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Importance: Uninterrupted targeted therapy until disease progression or intolerable toxic effects is currently the routine therapy for advanced non-small cell lung cancer (NSCLC) involving driver gene variations. However, drug resistance is inevitable. Objective: To assess the clinical feasibility of adaptive de-escalation tyrosine kinase inhibitor (TKI) treatment guided by circulating tumor DNA (ctDNA) for achieving complete remission after local consolidative therapy (LCT) in patients with advanced NSCLC. Design, Setting, and Participants: This prospective nonrandomized controlled trial was conducted at a single center from June 3, 2020, to July 19, 2022, and included 60 patients with advanced NSCLC with driver variations without radiologically detectable disease after TKI and LCT. The median (range) follow-up time was 19.2 (3.8-29.7) months. Data analysis was conducted from December 15, 2022, to May 10, 2023. Intervention: Cessation of TKI treatment and follow-up every 3 months. Treatment was restarted in patients with progressive disease (defined by the Response Evaluation Criteria in Solid Tumors 1.1 criteria), detectable ctDNA, or elevated carcinoembryonic antigen (CEA) levels, whichever manifested first, and treatment ceased if all indicators were negative during follow-up surveillance. Main Outcomes and Measures: Progression-free survival (PFS). Secondary end points were objective response rate, time to next treatment, and overall survival. Results: Among the total study sample of 60 participants (median [range] age, 55 [21-75] years; 33 [55%] were female), the median PFS was 18.4 (95% CI, 12.6-24.2) months and the median (range) total treatment break duration was 9.1 (1.5-28.1) months. Fourteen patients (group A) remained in TKI cessation with a median (range) treatment break duration of 20.3 (6.8-28.1) months; 31 patients (group B) received retreatment owing to detectable ctDNA and/or CEA and had a median PFS of 20.2 (95% CI, 12.9-27.4) months with a median (range) total treatment break duration of 8.8 (1.5-20.6) months; and 15 patients (group C) who underwent retreatment with TKIs due to progressive disease had a median PFS of 5.5 (95% CI, 1.5-7.2) months. For all participants, the TKI retreatment response rate was 96%, the median time to next treatment was 29.3 (95% CI, 25.3-35.2) months, and the data for overall survival were immature. Conclusions and Relevance: The findings of this nonrandomized controlled trial suggest that this adaptive de-escalation TKI strategy for patients with NSCLC is feasible in those with no lesions after LCT and a negative ctDNA test result. This might provide a de-escalation treatment strategy guided by ctDNA for the subset of patients with advanced NSCLC. Trial Registration: ClinicalTrials.gov Identifier: NCT03046316.
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Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Masculino , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Idoso , Adulto , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/administração & dosagem , Estudos Prospectivos , Terapia de Alvo Molecular/métodosRESUMO
OBJECTIVES: To elucidate the impact of [18F]FDG positron emission tomography/computed tomography (PET/CT) vs. CT workup on staging and prognostic evaluation of clinical stage (c) I-II NSCLC. METHODS: We retrospectively identified 659 cI-II NSCLC who underwent CT (267 patients) or preoperative CT followed by PET/CT (392 patients), followed by curative-intended complete resection in our hospital from January 2008 to December 2013. Differences were assessed between preoperative and postoperative stage. Five-year disease-free survival (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier approach and compared with log-rank test. Impact of preoperative PET/CT on survival was assessed by Cox regression analysis. RESULTS: The study included 659 patients [mean age, 59.5 years ± 10.8 (standard deviation); 379 men]. The PET/CT group was superior over CT group in DFS [12.6 vs. 6.9 years, HR 0.67 (95% CI 0.53-0.84), p < 0.001] and OS [13.9 vs. 10.5 years, HR 0.64 (95% CI 0.50-0.81), p < 0.001]. In CT group, more patients thought to have cN0 migrated to pN1/2 disease as compared with PET/CT group [26.4% (66/250) vs. 19.2% (67/349), p < 0.001], resulting in more stage cI cases being upstaged to pII-IV [24.7% (49/198) vs. 16.1% (47/292), p = 0.02], yet this was not found in cII NSCLC [27.5% (19/69) vs. 27.0% (27/100), p = 0.94]. Cox regression analysis identified preoperative PET/CT as an independent prognostic factor of OS and DFS (p = 0.002, HR = 0.69, 95% CI 0.54-0.88; p = 0.004, HR = 0.72, 95% CI 0.58-0.90). CONCLUSION: Addition of preoperative [18F]FDG PET/CT was associated with superior DFS and OS in resectable cI-II NSCLC, which may result from accurate staging and stage-appropriate therapy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Humanos , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Seguimentos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Prognóstico , Estadiamento de Neoplasias , Compostos RadiofarmacêuticosRESUMO
