Node-Negative Non-small Cell Lung Cancer: Pathological Staging and Survival in 1765 Consecutive Cases

IntroductionThis study aimed to evaluate prognostic factors in patients with node-negative non-small cell lung cancer and to assess revised International Association for the Study of Lung Cancer staging recommendations for this group.MethodsA retrospective analysis of 1765 consecutive pathologically node-negative patients treated by surgical resection between 1984 and 2007 was performed. Survival analysis was conducted using the Kaplan-Meier method. The independence of prognostic factors was analyzed using multivariate Cox proportional hazards modeling.ResultsThe median age of patients was 68 years, and the average length of follow-up was 6.3 years. Perioperative mortality was 1.7%. The median survival was 6.5 years, with a 56% of the cohort surviving 5 years. Factors associated with poorer prognosis were male gender (hazard ratio [HR]: 1.30, p = <0.001), age (HR: 1.04 per year of increase, p < 0.001), limited resection (HR: 1.30, p = 0.002) tumor size (HR: 1.10 per 10 mm increase, p < 0.001), large cell histopathological cell type (HR: 1.35, p < 0.001), and positive resection margins (HR: 1.58, p = 0.002). T stage was a superior predictor of survival than tumor size (p < 0.001). There was no difference in survival by T-stage descriptor within stage T2 or T3.ConclusionsIn surgically treated, node-negative non-small cell lung cancer, revised International Association for the Study of Lung Cancer staging criteria stratify survival well. Age, gender, and extent of resection are also important predictors of survival. Current T-stage descriptor groupings are appropriate

Extrapleural pneumonectomy for malignant pleural mesothelioma: Outcomes of treatment and prognostic factors

ObjectiveThis study aimed to evaluate the perioperative and long-term outcomes associated with extrapleural pneumonectomy for patients with malignant pleural mesothelioma.MethodsFrom October 1994 to April 2008, 70 patients were selected for extrapleural pneumonectomy. Univariate analysis was performed using the Kaplan–Meier method and compared using the log-rank test. Multivariate analysis with entering and removing limits of P less than .10 and P greater than .05, respectively, was used. The prognostic factors included age, gender, side of disease, asbestos exposure, histology, positron emission tomography, date of surgery, neoadjuvant chemotherapy, completeness of cytoreduction, lymph node involvement, perioperative morbidity, adjuvant radiotherapy, and pemetrexed-based chemotherapy.ResultsThe mean age of patients was 55 years (standard deviation = 10). Fifty-eight patients had epithelial tumors. Six patients received neoadjuvant chemotherapy, 28 patients received adjuvant radiotherapy, and 16 patients received postoperative pemetrexed-based chemotherapy. Forty-four patients had no lymph node involvement. The perioperative morbidity and mortality were 37% and 5.7%, respectively. Complications included hemothorax (n = 7), atrial fibrillation (n = 6), empyema (n = 4), bronchopulmonary fistula (n = 3), right-sided heart failure (n = 2), pneumonia (n = 1), constrictive pericarditis (n = 1), acute pulmonary edema (n = 1), small bowel herniation (n = 1), and disseminated intravascular coagulopathy (n = 1). The median survival was 20 months, with a 3-year survival of 30%. Asbestos exposure, negative lymph node involvement, and receipt of adjuvant radiation or postoperative pemetrexed-based chemotherapy were associated with improved survival on both univariate and multivariate analyses.ConclusionThe present study supports the use of extrapleural pneumonectomy-based multimodal therapy in carefully selected patients with malignant pleural mesothelioma

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Intrathoracic application of a vacuum-assisted closure device in managing pleural space infection after lung resection : is it an option?

