Joshua E. Rosen

Using the National Cancer Database for Outcomes Research: A Review

Importance The National Cancer Database (NCDB), a joint quality improvement initiative of the American College of Surgeons Commission on Cancer and the American Cancer Society, has created a shared research file that has changed the study of cancer care in the United States. A thorough understanding of the nuances, strengths, and limitations of the database by both readers and investigators is of critical importance. This review describes the use of the NCDB to study cancer care, with a focus on the advantages of using the database and important considerations that affect the interpretation of NCDB studies. Observations The NCDB is one of the largest cancer registries in the world and has rapidly become one of the most commonly used data resources to study the care of cancer in the United States. The NCDB paints a comprehensive picture of cancer care, including a number of less commonly available details that enable subtle nuances of treatment to be studied. On the other hand, several potentially important patient and treatment attributes are not collected in the NCDB, which may affect the extent to which comparisons can be adjusted. Finally, the NCDB has undergone several significant changes during the past decade that may affect its completeness and the types of available data. Conclusions and Relevance The NCDB offers a critically important perspective on cancer care in the United States. To capitalize on its strengths and adjust for its limitations, investigators and their audiences should familiarize themselves with the advantages and shortcomings of the NCDB, as well as its evolution over time.

Impact of Adjuvant Treatment for Microscopic Residual Disease After Non-Small Cell Lung Cancer Surgery

BACKGROUND Incomplete resection of non-small cell lung cancer (NSCLC) portends a dramatic decline in survival. Historically, postoperative radiation and chemotherapy have been offered to treat residual disease at the surgical margins, yet the efficacy is unknown. We examined the survival among incompletely resected NSCLC patients to identify the optimal response to positive NSCLC surgical margins. METHODS The National Cancer Data Base was queried for surgically managed pathologic stage I-III NSCLC between 2003 and 2006 (n = 54,512). The prevalence, predictors, impact, and optimal treatment approaches to positive surgical margins were investigated. RESULTS A positive surgical margin was identified in 3,102 NSCLC patients (5.7% of resections), including 1,688 with microscopically positive (R1) margins (3.1%). Compared with complete resections, patients with R1 resections had a worse 5-year survival; stage pI (62% vs 37%; p < 0.0001), stage pII (41% vs 29%; p < 0.0001), and stage pIII (33% vs 19%; p < 0.0001). Postoperative administration of both chemotherapy and radiation were associated with superior survival compared with surgery alone at all stages; stage pI (44% vs 35%; p = 0.05), stage pII (33% vs 21%; p = 0.0013), and stage pIII NSCLC (30% vs 12%; p < 0.0001). Administration of chemotherapy or radiation alone was less consistently associated with improved outcome in R1 patients. Of note, radiation alone did not improve survival for stage pI patients with R1 resections (26% vs 35%; p = 0.0399). CONCLUSIONS The administration of both chemotherapy and radiation is associated with an improved survival in patients with microscopically positive surgical margins, irrespective of stage. Further study is needed to clarify the optimal stage-specific adjuvant approach to incompletely resected NSCLC.

Now or later: evaluating the importance of chemotherapy timing in resectable stage III (N2) lung cancer in the National Cancer Database.

BACKGROUND Preoperative chemotherapy improves the survival of surgically managed stage III non-small cell lung cancer (NSCLC). A proportion of stage III NSCLC patients in the United States have undergone operations primarily and been given chemotherapy postoperatively. It is unclear whether postoperative chemotherapy is as effective as preoperative chemotherapy. Our objective was to determine the survival of resected stage III NSCLC according to the timing of chemotherapy. METHODS The National Cancer Database (NCDB) was queried for clinical T1-4N2M0 NSCLC (cstage III-cN2) undergoing lobectomy or pneumonectomy between 2003 and 2006. RESULTS 1,356 patients with surgically managed cstage III-cN2 disease who received preoperative chemotherapy were compared with 649 patients receiving postoperative chemotherapy. In a Cox proportional hazards model with adjustment for demographics, comorbidities, and tumor attributes, the results of postoperative chemotherapy appeared similar to those of preoperative chemotherapy (hazard ratio [HR] = 1.05, 95% confidence interval [CI] 0.93-1.19, p = 0.438). In separate Cox models, the results of postoperative chemotherapy alone were similar to those of preoperative chemotherapy alone (HR = 1.106, 95% CI 0.91-1.344, p = 0.3124). The results of postoperative chemotherapy + radiation were similar to those of preoperative chemotherapy + radiation (HR = 1.125, 95% CI 0.949-1.333, p = -0.175). CONCLUSIONS Adjusted comparison of preoperative and postoperative chemotherapy results for cstage III-N2 NSCLC in the NCDB failed to identify a superior chemotherapy approach. This suggests that a more rigorous examination of the widely held view that preoperative chemotherapy is superior may be warranted.

