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Importance: The randomized clinical trial Cancer and Leukemia Group B (CALGB) 140503 showed that for patients with clinically staged T1N0 non-small cell lung cancer (NSCLC; ≤2 cm), sublobar resections were associated with similar oncological outcomes to those after lobar resection. The association of the extent of parenchymal resection with recurrence and survival in patients with tumors pathologically upstaged to T2 based on visceral pleural invasion (VPI) is controversial. Objective: To determine survival and recurrence rates in patients with small peripheral pT2 NSCLC (≤2 cm) that was treated by either lobar or sublobar resection in CALGB 140503. Design, Participants, and Setting: CALGB 140503, a randomized multicenter noninferiority trial, included 697 patients with small peripheral NSCLC that was clinically staged as T1N0. Enrollment was from June 2007 through March 2017 at 83 participating institutions, and after a median follow-up of 7 years, the primary outcome of disease-free survival after sublobar resection was noninferior to that after lobar resection. Intervention: Lobar or sublobar resection. Main Outcomes and Measures: Survival end points were estimated by the Kaplan-Meier estimator. Hazard ratios and 95% CIs were estimated using stratified Cox proportional hazard models. Results: Of 679 participants, 390 (57.4%) were female, and the median (range) age was 67.8 (37.8-89.7) years. Among 697 patients randomized, 566 (81.2%) had pT1 tumors (no VPI) and 113 (16.2%) had pT2 tumors (VPI). Five-year disease-free survival was 65.9% (95% CI, 61.9%-70.2%) in patients with pT1 compared with 53.3% (95% CI, 44.3%-64.1%) in patients with pT2 tumors (stratified log-rank: P = .02). Disease recurrence developed in 27.6% of patients with pT1 (locoregional only: 60 [10.8%]; distant only: 81 [14.6%]) and 41.6% of those with pT2 (locoregional only: 17 [15.0%]; distant only: 27 [23.9%]). Five-year recurrence-free survival was 73.1% (95% CI, 69.2%-77.1%) for pT1 tumors and 58.2% (95% CI, 49.2%-68.8%) for pT2 tumors (stratified log-rank: P = .01). There were no intergroup differences in disease-free or recurrence-free survival based on the extent of parenchymal resection. Conclusions and Relevance: The results of this secondary analysis suggest that compared with patients with tumors without VPI, patients who had tumors with VPI had worse disease-free and recurrence-free survival and a higher rate of local and distant disease recurrence. These high rates of recurrence were independent of the extent of parenchymal resection, and these data support the inclusion of these patients in adjuvant therapy trials. Trial Registration: ClinicalTrials.gov Identifier: NCT0049933.
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Background: Long-standing controversy has existed over whether sublobar resection is an adequate oncological procedure for clinical stage IA non-small cell lung cancer (NSCLC) ≤2 cm, despite the recent randomized trial reports of Japanese Clinical Oncology Group (JCOG) 0802 and Cancer and Leukemia Group B (CALGB) 140503 demonstrating non-inferior outcomes with sublobar resection compared to lobectomy. As practice patterns shift, we sought to compare oncologic outcomes in patients with these early-stage tumors after wedge resection, segmentectomy, or lobectomy in a contemporary, real-world, cohort. Methods: A retrospective review of a prospectively maintained database from a single institution was conducted from 2011 to 2020 to identify all patients with clinically staged IA1 or IA2 NSCLC (tumors ≤2 cm with no nodal involvement). The primary outcomes of interest were overall survival (OS) and disease-free survival (DFS), with secondary outcomes of lung cancer-specific survival (LCSS), recurrence patterns, and perioperative morbidity and mortality. Results: A total of 480 patients were identified; 93 (19.4%) patients underwent wedge resection, 90 (18.7%) received segmentectomy, and 297 (61.9%) underwent lobectomy. Patients who underwent wedge resection had worse Eastern Cooperative Oncology Group (ECOG) performance status (23.7% ECOG 1 or 2 vs. 5.6% among segmentectomy and 5.4% among lobectomy, P<0.05). Both wedge resection and segmentectomy patients had lower preoperative mean percentage of predicted forced expiratory volume in one second (%FEV1) compared to the lobectomy group (81.8% and 82.6% vs. 89.6%, P=0.002), a higher proportion of patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), and a higher Charlson Comorbidity Index. There were no statistically significant differences in 5-year OS, DFS, or LCSS between groups: 90%, 61%, 78% for wedge resections compared with 85%, 75%, 86% for segmentectomy, and 87%, 77%, 87% for lobectomy, respectively. Recurrence was observed in 17 patients who underwent wedge resection (18.3%, 8 local, 9 distant), 12 patients who received segmentectomy (13.4%, 6 local, 6 distant), and 38 patients who underwent lobectomy (12.8%, 11 local, 27 distant), which was not significantly different (P=0.36). Conclusions: Patients with inferior performance status or lower baseline pulmonary function are more likely to receive wedge resection for clinical stage IA NSCLC ≤2 cm in size. For these small tumors, lobectomy, segmentectomy, and wedge resection provide comparable oncologic outcomes.
