Background Conflicting evidence currently exists regarding the causes and effects of delay of care in non-small cell lung cancer (NSCLC). We hypothesized that delayed surgery in early-stage NSCLC is associated with worse short- and long-term outcomes. Methods Treatment data of clinical stage I NSCLC patients undergoing surgical resection was obtained from the National Cancer Database (NCDB). Treatment delay was defined as resection 8 weeks or more after diagnosis. Propensity score matching for patient and tumor characteristics was performed to create comparable groups of patients receiving early (less than 8 weeks from diagnosis) and delayed surgery. Multivariable regression models were fitted to evaluate variables influencing delay of surgery. Results From 1998-2010, 39,995 patients with clinical stage I NSCLC received early surgery, while 15,658 patients received delayed surgery. Of these 27,022 propensity-matched patients were identified. Those with a delay in care were more likely to be pathologically upstaged (18.3% stage 2 or higher vs. 16.6%, p<0.001), have an increased 30-day mortality (2.9% vs. 2.4%, p = 0.01), and have decreased median survival (57.7 ± 1.0 months versus 69.2 ± 1.3 months, p <0.001). Delay in surgery was associated with increasing age, non-Caucasian race, treatment at an academic center, urban location, income less than $35,000 and increasing Charlson comorbidity score (p<0.0001 for all). Delayed patients were more likely to receive a sublobar resection (17.2% vs. 13.1%, p <0.001). Conclusions Patients receiving delayed resection for clinical stage I NSCLC have higher comorbidity scores that may affect ability to perform lobectomy and result in higher peri-operative mortality. However, delay in resection is independently associated with increased rates of upstaging and decreased median survival. Strategies to minimize delay while medically optimizing higher risk patients are needed.

Purpose To investigate the impact of modern postoperative radiotherapy (PORT) on overall survival (OS) for patients with N2 non–small-cell lung cancer (NSCLC) treated nationally with surgery and adjuvant chemotherapy. Patients and Methods Patients with pathologic N2 NSCLC who underwent complete resection and adjuvant chemotherapy from 2006 to 2010 were identified from the National Cancer Data Base and stratified by use of PORT (≥ 45 Gy). A total of 4,483 patients were identified (PORT, n = 1,850; no PORT, n = 2,633). The impact of patient and treatment variables on OS was explored using Cox regression. Results Median follow-up time was 22 months. On univariable analysis, improved OS correlated with younger age, treatment at an academic facility, female sex, urban population, higher income, lower Charlson comorbidity score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT. On multivariable analysis, improved OS remained independently predicted by younger age, female sex, urban population, lower Charlson score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT (hazard ratio, 0.886; 95% CI, 0.798 to 0.988). Use of PORT was associated with an increase in median and 5-year OS compared with no PORT (median OS, 45.2 v 40.7 months, respectively; 5-year OS, 39.3% [95% CI, 35.4% to 43.5%] v 34.8% [95% CI, 31.6% to 38.3%], respectively; P = .014). Conclusion For patients with N2 NSCLC after complete resection and adjuvant chemotherapy, modern PORT seems to confer an additional OS advantage beyond that achieved with adjuvant chemotherapy alone.

Structured abstract Objective To study causes and implications of intraoperative conversions to thoracotomy during VATS lobectomy. Methods We performed an institutional review of patients undergoing lobectomy for known or suspected lung cancer with root cause analysis of every conversion from VATS to open thoracotomy. Results Between 2004 and 2012, 1227 patients underwent lobectomy. Of these, 517 (42%) were completed VATS, 87 (7%) converted to open, and 623 (51%) were performed via planned thoracotomy. Patients undergoing thoracotomy were younger and had a higher incidence of prior lung cancers. Planned thoracotomy and conversion group patients had higher clinical T stage than the VATS group while the planned thoracotomy group had higher pathologic stage than the other groups. Postoperative complications were more frequent in the conversion group (46%) than VATS (23%, p<0.001), but similar to the open group (42%, p=0.56). Validating a previous classification of causes for conversion, 22/87 (25%) were due to vascular causes, 56 (64%) for anatomy (adhesions/tumor size), and 8 (9%) for lymph nodes. No specific imaging variables predicted conversion. Within the conversions, emergent (20/87, 23%) and planned (67/87, 77%) conversion groups were similar in patient- and tumor characteristics and incidence of perioperative morbidity. The conversion rate for VATS lobectomy dropped from 21/74 (28%), to 29/194 (15%), to 37/336 (11%) (p<0.001) over 3-year intervals. Over the same periods, the proportion of operations started VATS increased significantly. Conclusions With increasing experience, a higher proportion of lobectomy operations can be completed thoracoscopically. VATS should be strongly considered as the initial approach for the majority of patients undergoing lobectomy.

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Background Adjuvant chemotherapy improves survival in patients with completely resected stage II and III NSCLC. However, its role in patients with stage IB NSCLC disease remains unclear. We evaluated the role of adjuvant chemotherapy in a large data set of patients with completely resected T2N0M0 NSCLC. Methods Patients with pathologic stage T2N0M0 NSCLC who underwent complete (R0) resection between 2004 and 2011 were identified from the National Cancer Data Base and classified into four groups based on tumor size: 3.1 to 3.9 cm, 4 to 4.9 cm, 5 to 5.9 cm, and 6 to 7 cm. Patients who died within 1 month after their operation were excluded. Survival curves were estimated by the Kaplan-Meier product-limit method and compared by log-rank test. Results Among the 25,267 patients who met the inclusion criteria, there were 4996 (19.7%) who received adjuvant chemotherapy. Adjuvant chemotherapy was associated with improved median and 5-year overall survival compared with observation for all tumor size groups. In patients with T2 tumors smaller than 4 cm, adjuvant chemotherapy was associated with improved median and 5-year overall survival in univariate (101.6 versus 68.2 months [67% versus 55%], hazard ratio [HR] = 0.66, 95% confidence interval [CI]: 0.61–0.72, p < 0.0001) and multivariable analysis (HR = 0.77, 95% CI: 0.70–0.83, p < 0.001) as well as propensity-matched score (101.6 versus 78.9 months [68% versus 60%], HR = 0.75, 95% CI: 0.70–0.86; p < 0.0001). Conclusions In patients with completely resected T2N0M0, adjuvant chemotherapy is associated with improved survival in all tumor size groups. The benefit in patients with tumors smaller than 4 cm strongly suggests a role for chemotherapy in this patient population and counters its current status as an exclusion criteria for adjuvant trials.

