Survival In Early-stage Lung Cancer Research Articles

Checkpoint Inhibitors Up Survival in Early-Stage Lung Cancer.

Long-awaited results from the KEYNOTE-671 and CheckMate 816 trials indicate that neoadjuvant use of immune checkpoint inhibitors can extend event-free and overall survival in patients with non-small cell lung cancer.

Investigation of factors associated with static and dynamic balance in early-stage lung cancer survivors.

Balance impairment and falls are common among patients after cancer treatment. This study aimed to compare static and dynamic balance functions in lung cancer survivors (LCS) and healthy controls and to investigate the factors related to balance in LCS. Cross-sectional data were collected from lung cancer patients whose treatment had been completed within the previous 3 months (n = 60) and age and gender-matched healthy controls (n = 60). Clinical characteristics and history of falls were recorded. Pulmonary function tests and measurements of respiratory muscle strength were performed. Dynamic and static balance, fear of falling, knee-extension strength, physical activity level, dyspnea, comorbidity,and quality of life (QoL) were assessed using the Time Up and Go Test, Single Leg Standing Test, the Fall Efficacy Scale-International, hand-held dynamometer, the International Physical Activity Questionnaire, the Modified Medical Research Dyspnea Scale, the Charlson Comorbidity Index,and the European Organization for Research and Treatment of Cancer QoL Scale. LCS reported a higher fall rate and exhibited lower dynamic balance compared to controls (p < 0.05). The number of chemotherapy cycles, number of falls in the past year, fear of falling, perceived dyspnea, forced expiratory volume in 1 s (%), maximal inspiratory pressure (%), knee-extension strength, physical activity score, and QoL score related to physical function were correlated with balance function in LCS (p < 0.05). LCS had a higher risk of falls and lower dynamic balance function which might be related to various clinical and physical parameters. Identifying factors related to balance should be considered within the scope of fall prevention approaches for these patients.

Evaluating the Optimal Time Between Diagnosis and Surgical Intervention for Early-Stage Lung Cancer

IntroductionThere is no consensus on the optimal timing for lung cancer surgery. We aim to evaluate the impact of timing of surgical intervention. We hypothesize delay in intervention is associated with worse overall survival and higher pathologic upstaging in early-stage lung cancer. MethodsWe identified patients with cT1/2N0M0 nonsmall cell lung cancer in the National Cancer Database from 2004 to 2018. Patients were categorized by time to surgery groups: early (<26 d), average (26-60 d), and delayed (61-365 d). Primary outcome was overall survival and secondary outcome was pathologic upstaging. Multivariate models and survival analyses were used to determine factors associated with time from diagnosis to surgery, pathologic upstaging, and overall survival. ResultsIn multivariate model, advanced age, non-Hispanic Black patients, nonprivate insurance, low median income and education, and treatment at low-volume facilities were less likely to undergo early intervention and compared to the average group were more likely to receive delayed intervention. Pathologic upstaging was more likely in the delayed group (odds ratio 1.11, 1.07-1.14) compared to early group (odds ratio 0.96, 0.93-0.99). Early intervention was associated with improved overall survival (hazard ratio 0.93, 0.91-0.95), while delayed intervention was associated with inferior survival (hazard ratio 1.11, 1.09-1.14). ConclusionsExpeditious surgical intervention is associated with lower rates of pathologic upstaging and improved overall survival in early-stage lung cancer. Delays in surgery are associated with social and economic factors, suggesting disparities in access to surgery. Lung cancer surgery should be performed as quickly as possible to maximize oncologic outcomes.

Lung Cancer Screening Is Just Part of the Equation for Improving Survival for Early-Stage Lung Cancer

Lung Cancer Screening Is Just Part of the Equation for Improving Survival for Early-Stage Lung Cancer

A Th1-like CD4+ T-cell Cluster That Predicts Disease-free Survival in Early-stage Lung Cancer.

Peripheral Th7R, a Th1-like CD4+ T-cell cluster reflecting priming status in draining LNs and immune status in the tumor microenvironment, predicts disease-free survival after complete resection and has significant clinical relevance in selecting appropriate therapeutic interventions in patients with early-stage lung cancer.