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OBJECTIVE: In 2022, the American College of Surgeons Commission on Cancer issued standard 5.8 quality metric for curative lung cancer resections requiring nodal resection from 3 N2 stations. In this report, we compare oncologic outcomes after resection of 3 N2 stations versus 2 N2 stations in stage I non-small cell lung cancer. METHODS: A retrospective review from a single institution database was conducted from 2011 to 2020 to identify patients with clinical stage I non-small cell lung cancer. Patients with a history of lung cancer, carcinoid tumors, and ground-glass lesions less than 50% solid component were excluded. The primary outcome was overall survival. Secondary outcomes included disease-free survival, recurrence patterns, and nodal upstaging. RESULTS: A total of 581 patients were identified and divided into 2 groups based on the number of N2 stations examined: Group A had 2 N2 stations examined (364 patients), and group B had 3 or more N2 stations examined (217 patients). Baseline demographic and clinical characteristics were similar between groups. In group A, N1 and N2 positive nodal stations were present in 8.2% (30/364) and 5.2% (19/364) of patients versus 7.4% (16/217) and 5.5% (12/217), respectively, in group B. Five-year overall survival and disease-free survival were 89% and 74% in group A versus 88% and 78% in group B, respectively. Recurrence occurred in 56 patients (15.4%) in group A (6.6% local and 8.8% distant) and 29 patients (13.4%) in group B (5.1% local and 8.3% distant; P = .73). CONCLUSIONS: There was no significant difference in oncological outcomes in stage I non-small cell lung cancer resections that included 2 N2 stations compared with at least 3 N2 stations examined.
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BACKGROUND: Low socioeconomic status is a well-characterized adverse prognostic factor in large lung cancer databases. However, such characterizations may be confounded as patients of lower socioeconomic status are more often treated at low-volume, non-academic centers. We evaluated whether socioeconomic status, as defined by ZIP code median income, was associated with differences in lung cancer resection outcomes within a high-volume academic medical center. METHODS: Consecutive patients undergoing resection for non-small cell lung cancer were identified from a prospectively maintained database (2011-18). Patients were assigned an income value based on the median income of their ZIP code as determined by census-based geographic data. We stratified the population into income quintiles representative of SES and compared demographics (chi-square), surgical outcomes, and survival (Kaplan-Meier). RESULTS: We identified 1,693 patients, representing 516 ZIP codes. Income quintiles were Q1: $24,421-53,151; Q2:$53,152-73,982; Q3:$73,983-99,063; Q4:$99,064-123,842; and Q5:$123,843-250,001. Compared to Q5 patients, Q1 patients were younger (median 69 vs. 73, p < 0.001), more likely male (44 vs. 36%, p = 0.035), and more likely Asian, Black, or self-identified as other than white, Asian, or Black. (67 vs. 11%, p = < 0.001). We found minor differences in surgical outcomes and no significant difference in 5-year survival between Q1 and Q5 patients (5-year: 86 vs. 85%, p = 0.886). CONCLUSIONS: Surgical care patterns at a high-volume academic medical center are similar among patients from varying ZIP codes. Surgical treatment at such a center is associated with no survival differences based upon socioeconomic status as determined by ZIP code. Centralization of lung cancer surgical care to high-volume centers may reduce socioeconomic outcome disparities.