Association of Delayed Adjuvant Chemotherapy With Survival After Lung Cancer Surgery.

Importance Adjuvant chemotherapy offers a survival benefit to a number of staging scenarios in non–small-cell lung cancer. Variable recovery from lung cancer surgery may delay a patient’s ability to tolerate adjuvant chemotherapy, yet the urgency of chemotherapy initiation is unclear. Objective To assess differences in survival according to the time interval between non–small-cell lung cancer resection and the initiation of postoperative chemotherapy to determine the association between adjuvant treatment timing and efficacy. Design, Setting, and Participants This retrospective observational study examined treatment-naive patients with completely resected non–small-cell lung cancer who received postoperative multiagent chemotherapy between 18 and 127 days after resection between January 2004 and December 2012. The study population was limited to patients with lymph node metastases, tumors 4 cm or larger, or local extension. Patients were identified from the National Cancer Database, a hospital-based tumor registry that captures more than 70% of incident lung cancer cases in the United States. The association between time to initiation of adjuvant chemotherapy and survival was evaluated using Cox models with restricted cubic splines. Exposures Adjuvant chemotherapy administered at different time points after surgery. Main Outcomes and Measures Effectiveness of adjuvant chemotherapy according to time to initiation after surgery. Results A total of 12 473 patients (median [interquartile range] age, 64 [57-70] years) were identified: 3073 patients (25%) with stage I disease; 5981 patients (48%), stage II; and 3419 patients (27%), stage III. A Cox model with restricted cubic splines identified the lowest mortality risk when chemotherapy was started 50 days postoperatively (95% CI, 39-56 days). Initiation of chemotherapy after this interval (57-127 days; ie, the later cohort) did not increase mortality (hazard ratio [HR], 1.037; 95% CI, 0.972-1.105; P = .27). Furthermore, in a Cox model of 3976 propensity-matched pairs, patients who received chemotherapy during the later interval had a lower mortality risk than those treated with surgery only (HR, 0.664; 95% CI, 0.623-0.707; P < .001). Conclusions and Relevance In the National Cancer Database, adjuvant chemotherapy remained efficacious when started 7 to 18 weeks after non–small-cell lung cancer resection. Patients who recover slowly from non–small-cell lung cancer surgery may still benefit from delayed adjuvant chemotherapy started up to 4 months after surgery.

Length of Stay From the Hospital Perspective: Practice of Early Discharge Is Not Associated With Increased Readmission Risk After Lung Cancer Surgery.

Objective: To determine if hospitals that routinely discharge patients early after lobectomy have increased readmissions. Background: Hospitals are increasingly motivated to reduce length of stay (LOS) after lung cancer surgery, yet it is unclear if a routine of early discharge is associated with increased readmissions. The relationship between hospital discharge practices and readmission rates is therefore of tremendous clinical and financial importance. Methods: The National Cancer Database was queried for patients undergoing lobectomy for lung cancer from 2004 to 2013 at Commission on Cancer-accredited hospitals, which performed at least 25 lobectomies in a 2-year period. Facility discharge practices were characterized by a facilitys median LOS relative to the median LOS for all patients in that same time period. Results: In all, 59,734 patients met inclusion criteria; 2687 (4.5%) experienced an unplanned readmission. In a hierarchical logistic regression model, a routine of early discharge (defined as a facilitys tendency to discharge patients faster than the population median in the same time period) was not associated with increased risk of readmission (odds ratio 1.12, 95% confidence interval 0.97–1.28, P = 0.12). In a risk-adjusted hospital readmission rate analysis, hospitals that discharged patients early did not experience more readmissions (P = 0.39). The lack of effect of early discharge practices on readmission rates was observed for both minimally invasive and thoracotomy approaches. Conclusions: It is possible for hospitals to develop early discharge practices without increasing readmissions. Further study is needed to identify the critical practice elements that have enabled hospitals to aggressively discharge patients without increasing readmission risk.