This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive (N) and nivolumab-chemotherapy (N/C) combinations based on PD-L1 expression. Eligible patients exhibited resectable clinical stage IIA-IIIB (AJCC 8th edition) NSCLC without EGFR/ALK alterations. Patients received either mono-nivolumab (N) or nivolumab + nab-paclitaxel+ carboplatin (N/C) for three cycles based on PD-L1 expression. The primary endpoint was the major pathological response (MPR). Key secondary endpoints included the pathologic complete response (pCR), objective response rate (ORR), and event-free survival (EFS). Baseline PD-L1 expression and perioperative circulating tumor DNA (ctDNA) status were correlated with pCR and EFS. Fifty-two patients were enrolled, with 46 undergoing surgeries. The MPR was 50.0% (26/52), with 25.0% (13/52) achieving pCR, and 16.7% and 66.7% for patients with PD-L1 ≥ 50% in N and N/C groups, respectively. Thirteen (25.0%) patients experienced grade 3 or higher immune-related adverse events during neoadjuvant treatment. Patients with post-neoadjuvant ctDNA negativity was more likely to have pCR (39.1%) compared with those remained positive (6.7%, odds ratio = 6.14, 95% CI 0.84-Inf, p = 0.077). With a median follow-up of 25.1 months, the 18-month EFS rate was 64.8% (95% CI 51.9-81.0%). For patients with ctDNA- vs. ctDNA + , the 18m-EFS rate was 93.8% vs 47.3% (HR, 0.15; 95% CI 0.04, 0.94; p = 0.005). Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression ≥ 50%. ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits, which requires further confirmation in a prospective clinical trial (NCT04015778).
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Nivolumabe/uso terapêutico , Terapia Neoadjuvante/efeitos adversos , Platina/uso terapêutico , Antígeno B7-H1/genética , Estudos Prospectivos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologiaRESUMO
Background: Estimating the growth of pulmonary sub-solid nodules (SSNs) is crucial to the successful management of them during follow-up periods. The purpose of this study is to (1) investigate the measurement sensitivity of diameter, volume, and mass of SSNs for identifying growth and (2) seek to establish a deep learning-based model to predict the growth of SSNs. Methods: A total of 2,523 patients underwent at least 2-year examination records retrospectively collected with sub-solid nodules. A total of 2,358 patients with 3,120 SSNs from the NLST dataset were randomly divided into training and validation sets. Patients from the Yibicom Health Management Center and Guangdong Provincial People's Hospital were collected as an external test set (165 patients with 213 SSN). Trained models based on LUNA16 and Lndb19 datasets were employed to automatically obtain the diameter, volume, and mass of SSNs. Then, the increase rate in measurements between cancer and non-cancer groups was studied to evaluate the most appropriate way to identify growth-associated lung cancer. Further, according to the selected measurement, all SSNs were classified into two groups: growth and non-growth. Based on the data, the deep learning-based model (SiamModel) and radiomics model were developed and verified. Results: The double time of diameter, volume, and mass were 711 vs. 963 days (P = 0.20), 552 vs. 621 days (P = 0.04) and 488 vs. 623 days (P< 0.001) in the cancer and non-cancer groups, respectively. Our proposed SiamModel performed better than the radiomics model in both the NLST validation set and external test set, with an AUC of 0.858 (95% CI 0.786-0.921) and 0.760 (95% CI 0.646-0.857) in the validation set and 0.862 (95% CI 0.789-0.927) and 0.681 (95% CI 0.506-0.841) in the external test set, respectively. Furthermore, our SiamModel could use the data from first-time CT to predict the growth of SSNs, with an AUC of 0.855 (95% CI 0.793-0.908) in the NLST validation set and 0.821 (95% CI 0.725-0.904) in the external test set. Conclusion: Mass increase rate can reflect more sensitively the growth of SSNs associated with lung cancer than diameter and volume increase rates. A deep learning-based model has a great potential to predict the growth of SSNs.
