Effect of Lymph Node Assessment on Outcomes in Surgery for Limited Stage Small Cell Lung Cancer.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend surgery for limited stage small cell lung cancer (SCLC). However, there is no literature on minimum acceptable lymph node retrieval in surgery for SCLC. METHODS: The National Cancer Database was queried for adult patients undergoing lobectomy for limited stage (cT1-2N0M0) SCLC from 2004 to 2015. Patients with unknown survival, staging, or nodal assessment, and patients who received neoadjuvant therapy were excluded. The number of lymph nodes assessed was studied both as a continuous variable and as a categoric variable stratified into distribution quartiles. The primary outcome was overall survival and the secondary outcome was pathologic nodal upstaging. RESULTS: A total of 1051 patients met study criteria. In multivariable analysis, only a retrieval of eight to 12 nodes was associated with a significant survival benefit (hazard ratio 0.73; 95% confidence interval, 0.56 to 0.98). However, when modeled as a continuous variable, there was no association between number of nodes assessed and survival (hazard ratio 1.00; 95% confidence interval, 0.98 to 1.02). The overall rate of pathologic nodal upstaging was 19%. Modeled as a continuous variable, more than seven lymph nodes assessed at time of resection was significantly associated with nodal upstaging in multivariable regression (odds ratio 1.03; 95% confidence interval, 1.01 to 1.06). CONCLUSIONS: In this study, there was no clear difference in survival based on increasing the number of lymph nodes assessed during lobectomy for limited stage SCLC. However, the number of retrieved lymph nodes was associated with pathologic nodal upstaging. Therefore, patients may benefit from retrieval of more than seven lymph nodes during lobectomy for SCLC.

National Comprehensive Cancer Network Guidelines: Who Makes Them? What Are They? Why Are They Important?

The National Comprehensive Cancer Network (NCCN) is a not-for-profit alliance of 28 leading cancer centers dedicated to improving and facilitating quality, effective, efficient, and accessible cancer care so that patients can live better lives. The NCCN offers a number of programs and resources to give clinicians access to tools and knowledge that can help guide decision making in the management of cancer, including the flagship product, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). The NCCN Guidelines provide evidence-based, consensus-driven guidance for cancer management to ensure that all patients receive preventive, diagnostic, therapeutic, and supportive services that are most likely to lead to optimal outcomes. They are intended to assist all individuals who impact decision making in cancer care, including physicians, nurses, pharmacists, payers, patients and their families, and many others. The development of the NCCN Guidelines is an ongoing and iterative process based on a critical review of the best available evidence and the consensus recommendations made by a multidisciplinary panel of oncology experts. The NCCN Guidelines are the most detailed and frequently updated clinical practice guidelines available in any area of medicine and are the recognized standard for cancer care throughout the world. NCCN Guidelines are used by clinicians, payers, and other health care decision makers around the world to ensure delivery of high-quality, accessible, patient-centered care aimed at optimizing patient outcomes.

Disparities in guideline-concordant treatment for node-positive, non-small cell lung cancer following surgery.

OBJECTIVES: To examine guideline concordance across a national sample and determine the relationship between socioeconomic factors, use of recommended postoperative adjuvant therapy, and outcomes for patients with resected pN1 or pN2 non-small cell lung cancer. METHODS: All margin-negative pT1-3 N1-2 M0 non-small cell lung cancers treated with lobectomy or pneumonectomy without induction therapy in the National Cancer Database between 2006 and 2013 were included. Use of guideline-concordant adjuvant treatment, defined as chemotherapy for pN1 disease and chemotherapy with or without radiation for pN2 disease, was examined. Multivariable regression models were developed to determine associations of clinical factors with guideline adherence. Survival was estimated using Kaplan-Meier and Cox proportional hazard analyses. RESULTS: Of 13,462 patients, 10,113 had pN1 disease and 3349 had pN2 disease. Guideline-concordant adjuvant therapy was used in 6844 (67.7%) patients with pN1 disease and 2622 (78.3%) patients with pN2 disease. After multivariable adjustment, insurance status, older age, pneumonectomy, readmission, and longer postoperative stays were associated with lower likelihood of guideline concordance. Conversely, increased education level, later year of diagnosis, and greater nodal stage were associated with greater concordance. Overall, patients treated with guideline-concordant therapy had superior survival (5-year survival: 51.6 vs 36.0%; hazard ratio, 0.66; 95% confidence interval, 0.62-0.70, P < .001). CONCLUSIONS: Socioeconomic factors, including insurance status and geographic region, are associated with disparities in use of adjuvant therapy as recommended by National Comprehensive Cancer Network guidelines. These disparities significantly impact patient survival. Future work should focus on improving access to appropriate adjuvant therapies among the under insured and socioeconomically disadvantaged.

