Stage IA Non-small Cell Lung Cancer Research Articles

Interstitial lung disease and wedge resection are poor prognostic factors for non-small cell lung cancer.

BackgroundAlthough several prognostic factors in patients undergoing pulmonary resection with early-stage non-small cell lung cancer (NSCLC) have been reported, the risk factors are varied and have not been consistent among reports.MethodsClinical data of 540 patients with pathological stage IA NSCLC were analyzed. Patient factors, such as the sex, age, comorbidities, carcinoembryonic antigen (CEA) level, and smoking history, and surgical factors, such as the operative approach and procedure, were collected and analyzed.ResultsThere were significant prognostic differences in the relapse-free survival (RFS) depending on the presence of interstitial lung disease (P<0.0001), CEA level (P=0.007), and wedge resection (P=0.002). There were significant prognostic differences in the overall survival (OS) depending on the presence of interstitial lung disease (P=0.0015), CEA level (P<0.0001), and smoking history (P=0.0003). Interstitial lung disease [hazard ratio (HR): 7.725, P=0.003], the CEA level (HR: 1.923, P=0.045), and operative procedure (HR: 2.086, P=0.025) were risk factors for the RFS in a multivariate analysis. The smoking history (HR: 2.539, P=0.002) and CEA level (HR: 2.464, P=0.002) were risk factors for the OS in a multivariate analysis.ConclusionsInterstitial lung disease, the CEA level, and operative procedure were risk factors for the RFS, while the smoking history and CEA level were risk factors for the OS.

Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): a multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial

Lobectomy is the standard of care for early-stage non-small-cell lung cancer (NSCLC). The survival and clinical benefits of segmentectomy have not been investigated in a randomised trial setting. We aimed to investigate if segmentectomy was non-inferior to lobectomy in patients with small-sized peripheral NSCLC. We conducted this randomised, controlled, non-inferiority trial at 70 institutions in Japan. Patients with clinical stage IA NSCLC (tumour diameter ≤2 cm; consolidation-to-tumour ratio >0·5) were randomly assigned 1:1 to receive either lobectomy or segmentectomy. Randomisation was done via the minimisation method, with balancing for the institution, histological type, sex, age, and thin-section CT findings. Treatment allocation was not concealed from investigators and patients. The primary endpoint was overall survival for all randomly assigned patients. The secondary endpoints were postoperative respiratory function (6 months and 12 months), relapse-free survival, proportion of local relapse, adverse events, proportion of segmentectomy completion, duration of hospital stay, duration of chest tube placement, duration of surgery, amount of blood loss, and the number of automatic surgical staples used. Overall survival was analysed on an intention-to-treat basis with a non-inferiority margin of 1·54 for the upper limit of the 95% CI of the hazard ratio (HR) and estimated using a stratified Cox regression model. This study is registered with UMIN Clinical Trials Registry, UMIN000002317. Between Aug, 10, 2009, and Oct 21, 2014, 1106 patients (intention-to-treat population) were enrolled to receive lobectomy (n=554) or segmentectomy (n=552). Patient baseline clinicopathological factors were well balanced between the groups. In the segmentectomy group, 22 patients were switched to lobectomies and one patient received wide wedge resection. At a median follow-up of 7·3 years (range 0·0-10·9), the 5-year overall survival was 94·3% (92·1-96·0) for segmentectomy and 91·1% for lobectomy (95% CI 88·4-93·2); superiority and non-inferiority in overall survival were confirmed using a stratified Cox regression model (HR 0·663; 95% CI 0·474-0·927; one-sided p<0·0001 for non-inferiority; p=0·0082 for superiority). Improved overall survival was observed consistently across all predefined subgroups in the segmentectomy group. At 1 year follow-up, the significant difference in the reduction of median forced expiratory volume in 1 sec between the two groups was 3·5% (p<0·0001), which did not reach the predefined threshold for clinical significance of 10%. The 5-year relapse-free survival was 88·0% (95% CI 85·0-90·4) for segmentectomy and 87·9% (84·8-90·3) for lobectomy (HR 0·998; 95% CI 0·753-1·323; p=0·9889). The proportions of patients with local relapse were 10·5% for segmentectomy and 5·4% for lobectomy (p=0·0018). 52 (63%) of 83 patients and 27 (47%) of 58 patients died of other diseases after lobectomy and segmentectomy, respectively. No 30-day or 90-day mortality was observed. One or more postoperative complications of grade 2 or worse occurred at similar frequencies in both groups (142 [26%] patients who received lobectomy, 148 [27%] who received segmentectomy). To our knowledge, this study was the first phase 3 trial to show the benefits of segmentectomy versus lobectomy in overall survival of patients with small-peripheral NSCLC. The findings suggest that segmentectomy should be the standard surgical procedure for this population of patients. National Cancer Center Research and the Ministry of Health, Labour, and Welfare of Japan.

