Early-stage Non-small Cell Lung Research Articles

Atezolizumab plus stereotactic ablative therapy for medically inoperable patients with early-stage non-small cell lung cancer.

9011 Background: Stereotactic ablative radiation therapy (SABR) is the standard-of-care for medically inoperable, early stage non-small cell lung cancer (NSCLC), but regional and distant failures remain problematic. Based on our in vivo data showing synergy between radiation and immune checkpoint inhibitors (ICI) and the known efficacy and mild toxicity profile of ICI in NSCLC, we conducted a phase I study to determine the maximum tolerated dose of neoadjuvant, concurrent, and adjuvant atezolizumab with SABR for early stage NSCLC patients (pts). Methods: Eligible pts had histologically confirmed T1-3 NSCLC with at least one feature predictive of increased recurrence risk: diameter ≥1 cm, SUV ≥6.2 on PET, or moderately/poorly differentiated histology, were medically inoperable or refused surgery and had a Zubrod PS ≤2. Patients received 6 cycles of atezolizumab. A 3+3 dose finding design was employed with 3 dose levels: 3 mg/kg, 10 mg/kg, and 1200 mg flat dosing. SABR was delivered starting cycle 3 to 50 Gy over 4-5 fractions. Dose limiting toxicity (DLT) was assessed during the first 9 weeks. Results: 20 pts were enrolled, 15 pts in the dose finding and 5 pts at the recommended phase II dose (RP2D). Patient factors: MedIan age 77; 45% male, 85% smoking history, 85% PS 0-1 and 35% squamous. One pt on dose level 2 had a DLT – a grade 3 rash. Atezolizumab 1200 mg flat dosing was the RP2D. Grade 3 pneumonitis was not observed. Partial responses after 2 cycles were seen in 3/17 evaluable pts (18%) and 1 pt had a minor response. No patient progressed on treatment. PD-L1 expression was 0% 8/13 (62%), >1% - 50% 4/13 (31%), >50% 1/13 (8%) in pts with sufficient tissue. Of 5 pts with PD-L1 expression 3 (60%) were responders and 1 (12.5%) of 8 pts with 0% PD-L1 expression responded. Multi-plex Quantitative Immunofluorescence (QIF) using a T cell activation panel demonstrated to correlate with ICI response was performed on 9 samples (including 2 responders, 1 minor responder). The CD3 QIF score was > two-fold higher in the responders compared to non-responders, and the levels of proliferating and activated T cells were likewise > two-fold higher. Comprehensive stool and serial blood analyses have been completed. Correlative endpoints will be reported along with additional efficacy outcomes. Conclusions: Atezolizumab plus SABR is feasible, safe and shows an efficacy signal in medically inoperable early stage NSCLC. This combination will be tested in a randomized phase III trial SWOG/NRG S1914. Funding: This work was supported by the DOD CDMRP W81XWH-15-2-0063 and Genentech. Clinical trial information: NCT02599454.

Early-stage KRAS G12C-mutated non-small cell lung cancer (NSCLC) in Australia.

