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: Adjuvant chemotherapy is recommended for most patients submitted to resection due to non-small cell lung cancer (NSCLC) staged as II or IIIA. However, although various chemotherapy regimens that include cisplatin have been used in phase III trials, the best choice remains unclear. The objective of this study was to describe the experience of the Instituto Nacional do Câncer (INCA, Brazilian National Cancer Institute), located in the city of Rio de Janeiro, Brazil, with the use of the cisplatin-etoposide combination in such patients, with a special focus on survival data. Methods: We retrospectively evaluated the medical charts of the patients receiving adjuvant therapy for NSCLC at the INCA between 2004 and 2008. Results: We included 51 patients, all of whom were treated with the cisplatin-etoposide combination. The median follow-up period was 31 months, and the median overall survival was 57 months. In the univariate analysis, median survival was lower in the patients submitted to chemotherapy plus radiotherapy than in those submitted to chemotherapy alone (19 vs. 57 months; p < 0.001), and there was a trend toward lower median survival in stage III patients than in stage I-II patients (34 vs. 57 months; p = 0.22). Overall survival was not significantly associated with gender (p = 0.70), histological pattern (p = 0.33), or cisplatin dose (p = 0.13). Conclusions: Our results support the use of adjuvant chemotherapy, and our survival data are similar to those reported in major randomized clinical trials. However, long-term follow-up is warranted in this population.

Keywords: Lung neoplasms; Chemotherapy, adjuvant; Survival analysis.

Objective: To evaluate the effect of chemotherapy on the physical condition of patients with advanced lung cancer. Methods: We evaluated 50 patients with non-small cell lung cancer (in stages IIIB and IV) and Eastern Cooperative Oncology Group (ECOG) performance status scale scores between zero and two. All patients underwent chemotherapy using paclitaxel and platinum derivatives and were evaluated at three time points (prechemotherapy, postchemotherapy and six months after starting the treatment), at which the ECOG scale, the body mass index (BMI) and the six-minute walk distance (6MWD) were assessed. Results: Of the 50 patients included in the study, 14 died, 5 were excluded due to the worsening of their performance status, and 31 completed the six-month follow-up. There was no statistically significant difference between the time points of assessment for BMI (prechemotherapy vs. postchemotherapy, p = 1.00; and prechemotherapy vs. six months later, p = 0.218) or for 6MWD. Performance status improved, and this was especially due to the increase in the number of asymptomatic patients after the six-month follow-up (p = 0.031). Conclusions: Chemotherapy had a beneficial effect on the performance status of the patients. No significant changes in BMI or 6MWD were found during the study period, which might suggest the maintenance of the physical condition of the patients.

Keywords: Drug therapy; Lung neoplasms; Exercise tolerance.

Surgical resection is the primary treatment option for early-stage non-small cell lung cancer, lobectomy being considered the standard of care. In elderly patients, physiological characteristics can limit the suitability for surgery and the extent of resection. Sublobar resection (SLR) can be offered as an alternative. The aim of this real-world analysis was to compare lobectomy and SLR in terms of recurrence and survival rates in patients over 70 years of age.

Keywords: Carcinoma, non-small-cell lung/mortality; Carcinoma, non-small-cell lung/surgery; Recurrence; Aged; Aged, 80 and over.

