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Journal of Clinical Oncology : Official... Feb 2022Cisplatin-based adjuvant chemotherapy remains the standard of care for patients with resected stage II or III non-small-cell lung cancer. However, biomarker-informed... (Review)
Review
Cisplatin-based adjuvant chemotherapy remains the standard of care for patients with resected stage II or III non-small-cell lung cancer. However, biomarker-informed clinical trials are starting to push the management of early-stage lung cancer beyond cytotoxic chemotherapy. This review explores recent and ongoing studies focused on improving cytotoxic chemotherapy and incorporating targeted and immunotherapies in the management of early-stage, resectable lung cancer. Adjuvant osimertinib for patients with -mutant tumors, preoperative chemoimmunotherapy, and adjuvant immunotherapy could improve outcomes for selected patients with resectable lung cancer, and ongoing or planned studies leveraging biomarkers, immunotherapy, and targeted therapy may further improve survival. We also discuss the unique barriers associated with clinical trials of early-stage lung cancer and the need for innovative trial designs to overcome these challenges.
Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Clinical Decision-Making; Humans; Immunotherapy; Lung Neoplasms; Molecular Targeted Therapy; Neoadjuvant Therapy; Neoplasm Staging; Pneumonectomy; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 34985966
DOI: 10.1200/JCO.21.01589 -
The New England Journal of Medicine Feb 2023The increased detection of small-sized peripheral non-small-cell lung cancer (NSCLC) has renewed interest in sublobar resection in lieu of lobectomy. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The increased detection of small-sized peripheral non-small-cell lung cancer (NSCLC) has renewed interest in sublobar resection in lieu of lobectomy.
METHODS
We conducted a multicenter, noninferiority, phase 3 trial in which patients with NSCLC clinically staged as T1aN0 (tumor size, ≤2 cm) were randomly assigned to undergo sublobar resection or lobar resection after intraoperative confirmation of node-negative disease. The primary end point was disease-free survival, defined as the time between randomization and disease recurrence or death from any cause. Secondary end points were overall survival, locoregional and systemic recurrence, and pulmonary functions.
RESULTS
From June 2007 through March 2017, a total of 697 patients were assigned to undergo sublobar resection (340 patients) or lobar resection (357 patients). After a median follow-up of 7 years, sublobar resection was noninferior to lobar resection for disease-free survival (hazard ratio for disease recurrence or death, 1.01; 90% confidence interval [CI], 0.83 to 1.24). In addition, overall survival after sublobar resection was similar to that after lobar resection (hazard ratio for death, 0.95; 95% CI, 0.72 to 1.26). The 5-year disease-free survival was 63.6% (95% CI, 57.9 to 68.8) after sublobar resection and 64.1% (95% CI, 58.5 to 69.0) after lobar resection. The 5-year overall survival was 80.3% (95% CI, 75.5 to 84.3) after sublobar resection and 78.9% (95% CI, 74.1 to 82.9) after lobar resection. No substantial difference was seen between the two groups in the incidence of locoregional or distant recurrence. At 6 months postoperatively, a between-group difference of 2 percentage points was measured in the median percentage of predicted forced expiratory volume in 1 second, favoring the sublobar-resection group.
CONCLUSIONS
In patients with peripheral NSCLC with a tumor size of 2 cm or less and pathologically confirmed node-negative disease in the hilar and mediastinal lymph nodes, sublobar resection was not inferior to lobectomy with respect to disease-free survival. Overall survival was similar with the two procedures. (Funded by the National Cancer Institute and others; CALGB 140503 ClinicalTrials.gov number, NCT00499330.).