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Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Male , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/surgery , Income , Social ClassABSTRACT
BACKGROUND: Anastomotic leak after esophagectomy carries important short and long-term sequelae. We conducted a systematic review and meta-analysis to determine its association with surgical volume. MATERIALS AND METHODS: A systematic literature review was performed to identify all studies reporting on anastomotic leak after esophagectomy. Studies with <100 cases were excluded. The primary outcome was post-esophagectomy anastomotic leak, while secondary outcomes were operative mortality overall and after anastomotic leak. Pooled event rates (PER) were calculated and association with annual esophagectomy volume by center was investigated. RESULTS: Of the 3,932 retrieved articles, 472 were included (n=177,566 patients). The PER of anastomotic leak was 8.91% [95%CI=8.32; 9.53%]. The PER of early mortality overall and after anastomotic leak was 2.49% [95%CI=2.27; 2.74] and 11.39% [95%CI=9.66; 13.39], respectively. Centers with <37 annual esophagectomies had a higher leak rate compared to those with ≥37 annual esophagectomies (9.58% vs. 8.34%; P=0.040). On meta-regression, surgical volume was inversely associated with the PER of esophageal leak and of early mortality. CONCLUSION: The frequency of anastomotic leaks after esophagectomy, perioperative and leak associated mortality are inversely associated with esophagectomy volume.
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BACKGROUND: The increased detection of small-sized peripheral non-small-cell lung cancer (NSCLC) has renewed interest in sublobar resection in lieu of lobectomy. METHODS: We conducted a multicenter, noninferiority, phase 3 trial in which patients with NSCLC clinically staged as T1aN0 (tumor size, ≤2 cm) were randomly assigned to undergo sublobar resection or lobar resection after intraoperative confirmation of node-negative disease. The primary end point was disease-free survival, defined as the time between randomization and disease recurrence or death from any cause. Secondary end points were overall survival, locoregional and systemic recurrence, and pulmonary functions. RESULTS: From June 2007 through March 2017, a total of 697 patients were assigned to undergo sublobar resection (340 patients) or lobar resection (357 patients). After a median follow-up of 7 years, sublobar resection was noninferior to lobar resection for disease-free survival (hazard ratio for disease recurrence or death, 1.01; 90% confidence interval [CI], 0.83 to 1.24). In addition, overall survival after sublobar resection was similar to that after lobar resection (hazard ratio for death, 0.95; 95% CI, 0.72 to 1.26). The 5-year disease-free survival was 63.6% (95% CI, 57.9 to 68.8) after sublobar resection and 64.1% (95% CI, 58.5 to 69.0) after lobar resection. The 5-year overall survival was 80.3% (95% CI, 75.5 to 84.3) after sublobar resection and 78.9% (95% CI, 74.1 to 82.9) after lobar resection. No substantial difference was seen between the two groups in the incidence of locoregional or distant recurrence. At 6 months postoperatively, a between-group difference of 2 percentage points was measured in the median percentage of predicted forced expiratory volume in 1 second, favoring the sublobar-resection group. CONCLUSIONS: In patients with peripheral NSCLC with a tumor size of 2 cm or less and pathologically confirmed node-negative disease in the hilar and mediastinal lymph nodes, sublobar resection was not inferior to lobectomy with respect to disease-free survival. Overall survival was similar with the two procedures. (Funded by the National Cancer Institute and others; CALGB 140503 ClinicalTrials.gov number, NCT00499330.).
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Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Pneumonectomy , Humans , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Disease-Free Survival , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Neoplasm Staging , Pneumonectomy/adverse effects , Pneumonectomy/methods , Retrospective Studies , Neoplasm Recurrence, Local , Recurrence , Lymph Nodes/pathologyABSTRACT
OBJECTIVE: Several trials have recently reported the safety of pulmonary resection after neoadjuvant immunotherapy with encouraging major pathological response rates. We report the detailed adverse events profile from a recently conducted randomized phase II trial in patients with resectable non-small cell lung cancer treated with neoadjuvant durvalumab alone or with sub-ablative radiation. METHODS: We conducted a randomized phase II trial in patients with non-small cell lung cancer clinical stages I to IIIA who were randomly assigned to receive neoadjuvant durvalumab alone or with sub-ablative radiation (8Gyx3). Secondary end points included the safety of 2 cycles of preoperative durvalumab with and without radiation followed by pulmonary resection. Postoperative adverse