Associations of high-grade glioma with glioma risk alleles and histories of allergy and smoking.

Glioma risk has consistently been inversely associated with allergy history but not with smoking history despite putative biologic plausibility. Data from 855 high-grade glioma cases and 1,160 controls from 4 geographic regions of the United States during 1997-2008 were analyzed for interactions between allergy and smoking histories and inherited variants in 5 established glioma risk regions: 5p15.3 (TERT), 8q24.21 (CCDC26/MLZE), 9p21.3 (CDKN2B), 11q23.3 (PHLDB1/DDX6), and 20q13.3 (RTEL1). The inverse relation between allergy and glioma was stronger among those who did not (odds ratio(allergy-glioma) = 0.40, 95% confidence interval: 0.28, 0.58) versus those who did (odds ratio(allergy-glioma) = 0.76, 95% confidence interval: 0.59, 0.97; P(interaction) = 0.02) carry the 9p21.3 risk allele. However, the inverse association with allergy was stronger among those who carried (odds ratio(allergy-glioma) = 0.44, 95% confidence interval: 0.29, 0.68) versus those who did not carry (odds ratio(allergy-glioma) = 0.68, 95% confidence interval: 0.54, 0.86) the 20q13.3 glioma risk allele, but this interaction was not statistically significant (P = 0.14). No relation was observed between glioma risk and smoking (odds ratio = 0.92, 95% confidence interval: 0.77, 1.10; P = 0.37), and there were no interactions for glioma risk of smoking history with any of the risk alleles. The authors' observations are consistent with a recent report that the inherited glioma risk variants in chromosome regions 9p21.3 and 20q13.3 may modify the inverse association of allergy and glioma.

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.

Timing of chronic obstructive pulmonary disease diagnosis in lung cancer prognosis: a clinical and genomic-based study.

BACKGROUND: A two-phase study (clinical and genomic-based) was conducted to evaluate the effect of timing of chronic obstructive pulmonary disease (COPD) diagnosis on lung cancer outcomes. METHODS: The prognostic influence of COPD was investigated in a clinical cohort of 1,986 patients who received surgery for stage I lung cancer; 823 (41.4%) of them also had COPD, including 549 (27.6%) incidental COPD (diagnosed within 6-months of lung cancer diagnosis) and 274 (13.8%) prior COPD (>6 months before lung cancer diagnosis). The genomic variations were analyzed from another cohort of 1,549 patients for association with 384 lung cancer-related single nucleotide polymorphisms (SNPs). RESULTS: Older age (≥70 years), smokers, and respiratory symptoms were independent predictors of incidental COPD in lung cancer (all P<0.05). Similar to prior COPD, incidental COPD increased postoperative complications and worsened quality-of-life related to dyspnea (both P<0.05). Multivariate Cox regression analysis showed lung cancer survival decreased significantly in incidental COPD (HR, 1.30; 95% CI, 1.02-1.66), but not in prior COPD (HR, 1.15; 95% CI, 0.87-1.52). Among prior COPD, median survival showed a trend for being better in those with fewer exacerbations (0-1 vs. ≥2 exacerbation/year; 6.1 vs. 4.1 years; P=0.10). The SNP-based analysis identified ADCY2:rs52827085 was significantly associated with risk of incidental COPD (OR, 1.76; 95% CI, 1.30-2.38) and NRXN1:rs1356888 associated with prior COPD complicated with lung cancer (OR, 1.73; 95% CI, 1.29-2.33). CONCLUSIONS: Different long-term survival and genomic variants were observed between lung cancer patients with incidental and with prior COPD, suggesting timing of COPD diagnosis should be considered in lung cancer clinical management and mechanistic research.

Sarcomatoid Carcinoma of the Lung: The Mayo Clinic Experience in 127 Patients.

BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is an unusual form of non-small-cell lung cancer (NSCLC). Because of its rarity and heterogeneity, the treatment and prognosis of PSC have not been clearly described. METHODS AND MATERIALS: We retrospectively evaluated all patients with a diagnosis of PSC from 1997 to 2015 at the Mayo Clinic (Rochester, MN). The clinical characteristics, treatment details, and outcomes were collected. The survival rates of the PSC patients were compared with those for other subtypes of NSCLC. We used propensity score matching to minimize the bias resulting from to imbalanced comparison groups. RESULTS: The study included 127 PSC patients. The median age at diagnosis was 68 years (range, 32-89 years), most of whom were men (61%) and smokers (82%). The clinical stage was I, II, III, and IV in 15.9%, 20.6%, 22.2%, and 41.3%, respectively. The median survival time was 9.9 months (95% confidence interval [CI], 7.6-12.6 months). The 1-, 2-, and 5-year survival rates were 42%, 23%, and 15%, respectively. Most patients received multimodality treatment. Of the 3 patients who received neoadjuvant chemotherapy, a partial response was demonstrated in 2. Twenty-five patients who underwent palliative chemotherapy were evaluated for tumor response: 52% experienced progression, 40% stable disease, 8.0% a partial response, and 0% a complete response. Multivariate analysis showed T stage, M stage, and treatment with surgery plus neoadjuvant chemotherapy or surgery plus adjuvant therapy were independent prognostic factors (P < .05). In matched analysis, multivariate models revealed worse overall survival for PSC compared with adenocarcinoma (hazard ratio, 2.38; 95% CI, 1.61-2.53) and squamous cell carcinoma (hazard ratio, 2.20; 95% CI, 1.44-2.34). CONCLUSION: We found the outcome of PSC to be significantly worse than that of adenocarcinoma and squamous cell carcinoma. Neoadjuvant or adjuvant chemotherapy, in addition to surgical resection, should be considered.

T category of non-small cell lung cancer invading the fissure to the adjacent lobe.

BACKGROUND: Dispute arises in the tumor category of non-small cell lung cancer invading the fissure to the adjacent lobe. The purpose of this study is to determine the long-term prognosis of non-small cell lung cancer with such an invasion and to propose an appropriate T category. METHODS: In total, 53 cases of non-small cell lung cancer invading the fissure to the adjacent lobe (fissure group) were identified in patients who underwent pulmonary resection from 1997 to 2014. Propensity score matching was applied to balance known confounders for prognosis between each paired group, resulting in 3 matched sets (fissure vs T2a, fissure vs T2b, and fissure vs T3). The overall survival of the fissure group was compared with the survival of patients with T2a, T2b, and T3 diseases, as classified in the eighth edition of TNM classification. RESULTS: The 5-year survivals of the T2a, T2b, T3, and fissure groups were 64.2% (95% confidence interval, 53.2-72.6), 54.6% (95% confidence interval, 44.7-65.8), 35.8% (95% confidence interval, 22.8-44.2), and 38.6% (95% confidence interval, 25.0-52.2), respectively. Specifically, the difference between the fissure group and T2a is statistically significant at P = .01; between the fissure group and T2b at P = .02; and between the fissure group and T3 at P = .93. Multivariate analyses indicate that the fissure group had a similar risk of dying as the T3 disease group (hazard ratio, 1.10; 95% confidence interval, 0.69-1.37) and was at a significantly higher risk compared with the T2a group (hazard ratio, 2.34; 95% confidence interval, 1.50-3.39) and T2b group (hazard ratio, 1.71; 95% confidence interval, 1.19-2.76). CONCLUSIONS: On the basis of our single-institution study, we propose that non-small cell lung cancer invading the fissure to the adjacent lobe should be further investigated and the impact on patients' prognoses validated as a T3 disease.

Regional Emphysema Score Predicting Overall Survival, Quality of Life, and Pulmonary Function Recovery in Early-Stage Lung Cancer Patients.