Postoperative venous thromboembolism after surgery for stage IA non-small-cell lung cancer: A single-center, prospective cohort study.

BackgroundVenous thromboembolism (VTE) is a common postoperative complication of lung cancer, but the incidence and risk stratification of postoperative VTE in stage IA non‐small‐cell lung cancer (NSCLC) patients remains unclear, therefore we conducted a single‐center prospective study.MethodsA total of 314 consecutive patients hospitalized for lung cancer surgery and diagnosed with stage IA NSCLC from January 2017 to July 2021 were included. The patients were divided into the VTE group and the non‐VTE group according to whether VTE occurred after the operation. The patient's age, operation time, D‐dimer (D‐D) value, tumor pathology, and Caprini score were recorded. The different items were compared and included in logistic regression analysis to obtain independent risk factors, and the area under the receiver operating characteristics curve (AUC) was calculated.ResultsThe incidence of VTE was 7.3%. Significant differences in age, operation time, preoperative and postoperative day 1 D‐D value, neuron‐specific enolase value, forced expiratory volume in 1 second, maximum ventilation, carbon monoxide diffusion capacity, and pathological diameter were noted between the two groups. Age (95% confidence interval [CI] 1.056–1.216) and postoperative day 1 D‐D value (95% CI 1.125–1.767) were independent risk factors. The incidence of VTE in the low‐, medium‐, and high‐risk groups with Caprini scores was 0%, 7.3%, and 11.5%, respectively. The AUC of the Caprini score was 0.704 (p < 0.05).ConclusionsThe incidence of postoperative VTE in patients with stage IA NSCLC was 7.3%. Age and postoperative day 1 D‐D value were independent risk factors for VTE. The Caprini score has a certain value in the diagnosis of postoperative VTE of stage IA NSCLC.

The prognostic impact of the ground-glass opacity component in nearly pure-solid stage IA non-small-cell lung cancer.

The aim of this study was to assess the clinical effects of a small ground-glass opacity (GGO) component of a radiologically nearly pure-solid tumour on tumour aggressiveness in patients with clinical stage IA non-small-cell lung cancer (NSCLC). Data of 988 patients with clinical stage IA NSCLC who had a consolidation-to-tumour ratio of ≥0.75 on high-resolution computed tomography were retrospectively analysed. The cumulative incidence of recurrence (CIR) was compared between patients with GGO (nearly pure-solid, n = 297) and those without GGO (pure-solid, n = 691). In patients with clinical T1mi + T1a and T1b, the CIR was significantly higher in the pure-solid group than in the nearly pure-solid group (5-year CIR, 15.2% and 19.3% vs 0% and 6.4%; P < 0.001); however, this was not the case for patients with clinical T1c (5-year CIR, 23.1% vs 26.5%; P = 0.580). In the multivariable analysis, pure-solid tumours were independently associated with a higher CIR than nearly pure-solid tumours in patients with clinical T1mi + T1a + T1b (solid tumour size ≤2 cm; subdistribution hazard ratio, 3.25; 95% confidence interval, 1.59-6.63; P = 0.001) but not in those with clinical T1c tumours (2-3 cm; subdistribution hazard ratio, 0.67; 95% confidence interval, 0.39-1.13; P = 0.130). Nearly pure-solid tumours with a small GGO component influence tumour aggressiveness based on solid tumour size, with a threshold of 2 cm in patients with clinical stage IA NSCLC. For tumours sized 2-3 cm, nearly pure-solid tumours had a similar tumour aggressiveness as pure-solid tumours.

Preoperative Helical Dynamic Enhanced Multidetector Row Computed Tomography: Can It Be a Prognostic Indicator in Early-Stage Non–small Cell Lung Cancer?

ObjectiveThis study aimed to investigate the prognostic significance of dynamic contrast-enhanced computed tomography in patients with stage IA non–small cell lung cancer (NSCLC).MethodsWe retrospectively enrolled 139 patients (77 men, 62 women; mean age, 59 years) with stage IA NSCLC who underwent dynamic contrast-enhanced computed tomography. Data on age, pathologic subtype, peak enhancement, and net enhancement of primary lung cancer were collected and correlated with 5-year survival.ResultsPeak enhancement had a significant correlation with overall survival in the univariable analysis (hazard ratio [HR], 1.18, confidence interval [CI], 1.01–1.38; P = 0.04) and in the multivariable analysis (HR, 1.19; CI, 1.01–1.39; P = 0.04). Patients with peak enhancement of 90 Hounsfield unit or higher had a significantly increased risk of death compared with patients with less enhancement after curative surgery (HR, 4.15; CI, 1.23–13.95; P = 0.02).ConclusionsOur study confirmed the prognostic significance of peak enhancement as an indicator for the overall survival of stage IA NSCLC.