Empyema after lung resection is a challenging condition to manage and is associated with a high mortality. Intrathoracic application of a vacuum-assisted closure (VAC) device is recently introduced as an adjunct in the management of this condition. A best evidence topic was constructed to address whether this approach is effective in successful chest closure and reducing hospital stay. Twenty-three papers were found using the reported search, of which nine papers were identified that provided the best evidence to answer the question. All papers were retrospective and included a total of 69 patients treated with intrathoracic VAC. There was only one cohort study and the rest were either case series or case reports. In a cohort of 19 patients reported by Palmen et al. the average duration of an open window thoracostomy in a group of patients with VAC (n = 11) was 39 ± 17 days and in those without VAC (n = 8) was 933 ± 1422 days. Median length of VAC treatment was 22 days (range 6-66 days) in a series of 28 patients reported by Saadi et al. Some authors excluded patients with a bronchopleural fistula (BPF) from VAC treatment. However, Groetzner et al. have safely used VAC in patients with BPF after covering the bronchus stump with an intrathoracic muscle flap. The mediastinum and the bronchus can be covered using a polyvinyl-alcohol foam. Polyurethane foam is commonly used to fill the intrathoracic cavity up to the superficial wound. The suggested starting level of negative pressure is as low as -25 mmHg to -75 mmHg depending on the presence or absence of signs of mediastinal traction; this negative pressure can gradually be increased to -125 mmHg over time. The recommended interval between VAC changes is two to five days. Accumulated evidence in this article, although limited, suggests that VAC, as an adjunct to the standard treatment, can potentially alleviate the morbidity and decrease hospital stay in patients with empyema after lung resection. VAC can reduce inpatient length of treatment and can make the condition manageable in an outpatient setting. These results are yet to be proven by larger studies and clinical trials.7 page(s

Summary of prognostic factors and patient selection for extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma

Background: Extrapleural pneumonectomy (EPP) has been shown to improve long-term survival outcomes in selected patients with malignant pleural mesothelioma (MPM). The present study aimed to evaluate potential prognostic factors on overall survival for patients who underwent EPP for MPM and to examine the patient selection process in major referral centers that perform EPP. Methods: A systematic review of the current literature was performed using 5 electronic databases. Relevant studies with prognostic data on overall survival for patients with MPM treated by EPP were included for review. Two reviewers independently assessed each included study. Results: A total of 17 studies from 13 institutions containing the most updated and complete data on prognostic factors for patients with MPM who underwent EPP were included for review. A number of quantitative, clinical, and treatment-related factors were identified to have significant impact on overall survival. Conclusions: Patients with nonepithelial MPM and nodal involvement have consistently demonstrated to have a worse prognosis after EPP. Their eligibility as candidates for EPP should be questioned. The preoperative patient selection process currently differs greatly between institutions and should focus on identifying patients with nonepithelial histologic subtypes and nodal involvement to exclude them as EPP surgical candidates in the future.7 page(s

A Systematic review of extrapleural pneumonectomy for malignant pleural mesothelioma

INTRODUCTION: The primary objective of the present systematic review was to evaluate the safety and efficacy of extrapleural pneumonectomy (EPP) for patients with malignant pleural mesothelioma. METHODS: A systematic review of relevant studies identified through five online search databases was performed. Two reviewers independently appraised each study. RESULTS: Thirty-four of 58 relevant studies from 26 institutions containing the most updated data were evaluated for survival and perioperative outcomes after EPP. The median overall survival varied from 9.4 to 27.5 months, and 1-, 2-, and 5-year survival rates ranged from 36 to 83%, 5 to 59%, and 0 to 24%, respectively. Overall perioperative mortality rates ranged from 0 to 11.8%, and the perioperative morbidity rates ranged from 22 to 82%. Quality of life assessments from three studies reported improvements in nearly all domains at 3 months postoperatively. Patients who underwent trimodality therapy involving EPP and adjuvant chemoradiotherapy had a median overall survival of 13 to 23.9 months. DISCUSSIONS: The current evidence suggests that selected patients with malignant pleural mesothelioma may benefit from EPP, especially when combined with neoadjuvant or adjuvant chemotherapy and adjuvant radiotherapy.12 page(s