INTRODUCTION: Pulmonary emphysema is a frequent comorbidity in lung cancer, but its role in tumor prognosis remains obscure. Our aim was to evaluate the impact of the regional emphysema score (RES) on a patient's overall survival, quality of life (QOL), and recovery of pulmonary function in stage I to II lung cancer. METHODS: Between 1997 and 2009, a total of 1073 patients were identified and divided into two surgical groups-cancer in the emphysematous (group 1 [n = 565]) and nonemphysematous (group 2 [n = 435]) regions-and one nonsurgical group (group 3 [n = 73]). RES was derived from the emphysematous region and categorized as mild (≤5%), moderate (6%-24%), or severe (25%-60%). RESULTS: In group 1, patients with a moderate or severe RES experienced slight decreases in postoperative forced expiratory volume in 1 second, but increases in the ratio of forced expiratory volume in 1 second to forced vital capacity compared with those with a mild RES (p < 0.01); however, this correlation was not observed in group 2. Posttreatment QOL was lower in patients with higher RESs in all groups, mainly owing to dyspnea (p < 0.05). Cox regression analysis revealed that patients with a higher RES had significantly poorer survival in both surgical groups, with adjusted hazard ratios of 1.41 and 1.43 for a moderate RES and 1.63 and 2.04 for a severe RES, respectively; however, this association was insignificant in the nonsurgical group (adjusted hazard ratio of 0.99 for a moderate or severe RES). CONCLUSIONS: In surgically treated patients with cancer in the emphysematous region, RES is associated with postoperative changes in lung function. RES is also predictive of posttreatment QOL related to dyspnea in early-stage lung cancer. In both surgical groups, RES is an independent predictor of survival.

Chest wall resection for non-small cell lung cancer: A case-matched study of postoperative pulmonary function and quality of life.

BACKGROUND: To assess the pulmonary function and quality of life (QOL) after chest wall resection for non-small cell lung cancer. MATERIAL AND METHODS: One hundred and thirty-five patients (cases) who underwent pulmonary resection with chest wall removal were identified from January 1997 to December 2015. Propensity score matching (1:3) was applied to balance known confounders for pulmonary function and QOL between the cases and the control group who underwent pulmonary resection without chest wall invasion. Matched analyses were performed to compare perioperative mortality and morbidity, postoperative pulmonary function, overall QOL, and specific symptoms. RESULTS: Perioperative mortality and morbidity did not differ significantly between cases and controls, but the hospital stay was longer in cases than in controls (mean, 12.8 vs 8.9days; p<0.001), The decline of postoperative pulmonary forced vital capacity (FVC) and the percentage of predicted FVC (FVC%) was more obvious in cases than in controls at 6 months and 2 years after surgery, but there was no obvious decline in the forced expiratory volume in one second (FEV1), the percentage of predicted FEV1 (FEV1%), the diffusion capacity of the lung for carbon monoxide (DLCO) and the percentage of predicted DLCO (DLCO%) in cases compared with controls. No significant difference was observed between the two groups in scores for overall QOL, pain, fatigue, cough, dyspnea, appetite, hemoptysis, lung cancer symptoms, and normal activities. CONCLUSIONS: When chest wall resection is inevitable, it does not worse the QOL and pulmonary function of patients who underwent pulmonary resection with chest wall removal obviously compared with patients underwent pulmonary resection without chest wall invasion.

Metformin use and young age lung cancer: A case series report.

