What is the optimal management of potentially resectable stage III-N2 NSCLC? Results of a fixed-effects network meta-analysis and economic modelling.

Introduction: There is a critical need to understand the optimal treatment regimen in patients with potentially resectable stage III-N2 nonsmall cell lung cancer (NSCLC). Methods: A systematic review of randomised controlled trials was carried out using a literature search including the CDSR, CENTRAL, DARE, HTA, EMBASE and MEDLINE bibliographic databases. Selected trials were used to perform a Bayesian fixed-effects network meta-analysis and economic modelling of treatment regimens relevant to current-day treatment options: chemotherapy plus surgery (CS), chemotherapy plus radiotherapy (CR) and chemoradiotherapy followed by surgery (CRS). Findings: Six trials were prioritised for evidence synthesis. The fixed-effects network meta-analyses demonstrated an improvement in disease-free survival (DFS) for CRS versus CS and CRS versus CR of 0.34 years (95% CI 0.02-0.65) and 0.32 years (95% CI 0.05-0.58) respectively, over a 5-year period. No evidence of effect was observed in overall survival although point estimates favoured CRS. The probabilities that CRS had a greater mean survival time and greater probability of being alive than the reference treatment of CR at 5 years were 89% and 86% respectively. Survival outcomes for CR and CS were essentially equivalent. The economic model calculated that CRS and CS had incremental cost-effectiveness ratios of £19 000/quality-adjusted life-year (QALY) and £78 000/QALY compared to CR. The probability that CRS generated more QALYs than CR and CS was 94%. Interpretation: CRS provides an extended time in a disease-free state leading to improved cost-effectiveness over CR and CS in potentially resectable stage III-N2 NSCLC.

Ninety-day mortality following lung cancer surgery: outcomes from the English national clinical outcomes audit.

Accurately explaining perioperative mortality and risk to patients is an essential part of shared decision making. In the case of lung cancer surgery, the currently available multivariable mortality prediction tools perform poorly, and could mislead patients. Using data from 2004 to 2012, this group has previously produced data tables for 90-day postoperative mortality, to be used as a communication aid in the consenting process. Using National Lung Cancer Clinical Outcomes audit data from 2017 to 2018, we have produced updated early mortality tables, to reflect current thoracic surgery practice.

Development and internal validation of a clinical prediction model for 90-day mortality after lung resection: the RESECT-90 score.

OBJECTIVES: The ability to accurately estimate the risk of peri-operative mortality after lung resection is important. There are concerns about the performance and validity of existing models developed for this purpose, especially when predicting mortality within 90 days of surgery. The aim of this study was therefore to develop a clinical prediction model for mortality within 90 days of undergoing lung resection. METHODS: A retrospective database of patients undergoing lung resection in two UK centres between 2012 and 2018 was used to develop a multivariable logistic risk prediction model, with bootstrap sampling used for internal validation. Apparent and adjusted measures of discrimination (area under receiving operator characteristic curve) and calibration (calibration-in-the-large and calibration slope) were assessed as measures of model performance. RESULTS: Data were available for 6600 lung resections for model development. Predictors included in the final model were age, sex, performance status, percentage predicted diffusion capacity of the lung for carbon monoxide, anaemia, serum creatinine, pre-operative arrhythmia, right-sided resection, number of resected bronchopulmonary segments, open approach and malignant diagnosis. Good model performance was demonstrated, with adjusted area under receiving operator characteristic curve, calibration-in-the-large and calibration slope values (95% confidence intervals) of 0.741 (0.700, 0.782), 0.006 (-0.143, 0.156) and 0.870 (0.679, 1.060), respectively. CONCLUSIONS: The RESECT-90 model demonstrates good statistical performance for the prediction of 90-day mortality after lung resection. A project to facilitate large-scale external validation of the model to ensure that the model retains accuracy and is transferable to other centres in different geographical locations is currently underway.

Ninety-Day Mortality: Redefining the Perioperative Period After Lung Resection.

