Project description:Novel diagnostic techniques for lung cancer are rapidly evolving. Specifically, several novel changes to bronchoscopy are reaching clinical evaluation. It is critical to think about historical standards for evaluating new diagnostic testing, and put those concepts into the framework of lung cancer. Often a thorough evaluation of new technology is not performed as a part of regulatory marketing clearance. Therefore, we must consider how to best study novel testing beyond these regulatory minimums. There are several methodological principles that can achieve this goal such as using a control arm, more thorough reporting of enrolled patients, consecutive patient enrollment, and adequate sample size. We hope clinicians, particularly those performing bronchoscopy for lung nodules, will feel empowered to critically appraise the evaluation of new diagnostic testing for lung cancer moving forward.
Project description:BackgroundPatients with early-stage lung cancer are sometimes medically inoperable, and for patients with multiple primary lung cancers, surgical resection alone sometimes proves to be impractical. Local treatments like microwave ablation (MWA) are investigational alternatives for these patients. Most reported MWA procedures for lung cancers are performed percutaneously under CT guidance. MWA navigated by electromagnetic bronchoscopy (ENB) has been limitedly studied. In this study, we aimed to evaluate the safety and feasibility of MWA under ENB guidance in patients with inoperable early-stage lung cancers or multiple primary lung cancers which cannot be completely resected.MethodsFrom June 2019 to December 2020, preliminary attempts of ENB-guided MWA were made in five medically inoperable patients with a single early-stage lung cancer and ten patients with multiple primary lung cancers which were difficult to resect at the same time. For patients with concomitant pulmonary nodules which needed surgical resection, thoracoscopic resections were performed following ENB-guided MWA. The safety, feasibility, and technique effectiveness of treatments were evaluated.ResultsENB-guided MWA for 15 ground glass nodules (GGNs) in 15 patients was completed in accordance with the planned protocol. Biopsy of 13 GGNs showed malignancy. Five patients received simple ENB-guided MWA without simultaneous surgical resection and ten patients received simultaneous surgical resection for 13 concomitant pulmonary nodules. CT scan by the first postoperative week showed technique effectiveness of ablation for 11 nodules indicated for MWA. Four patients had mild complications after the procedure and recovered shortly after treatment.ConclusionsFor medically inoperable patients with a single GGN manifesting early-stage lung cancer and patients with multiple primary early-stage lung cancers which cannot be resected at the same time, ENB-guided MWA might be a safe and feasible alternative local treatment, whether combined with surgical resection or not. However, large, prospective, randomized, multicenter studies are needed to confirm its role in the treatment of early-stage lung cancer.
Project description:BackgroundThe correlation between the preoperative splenic area measured on CT scans and the overall survival (OS) of early-stage non-small cell lung cancer (NSCLC) patients remains unclear.MethodsA retrospective discovery cohort and validation cohort consisting of consecutive NSCLC patients who underwent resection and preoperative CT scans were created. The patients were divided into two groups based on the measurement of their preoperative splenic area: normal and abnormal. The Cox proportional hazard model was used to analyse the correlation between splenic area and OS.ResultsThe discovery and validation cohorts included 2532 patients (1374 (54.27%) males; median (IQR) age 59 (52-66) years) and 608 patients (403 (66.28%) males; age 69 (62-76) years), respectively. Patients with a normal splenic area had a 6% higher 5-year OS (n = 727 (80%)) than patients with an abnormal splenic area (n = 1805 (74%)) (p = 0.007) in the discovery cohort. A similar result was obtained in the validation cohort. In the univariable analysis, the OS hazard ratios (HRs) for the patients with abnormal splenic areas were 1.32 (95% confidence interval (CI): 1.08, 1.61) in the discovery cohort and 1.59 (95% CI: 1.01, 2.50) in the validation cohort. Multivariable analysis demonstrated that abnormal splenic area was independent of shorter OS in the discovery (HR: 1.32, 95% CI: 1.08, 1.63) and validation cohorts (HR: 1.84, 95% CI: 1.12, 3.02).ConclusionPreoperative CT measurements of the splenic area serve as a prognostic indicator for early-stage NSCLC patients, offering a novel metric with potential implications for personalized therapeutic strategies in top-tier oncology research.