events within 30 days were recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: Sixty patients were enrolled and randomly assigned, with planned resection performed in 26 patients in each arm. Baseline demographics and clinical variables were balanced between groups. The median operative time was similar between arms: 128 minutes (97-201) versus 146 minutes (109-214) (P = .314). There was no 30- or 90-day mortality. Grade 3/4 adverse events occurred in 10 of 26 patients (38%) after monotherapy and in 10 of 26 patients (38%) after dual therapy. Anemia requiring transfusion and hypotension were the 2 most common adverse events. The median length of stay was similar between arms (5 days vs 4 days, P = .172). CONCLUSIONS: In this randomized trial, the addition of sub-ablative focal radiation to durvalumab in the neoadjuvant setting was not associated with increased mortality or morbidity compared with neoadjuvant durvalumab alone.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Neoadjuvant Therapy/adverse effects , Neoadjuvant Therapy/methods , Antibodies, Monoclonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
OBJECTIVE: The aim was to determine the prevalence of metastases to the cervical and recurrent laryngeal cervicothoracic (CT) nodes as well as survival and recurrence patterns after esophagectomy with three-field lymph node dissection (TFD) in patients with predominately adenocarcinoma (AC) of the esophagus. BACKGROUND: Although esophagectomy with TFD is commonly practiced in Japan and Southeast Asia for squamous cell cancer (SCC) of the esophagus, there are only a handful of reports about its' utilization and survival benefit in North American patients. METHODS: This is a retrospective case series of patients who had an esophagectomy with TFD. The primary outcomes of interest were the prevalence of nodal metastases to the CT nodes as well as overall survival (OS) and disease-free survival. Secondary outcomes included time to recurrence, recurrence patterns, operative morbidity as well as 30 and 90-day mortality. RESULTS: Two hundred forty-two patients with esophageal cancer (AC: 67%) underwent esophagectomy with TFD. Metastases to the CT nodes were present in 56 patients (23%: AC 20% and SCC 30%). Positive CT nodes were present in 14% of pT1/T2 tumors and 30% of pT3 tumors. For the 56 patients with CT positive nodes, 5-year OS was 25% (AC:16%; SCC:39%). Fifteen of 56 (26.7%) patients with metastases to the CT nodes were alive and disease-free at a minimum of 5 years postoperatively. Ten-year OS was 43% for all patients with SCC and 28% for patients with AC. CONCLUSIONS: Metastases to the CT nodes are common in both SCC and AC of the esophagus and may be present in at least 14% of early lesions. Five-year survival is encouraging particularly for patients with esophageal SCC cancer.
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Adenocarcinoma , Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Retrospective Studies , Neoplasm Staging , Lymph Node Excision , Esophageal Squamous Cell Carcinoma/surgery , Esophageal Squamous Cell Carcinoma/pathology , Epithelial Cells , Esophagectomy , Lymph Nodes/pathologyABSTRACT
OBJECTIVES: The aim of this study was to explore the potential value of extended nodal-dissection following neoadjuvant chemoradiation (CRT), by analyzing data from the National Cancer Database (NCDB). BACKGROUND: A CROSS-trial post-hoc analysis showed that the number of dissected lymph nodes was associated with improved survival in patients undergoing upfront surgery but not in those treated with neoadjuvant CRT. METHODS: The NCDB was queried (2004-2014) for patients who underwent esophagectomy following induction CRT. Predictors of overall survival (OS) were assessed. The optimal number of dissected LNs associated with highest survival benefit was determined by multiple regression analyses and receiveroperating characteristic curve analysis. The whole cohort was divided into 2 groups based on the predefined cutoff number. The two groups were propensity-matched (PMs). RESULTS: Esophagectomy following induction-CRT was performed in 14,503 patients. The number of resected nodes was associated with improved OS in the multivariable analysis (hazard ratio for every 10 nodes: 0.95 (95% confidence interval: 0.93-0.98). The cutoff number of resected LNs that was associated with the highest survival benefit was 20 nodes. In the PM groups, patients in the "≥20 LNs" group had a 14% relative-increase in OS ( P = 0.002), despite having more advanced pathological stages (stage II-IV: 76% vs 72%, P < 0.001), and higher number of positive nodes (0-2 vs 0-1, P < 0.001). CONCLUSIONS: The total number of resected nodes is a significant determinant of improved survival following induction CRT in patients with either node negative or node positive disease. In the matched groups, patients with higher number of resected lymph nodes had higher OS rate, despite having more advanced pathological disease and higher number of resected positive lymph nodes.
