Objective: To evaluate the prevalence of anorexia and weight loss at diagnosis (pre-treatment), to identify the factors associated with pre-treatment weight loss, and to determine the prognostic role of anorexia and weight loss in the overall survival of patients with stage IV lung cancer. Methods: This was a retrospective observational cohort study. The patients were stratified by the presence/absence of anorexia and of pre-treatment weight loss, which generated a measure composed of four categories, which were the independent variables. Results: Among the 552 patients included in the study, anorexia and pre-treatment weight loss were present in 39.1% and 70.1%, respectively. After adjusting for age, male gender, and Karnofsky performance status, we found that anorexia and tumor size were significantly associated with pre-treatment weight loss. In a Cox multivariate analysis, adjusted for age, male gender and low Karnofsky performance status were found to be independent predictors of worse survival, as was concomitance of anorexia and weight loss. Conclusions: Anorexia and pre-treatment weight loss appear to be relevant problems in the follow-up of patients with advanced (stage IV) lung cancer Specific interventions are of crucial importance in individualized treatment plans, even within the context of palliative care.

Keywords: Lung neoplasms; Anorexia; Weight loss; Neoplasms/mortality.

Objective: To evaluate different weight loss (WL) cut-off points as prognostic markers of 3-month survival after diagnosis of stage IV non-small cell lung cancer (NSCLC). Methods: This was a prospective study involving 104 patients with metastatic (stage IV) NSCLC who were admitted to a cancer treatment center in southern Brazil between January of 2014 and November of 2016. We evaluated total WL and WL per month, as well as WL and WL per month in the 6 months preceding the diagnosis. The patients were followed for 3 months after diagnosis. A Cox proportional hazards regression model and Kaplan-Meier curves were used in order to evaluate 3-month survival. Results: The median WL in the 6 months preceding the diagnosis was 6% (interquartile range, 0.0- 12.9%). Patients with WL ≥ 5% had a median survival of 78 days, compared with 85 days for those with WL < 5% (p = 0.047). Survival at 3 months was 72% for the patients with WL ≥ 5% (p = 0.047), 61% for those with WL ≥ 10% (p < 0.001), and 45% for those with WL ≥ 15% (p < 0.001). In the multivariate analysis, the hazard ratio for risk of death was 4.51 (95% CI: 1.32-15.39) for the patients with WL ≥ 5%, 6.34 (95% CI: 2.31-17.40) for those with WL ≥ 10%, and 14.17 (95% CI: 5.06-39.65) for those with WL ≥ 15%. Conclusions: WL in the 6 months preceding the diagnosis of NSCLC is a relevant prognostic factor and appears to be directly proportional to the rate of survival at 3 months.

Keywords: Weight loss; Carcinoma, non-small-cell lung; Prognosis.

Objective: To determine the demographic and clinical characteristics of patients with non-small cell lung cancer (NSCLC), as well as their disease course, by age group and gender. Methods: This was a retrospective cohort study of patients diagnosed with NSCLC from 2000 to 2012 and followed until July 2015 in a tertiary referral hospital in the city of São Paulo, Brazil. Based on the 25th and 75th percentiles of the age distribution, patients were stratified into three age groups: < 55 years; ≥ 55 and < 72 years; and ≥ 72 years. Survival time was evaluated during the follow-up period of the study. Functions of overall and gender-specific survival stratified by age groups (event: all-cause mortality) were calculated using the Kaplan-Meier method. Differences among survival curves were assessed via the log-rank test. Results: We included 790 patients with the following age distribution: < 55 years, 165 patients; ≥ 55 and < 72 years, 423; and ≥ 72 years, 202. In the entire sample, there were 493 men (62.4%). Adenocarcinoma was the most common histological pattern in the < 72-year age groups; 575 patients (73%) presented with advanced disease (stages IIIB-IV). The median 5-year survival was 12 months (95% CI: 4-46 months), with no significant differences among the age groups studied. Conclusions: NSCLC remains more common in men, although we found an increase in the proportion of the disease in women in the < 55-year age group. Adenocarcinoma predominated in women. In men, squamous cell carcinoma predominated in the ≥ 72-year age group. Most patients presented with advanced-stage disease at diagnosis. There were no statistical differences in survival between genders or among age groups.

Keywords: Lung neoplasms; Age groups, Sex; Survival.

