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Tumor genotyping is not routinely performed in localized non-small cell lung cancer (NSCLC) due to lack of associations of mutations with outcome. Here, we analyze 232 consecutive patients with localized NSCLC and demonstrate that KEAP1 and NFE2L2 mutations are predictive of high rates of local recurrence (LR) after radiotherapy but not surgery. Half of LRs occurred in tumors with KEAP1/NFE2L2 mutations, indicating that they are major molecular drivers of clinical radioresistance. Next, we functionally evaluate KEAP1/NFE2L2 mutations in our radiotherapy cohort and demonstrate that only pathogenic mutations are associated with radioresistance. Furthermore, expression of NFE2L2 target genes does not predict LR, underscoring the utility of tumor genotyping. Finally, we show that glutaminase inhibition preferentially radiosensitizes KEAP1-mutant cells via depletion of glutathione and increased radiation-induced DNA damage. Our findings suggest that genotyping for KEAP1/NFE2L2 mutations could facilitate treatment personalization and provide a potential strategy for overcoming radioresistance conferred by these mutations. SIGNIFICANCE: This study shows that mutations in KEAP1 and NFE2L2 predict for LR after radiotherapy but not surgery in patients with NSCLC. Approximately half of all LRs are associated with these mutations and glutaminase inhibition may allow personalized radiosensitization of KEAP1/NFE2L2-mutant tumors.This article is highlighted in the In This Issue feature, p. 1775.

OBJECTIVE: This study evaluated the impact of local treatment modalities in the management of large non-small cell lung cancer (NSCLC) tumors using a nationwide population-based dataset. MATERIAL AND METHODS: Patients with NSCLC tumors >7 cm that were cN0-1M0 in the Surveillance, Epidemiology, and End Results (SEER) registry from 2010 to 2015 were stratified by local management strategy (surgery, radiation therapy, no local treatment) and evaluated using Kaplan–Meier survival analyses, Cox proportional-hazard methods, and propensity-matched analysis. RESULTS: A total of 3156 patients were identified, of which 1580 (50.1%) underwent surgical resection, 920 (29.2%) received radiation only, 655 (20.7%) received no local treatment. Overall, the 5-year survival of patients undergoing surgical resection was 40.7%, compared to 14.7% and 5.3% for the radiation only and no local treatment groups, respectively (P < .001). Surgery with or without radiation continued to have an independent association with improved survival in multivariable analysis (HR 0.23, P < .0001). Other factors associated with improved survival included younger age, negative nodal disease, and chemotherapy use. In propensity-matched sub-analyses, 5-year survival remained significantly better after surgery alone compared to radiation alone (38.5% vs. 13.6%, P < .001), while survival after radiation alone was better than no local treatment, though both were largely poor (12.4% vs. 7.5%, P < .001). CONCLUSIONS: Survival of patients with large NSCLC managed non-surgically is very poor. Despite the significant long-term survival benefit with surgical intervention, nearly half of the study cohort did not undergo surgery. Patients and clinicians can use these results to estimate specific potential benefits when considering possible treatment strategies for large NSCLC tumors. [ABSTRACT FROM AUTHOR]

We sought to develop and evaluate a personalized multimedia education (ME) tool for preoperative patient education to improve patient health knowledge, quality of life and satisfaction with care in thoracic surgery. The ME tool was developed and deployed in outpatient clinic during preoperative teaching for patients undergoing surgical resection for lung cancer for quality improvement. Patients were given an electronic survey prior to preoperative teaching and at initial postoperative visit to assess teaching effectiveness and care satisfaction. Sequential patients received either standard preoperative teaching or teaching using the ME tool. Pre- and postoperative survey responses were compared using independent sample paired t test and multivariable linear regression modeling for adjustment. The final ME tool was an iPad application that incorporated real-time annotations of 3-dimensional, interactive anatomic diagrams. The tool featured video tours of operations, and radiology image import for annotation by the surgeon. Forty-eight patients were included in this pilot study (standard education n = 26; ME, n = 22). ME patients had significantly higher satisfaction scores compared to SE patients with respect to length of education materials, clarity of content, supportiveness of content and willingness to recommend materials to others. There was no difference in length of clinic visit between groups. Both patient and provider input can be used to create an innovative electronic preoperative educational tool that prepares and empowers patients in shared decision-making before surgery. Improvements in health literacy and self-efficacy may be more difficult to achieve but remain important as multimedia teaching tools are further developed. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text Objective: To compare outcomes after open versus thoracoscopic (VATS) lobectomy for clinical stage II (cN1) non-small-cell lung cancer (NSCLC). Background: There have been no published studies evaluating the impact of a VATS approach to lobectomy for N1 NSCLC on short-term outcomes and survival. Methods: Outcomes of patients with clinical T1-2, N1, M0 NSCLC who underwent lobectomy without induction therapy in the National Cancer Data Base (2010–2012) were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis. Results: Median follow-up of 1559 lobectomies (1204 open and 355 VATS) was 43.2 months. The VATS approach was associated with a shorter median hospitalization (5 vs 6 d, P < 0.001) than the open approach. There were no significant differences between the VATS and open approach with regard to nodal upstaging (12.0% vs 10.5%, P = 0.41), 30-day mortality (2.3% vs 3.1%, P = 0.31), and overall survival (5-yr survival: 48.6% vs 48.7%, P = 0.76; multivariable-adjusted HR for VATS approach: 1.08, 95% CI: 0.90–1.30, P = 0.39). A propensity score-matched analysis of 334 open and 334 VATS patients who were well matched by 14 common prognostic covariates, including tumor size, and comorbidities, continued to show no significant differences in nodal upstaging, 30-day mortality, and 5-year survival between the VATS and open groups. Conclusion: In this national analysis, VATS lobectomy was used in the minority of N1 NSCLC cases but was associated with shorter hospitalization and similar nodal upstaging rates, 30-day mortality, and long-term survival when compared to open lobectomy. These findings suggest thoracoscopic techniques are feasible for the treatment of stage II (cN1) NSCLC. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text Objective: The objective of this study was to compare the long-term survival of open versus thoracoscopic (VATS) lobectomy for early stage non-small-cell lung cancer (NSCLC). Background: Data from national studies on long-term survival for VATS versus open lobectomy are limited. Methods: Outcomes of patients who underwent open versus VATS lobectomy for clinical T1–2, N0, M0 NSCLC in the National Cancer Data Base were evaluated using propensity score matching. Results: The median follow-up of 7114 lobectomies (5566 open and 1548 VATS) was 52.0 months. The VATS approach was associated with a better 5-year survival when compared to the open approach (66.0% vs. 62.5%, P = 0.026). Propensity score matching resulted in 1464 open and 1464 VATS patients who were well matched by 14 common prognostic covariates including tumor size and comorbidities. After propensity score matching, the VATS approach was associated with a shorter median length of stay (5 vs. 6 days, P < 0.001). The VATS approach was not significantly different compared with the open approach with regard to nodal upstaging (11.6% vs 12.3%, P = 0.53), 30-day mortality (1.7% vs 2.3%, P = 0.50) and 5-year survival (66.3% vs 65.8%, P = 0.92). Conclusions: In this national analysis, VATS lobectomy was used in the minority of patients with stage I NSCLC. VATS lobectomy was associated with shorter length of stay and noninferior long-term survival when compared with open lobectomy. These results support previous findings from smaller single- and multi-institutional studies that suggest that VATS does not compromise oncologic outcomes when used for early-stage lung cancer and suggest the need for broader implementation of VATS techniques. [ABSTRACT FROM AUTHOR]

Background: Because the relationship between the timing of surgery following diagnosis of lung cancer and survival has not been precisely described, guidelines on what constitutes a clinically meaningful delay of resection of early-stage lung cancer do not exist. This study tested the hypothesis that increasing the time between diagnosis and lobectomy for stage IA squamous cell carcinoma (SCC) would be associated with worse survival.Methods: The association between timing of lobectomy and survival for patients with clinical stage IA SCC in the National Cancer Data Base (2006-2011) was assessed using multivariable Cox proportional hazards analysis and restricted cubic spline (RCS) functions.Results: The 5-year overall survival of 4,984 patients who met study inclusion criteria was 58.3% (95% CI, 56.3-60.2). Surgery was performed within 30 days of diagnosis in 1,811 (36%) patients, whereas the median time to surgery was 38 days (interquartile range, 23, 58). In multivariable analysis, patients who had surgery 38 days or more after diagnosis had significantly worse 5-year survival than patients who had surgery earlier (hazard ratio, 1.13 [95% CI, 1.02-1.25]; P = .022). Multivariable RCS analysis demonstrated the hazard ratio associated with time to surgery increased steadily the longer resection was delayed; the threshold time associated with statistically significant worse survival was ∼90 days or greater.Conclusions: Longer intervals between diagnosis of early-stage lung SCC and surgery are associated with worse survival. Although factors other than the timing of treatment may contribute to this finding, these results suggest that efforts to minimize delays beyond those needed to perform a complete preoperative evaluation may improve survival. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The objective of this study was to evaluate outcomes of induction therapy prior to an operation in patients with cT3 non-small-cell lung cancer (NSCLC). METHODS: Patients diagnosed with cT3N0M0 NSCLC from 2006 to 2011 in the National Cancer Database who were treated with lobectomy or pneumonectomy were stratified by treatment strategy: an operation first versus induction chemotherapy. Propensity scores were developed and matched cohorts were generated. Short-term outcomes included margin status, 30- and 90-day mortality rates, readmission and length of stay. Survival analyses using Kaplan–Meier methods were performed on both the unadjusted and propensity matched cohorts. RESULTS: A total of 3791 cT3N0M0 patients were identified for inclusion, of which 580 (15%) were treated with induction chemotherapy. Prior to adjustment, patients treated with induction chemotherapy were younger, had a higher comorbidity burden and were more likely to have private insurance (all P < 0.001). Following matching, patients receiving induction chemotherapy were more likely to subsequently undergo an open procedure (87.3 vs 77.8%, P = 0.005). These patients were more likely to obtain R0 resection (93.1% vs 90.0%, P = 0.04) and were thereby less likely to have positive margins at the time of resection (6.9% vs 10.0%, P = 0.03). Patients who received induction therapy had higher rates of 90-day mortality (6.6% vs 3.4%) but there was no difference in long-term survival between the groups. CONCLUSIONS: Despite yielding increased rates of R0 resection, induction chemotherapy for cT3N0M0 NSCLC is not associated with improved survival and should not be considered routinely. Further studies are warranted to elucidate cohorts that may benefit from induction therapy. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Video-assisted thoracoscopic (VATS) lobectomy is increasingly accepted for the management of early-stage non-small cell lung cancer (NSCLC), but its role for locally advanced cancers has not been as well characterized. We compared outcomes of patients who received induction therapy followed by lobectomy, via VATS or thoracotomy. METHODS: Perioperative complications and long-term survival of all patients with NSCLC who received induction chemotherapy (ICT) (with or without induction radiation therapy) followed by lobectomy from 1996-2012 were assessed using Kaplan-Meier and Cox proportional hazard analysis. Propensity score-matched comparisons were used to assess the potential impact of selection bias. RESULTS: From 1996 to 2012, 272 patients met inclusion criteria and underwent lobectomy after ICT: 69 (25%) by VATS and 203 (75%) by thoracotomy. An 'intent-to-treat' analysis was performed. Compared with thoracotomy patients, VATS patients had a higher clinical stage, were older, had greater body mass index, and were more likely to have coronary disease and chronic obstructive pulmonary disease. Induction radiation was used more commonly in thoracotomy patients [VATS 28% (n = 19) vs open 72% (n = 146), P < 0.001]. Thirty-day mortality was similar between the VATS [3% (n = 2)] and open [4% (n = 8)] groups (P = 0.69). Seven (10%) of the VATS cases were converted to thoracotomy due to difficulty in dissection from fibrotic tissue and adhesions (n = 5) or bleeding (n = 2); none of these conversions led to perioperative deaths. In univariate analysis, VATS patients had improved 3-year survival compared with thoracotomy (61% vs 43%, P = 0.010). In multivariable analysis, the VATS approach showed a trend towards improved survival, but this did not reach statistical significance (hazard ratio, 0.56; 95% confidence interval, 0.32-1.01; P = 0.053). Moreover, a propensity score-matched analysis balancing patient characteristics demonstrated that the VATS approach had similar survival to an open approach (P = 0.56). CONCLUSIONS: VATS lobectomy in patients treated with induction therapy for locally advanced NSCLC is feasible and effective and does not appear to compromise oncologic outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We evaluated the impact of patient selection and treatment strategies on long-term outcomes of patients who had lobectomy after induction therapy for stage IIIA pN2 non-small cell lung cancer (NSCLC). METHODS: The impact of various patient selection, induction therapy and operative strategies on survival of patients with biopsy-proven stage IIIA pN2 NSCLC who received induction chemotherapy ± radiation followed by lobectomy from 1995 to 2012 was assessed using Cox proportional hazards