Metformin, a widely-prescribed antihyperglycemic drug for the treatment of diabetes mellitus type 2 (DM-II), has been demonstrated to be antineoplastic in vivo and in vitro. However, various preclinical and epidemiological studies investigating the effects of metformin on lung cancer have obtained inconclusive results. The aim of the present study was to retrospectively investigate the effects of metformin, for the treatment of diabetes mellitus type 2 (DM-II), on the onset of lung cancer. In the present study, the pathological features of ten consecutive young age lung cancer cases, aged between 15 and 45 years old at the time of diagnosis and exhibiting existing primary DM, were investigated using the Mayo Clinic Lung Cancer Cohort database. Amongst this cohort, there were 2 cases of DM type 1 (DM-I) and 8 cases of DM-II. Of these patients, two exhibiting adenocarcinoma and DM-II had not been administered metformin; however, 1 patient exhibiting lymphoma and 4 patients with pulmonary neuroendocrine tumors (NETs) had been administered metformin at least 12 months prior to lung cancer diagnosis. The remaining 3 patients exhibiting NETs and DM-II had been treated with insulin therapy. The present study hypothesized that the high proportion of NETs observed in the cases of metformin-treated DM-II was unlikely to be a random event. It was suggested that metformin treatment was not effective in the prevention of pulmonary NETs, and that metformin may instead induce the occurrence of NETs via as yet unknown signaling pathways. The present hypothesis may potentially serve as a novel indicator for the requirement to monitor young patients with diabetes, who are being treated with metformin, for the occurrence of pulmonary NETs.

Trends in Subpopulations at High Risk for Lung Cancer.

INTRODUCTION: Two-thirds of patients in the United States with newly diagnosed lung cancer would not meet the current U.S. Preventive Services Task Force (USPSTF) screening criteria, which suggests a need for amendment of the definition of high risk. To provide evidence of additional high-risk subpopulations and estimated gains and losses from using different criteria for screening eligibility, we conducted a two-step study using three cohorts. METHODS: The two prospective cohorts comprised 5988 patients in whom primary lung cancer was diagnosed between 1997 and 2011 (the hospital cohort) and 850 defined-community residents (the community cohort); the retrospective cohort consisted of the population of Olmsted County, Minnesota, which was observed for 28 years (1984-2011). Subgroups of patients with lung cancer who might have been identified using additional determinates were estimated and compared between the community and hospital cohorts. The findings were supported by indirect comparative projections of two ratios: benefit to harm and cost to effectiveness. RESULTS: Former cigarette smokers who had a smoking history of 30 or more pack-years and 15 to 30 quit-years and were 55 to 80 years old formed the largest subgroup not meeting the current screening criteria; they constituted 12% of the hospital cohort and 17% of community cohort. Using the expanded criteria suggested by our study may add 19% more CT examinations for detecting 16% more cases when compared with the USPSTF criteria. Meanwhile, the increases in false-positive results, overdiagnosis, and radiation-related lung cancer deaths are 0.6%, 0.1%, and 4.0%, respectively. CONCLUSIONS: Current USPSTF screening criteria exclude many patients who are at high risk for development of lung cancer. Including individuals who are younger than 81 years, have a smoking history of 30 or more pack-years, and have quit for 15 to 30 years may significantly increase the number of cases of non-overdiagnosed screen-detected lung cancer, does not significantly add to the number of false-positive cases, and saves more lives with an acceptable amount of elevated exposure to radiation and cost.

Receptivity and Preferences for Lifestyle Programs to Reduce Cancer Risk among Lung Cancer Family Members.

BACKGROUND: Lifestyle factors and genetic information has been found to contribute to the occurrence of lung cancer. This study assessed receptivity to participating in lifestyle programs to reduce cancer risk among unaffected lung cancer family members. We also explored demographic, medical, and psychosocial correlates of willingness to participate in lifestyle programs. METHODS: Family members who are part of a lung Cancer Family Registry were asked to fill out a survey assessing their receptivity to cancer risk reduction programs including preferences for an individual or family-based program. RESULTS: Of the 583 respondents, 85% were "Somewhat" or "Definitely" willing to participate in a lifestyle program. Among those receptive, about half (56%) preferred a family-based approach. Preferred programs included weight management (36%) and nutritional information (30%). Preferred delivery channels were Internet (45%) and mail-based (29%) programs. On multivariate analysis, those definitely/somewhat receptive reported greater exercise self-efficacy scores (p=0.025). CONCLUSION: The majority of the sample was receptive to lifestyle programs that might decrease cancer risk. There was a large preference for family-based weight management and nutritional programs. Further research is indicated to determine how to best incorporate a family-based approach to lifestyle programs for cancer family members.