Objective: Bone disease is a common comorbidity in patients with cystic fibrosis (CF). We sought to determine risk factors and identify potential biochemical markers for CF-related bone disease (CFBD) in a unique cohort of CF patients with end-stage lung disease undergoing lung transplantation (LTx) evaluation. Methods: All of the CF patients who were evaluated for LTx at our center between November of 1992 and December of 2010 were included in the study. Clinical data and biochemical markers of bone turnover, as well as bone mineral density (BMD) at the lumbar spine and femoral neck, were evaluated. Spearman's rho and multivariate logistic regression analysis were used. Results: A total of 102 adult CF patients were evaluated. The mean age was 28.1 years (95% CI: 26.7-29.5), and the mean body mass index was 17.5 kg/m2 (95% CI: 17.2-18.2). Mean T-scores were −2.3 and −1.9 at the lumbar spine and femoral neck, respectively, being lower in males than in females (−2.7 vs. −2.0 at the lumbar spine and −2.2 vs. −1.7 at the femoral neck). Overall, 52% had a T-score of < −2.5 at either skeletal site. The homozygous Phe508del genotype was found in 57% of patients without osteoporosis and in 60% of those with low BMD. Mean T-scores were not particularly low in patients with severe CFTR mutations. Although the BMI correlated with T-scores at the femoral neck and lumbar spine, serum 25-hydroxyvitamin D and parathyroid hormone levels did not. Conclusions: CFBD is common in CF patients with end-stage lung disease, particularly in males and patients with a low BMI. It appears that CF mutation status does not correlate with CFBD. In addition, it appears that low BMD does not correlate with other risk factors or biochemical parameters. The prevalence of CFBD appears to have recently decreased, most likely reflecting increased efforts at earlier diagnosis and treatment.

Keywords: Lung transplantation; Cystic fibrosis; Bone density; Osteoporosis.

The authors analyze the nutritional status of patients with lung cancer. 131 patients, 96 (73.3%) male and 35 (26.7%) female, were classified into three groups: I - malnourished patients; II - eutrophic patients and III - obese patients. Most of the malnourished had anorexia (59.7%), which was not seen in the eutrophic (25%) and obese patients (26.1%). More than 70% of patients reported some degree of previous weight loss at the initial evaluation, weight loss being higher among malnourished patients. Weight loss was observed in more than 60% of the patients during the follow-up period of 3 months after the first evaluation. Patients with squamous carcinoma neoplasms prevailed in the malnourished group whereas adenocarcinoma was more prevalent in the other two groups. Most patients had advanced stages of the disease.

Keywords: Lung cancer. Nutritional status.

Objective: Patients with lung cancer experience different feelings and reactions, based on their family, social, cultural, and religious backgrounds, which are a source of great distress, not only for the patients but also for their family caregivers. This study aimed to evaluate the impact that lung cancer stage and quality of life (QoL) of lung cancer patients have on caregiver burden. Methods: This was a prospective cross-sectional study. Consecutive patient-caregiver dyads were selected and asked to complete the Hospital Anxiety and Depression Scale and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). Family caregivers also completed the Caregiver Burden Scale. Group-based modeling was used in order to identify patients with early- or advanced-stage cancer (IA to IIIA vs. IIIB to IV) plus non-impaired or impaired QoL (SF-36 total score > 50 vs. ≤ 50). Patient-caregiver dyads were stratified into four groups: early-stage cancer+non-impaired QoL; advanced-stage cancer+non-impaired QoL; early-stage cancer+impaired QoL; and advanced-stage cancer+impaired QoL. Results: We included 91 patient-caregiver dyads. The majority of the patients were male and heavy smokers. Family caregivers were younger and predominantly female. The burden, QoL, level of anxiety, and level of depression of caregivers were more affected by the QoL of the patients than by their lung cancer stage. The family caregivers of the patients with impaired QoL showed a higher median burden than did those of the patients with non-impaired QoL, regardless of disease stage. Conclusions: Caregiver burden is more affected by patient QoL than by lung cancer stage.

Keywords: Lung neoplasms; Quality of life; Caregivers; Anxiety; Depression; Cost of illness.

Epidemiological studies have demonstrated a causal relationship between smoking and lung cancer. Although most lung cancer cases are linked to smoking, only a minority of heavy smokers develop lung cancer, leading to the notion that genetic factors affect individual susceptibility. The principal molecular changes in lung cancer are seen in tumor suppressor genes, proto-oncogenes, growth factors, telomerase activity, and methylation status of promoters. Well-known agents include angiogenesis-stimulating factors (such as vascular endothelial growth factor), as well as factors related to tumor cell proliferation and apoptosis (epidermal growth factor receptor, p53, K-ras, retinoblastoma and BCL-2). Several of these genetic factors have already been investigated, but no single parameter has yet presented sufficient selectivity regarding prognostic value or therapeutic efficacy. Treatment strategies to cure lung cancer should focus on these early genetic lesions in order to promote their repair or to eliminate these lung cancer cells.

