistochemical study suggested that some human pulmonary tumors (including BAC) may be associated with a Jaagsiekte sheep retrovirus-related retrovirus,but so far no molecular study has confirmed this observation. Thus, OPA is an exquisite model of carcinogenesis for human lung adenocarcinomas.

Bronchioloalveolar carcinoma in small pulmonary nodules: clinical relevance.

Increased use of chest computed tomography (CT) as well as improvements in CT resolution has led to increased detection of subcentimeter pulmonary nodules. Although the majority of these nodules are benign in etiology, a subset will harbor bronchioloalveolar carcinoma. The diagnosis of malignancy in this setting can be challenging to radiologists, surgeons, and occasionally pathologists as well. The challenge is compounded by a lack of knowledge about the natural course of these lesions--specifically, whether they represent life-threatening aggressive malignancies or indolent lesions of little or no consequence. Given the relative infrequency of these abnormalities, it will be essential to establish a sufficiently large database, to organize multi-institutional registries, and to collaborate on correlative studies. Only in this way will we be able to determine the clinical and molecular characteristics of these lesions and thus hopefully gain insight into their clinical relevance.

Epidemiology of bronchioloalveolar carcinoma.

Descriptive features of bronchioloalveolar carcinoma (BAC) are presented using Surveillance, Epidemiology and End Results Program population-based incidence data from 1973 through 1987, along with risk factors from histologically confirmed cases of BAC identified in a hospital-based case-control study conducted in Louisiana between 1979 and 1982. Compared to the rising incidence of lung cancer overall, BAC rates have remained relatively constant, accounting for less than 3% of all lung cancer. BAC incidence rates were higher in males, yet it explained proportionately more of the total lung cancer incidence in females. In the case-control study, 21 of the 33 cases originally ascertained from hospital pathology records were histologically confirmed as BAC. Most cases smoked cigarettes, with a 4-fold risk for ever smoking. Risks tended to increase with smoking intensity (reaching 10-fold for more than 1.5 packs/day) and duration (reaching 5-fold for more than 45 years of smoking). Following 10 or more years of employment, there was a 4-fold risk associated with motor freight occupations, along with nonsignificant excesses among construction workers, petroleum manufacturers, and sugar cane farmers. Cases were more likely than controls to have had emphysema or to have had a close family member with lung cancer. Although based on small numbers, this study suggests that BAC shares many of the epidemiological characteristics of lung adenocarcinoma.

Alpha1-antitrypsin deficiency allele carriers among lung cancer patients.

Lung cancer (LC) and chronic obstructive pulmonary lung diseases (COPDs; including emphysema and chronic bronchitis) share a common etiology. Despite the known associations of alpha1-antitrypsin deficiency (alpha1AD) with COPD and COPD with LC, few studies examined the association of alpha1AD alleles and LC. We hypothesize that heterozygous individuals who carry a deficient allele of the alpha1AD gene Pi (protease inhibitor locus) are at an increased risk of developing LC. The Pi locus is highly polymorphic with >70 variants reported. There are at least 10 alleles associated with deficiency in alpha1-antitrypsin. Using an exact binomial test, we compared the alpha1AD carrier rate in 260 newly diagnosed Mayo Clinic LC patients to the reported carrier rate in Caucasians in the United States (7%). alpha1AD carrier status, determined by isoelectric focusing assay, was examined with respect to the history of cigarette smoking, COPD, and histological types. Thirty-two of the 260 patients (12.3%; 95% confidence interval, 8.6-16.9%) carried an alpha1AD allele, which was significantly higher than expected (P = 0.002). Twenty-four of the 32 carriers had allele S, 6 had allele Z, and 2 had allele I. Patients who never smoked cigarettes were three times more likely to carry a deficient allele (20.6%; P = 0.008), although smokers had a higher carrier rate (11.1%; P = 0.025) when compared with the 7% rate. Patients with squamous cell or bronchoalveolar carcinoma had a significantly higher carrier rate than expected (15.9% and 23.8%, P < or = 0.01, respectively). Our preliminary findings suggest that individuals who carry an alpha1AD allele may have an increased risk for developing LC, specifically squamous cell or bronchoalveolar carcinoma.