analysis. RESULTS: From 1995 to 2012, 111 patients had lobectomy for stage IIIA pN2 NSCLC after chemotherapy ± radiation with an overall 5-year survival of 39%. The use of induction chemoradiation decreased over time; from 1996 to 2007, 46/65 (71%) patients underwent induction chemoradiation, whereas from 2007 to 2012, 36/46 (78%) patients underwent induction chemotherapy. The use of video-assisted thoracoscopic surgery (VATS) increased over the time period of the study, from 0/26 (0%) in 1996-2001, to 4/39 (10%) in 2002-07 to 33/46 (72%) in 2008-12. Compared with patients given induction chemotherapy alone, patients given additional induction radiation were more likely to have complete pathologic response (30 vs 11%, P = 0.01) but had worse 5-year survival in univariable analysis (31 vs 48%, log-rank P = 0.021). Patients who underwent pathologic mediastinal restaging following induction therapy but prior to resection had an improved overall survival compared with patients who did not undergo pathologic mediastinal restaging {5-year survival: 45.2 [95% confidence interval (CI): 33.9-55.9] vs 13.9% (95% CI: 2.5-34.7); log-rank, P = 0.004}. In multivariable analysis, the particular induction therapy strategy and the surgical approach used, as well as the extent of mediastinal disease were not important predictors of survival. However, pathologic mediastinal restaging was associated with improved survival (HR 0.39; 95% CI: 0.21-0.72; P = 0.003). CONCLUSIONS: For patients with stage IIIA pN2 NSCLC, the VATS approach or the addition of radiation to induction therapy can be selectively employed without compromising survival. The strategy of assessing response to induction therapy with pathologic mediastinal restaging allows one to select appropriate patients for complete resection and is associated with a 5-year overall survival of 39% in this population. [ABSTRACT FROM AUTHOR]

OBJECTIVES Pulmonary hypertension is considered a poor prognostic factor for or even a contraindication to major lung resection, but evidence for this claim is lacking. This study evaluates the impact of pulmonary hypertension on morbidity and mortality following pulmonary lobectomy. METHODS Adult patients who underwent a lobectomy for cancer and had a transthoracic echocardiogram (TTE) performed within the year prior to the operation were included. Pulmonary hypertension was defined as an estimated right ventricular systolic pressure (RVSP) of ≥36 mmHg by TTE. The preoperative characteristics, intraoperative data and postoperative outcomes of patients with and those without pulmonary hypertension based on TTE were compared. A model for morbidity including published risk factors as well as pulmonary hypertension was developed by multivariable logistic regression. RESULTS There were 279 patients without pulmonary hypertension and 19 patients with pulmonary hypertension. Patients with pulmonary hypertension had a lower preoperative forced expiratory volume in 1 s and diffusing capacity of the lung for carbon monoxide than patients without pulmonary hypertension and a higher incidence of tricuspid regurgitation and mitral regurgitation, but the groups were otherwise similar. The mean RVSP in the group of patients with pulmonary hypertension was 47 mmHg. Perioperative mortality (0.0 vs 2.9%; P = 1.0) and postoperative complications (57.9 vs 47.7%; P = 0.48) were not significantly different between patients with and those without pulmonary hypertension. The presence of pulmonary hypertension was not a predictor of adverse outcomes in either univariate or multivariate analysis. CONCLUSIONS Lobectomy may be performed safely in selected patients with pulmonary hypertension, with complication rates comparable with those experienced by patients without pulmonary hypertension. [ABSTRACT FROM AUTHOR]

Background: To evaluate the effect of diabetes mellitus (DM) on clinical outcomes in patients managed surgically for non-small cell lung cancer (NSCLC). Methods: Patients who underwent surgery for pathological I-IIIA NSCLC at Duke University from 1995-2005 were analyzed. Postoperative mortality was defined as any death occurring within 30 days of resection or during the initial hospitalization after surgery. Disease recurrence at the surgical margin, ipsilateral hilum, and/or mediastinum was considered a local/regional recurrence (LRR). Survival and LRR rates were estimated using the Kaplan-Meier method and compared using a log rank test. A multivariate regression analysis assessed the association between candidate factors, including DM, and disease recurrence and survival. Results: Of 957 patients, DM was present in 122 (13%). DM was associated with an increased risk of postoperative mortality (7.4% vs. 3.2%, P= 0.04). However, the proportion of patients undergoing sublobar resections, mediastinal lymph node dissection, and receiving adjuvant chemotherapy, was no different among patients with or without DM. Five-year LRR rates were 27% in patients with DM, versus 21% in patients without DM ( P= 0.23). Survival at five years was 43% for patients with DM, and 47% for patients without DM ( P= 0.10). On multivariate analysis, DM was not independently associated with a higher risk of LRR (hazard ratio [HR] 1.33, P= 0.34), distant recurrence (HR 0.86, P= 0.58), or overall survival (HR 1.08, P= 0.63). Conclusions: Although a higher risk of postoperative mortality was noted in patients with DM, a detriment in local or distant disease control or overall survival was not observed. [ABSTRACT FROM AUTHOR]