Extent of Resection Influences Survival in Early-Stage Lung Cancer With Occult Nodal Disease

BackgroundMinimal literature exists evaluating the impact of the extent of resection on survival in patients with small, early-stage non-small cell lung cancer (NSCLC) found to have occult nodal disease. We hypothesized that sublobar resection has comparable overall survival to patients undergoing lobectomy for clinical stage IA NSCLC that harbors occult nodal disease. MethodsThe National Cancer Database was reviewed for identification of patients with clinical stage IA NSCLC who underwent wedge resection, segmentectomy, or lobectomy and were found to have occult nodal disease. Overall survival was compared between groups, and a multivariate Cox regression model identified factors associated with worse survival. ResultsOccult nodal disease occurred in 6.1% of all patients with clinical stage IA disease undergoing resection. Patients undergoing wedge resection and segmentectomy found to have occult nodal disease were older (67.6 ± 9.6 years of age vs 66.1 ± 9.3 years of age vs 65.6 ± 9.5 years of age; P = .004) and had more advanced pathologic stage (pStage III: 68.7% vs 50.5% vs 41.5%; P < .001) than those receiving lobectomy. There was no difference in the median overall survival between segmentectomy and lobectomy (68.5 months vs 57.6 months; P = .200). However, wedge resection was independently associated with worse overall survival when controlling for other preoperative variables (hazard ratio, 1.23; 95% confidence interval, 1.01-1.51; P = .042). ConclusionsReview of the National Cancer Database suggests that there is no improvement in overall survival in patients undergoing lobectomy vs segmentectomy in carefully selected patients with clinical stage IA NSCLC harboring occult nodal disease. However, those undergoing wedge resection may have worse overall survival than those undergoing both lobectomy and segmentectomy.

Multidimensional profiling depicts infiltrating immune cell heterogeneity in the tumor microenvironment of stage IA non-small cell lung cancer.

BackgroundEmerging evidence has underscored infiltrating immune cells in the tumor microenvironment (TME) of non‐small cell lung cancer (NSCLC). Owing to screening programs, the prevalence of early‐stage NSCLC is growing, but its high recurrence risk and poor survival impose an increasing demand for further understanding the TME.MethodsTissue and plasma samples from 33 resectable stage IA NSCLC patients were collected from the surgery and subject to histological and genomic analyses. The distribution of CD8+ T cells, tumor‐associated macrophages (TAMs, M1 polarization and M2 polarization), and natural killer (NK) cells (CD56dim and CD56bright) was analyzed. The impact of clinical characteristics and immunotherapy‐related biomarkers on immune cell infiltration were also investigated.ResultsUsing multiplex immunohistochemistry (mIHC), we found a significantly higher M1 polarization proportion of total TAMs in tumor parenchyma than in other tissues, while other immune cells remained stable. Patients under 50 showed higher infiltrating CD8+ T cell density and M1 ratio in tumor tissues. Tumors carrying RAS‐MAPK mutations were associated with significantly increased infiltration of CD8+ T cells. We also identified significantly higher infiltration of CD8+ T cells and enrichment of CD56bright NK cells in high tumor mutation burden (TMB) and high programmed cell death ligand 1 (PD‐L1) samples, respectively.ConclusionsOur study highlighted the heterogeneity and dynamics of infiltrating immune cells in stage IA NSCLC TME, featured by M1 TAM enrichment in tumor parenchyma. Age, driver mutation type, TMB, and PD‐L1 level were found to associate with immune cell infiltration in the TME, shedding light on immunotherapy development.

Segmentectomy Provides Comparable Outcomes to Lobectomy for Stage IA Non-small Cell Lung Cancer with Spread through Air Spaces

This study aimed to compare the recurrence-free survival (RFS) and overall survival (OS) among wedge resection (non-anatomical resection), segmentectomy and lobectomy for pathological stage IA non-small cell lung cancer (NSCLC) with spread through air spaces (STAS). Patients underwent surgical treatment for pathological stage IA NSCLC between January 1, 2005, and March 31, 2016, at our hospital. Surgical procedures were classified as lobectomy, segmentectomy, and wedge resection. Among the 555 analyzed cases, STAS was observed in 148 patients (26.7%). STAS was correlated with worse RFS (P < 0.001) and OS (P < 0.001) and was an independent poor prognostic factor for RFS (hazard ratio: 2.37, P < 0.001) and OS (hazard ratio: 2.02, P < 0.001) in the multivariate analysis. In patients with STAS, the RFS and OS in the segmentectomy group were comparable to those in the lobectomy group. However, the RFS and OS in the wedge resection group were significantly lower than those in the lobectomy group (RFS, P < 0.001; OS, P=0.001). Wedge resection was an independent prognostic factor for poor RFS (hazard ratio [HR]=3.87; 95% confidence interval [CI]=1.84 - 8.12, P < 0.001), and poor OS (hazard ratio [HR]=3.39; 95% confidence interval [CI]=1.33 - 8.76, P=0.011) in the multivariate analysis. Segmentectomy is an adequate operation for patients with stage IA NSCLC with or without STAS. However, wedge resection is associated with a higher risk of recurrence in this patient population.