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OBJECTIVE: In recent years, the lung cancer incidence has grown and the population is younger. We intend to find out the true detection rate of pulmonary nodules and the incidence of lung cancer in the population and search for the risk factors. METHOD: Hospital employees ≥40 years old who underwent low-dose computed tomography (CT) lung cancer screening from January 2019 to March 2022 were selected to record CT-imaging characteristics, pathology, staging, and questionnaires to investigate past history, smoking history, diet, mental health, etc. PM2.5 and radiation intake in radiation-related occupation received monitoring in hospital. RESULT: The detection rate of suspicious pulmonary nodules was 9.1% (233/2552), and the incidence rate of lung cancer (including adenocarcinoma in situ) was 4.0% (103/2552). Morbidity among doctors, nurses, technicians, administers, and logistics was no difference (p = 0.184), but higher in women than in men (4.7% vs 2.4% p = 0.002). The invasiveness increased with age and CT density of nodules (p = 0.018). The relationship between lung cancer morbidity and PM2.5 was not clear (p = 0.543); and no lung cancer has been found in employees related ionizing radiation. CONCLUSION: The high screening rate has brought about a high incidence of lung cancer. At present, the risk factor analysis of lung cancer based on small samples cannot find the direct cause. Most of the ground glass opacity (GGO)s detected by LDCT screening are indolent, but there are also rapidly progressive lung cancer. A predictive model to identify active and indolent GGO is necessary.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Adulto , China/epidemiologia , Detecção Precoce de Câncer/métodos , Feminino , Hospitais , Humanos , Incidência , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Masculino , Fatores de RiscoRESUMO
The efficacy and potential limitations of molecular residual disease (MRD) detection urgently need to be fully elucidated in a larger population of non-small cell lung cancer (NSCLC). We enrolled 261 patients with stages I to III NSCLC who underwent definitive surgery, and 913 peripheral blood samples were successfully detected by MRD assay. Within the population, only six patients (3.2%) with longitudinal undetectable MRD recurred, resulting in a negative predictive value of 96.8%. Longitudinal undetectable MRD may define the patients who were cured. The peak risk of developing detectable MRD was approximately 18 months after landmark detection. Correspondingly, the positive predictive value of longitudinal detectable MRD was 89.1%, with a median lead time of 3.4 months. However, brain-only recurrence was less commonly detected by MRD (n = 1/5, 20%). Further subgroup analyses revealed that patients with undetectable MRD might not benefit from adjuvant therapy. Together, these results expound the value of MRD in NSCLC. SIGNIFICANCE: This study confirms the prognostic value of MRD detection in patients with NSCLC after definitive surgery, especially in those with longitudinal undetectable MRD, which might represent the potentially cured population regardless of stage and adjuvant therapy. Moreover, the risk of developing detectable MRD decreased stepwise after 18 months since landmark detection. This article is highlighted in the In This Issue feature, p. 1599.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Neoplasia Residual/diagnóstico , PrognósticoRESUMO
A 48-year-old woman presented to our department and chest computed tomography (CT) revealed five pulmonary nodules, two of which were in the left upper lobe of the lung and three in the superior segment of the left lower lobe., All the lesions were resected for comprehensive histological assessment in order to distinguish synchronous multiple primary lung cancers (SMPLCs) from intrapulmonary metastases. The nodules were all successfully removed by minimally invasive surgery under the guidance of three dimensional (3D) reconstruction, in order to preserve as much lung function for the patient as possible. Postoperative histopathological examination demonstrated the presence of SMPLC. The patient was discharged from hospital on postoperative day 4 without any complications.