Project description:Management of early-stage non-small cell lung cancer (NSCLC) consists in multimodal treatment, including surgery, radiotherapy and chemotherapy. The mainstay of treatment is radical surgery. Definitive radiotherapy using stereotactic techniques can provide adequate local disease control, and is the treatment of choice in medically inoperable patients. Most early-stage patients are at significant risk of disease relapse after local treatment. Adjuvant platinum-based chemotherapy has demonstrated to provide an absolute survival benefit of 5% compared to observation. However, unlike advanced/metastatic disease, little progress has been made in the treatment of early-stage NSCLC over the past decade. In recent years, plenty of research has focused on the optimization of adjuvant and neoadjuvant treatment. Several trials with novel drugs, such as targeted agents and immune-checkpoint inhibitors are currently underway, with preliminary positive results. Customization of treatment on patients' characteristics before, and major pathological response after therapy, will further improve survival outcomes in this subset of patients.
Project description:Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, clinical applications are constrained by the sensitivity of clinically validated ctDNA detection approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically validated for ultrasensitive ctDNA detection at 1-3 ppm of ctDNA with 99.9% specificity. Through an analysis of 171 patients with early-stage lung cancer from the TRACERx study, we detected ctDNA pre-operatively within 81% of patients with lung adenocarcinoma (LUAD), including 53% of those with pathological TNM (pTNM) stage I disease. ctDNA predicted worse clinical outcome, and patients with LUAD with <80 ppm preoperative ctDNA levels (the 95% limit of detection of a ctDNA detection approach previously published in TRACERx) experienced reduced overall survival compared with ctDNA-negative patients with LUAD. Although prospective studies are needed to confirm the clinical utility of the assay, these data show that our approach has the potential to improve disease stratification in early-stage LUADs.
Project description:BACKGROUND: Recently, fibroblast growth factor receptor 1 (FGFR1) was discovered in squamous cell carcinomas (SCC) of the lung with FGFR1 amplification described as a promising predictive marker for anti-FGFR inhibitor treatment. Only few data are available regarding prevalence, prognostic significance and clinico-pathological characteristics of FGFR1-amplified and early-stage non-small cell lung carcinomas (NSCLC). We therefore investigated the FGFR1 gene status in a large number of well-characterised early-stage NSCLC. METHODS: FGFR1 gene status was evaluated using a commercially available fluorescent in situ hybridisation (FISH) probe on a tissue microarray (TMA). This TMA harbours 329 resected, formalin-fixed and paraffin-embedded, nodal-negative NSCLC with a UICC stage I-II. The FISH results were correlated with clinico-pathological features and overall survival (OS). RESULTS: The prevalence of an FGFR1 amplification was 12.5% (41/329) and was significantly (P<0.0001) higher in squamous cell carcinoma (SCC) (20.7%) than in adenocarcinoma (2.2%) and large cell carcinoma (13%). Multivariate analysis revealed significantly (P=0.0367) worse 5-year OS in patients with an FGFR1-amplified NSCLC. CONCLUSIONS: FGFR1 amplification is common in early-stage SCC of the lung and is an independent and adverse prognostic marker. Its potential role as a predictive marker for targeted therapies or adjuvant treatment needs further investigation.