Operative mortality is an important outcome for patients, surgeons, healthcare institutions, and policy makers. Although measures of perioperative mortality have conventionally been limited to in-hospital and 30-day mortality (or a composite endpoint combining both), there is a large body of evidence emerging to support the extension of the perioperative period after lung resection to a minimum of 90 days after surgery. Several large-volume studies from centers across the world have reported that 90-day mortality after lung resection is double 30-day mortality. Hence, true perioperative mortality after lung resection is likely to be significantly higher than what is currently reported. In the contemporary era, where new treatment modalities such as stereotactic ablative body radiotherapy are emerging as viable nonsurgical alternatives for the treatment of lung cancer, accurate estimation of perioperative risk and reliable reporting of perioperative mortality are of particular importance. It is likely that shifting the discussion from 30-day to 90-day mortality will lead to altered decision making, particularly for specific patient subgroups at an increased risk of 90-day mortality. We believe that 90-day mortality should be adopted as the standard measure of perioperative mortality after lung resection and that strategies to reduce the risk of mortality within 90 days of surgery should be investigated.

Post-treatment survival difference between lobectomy and stereotactic ablative radiotherapy in stage I non-small cell lung cancer in England.

BACKGROUND: Approximately 15%-20% of all non-small cell lung cancer (NSCLC) cases present with stage I disease. Surgical resection traditionally offers the best chance of a cure but some patients will not have this treatment due to older age, comorbidities or personal choice. Stereotactic ablative radiotherapy (SABR) has become an established curative intent treatment option for patients who are not selected for or do not choose surgery. The aim of this study is to compare survival at 90 days, 6 months, 1 year and 2 years for patients who received either lobectomy or SABR. METHODS: We used data from the 2015 National Lung Cancer Audit database and linked with Hospital Episode Statistics and the radiotherapy dataset to identify patients with NSCLC stage IA-IB and performance status (PS) 0-2 who underwent surgery or SABR treatment. We assessed the likelihood of death at 90 days, 6 months, 1 year and 2 year after diagnosis and procedure date to observe survival between two patient groups. RESULTS: We identified 2373 patients in our cohort, 476 of whom had SABR. The median difference between date of diagnosis and date of treatment for surgery patients was 17 days while for SABR patients it was 73 days. Increasing age and worsening PS were associated with having SABR rather than surgery. Survival between the two treatment modalities was similar early on but by 1-year people who had surgery did better than those who had SABR (adjusted ORs 2.12, 95% CI 1.35 to 2.31). This difference persisted at 2 years and when the analysis was restricted to patients aged <80 years and with PS 0 or 1 and stage IA only. CONCLUSION: Our analysis suggests that patients who have lobectomy have a better survival compared with SABR patients; however, we found considerable delays in patients receiving SABR which may contribute to poorer long-term outcomes with this treatment option. Reducing these delays should be a key focus in development and reorganisation of services.

Impact on Health-Related Quality of Life of Video-Assisted Thoracoscopic Surgery for Lung Cancer.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) approaches are increasingly used in lung cancer surgery, but little is known about their impact on patients' health-related quality of life (HRQL). This prospective study measured recovery and HRQL in the year after VATS for non-small cell lung cancer (NSCLC) and explored the feasibility of HRQL data collection in patients undergoing VATS or open lung resection. PATIENTS AND METHODS: Consecutive patients referred for surgical assessment (VATS or open surgery) for proven/suspected NSCLC completed HRQL and fatigue assessments before and 1, 3, 6 and 12 months post-surgery. Mean HRQL scores were calculated for patients who underwent VATS (segmental, wedge or lobectomy resection). Paired t-tests compared mean HRQL between baseline and expected worst (1 month), early (3 months) and longer-term (12 months) recovery time points. RESULTS: A total of 92 patients received VATS, and 18 open surgery. Questionnaire response rates were high (pre-surgery 96-100%; follow-up 67-85%). Pre-surgery, VATS patients reported mostly high (good) functional health scores [(European Organisation for Research and Treatment of Cancer) EORTC function scores > 80] and low (mild) symptom scores (EORTC symptom scores < 20). One-month post-surgery, patients reported clinically and statistically significant deterioration in overall health and physical, role and social function (19-36 points), and increased fatigue, pain, dyspnoea, appetite loss and constipation [EORTC 12-26; multidimensional fatigue inventory (MFI-20) 3-5]. HRQL had not fully recovered 12 months post-surgery, with reduced physical, role and social function (10-14) and persistent fatigue and dyspnoea (EORTC 12-22; MFI-20 2.7-3.2). CONCLUSIONS: Lung resection has a considerable detrimental impact on patients' HRQL that is not fully resolved 12 months post-surgery, despite a VATS approach.