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Imageamento Tridimensional/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Mutations in TP53 are commonly found in patients with epidermal growth factor receptor (EGFR) mutant advanced non-small-cell lung cancer (NSCLC). In this study, we determined the predictive and prognostic potential of different subtypes of TP53 using data from a phase III randomized trial (CTONG 0901). PATIENTS AND METHODS: The trial enrolled 195 patients who had undergone next-generation sequencing of 168 genes before treatment with EGFR tyrosine kinase inhibitors. Mutations in TP53 (exon 4 or 7, other mutations, and wild-type) were analyzed based on the therapeutic response and survival. A Cox proportional hazards model was used to determine the potential of the predictive and prognostic factors. RESULTS: All 195 patients harbored activating EGFR mutations: the most common concomitant mutations were TP53 (134/195, 68.7%), CTNNB1 (20/195, 10.3%), and RB1 (16/195, 8.2%). The genetic profiles between patient subgroups administered first-line (132, 67.7%) or later-line (63, 32.3%) treatments did not significantly differ. The median progression-free survival in patients with mutations in exon 4 or 7 of TP53, other TP53 mutations, and wild-type TP53 were 9.4, 11.0, and 14.5 months (P = .009), respectively. Overall survival times were 15.8, 20.0, and 26.1 months (P = .004), respectively. Mutations in exon 4 or 7 of TP53 served as independent prognostic factors for progression-free (P = .001) and overall survival (P = .004) in patients. CONCLUSION: Mutations in exon 4 and/or 7 in TP53 are promising predictive and prognostic indicators in EGFR-mutated NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteína Supressora de Tumor p53/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Éxons/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Análise de SobrevidaRESUMO
PURPOSE: To develop a prediction model based on 18F-fludeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for solid pulmonary nodules (SPNs) with high malignant probability. PATIENTS AND METHODS: We retrospectively reviewed the records of CT-undetermined SPNs, which were further evaluated by PET/CT between January 2008 and December 2015. A total of 312 cases were included as a training set and 159 as a validation set. Logistic regression was applied to determine independent predictors, and a mathematical model was deduced. The area under the receiver operating characteristic curve (AUC) was compared to other models. Model fitness was assessed based on the American College of Chest Physicians guidelines. RESULTS: There were 215 (68.9%) and 127 (79.9%) malignant lesions in the training and validation sets, respectively. Eight independent predictors were identified: age [odds ratio (OR) = 1.030], male gender (OR = 0.268), smoking history (OR = 2.719), lesion diameter (OR = 1.067), spiculation (OR = 2.530), lobulation (OR = 2.614), cavity (OR = 2.847), and standardized maximum uptake value of SPNs (OR = 1.229). Our AUCs (training set, 0.858; validation set, 0.809) was better than those of previous models (Mayo: 0.685, P = .0061; Peking University People's Hospital: 0.646, P = .0180; Herder: 0.708, P = .0203; Zhejiang University: 0.757, P = .0699). The C index of the nomogram was 0.858. Our model reduced the diagnosis of indeterminate nodules (26.4% vs. 79.2%, 53.5%, 39.6%, and 34.0%, respectively) while improved sensitivity (81.3% vs. 16.4%, 49.2%, 62.5%, and 68.0%, respectively) and accuracy (65.4% vs. 16.4%, 39.6%, 52.8%, and 58.5%, respectively). CONCLUSION: Our model could permit accurate diagnoses and may be recommended to identify malignant SPNs with high malignant probability, as our data pertain to a very high-prevalence cohort only.