Surgery Is Associated With Survival Benefit in T4a Esophageal Adenocarcinoma: A National Analysis.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend consideration of surgery for clinical T4a esophageal adenocarcinoma. There are limited data on the outcomes of patients with T4a adenocarcinoma treated with surgery vs definitive chemoradiation, however. METHODS: The National Cancer Database was used to identify patients from 2010-2015 with clinical T4aN0-3M0 esophageal adenocarcinoma, and grouped by receipt of surgery (with or without perioperative therapy) or definitive, concurrent chemoradiation. Patients receiving incomplete definitive therapy or with missing survival information were excluded. Overall survival was evaluated with Kaplan-Meier and Cox proportional hazard analyses. RESULTS: Of 182 patients in the study, 85 (47%) underwent esophagectomy and 97 (53%) underwent chemoradiation. In the surgery cohort, 79 patients (93%) received perioperative chemotherapy. Unadjusted and multivariable analyses demonstrated a significant survival benefit associated with surgery compared with definitive chemoradiotherapy (adjusted hazard ratio 0.32; 95% confidence interval 0.21, 0.50). A 1:1 propensity score-matched analysis of 63 patient pairs also revealed a significant overall survival benefit with surgery compared with chemoradiotherapy alone (hazard ratio 0.26; 95% confidence interval 0.16, 0.43). CONCLUSIONS: In this national analysis, surgery for cT4a esophageal adenocarcinoma was associated with improved outcomes when compared with definitive chemoradiation. Surgery should be considered for medically fit patients with cT4aN0-3M0 esophageal adenocarcinoma.

Minimally Invasive Versus Open Esophagectomy for Esophageal Cancer: A Population-Based Analysis.

BACKGROUND: The objective of this study was to evaluate outcomes of minimally invasive approaches to esophagectomy using population-level data. METHODS: Multivariable regression modeling was used to determine predictors associated with the use of minimally invasive approaches for patients in the National Cancer Data Base who underwent resection of middle and distal clinical T13N03M0 esophageal cancers from 2010 to 2012. Perioperative outcomes and 3-year survival were compared between propensity-matched groups of patients with esophageal cancer who underwent minimally invasive esophagectomy (MIE) or open esophagectomy (OE). A subgroup analysis was performed to evaluate the impact of using robotic-assisted operations as part of the minimally invasive approach. RESULTS: Among 4,266 patients included, 1,308 (30.6%) underwent MIE. It was more likely to be used in patients treated at academic (adjusted odds ratio [OR], 10.1; 95% confidence interval [CI], 4.2-33.1) or comprehensive cancer facilities (adjusted OR, 6.4; 95% CI, 2.6-21.1). Compared with propensity-matched patients who underwent OE, patients who underwent MIE had significantly more lymph nodes examined (15 versus 13; p = 0.016) and shorter hospital lengths of stay (10 days versus 11 days; p = 0.046) but similar resection margin positivity, readmission, and 30-day mortality (all p > 0.05). Survival was similar between the matched groups at 3 years for both adenocarcinoma and squamous cell carcinoma (p > 0.05). Compared with MIE without robotic assistance, use of a robotic approach was not associated with any significant differences in perioperative outcomes (p > 0.05). CONCLUSIONS: The use of minimally invasive techniques to perform esophagectomy for esophageal cancer is associated with modestly improved perioperative outcomes without compromising survival.

Variation in Definitive Therapy for Localized Non-Small Cell Lung Cancer Among National Comprehensive Cancer Network Institutions.

PURPOSE: This study determined practice patterns in the staging and treatment of patients with stage I non-small cell lung cancer (NSCLC) among National Comprehensive Cancer Network (NCCN) member institutions. Secondary aims were to determine trends in the use of definitive therapy, predictors of treatment type, and acute adverse events associated with primary modalities of treatment. METHODS AND MATERIALS: Data from the National Comprehensive Cancer Network Oncology Outcomes Database from 2007 to 2011 for US patients with stage I NSCLC were used. Main outcome measures included patterns of care, predictors of treatment, acute morbidity, and acute mortality. RESULTS: Seventy-nine percent of patients received surgery, 16% received definitive radiation therapy (RT), and 3% were not treated. Seventy-four percent of the RT patients received stereotactic body RT (SBRT), and the remainder received nonstereotactic RT (NSRT). Among participating NCCN member institutions, the number of surgeries-to-RT course ratios varied between 1.6 and 34.7 (P<.01), and the SBRT-to-NSRT ratio varied between 0 and 13 (P=.01). Significant variations were also observed in staging practices, with brain imaging 0.33 (0.25-0.43) times as likely and mediastinoscopy 31.26 (21.84-44.76) times more likely for surgical patients than for RT patients. Toxicity rates for surgical and for SBRT patients were similar, although the rates were double for NSRT patients. CONCLUSIONS: The variations in treatment observed among NCCN institutions reflects the lack of level I evidence directing the use of surgery or SBRT for stage I NSCLC. In this setting, research of patient and physician preferences may help to guide future decision making.