Objective: To evaluate the efficacy of the joint use of cervical mediastinoscopy and video-assisted thoracoscopy for the sampling of mediastinal lymph nodes in patients with non-small cell lung cancer (NSCLC) and candidates for pulmonary resection. Methods: Sixty-two patients diagnosed with NSCLC were submitted to cervical mediastinoscopy and video-assisted thoracoscopy. The samples obtained (from paratracheal chains, anterior and posterior subcarinal chains, paraesophageal chains and pulmonary ligament) were submitted to frozen section analysis. The following variables were also evaluated: age; gender; weight loss; diagnostic method; tomographic findings; histological type; staging; and location and size of the primary tumor. Results: In 11 patients, mediastinoscopy showed no involvement of the subcarinal chain, whereas such involvement was identified when video-assisted thoracoscopy was used: positive predictive value = 88.89% (95% CI: 51.75-99.72); negative predictive value = 94.34% (95% CI: 84.34-98.82); prevalence = 17.74% (95% CI: 9.2-29.53); sensitivity = 72.73% (95% CI: 39.03-93.98); and specificity = 98.77% (95% CI: 93.31-99.97). In 60% of the patients with involvement of the posterior subcarinal chain, the primary tumor was in the right inferior lobe. (p = 0.029) Conclusions: The joint use of cervical mediastinoscopy and video-assisted thoracoscopy for the evaluation of posterior mediastinal lymph nodes proved to be an efficacious method. When there is no access to posterior chains by means of ultrasound with transbronchial or transesophageal biopsy, which dispenses with general anesthesia, this should be the method of choice for the correct evaluation of mediastinal lymph nodes in patients with NSCLC.

Keywords: Neoplasm staging; Mediastinoscopy; Biopsy; Lymphatic metastasis.

Objective: To determine the role of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC). Methods: We searched various databases, selecting randomized clinical trials published in journals or conference proceedings within the last 30 years and investigating the role of PCI in the mortality of patients with SCLC, submitted to PCI or not. Results: Sixteen randomized clinical trials, collectively involving 1,983 patients, were considered eligible for inclusion. Of those 1,983 patients, 1,021 were submitted to PCI and 962 were not. Overall mortality was 4.4% lower in the patients submitted to PCI than in those who were not (OR = 0.73; 95% CI: 0.57-0.97; p = 0.01), especially among the patients showing a complete response after induction chemotherapy (OR = 0.68; 95% CI: 0.50-0.93; p = 0.02) and in those submitted to PCI after that treatment (OR = 0.68; 95% CI: 0.49-0.94; p = 0.03). That decrease did not correlate with the stage of the disease: limited disease (OR = 0.73; 95% CI: 0.55-0.97; p = 0.03); and extensive disease (OR = 0.48; 95% CI: 0.26-0.87; p = 0.02). Conclusions: Our findings suggest that PCI decreases mortality in patients with SCLC, especially in those showing a complete response after induction chemotherapy and in those submitted to PCI after that treatment, regardless of the stage of the disease.

Keywords: Small cell lung carcinoma; Radiotherapy; Survival analysis.

Objective: Lung cancer is a global public health problem and is associated with high mortality. Lung cancer could be largely avoided by reducing the prevalence of smoking. The objective of this study was to analyze the effects of social, behavioral, and clinical factors on the survival time of patients with non-small cell lung cancer treated at Cancer Hospital I of the José Alencar Gomes da Silva National Cancer Institute, located in the city of Rio de Janeiro, Brazil, between 2000 and 2003. Methods: This was a retrospective hospital cohort study involving 1,194 patients. The 60-month disease-specific survival probabilities were calculated with the Kaplan-Meier method for three stage groups. The importance of the studied factors was assessed with a hierarchical theoretical model after adjustment by Cox multiple regression. Results: The estimated 60-month specific-disease lethality rate was 86.0%. The 60-month disease-specific survival probability ranged from 25.0% (stages I/II) to 2.5% (stage IV). The performance status, the intention to treat, and the initial treatment modality were the major prognostic factors identified in the study population. Conclusions: In this cohort of patients, the disease-specific survival probabilities were extremely low. We identified no factors that could be modified after the diagnosis in order to improve survival. Primary prevention, such as reducing the prevalence of smoking, is still the best method to reduce the number of people who will suffer the consequences of lung cancer.

Keywords: Lung neoplasms/epidemiology; Carcinoma, non-small-cell lung; Survival analysis.