Implementation of an early-stage lung cancer survivorship clinic in a comprehensive cancer center.

e13515 Background: Early-stage lung cancer survivors are a growing population. A comprehensive plan to address needs relevant to longer survival (e.g., psychological distress, persistent symptoms, physical function) and clinic capacity is necessary. How to deliver comprehensive survivorship care that meets national standards and results in improved patient outcomes is a challenge. Survivorship clinics staffed by advanced practice providers (APP) are an option to address these needs. Methods: In June 2019, Atrium Health Wake Forest Baptist Comprehensive Cancer Center (AHWFB-CCC) opened a dedicated survivorship clinic. Stakeholders from the lung cancer disease-oriented team developed a standard referral pathway for patients to survivorship. A standard workflow was developed in the electronic medical record (EPIC). Eligible lung cancer survivors were referred to the Lung Cancer Survivorship Clinic for a survivorship orientation visit (SOV) with a lung cancer specific APP. Prior to the SOV, a welcome video, disease-specific questionnaire, and electronic patient reported outcome (ePRO) tools (i.e., PROMIS-29 and Distress Thermometer) were sent to the patients’ electronic chart. At the SOV, the ePRO responses and survivorship care plan were reviewed. Analysis of survivor demographic and clinical characteristics (i.e., age, gender, race, residence according to rural-urban commuting area (RUCA) codes, treatment modality, and method used to complete ePROs) and ePRO responses was performed using several regression methods. Patients were offered a post visit survey. Results: From January 2020 to December 2022, 285 lung cancer patients completed a SOV. Most patients were able to complete the pre-visit questions via the electronic chart. AHWFB-CCC survivors reported improved PROMIS-29 T-Scores compared to the average United States (US) early-stage lung cancer survivor, with meaningfully better scores (≥ 3 pts) in five of the seven health-related domains measured. We found no significant interactions between T-Scores and a survivor’s demographic or clinical characteristic, except for gender (p &lt; .001). Most notably, we found a lack of interaction between PROMIS-29 T-Scores and treatment modality (p=.27). Most patients found the SOV helpful and expressed better understanding of their cancer treatment and side effects after the SOV. Conclusions: Our model of an optimized electronic medical record pathway paired with an APP led survivorship visit is feasible and can address current challenges in providing survivorship care to early-stage lung cancer survivors. Survivors had similar ePRO regardless of treatment modality, indicating their survivorship care could be consolidated. Future evaluation is needed to establish if this care model improves outcomes over subsequent visits, minimizes the effect of health disparities, or enhances care capacity.

Robotic segmentectomy for early-stage lung cancer.

Lobectomies have long been the gold standard for surgical treatment of early-stage non-small cell lung cancer (NSCLC), with segmentectomies limited to instances of benign disease or as an alternative in patients where lung preservation is indicated. However, a recently published randomized control trial has demonstrated the superiority of segmentectomy over lobectomy in terms of overall survival for early-stage lung cancer. Segmentectomy could thus be considered a standard procedure for small-sized peripheral NSCLC. While segmentectomy via video-assisted thoracic surgery (VATS) is the most widespread approach, development in video instrumentation and thoracic robotic surgery is rapidly gaining interest. Indeed, robotic surgery pioneers boast the advantages in three-dimensional view, improved magnification, ergonomics, dexterity, safety, and ease of surgery with this technology. This review aims to outline robotic-assisted segmentectomy indications, preoperative evaluation, and the operative conduct for the different lung segments from a single surgeon console. There are many ways to perform segmentectomies and therefore this review describes generalized approaches that can be tailored based on experience.

Impact of Low-dose Chest CT Screening on the Association Between Rurality and Lung Cancer Outcomes.