The epidemiology of bronchioloalveolar carcinoma over the past two decades: analysis of the SEER database.

Bronchioloalveolar carcinoma of the lung (BAC) is a subtype of adenocarcinoma of the lung. Although traditionally grouped with other non-small cell lung carcinomas (NSCLC), BAC has unique morphological features and clinical behavior such as bilateral lung involvement, indolent course and lack of association with smoking. Some epidemiologic studies report a significant increase in the incidence of BAC. We used the SEER database to compare the incidence, demographics, and overall survival of BAC patients as compared to other NSCLC types over the past two decades (1979-1998). Although the incidence of BAC has increased over the past two decades, BAC represents less than 4% of all NSCLC in every time period evaluated. The 1 year survival rate is significantly better for BAC patients relative to other histological subtypes of NSCLC. There has not been a marked increase in the incidence of BAC reported to SEER over the past 20 years.

Bronchoalveolar carcinoma: current treatment and future trends.

Bronchoalveolar carcinoma (BAC) is a subtype of non-small-cell lung cancer (NSCLC) with unique clinical and pathologic characteristics. The most recent classification system defines BAC as a primary lung cancer that tends to be peripheral and grow in a lepedic fashion along the alveolar septae without parenchymal invasion. Most of the clinical information on BAC comes from retrospective institutional reviews; however, recent studies have focused more specifically on BAC. In particular, clinical trials of molecular-targeted anticancer therapies against the epidermal growth factor receptor have led to a deeper understanding of the distinct features of this cancer and suggest that BAC may require a therapeutic paradigm different from that of other NSCLCs.

Benign tumors of the lung and bronchus.

Benign tumors of the lung and bronchus are a heterogeneous group of lesions that usually present as asymptomatic, solitary, peripheral lung nodules or, less commonly, as endobronchial lesions causing obstructive symptoms. All endobronchial lesions should be removed surgically to alleviate symptoms and to prevent destruction of distal lung tissue. Parenchymal lesions may present challenging problems in clinical diagnosis and management. Most patients will ultimately require thoracotomy for histologic confirmation of benignity. It is probable that newer diagnostic procedures will allow a more accurate nonoperative diagnosis in certain patients in the near future. At the present time, expeditious limited thoracotomy affords a safe, rapid, and effective treatment for patients with a benign tumor of the lung or bronchus.

Time trend in the surgical management of patients with lung carcinoma.

OBJECTIVE: The goal of the study was to analyze the histological and clinical trends in lung carcinoma and their influence upon the preoperative evaluation, surgical procedures and survival. METHODS: We retrospectively reviewed the charts of 1079 consecutive patients who underwent surgery for primary lung carcinoma between 1977 and 1996 in our institution. Patients were divided into five equal 4-year periods according to the year of surgery (1977-1980; 1981-1984; 1985-1988; 1989-1992; 1993-1996). RESULTS: Between 1977-1980 and 1993-1996, the incidence of squamous cell carcinoma significantly declined, whereas the incidence of adenocarcinoma and bronchioloalveolar carcinoma increased. During the same period, the proportion of squamous cell carcinoma visualized at bronchoscopy and the rate of preoperative histological diagnosis significantly decreased. An increasing proportion of lobectomy and less extended resection was associated with an increasing number of patients with stage I carcinoma. Meanwhile, the operative mortality significantly declined from 9 to 4% and the 5-year survival improved from 25 up to 40%. CONCLUSION: Over the last two decades, the shift in histological distribution was associated with an increasing proportion of patients with stage I disease, a lower operative mortality and a better 5-year survival.

[Bronchioalveolar carcinoma]. / Das bronchioalveoläre Karzinom.