Impact of marital status on survival in patients with stage 1A NSCLC.

Objectives: To study how marital status influences overall survival (OS) in patients with stage IA non-small cell lung cancer (NSCLC). And whether the result is valid in different time periods.Materials and Methods: We retrospectively analyzed 55,207 cases of stage IA NSCLC from 1995 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Marital status was classified as follows: married or with unmarried/domestic partner (MR/W.P), divorced or separated (DV/SP), widowed (WD), and single (never married). Patients diagnosed in 1995-2005 and 2006-2015 were analyzed separately as groups 1 and 2, respectively, to validate the results. Within each group, age-stratified demographic, clinicopathologic features, and OS were compared among different marital statuses.Results and Conclusions: A total of 55,207 cases were included (group 1 n=20,223, group 2 n=34,984). From 1995-2005 to 2006-2015, median OS was prolonged significantly in all patients besides the DV/SP subgroup. In general, being MR/W.P was associated with the lowest relative risk of death in the study population (Group 1, HR= 0.854, 95%CI: 0.816-0.893; Group 2, HR = 0.799, 95%CI: 0.758-0.842). Meanwhile, OS of DV/SP and widowed patients was similar. In group 2, being single was associated with lower risk of death beyond 60-year-old.

Prediction of lymph node metastasis of clinical stage IA non-small cell lung cancer based on the tumor volume doubling time.

To investigate whether the volume doubling time is a preoperative predictor of lymph node metastasis of clinical stage IA non-small cell lung cancer (NSCLC). The subjects of this retrospective study were 204 patients who underwent lobectomy and mediastinal lymph node dissection for clinical stage IA NSCLC. We analyzed the relationship between lymph node metastasis and clinicopathological factors, including the volume doubling time. Lymph node metastasis developed in 24 (11.8%) patients. Multivariable analysis identified consolidation diameter (Odds ratio = 1.407; 95% confidence interval, 1.007-1.966, p = 0.046) and the solid-part tumor volume doubling time (Odds ratio = 0.982; 95% confidence interval, 0.973-0.991, p < 0.001) as independent predictors of lymph node metastasis. The combination of a larger consolidation diameter (> 1.9cm) and a shorter solid-part tumor volume doubling time (< 132days) had sensitivity, specificity, and accuracy of 79.2%, 94.4%, and 92.6%, respectively. The consolidation diameter and solid-part tumor volume doubling time can be useful preoperative predictors of lymph node metastasis of clinical stage IA NSCLC.

Clinical significance of epidermal growth factor receptor mutations in resected stage IA non-small cell lung cancer

Background: Epidermal growth factor receptor (EGFR) gene mutation is a known predictor of the response to EGFR tyrosine kinase inhibitors. However, detecting EGFR mutations is a potential challenge because of the ground-glass opacity component, and its prognostic value for stage IA lung adenocarcinoma remains controversial. This study aimed to investigate the associations between EGFR mutation status, clinicopathological characteristics, and prognosis in surgically resected stage IA non-small cell lung cancer (NSCLC). Materials and Methods: We retrospectively examined the data of patients who underwent surgical resection for lung cancer between 2004 and 2014. The clinical data, imaging characteristics of nodules, surgical approaches, and outcomes were analyzed. Results: A total of 429 patients (female, n = 303; male, n = 126) with surgically resected stage IA NSCLC were analyzed and 343 were nonsmokers. The EGFR mutation rate was 48.3% (n = 207). Of the patients, 192 (44.8%) had stage IA1, 165 (38.5%) had stage IA2, and 72 (16.8%) had stage IA3 NSCLC. In the analysis of the correlations between clinicopathological features and EGFR status, older age (P = 0.032), nonsmoking history (P = 0.039), and pathological stage (P < 0.05) were related to EGFR mutation. Patients with stage IA2 NSCLC had a higher positive expression of EGFR than patients with stages IA1 and IA3. The 5-year overall survival rates and disease-free survival rates were better in the EGFR mutation group; however, the difference was not statistically significant. Conclusion: EGFR mutations are common in older and nonsmoking patients with stage IA NSCLC. Further separate analyses of EGFR gene mutations and pathological stage could improve the diagnostic performance and predict patients with unavailable EGFR gene testing who may benefit from targeted drug treatment.

The Independent Prognostic Effect of Lymph Node Dissection on Patients With Stage IA NSCLC With Different T Stages.