Background: Studies evaluating risk factors for complications after lobectomy in elderly patients have not adequately analyzed the effect of using minimally invasive approaches. Methods: A model for morbidity including published preoperative risk factors and surgical approach was developed by multivariable logistic regression. All patients aged 70 years or older who underwent lobectomy for primary lung cancer without chest wall resection or airway procedure between December 1999 and October 2007 at a single institution were reviewed. Preoperative, histopathologic, perioperative, and outcome variables were assessed using standard descriptive statistics. Morbidity was measured as a patient having any perioperative complication. The impact of bias in the selection of surgical approach was assessed using propensity scoring. Results: During the study period, 338 patients older than 70 years (mean age, 75.7 ± 0.2) underwent lobectomy (219 thoracoscopy, 119 thoracotomy). Operative mortality was 3.8% (13 patients) and morbidity was 47% (159 patients). Patients with at least one complication had increased length of stay (8.3 ± 0.6 versus 3.8 ± 0.1 days; p < 0.0001) and mortality (6.9% [11 of 159] versus 1.1% [2 of 179]; p = 0.008). Significant predictors of morbidity by multivariable analysis included age (odds ratio, 1.09 per year; p = 0.01) and thoracotomy as surgical approach (odds ratio, 2.21; p = 0.004). Thoracotomy remained a significant predictor of morbidity when the propensity to undergo thoracoscopy was considered (odds ratio, 4.9; p= 0.002). Conclusions: Patients older than 70 years of age can undergo lobectomy for lung cancer with low morbidity and mortality. Advanced age and the use of a thoracotomy increased the risk of complications in this patient population. [Copyright &y& Elsevier]

Thoracoscopic strategies are becoming increasingly utilized in the management of patients with thoracic disease processes, including primary pulmonary malignancy, secondary pulmonary malignancy, granulomatous lung disease, and pleural processes. Although minimally invasive approaches have been demonstrated to improve outcomes and reduce complications, as compared to the conventional approach, the prevention, early recognition, and effective management of complications after thoracoscopic pulmonary resection are still critical factors in optimizing outcomes. [Copyright &y& Elsevier]

The objective of this study was to evaluate the impact of the video-assisted thoracoscopic (VATS) approach on the outcomes of patients who underwent pneumonectomy. The effect of the surgical approach on perioperative complications and survival in patients who underwent pneumonectomy for nonmetastatic non–small cell lung cancer across 3 institutions (2000-2016) was assessed using multivariable logistic regression, Cox proportional hazards analysis, and propensity-score matching. Completion pneumonectomies were excluded from this study, and an "intent-to-treat" analysis was performed. During the study period, 359 patients met inclusion criteria and underwent pneumonectomy for nonmetastatic non–small cell lung cancer; 124 (35%) underwent pneumonectomy via VATS and 235 (65%) via thoracotomy. Perioperative mortality (VATS, 7% [n = 9] vs open, 8% [n = 19]; P =.75) and morbidity (VATS, 28% [n = 35] vs open, 28% [n = 65]; P =.91) were similar between the groups, even after multivariable adjustment. VATS showed similar 5-year survival when compared with thoracotomy in unadjusted analysis (47% [95% confidence interval (CI), 36-56] vs 33% [95% CI, 27-40]; P =.19), even after multivariable adjustment (hazard ratio, 0.76 [95% CI, 0.50-1.18]; P =.23). In a propensity score–matched analysis that balanced patient characteristics, there were no significant differences found in overall survival between the 2 groups (P =.69). Although the role of VATS pneumonectomy will likely become clearer as more surgeons report results, this multicenter study suggests that the VATS approach for pneumonectomy can be performed safely, with at least equivalent oncologic outcomes when compared with thoracotomy. [ABSTRACT FROM AUTHOR]