e21053 Background: KRAS is frequently mutated in NSCLC, especially in Caucasian populations. Until recently there have not been effective targeted therapies against KRAS but the recent advent of active agents has thrown a spotlight on this disease. Methods: A database of NSCLC cases undergoing lobectomy or pneumonectomy with curative intent at Austin Health, Victoria, Australia was examined. Analysis for KRAS mutations was carried out using the LungCarta panel. Results: Four hundred and fifty nine cases underwent mutation analysis and 203/459 (44%) were wild type. KRAS mutations were identified in 100/459 cases (21.8%), including 3 cases where the specific mutation was not specified. KRAS G12C cases comprised 40/97 (8.5% of all cases, 41% of specified mutation KRAS cases) and other KRAS mutations comprised 57/97 (59%) - most commonly G12V (25 cases) and G12D (13 cases). Additional mutations were identified in 14/40 (36%) G12C mutation cases (10 dual and 4 triple – most commonly TP53 9, STK11 3 and PIC3CA 2). In non-G12C cases, multiple mutations were identified in 24% of cases. Considering the 40 G12C cases, histology was squamous cell in 21 cases, adenocarcinoma 13 and other 5. Males comprised 21/40 cases, median age at diagnosis was 61 year (range 34 – 78), with stage I 22 cases, stage II 12; stage IIIA 5 and one stage 4 (solitary brain metastasis). Thirty six patients (90%) had smoked tobacco with median exposure of 44 pack years (range 13-100) including 18 ex-smokers who had ceased a median 9 years (range 1 - 28) prior to the diagnosis of lung cancer. PD-L1 expression was analysed using the 28-8 antibody. For the 38 cases analysed, PD-L1 expression was ≥ 50% in 6 (16%), ≥ 5% in 12 (32%) and < 1% in 24 (63%). The estimated median overall survival was 4.9 years with 27% 10 year survival. Twenty three patients (58%) died from the index lung cancer, 8 (20%) remain alive and 9 (23%) died of other causes: 4 from a 2nd lung cancer, 4 from a non-lung cancer and one from liver failure. Data on sites of recurrence were available for 16 of the 23 cases who died from the index lung cancer, with initial recurrence sites being lung/local 7 patients, brain 6, bone 2, liver 1. A total of 9 patients (56%) developed brain metastases at some time. Conclusions: KRAS G12C is a common subgroup of NSCLC in the Australian population and almost all of cases were tobacco smokers. Additional mutations were identified in over a third of cases. Locally recurrent disease or brain metastases are the most frequent sites of relapse and over half of patients with recurrent disease develop brain metastases.

The impact of programmed death-ligand 1 expression on the prognosis of early-stage resected non-small cell lung cancer: A meta-analysis of literatures.

e21004 Background: Previous studies have demonstrated that programmed cell death-ligand 1 (PD-L1) serves as a poor prognostic biomarker for the survival in advanced-stage non-small-cell lung cancer (NSCLC) patients. However, the value of PD-L1 expression for the prognosis of early-stage NSCLC patients after complete resection remains controversial. Here, we conduct a meta-analysis to investigate the relationship between PD-L1 expression and prognosis in resected NSCLC. Methods: Electronic databases, including PubMed, EMBASE, and the Cochrane Library, were searched up until June 30 2019, for studies evaluating the expression of PD-L1 and prognosis of the resected NSCLC. Hazard ratios (HRs) with 95% confidence interval (CI) of overall survival (OS) and disease-free survival (DFS) were pooled and analyzed. Heterogeneity and publication bias analyses were also performed. Results: A total of 15 studies involving 3501 patients were enrolled. The pooled hazard ratio (HR) showed that PD-L1 expression was related to a much shorter DFS (HR = 1.63, 95% CI: 1.26-2.12, P = 0.022), as well a significantly worse OS (HR = 1.68, 95% CI: 1.32-2.14, P = 0.000). Furthermore, our analysis indicated that PD-L1 expression was significantly associated with gender (male vs. female: HR = 1.25, 95% CI:1.02-1.52, p = 0.028), tumor stage (III/IV vs. I/ II: HR = 2.39, 95% CI:1.85-3.08, p = 0.000), lymph node metastasis (N+ vs N-: HR = 3.54, 95%CI:2.56-4.88, p = 0.000) and smoking status (Yes vs No: HR = 1.37,95% CI:1.20-1.560, p = 0.000). Conclusions: The results of this meta-analysis suggest that PD-L1 expression predict an unfavorable prognosis in early-stage resected NSCLC. The role of individualized anti-PD-L1/PD-1immunotherapy in the adjuvant settings of resected NSCLC is worthy of being further investigated.