Lung cancer mortality is higher among rural United States populations compared with nonrural ones. Little is known about screening low-dose chest computed tomography (LDCT) outcomes in rural settings. This retrospective cohort study examined all patients (n=1805) who underwent screening LDCT in a prospective registry from March 1, 2015, through December 31, 2019, in a majority-rural health care system. We assessed the proportion of early-stage lung cancers (American Joint Committee on Cancer stage I-II) diagnosed among LDCT-screened patients, and analyzed overall survival after early-stage lung cancer diagnosis according to residency location. The screening cohort had a median age of 63 and median 40-pack-year smoking history; 62.4% had a rural residence, 51.2% were female, and 62.7% completed only 1 LDCT scan. Thirty-eight patients were diagnosed with lung cancer (2.1% of the cohort), of which 65.8% were early-stage. On multivariable analysis, rural (vs nonrural) residency was not associated with a lung cancer diagnosis (adjusted hazard ratio 1.59; 95% CI, 0.74-3.40; P =0.24). At a median follow-up of 37.1 months (range, 3.3 to 67.2 months), 88.2% of rural versus 87.5% of nonrural patients with screen-diagnosed early-stage lung cancer were alive ( P =0.93). In a majority-rural United States population undergoing LDCT, most screen-detected lung cancers were early-stage. There were no significant differences observed between rural and nonrural patients in lung cancer diagnosis rate or early-stage lung cancer survival. Increased implementation of LDCT might blunt the historical association between rural United States populations and worse lung cancer outcomes.

Imaging-Based Deep Graph Neural Networks for Survival Analysis in Early Stage Lung Cancer Using CT: A Multicenter Study.

BackgroundLung cancer is the leading cause of cancer-related mortality, and accurate prediction of patient survival can aid treatment planning and potentially improve outcomes. In this study, we proposed an automated system capable of lung segmentation and survival prediction using graph convolution neural network (GCN) with CT data in non-small cell lung cancer (NSCLC) patients.MethodsIn this retrospective study, we segmented 10 parts of the lung CT images and built individual lung graphs as inputs to train a GCN model to predict 5-year overall survival. A Cox proportional-hazard model, a set of machine learning (ML) models, a convolutional neural network based on tumor (Tumor-CNN), and the current TNM staging system were used as comparison.FindingsA total of 1,705 patients (main cohort) and 125 patients (external validation cohort) with lung cancer (stages I and II) were included. The GCN model was significantly predictive of 5-year overall survival with an AUC of 0.732 (p < 0.0001). The model stratified patients into low- and high-risk groups, which were associated with overall survival (HR = 5.41; 95% CI:, 2.32–10.14; p < 0.0001). On external validation dataset, our GCN model achieved the AUC score of 0.678 (95% CI: 0.564–0.792; p < 0.0001).InterpretationThe proposed GCN model outperformed all ML, Tumor-CNN, and TNM staging models. This study demonstrated the value of utilizing medical imaging graph structure data, resulting in a robust and effective model for the prediction of survival in early-stage lung cancer.

Abstract 1018: Time to secondary treatment initiation affects overall survival in early-stage lung cancer

Abstract Rationale: Lung cancer is the leading cause of cancer-related deaths in the US and worldwide. The 5-year overall survival (OS) for lung cancer patients is below 20%, lower than most other common cancers. In general, timely care can positively affect the survival of patients. However, previous studies of lung cancer and the effect of time-to-treatment on patient outcomes have been inconclusive. Some studies report adverse effects, while others report the association referred to as the ‘waiting time paradox’, where patients with severe diagnosis receive quicker care, but have poorer outcomes due to advanced disease. These studies investigate time-to-treatment of any type, but association between time-to-treatment for secondary treatments and outcomes for lung cancer has not been conclusively defined. Methods: Treatment data from 714 patients with lung cancer diagnosis at Vanderbilt University Medical Center between 2001 and 2021 was used for this analysis. Secondary treatment data included data in three categories: chemotherapy (N=577), radiation therapy (N=126), and target therapies(N=11). Cox regression and Kaplan-Meir curves were used to model the effect of time-to-treatment on overall survival, adjusted for demographic and clinical factors, including if surgical resection was performed before secondary treatment start date. Time-to-treatment was defined as the interval of days between diagnosis or initial surgical procedure and treatment start date in four categories: 0-10 days (1), 11-20 days (2), 21-30 days (3), 31-45 days (4). Results: Cox proportion regression analysis of patients treated within 30 days, including stage and time-to-treatment, had a significant difference in overall survival when stratified by cox linear predictor median (value = 0.0912). Patients with linear predictors values above the median (high) in the cox proportion model had a lower 3-year survival than patients with linear predictor values lower than the median (low) (p=0.0021). This contrast is seen clearly in early-stage lung cancer patients, who received chemotherapy as secondary treatment, where patients with longer time-to-treatment start (15-30 days) had a lower 3-year survival than patients with shorter time-to-treatment (0-15 days) (p=0.047). Conclusions: The effect of changes in time-to-treatment initiation in lung cancer patients receiving secondary treatment appears to be sensitive to initiation within a 30-day period. Although past studies have focused on treatment start time initiation categories within weeks or months, our study is the first to elucidate a possible sensitivity to secondary initiation within just a few days period. Further examination aims to further detail treatment types, by investigating changes in dosage, treatment combinations, or institutions differences to better understand time-to-treatment effects on the survival rates of lung cancer patients. Citation Format: Dianna J. Rowe, Michael Kammer, Jonathan Lehman, Fabien Maldonado. Time to secondary treatment initiation affects overall survival in early-stage lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1018.