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Lung Neoplasms; Neoplasm Staging; Pneumonectomy; Retrospective Studies; Neoplasm Recurrence, Local; Recurrence; Lymph Nodes
PubMed: 36780674
DOI: 10.1056/NEJMoa2212083 -
Archives of Physical Medicine and... Dec 2021To determine the benefits of preoperative breathing exercises on hospital length of stay (LOS), pneumonia, postoperative pulmonary complications (PPC), 6-minute walk... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the benefits of preoperative breathing exercises on hospital length of stay (LOS), pneumonia, postoperative pulmonary complications (PPC), 6-minute walk distance (6MWD), forced expiratory volume in 1 second (FEV), and health-related quality of life (HRQOL) in patients undergoing surgical lung cancer resection.
DATA SOURCES
PubMed, EMBASE, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials were comprehensively searched from inception to March 2021.
STUDY SELECTION
Only studies including preoperative inspiratory muscle training (IMT) and/or breathing exercises compared with a nontraining control group were included. The meta-analysis was done using Cochrane software for multiple variables including LOS, pneumonia, PPC, 6MWD, FEV, mortality, and HRQOL.
DATA EXTRACTION
Two authors extracted the data of the selected studies. The primary outcomes were LOS and PPC.
DATA SYNTHESIS
A total of 10 studies were included in this meta-analysis, 8 of which had both IMT and aerobic exercise. Pooled data for patients who performed preoperative breathing exercises, compared with controls, demonstrated a decrease in LOS with a pooled mean difference of -3.44 days (95% confidence interval [CI], -4.14 to -2.75; P<.01). Subgroup analysis also demonstrated that LOS was further reduced when breathing exercises were combined with aerobic exercise (χ, 4.85; P=.03). Preoperative breathing exercises reduce pneumonia and PPCs with an odds ratio of 0.37 (95% CI, 0.18-0.75; P<.01) and 0.37 (95% CI, 0.21-0.65; P<.01), respectively. An increase in 6MWD of 20.2 meters was noted in those performing breathing exercises (95% CI, 9.12-31.21; P<.01). No significant differences were noted in FEV, mortality, or HRQOL.
CONCLUSIONS
Preoperative breathing exercises reduced LOS, PPC, and pneumonia and potentially improved 6MWD in patients undergoing surgical lung cancer resection. Breathing exercises in combination with aerobic exercise yielded greater reductions in LOS. Randomized controlled trials are needed to test the feasibility of introducing a preoperative breathing exercise program in this patient population.
Topics: Breathing Exercises; Forced Expiratory Volume; Humans; Length of Stay; Lung Neoplasms; Pneumonectomy; Postoperative Complications; Postoperative Period; Preoperative Period; Quality of Life; Walk Test
PubMed: 33930327
DOI: 10.1016/j.apmr.2021.03.028 -
The Journal of Thoracic and... Jan 2022The optimal mode of surgery for ground-glass opacity dominant peripheral lung cancer defined with thoracic thin-section computed tomography remains unknown.
BACKGROUND
The optimal mode of surgery for ground-glass opacity dominant peripheral lung cancer defined with thoracic thin-section computed tomography remains unknown.
METHODS
We conducted a single-arm confirmatory trial to evaluate the efficacy and safety of sublobar resection for ground-glass opacity dominant peripheral lung cancer. Lung cancer with maximum tumor diameter 2.0 cm or less and with consolidation tumor ratio 0.25 or less based on thin-section computed tomography were registered. The primary end point was 5-year relapse-free survival. The planned sample size was 330 with the expected 5-year relapse-free survival of 98%, threshold of 95%, 1-sided α of 5%, and power of 90%. The trial is registered with University Hospital Medical Information Network Clinical Trials Registry, number University Hospital Medical Information Network 000002008.
RESULTS
Between May 2009 and April 2011, 333 patients were enrolled from 51 institutions. Median age was 62 years (interquartile range, 56-68), and 109 were smokers. Median maximum tumor diameter was 1.20 cm (1.00-1.54). Median maximum tumor diameter of consolidation was 0 (0.00-0.20). The primary end point, 5-year relapse-free survival, was estimated on 314 patients who underwent sublobar resection. Operative modes were 258 wide wedge resections and 56 segmentectomies. Median pathological surgical margin was 15 mm (0-55). The 5-year relapse-free survival was 99.7% (90% confidence interval, 98.3-99.9), which met the primary end point. There was no local relapse. Grade 3 or higher postoperative complications based on Common Terminology Criteria for Adverse Effect v3.0 were observed in 17 patients (5.4%), without any grade 4 or 5.