Defining outcomes of patients with clinical stage I small cell lung cancer upstaged at surgery

BACKGROUND A proportion of patients with clinical stage I small cell lung cancer (SCLC) will be upstaged following surgical resection. The existing data regarding the management of upstaged SCLC patients and guidelines for their treatment remains sparse. The primary objective was to describe the impact of pathologic upstaging following surgical resection. METHODS The National Cancer Database was queried for patients with clinical stage I SCLC (cT1-2a,N0,M0) who underwent resection with curative intent followed by adjuvant therapy, excluding patients who underwent surgery alone. Clinical and pathologic T, N, and M staging were compared to identify patients that were upstaged. RESULTS Four-hundred and seventy-seven patients were identified with clinical stage I SCLC. Pathologic upstaging occurred in 25% (117). Of those upstaged, 30% (35) were due to a higher pathologic T descriptor and 81% (95) were due to the presence of nodal disease. Overall 5-year survival was significantly worse for upstaged patients compared with those patients who remained a pathologically stage I (36% vs 52%, p<0.001). Among patients with positive lymph node involvement, adjuvant chemotherapy and radiation therapy was associated a significantly improved 5-year survival compared to adjuvant chemotherapy alone (20% vs 55%, respectively, p<0.01). The use of adjuvant chemotherapy and radiation therapy in patients with nodal disease after surgical resection was an independent predictor of improved survival (HR 0.36, 95% CI 0.18-0.73, p<0.01). CONCLUSIONS Pathologic upstaging is common after surgical resection of stage I SCLC, and is associated with significantly inferior survival. These data provide evidence that recommend the use of adjuvant chemotherapy and radiation therapy in the setting of nodal upstaging after resection of clinical stage I SCLC patients.

Lung Cancer in the Very Young: Treatment and Survival in the National Cancer Data Base

Introduction: Young patients with lung cancer represent a distinct subset of patients with this disease. The National Cancer Data Base includes patients of all ages and contains detailed staging, treatment, and survival information. The objective of this study was to examine treatment patterns and outcomes in young patients with non–small cell lung cancer (NSCLC). Methods: The National Cancer Data Base was queried for NSCLC cases from 2003 to 2009. Younger patients were defined as those aged 20 to 46 years. Older patients were defined as those aged 47 to 89 years. Patient demographics, tumor characteristics, treatment, and survival were analyzed. The primary outcomes were 5‐year overall and relative survival. Results: The study included 173,856 patients; 5657 were 20 to 46 years of age. Younger patients were treated differently and received more aggressive therapy at each stage. At stage I, 64% of younger patients received surgery only versus 55% of the older patients (p < 0.0001). Younger patients had improved survival at all stages. This effect was more pronounced at earlier stages (the hazard ratios for the older group were 1.84, 1.62, 1.18, and 1.14 for stages I through IV, respectively [all p < 0.0001]). The absolute differences in 5‐year overall survival between the younger and older groups were 25% for stages I and II but only 9% and 2% for stages III and IV, respectively. Conclusions: Overall and relative survival in younger patients with NSCLC is better than in older patients, with greater benefit seen in earlier stages. Despite having fewer comorbidities and undergoing more aggressive treatment, younger patients with advanced‐stage NSCLC have only marginally better overall and relative survival than older patients.