Adjuvant chemotherapy following SBRT for early stage non-small cell lung cancer (NSCLC) in older patients

Adjuvant chemotherapy improves overall survival (OS) following stereotactic body radiotherapy (SBRT) in patients with early stage non-small cell lung cancer and tumors ≥four cm. Here, we aim to evaluate its role following SBRT in older patients. Patients >70 years diagnosed with clinical stages I-II NSCLC, (N0 disease), who received SBRT, were identified using the National Cancer Database (n = 7042). The Kaplan-Meier method was used to estimate OS, and the log-rank test was used to compare distributions by treatment strategy overall and within clinical stages I and II. There were 3533 female patients (50.2%), and 6074 (86.3%) had stage I disease. Among stage I patients, 643 (10.6%) received adjuvant chemotherapy, compared to 372 stage II patients (38.4%). Median OS was better with SBRT in patients with stage I disease (25.4 vs. 20.3 months; p < .001); while patients with stage II NSCLC had better OS with SBRT + chemotherapy (20.2 vs. 14.2 months; p < .001). On multivariate analysis, patients with stage I NSCLC who received SBRT alone had better overall survival (HR: 0.79; 95% CI, 0.73, 0.87). SBRT alone was associated with an increased risk of death in patients with stage II disease (HR: 1.34; 95% CI, 1.15, 1.55). Patients with tumors ≥4 cm had better OS with SBRT + chemotherapy (18.5 vs. 15.5 months; p = .003), while patients with tumors <4 cm did better with SBRT (median OS of 24.1 vs. 20.3 months; p < .001). In >70 years old patients with tumors ≥4 cm, adjuvant chemotherapy following SBRT was associated with improved OS.

Outcomes of lobectomy on pulmonary function for early stage non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD).

BackgroundLung cancer is the first cause of cancer mortality worldwide. Chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer. An epidemiological survey discovered that the presence of COPD increases the risk of lung cancer by 4.5‐fold. Lobectomy is considered to be the standard surgical method for early stage non‐small cell lung cancer (NSCLC). However, the influence of lobectomy on the loss of pulmonary function has not been fully investigated in NSCLC patients with COPD.MethodsWe searched the PubMed database using the following strategies: COPD and pulmonary function test (MeSH term) and lobectomy (MeSH term) from 01 January 1990 to 01 January 2019. We selected the articles of patients with COPD. A total of six studies, including 195 patients with COPD, provided lung function values before and after surgery.ResultsFive out of six studies focused on the short‐term change of pulmonary function (within 3–6 months) after lobectomy, and the average loss of FEV1 was 0.11 L (range: −0.33–0.09 L). One study investigated the long‐term change of pulmonary function (within 1–2 years) after lobectomy, and the average loss of FEV1 was 0.15 L (range: −0.29–0.05 L).ConclusionsA short‐term (3–6 months) loss of pulmonary function after operation is acceptable for lung cancer patients with COPD. However, there may be a high risk of postoperative complications in NSCLC patients with COPD. Therefore, surgical treatment needs to be carefully considered for these patients.

Differences in failure patterns according to the EGFR mutation status after proton beam therapy for early stage non-small cell lung cancer

We analyzed 135 patients (including 27 EGFR-mutant and 29 EGFR-wild) with T1-3N0M0 non-squamous NSCLC treated by PBT. Considering the 3-year cumulative incidence, the EGFR-mutant group showed a significantly lower infield failure rate (9% vs 27%, p = 0.02) and higher out-of-field failure rate (67% vs 40%, p = 0.02) than the EGFR-wild group.

Uptake of minimally invasive surgery and stereotactic body radiation therapy for early stage non-small cell lung cancer in the USA: an ecological study of secular trends using the National Cancer Database

BackgroundWe aimed to assess the uptake of minimally invasive surgery (MIS) and stereotactic body radiation therapy (SBRT) among early stage (stage IA–IIB) non-small cell lung cancer (NSCLC) cases in the...

Tumor volume reduction evaluated by cone beam computed tomography during stereotactic body radiotherapy for early stage non-small cell lung cancer.