Resectable Clinical N2 Non-Small Cell Lung Cancer; What Is the Optimal Treatment Strategy? An Update by the British Thoracic Society Lung Cancer Specialist Advisory Group.

Patients and clinicians are faced with uncertainty as to the optimal treatment strategy for potentially resectable NSCLC in which there is clinical evidence of involvement of the ipsilateral mediastinum. Randomized controlled trials and meta-analyses have failed to demonstrate superiority of one bimodality strategy over another (chemotherapy plus surgery versus chemotherapy plus radiotherapy). One trial of trimodality treatment with chemotherapy, radiotherapy, and surgery demonstrated an improvement in progression-free, but not overall, survival versus chemotherapy and radiotherapy. There are a number of limitations to the data in this complex and heterogenous patient group. No randomized controlled trial has specifically studied patients with single-station N2 disease versus multistation N2 disease. When discussing treatment for fit patients with potentially resectable cN2 NSCLC, lung cancer teams should consider trimodality treatment with chemotherapy, radiotherapy, and surgery or bimodality treatment with chemotherapy and either surgery or radiotherapy. We advocate that all patients see both a thoracic surgeon and the oncology team to discuss these different approaches.

Predictors of Outcome in Modern Surgery for Lung Abscess.

Background Surgery for lung abscess is a challenging task. Timing and indications for surgery are not well established. Identification of predictors of outcome could help to clarify the role of surgery. Methods Patients who underwent major thoracic surgery for infectious lung abscess were identified at six centers for general thoracic surgery in Germany, Spain, the United Kingdom, and the United States. Study period was 2000 to 2016. Results There were 91 patients. Pulmonary sepsis (48), pleural empyema (43), persistent air leakage (25), acute renal failure (12), and respiratory failure with mechanical ventilation (25) were already preoperatively present. The mean Charlson index of comorbidity was 3.0 (median: 2.0; interquartile range: 3). Procedures were segmentectomy (18), lobectomy (58), and pneumonectomy (15). The 30-day mortality following surgery was 13/91.Preoperative sepsis (odds ratio [OR]: 13.69; 95% confidence interval [CI]: 1.86-610.53; p < 0.01), preoperative persistent air leak (OR: 13.46, 95% CI: 3.00-85.37, p < 0.01), respiratory failure (OR: 5.60; 95% CI: 1.41-24.84; p < 0.01), acute renal failure (OR: 6.15 ; 95% CI: 1.24-29.56 ; p = 0.01), and Charlson index of comorbidity ≥ 3 (OR: 7.19 ; 95% CI: 1.43-71.21 ; p < 0.01) are associated with higher mortality, whereas age > 70 years (p = 0.46) and the extent of pulmonary resection (segmentectomy, lobectomy, pneumonectomy) have no significant influence on mortality. Patients with fatal outcome have significantly higher Charlson index of comorbidity (p < 0.01). Conclusions Delayed referral for surgery is common. Significant predictors for fatal outcome are pulmonary sepsis, septic complications (air leak, pleural empyema), septic organ failure (respiratory, acute renal failure), and preexisting comorbidity (Charlson index of comorbidity ≥ 3). The extent of surgical resection shows no significant influence.

Patient characteristics, treatment and survival in pulmonary carcinoid tumours: an analysis from the UK National Lung Cancer Audit.