A study of 21 patients suffering from bronchioalveolar carcinoma and 1028 comparable cases of the literature is presented. By this we gained statistical data concerning radiological and clinical manifestations of this rare tumour. However, radiological signs estimated to be typical of this carcinoma, like "rabbit ear sign" and positive "air bronchogram" are too rare to be really helpful for putting up the diagnosis. At time of diagnosis the mean age was 58 years. Men are hardly more frequently concerned than women. Smoking seems to have no aetiological significance. The most common clinical symptom was chronic cough followed by chest pain. A large amount of sputum--a symptom which sometimes has been estimated to be typical of this tumour--occurred only very rarely.

Combined bilateral lung resections and off-pump coronary artery bypass grafting.

We report herein a 74 year old man with angina who had an abnormal chest roentgenogram. Computed tomography of the chest showed a solitary 1.0-cm peripheral, noncalcified lesion in the apical segment of the left lower lobe and a 1.5-cm peripheral lesion in the posterior basal segment of the right lower lobe. Coronary angiography revealed the left anterior descending coronary artery to have a long 90% stenosis. We report here a case of a combined bilateral lung resection and off-pump coronary surgery though a midline sternotomy in a compromised lung function patient with both severe coronary artery disease and bilateral synchronous primary lung cancer.

A clinical statistical analysis of 4,931 lung cancer cases in Japan according to histological type--field study results. A report from the Japanese Joint Committee of Lung Cancer Associated with the TNM System of Clinical Classification (UICC).

From records of 4,931 cases of lung cancer during the period 1975-1977, a clinical statistical analysis according to histological type was performed. Epidermoid carcinoma accounted for 46.6% of male cases and 18.8% of female cases, while adenocarcinoma was the histological type in 61.2% of female cases and 30.3% of male cases. Five-year survival rates were 14.4%, 14.4%, 11.9%, 5.4% and 1.3% for epidermoid carcinoma, adenocarcinoma, large cell carcinoma, and small cell carcinoma of the intermediate cell type and oat cell type, respectively. Of the adenocarcinoma cases, 32.9% were in Stage Ia, and 52.1% showed overall operability and 43.0% curative operability. For small cell carcinoma of the intermediate cell type and oat cell type, 75% and 79% of cases were in Stages III and IV, respectively. The operability of oat cell carcinoma was 15.2%; 72.2% underwent radiation, and 84.8% underwent chemotherapy.

[Clinical data and descriptive epidemiology of primary bronchial cancer. 9 years of activity of the Isère Registry]. / Données cliniques et épidémiologie descriptive du cancer bronchique primitif. Neuf années d'activité du Registre de l'Isère.

Systematical registration of morbidity for lung carcinoma of the primary type was performed since January 1979 for the department of Isere, where a population of 940,000 inhabitants are living. Results for nine years registration (1979-1987) are dealing with 2,590 new cases. Crude incidence for primary lung carcinoma is 55.7 per 100,000 among men, and 5.9 for women (sex ratio: 11.7). Upper lobe is the site more concerned. There is no preference as regard laterality. When lymphatic nodes are explored (32%), there is an extension of the carcinoma for 75.2% of them. At the moment of the diagnostic, there is already a metastasis for 24% of the patients, mainly for bones. Among men and women, proportions for the squamous cell type are respectively 52.6% and 22.3% (60.8% and 28.7% of histologically identified cases), for the small cell type: 18.4% and 16.3% (21.2% and 21.0% of histologically identified cases), and for glandular carcinomas: 13.2% and 32.1% (11.9% and 41.5% of histologically identified cases). Results of the pathological examination are known in 92.8% for primary lung carcinoma cases. As regard first course treatment, surgery is performed in 34.9% of the cases, radiotherapy in 60.4%, and chemotherapy in 32.2%. Fairly high incidence of lung carcinoma in man in Isere, contrasts with rather low incidence in woman, a situation rather different that the one in England and North America, where figures for women are slowly gaining over the one's for men.