Clinical outcomes and changes in lung function after segmentectomy versus lobectomy for lung cancer cases.

OBJECTIVE: We compared the clinical outcomes and changes in pulmonary function test (PFT) results after segmentectomy or lobectomy for non-small cell lung cancer. METHODS: The retrospective study included 212 patients who had undergone segmentectomy (group S) and 2336 patients who had undergone lobectomy (group L) from 1997 to 2012. The follow-up and medical record data were collected. We used all the longitudinal PFT data within 24 months postoperatively and performed linear mixed modeling. We analyzed the 5-year overall and disease-free survival in stage IA patients. We used propensity score case matching to minimize the bias due to imbalanced group comparisons. RESULTS: During the perioperative period, 1 death (0.4%) in group S and 7 (0.3%) in group L occurred. The hospital stay for the 2 groups was similar (median, 5.0 vs 5.0 days; range, 2-99 vs 2-58). The mean overall and disease-free survival period of those with T1a after segmentectomy or lobectomy seemed to be similar (4.2 vs 4.5 years, P=.06; and 4.1 vs 4.4 years, P=.07, respectively). Compared with segmentectomy, lobectomy yielded marginally significantly better overall (4.4 vs 3.9 years, P=.05) and disease-free (4.1 vs 3.6 years; P=.05) survival in those with T1b. We did not find a significantly different effect on the PFTs after segmentectomy or lobectomy. CONCLUSIONS: Both surgical types were safe. We would advocate lobectomy for patients with stage IA disease, especially those with T1b. A retrospective study with a large sample size and more detailed information should be conducted for PFT evaluation, with additional stratification by lobe and laterality.

Network-based approach identified cell cycle genes as predictor of overall survival in lung adenocarcinoma patients.

Lung adenocarcinoma is the most common type of primary lung cancer. The purpose of this study was to delineate gene expression patterns for survival prediction in lung adenocarcinoma. Gene expression profiles of 82 (discovery set) and 442 (validation set 1) lung adenocarcinoma tumor tissues were analyzed using a systems biology-based network approach. We also examined the expression profiles of 78 adjacent normal lung tissues from 82 patients. We found a significant correlation of an expression module with overall survival (adjusted hazard ratio or HR=1.71; 95% CI=1.06-2.74 in discovery set; adjusted HR=1.26; 95% CI=1.08-1.49 in validation set 1). This expression module contained genes enriched in the biological process of the cell cycle. Interestingly, the cell cycle gene module and overall survival association were also significant in normal lung tissues (adjusted HR=1.91; 95% CI, 1.32-2.75). From these survival-related modules, we further defined three hub genes (UBE2C, TPX2, and MELK) whose expression-based risk indices were more strongly associated with poor 5-year survival (HR=3.85, 95% CI=1.34-11.05 in discovery set; HR=1.72, 95% CI=1.21-2.46 in validation set 1; and HR=3.35, 95% CI=1.08-10.04 in normal lung set). The 3-gene prognostic result was further validated using 92 adenocarcinoma tumor samples (validation set 2); patients with a high-risk gene signature have a 1.52-fold increased risk (95% CI, 1.02-2.24) of death than patients with a low-risk gene signature. These results suggest that a network-based approach may facilitate discovery of key genes that are closely linked to survival in patients with lung adenocarcinoma.

Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma.