BackgroundWe hypothesized that significant tumor volume reduction (TVR) occurs over the course of stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer (NSCLC), and that TVR correlates with clinical outcomes.MethodsWe conducted a retrospective review of patients treated with SBRT for early stage NSCLC across two academic centers. For each patient, we contoured the tumor volume (TV) on cone beam computed tomography (CBCT) images obtained before each treatment fraction. We then calculated TVR based on the TV from the first and last days of treatment. We used log-rank tests to quantify differences in overall survival (OS), progression-free survival (PFS) and recurrence based on TVR.ResultsData from 69 patients and a total of 73 treated tumors were analyzed. The median follow-up for survivors was 51.8 months (range, 6.9 to 80.0 months). The median TVR for the cohort was 10.1% (range, −5.7% to 43.5%). There was no significant difference in either OS (median 33.4 vs. 29.1 months, P=0.79) or PFS (median 26.3 vs. 12.3 months, P=0.43) for those with high TVRs (≥10.1%) vs. low TVRs (<10.1%), respectively. There was a trend toward superior 2-year PFS in the high TVR group (52.2% vs. 36.7%, P=0.062), but this effect diminished on longer follow-up (4-year PFS 31.9% vs. 26.7%, P=0.15). No associations were observed between TVR and local, regional or distant recurrence.ConclusionsWe were not able to demonstrate that TVR is a reliable predictive imaging marker for stage I/II NSCLC treated with SBRT. Future studies with larger sample sizes are needed to clarify a potential relationship between TVR and early outcomes.

Analyzing the Time From Discovery to Definitive Surgical Therapy for Lung Cancer Based on Referral Patterns.

Surgery for early stage non-small cell lung cancer can be curative. A delay from diagnosis to surgery can lead to increased mortality. Our objective was to determine if referring patients to specialists before a thoracic surgeon caused a delay in definitive treatment. A retrospective review was conducted of patients who had surgery for non-small cell lung cancer by a single surgeon at our institution from 2013 to 2016. Patients were divided into 2 groups: those who saw a specialist before a thoracic surgeon and patients who were referred directly to a surgeon once the pulmonary nodule was identified on computed tomography (CT). The time from initial CT to resection was compared. Secondary analysis compared private insurance versus Medicare/Medicaid. Percentage of patients upstaged was compared. There was no significant difference between groups when comparing time from CT to surgery (79.88 vs. 79.90 d; P=0.58). There was a significant decrease in time from CT to surgery for patients with private insurance compared with Medicare/Medicaid patients (66.05 vs. 86.99 d; P=0.03) and fewer private insurance patients were upstaged (22.9% vs. 31.8%; P=0.32). More patients who saw a different specialist first were upstaged compared with patients sent directly to thoracic surgery (32.6% vs. 22.2%; P=0.22). When comparing time from CT detection of a lung nodule to surgery, no significant difference was found between patients sent to nonthoracic specialists first and those referred directly to a thoracic surgeon. There was a significant decrease in time from CT to surgery for patients with private insurance compared with Medicare/Medicaid.

Stereotactic Ablative Body Radiotherapy in Non-small Cell Carcinoma Lung in Elderly: Initial Experience from a Rural Tertiary Cancer Centre

Aim: The aim of this study was to evaluate the efficacy and outcome of early stage non-small cell lung carcinoma in elderly patients treated with SABR in a tertiary care cancer centre in rural India. Materials and methods: This was a retrospective study. All cases of histopathologically proven, stage 1 lung cancer patients in whom surgical management was not feasible due to various reasons were included. It included patients treated from 2013 to 2018 at our centre. Case records and radiation treatment plans were reviewed and data was collected. All were T1/T2N0 cases. Dose schedules employed were 48 Gy in 4 fractions, 60 Gy in 5 fractions and 60 Gy in 3 fractions. The primary end point was the tolerance and toxicity profile. Results: A total of 5 patients were treated at our center from 2013 to 2017. All were males. Mean age was 72 years. One had squamous cell and four had adenocarcinoma histology. The dose fractionation schedules employed where 48 Gy in 4 fractions, 60 Gy in 5 fractions and 60 Gy in 3 fractions. All tolerated treatment well. No grade 3 or 4 toxicities were observed. Conclusion: SABR is a feasible alternative curative treatment modality in stage 1 NSCLC. It is feasible and was tolerated well even in the elderly age group. This can be offered to medically inoperable patients as a curative treatment and is possible in a resource constrained setting also. This modality is a promise to future for operable stage 1 NSCLC also. But more randomized studies need to be carried out before applying it to operable lung cancer patients.