Objective To study incidence, predictors, and implications of unanticipated early postoperative readmission after lung resection for non-small cell lung cancer (NSCLC). Methods Patients undergoing surgery for clinical stage I–III NSCLC were abstracted from the National Cancer Database (NCDB). Regression models were fitted to identify predictors of 30-day readmission, and to study the association of unplanned readmission with 30-day and long-term survival. Results Between 1998 and 2010, 129893 patients underwent resection for stage I–III NSCLC. Of these, 5624 (4.3%) were unexpectedly readmitted within 30 days. In a multivariate regression model, increasing age, male gender, preoperative radiation, and pneumonectomy (OR 1.77, 1.56–2.00) were associated with unexpected readmissions. Longer index hospitalization and higher Charlson comorbidity score were also predictive of readmission. The 30-day mortality for readmitted patients was higher (3.9% vs. 2.8%), as was the 90-day mortality (7.0% vs. 3.3%, both p<0.001). In a multivariate cox proportional hazards model of long-term survival, increasing age, higher Charlson comorbidity score, and higher pathologic stage (HR for stage III 1.81, 1.42–2.29) were associated with greater risk of mortality. Unplanned readmission was independently associated with higher risk of long-term mortality (HR 1.40, 1.34–1.47). The median survival for readmitted patients was significantly shorter (38.7 months vs. 58.5 months, p<0.001). Conclusions Unplanned readmissions are not rare after resection for NSCLC. Such events are associated with a greater risk of short- and long-term mortality. With the renewed national focus on readmissions and potential financial disincentives, greater resource allocation is needed to identify patients at risk and develop measures to avoid the associated adverse outcomes.

Background A substantial proportion of patients with clinical stage I NSCLC have more advanced disease on final pathologic review. We studied potentially modifiable factors that may predict pathologic upstaging. Methods Data of patients with clinical stage I NSCLC undergoing resection were obtained from the National Cancer Database (NCDB). Univariate and multivariate analyses were performed to identify variables that predict upstaging. Results From 1998–2010, 55,653 patients with clinical stage I NSCLC underwent resection; of these 9,530 (17%) had more advanced disease on final pathologic review. Of the 9,530 upstaged patients, 27% had T3 or T4 tumors, 74% had positive lymph nodes (N>0), and 4% were found to have metastatic disease (M1). Patients with larger tumors (38mm vs. 29mm, p<0.001) and a delay >8 weeks from diagnosis to resection were more likely to be upstaged. Upstaged patients also had more lymph nodes examined (10.9 vs. 8.2, p<0.001) and were more likely to have positive resection margins (10% vs. 2%, p<0.001). Median survival was lower in upstaged patients (39 months vs. 73 months). Predictors of upstaging in multivariate regression analysis included larger tumor size, delay in resection >8 weeks, positive resection margins, and number of lymph nodes examined. There was a linear relationship between the number of lymph nodes examined and the odds of upstaging (1–3 nodes, OR 2.01; >18 nodes OR 6.14). Conclusions Pathologic upstaging is a common finding with implications for treatment and outcomes in clinical stage I NSCLC. A thorough analysis of regional lymph nodes is critical to identify patients with more advanced disease.

Background The role of multi-modality therapy in stage IIIB NSCLC remains inadequately studied. Although chemoradiation is currently the mainstay of treatment, randomized trials evaluating surgery are lacking and resection is offered selectively. Methods Data of clinical stage IIIB NSCLC patients (T4N2 or any N3) undergoing definitive multimodality therapy were obtained from the National Cancer Database (NCDB). Multivariable Cox regression models were fitted to evaluate variables influencing overall survival (OS). Results From 1998-2010, 7,459 clinical stage IIIB NSCLC patients were treated with definitive chemoradiation (CR group), while 1,714 patients underwent chemotherapy, radiation, and surgery in any sequence (CRS group). CRS patients were more likely to be younger, Caucasian, and have slightly smaller tumors (all p < 0.01). There was no difference in Charlson Comorbidity Index (CCI) between the groups (p = 0.5). In the CRS group, 79% of patients received neoadjuvant therapy. Thirty-day surgical mortality was 3%. Factors associated with improved OS in multivariate analysis included younger age, female gender, decreased CCI, smaller tumor size, and surgical resection (HR 0.57, 95% CI 0.52-0.63). Among patients treated with surgery, incomplete resection was associated with decreased OS (HR 1.52, 95% CI 1.20-1.92). Median OS was longer in CRS patients (25.9 months vs. 16.3 months, p<0.001). Propensity matched analysis on 631 patient-pairs treated with CRS vs. CR confirmed these findings (median OS = 28.9 vs. 17.2 months, p<0.001). Conclusions Surgical resection as a part of multimodality therapy may be associated with improved overall survival in highly selected patients with stage IIIB NSCLC. Multidisciplinary evaluation of these patients is critical.