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Carcinoma Pulmonar de Células não Pequenas/patologia , Fluordesoxiglucose F18/metabolismo , Neoplasias Pulmonares/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Valor Preditivo dos Testes , Curva ROC , Compostos Radiofarmacêuticos/metabolismo , Estudos RetrospectivosRESUMO
In this study, we evaluated the diagnostic value and molecular characteristics of plasma extracellular vesicles (EVs)-derived miRNAs for patients with solitary pulmonary nodules (SPNs), particularly ground-glass nodules (GGNs). This study was registered at www.clinicaltrials.gov under registration number NCT03230019. Small RNA sequencing was performed to assess plasma EVs miRNAs in 59 patients, including 12 patients with benign nodules (2017, training set). MiRNA profiles of 40 an additional individuals were sequenced (2018, validation set). Overall, 16 pure GGNs, 21 mixed GGNs, and 42 solid nodules were included, with paired post-operative plasma samples available for 20 patients. The target miRNA/reference miRNA ratio was used to construct a support vector machine (SVM) model. The SVM model with the best specificity showed 100% specificity in both the training and validation sets independently. The model with the best sensitivity showed 100% and 96.9% sensitivity in the training and validation sets, respectively. Principal component analysis revealed that pure GGN distributions were distinct from those of solid nodules, and mixed GGNs had a diffuse distribution. Among differentially expressed miRNAs, miR-500a-3p, miR-501-3p, and miR-502-3p were upregulated in tumor tissues and enhanced overall survival. The SVM classifier accurately distinguished malignant GGNs and benign nodules. The distinct profile characteristics of miRNAs provided insights into the feasibility of EVs miRNAs as prognostic factors in lung cancer.
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BACKGROUND: We aimed to validate the tumor (T) descriptors of visceral pleural invasion (VPI) for T1 tumors (<3 cm) in the 8th edition of the tumor-node-metastasis (TNM) classification system and the prognostic value of VPI for resected T1a tumors. METHODS: The external cohort consisted of 23,501 patients with resected pN0 non-small cell lung cancer (NSCLC) selected from the Surveillance, Epidemiology, and End Results (SEER) database (2010 to 2013). The classification of T1 tumors with VPI was investigated using survival curves. The internal cohort consisted of patients diagnosed with pN0 NSCLC between 2011 and 2013 at Guangdong Lung Cancer Institute. The prognostic value of VPI for T1a tumors (<1 cm) was further assessed in these two cohorts. RESULTS: The overall survival (OS) and lung cancer-specific survival (LCSS) of the T1-VPI group and groups of each T stage (size only) were compared in the external (SEER) cohort. There were no significant survival differences between the T1-VPI and T2a groups (OS: P=0.706; LCSS: P=0.792) and T1-VPI and T2b groups, although the latter showed a trend toward lower P-values (OS: P=0.117; LCSS: P=0.094). In the internal cohort, a significant difference in OS was observed between patients with T1-VPI and those with T2b (P=0.049). Among patients with T1a tumors and VPI in the SEER database, the prognosis of the non-sub-lobectomy group was superior to that of the sub-lobectomy group, with intrathoracic recurrence as the predominant relapse pattern of T1 tumors with VPI (69.2%). CONCLUSIONS: T1 tumors (<3 cm) with VPI can be staged as T2a in the 8th TNM staging system and surgical resection of T1a tumors is a concern when VPI is present.
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BACKGROUND: Since the conception of enhanced recovery after surgery protocols, tubeless strategies have become popular. Herein, we introduce a previously unreported alternative air-extraction strategy for patients who have undergone thoracoscopic wedge resection and explore its feasibility and safety. METHODS: Between January 2015 and June 2017, 264 consecutive patients underwent thoracoscopic wedge resection with different drainage strategies. Patients were divided according to the postoperative drainage strategies used: routine chest tube drainage (RT group), complete omission of chest tube drainage (OT group), and prophylactic air-extraction catheter insertion procedure (PC group). Using the propensity score matching method, clinical parameters and objective operative qualities were compared among the three groups. RESULTS: Optimal 1:1 matching was used to form pairs of RT (n =36) and PC (n =36) groups and balance baseline characteristics among the three groups. The incidence rates of pneumothorax were 5.6% (2/36), 9.8% (5/51), and 19.4% (7/36) in the RT, OT, and PC groups, respectively (P = 0.07). Chest tube reinsertion incidence for postoperative pneumothorax was 19.4% (1/7) in the PC group and 60% (3/5) in the OT group. Other postoperative complications were comparable among these groups. CONCLUSIONS: The prophylactic air-extraction strategy may be an alternative procedure for selected patients. Remedial air extraction may reduce the occurrence of chest tube reinsertion for pneumothorax patients, but further investigation is required.