Lymph node assessment in early stage non-small cell lung cancer lymph node dissection or sampling?

Lymph node assessment is an essential component of the treatment of lung cancer. Identification of the correct "N" stage is important for staging which in turn determines treatment. Assessment of lymph nodes may be accomplished using imaging with CT scan and PET-CT, invasive techniques such as mediastinoscopy, endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) or endoscopic ultrasound fine needle aspiration (EUS-FNA). Ultimately, regardless of any pre-resection assessment, lymph nodes must be assessed at the time of resection. The question to be addressed in this report is the role of mediastinal lymph node dissection versus lymph node sampling. However, the issues surrounding lymph node assessment in NSCLC are complex, depending on clinical stage, imaging and histology.

Non-invasive Detection of Exosomal MicroRNAs via Tethered Cationic Lipoplex Nanoparticles (tCLN) Biochip for Lung Cancer Early Detection.

Circulating microRNAs carried by exosomes have emerged as promising diagnostic biomarkers for cancer because of their abundant amount and remarkable stability in body fluids. Exosomal microRNAs in blood are typically quantified using the RNA isolation-qRT-PCR workflow, which cannot distinguish circulating microRNAs secreted by cancer cells from those released by non-tumor cells, making it potentially less sensitive in detecting cancer-specific microRNA biomarkers. We have developed a sensitive and simple tethered cationic lipoplex nanoparticles (tCLN) biochip to detect exosomal microRNAs in human sera. The tCLN biochip allows the discrimination of tumor-derived exosomes from their non-tumor counterparts, and thus achieves higher detection sensitivity and specificity than qRT-PCR. We have demonstrated the clinical utility of the tCLN biochip in lung cancer diagnosis using sera from normal controls, therapy-naive early stage and late stage non-small cell lung cancer (NSCLC) patients. Total five microRNAs (miR-21, miR-25, miR-155, miR-210, and miR-486) were selected as the biomarkers. Each microRNA biomarker measured by tCLN assay showed higher sensitivity and specificity in lung cancer detection than that measured by qRT-PCR. When all five microRNAs were combined, the tCLN assay distinguished normal controls from all NSCLC patients with sensitivity of 0.969, specificity of 0.933 and AUC of 0.970, and provided much better diagnostic accuracy than qRT-PCR (sensitivity = 0.469, specificity = 1.000, AUC = 0.791). Remarkably, the tCLN assay achieved absolute sensitivity and specificity in discriminating early stage NSCLC patients from normal controls, demonstrating its great potential as a liquid biopsy assay for lung cancer early detection.

Initial experience of robotic anatomical segmentectomy for non-small cell lung cancer

Anatomical segmentectomy has the potential to replace lobectomy as the standard procedure for early stage non-small cell lung cancer. We investigated the safety and feasibility of robotic anatomical segmentectomy for non-small cell lung cancer. Overall 20 patients underwent robotic anatomical segmentectomy at Hiroshima University Hospital between January 2014 and January 2018. The clinicopathological characteristics, surgical outcomes, complications and prognosis were analyzed. The median age was 68 (range 42-86) years, and 15 patients were female. Six patients were non-smokers. The most common clinical stage was IA1 (nine patients). Complex segmentectomies were performed in four patients (one right S3 segmentectomy, two right S8 segmentectomies and one left S8+S9 segmentectomy). The median operation time was 163.5 (range, 114-314) minutes, and the median console time was 104 (range, 60-246) minutes. The median blood loss was 26.5 (range, 5-247) ml. The median resection margin and number of dissected lymph node were 15 (range, 2-60) mm and 5 (range, 1-15), respectively. Although five (25.0%) patients had grade IIIa complications (pleurodesis for prolonged air leakage) and one (5.0%) had a grade IIIb complication (reoperation for prolonged air leakage), no post-operative deaths occurred. The surgical outcomes were comparable with those of anatomical segmentectomy performed under hybrid video-assisted thoracoscopic surgery during the same period. In our initial experience of robotic anatomical segmentectomy for early stage non-small cell lung cancer, the procedure seems to be safe and feasible.

