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: 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: 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.

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 investigate the efficacy of upper limb exercise training (ULExT) in improving the performance of activities of daily living (ADL) that involve the upper limbs (UL) in patients with COPD. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review. PubMed and EBSCOhost databases were searched to identify randomized controlled trials involving adults with COPD who underwent ULExT, compared with those who underwent other types of exercise or no exercise, in order to assess the performance of ADL that involve the UL. The methodological quality of the selected studies was assessed using the Physiotherapy Evidence Database scale. Results: Five studies, with a total sample of 173 subjects, met the inclusion criteria. The results of the selected studies showed that ULExT is safe and can significantly improve the performance of ADL that involve the UL in patients with COPD. However, there were inconsistencies in the results, especially regarding the perception of symptoms during ADL. The small number of studies included and their methodological quality do not allow for firm conclusions. Conclusions: The findings of this review revealed that ULExT is a safe therapeutic approach and can improve the performance of ADL that involve the UL in patients with COPD, but the results are unclear. Further investigation through well-designed randomized trials is warranted to determine the effectiveness of ULExT in improving the performance of ADL that involve the UL in patients with COPD.

Keywords: Upper extremity; Pulmonary disease, chronic obstructive; Activities of daily living, Exercise therapy.

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.

Objective: EBUS-TBNA cytological sampling is routinely performed for pathological diagnosis, mediastinal staging, and molecular testing in lung cancer patients. EBUS-TBNA samples are not formally accepted for testing programmed death-ligand 1 (PD-L1) expression. The objective of the study was to compare the feasibility, reproducibility, and accuracy of PD-L1 expression assessment in cytological specimens and histological samples. Methods: We prospectively collected histological (transbronchial forceps biopsy) and cytological (EBUS-TBNA) samples from peribronchial neoplastic lesions during an endoscopic procedure at the same target lesion for the pathological diagnosis and molecular assessment of stage IV non-small cell lung cancer (NSCLC). Results: Fifteen patients underwent the procedure. Adequate cytological samples (at least 100 neoplastic cells) were obtained in 12 cases (92.3%). Assessment of PD-L1 expression was similar between histological and cytological samples (agreement rate = 92%). Sensitivity and diagnostic accuracy of EBUS-TBNA cytological specimens were 88.9% and 100%, respectively. Conclusions: The evaluation of PD-L1 expression in EBUS-TBNA cytological specimens is feasible and presents good reproducibility when compared with routine histological samples. EBUS-TBNA cytological samples could be used for the assessment of PD-L1 expression in patients with NSCLC as a minimally invasive approach in stage IV NSCLC cancer patients.

Keywords: Ultrasonography; Biopsy, needle; Lung neoplasms; Molecular targeted therapy.

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.

The usefulness of serum tumor markers in lung cancer is not well defined. Objective: The aim of this study is to examine the correlation between serum tumor markers and tumor extension and its prognostic value. Patients and method: From February 1995 to September 1997, 103 patients with non-small cell lung carcinoma were evaluated at the Department of Thoracic Surgery. Serum levels of CEA, CYFRA21.1, CA15.3, CA19.9, CA72.4, and NSE were determined before treatment. Results: The serum level of CYFRA21.1 was the most frequent elevated tumor marker (55%). Patients with advanced tumor had higher mean serum level of CEA (90.8 ng/ml), CYFRA21.1 (20.3 ng/ml) and CA15.3 (56.5%) than those with localized carcinoma, respectively 10.2 ng/ml, 12.6 ng/ml and 22.2 ng/ml. Considering all serum tumor markers evaluated in this study, only patients with elevated CEA had greater chance (5.6) of presenting with advanced non-small lung carcinoma than patients with normal CEA. Overall survival was influenced by performance status (p = 0.001), tumor extension (p = 0.006), elevated serum level of CEA (p = 0.043), more than two elevated serum tumor markers (p < 0.001), and type of treatment (p < 0.001). The prognostic value of anatomical tumor extension reached the limit of significance (p = 0.052); however, two or more elevated serum tumor markers and type of treatment had independent prognostic value (respectively, p = 0.035 and p = 0.005). Conclusion: None of these serum tumor markers had clinical value in the management of NSCLC patients.

Keywords: biological tumor markers, neoplasm staging, non-small cell lung carcinoma, prognosis

Objectives: Non-small cell lung cancer (NSCLC) is an incidental and aggressive type of cancer. Although curative treatment can be offered, the recurrence rate is relatively high. Identifying factors that have a prognostic impact may guide changes in the staging system and recommendations for adjuvant therapy. The aim of this study was to evaluate the impact of microvascular invasion on the 5-year overall survival (OS) of patients with resected NSCLC treated at a reference cancer center. Methods: This retrospective, observational cohort study included patients diagnosed with early-stage NSCLC (clinical stages I-IIIA), treated with curative-intent surgery at the Brazilian National Cancer Institute between 2010 and 2016. Results: The dataset comprised 91 surgical patients, mostly females and white, with a mean age of 62 years (range between 29-83). Cases were distributed as stages I, II, and III in 55%, 29%, and 16%. Adenocarcinoma was the predominant histological subtype (67%), and microvascular invasion was present in 25% of the patients. The 5-year OS probability was 60% (95% CI, 48.3-68.9). Among all characteristics, advanced stages (p = 0.001) and the presence of microvascular invasion (p< 0.001) were related to a worse 5-year OS. After adjusting for age group and pathological stage, the presence of microvascular invasion was associated with a 4-fold increased risk of death (HR 3.9, 95% CI, 1.9-8.2). Conclusion: The presence of microvascular invasion was an independent factor related to worse survival and, therefore, should be routinely assessed in resected specimens.

Keywords: non-small cell lung cancer, thoracic surgery, survival analysis, microvascular invasion.

This will be my last editorial as the editor of the Jornal Brasileiro de Pneumologia (JBP, Brazilian Journal of Pulmonology).

Objective: To evaluate systematically the effects of continuous positive airway pressure (CPAP) on blood pressure in patients with resistant hypertension and obstructive sleep apnea (OSA). Methods: The Cochrane Library, PubMed, ScienceDirect, and the Web of Science were searched for studies investigating the effects of CPAP on blood pressure in patients with resistant hypertension and OSA. The selected studies underwent quality assessment and meta-analysis, as well as being tested for heterogeneity. Results: Six randomized controlled trials were included in the meta-analysis. The pooled estimates of the changes in mean systolic blood pressure and mean diastolic blood pressure (as assessed by 24-h ambulatory blood pressure monitoring) were −5.40 mmHg (95% CI: −9.17 to −1.64; p = 0.001; I2 = 74%) and −3.86 mmHg (95% CI: −6.41 to −1.30; p = 0.00001; I2 = 79%), respectively. Conclusions: CPAP therapy can significantly reduce blood pressure in patients with resistant hypertension and OSA.

Keywords: Continuous positive airway pressure; Sleep apnea, obstructive; Hypertension; Meta-analysis.