Background: Currently, the extent of lymph node evaluation necessary for patients with early-stage non-small-cell lung cancer (NSCLC) remains controversial according to the latest ESMO and NCCN guidelines. In this study, we aimed to evaluate the survival effect of different numbers of lymph nodes examined (LNE) and regions of lymph nodes removed (LNR) in patients with stage IA NSCLC.Method: All patients with stage IA NSCLC undergoing lobectomy or bilobectomy were selected from the surveillance, epidemiology, and end results (SEER) database. The number of LNE and LNR were stratified into 4 groups (0, 1–2, 3–8, and ≥9 lymph nodes) and 3 groups (0, 1–3, and ≥4 regions) respectively. Additionally, the survival curves of overall survival (OS) and cancer-specific survival (CSS) were plotted and compared with the Kaplan-Meier method and log-rank test. Independent prognostic clinicopathological factors were evaluated via Cox proportional hazard regression and subgroup analysis.Results: Totally, 12,490 patients with stage IA NSCLC were enrolled in our study. Patients with ≥9 LNE and ≥4 LNR in both the T1b and T1c stages consistently demonstrated the significantly best OS and CSS outcomes. In the multivariate analysis, patients with ≥9 LNE consistently had a significantly better CSS [hazards ration (HR) (95% CI):0.539 (0.438–0.663)], and those with ≥4 LNR consistently had a significantly better OS [HR (95% CI):0.678 (0.476–0.966)]. Furthermore, ≥9 LNE and ≥4 LNR were associated with better survival in most subgroups.Conclusion: This study demonstrated that ≥9 LNE and ≥4 LNR are highly recommended for stage IA2 and stage IA3 patients but optional for stage IA1 patients.

Analysis of incidence and risk factors for postoperative venous thromboembolism in patients with stageⅠ a non-small-cell lung cancer

Objective: To analyze the incidence and risk factors for postoperative venous thromboembolism(VTE) in patients with stage Ⅰa non-small-cell lung cancer(NSCLC), so as to find evidence for further research of prophylactic anticoagulation. Methods: A total of 132 patients with stage Ⅰa NSCLC, 42 males and 90 females aged from 26 to 79 years with an average of (57±10) years, were retrospectively included in this study. All of them underwent surgical treatment at the Department of Thoracic Surgery of Beijing Chaoyang Hospital Affiliated with Capital Medical University from January 2017 to October 2020. A lower extremity venous ultrasound was performed before and after the operation. Participants were divided into VTE group (n=11) or non-VTE group (n=121) according to whether or not VTE occurred after operation. The surgical conditions, test indicators, imaging information, pathology information were compared between the two groups. Logistic regression analysis was performed to test the associations of VET with putative risks factors in which significant differences were observed. The independent risk factors of VET were determined by this way. Results: Postoperative VTE occurred in 11 cases (8.3%), including 10 cases (90.9%) of deep vein thrombosis (DVT) of lower limbs and 1 case (9.1%) of DVT complicated with pulmonary embolism (PE). The mean age of Patients in the VTE group was older than that in non-VTE Group ((65±9) years vs (57±10) years, P=0.009). On the fifth day after operation, patients in both groups had significantly higher D-dimer level compared with that before operation (3.18(1.55, 5.15) vs 1.54(1.09, 2.57); 2.66(1.17, 4.65) vs 1.34(0.78, 2.04))(both P<0.05). The value of neuron-specific enolase (NSE) and the number of lymph nodes removed during the operation in the VTE group were significantly higher than those in the non-VTE group ((21.54±12.37) vs (14.72±5.75); (19.7±8.2) vs (13.0±7.9)) (both P<0.05). There was no statistically significant difference in the approach of surgery, imaging features (tumor location, vascular cluster signs, etc.), and pathological information (pathological types, etc.) (all P>0.05). The logistic regression analysis showed that the number of lymph nodes removed during the operation was an independent risk factor related to the occurrence of VTE (OR=1.306, 95%CI:1.000-1.600,P<0.05). Conclusions: The incidence of postoperative VTE in patients with stage Ⅰa NSCLC is approximately 8.3%. The number of lymph nodes removed during the operation may be an independent risk factor for postoperative VTE in patients with stage Ⅰa NSCLC.

Association of Clinicopathologic and Molecular Tumor Features With Recurrence in Resected Early-Stage Epidermal Growth Factor Receptor–Positive Non–Small Cell Lung Cancer