Minimally Invasive Therapies for Early Stage Non-small Cell Lung Cancer

肺癌是目前全球最常见的癌症和癌症死亡的主要原因，其中非小细胞肺癌（non-small-cell lung cancer, NSCLC）约占肺癌总数的85%。随着计算机断层扫描（computed tomography, CT）等影像学筛查手段得到不断普及，肺癌的病理类型从以往以晚期中央型肺鳞癌为主，转变为现在的以早期周围型磨玻璃样结节等为表现的肺腺癌为主。肺癌的早诊早治有着重要意义，而微创介入技术的不断发展完善，使得肺癌治疗有了更多的选择，例如立体定向放射、经皮穿刺消融、支气管介入等。本文将就目前临床常见的这些微创介入治疗的作用原理、优势、不足及展望做一评述。

Stable and discriminating radiomic predictor of recurrence in early stage non-small cell lung cancer: Multi-site study

ObjectivesTo evaluate whether combining stability and discriminability criteria in building radiomic classifiers will improve the prognosis of cancer recurrence in early stage non-small cell lung cancer on non-contrast computer tomography (CT). Materials and MethodsCT scans of 610 patients with early stage (IA, IB, IIA) NSCLC from four independent cohorts were evaluated. A total of 350 patients from Cleveland Clinic Foundation and University of Pennsylvania were divided into two equal sets for training (D1) and validation set (D2). 80 patients from The Cancer Genome Atlas Lung Adenocarcinoma and Squamous Cell Carcinoma and 195 patients from The Cancer Imaging Archive, were used as independent second (D3) and third (D4) validation sets. A linear discriminant analysis (LDA) classifier was built based on the most stable and discriminate features. In addition, a radiomic risk score (RRS) was generated by using least absolute shrinkage and selection operator, Cox regression model to predict time to progression (TTP) following surgery. ResultsA feature selection strategy focusing on both feature discriminability and stability resulted in the classifier having a higher discriminability on validation datasets compared to the discriminability alone criteria in discriminating cancer recurrence (D2, AUC of 0.75 vs. 0.65; D3, 0.74 vs. 0.62; D4, 0.76 vs. 0.63). The RRS generated by most stable-discriminating features was significantly associated with TTP compared to discriminating alone criteria (HR = 1.66, C-index of 0.72 vs. HR = 1.04, C-index of 0.62). ConclusionAccounting for both stability and discriminability yielded a more generalizable classifier for predicting cancer recurrence and TTP in early stage NSCLC.

Blood test shows high accuracy in detecting stage I non-small cell lung cancer

BackgroundIn a previous study (Goebel et. al, Cancer Genomics Proteomics 16:229-244, 2019), we identified 33 biomarkers for an early stage (I-II) Non-Small Cell Lung Cancer (NSCLC) test with 90% accuracy, 80.3% sensitivity, and 95.4% specificity. For the current study, we used a narrowed ensemble of 21 biomarkers while retaining similar accuracy in detecting early stage lung cancer.MethodsA multiplex platform, 486 human plasma samples, and 21 biomarkers were used to develop and validate our algorithm which detects early stage NSCLC. The training set consisted of 258 human plasma with 79 Stage I-II NSCLC samples. The 21 biomarkers with the statistical model (Lung Cancer Detector Test 1, LCDT1) was then validated using 228 novel samples which included 55 Stage I NSCLC.ResultsThe LCDT1 exhibited 95.6% accuracy, 89.1% sensitivity, and 97.7% specificity in detecting Stage I NSCLC on the blind set. When only NSCLC cancers were analyzed, the specificity increased to 99.1%.ConclusionsCompared to current approved clinical methods for diagnosing NSCLC, the LCDT1 greatly improves accuracy while being non-invasive; a simple, cost-effective, early diagnostic blood test should result in expanding access and increase survival rate.