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Tubos Torácicos/normas , Pneumotórax/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
INTRODUCTION: Subtype classification of lung adenocarcinoma (LUAD) divides different survivals and therapeutic vulnerabilities; however, little is known about the disease's underlying molecular mechanism. This study sought to determine the genetic and immune profiles of histologic subtypes and identify the evidence for adjuvant immunotherapy. METHODS: We performed an integrated analysis of multidimensional data from a discovery set consisting of cohorts of The Cancer Genome Atlas and the Broad Institute data set from the LUAD public database and a validation set from the Guangdong Lung Cancer Institute. Immunohistochemical staining was carried out to determine the expression of the proteins programmed cell death 1 ligand (PD-L1) and CD8. RESULTS: Patients with solid predominant LUAD showed poor disease-free survival and a high frequency of relapse/metastasis compared with those with the nonsolid subtype of LUAD. The solid subtype tended to occur more frequently in those with a history of smoking. Solid predominant LUAD exclusively showed increased expression of PD-L1 and a high proportion of dual positive PD-L1- and tumor-infiltrating lymphocytes. Meanwhile, a notable increase in the tumor mutation burden and higher frequency of GC>TA transversions were specifically identified in tumors of the solid subtype. Furthermore, the solid subtype of tumor displayed an active cytotoxic immune signature and increased incidence of genetic mutations related to immunogenicity. CONCLUSION: Solid predominant LUAD was identified as a subtype with adaptive immune resistance, higher cytotoxic activity, and enhanced immunogenicity. These findings suggest that patients with solid predominant LUAD may represent a potential selective group that will benefit from adjuvant programmed cell death 1 blockade immunotherapy.
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Adenocarcinoma/genética , Adenocarcinoma/imunologia , Biomarcadores Tumorais/genética , Imunoterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Mutação , Adenocarcinoma/terapia , Antígeno B7-H1/genética , Estudos de Coortes , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
As surgical proficiency and the development of medical techniques have improved, uniportal video-assisted thoracoscopic surgery (VATS) has emerged as a minimally invasive alternative in the surgical management of lung cancer. The spectrum of uniportal VATS indications is now almost equal to that of conventional VATS. Recent decades have witnessed the emergence of numerous uniportal VATS techniques. A significant proportion of these have to be converted into a multiport approach and even open thoracotomy due to the difficulty of managing the upper lobe vein and bronchus, particularly for the technically challenging left upper lobectomy. Although many successfully uniportal VATS left upper lobectomies have been reported, their procedures were modularized without describing refined techniques or operative improvements. This report describes a patient who was clinically diagnosed with stage IB (T2aN0M0) primary lung cancer of the left upper lobe (LUL), and who underwent left upper lobectomy and systematic lymph node dissection. During the operation, the placement of a single incision was readjusted to obtain optimal angulation; the versatile electrocautery hook and curved suction tube were used in conjunction with each other; accessible, cost-effective modified instruments were used; and new operative tricks were created; in addition, the operative sequence was alternated and the nerves were preserved to ensure a smooth procedure, improve efficiency, embody tumor-free operation and ensure safety. These are all good ideas that are worth disseminating.
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BACKGROUND: Video-assisted thoracoscopic surgery (VATS) lobectomy has emerged as a safe and effective technique for treating early-stage lung cancer. Novel three-dimensional, high-definition (3D HD) imaging has removed this technical obstacle and is increasingly used in laparoscopic surgery. We compared our initial experience of 3D HD VATS with standard two-dimensional (2D) HD VATS to identify the advantages and disadvantages of 3D HD visualization in VATS. METHODS: The data of consecutive patients diagnosed with lung cancer who underwent 2D or 3D thoracoscopic lobectomy or bilobectomy at the Guangdong Lung Cancer Institute from July 2013 to October 2014 were retrospectively analyzed. Operation duration, estimated blood loss, length of postoperative stay, major complications, and mortality were recorded for each patient. RESULTS: In total, 359 patients were enrolled in the study. Lobectomy was performed in 339 patients and bilobectomy in 20; the 3D HD system was used for 178 of the 359 patients, and the 2D HD system for 181. Tumor size, distribution of the resected lobes, and the demographic characteristics of the patients were matched between the two groups. The mean operative time for 3D VATS was 163 minutes (range 60-330), whereas 2D VATS required 184 minutes (range 75-360; P < 0.001). The volume of blood loss was 109 and 144 mL in the 3D and 2D VATS groups, respectively (P = 0.064). CONCLUSIONS: The new-generation 3D HD imaging system is feasible and safe for thoracic lobectomy. The 3D system required a shorter operative duration.