OBJECTIVES: Pulmonary carcinoid (PC) is a rare tumour with good prognosis following surgical resection. However, little is known regarding patient characteristics and use of other treatments modalities. Our objective was to review patient characteristics, treatment and survival for patients with PC and contrast these results with other forms of non-small cell lung cancer (NSCLC). SETTING: Audit data from UK National Lung Cancer Audit (NLCA) 2008-2013. PARTICIPANTS: 184 906 lung cancer cases were submitted to the NLCA. OUTCOME MEASURES: Primary outcome-survival rates between PC and NSCLC. Secondary outcome-differences in performance status, lung function and treatment modality between PC and NSCLC. RESULTS: PC histology was recorded in 1341 (0.73%) patients and non-carcinoid NSCLC histology in 162 959 (87.4%) cases. 91% of patients with PC had good performance status (Eastern Cooperative Oncology Group (ECOG) 0-1), compared with only 53% of NSCLC. 66% of PC had localised disease. Of all PC cases, 77% were treated with surgery, 6.2% received chemotherapy and 3.6% received radiotherapy, with the remainder treated with best supportive care. Overall 1-year and 3-year survival rates for PC were 92% and 84.7%, respectively. In contrast, 1-year and 3-year survival rates for NSCLC were 36.2% and 15.6%, However, 3-year survival for PC markedly decreased with worsening performance status and advanced disease to 23.8% for performance status ECOG 3-4 and 33.6% for stage IV disease. CONCLUSIONS: In contrast to other forms of NSCLC, the majority of patients with PC present with good performance status, preserved lung function and early stage disease amenable to surgical resection. However, 1 in 5 patients with PC has metastatic disease which is associated with poor prognosis, as is poor performance status at presentation. We believe these data will help clinicians provide accurate prognostic predictions stratified according to patient characteristics at presentation, as well as guide future clinical trials.

Test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumours.

Positron emission tomography-CT (PET-CT) is one of the initial mediastinal staging modality for non-small cell lung cancer; however, the clinical utility in carcinoid tumours is uncertain. We sought to determine the test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumours. We collated data from seven institutions, performing a retrospective search on pathological databases for a consecutive series of patients who underwent thoracic surgery (with lymph nodal dissection) for carcinoid tumours with preoperative PET-CT staging. PET-CT results were compared with the reference standard of pathologic results obtained from lymph node dissection and test performance reported using sensitivity and specificity. From November 1999 to January 2013, 247 patients from seven institutions underwent surgery for carcinoid tumours with a corresponding preoperative PET-CT scan. The mean age of the patients was 61 (SD 15, range 73) and 84 were male patients (34%). The pathologic subtype was typical carcinoid in 217 patients (88%) and atypical carcinoid in 30 patients (12%). Results from lymph node dissection were obtained in 207 patients. The calculated sensitivity and specificity of PET-CT to identify mediastinal lymph node disease was 33% (95% CI 4% to 78%) and 94% (95% CI 89% to 97%), respectively. Our results indicate that PET-CT has a poor sensitivity but good specificity to detect the presence of mediastinal lymph node metastases in pulmonary carcinoid tumours. Mediastinal lymph node metastases cannot be ruled out with negative PET-CT uptake, and if the absence of mediastinal lymph node disease is a prerequisite for directing management, tissue sampling should be undertaken.

Infant vesicoureteral reflux: a comparison between patients presenting with a prenatal diagnosis and those presenting with a urinary tract infection.

OBJECTIVES: To evaluate the severity, laterality, and gender distribution of infant vesicoureteral reflux (VUR) and its potential impact on renal outcome, we compared patients presenting fetally (FDR group) and those presenting with a urinary tract infection (INF group). METHODS: A retrospective review of 202 patients with the diagnosis of VUR before 6 months of age was performed. The grade of VUR, gender, laterality, initial renal scarring, breakthrough urinary tract infections, new renal scarring, and surgical intervention were compared between the INF group (n = 146) and FDR group (n = 56). RESULTS: The male/female ratio in the FDR group was 1.67:1 compared with 0.60:1 in the INF group. The FDR group had more unilateral VUR than the INF group (P <0.001), and no significant difference was found between the two groups in terms of VUR grade distribution (P = 0.13), percentage of initial damage (28% of FDR patients versus 23% of INF patients), or clinical course. In either group, boys and girls exhibited a very similar distribution of grade and renal damage. CONCLUSIONS: Our findings do not support the commonly held belief that fetally diagnosed reflux is an overwhelmingly male, bilateral, and high-grade phenomenon. Few differences were observed between infants diagnosed fetally and those diagnosed subsequent to urinary tract infection. Once diagnosed, from either group, infant reflux has neither great morbidity nor a frequent need for surgery.