Adjuvant Chemotherapy for T3 Non–Small Cell Lung Cancer with Additional Tumor Nodules in the Same Lobe

Introduction: Adjuvant chemotherapy after surgical resection of non–small cell lung cancer is associated with a survival advantage in several staging scenarios. T3 tumors associated with a separate tumor nodule in the same lobe (formerly “satellite nodules”) have a significant risk for systemic failure, yet the efficacy of adjuvant chemotherapy in this setting is unknown. The survival of patients with T3 tumors and additional tumor nodules in the same lobe treated with and without postoperative chemotherapy was evaluated to understand the role of adjuvant chemotherapy in this setting. Methods: The National Cancer Data Base was queried for patients with T3 tumors with additional tumor nodules in the same lobe between 2010 and 2012. Primary outcomes were 3‐year overall and relative survival (a surrogate of cancer‐specific survival). Results: A total of 1013 patients with T3 tumors and additional tumor nodules in the same lobe were identified; 56% received multiagent postoperative chemotherapy and 44% were treated with surgical resection only. The use of adjuvant chemotherapy versus resection alone was associated with improved 3‐year overall survival (70% versus 59%, p < 0.001). A Cox model adjusting for patient, tumor, and treatment factors demonstrated that adjuvant chemotherapy was associated with a survival advantage compared with resection alone (hazard ratio = 0.544, p < 0.0001). Relative 3‐year survival was also improved in the adjuvant chemotherapy subgroup (74% versus 64% for the surgery‐only subgroup). Conclusions: Adjuvant chemotherapy is associated with increased overall survival among patients with T3 tumors with additional pulmonary nodules. Further study is warranted to clarify the role of adjuvant chemotherapy in this setting.

Effectiveness of local therapy for stage I non–small-cell lung cancer in nonagenarians

Background: Stage I non–small‐cell lung cancer is potentially curable, yet older patients undergo treatment at lower rates than younger patients. This analysis sought to describe the treatment outcomes of nonagenarians with stage I non–small‐cell lung cancer to better guide treatment decisions in this population. Methods: The National Cancer DataBase was queried for patients age ≥90 years old with stage I non–small‐cell lung cancer (tumors ≤4 cm). Patients were divided into 3 groups: local therapy, other therapy, or no treatment. The primary outcomes were 5‐year overall and relative survival. Results: Of the 616 patients identified, 33% (202) were treated with local therapy, 34% (207) were treated with other therapy, and 34% (207) underwent no treatment. Compared with local therapy, overall mortality was significantly higher with no treatment (hazard ratio 2.50, 95% confidence interval, 1.95–3.21) and other therapy (hazard ratio 1.43, 95% confidence interval, 1.11–1.83). The 5‐year relative survival was 81% for local therapy, 49% for other therapy, and 32% for no treatment (P < .0001). Conclusion: Nonagenarians managed with local therapy for stage I non–small‐cell lung cancer (tumors ≤4 cm) have better overall survival than those receiving other therapy or no treatment and should be considered for treatment with either operation or stereotactic body radiation therapy if able to tolerate treatment.

Validating the Thoracic Revised Cardiac Risk Index Following Lung Resection

BACKGROUND The Thoracic Revised Cardiac Index (ThRCRI) is a tool that differentiates patients who may proceed to lung resection (classes A or B) from those who should receive additional cardiac evaluation (classes C or D). This study aims to describe the ability of the ThRCRI to stratify patients based on major cardiac complication rates using a large multi-institutional dataset. METHODS Patients undergoing lobectomy or pneumonectomy were identified in the American College of Surgeons National Surgical Quality Improvement Program dataset from 2005 to 2012. Patients were grouped into 4 risk classes based on a summary score of preoperative risk factors: ischemic heart disease, cerebrovascular disease, renal comorbidity, and pneumonectomy. The primary outcome was the incidence of perioperative major cardiac complication in each of the 4 risk classes. RESULTS Of the 4,625 patients identified, the majority underwent surgery for malignant disease (78%) and had an open procedure (70%). Among ThRCRI risk factors, 9% of patients had ischemic heart disease, 7% had cerebrovascular disease, 2% had renal comorbidity, and 6% underwent pneumonectomy. Incidence of cardiac complication in all patients was 2%. Incidence of cardiac complication within risk classes A, B, C, and D were 1%, 3%, 9%, and 4%, respectively (p < 0.01). CONCLUSIONS Using a large multi-institutional dataset, the ThRCRI can differentiate patients at higher risk for cardiac complication following lung resection (classes C and D) and can be a useful preoperative instrument. The ThRCRI may allow for identifying patients who would benefit from additional cardiac evaluation.