Project description:Non-small cell lung cancer (NSCLC) is the primary cause of cancer-related death worldwide, with a low 5-year survival rate even in fully resected early-stage disease. Novel biomarkers to identify patients at higher risk of relapse are needed. We studied the prognostic value of 84 circulating microRNAs (miRNAs) in 182 patients with resected early-stage NSCLC (99 adenocarcinoma (ADC), 83 squamous cell carcinoma (SCC)) from whom peripheral blood samples were collected pre-surgery. miRNA expression was analyzed in relation to disease-free survival (DFS) and overall survival (OS). In univariable analyses, five miRNAs (miR-26a-5p, miR-126-3p, miR-130b-3p, miR-205-5p, and miR-21-5p) were significantly associated with DFS in SCC, and four (miR-130b-3p, miR-26a-5p, miR-126-3p, and miR-205-5p) remained significantly associated with OS. In ADC, miR-222-3p, miR-22-3p, and mir-93-5p were significantly associated with DFS, miR-22-3p remaining significant for OS. Given the high-dimensionality of the dataset, multivariable models were obtained using a regularized Cox regression including all miRNAs and clinical covariates. After adjustment for disease stage, only miR-126-3p showed an independent prognostic role, with higher values associated with longer DFS in SCC patients. With regard to ADC and OS, no miRNA remained significant in multivariable analysis. Further investigation into the role of miR-126 as a prognostic marker in early-stage NSCLC is warranted.
Project description:BackgroundEmphysema is generally considered a poor prognostic factor for patients with nonsmall cell lung cancer; however, whether the poor prognosis is due to highly malignant tumors or emphysema itself remains unclear. This study was designed to determine the prognostic value of emphysema in patients with early-stage nonsmall cell lung cancer.MethodsA total of 721 patients with clinical stage IA nonsmall cell lung cancer who underwent complete resection between April 2007 and December 2018 were retrospectively analyzed regarding clinicopathological findings and prognosis related to emphysema.ResultsThe emphysematous and normal lung groups comprised 197 and 524 patients, respectively. Compared with the normal lung group, lymphatic invasion (23.9% vs. 14.1%, P = 0.003), vascular invasion (37.6% vs. 17.2%, P < 0.001), and pleural invasion (18.8% vs. 10.9%, P = 0.006) were observed more frequently in the emphysema group. Additionally, the 5-year overall survival rate was lower (77.1% vs. 91.4%, P < 0.001), and the cumulative incidence of other causes of death was higher in the emphysema group (14.0% vs. 3.50%, P < 0.001). Multivariable Cox regression analysis of overall survival revealed that emphysema (vs. normal lung, hazard ratio 2.02, P = 0.0052), age > 70 years (vs. < 70 years, hazard ratio 4.03, P < 0.001), and SUVmax > 1.8 (vs. ≤ 1.8, hazard ratio 2.20, P = 0.0043) were independent prognostic factors.ConclusionsEarly-stage nonsmall cell lung cancer with emphysema has a tendency for the development of highly malignant tumors. Additionally, emphysema itself may have an impact on poor prognosis.
Project description:BackgroundLung cancer patients often have comorbidities that may impact survival. This observational cohort study examines whether coronary artery calcifications (CAC) impact all-cause mortality in patients with resected stage I non-small cell lung cancer (NSCLC).MethodsVeterans with stage I NSCLC who underwent resection at a single institution between 2005 and 2018 were selected from a prospectively collected database. Radiologists blinded to patient outcomes graded CAC severity (mild, moderate, or severe) in preoperative CT scans using a visual estimation scoring system. Inter-rater reliability was calculated using the kappa statistic. All-cause mortality was the primary outcome. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to compare time-to-death by varying CAC.ResultsThe Veteran patients (n=195) were predominantly older (median age of 67) male (98%) smokers (96%). The majority (68%) were pathologic stage IA. Overall, 12% of patients had no CAC, 27% mild, 26% moderate, and 36% severe CAC. Median unadjusted survival was 8.8 years for patients with absent or mild CAC versus 6.3 years for moderate and 5.9 years for severe CAC (P=0.01). The adjusted hazard ratio for moderate CAC was 1.44 (95% CI, 0.85-2.46) and for severe CAC was 1.73 (95% CI, 1.03-2.88; P for trend <0.05).ConclusionsThe presence of severe CAC on preoperative imaging significantly impacted the all-cause survival of patients undergoing resection for stage I NSCLC. This impact on mortality should be taken into consideration by multidisciplinary teams when making treatment plans for patients with early-stage disease.