Objective Review of Mediastinal Lymph Node Examination in a Lung Cancer Resection Cohort

Background:Accurate staging of resected lung cancer requires mediastinal lymph node (MLN) examination. MLN dissection (MLND) and systematic sampling (SS) are acceptable procedures; random sampling (RS) and no sampling (NS) are not. Forty percent of US lung cancer resections have NS. We closely examined the pattern of MLN examination in a lung resection cohort.Methods:This is a retrospective review of all lung cancer resections in Memphis, TN, from 2004 to 2007. We compared operating surgeons' claims to the pathology report and an audit of the operation narrative by an independent surgeon.Results:Forty-five percent of resections were reported by surgeons as MLND, 8% RS, and 48% NS. None met pathology criteria for MLND, 9% were SS, 50% were RS, and 42% were NS. The concordance rate between the operating surgeon and pathology report was 39%. The surgeon audit suggested 29% of resections had MLND, 26% RS, and 45% NS. Concordance between operating and auditing surgeons was 71%. Sublobar resection, T1 stage, and age were associated with NS.Conclusions:Most resections had suboptimal MLN examination. Concordance was poor between surgeon claims, objective review of pathology reports, and an independent surgeon audit. The higher concordance between operating and auditing surgeons may suggest incomplete pathology examination of MLN material. The terms used by operating surgeons to describe MLN retrieval were often inaccurate

Survival impact of postoperative therapy modalities according to margin status in non–small cell lung cancer patients in the United States

Objective Unlike complete (R0) resection guidelines, current National Comprehensive Cancer Network (NCCN) adjuvant therapy guidelines after incomplete (R1/R2) resection of non–small cell lung cancer (NSCLC) are based on low-level evidence. We attempted to validate them. Methods Patients with pathologic stage I-IIIA NSCLC from 2004 to 2011 in the National Cancer Database were stratified by margin status, NCCN-specified stage groupings, and adjuvant therapy exposure (none, radiotherapy, chemotherapy, or both). Five-year overall survival (OS) and hazard ratios, adjusted for patient and institutional characteristics, were compared. We used a parallel analysis of R0 resections to validate our methodology. Results We analyzed 3461 R1/R2, and 78,979 R0 resections. After R0 resection, the NCCN-recommended option was associated with the best survival across all stage groups, supporting our analytic approach. Patients with R1/R2 stage IA treated with radiation had a 26% OS, compared with 58% with no treatment (P = .003). In patients with stage IB/IIA(N0) R1/R2, radiation was associated with a 25% OS compared with 47% with no treatment (P = .025) and 62% with chemotherapy (P < .007). Chemoradiation was not associated with a survival benefit in either group. Patients with IIA(N1)/IIB and IIIA had better survival with chemotherapy or chemoradiation. No group had a survival benefit with radiation alone. Conclusions NCCN adjuvant therapy guidelines after complete resection, based on high-level evidence, are validated, but not guidelines for patients with incompletely resected early-stage NSCLC, which are based on low-level evidence. Monomodality postoperative radiotherapy was not validated for any stage. Specific studies are needed to determine optimal management after incomplete resection

Prognostic value of lymph node ratio in patients with pathological N1 non-small cell lung cancer: A systematic review with meta-analysis

Background: Non-small cell lung cancer (NSCLC) patients with N1 disease have variable outcomes, and additional prognostic factors are needed. The number of positive lymph nodes (LNs) has been proposed as a prognostic indicator. However, the number of positive LNs depends on the number of LNs examined from the resection specimen. The lymph node ratio (LNR) can circumvent this limitation. The purpose of this study is to evaluate LNR as a predictor of survival and recurrence in patients with pathologic N1 NSCLC. Methods: We systematically reviewed studies published before March 17, 2016, on the prognostic value of LNR in patients with pathologic N1 NSCLC. The hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to combine the data. We also evaluated heterogeneity and publication bias. Results: Five studies published between 2010 and 2014 were eligible for this systematic review with metaanalysis. The total number of patients included was 6,130 ranging from 75 to 4,004 patients per study. The combined HR for all eligible studies evaluating the overall survival (OS) and disease-free survival (DFS) of N1 LNR in patients with pathologic N1 NSCLC was 1.53 (95% CI: 1.22-1.85) and 1.64 (95% CI: 1.19-2.09), respectively. We found no heterogeneity and publication bias between the reports. Conclusions: LNR is a worthy predictor of survival and cancer recurrence in patients with pathological N1 NSCLC