The recently published ADAURA study has posed a significant dilemma for clinicians in selecting patients for adjuvant osimertinib. Risk factors for recurrence in early-stage epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) also remain undefined. To determine clinicopathologic characteristics and recurrence patterns of resected early-stage EGFR-positive NSCLC, using wildtype EGFR as a comparator cohort, and identify features associated with recurrence. This is a cohort study including patients diagnosed with AJCC7 Stage IA to IIIA NSCLC between January 1, 2010, and June 30, 2018, who underwent curative surgical procedures at a specialist cancer center in Singapore. The cutoff for data analysis was October 15, 2020. Patient demographic characteristics, treatment history, and survival data were collated. In exploratory analysis, whole-exome sequencing was performed in a subset of 86 patients. Data were analyzed from September 3, 2020, to June 6, 2021. Adjuvant treatment was administered per investigator's discretion. The main outcome was 2-year disease-free survival (DFS). A total of 723 patients were included (389 patients with EGFR-positive NSCLC; 334 patients with wildtype EGFR NSCLC). There were 366 women (50.6%) and 357 men (49.4%), and the median (range) age was 64 (22-88) years. A total of 299 patients (41.4%) had stage IA NSCLC, 155 patients (21.4%) had stage IB NSCLC, 141 patients (19.5%) had stage II NSCLC, and 125 patients (17.3%) had stage IIIA NSCLC. Compared with patients with wildtype EGFR NSCLC, patients with EGFR-positive NSCLC were more likely to be women (106 women [31.7%] vs 251 women [64.5%]) and never smokers (121 never smokers [36.2%] vs 317 never smokers [81.5%]). At median (range) follow up of 46 (0-123) months, 299 patients (41.4%) had cancer recurrence. There was no statistically significant difference in 2-year DFS for EGFR-positive and wildtype EGFR NSCLC (70.2% [95% CI, 65.3%-74.5%] vs 67.6% [95% CI, 62.2%-72.4%]; P = .70), although patients with EGFR-positive NSCLC had significantly better 5-year overall survival (77.7% [95% CI, 72.4%-82.1%] vs 66.6% [95% CI, 60.5%-72.0%]; P = .004). Among patients with EGFR-positive NSCLC, 2-year DFS was 81.0% (95% CI, 74.0%-86.3%) for stage IA, 78.4% (95% CI, 68.2%-85.6%) for stage IB, 57.1% (95% CI, 43.7%-68.4%) for stage II, and 46.6% (95% CI, 34.7%-57.7%) for stage IIIA. Overall, 5-year DFS among patients with stage IB through IIIA was 37.2% (95% CI, 30.1%-44.3%). Sites of disease at recurrence were similar between EGFR-positive and wildtype EGFR NSCLC, with locoregional (64 patients [16.5%] vs 56 patients [16.8%]), lung (41 patients [10.5%] vs 40 patients [12.0%]), and intracranial (37 patients [9.5%] vs 22 patients [6.6%]) metastases being the most common. A risk estimation model incorporating genomic data and an individual patient nomogram using clinicopathologic features for stage I EGFR-positive NSCLC was developed to improve risk stratification. This cohort study found that recurrence rates were high in early-stage EGFR-positive NSCLC including stage IA, yet 37.2% of patients with stage IB through IIIA were cured without adjuvant osimertinib. Further studies are needed to elucidate individualized surveillance and adjuvant treatment strategies for early-stage EGFR-positive NSCLC.

The Prognostic Significance of the Histological Types in Patients With Nonsmall Cell Lung Cancer ≤2 cm.

Background: Few studies attempt to investigate the impact of histology on the outcome of nonsmall-cell lung cancer (NSCLC) patients. In this study, we aim to determine whether the type of histology influenced the outcome of stage IA NSCLC patients with tumor size (TS) ≤20 mm.Methods: The data of the population in our study was collected from the Surveillance, Epidemiology, and End Results (SEER) program, which is supported by the National Cancer Institute of the United States. The primary outcome was overall survival (OS). Cox-regression proportional hazards models were performed to identify prognostic factors for OS. The secondary outcome was lung cancer-specific mortality (LCSM). A competing risk model was used to identify risk factors associated with LCSM.Results: A total of 4,424 eligible patients (T1a-bN0M0) who received sublobar resection [wedge resection (WR) and segmentectomy] were identified and included in the study for further analysis. For patients with TS ≤ 10 mm, multivariate Cox-regression analyses for OS showed that lung squamous cell carcinoma (LUSC) yielded poorer OS compared with lung adenocarcinoma (LUAD), and no difference was observed between LUSC and LUAD for LCSM in competing risk models. For patients with TS > 10 and ≤20 mm, multivariate analyses revealed that LUSC patients experienced poorer OS compared with that of LUAD; the univariate competing risk analysis indicated SCC pathology predicted an increased risk of death from lung cancer, whereas no difference is observed in the multivariate competing analysis. In addition, segmentectomy was associated with longer OS in patients with >10 and ≤20 mm but not in patients with ≤10 mm compared with WR.Conclusion: Our study demonstrated that squamous pathology was associated with the worse OS but not LCSM for patients with ≤20 mm compared with adenocarcinoma. Moreover, segmentectomy when compared to wedge resection appears to be associated with a better prognosis in patients with neoplasm >10 mm, but not in the case of nodule ≤10 mm.

Surgery versus SABR for early-stage lung cancer-time to call it a draw?