Stereotactic Ablative Radiotherapy With Nivolumab for Early-Stage Operable Non-Small Cell Lung Cancer

Stereotactic Ablative Radiotherapy With Nivolumab for Early-Stage Operable Non-Small Cell Lung Cancer

Analysis of Driver Gene Mutation in Early Stage Non-small Cell Lung Cancer

Analysis of Driver Gene Mutation in Early Stage Non-small Cell Lung Cancer

Definitive Management of Presumed Synchronous Early Stage Non-Small Cell Lung Cancers: Outcomes and Utility of Stereotactic Ablative Radiation Therapy

Management of synchronous early-stage non-small cell lung cancer (NSCLC) remains controversial because resection is not always feasible. This study evaluates efficacy and patterns of failure after SABR for synchronous early-stage NSCLC. From 2005 to 2015, patients presenting with ≥2 synchronous NSCLC tumors (T1a-T2b) and receiving SABR to ≥1 lesion were reviewed. The most common prescriptions were 50 Gy in 4 or 70 Gy in 10 fractions. Patients underwent multidisciplinary management with workup including chest computed tomography and positron emission tomography/computed tomography, plus brain imaging and endoscopic bronchial ultrasound for most patients to rule out mediastinal and distant disease. Synchronous lesions were defined as multiple ipsilateral or contralateral intrapulmonary lesions diagnosed within 6 months. Of 912 patients treated with SABR for early-stage NSCLC at our institution, 82 (9%) presented with synchronous disease, with a total of 169 lesions. SABR was delivered to 142 lesions (84%), with 57 patients (69.5%) receiving SABR for all sites. Median overall survival (OS) and progression-free survival (PFS) were 5.1 and 2.7 years, respectively. At a median follow-up of 58 months, OS was 67% and 52% at 3 and 5 years, and corresponding PFS was 47% and 29%. Thirty-nine patients (48%) had progression, with 21 (26%) experiencing distant failure, and intralobar recurrence was among the first failure for 15 patients (18%). Of the 142 SABR-treated sites, these included 6 in-field (4%) and 4 marginal (3%) recurrences. There were no grade ≥3 adverse events. Among patients receiving SABR for all sites, there were no differences in OS (P = .946), PFS (P = .980), local control (P = .683), regional and distant control (P = .656), or toxicity (P = .791). On multivariable analysis, ipsilateral synchronous disease was associated with greater regional and distant failure (hazard ratio, 2.691; P = .025). Synchronous NSCLC can be managed with definitive local therapy. With high control rates and favorable outcomes, SABR is an effective and feasible treatment for synchronous early-stage NSCLC.

Liver kinase B1 correlates with prognosis and epithelial-mesenchymal transition of resectable early stage non-small cell lung cancer.

BackgroundRecent evidences support that low expression of liver kinase B1 (LKB1) triggers epithelial-mesenchymal transition (EMT) through induction of Zinc finger E-box binding homeobox 1 (ZEB1) expression, which downregulates E-cadherin in human lung cancer cell lines. However, the clinicopathological significance of LKB1, EMT, salt-inducible kinase 1 (SIK1), ZEB1 and their relationship in early stage non-small cell lung cancer (ES-NSCLC) patients remain to be determined. In this study, the correlation among expression of LKB1, risk of distant metastasis, prognostic significance, and EMT in ES-NSCLC after surgery was investigated by immunohistochemistry.MethodsCase notes and pathology records of 103 patients with ES-NSCLC were retrospectively analyzed. Immunohistochemical staining was employed to detect LKB1, EMT biomarkers (E-cadherin and vimentin), SIK1 and ZEB1 expression in ES-NSCLC tissues.ResultsLKB1 expression is associated with distant metastasis after treatment (P=0.017). LKB1-high expression group has better overall survival (OS) (P=0.000) and disease-free survival (DFS) (P=0.000). LKB1 expression is correlated with E-cadherin (r=0.231, P=0.019), vimentin (r=−0.225, P=0.022), SIK1 (r=0.218, P=0.027) and ZEB1 (r=−0.242, P=0.014).ConclusionsOur findings suggest that LKB1-high expression is possibly associated with favourable prognosis and LKB1 expression is correlated with EMT and expression of SIK1 and ZEB1.