CONCLUSIONS
Sublobar resection with enough surgical margin offered sufficient local control and relapse-free survival for lung cancer clinically resectable N0 staged by computed tomography with 3 or fewer peripheral lesions 2.0 cm or less amenable to sublobar resection and with a consolidation tumor ratio of 0.25 or less.
Topics: Female; Humans; Japan; Lung; Lung Neoplasms; Male; Margins of Excision; Middle Aged; Multidetector Computed Tomography; Neoplasm Staging; Pneumonectomy; Postoperative Complications; Prognosis; Progression-Free Survival; Treatment Outcome; Tumor Burden
PubMed: 33487427
DOI: 10.1016/j.jtcvs.2020.09.146 -
The Journal of Thoracic and... Sep 2019No definitive comparisons of surgical morbidity between segmentectomy and lobectomy for non-small cell lung cancer have been reported. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
No definitive comparisons of surgical morbidity between segmentectomy and lobectomy for non-small cell lung cancer have been reported.
METHODS
We conducted a randomized controlled trial to confirm the noninferiority of segmentectomy to lobectomy in regard to prognosis (trial No. JCOG0802/WJOG4607L). Patients with invasive peripheral non-small cell lung cancer tumor of a diameter ≤2 cm were randomized to undergo either lobectomy or segmentectomy. The primary end point was overall survival. Here, we have focused on morbidity and mortality. Predictors of surgical morbidity were evaluated by the mode of surgery. Segmentectomy was categorized into simple and complex. Simple segmentectomy was defined as segmental resection of the right or left segment 6, left superior, or lingular segment. Complex segmentectomy was resection of the other segment. This trial is registered with the University Hospital Medical Information Network--Clinical Trial Registry (UMIN000002317).
RESULTS
Between August 10, 2009, and October 21, 2014, 1106 patients (lobectomy n = 554 and segmentectomy n = 552) were enrolled. No mortality was noted. Complications (grade ≥ 2) occurred in 26.2% and 27.4% in the lobectomy and segmentectomy arms (P = .68), respectively. Fistula/pulmonary-lung (air leak) was detected in 21 (3.8%) and 36 (6.5%) patients in the lobectomy and segmentectomy arms (P = .04), respectively. Multivariable analysis revealed that predictors of pulmonary complications, including air leak and empyema (grade ≥ 2) were complex segmentectomy (vs lobectomy) (odds ratio, 2.07; 95% confidence interval, 1.11-3.88; P = .023), and > 20 pack-years of smoking (odds ratio, 2.61; 95% confidence interval, 1.14-5.97; P = .023).
CONCLUSIONS
There was no difference in almost any postoperative measure of intraoperative and postoperative complication in segmentectomy and lobectomy patients, except more air leakage was observed in the segmentectomy arm. Segmentectomy will be a standard treatment if the superior pulmonary function and noninferiority in overall survival are confirmed.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pneumonectomy; Postoperative Complications; Risk Assessment; Risk Factors; Time Factors; Tokyo; Treatment Outcome; Tumor Burden
PubMed: 31078312
DOI: 10.1016/j.jtcvs.2019.03.090 -
The Journal of Thoracic and... Jul 2020
Topics: Humans; Patient Readmission; Pneumonectomy
PubMed: 32381331
DOI: 10.1016/j.jtcvs.2020.03.110 -
Therapeutic Advances in Respiratory... 2023Bronchopleural fistula is a potentially fatal disease most often caused after pneumonectomy. Concomitant problems such as pulmonary infection and respiratory failure are... (Review)
Review
Bronchopleural fistula is a potentially fatal disease most often caused after pneumonectomy. Concomitant problems such as pulmonary infection and respiratory failure are typically the main contributors to patient mortality because of the improper contact between the bronchial and pleural cavity. Therefore, bronchopleural fistulas need immediate treatment, which requires the accurate location and timely closure of the fistula. Currently, bronchoscopic interventions, because of their flexibility and versatility, are reliable alternative therapies in patients for whom surgical intervention is unsuitable. Possible interventions include bronchoscopic placement of blocking agents, atrial septal defect (ASD)/ventricular septal defect (VSD) occluders, airway stents, endobronchial valves (EBVs) and endobronchial Watanabe spigots (EWSs). Recent developments in mesenchymal stem cells (MSCs) transplantation technology and three-dimensional (3D) printed stents have also contributed to the treatment of bronchopleural fistula, but more research is needed to investigate the long-term benefits. This review focuses on the effectiveness of various bronchoscopic measures for the treatment of bronchopleural fistula and the directions for future development.