Randomised controlled trials comparing surgery with non-surgical treatment for cancer have been notoriously difficult to complete, owing to challenges in both equipoise and preference in patients and providers alike. 1 Nguyen TK Nguyen EK Warner A Louie AV Palma DA Failed randomized clinical trials in radiation oncology: what can we learn?. Int J Radiat Oncol Biol Phys. 2018; 101: 1018-1024 Summary Full Text Full Text PDF PubMed Scopus (20) Google Scholar Debate on the relative merit of stereotactic ablative radiotherapy (SABR) versus surgery for early-stage non-small-cell lung cancer (NSCLC) is no exception. Prospective randomised controlled trials designed to identify a so-called winner between surgery and SABR have not been able to accrue, and the pooled analysis from the prematurely closed original STARS and ROSEL studies has been a lightning rod for discussion among thoracic oncologists. 2 Jones DR Do we know bad science when we see it?. J Thorac Cardiovasc Surg. 2015; 150: 472-473 Summary Full Text Full Text PDF PubMed Scopus (6) Google Scholar Even with other comparative effectiveness studies attempting to adjust for confounding, inherent limitations engender polarising opinions. 3 Chen H Laba JM Boldt RG et al. Stereotactic ablative radiation therapy versus surgery in early lung cancer: a meta-analysis of propensity score studies. Int J Radiat Oncol Biol Phys. 2018; 101: 186-194 Summary Full Text Full Text PDF PubMed Scopus (50) Google Scholar Stereotactic ablative radiotherapy for operable stage I non-small-cell lung cancer (revised STARS): long-term results of a single-arm, prospective trial with prespecified comparison to surgeryLong-term survival after SABR is non-inferior to VATS L-MLND for operable stage IA NSCLC. SABR remains promising for such cases but multidisciplinary management is strongly recommended. Full-Text PDF

Recurrence and disease-free survival outcomes after computed tomography-guided needle biopsy in stage IA non-small cell lung cancer patients in China: a propensity score matching analysis.

Whether preoperative biopsy before radical resection can lead to recurrence and impact patient survival in non-small cell lung cancer (NSCLC) remains controversial. In this study, we carried out a retrospective analysis to determine whether preoperative biopsy can cause disease recurrence and influence disease-free survival (DFS) in patients with stage IA NSCLC. Patients diagnosed with stage IA NSCLC (solid nodule) between January 2010 and December 2014 were identified from the databases of 7 Chinese medical centers and divided into two groups: a preoperative computed tomography (CT)-guided needle biopsy (CTNB) plus radical resection group, and a non-CTNB group. The propensity score matching (PSM) method was adopted to balance the observed covariates, and Kaplan-Meier estimates were used for survival analysis. Cox regression was used in a single-factor analysis to identify the factors affecting DFS in stage IA NSCLC. After initial screening, 730 patients were enrolled in this study, with 186 and 544 patients in the CTNB group and the non-CTNB group, respectively. After PSM, 186 patients were eventually included in each group. No significant differences in basic clinical features were identified between the two groups (P>0.05). The rates of recurrence were 17.2% and 14.0% in the CTNB and non-CTNB groups (χ2=0.735, P=0.391), respectively. No notable differences in DFS (χ2=1.895, P=0.173) or overall survival (OS, χ2=1.785, P=0.182) were observed. Lung adenocarcinoma [hazard ratio (HR), 0.167, P=0.001] and lesion size (>2 cm) (HR, 2.712, P=0.000) were identified as risk factors for DFS in stage IA NSCLC. CTNB does not increase the incidence of recurrence in stage IA NSCLC or affect patient survival; therefore, it is not a risk factor for DFS. Lung adenocarcinoma and lesion size are risk factors for DFS.

Nomogram to Predict Cancer Specific Survival in Patients with Pathological Stage IA Non-small Cell Lung Cancer

We identified the prognostic factors of resected stage IA non-small cell lung cancer (NSCLC) and developed a nomogram, with purpose of defining the high-risk population who may need closer follow-up or more intensive care. Eligible stage IA NSCLC cases from the Surveillance, Epidemiology, and End Results (SEER) database and the Sun Yat-sen University Cancer Center (SYSUCC) were included. Stage IB NSCLCs were also included for evaluating the risk stratification efficacy. Cancer specific survival (CSS) was compared between groups. Statistically significant factors from multivariate analysis were entered into the nomogram. The performance of the nomogram was evaluated by concordance index (C-index) and calibration plots. A total of 23,112 NSCLC cases (SEER stage IA training cohort, N=7,777; SEER stage IA validation cohort, N=7,776; SEER stage IB cohort, N=7,559) from the SEER database were included. 1,304 NSCLC cases (SYSUCC stage IA validation cohort, N=684; SYSUCC stage IB cohort, N=620) from the SYSUCC were also included. Younger age, female, lobectomy, well differentiated, smaller size and more examined lymph nodes were identified as favorable prognostic factors. A nomogram was established. The C-index was 0.68 (95%CI, 0.67-0.69), 0.66 (95% CI, 0.64-0.68) and 0.66 (95% CI, 0.61-0.71) for the SEER training cohort, SEER validation cohort and SYSUCC validation cohort. A risk classification system was constructed to stratify stage IA NSCLC into low-risk subgroup and high-risk subgroup. The CSS curves of these two subgroups showed statistically significant distinctions. This nomogram delivered a prognostic prediction for stage IA NSCLC and may aid individual clinical practice.