Racial disparities in follow-up care of early-stage lung cancer survivors.

To investigate if race impacts receipt of follow-up care in lung cancer survivors, we conducted a cross-sectional study in lung cancer survivors recruited through the New Jersey State Cancer Registry (NJSCR). Between May 2019 and December 2019, survivors of early-stage NSCLC were identified and recruited from the NJSCR. Eligible participants were asked to complete a paper survey questionnaire and medical record release form sent to them by mail. Of the 112 survivors included in the analysis, 78 (70%) were non-Hispanic (NH) Whites and 34 (30%) were NH Blacks. Mean age was 67years, 61% were female, and 92% had cancer in remission. A total of 82% of participants reported receiving a surveillance scan (CT or PET) within 1year of completing the study survey. More NH White survivors received a scan within a year compared to NH Black survivors (89% vs 70%; p = 0.02). More NH White survivors (94%) reported that they were informed of the need for follow-up care by their provider compared to NH Blacks (71%; p = 0.002). Only 57% survivors reported receiving a treatment summary. Significant barriers to care were out-of-pocket costs (24%), non-coverage of test (12.5%), and lack of insurance (10%). Significant disparity was identified between NH Blacks and NH Whites in receipt of surveillance scans, as well as in receiving information about need for follow-up care. Low income, lack of insurance, and other financial concerns were identified as significant barriers to follow-up care. Future interventions to increase survivorship care should target specific unmet needs identified in each survivor population.

Racial disparities in follow-up care of early-stage lung cancer survivors.

12025 Background: Follow-up care and surveillance in lung cancer survivors is essential formanagement of treatment- and disease-related symptoms as well as for the early detection of cancer recurrence. To investigate if race impacts receipt of follow-up care in lung cancer survivors, we conducted a cross-sectional study in lung cancer survivors recruited through the New Jersey State Cancer Registry (NJSCR). Methods: Between May 2019 and December 2019, survivors of early-stage NSCLC were identified and recruited from the NJSCR. Participants were eligible if they had surgery for stage I or II NSCLC between 2014 and 2017 and, completed all treatment at least one year prior to enrollment. Eligible participants were asked to complete a paper survey questionnaire and medical record release form sent to them by mail. The survey had questions about demographics, smoking, cancer history and treatment, quality of life, follow-up care, barriers to care and informational needs. Study measures were compared between the groups using t-test or chi-square test as applicable. Results: Of the 482 survivors contacted, 23% (n = 114) mailed back the survey questionnaire. Of the 112 survivors who returned a completed survey; 78 (70%) were non-Hispanic (NH) Whites and 34 (30%) were NH Blacks. Mean age was 67 years, 61% were female, 92% had cancer in remission. 82% of participants reported receiving a surveillance scan (CT or PET) within one year of completing the study survey. More NH White survivors received a scan within a year compared to NH Black survivors (89% vs 64%; p = 0.006). Also, 88% of survivors reported that they were informed of the need for follow-up care by their provider with more NH White survivors reporting receiving this information (94%) compared to NH Blacks (71%; p = 0.002). About 57% of the survivors reported receiving a written treatment summary and 92% reported being seen by a physician within the past year; no racial differences in these measures were noted.There was also no racial difference in receipt of age-appropriate cancer screening; 66% and 80% reported receiving regular colon and breast cancer screening, respectively. A significantly higher percentage of NH Blacks reported currently smoking compared to NH Whites (16% vs 12%). The most significant barriers to care for both populations were concern for out-of-pocket costs (26% NH Whites, 19% NH Blacks), non-coverage of test (14% NH Whites, 10% NH Blacks) and lack of insurance (8% NH Whites, 16% NH Blacks). Conclusions: Significant racial disparity was identified between NH Blacks and NH Whites in receipt of surveillance scans, guidance about follow-up care and smoking cessation. The most significant barriers to follow-up care was lack of insurance in NH Blacks and financial concerns about cost and coverage of tests in NH Whites. Future interventions to increase survivorship care should target these specific needs in survivor populations.