Objective To determine whether surgeon selection of instrumentation and other supplies during video-assisted thoracoscopic lobectomy (VATSL) can safely reduce intraoperative costs. Methods In this retrospective, cost-focused review of all video-assisted thoracoscopic surgery anatomic lung resections performed by 2 surgeons at a single institution between 2010 and 2014, we compared VATSL hospital costs and perioperative outcomes between the surgeons, as well as costs of VATSL compared with thoracotomy lobectomy (THORL). Results A total of 100 VATSLs were performed by surgeon A, and 70 were performed by surgeon B. The preoperative risk factors did not differ significantly between the 2 groups of surgeries. Mean VATSL total hospital costs per case were 24% percent greater for surgeon A compared with surgeon B ( P = .0026). Intraoperative supply costs accounted for most of this cost difference and were 85% greater for surgeon A compared with surgeon B ( P < .0001). The use of nonstapler supplies, including energy devices, sealants, and disposables, drove intraoperative costs, accounting for 55% of the difference in intraoperative supply costs between the surgeons. Operative time was 25% longer for surgeon A compared with surgeon B ( P < .0001), but this accounted for only 11% of the difference in total cost. Surgeon A's overall VATSL costs per case were similar to those of THORLs (n = 100) performed over the same time period, whereas surgeon B's VATSL costs per case were 24% less than those of THORLs. On adjusted analysis, there was no difference in VATSL perioperative outcomes between the 2 surgeons. Conclusions The costs of VATSL differ substantially among surgeons and are heavily influenced by the use of disposable equipment/devices. Surgeons can substantially reduce the costs of VATSL to far lower than those of THORL without compromising surgical outcomes through prudent use of costly instruments and technologies. [ABSTRACT FROM AUTHOR]

Objective Lobectomy is considered optimal therapy for early-stage non–small cell lung cancer, but sublobar wedge resection and stereotactic body radiation therapy are alternative treatments. This study compared outcomes between wedge resection and stereotactic body radiotherapy. Methods Overall survival of patients with cT1N0 and tumors ≤2 cm who underwent stereotactic body radiotherapy or wedge resection in the National Cancer Data Base from 2008 to 2011 was assessed via a Kaplan-Meier and propensity score–matched analysis. A center-level sensitivity analysis that used observed/expected mortality ratios was conducted to identify an association between center use of stereotactic body radiotherapy and mortality. Results Of the 6295 patients included, 1778 (28.2%) underwent stereotactic body radiotherapy, and 4517 (71.8%) underwent wedge resection. Stereotactic body radiotherapy was associated with significantly reduced 5-year survival compared with wedge resection in both unmatched analysis (30.9% vs 55.2%, P < .001) and after adjustment for covariates (31.0% vs 49.9%, P < .001). Stereotactic body radiotherapy also was associated with worse overall survival than wedge resection after 2 subgroup analyses of propensity-matched patients ( P < .05 for both). Centers that used stereotactic body radiotherapy more often as opposed to surgery for patients with cT1N0 patients with tumors <2 cm were more likely to have an observed/expected mortality ratio > 1 for 3-year mortality ( P = .034). Conclusions In this national analysis, wedge resection was associated with better survival for stage IA non–small cell lung cancer than stereotactic body radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate actuarial rates of local failure in patients with pathologic N1 non–small-cell lung cancer and to identify clinical and pathologic factors associated with an increased risk of local failure after resection. Methods and Materials: All patients who underwent surgery for non–small-cell lung cancer with pathologically confirmed N1 disease at Duke University Medical Center from 1995–2008 were identified. Patients receiving any preoperative therapy or postoperative radiotherapy or with positive surgical margins were excluded. Local failure was defined as disease recurrence within the ipsilateral hilum, mediastinum, or bronchial stump/staple line. Actuarial rates of local failure were calculated with the Kaplan-Meier method. A Cox multivariate analysis was used to identify factors independently associated with a higher risk of local recurrence. Results: Among 1,559 patients who underwent surgery during the time interval, 198 met the inclusion criteria. Of these patients, 50 (25%) received adjuvant chemotherapy. Actuarial (5-year) rates of local failure, distant failure, and overall survival were 40%, 55%, and 33%, respectively. On multivariate analysis, factors associated with an increased risk of local failure included a video-assisted thoracoscopic surgery approach (hazard ratio [HR], 2.5; p = 0.01), visceral pleural invasion (HR, 2.1; p = 0.04), and increasing number of positive N1 lymph nodes (HR, 1.3 per involved lymph node; p = 0.02). Chemotherapy was associated with a trend toward decreased risk of local failure that was not statistically significant (HR, 0.61; p = 0.2). Conclusions: Actuarial rates of local failure in pN1 disease are high. Further investigation of conformal postoperative radiotherapy may be warranted. [ABSTRACT FROM AUTHOR]