INTRODUCTION: The EML4-anaplastic lymphoma kinase (ALK) translocation is a recognized oncogenic driver in non-small cell lung cancer. We investigated immunohistochemistry (IHC) screening with fluorescence in situ hybridization (FISH) confirmation for ALK detection and estimated the prevalence of ALK positivity in our patient cohort of never-smokers, together with differences in clinical outcomes and prognostic factors for patients with ALK-positive and ALK-negative tumors. METHODS: We designed a three-phase study (training, validation, and testing) in 300 never-smokers with lung adenocarcinoma from the observational Mayo Clinic Lung Cancer Cohort. Tumor samples were tested using IHC and FISH, and concordance between the methods was assessed. Clinical outcomes were assessed via 5-year progression- or recurrence-free survival from diagnosis. Prognostic factors for ALK-positive tumors and metastases were also investigated. RESULTS: ALK-positive patients were significantly (p < 0.05) younger and had higher grade tumors than ALK-negative patients. ALK positivity was 12.2% by IHC and confirmed at 8.2% of tumors by FISH, with complete concordance between IHC 3+/0 and FISH+/- assessments, respectively. Five-year risk of progression or recurrence was doubled for patients with ALK-positive compared with ALK-negative tumors; ALK-positive tumors also appeared to be associated with a higher risk of brain and liver metastases. CONCLUSIONS: Our findings suggest that ALK positivity is associated with a significantly poor outcome in nonsmoking-related adenocarcinoma and that ALK-positive tumors may be associated with an increased risk of brain and liver metastases compared with ALK-negative disease. Consequently, an unmet medical need exists in ALK-positive lung cancer patients, and effective ALK-specific therapies are needed.

Correlation of IHC and FISH for ALK gene rearrangement in non-small cell lung carcinoma: IHC score algorithm for FISH.

INTRODUCTION: Accurate, cost-effective methods for testing anaplastic lymphoma kinase gene rearrangement (ALK+) are needed to select patients with non-small cell lung carcinoma for ALK-inhibitor therapy. Fluorescent in situ hybridization (FISH) is used to detect ALK+, but it is expensive and not routinely available. We explored the potential of an immunohistochemistry (IHC) scoring system as an affordable, accessible approach. METHODS: One hundred one samples were obtained from an enriched cohort of never-smokers with adenocarcinoma from the Mayo Clinic Lung Cancer Cohort. IHC was performed using the ALK1 monoclonal antibody with ADVANCE detection system (Dako) and FISH with dual-color, break-apart probe (Abbott Molecular) on formalin-fixed, paraffin-embedded tissue. RESULTS: Cases were assessed as IHC score 0 (no staining; n = 69), 1+ (faint cytoplasmic staining, n = 21), 2+ (moderate, smooth cytoplasmic staining; n = 3), or 3+ (intense, granular cytoplasmic staining in ≥10% of tumor cells; n = 8). All IHC 3+ cases were FISH+, whereas 1 of 3 IHC 2+ and 1 of 21 IHC 1+ cases were FISH+. All 69 IHC 0 cases were FISH-. Considering FISH a gold-standard reference in this study, sensitivity and specificity of IHC were 90 and 97.8%, respectively, when 2+ and 3+ were regarded as IHC positive and 0 and 1+ as IHC negative. CONCLUSIONS: IHC scoring correlates with FISH and may be a useful algorithm in testing ALK+ by FISH in non-small cell lung carcinoma, similar to human epidermal growth factor-2 testing in breast cancer. Further study is needed to validate this approach.

Effect of emphysema on lung cancer risk in smokers: a computed tomography-based assessment.