Abstract 5784: Integration of multiple omics underlying extreme phenotype strategy identify non-invasive prognostic biomarkers specific to early-stage lung cancer

Abstract Background Emerging studies have reported that approximately 30% of patients in stage I/II die within 5 years due to the progression and recurrence. There is a great need to identify sensitive and specific non-invasive biomarkers for the prognosis and survival prediction in early-stage lung cancer. Methods The strategy of extreme phenotype was applied for the quick identification of biomarkers associated with early-stage lung cancer survival in Boston Lung Cancer Study (BLCS) cohort. Multiple omics platforms, including SOMAscan and Infinium MethylationEPIC Array, were carried out to recognize biomarkers from the circulating (blood or serum) and solid (tissue) in different molecular levels. Public databases (e.g., TCGA, HPA and GEO) were used to be external validations. Differential analysis was performed by t-test with normalization data. Kaplan-Meier curves with the log-rank test were used to plot and compare the survival between candidate groups. Results Among the lung cancer patients in stage I registered in BLCS, we selected randomly 77 samples for omics detection, of which 37 had long time survival (mean = 157.36 mos) and 40 had short survival (mean = 19.79 mos). At the protein level, we found 120 circulating differentially expressed proteins (C-DEPs) between two extreme groups (P &amp;lt; 0.05), and six of them were beyond the fold change (FC) &amp;gt; 2 [i.e., ApoB (APOB), CK-MB (CKB CKM) and CK-MM (CKM) are up in the long; GAPDH (GAPDH), RAN (RAN) and SPHK1 (SPHK1) are up in the short]. As for their lung cancer tissues, both ApoB (APOB) and CK-MM (CKM) rarely expressed at the RNA and protein levels. Thus, we considered both ApoB and CK-MM as serum-specific proteins and the others as widespread biomarkers. At the DNA methylation level, 19,084 CpGs were identified in circulating differentially methylated positions (C-DMPs) and 80,342 in tumor DMPs (T-DMPs) with P &amp;lt; 0.05. Next, we integrated C-DEPs, C-DMPs and T-DMPs to interpret the origin and expression pattern of specific biomarkers. Intriguingly, several T-DMPs and C-DMPs existed only in genes of serum-specific proteins (ApoB and CK-MM) along with high correlation, but not in the widespread biomarkers. These findings indicate two separate origins where the proteins specific to serum skipped the products of RNA and protein and were directly released from the solid tissue into the circulatory system, while the widespread proteins left RNA and protein behind in situ. Furthermore, among four widespread biomarkers, we observed that the RNA of SPHK1 highly expressed in lung cancer tumors and this higher expression was associated with worse survival (Plog-rank = 1.20 × 10−6), especially in stage I (Plog-rank = 1.20 × 10−5). Similar results were found with the SPHK1 protein in tumors. These findings reveal that the prognostic effect of SPHK1 at both RNA and protein levels was particularly limited to the patients in stage I, but not in advanced stages. Conclusion This is the first study to our knowledge using extreme a phenotype strategy to identify non-invasive prognostic biomarkers for early-stage lung cancer. Utilizing integration of multiple omic platform, it is plausible to recognize and evaluate the circulating biomarkers for prognosis assessment of lung cancer. Citation Format: Mulong Du, Qianyu Yuan, Li Su, Feng Chen, David C. Christiani. Integration of multiple omics underlying extreme phenotype strategy identify non-invasive prognostic biomarkers specific to early-stage lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5784.

Lifestyle behaviors and intervention preferences of early-stage lung cancer survivors and their family caregivers.