Colorectal Cancers from Distinct Ancestral Populations Show Variations in BRAF Mutation Frequency

It has been demonstrated for some cancers that the frequency of somatic oncogenic mutations may vary in ancestral populations. To determine whether key driver alterations might occur at different frequencies in colorectal cancer, we applied a high-throughput genotyping platform (OncoMap) to query 385 mutations across 33 known cancer genes in colorectal cancer DNA from 83 Asian, 149 Black and 195 White patients. We found that Asian patients had fewer canonical oncogenic mutations in the genes tested (60% vs Black 79% (P = 0.011) and White 77% (P = 0.015)), and that BRAF mutations occurred at a higher frequency in White patients (17% vs Asian 4% (P = 0.004) and Black 7% (P = 0.014)). These results suggest that the use of genomic approaches to elucidate the different ancestral determinants harbored by patient populations may help to more precisely and effectively treat colorectal cancer

Comparison of Prevalence and Types of Mutations in Lung Cancers Among Black and White Populations

Importance Lung cancer is the leading cause of cancer death in the United States in all ethnic and racial groups. The overall death rate from lung cancer is higher in black patients than in white patients. Objective To compare the prevalence and types of somatic alterations between lung cancers from black patients and white patients. Differences in mutational frequencies could illuminate differences in prognosis and lead to the reduction of outcome disparities by more precisely targeting patients’ treatment. Design, Setting, and Participants Tumor specimens were collected from Baptist Cancer Center (Memphis, Tennessee) over the course of 9 years (January 2004-December 2012). Genomic analysis by massively parallel sequencing of 504 cancer genes was performed at Dana-Farber Cancer Institute (Boston, Massachusetts). Overall, 509 lung cancer tumors specimens (319 adenocarcinomas; 142 squamous cell carcinomas) were profiled from 245 black patients and 264 white patients. Main Outcomes and Measures The frequencies of genomic alterations were compared between tumors from black and white populations. Results Overall, 509 lung cancers were collected and analyzed (273 women [129 black patients; 144 white patients] and 236 men [116 black patients; 120 white patients]). Using 313 adenocarcinomas and 138 squamous cell carcinomas with genetically supported ancestry, overall mutational frequencies and copy number changes were not significantly different between black and white populations in either tumor type after correcting for multiple hypothesis testing. Furthermore, specific activating alterations in members of the receptor tyrosine kinase/Ras/Raf pathway including EGFR and KRAS were not significantly different between populations in lung adenocarcinoma. Conclusions and Relevance These results demonstrate that lung cancers from black patients are similar to cancers from white patients with respect to clinically actionable genomic alterations and suggest that clinical trials of targeted therapies could significantly benefit patients in both groups

The IASLC Lung Cancer Staging Project: A Renewed Call to Participation

Over the past two decades, the International Association for the Study of Lung Cancer (IASLC) Staging Project has been a steady source of evidence-based recommendations for the TNM classification for lung cancer published by the Union for International Cancer Control and the American Joint Committee on Cancer. The Staging and Prognostic Factors Committee of the IASLC is now issuing a call for participation in the next phase of the project, which is designed to inform the ninth edition of the TNM classification for lung cancer. Following the case recruitment model for the eighth edition database, volunteer site participants are asked to submit data on patients whose lung cancer was diagnosed between January 1, 2011, and December 31, 2019, to the project by means of a secure, electronic data capture system provided by Cancer Research And Biostatistics in Seattle, Washington. Alternatively, participants may transfer existing data sets. The continued success of the IASLC Staging Project in achieving its objectives will depend on the extent of international participation, the degree to which cases are entered directly into the electronic data capture system, and how closely externally submitted cases conform to the data elements for the project

Mediastinal lymph node examination and survival in resected early-stage non-small-cell lung cancer in the surveillance, epidemiology, and end results database