Interinstitutional variation in management decisions for treatment of 4 common types of cancer: A multi-institutional cohort study.

BACKGROUND: When clinical practice is governed by evidence-based guidelines and there is consensus about their validity, practice variation should be minimal. For areas in which evidence gaps exist, greater variation is expected. OBJECTIVE: To systematically assess interinstitutional variation in management decisions for 4 common types of cancer. DESIGN: Multi-institutional, observational cohort study of patients with cancer diagnosed between July 2006 through May 2011 and observed through 31 December 2011. SETTING: 18 cancer centers participating in the formulation of treatment guidelines and systematic outcomes assessment through the National Comprehensive Cancer Network. PATIENTS: 25 589 patients with incident breast cancer, colorectal cancer, lung cancer, or non-Hodgkin lymphoma. MEASUREMENTS: Interinstitutional variation for 171 binary management decisions with varying levels of supporting evidence. For each decision, variation was characterized by the median absolute deviation of the center-specific proportions. RESULTS: Interinstitutional variation was high (median absolute deviation >10%) for 35 of 171 (20%) oncology management decisions, including 9 of 22 (41%) decisions for non-Hodgkin lymphoma, 16 of 76 (21%) for breast cancer, 7 of 47 (15%) for lung cancer, and 3 of 26 (12%) for colorectal cancer. Forty-six percent of high-variance decisions involved imaging or diagnostic procedures and 37% involved choice of chemotherapy regimen. The evidence grade underpinning the 35 high-variance decisions was category 1 for 0%, 2A for 49%, and 2B/other for 51%. LIMITATION: Physician identifiers were unavailable, and results may not generalize outside of major cancer centers. CONCLUSION: The substantial variation in institutional practice manifest among cancer centers reveals a lack of consensus about optimal management for common clinical scenarios. For clinicians, awareness of management decisions with high variation should prompt attention to patient preferences. For health systems, high variation can be used to prioritize comparative effectiveness research, patient-provider education, or pathway development. PRIMARY FUNDING SOURCE: National Cancer Institute and National Comprehensive Cancer Network.

Patterns of recurrence after trimodality therapy for esophageal cancer.

BACKGROUND: Patterns of failure after neoadjuvant chemoradiotherapy and surgery for esophageal cancer are poorly defined. METHODS: All patients in the current study were treated with trimodality therapy for nonmetastatic esophageal cancer from 1995 to 2009. Locoregional failure included lymph node failure (NF), anastomotic failure, or both. Abdominal paraaortic failure (PAF) was defined as disease recurrence at or below the superior mesenteric artery. RESULTS: Among 155 patients, the primary tumor location was the upper/middle esophagus in 18%, the lower esophagus in 32%, and the gastroesophageal junction in 50% (adenocarcinoma in 79% and squamous cell carcinoma in 21%) of patients. Staging methods included endoscopic ultrasound (73%), computed tomography (46%), and positron emission tomography/computed tomography (54%). Approximately 40% of patients had American Joint Committee on Cancer stage II disease and 60% had stage III disease. The median follow-up was 1.3 years. The 2-year locoregional control, event-free survival, and overall survival rates were 86%, 36%, and 48%, respectively. The 2-year NF rate was 14%, the isolated NF rate was 3%, and the anastomotic failure rate was 6%. The 2-year PAF rate was 9% and the isolated PAF rate was 5%. PAF was found to be increased among patients with gastroesophageal junction tumors (12% vs 6%), especially for the subset with ≥ 2 clinically involved lymph nodes at the time of diagnosis (19% vs 4%). CONCLUSIONS: Few patients experience isolated NF or PAF as their first disease recurrence. Therefore, it is unlikely that targeting additional regional lymph node basins with radiotherapy would significantly improve clinical outcomes.

Smoking status and survival in the national comprehensive cancer network non-small cell lung cancer cohort.