Bronchopulmonary carcinoid tumors : long-term outcomes after resection

Background Bronchopulmonary carcinoid tumors are considered as a relatively uncommon and less malignant group of lung cancers. However, patients with histologically atypical disease are known to have a worse prognosis. The present study aims to evaluate the long-term outcomes after resection of bronchopulmonary carcinoid tumors according to the new tumor, nodes, metastasis (TNM) staging system. Methods Patients with histologically proven bronchopulmonary carcinoid tumors who underwent surgery in our thoracic unit over the last 25 years were identified from a prospectively collected database. Results One hundred and eighty-six patients were identified from our electronic database. Of these, 164 were known to have typical disease, while 22 had atypical disease. Median overall survival was 20.0 years. The mean follow-up was 8.0 years (median 7.0 years). Univariate analysis found age over 60, atypical disease, TNM staging, N status, and M status to have a statistically significant influence on overall survival. Multivariate analysis found age over 60 and atypical histopathology to have a detrimental impact on overall survival. Patients in the atypical subgroup were found to be significantly older, and presented with higher stage disease. Conclusions It is clear from the current study and previous reports that patients with atypical histopathology have different baseline characteristics, disease behavior, and prognosis compared with patients with typical disease. The proposed TNM staging system appears to be applicable to patients in our surgical experience, and may offer more accurate prognostic information and assist in the management plans for individuals.5 page(s

Treatment Failure after Extrapleural Pneumonectomy for Malignant Pleural Mesothelioma

Background: Extrapleural pneumonectomy (EPP) has been used as a treatment option for selected patients with malignant pleural mesothelioma (MPM). The primary end-point of this study was disease-free survival (DFS). Prognostic indicators for local and overall DFS were statistically analyzed. Methods: Between October 1994 to April 2008, 59 patients who had complete macroscopic cytoreduction after EPP formed the basis of this report. In recent years, selected patients received adjuvant radiotherapy and pemetrexed combined with cisplatin or carboplatin. The clinicopathologic data of all patients were prospectively collected in a computerized database. Statistical analysis was performed by using Kaplan-Meier method and compared using the log-rank test. Cox-regression model was used for multivariate analysis. Results: The mean age at the time of EPP was 59 (S.D. = 8) years. Nineteen patients (32%) experienced perioperative complications. The median survival was 21 months (range 2 to 104). The local disease recurrence rate was 51%. The median local DFS was 22 months (0 to 73). The overall disease recurrence rate was 64%. The median overall DFS was 18 months (range 0 to 73). In multivariate analysis, epithelial subtype (p = 0.026) and adjuvant radiotherapy (p = 0.023) were independently associated with an improved local DFS. Adjuvant radiotherapy (p = 0.011) was also independently associated with an improved overall DFS. Conclusions: This study demonstrated that that local disease failure was still a considerable clinical problem following complete EPP. The data also showed that patients with epithelial histology and receiving adjuvant radiotherapy were associated with an improved disease control.6 page(s

Surgical management of melanoma lung metastasis : an analysis of survival outcomes in 292 consecutive patients

Background. The role of surgical resection of melanoma lung metastases (MLM) remains controversial. Some authorities advocate an aggressive surgical approach, while others recommend a conservative strategy. This study sought to identify the clinicopathologic and predictors of outcome after surgical management of MLM in a large series of melanoma patients from a single institution. Methods. All patients undergoing surgical management of MLM between November 1984 and April 2010 were identified and predictors of outcome analyzed. Results. Of the 292 patients eligible for the study, 112 (38%) had previously undergone surgery for nonpulmonary recurrences. Four patients (1%) died within 30 days of surgery for MLM. The median progression-free survival time was 10 months. The median overall survival and 3- and 5-year survival were 23 months [95% confidence interval (CI) 17-30], 41 and 34%, respectively. Metastasis size >2 cm [hazard ratio (HR) 1.4, 95% CI 1.0-1.8, P = 0.03, HR 1.6, 95% CI 1.2-2.2; P = 0.002] and positive surgical margin (HR 1.5, 95% CI 1.2-1.9, P<0.001; HR 1.4, 95% CI 1.1-1.7, P = 0.003) were independently associated with poorer progression-free survival and overall survival, respectively. The presence of more than one metastasis (HR 1.4, 95% CI 1.1-1.7, P = 0.013) was independently associated with poorer overall survival. Conclusions. The results support the role of pulmonary metastasectomy in selected patients with MLM. Patients with small (<2 cm) and solitary tumors that can be completely resected with a negative margin are most likely to experience prolonged survival.8 page(s