Topics: Humans; Bronchoscopy; Postoperative Complications; Pleural Diseases; Bronchial Fistula; Pneumonia; Pneumonectomy
PubMed: 37067054
DOI: 10.1177/17534666231164541 -
The European Respiratory Journal Apr 2023Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months.
METHODS
This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population.
RESULTS
88 participants (48% female, mean±sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS -1.10±1.44 BLVR -0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS -36.1% (95% CI -54.6- -10%) BLVR -30.1% (95% CI -53.7- -9%); p=0.81). There was one death in each treatment arm.
CONCLUSION
Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments.
Topics: Humans; Female; Middle Aged; Aged; Male; Pneumonectomy; Single-Blind Method; Lung; Pulmonary Emphysema; Forced Expiratory Volume; Treatment Outcome; Bronchoscopy
PubMed: 36796833
DOI: 10.1183/13993003.02063-2022 -
The Journal of Thoracic and... Jul 2020
Topics: Humans; Patient Readmission; Pneumonectomy
PubMed: 32340808
DOI: 10.1016/j.jtcvs.2020.03.115 -
Interactive Cardiovascular and Thoracic... Jun 2022Completion lobectomy (CL) after anatomical segmentectomy in the same lobe can be complicated by severe adhesions around the hilar structures and may lead to fatal...
OBJECTIVES
Completion lobectomy (CL) after anatomical segmentectomy in the same lobe can be complicated by severe adhesions around the hilar structures and may lead to fatal bleeding and lung injury. Therefore, we aimed to investigate the perioperative outcomes of CL after anatomical segmentectomy.
METHODS
Among 461 patients who underwent anatomical segmentectomy (thoracotomy, 62 patients; thoracoscopic surgery, 399 patients) between January 2005 and December 2019, data of patients who underwent CL after segmentectomy were extracted and analysed in this study.
RESULTS
Eight patients underwent CL after segmentectomy. CL was performed via video-assisted thoracic surgery in 3 patients and thoracotomy in 5 patients. In each case, there were moderate to severe adhesions. Four patients required simultaneous resection of the pulmonary parenchyma and pulmonary artery. Thoracotomy was not required after thoracoscopic surgery in any patient. Two patients experienced complications (air leakage and arrhythmia). The median duration of hospitalization after CL was 6 (range, 5-7) days. No postoperative mortality or recurrence of lung cancer was observed. All the patients with lung cancer were alive and recurrence-free at the time of publication.
CONCLUSIONS
Although individual adhesions render surgery difficult, CL after anatomical segmentectomy shows acceptable perioperative outcomes. However, CL by video-assisted thoracoscopic surgery may be considered on a case-by-case basis depending on the initial surgery.
Topics: Humans; Lung Neoplasms; Mastectomy, Segmental; Pneumonectomy; Retrospective Studies; Thoracic Surgery, Video-Assisted; Thoracotomy
PubMed: 34962577
DOI: 10.1093/icvts/ivab323