For patients with stage III (A or B) non-small cell lung cancer, radiation is still the standard treatment. However, long-term survival remains poor and new alternatives and therapeutic associations are being studied. Recently, chemotherapy has been in focus, with several combinations with radiation therapy and/or surgery. An update of the recently published data about the controversies on whether or not one should combine chemotherapy with radiation in locally advanced lung tumors was done. Cisplatin-based chemotherapy regimens combined with radiation are favorable, with a possible increase in survival of 3% in 2 years and 2% in 5 years. Neither the best drug combination nor the ideal association regimen have been defined yet. The indication of a combined treatment must be based on patient's clinical conditions and on a balance between quality of life, toxicity, and cost of chemotherapy.

Keywords: Lung neoplasms. Radiation therapy. Chemotherapy.

Objective: Although EBUS-TBNA combined with EUS-FNA or EUS-B-FNA stands as the primary approach for mediastinal staging in lung cancer, guidelines recommend mediastinoscopy confirmation if a lymph node identified on chest CT or showing increased PET scan uptake yields negativity on these techniques. This study aimed to assess the staging precision of EBUS/EUS. Methods: We conducted a retrospective study comparing the clinical staging of non-small cell lung cancer patients undergoing EBUS/EUS with their post-surgery pathological staging. We analyzed the influence of histology, location, tumor size, and the time lapse between EBUS and surgery. Patients with N0/N1 staging on EBUS/EUS, undergoing surgery, and with at least one station approached in both procedures were selected. Post-surgery, patients were categorized into N0/N1 and N2 groups. Results: Among the included patients (n = 47), pathological upstaging to N2 occurred in 6 (12.8%). Of these, 4 (66.7%) had a single N2 station, and 2 (33.3%) had multiple N2 stations. The adenopathy most frequently associated with upstaging was station 7. None of the analyzed variables demonstrated a statistically significant difference in the occurrence of upstaging. PET scan indicated increased uptake in only one of these adenopathies, and only one was visualized on chest CT. Conclusions: Upstaging proved independent of the studied variables, and only 2 patients with negative EBUS/EUS would warrant referral for mediastinoscopy. Exploring other noninvasive methods with even greater sensitivity for detecting micrometastatic lymph node disease is crucial.

Keywords: Carcinoma, non-small cell lung; Neoplasm staging; Endoscopic ultrasound-guided fine needle aspiration.

Objective: To compare clinical and pathological staging in patients with non-small cell lung cancer submitted to surgical treatment, as well as to identify the causes of discordance. Methods: Data related to patients treated at the Department of Thoracic Surgery of the Pontifical Catholic University of Rio Grande do Sul São Lucas Hospital were analyzed retrospectively. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for clinical stages IA, IB, and IIB. The kappa index was used to determine the concordance between clinical and pathological staging. Results: Of the 92 patients studied, 33.7% were classified as clinical stage IA, 50% as IB, and 16.3% as IIB. The concordance between clinical and pathological staging was 67.5% for stage IA, 54.3% for IB, and 66.6% for IIB. The accuracy of the clinical staging was greater for stage IA, and a kappa of 0.74, in this case, confirmed a substantial association with pathological staging. The difficulty in evaluating nodal metastatic disease is responsible for the low concordance in patients with clinical stage IB. Conclusions: The concordance between clinical and pathological staging is low, and patients are frequently understaged (in the present study, only one case was overstaged). Strategies are necessary to improve clinical staging and, consequently, the treatment and prognosis of patients with non-small cell lung cancer.

Keywords: Neoplasm staging; Lung neoplasms/diagnosis; Lung neoplasms/surgery; Prognosis.