Lung cancer (LC) is a highly prevalent disease with more survivors diagnosed and treated at earlier stages. There is a need to understand psychological and lifestyle behavior needs to design interventions for this population. Furthermore, understanding the needs and role of family caregivers, especially given the risks associated with second-hand smoke, is needed. Thirty-one early-stage (stages I or IIA) LC survivors of (52% men) and 22 (50% women) caregivers (N = 53 total) completed surveys after surgery (baseline) and at 3- and 6-month follow-ups. Participants reported on psychological functioning, smoking, and physical activity (PA) as well as intervention preferences. Survivors reported low levels of psychological distress and 3% were current smokers during the study. Approximately 79% were sedentary and not meeting national PA guidelines. Caregivers also reported minimal psychological distress and were sedentary (62% not meeting guidelines), but a larger proportion continued to smoke following the survivor's cancer diagnosis (14%). Both survivors and caregivers expressed interest in home-based PA interventions but differed regarding preferred format for delivery. Most (64%) caregivers preferred a dyadic format, where survivors and caregivers participate in the intervention together. However, most survivors preferred an individual or group format (57%) for intervention delivery. Both LC survivors and family caregivers could benefit from PA interventions, and flexible, dyadic interventions could additionally support smoking cessation for family caregivers.

The Academic Facility Type Is Associated With Improved Overall Survival for Early-Stage Lung Cancer

Early-stage non-small cell lung cancer (NSCLC) is potentially curable with surgical resection. The overall survival rate for early-stage NSCLC may be determined by the healthcare facility type where patients receive their lung cancer treatment. A total of 103,748 cases with the American Joint Committee on Cancer clinical stage I and II NSCLC that were reported to the National Cancer Database at over 1150 facilities were analyzed in this study. Healthcare facilities were dichotomized into the community and academic facility types. Marginal multivariable Cox proportional hazards models were used to evaluate differences in overall survival. Propensity score methodology with inverse probability of treatment weighting was used to adjust for facility volume and patient-related baseline differences between facility types. Patients with early-stage NSCLC who were treated at academic facility types had a significantly better median overall survival (63.2 months) compared with patients who received care at community healthcare facilities (54.2 months) (hazard ratio, 0.86; 95% confidence interval, 0.82-0.91; P < .0001). The surgical quality outcomes for NSCLC surgery, including 30-day mortality, 90-day mortality, and the median number of lymph nodes removed were significantly better for patients treated at the academic facility types. Patients with early-stage NSCLC who were treated at academic facility types had a significantly higher overall median survival compared with patients treated at community facility types. The short-term surgical quality outcomes were significantly better for patients who underwent surgery for early-stage NSCLC at academic facility types.

Early stage lung cancer survival after wedge resection and stereotactic body radiation.

The comparative effectiveness of stereotactic body radiation therapy (SBRT) and wedge resection in the treatment of early stage lung cancer is still under debate. This meta-analysis compares the 5-year overall survival (OS) of wedge resection and SBRT in patients with stage I non-small cell lung cancer (NSCLC). Original research articles published between 1995 and 2017 were identified through the National Library of Medicine and National Institutes of Health PubMed database and through the reference lists of reviewed articles. Data were processed and analyzed in R (version 3.4.2) and a summary estimate that accounted for the sample size of each study was calculated. The combined percent survival was calculated using random effect models. Funnel plots were used to assess publication bias. Heterogeneity was tested using the Q statistic and the I2 statistic. There were 16 studies totaling 1,984 patients with stage I NSCLC treated with wedge resection. The meta-estimate was 74% (95% CI, 66-81%), with significant heterogeneity across studies (Q =172.46, P<0.0001; I2=91.30%). Thirty-six studies including 3,309 patients with stage I NSCLC treated with SBRT/SABR produced a meta-estimate of 44% (95% CI, 38-50%), with significant heterogeneity (Q =423.55, P<0.0001; I2=91.74%). Two articles directly comparing stage I NSCLC patients treated with wedge resection to patients treated with SBRT both reported higher 5-year OS after wedge resection. SBRT is a treatment option reserved to medically inoperable patients, but could be an alternative to surgery in medically operable patients who prefer a less invasive treatment. More standardized methods for data collection and reporting are necessary to allow better comparisons across published studies.