BACKGROUND:: Pathologic nodal stage is the key prognostic factor in resectable non-small-cell lung cancer (NSCLC). Mediastinal lymph node (MLN) metastasis connotes a poor prognosis. Yet, some NSCLC resections exclude MLN examination. METHODS:: We analyzed U.S. Surveillance, Epidemiology, and End Results program data from 1998 to 2002 to quantify the long-term survival impact of failure to examine MLN in resected NSCLC. We used Kaplan-Meier methods to compare the unadjusted survival difference between patients with, and without, MLN examination, and Cox proportional hazards and competing risk models to serially adjust for the impact of risk factors on survival differences. RESULTS:: Sixty-two percent of patients with pathologic N0 or N1 NSCLC had no MLN examined. Overall 5-year survival rates were 52% for those with, versus 47% for those without, MLN examination; lung cancer-specific survival rates were 63% versus 58% respectively (p \u3c 0.001); nonlung cancer mortality was identical between cohorts. Adjusting for potential confounders, MLN examination was associated with a 7% reduction in all-cause mortality (hazard ratio, 0.93; confidence interval, 0.88-0.97; p = 0.002), and 11% reduction in lung cancer-specific mortality (hazard ratio, 0.89; 95% confidence interval, 0.84-0.95; p \u3c 0.001) rates. The excess risk in 1 year\u27s cohort of U.S. lung resections was 3150 lives over 5 years. CONCLUSIONS:: Failure to examine MLN was a common practice in MLN-negative NSCLC resections, which significantly impaired long-term survival. Efforts to understand the etiology of this quality gap, and measures to eliminate it, are warranted. © 2012 by the International Association for the Study of Lung Cancer

Mediastinal lymph node examination and survival in resected early-stage non-small-cell lung cancer in the surveillance, epidemiology, and end results database

BACKGROUND:: Pathologic nodal stage is the key prognostic factor in resectable non-small-cell lung cancer (NSCLC). Mediastinal lymph node (MLN) metastasis connotes a poor prognosis. Yet, some NSCLC resections exclude MLN examination. METHODS:: We analyzed U.S. Surveillance, Epidemiology, and End Results program data from 1998 to 2002 to quantify the long-term survival impact of failure to examine MLN in resected NSCLC. We used Kaplan-Meier methods to compare the unadjusted survival difference between patients with, and without, MLN examination, and Cox proportional hazards and competing risk models to serially adjust for the impact of risk factors on survival differences. RESULTS:: Sixty-two percent of patients with pathologic N0 or N1 NSCLC had no MLN examined. Overall 5-year survival rates were 52% for those with, versus 47% for those without, MLN examination; lung cancer-specific survival rates were 63% versus 58% respectively (p \u3c 0.001); nonlung cancer mortality was identical between cohorts. Adjusting for potential confounders, MLN examination was associated with a 7% reduction in all-cause mortality (hazard ratio, 0.93; confidence interval, 0.88-0.97; p = 0.002), and 11% reduction in lung cancer-specific mortality (hazard ratio, 0.89; 95% confidence interval, 0.84-0.95; p \u3c 0.001) rates. The excess risk in 1 year\u27s cohort of U.S. lung resections was 3150 lives over 5 years. CONCLUSIONS:: Failure to examine MLN was a common practice in MLN-negative NSCLC resections, which significantly impaired long-term survival. Efforts to understand the etiology of this quality gap, and measures to eliminate it, are warranted. © 2012 by the International Association for the Study of Lung Cancer

Nonexamination of lymph nodes and survival after resection of non-small cell lung cancer

Background Nonexamination of lymph nodes is an extreme example of the variability of pathologic nodal staging of non-small cell lung cancer. We compared the prevalence, characteristics, and survival of patients without lymph nodes (pNX) to patients with documented pathologic N0 and pathologic N1 non-small cell lung cancer. Methods A retrospective analysis was done of non-small cell lung cancer resections in the US Surveillance, Epidemiology, and End Results database from 1998 to 2009. Results Thirteen percent of all resections (18% of node negative resections) were pNX, including 6% of all node-negative lobar or greater resections and 51% of sublobar resections. Thirty-five percent of pNX resections were lobar or greater compared with 90% of pathologic N0 (p \u3c 0.0001). Advanced age and surgery in rural locations were also significantly associated with pNX resection. The median duration of survival was 3 years in the pNX cohort, 6.4 years in the N0 cohort (p \u3c 0.0001), and 2.8 years in the N1 group, with respective 5-year survival rates of 47%, 67%, and 45% (p \u3c 0.0001). These survival differences remained after adjustment for potentially confounding factors. Conclusions Patients with pNX resections are a high-risk subset, with survival approximating pathologic N1, not N0. They should have further attempts at retrieving lymph nodes for examination or be offered postoperative adjuvant chemotherapy. We predict that treatment modalities that fail to address lymph nodes are likely to yield inferior survival in comparison to surgery with proper lymph node examination. The proportion of pNX lung resections may be a sentinel quality indicator for lung cancer programs. © 2013 The Society of Thoracic Surgeons