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: Preoperative functional evaluation is central to optimizing the identification of patients with non-small cell lung cancer (NSCLC) who are candidates for surgery. The minute ventilation/carbon dioxide output (VE/VCO2) slope has proven to be a predictor of surgical complications and mortality. Pulmonary rehabilitation programs (PRPs) could influence short-term outcomes in patients with COPD undergoing lung resection. Our objective was to evaluate the effects of a PRP on the VE/VCO2 slope in a cohort of patients with COPD undergoing lung resection for NSCLC. Methods: We retrospectively evaluated 25 consecutive patients with COPD participating in a three-week high-intensity PRP prior to undergoing lung surgery for NSCLC, between December of 2015 and January of 2017. Patients underwent complete functional assessment, including spirometry, DLCO measurement, and cardiopulmonary exercise testing. Results: There were no significant differences between the mean pre- and post-PRP values (% of predicted) for FEV1 (61.5 ± 22.0% vs. 62.0 ± 21.1%) and DLCO (67.2 ± 18.1% vs. 67.5 ± 13.2%). Conversely, there were significant improvements in the mean peak oxygen uptake (from 14.7 ± 2.5 to 18.2 ± 2.7 mL/kg per min; p < 0.001) and VE/VCO2 slope (from 32.0 ± 2.8 to 30.1 ± 4.0; p < 0.01). Conclusions: Our results indicate that a high-intensity PRP can improve ventilatory efficiency in patients with COPD undergoing lung resection for NSCLC. Further comprehensive prospective studies are required to corroborate these preliminary results.

Keywords: Carcinoma, non-small-cell lung; Pulmonary disease, chronic obstructive/rehabilitation; Carbon dioxide/metabolism; Oxygen consumption/physiology; Risk assessment.

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: Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer. Most patients are diagnosed at an advanced stage, palliative chemotherapy therefore being the only treatment option. This study was aimed at evaluating the health-related quality of life (HRQoL) of advanced-stage NSCLC patients receiving palliative chemotherapy with carboplatin and paclitaxel. Methods: This was a multiple case study of advanced-stage NSCLC outpatients receiving chemotherapy at a public hospital in Rio de Janeiro, Brazil. The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire was used in conjunction with its supplemental lung cancer-specific module in order to assess HRQoL. Results: Physical and cognitive functioning scale scores differed significantly among chemotherapy cycles, indicating improved and worsened HRQoL, respectively. The differences regarding the scores for pain, loss of appetite, chest pain, and arm/shoulder pain indicated improved HRQoL. Conclusions: Chemotherapy was found to improve certain aspects of HRQoL in patients with advanced-stage NSCLC.

Keywords: Carcinoma, non-small-cell lung; Quality of life; Palliative care; Carboplatin; Paclitaxel.

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: To present an alternative method of detecting micrometastases in lymph nodes previously testing negative for non-small cell lung cancer (NSCLC) by routine hematoxylin-eosin staining. Methods: A total of 77 hilar and mediastinal lymph nodes resected from 18 patients with NSCLC were investigated for the presence of micrometastases using a combination of microarray analysis and immunohistochemistry. Results: Micrometastases were detected by identifying cytokeratin- and chromogranin-positive cells in lymph node microarrays. Of the 18 patients initially staged as pN0 through routine hematoxylin-eosin staining, 9 (50%) were restaged as N1, and the prognoses were re-evaluated in terms of histological and clinical parameters. The comparison of the survival curves revealed that survival was higher in the patients without micrometastases than in those with micrometastases. In addition, in the multivariate analysis adjusted for age, gender, histological type, and restaging, the presence of micrometastases proved to be an independent predictor of survival. Among patients who had been previously staged as pN0, the risk of death was found to be 7-times greater for those later diagnosed with micrometastases than for those in whom no micrometastases were identified. Conclusion: The combination of microarray analysis and immunohistochemistry might represent a low-cost and less time-consuming alternative for identifying occult micrometastases and predicting prognoses in surgically resected patients with pN0 NSCLC. Larger randomized, prospective studies are needed in order to determine the accuracy of this method.

Keywords: Lung neoplasms; Microarray analysis; Chromogranin A; Survival analysis.

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.