Keywords: Smoking; Lung neoplasms; Genetic markers; Prognosis

Objective: To analyze the clinicopathological aspects of bronchioloalveolar carcinoma (BAC) and the survival in a sample of patients at clinical stage I. Methods: A retrospective study involving 26 patients diagnosed with clinical stage I BAC and undergoing surgery at the Thoracic Diseases Institute of the Federal University of Rio de Janeiro, in the city of Rio de Janeiro, Brazil, between 1987 and 2007. We analyzed clinicopathological and radiological aspects, as well as mortality and survival. The data, which were collected from the medical charts of the patients, were statistically analyzed. Results: Females predominated (n = 16). The mean age at diagnosis was 68.5 years. Most patients were active smokers (69.2%). The most common forms of presentation of BAC were the asymptomatic form (84.6%) and the nodular form (88.5%). Involvement of the upper lobes predominated (57.7%). Stage IB was the most common pathological stage, followed by stages IA and IIB (46.2%, 38.4% and 15.4%, respectively). There was no in-hospital mortality. Four patients died during the postoperative follow-up, with a mean disease-free survival time of 21.3 months. The overall five-year survival rate was 83%. The probability of survival for the patients diagnosed after 1999 showed a trend toward an increase when compared with that for those diagnosed up through 1999 (three-year survival rate: 92% vs. 68%; p = 0.07). Conclusions: The clinicopathological aspects of this study sample were similar to those of patients with BAC evaluated in previous studies.

Keywords: Adenocarcinoma, bronchiolo-alveolar; Carcinoma, non-small-cell lung; Lung; Smoking.

Objective: To evaluate the efficacy of stereotactic body radiotherapy (SBRT) versus surgery for early-stage non-small cell lung cancer (NSCLC) by means of a meta-analysis of comparative studies. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines, searches were performed on PubMed, MEDLINE, Embase, and Cochrane Library for eligible studies. The meta-analysis compared the hazard ratios (HR) for overall survival (OS), cancer-specific survival (CSS), and local control (LC). Subgroup and meta-regression analyses evaluated the association of extent of surgical resection, study publication year, tumor staging, propensity score matching, proportion of chemotherapy use, and proportion of pathological lymph node involvement with CSS and OS. Results: Thirty studies involving 29,511 patients were included (surgery group: 17,146 patients and SBRT group: 12,365 patients). There was a significant difference in favor of surgery vs. SBRT in the 3-year OS (HR = 1.35; 95% CI: 1.22-1.44; I2 = 66%) and 3-year CSS (HR = 1.23; 95% CI: 1.09-1.37; I2 = 17%), but not in the 3-year LC (HR = 0.97; 95% CI: 0.93-1.08; I2 = 19%). In the subgroup analysis for OS, no significant difference between surgery and SBRT groups was observed in the T1N0M0 subgroup (HR = 1.26; 95% CI: 0.95-1.68; I2 = 0%). In subgroup analysis for CSS, no significant difference was detected between the sublobar resection subgroup and the SBRT group (HR = 1.21; 95% CI: 0.96-1.53; I2 = 16%). Conclusions: Surgery generally resulted in better 3-year OS and CSS than did SBRT; however, publication bias and heterogeneity may have influenced these findings. In contrast, SBRT produced LC results similar to those of surgery regardless of the extent of surgical resection. These findings may have important clinical implications for patients with comorbidities, advanced age, poor pulmonary reserve, and other factors that may contraindicate surgery.

Keywords: Carcinoma, Non-Small-Cell Lung/surgery; Radiosurgery; Meta-analysis.