The contribution of emphysema to lung cancer risk has been recognized, but the effect size needs to be further defined. In this study, 565 primary lung cancer cases were enrolled though a prospective lung cancer cohort at Mayo Clinic, and 450 controls were smokers participating in a lung cancer screening study in the same institution using spiral computed tomography (CT). Cases and controls were frequency matched on age, gender, race, smoking status, and residential region. CT imaging using standard protocol at the time of lung cancer diagnosis (case) or during the study (control) was assessed for emphysema by visual scoring CT analysis as a percentage of lung tissue destroyed. The clinical definition of emphysema was the diagnosis recorded in the medical documentation. Using multiple logistic regression models, emphysema (≥ 5% on CT) was found to be associated with a 3.8-fold increased lung cancer risk in Caucasians, with higher risk in subgroups of younger (<65 years old, OR = 4.64), heavy smokers (≥ 40 pack-years, OR = 4.46), and small-cell lung cancer (OR = 5.62). When using >0% or ≥ 10% emphysema on CT, lung cancer risk was 2.79-fold or 3.33-fold higher than controls. Compared with CT evaluation (using criterion ≥ 5%), the sensitivity, specificity, positive and negative predictive values, and the accuracy of the clinical diagnosis for emphysema in controls were 19%, 98%, 73%, 84%, and 83%, respectively. These results imply that an accurate evaluation of emphysema could help reliably identify individuals at greater risk of lung cancer among smokers.

Clinical features of bronchioloalveolar carcinoma with new histologic and staging definitions.

INTRODUCTION: To assess clinical features of bronchioloalveolar carcinoma (BAC) based on the 1999 World Health Organization Classification ("pure BAC"), compare patients with pure BAC with patients previously diagnosed as BAC not meeting the 1999 definition, and compare survival changes of pure BAC based on the old and new (2009) staging systems. METHODS: A pulmonary pathologist reviewed each BAC tumor diagnosed between January 1, 1997, and December 31, 2007, identifying cases meeting the new criteria. Cases were restaged according to the seventh edition of the tumor, node, metastasis classification introduced in 2009. Patients with pure BAC were analyzed under both staging systems for changes in overall survival estimation. RESULTS: Of 338 total patients who were diagnosed with BAC, 117 were classified as pure and 221 were non-pure BAC. Seventy-eight of the 117 and 178 of the 221 had no other primary lung cancer. One-year and 5-year survival for the 78 patients with pure BAC were 94.8 and 83.5%, and for the 178 patients were 92.6 and 46.4%, respectively. Restaging for pure BAC cases resulted in nine of the 78 cases (12%) changing stage. Compared with the old staging, patients with advanced stage under the new stage had a worse 5-year survival (53% versus 45%), but no change was observed for stage IA. CONCLUSIONS: For patients with pure BAC, the new pathologic system favorably affects survival and the new staging system may more accurately reflect prognosis in advanced stage cancer. Our results have important implications for researchers, clinicians, and patients.

Prognostic factors for limited-stage small cell lung cancer: a study of 284 patients.

Combined modality therapy is the standard care for limited stage-small cell lung cancer (LS-SCLC) and has led to a significant improvement in patients' survival. This study sought to investigate and define the importance of prognostic effects of known and controversial factors especially the impact of smoking status and treatment strategies. A total of 284 patients with LS-SCLC were diagnosed and prospectively followed from 1997 to 2008 at Mayo Clinic; their characteristics and survival outcome were assessed on the basis of age, gender, smoking history, performance status (PS), tumor recurrence or progression, and treatment using Cox proportional hazards models. Our main results are as follows: (1) Although neither smoking status (former or current smokers) nor intensity (pack-years smoked) at the time of SCLC diagnosis were significant survival predictors, compared to continued smokers (who never quit smoking), patients who quit at or after diagnosis cut the risk of death by 45% (HR=0.55, 95% CI 0.38-0.79); patients who quit before lung cancer diagnosis also experienced survival benefit (HR=0.72, 95% CI 0.52-1.00). (2) Thoracic radiotherapy and platinum-based chemotherapy could significantly improve survival but the timing (within or after one month of diagnosis) of starting chemotherapy or radiation therapy did not. (3) After adjusting for other known factors, a lower PS did not predict poorer survival, suggesting that PS should not be the only factor for making treatment decisions. In conclusion, this study demonstrated the negative impact of continued cigarette smoking on survival; therefore, clinicians and all care providers should strongly encourage smoking cessation at diagnosis of LS-SCLC.