Assuntos
Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVES: The management of non-small cell lung cancer (NSCLC) relies on the tumour-node-metastasis (TNM) stage, and the treatment regimen differs based on the N status. Positron emission tomography-computed tomography (PET-CT) has emerged as a powerful imaging tool for the detection of various cancers with a relatively low false-negative rate. We explored predictors to identify false-negative N2 disease in PET-CT. METHODS: A total of 284 consecutive cN0 patients with peripheral NSCLC who underwent PET-CT scans followed by curative intent resections were enrolled as a training set to identify predictors of occult N2 metastases by multivariable analysis. The accuracy and cut-off values for the predictors were calculated using a receiver operating characteristic curve. Clinical and pathological data were analysed retrospectively. An additional 151 patients were collected as a test set to validate the results, including the occult N2 rate and accuracy. RESULTS: In total, 8.5% (24/284) PET-CT-diagnosed N0 NSCLC cases had pathologically diagnosed N2 metastases. The SUVmax of the primary tumour was a unique independent risk factor for occult N2 NSCLC [P = 0.003, 95% confidence interval = 0.81-0.96, odds ratio (OR) = 0.88]. Occult N2 metastases occurred more frequently in the subcarinal (16/24) and right lower paratracheal lymph nodes (12/24). Accordingly, we divided the patients into two groups by SUVmax: the occult N2 rates in the SUVmax of <2.6 and SUVmax of ≥2.6 groups were 1.0% (1/100) and 12.5% (23/184), respectively (P = 0.001). In the test set, the occult N2 incidence rate was 9.3% (14/151), with the highest rates occurring in the subcarinal (9/14) and right lower paratracheal lymph nodes (6/14). In the two groups defined by SUVmax, the occult N2 rates were 4% (2/50) and 11.9% (12/101), respectively. CONCLUSIONS: The SUVmax of the primary tumour was an independent risk factor for occult N2 metastases in NSCLC patients diagnosed as clinical N0 by PET-CT. SUVmax of ≥2.6 of the primary tumour may indicate the risk of N2 metastases, and invasive mediastinal staging techniques or comprehensive therapy should not be ignored in these patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Reações Falso-Negativas , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Metástase Linfática , Masculino , Mediastino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Cuidados Pré-Operatórios/métodos , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Effective methods for managing patients with solitary pulmonary nodules (SPNs) depend critically on the predictive probability of malignancy. METHODS: Between July 2009 and June 2011, data on gender, age, cancer history, tumor familial history, smoking status, tumor location, nodule size, spiculation, calcification, the tumor border, and the final pathological diagnosis were collected retrospectively from 154 surgical patients with an SPN measuring 3-30 mm. Each final diagnosis was compared with the probability calculated by three predicted models-the Mayo, VA, and Peking University (PU) models. The accuracy of each model was assessed using area under the receiver operating characteristics (ROC) and calibration curves. RESULTS: The area under the ROC curve of the PU model [0.800; 95% confidence interval (CI): 0.708-0.891] was higher than that of the Mayo model (0.753; 95% CI: 0.650-0.857) or VA model (0.728; 95% CI: 0.623-0.833); however, this finding was not statistically significant. To varying degrees, calibration curves showed that all three models overestimated malignancy. CONCLUSIONS: The three predicted models have similar accuracy for prediction of SPN malignancy, although the accuracy is not sufficient. For Chinese patients, the PU model may has greater predictive power.