BACKGROUND: The objectives of this study were to evaluate survival among current smokers, former smokers, and never smokers who are diagnosed with non-small cell lung cancer (NSCLC). METHODS: The study included patients who participated in the National Comprehensive Cancer Network's NSCLC Database Project. Current, former, and never smokers were compared with respect to overall survival by fitting Cox regression models. RESULTS: Data from 4200 patients were examined, including 618 never smokers, 1483 current smokers, 380 former smokers who quit 1 to 12 months before diagnosis, and 1719 former smokers who quit >12 months before diagnosis. Among patients with stage I, II, and III disease, only never smokers had better survival than current smokers (hazard ratio, 0.47 [95% confidence interval, 0.26-0.85] vs 0.51 [95% confidence interval, 0.38-0.68], respectively). Among patients with stage IV disease, the impact of smoking depended on age: Among younger patients (aged ≤55 years), being a never smoker and a former smoker for ≥12 months increased survival. After age 85 years, smoking status did not have a significant impact on overall survival. CONCLUSIONS: Patients who were smoking at the time of diagnosis had worse survival compared with never smokers. Among younger patients with stage IV disease, current smokers also had worse survival compared with former smokers who quit >12 months before diagnosis. It is likely that tumor biology plays a major role in the differences observed; however, to improve survival, it is prudent to encourage all smokers to quit smoking if they are diagnosed with NSCLC.

Radiation therapy at the end of life in patients with incurable nonsmall cell lung cancer.

BACKGROUND: Receipt of chemotherapy at the end of life (EOL) is considered an indicator of poor quality of care for medical oncology. The objective of this study was to characterize the use of radiotherapy (RT) in patients with nonsmall cell lung cancer (NSCLC) during the same period. METHODS: Treatment characteristics of patients with incurable NSCLC who received RT at the EOL, defined as within 14 days of death, were analyzed from the National Comprehensive Cancer Network NSCLC Outcomes Database. RESULTS: Among 1098 patients who died, 10% had received EOL RT. Patients who did and did not receive EOL RT were similar in terms of sex, race, comorbid disease, and Eastern Cooperative Oncology Group performance status. On multivariable logistic regression analysis, independent predictors of receiving EOL RT included stage IV disease (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.09-3.83) or multiorgan involvement (OR, 1.75; 95% CI, 1.08-2.84) at diagnosis, age <65 years at diagnosis (OR, 1.85; 95% CI, 1.21-2.83), and treating institution (OR, 1.24-5.94; P = .02). Nearly 50% of EOL RT recipients did not complete it, most commonly because of death or patient preference. CONCLUSIONS: In general, EOL RT was received infrequently, was delivered more commonly to younger patients with more advanced disease, and often was not completed as planned. There also was considerable variation in its use among National Comprehensive Cancer Network institutions. Next steps include expanding this research to other cancers and settings and investigating the clinical benefit of such treatment.

Efficacy of mediastinal lymph node dissection during lobectomy for lung cancer by thoracoscopy and thoracotomy.

BACKGROUND: Mediastinal lymph node dissection (MLND) is an integral component of complete resection for non-small cell lung cancer (NSCLC). This study analyzed the National Comprehensive Cancer Network's (NCCN) NSCLC Database to compare the efficacy of MLND during lobectomy by video-assisted thoracoscopy surgery (VATS) and thoracotomy (open). METHODS: The NCCN NSCLC Database was queried to identify patients who underwent lobectomy to analyze the adequacy of MLND by the number of LN stations. The percentage of patients with at least three N2 stations, the number of N2 LN stations, and the total number of LN stations (N1+N2) resected was compared by approach. RESULTS: Of 4215 patients with NSCLC (January 2007 to September 2010), 388 patients underwent lobectomy (199 VATS and 189 open) and met entry criteria. The groups were similar in age, sex, comorbidities, performance status, and histology. MLN assessment was similar in both groups as measured by number of N2 stations (median, 3 stations; p=0.12). At least three MLN stations were assessed in 130 patients (66%) in the VATS group vs 107 patients (58%) in the open group (p=0.12). The total number of N1+N2 stations resected for each group was also similar (median, 4 in both groups (p=0.06). CONCLUSIONS: The NCCN database indicates at least three MLN stations were assessed in most patients who underwent lobectomy by either approach. As evaluated by the number of LN stations, there was no difference in the efficacy of MLN dissection by approach.

Paclitaxel-based chemoradiotherapy in the treatment of patients with operable esophageal cancer.