Surgery or Non-surgical Treatment of ≤8 mm Non-small Cell Lung Cancer: A Population-Based Study.

Background: Timing for intervention of small indeterminate pulmonary nodules has long been a topic of debate given the low incidence of malignancy and difficulty in obtaining a definite preoperative diagnosis. We sought to determine survival outcomes of surgical and non-surgical managements in non-small cell lung cancer (NSCLC) ≤8 mm, which may provide a reference for prospective decision-making for patients with suspected NSCLC.Method: A total of 1,652 patients with Stage IA NSCLC ≤8 mm were identified from the Surveillance, Epidemiology, and End Results (SEER) database and categorized into surgery and non-surgery groups. Chi-square test, t-test and Mann-Whitney U test were used to compare the baseline characteristics between groups. Survival curves were depicted using Kaplan-Meier method and compared by log-rank test. Cox proportional hazard model was used for univariate and multivariate analyses. Adjustment of confounding factors between groups was performed by propensity score matching.Results: The surgery and non-surgery groups included 1,438 and 208 patients, respectively. Patients in surgery group demonstrated superior survival outcome than patients in non-surgery group both before [overall survival (OS): HR, 16.22; 95% CI, 11.48–22.91, p < 0.001; cancer-specific survival (CSS): HR, 49.6; 95% CI, 31.09–79.11, p < 0.001] and after (OS: HR, 3.12; 95% CI, 2.40–4.05, p < 0.001; CSS: HR, 3.85; 95% CI, 2.74–5.40, p < 0.001) propensity score matching. The 30-day mortality rates were 3.1 and 12.0% in surgery and non-surgery groups, respectively. Multivariate analysis suggested age, sex, race, tumor size, grade, pathological stage were all independent prognostic factors in patients with ≤8 mm NSCLC. A comparison of surgical resections revealed a survival superiority of lobectomy over sub-lobectomy. In terms of CSS, no statistically significant difference was found between segmentectomy and wedge resection.Conclusion: The current SEER database showed better prognosis of surgical resection than non-surgical treatment in patients with ≤8 mm NSCLC. However, the factors that should be essentially included in the proper propensity-matched analysis, such as comorbidity, cardiopulmonary function and performance status were unavailable and the true superiority or inferiority should be examined further by ongoing randomized trial, especially comparing surgery and stereotactic body irradiation.

The genomic and transcriptomic characteristics of early recurrence patients in stage IA non-small cell lung cancer.

e20547 Background: Lung cancer is the leading cause of cancer-related death worldwide. The mortality risk is still high in early stage because of the high relapse rates about 30–45% within 5 years after surgery. The main purpose of this study was to depict the genomic and transcriptomic characteristics in stage IA non-small cell lung cancer (NSCLC) patients and elucidate the recurrence risk factors for providing more postoperative intervention management and treatment. Methods: We prospectively enrolled 60 patients with stage IA NSCLC from 2012 to 2018 including 29 non-relapse patients and 31 early-relapse patients within 5 years. A total of 60 primary tumor specimens and 10 relapse tumor specimens were obtained. The paired adjacent non-tumor tissues for each patient were collected as negative control. DNA and RNA were co-extracted and performed with whole exon and transcriptome sequencing. The immune cell infiltration scores were estimated using ssGSEA algorithm. Results: The most frequently mutated genes in our cohort were EGFR (46.4%), TP53 (38.0%), TTN (35.2%) and USH2A (21.1%). Notably, USHA was enriched in relapse patients (32.3% vs 3.4%, p = 0.006). The median tumor mutation burden of the post-relapse group was 6.14/Mb, significantly higher than the pre-relapse group (Median: 2.63/Mb, p = 0.047) and the non-relapse group (1.91/Mb, p = 0.025). Among the early-relapse patients, copy number amplification at 2q31.1 was prevalent in the pre-relapse group (p &lt; 0.05). Two patterns of clonal evolution were identified during the recurrence, including autonomous clonal evolution and acquired clonal evolution. Compared with non-tumor tissues, differentially expressed genes in pre-relapse affected the metabolism-associated pathways. Furthermore, post-relapse samples down-regulated antigen processing and presentation signaling pathway compared to non-relapse group. Interestingly, lower plasma dendritic cell infiltration was detected in post-relapse (p = 0.0078), indicating the defect of antigen presentation in recurrence. Concentrating on the primary tumor specimens, samples from relapse patients showed higher infiltration of CD8+T cell (p = 0.019), Helper T cells (p = 0.0036) and Treg cells (p = 0.0071) than that from non-relapse patients. Conclusions: This study elucidated the recurrence risk molecular and immune microenvironment in stage IA NSCLC patients. Findings in our research may help find out the subset of patients with early stage at high risk for recurrence who have the urgent need for postoperative intervention and guide therapeutic strategies.