Biological markers are cellular, structural and biochemical components that can define cellular as well as molecular changes in both normal and neoplastic cells. There are two types of biological markers: 1) intermediate markers that evaluate cellular and molecular alterations before malignancy occurs; and 2) diagnostic markers, present in association with malignancy. The identification and validation of biological markers for clinical use are performed in stages: initial identification in cell cultures of the tumor;
testing of the marker in tissues obtained in biopsies of patients with an established diagnosis of the tumor;
testing of biopsies of normal tissues and tissues with an inflammatory process;
sputum, blood or urine tests for validation as a non-invasive test that can be used in high-risk populations. Sorologic and histopathologic biological markers are cellular, structural and biochemical components found in both normal and neoplastic cells that can be quantitatively assessed by biochemical, immunological and molecular methods in the body fluids or tissues, respectively, and may be associated with malignancies and, possibly, with the neoplastic organ. Biological markers are studied in diverse primary neoplasms. However, few of them proved to be clinically valuable. The role of biological markers in lung cancer patients remains unclear because only a small number of markers has been properly identifiassessed. The aim of this paper is to understand the role of sorologic and histologic biological markers in the prognosis and survival of lung cancer patients based on our previous works. Furthermore, we present a future perspective of the early detection of lung cancer on the basis of the role of intermediate biological markers.

Keywords: Biologic markers. Lung cancer. Prognosis. Survival. Morphometric method.

The role of immunohistochemistry is to recognize antigens and, consequently, to identify and classify specific cells within a cell population whose morphology is heterogenous or apparently homogenous. The visualization of the antigen-antibody complex is made possible through the addition of either a fluorochrome conjugate or an enzyme to the antibody, which is then viewed under microscopy. Immunohistochemistry can be used in the routine diagnosis of lung cancer, in order to identify biological markers (diagnostic and prognostic). The essential immunohistochemistry panels will be discussed in this review.

Keywords: Immunohistochemistry; Tumor markers, biological; Lung neoplasms.

Objective: Adjuvant chemotherapy (AC) improves survival of patients with resected non-small cell lung cancer (NSCLC). However, the cisplatin-vinorelbine regimen has been associated with a significant risk of clinically relevant toxicity. We sought to evaluate the effectiveness, safety, and feasibility of AC for NSCLC patients in a real-world setting. Methods: This was a single-center, retrospective cohort study of patients with stage I-III NSCLC undergoing surgery with curative intent between 2009 and 2018. AC was administered at the discretion of physicians. The patients were divided into two groups: AC group and no AC (control) group. Study outcomes included overall survival (OS) and recurrence-free survival (RFS), as well as the safety profile and feasibility of the cisplatin-vinorelbine regimen in a real-world setting. Results: The study involved 231 patients, 80 of whom received AC. Of those, 55 patients received the cisplatin-vinorelbine regimen. Survival analyses stratified by tumor stage showed that patients with stage II NSCLC in the AC group had better RFS (p = 0.036) and OS (p = 0.017) than did those in the no AC group. Among patients with stage III NSCLC in the AC group, RFS was better (p < 0.001) and there was a trend toward improved OS (p = 0.060) in comparison with controls. Of those who received the cisplatin-vinorelbine regimen, 29% had grade 3-4 febrile neutropenia, and 9% died of toxicity. Conclusions: These results support the benefit of AC for NSCLC patients in a real-world setting. However, because the cisplatin-vinorelbine regimen was associated with alarming rates of toxicity, more effective and less toxic alternatives should be investigated.

Keywords: Lung neoplasms; Chemotherapy, adjuvant; Cisplatin/toxicity; Vinorelbine/toxicity.

Objective: To characterize the clinical and histological profile, as well as treatment patterns, of patients with early-stage, locally advanced (LA), or advanced/metastatic (AM) lung cancer, diagnosed between 2000 and 2014, in Brazil. Methods: This was an analytical cross-sectional epidemiological study employing data obtained for the 2000-2014 period from the hospital cancer registries of two institutions in Brazil: the José Alencar Gomes da Silva National Cancer Institute, in the city of Rio de Janeiro; and the São Paulo Cancer Center Foundation, in the city of São Paulo. Results: We reviewed the data related to 73,167 patients with lung cancer. The proportions of patients with early-stage, LA, and AM lung cancer were 13.3%, 33.2%, and 53.4%, respectively. The patients with early-stage lung cancer were older and were most likely to receive a histological diagnosis of adenocarcinoma; the proportion of patients with early-stage lung cancer remained stable throughout the study period. In those with LA lung cancer, squamous cell carcinoma predominated, and the proportion of patients with LA lung cancer decreased significantly over the period analyzed. Those with AM lung cancer were younger and were most likely to have adenocarcinoma; the proportion of patients with AM lung cancer increased significantly during the study period. Small cell carcinoma accounted for 9.2% of all cases. In our patient sample, the main treatment modality was chemotherapy. Conclusions: It is noteworthy that the frequency of AM lung cancer increased significantly during the study period, whereas that of LA lung cancer decreased significantly and that of early-stage lung cancer remained stable. Cancer treatment patterns, by stage, were in accordance with international guidelines.