Significance of Spread Through Air Spaces in Resected Lung Adenocarcinomas With Lymph Node Metastasis

BackgroundSpread through air spaces (STAS) is a recently recognized invasive pattern of lung cancer defined by the World Health Organization as micropapillary clusters, solid nests, or single cells spreading within air spaces beyond the edge of the main tumor. Although STAS has been shown to be a significant prognosticator for the postoperative survival in early-stage lung cancer treated with limited resection, its prognostic impact on the survival in completely resected adenocarcinomas with lymph node metastasis remains unclear. Patients and MethodsSTAS was assessed in a total of 63 adenocarcinomas with lymph node metastasis in patients who underwent complete resection. STAS was defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. We evaluated the association between STAS and the clinicopathologic characteristics and the postoperative survival. ResultsAmong 63 patients, 31 (49.2%) and 32 (50.8%) had disease that was pathologically positive for N1 and N2, respectively. STAS was observed in 45 patients (73.0%) and was not significantly associated with any clinicopathologic characteristics. Patients with the STAS had significantly shorter recurrence-free survival (RFS) but not overall survival than those without STAS (P = .04 and P = .35, respectively). The 5-year RFS in patients with and without STAS was 25.1% and 56.7%, respectively. According to a multivariate analysis, positivity for STAS remained an independent prognostic parameter for RFS (hazard ratio = 3.09; 95% confidence interval, 1.47-7.16; P < .01). ConclusionSTAS was predictive of a poor RFS in completely resected adenocarcinomas with lymph node metastasis.

Invited Commentary

Invited Commentary

Racial and Ethnic Disparities in Early-Stage Lung Cancer Survival

Black patients with lung cancer diagnosed at early stages-for which surgical resection offers a potential cure-experience worse overall survival than do their white counterparts. We undertook a population-based study to estimate the racial and ethnic disparity in death from competing causes and assessed its contribution to the gap in overall survival among patients with early-stage lung cancer. We collected survival time data for 105,121 Hispanic, non-Hispanic Asian, non-Hispanic black, and non-Hispanic white patients with early-stage (IA, IB, IIA, and IIB) lung cancer diagnosed between 2004 and 2013 from the Surveillance, Epidemiology, and End-Results registries. We modeled survival time using competing risk regression and included as covariates sex, age at diagnosis, race/ethnicity, stage at diagnosis, histologic type, type of surgical resection, and radiation sequence. Adjusting for demographic, clinical, and treatment characteristics, non-Hispanic blacks experienced worse overall survival compared with non-Hispanic whites (adjusted hazard ratio [aHR], 1.05; 95%CI, 1.02-1.08), whereas Hispanics and non-Hispanic Asians experienced better overall survival (aHR, 0.93; 95%CI, 0.89-0.98; and aHR, 0.82; 95%CI, 0.79-0.86, respectively). Worse survival from competing causes of death, such as cardiovascular disease and other cancers-rather than from lung cancer itself-led to the disparity in overall survival among non-Hispanic blacks (adjusted relative risk, 1.07; 95%CI, 1.02-1.12). Narrowing racial and ethnic disparities in survival among patients with early-stage lung cancer will rely on more than just equalizing access to surgical resection and will need to include better management and treatment of smoking-related comorbidities and diseases.

Baseline C-Reactive Protein Level Predicts Survival of Early-Stage Lung Cancer: Evidence from a Systematic Review and Meta-Analysis

The prognostic impact of baseline C-reactive protein (CRP) in non-small-cell lung cancer (NSCLC) is debated. To evaluate this issue, we performed a systematic review and meta-analysis to explore the role of CRP value in predicting early-stage NSCLC survival. Ten articles on early-stage NSCLC were eligible and included in our study. We performed a random-effects meta-analysis and assessed heterogeneity and publication bias. We pooled hazard ratio (HR) estimates and their 95% confidence intervals (CIs) on mortality for the comparison between the study-specific highest category of CRP level versus the lowest one. In overall analysis, elevated pretreatment CRP values were significantly associated with poor overall survival (HR 1.60, 95% CI 1.30-1.97, p&lt;0.001, I2 = 71.9%). Similar results were observed across considered strata. However, higher mortality risk was reported in studies in which CRP was combined with other factors (HR 1.96, 95% CI 1.58-2.45) and in those using a cutoff value of 3 mg/L (HR 1.89, 95% CI 1.52-2.35). Based on our analysis, baseline high CRP level is significantly associated with poor prognosis in early-stage NSCLC. Further prospective controlled studies are needed to confirm these data.