PURPOSE: To compare a neoadjuvant regimen of cisplatin/5-fluorouracil (5-FU) and concurrent radiation therapy (RT) with paclitaxel-based regimens and RT in the management of operable esophageal (EC)/gastroesophageal junction (GEJ) cancer. METHODS AND MATERIALS: All patients receiving neoadjuvant chemotherapy (CT) and RT for EC/GEJ cancer at Duke University between January 1995 and December 2004 were included. Clinical end points were compared for patients receiving paclitaxel-based regimens (TAX) vs. alternative regimens (non-TAX). Local control (LC), disease-free survival (DFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Chi-square analysis was performed to test the effect of TAX on pathologic complete response (pCR) rates and toxicity. RESULTS: A total of 109 patients received CT-RT followed by esophagectomy (95 M; 14 F). Median RT dose was 45 Gy (range, 36-66 Gy). The TAX and non-TAX groups comprised 47% and 53% of patients, respectively. Most (83%) TAX patients received three drug regimens including platinum and a fluoropyrimidine. In the non-TAX group, 89% of the patients received cisplatin and 5-FU. The remainder received 5-FU or capecitabine alone. Grade 3-4 toxicity occurred in 41% of patients receiving TAX vs. 24% of those receiving non-TAX (p = 0.19). Overall pCR rate was 39% (39% with TAX vs. 40% with non-TAX, p = 0.9). Overall LC, DFS, and OS at 3 years were 80%, 34%, and 37%, respectively. At 3 years, there were no differences in LC (75% vs. 85%, p = 0.33) or OS (37% vs. 37%, p = 0.32) between TAX and non-TAX groups. CONCLUSIONS: In this large experience, paclitaxel-containing regimens did not improve pCR rates or clinical end points compared to non-paclitaxel-containing regimens.

Improved survival with pulmonary metastasectomy: an analysis of 1720 patients with pulmonary metastatic melanoma.

OBJECTIVES: The outcomes of patients with metastatic melanoma are poor. Although prognostic models have been developed to predict the occurrence of pulmonary metastasis from cutaneous melanoma, few data exist to define the outcomes of these patients once metastasis has occurred. The objective of this study was to discriminate predictors of survival for patients with pulmonary metastatic melanoma. METHODS: We found 1720 patients with pulmonary metastasis listed in a prospective comprehensive cancer center database of 14,057 consecutive patients with melanoma (Jan 1, 1970-June 1, 2004). Demographic and histopathologic data, time and location of recurrences, number of pulmonary nodules, and subsequent therapies were collected. Univariate and multivariate Cox proportional hazards models were used to identify predictors of survival for patients with pulmonary metastatic melanoma. RESULTS: The median survival was 7.3 months after development of pulmonary metastasis. Significant predictors of survival from the multivariate model included nodular histologic type (P = .033), disease-free interval (P < .001), number of pulmonary metastases (P = .012), presence of extrathoracic metastasis (P < .001), and performance of pulmonary metastasectomy (P < .001). Interactions were identified between metastasectomy and disease-free interval and presence of extrathoracic metastasis. Surgery was associated with a survival advantage of 12 months for patients with a disease-free interval longer than 5 years (19 vs 7 months, P < .01) and of 10 months for patients without extrathoracic metastasis (18 vs 8 months, P < .01). CONCLUSIONS: When all other identified risk factors were controlled for mathematically, metastasectomy maintained a significant survival advantage for patients with pulmonary metastatic melanoma. These data support the role of surgery for a select subset of patients with pulmonary metastasis.

Outcomes after surgery for esophageal cancer.

Esophageal cancer is a virulent malignancy associated with a 5-year overall survival of approximately 5%. Treatment remains controversial-despite the results of prospective, randomized trials of combined-modality therapy-because results are poor with all strategies. The role of surgical resection in patients with esophageal cancer is controversial. The fact that most patients have advanced disease at the time of diagnosis makes surgery futile in the majority of cases. Nevertheless, surgery is the best option for cure in early-stage esophageal cancer and remains the superior modality for local control in locally advanced disease. The benefits and drawbacks of several surgical approaches are discussed in this review. Multiple factors are implicated in the etiology of postesophagectomy complications, the rate of which is quite high. Perhaps the most important contributor to morbidity and mortality after esophagectomy is the development of pulmonary complications. Over the past decade, there has been a trend toward the increased use of trimodality therapy in potentially operable patients-induction chemotherapy and radiation therapy, followed by surgery. The rationale for using induction therapy is that it allows simultaneous delivery of local (radiation therapy) and systemic (chemotherapy) modalities, provides for early tumor regression and symptom control, results in improved subsequent local control, and identifies responding patients who might benefit from adjuvant therapy. Thus, on the basis of recent studies and meta-analyses, there may be a modest survival advantage for patients who receive induction chemotherapy followed by surgery, compared with surgery alone. There is also an apparent increase in treatment-related mortality, mainly for patients receiving induction chemotherapy and radiotherapy. Currently, National Comprehensive Cancer Network guidelines support the use of induction therapy only in established clinical trial protocols.