Keywords: Lung neoplasms/epidemiology; Lung neoplasms/therapy; Neoplasm staging; Brazil.

Objective: To compile fiberoptic bronchoscopy findings in patients diagnosed with lung cancer and to correlate those with histopathological findings. Methods: This was a retrospective study involving 212 patients with a confirmed diagnosis of lung cancer by cytological evaluation of BAL specimens or by histopathological evaluation of endobronchial or transbronchial biopsy specimens. The data were collected at the Respiratory Endoscopy Section of Hospital São Salvador, located in the city of Goiânia, Brazil, between 2005 and 2010. The endoscopic findings were classified as endoscopically visible tumor, endoscopically invisible tumor, and mucosal injury, as well as being classified by the presence/type of secretion. The visible tumors were also classified according to their location in the tracheobronchial tree. Results: Endobronchial mass (64%) and mucosal infiltration (35%) were the main endoscopic findings. The histological type was determined in 199 cases, the most prevalent types being squamous carcinoma, in 78 (39%), adenocarcinoma, in 42 (21%), small cell carcinoma, in 24 (12%), and large cell carcinoma, in 2 (1%). More than 45% of the visible tumors were at the upper bronchi. Squamous carcinoma (n = 78) was most commonly visualized as an endobronchial mass (in 74%), mucosal infiltration (in 36%), luminal narrowing (in 10%), or external compression (in 6%). Conclusions: Our results show that an endobronchial mass is the most common bronchoscopic finding that is suggestive of malignancy. Proportionally, mucosal infiltration is the most common finding in small cell carcinoma. In adenocarcinoma, luminal narrowing, external compression, mucosal injury, and endobronchial secretion prevail.

Keywords: Lung neoplasms/diagnosis; Lung neoplasms/classification; Bronchoscopy.

Objective: To compare somatic growth, lung function, and level of physical activity in schoolchildren who had been very-low-birth-weight preterm infants (VLBWPIs) or normal-birth-weight full-term infants. Methods: We recruited two groups of schoolchildren between 8 and 11 years of age residing in the study catchment area: those who had been VLBWPIs (birth weight < 1,500 g); and those who had been normal-birth-weight full-term infants (controls, birth weight ≥ 2,500 g). Anthropometric and spirometric data were collected from the schoolchildren, who also completed a questionnaire regarding their physical activity. In addition, data regarding the perinatal and neonatal period were collected from the medical records of the VLBWPIs. Results: Of the 93 schoolchildren screened, 48 and 45 were in the VLBWPI and control groups, respectively. No significant differences were found between the groups regarding anthropometric characteristics, nutritional status, or pulmonary function. No associations were found between perinatal/neonatal variables and lung function parameters in the VLBWPI group. Although the difference was not significant, the level of physical activity was slightly higher in the VLBWPI group than in the control group. Conclusions: Among the schoolchildren evaluated here, neither growth nor lung function appear to have been affected by prematurity birth weight, or level of physical activity.

Keywords: Premature birth; Birth weight; Respiratory function tests; Motor activity; Pediatrics.

Objective: To translate the European Organisation for Research and Treatment of Cancer (EORTC) 29-item Quality of Life Questionnaire-Lung Cancer Module (QLQ-LC29, developed for the assessment of quality of life in patients with lung cancer) to Portuguese, conducting a pilot study of the Portuguese-language version and adapting it for use in Brazil. Methods: For the translation, cultural adaptation, and pilot testing of the QLQ-LC29, we followed the guidelines established by the EORTC. The translation (English → Portuguese) and back-translation (Portuguese → English) were both carried out by translators, working independently, who were native speakers of one language and fluent in the other. After review, a draft version was created for pilot testing in lung cancer patients in Brazil. Results: A total of 15 patients diagnosed with lung cancer completed the Portuguese-language version of the questionnaire. At the end of the process, we conducted a structured interview to identify any patient difficulty in understanding any of the questions. The final versions were sent to the EORTC and were approved. Conclusions: The Portuguese-language version of the EORTC QLQ-LC29 appears to be a useful, important, reliable questionnaire that is a valid tool for assessing quality of life in patients with lung cancer in Brazil.

Keywords: Surveys and Questionnaires; Lung neoplasms; Quality of Life; Brazil; Translations.