Subject(s)
Esophageal Neoplasms , Lymph Node Excision , Humans , Neoplasm Staging , Lymph Nodes/pathology , Esophageal Neoplasms/surgery , Chemoradiotherapy , Esophagectomy , Survival Rate , Retrospective Studies , PrognosisABSTRACT
BACKGROUND: The influence of SARS-CoV-2 on surgery for non-small cell lung cancer needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. OBJECTIVE: This study reports on the 90-day rate of infection as well as the morbidity and mortality of lung surgery for cancer in a tertiary care hospital located in a pandemic epicenter. METHODS: We conducted a retrospective review of a prospective database to identify consecutive patients who underwent lung cancer resection before (January 1, 2020-March 10, 2020, group 1; 57 patients) and during the COVID-19 pandemic (March 11, 2020-June 10, 2020, group 2; 41 patients). The primary end point was the occurrence of SARS-CoV-2 infection during the first 90-days after surgery. The secondary outcome measure was 90-day perioperative morbidity and mortality. RESULTS: Patient characteristics were not significantly different between the groups. Ninety-day COVID-19 infection rates was 7.3% (3 out of 41) for patients undergoing an operation during the pandemic and 3.5% (2 out of 57) in patients operated on immediately before the pandemic. All patients tested positive 10 to 62 days after the index surgical procedure following hospital discharge. Four COVID-19-positive patients were symptomatic and 4 out of 5 patients required hospitalization, were men, previous or current smokers with hyperlipidemia, and underwent a sublobar resection. Univariate analysis did not identify any differences in postoperative complications before or during the COVID-19 pandemic. Ninety-day mortality was 5% (2 out of 41) for lung cancer surgery performed during the pandemic, with all deaths occurring due to COVID-19, compared with 0% (0 out of 57) mortality in patients who underwent an operation before the pandemic. CONCLUSIONS: During the COVID-19 pandemic, COVID-19 infections occurred in 7.3% of patients who underwent surgery for non-small cell lung cancer. In this series all infections occurred after hospital discharge. Our results suggest that COVID-19 infections occurring within 90 days of surgery portend a 40% mortality, warranting close postoperative surveillance.
Subject(s)
COVID-19 , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , COVID-19/epidemiology , Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/surgery , Female , Humans , Lung Neoplasms/epidemiology , Lung Neoplasms/surgery , Male , Pandemics , Retrospective Studies , SARS-CoV-2ABSTRACT
BACKGROUND: Minimal literature exists evaluating the impact of the extent of resection on survival in patients with small, early-stage non-small cell lung cancer (NSCLC) found to have occult nodal disease. We hypothesized that sublobar resection has comparable overall survival to patients undergoing lobectomy for clinical stage IA NSCLC that harbors occult nodal disease. METHODS: The National Cancer Database was reviewed for identification of patients with clinical stage IA NSCLC who underwent wedge resection, segmentectomy, or lobectomy and were found to have occult nodal disease. Overall survival was compared between groups, and a multivariate Cox regression model identified factors associated with worse survival. RESULTS: Occult nodal disease occurred in 6.1% of all patients with clinical stage IA disease undergoing resection. Patients undergoing wedge resection and segmentectomy found to have occult nodal disease were older (67.6 ± 9.6 years of age vs 66.1 ± 9.3 years of age vs 65.6 ± 9.5 years of age; P = .004) and had more advanced pathologic stage (pStage III: 68.7% vs 50.5% vs 41.5%; P < .001) than those receiving lobectomy. There was no difference in the median overall survival between segmentectomy and lobectomy (68.5 months vs 57.6 months; P = .200). However, wedge resection was independently associated with worse overall survival when controlling for other preoperative variables (hazard ratio, 1.23; 95% confidence interval, 1.01-1.51; P = .042). CONCLUSIONS: Review of the National Cancer Database suggests that there is no improvement in overall survival in patients undergoing lobectomy vs segmentectomy in carefully selected patients with clinical stage IA NSCLC harboring occult nodal disease. However, those undergoing wedge resection may have worse overall survival than those undergoing both lobectomy and segmentectomy.
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Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , Humans , Lung Neoplasms/pathology , Middle Aged , Neoplasm Staging , Pneumonectomy , Proportional Hazards Models , Retrospective StudiesABSTRACT
Introduction: Pulmonary resections following neoadjuvant therapy (NT) can be technically demanding. There is a paucity of data regarding the use of minimally invasive surgery (MIS) approaches in that setting on the National level. In this study, we explored the trends of using MIS approaches following NT and its associated outcomes. Methods: The study included all adult patients with non-small cell lung cancer who underwent pulmonary resection following NT between 2010 and 2016. Propensity score (PS) matching (MIS versus open) was performed and the perioperative outcomes were compared. Results: The study included 11,287 patients who underwent pulomonary resection after NT. The percentage of patients undergoing MIS lung resection and the number of hospitals performing one or more MIS increased from 19% and 166 (2010) to 41% and 305 (2016), respectively. When compared with thoracotomy, MIS lung resections were more frequently performed in academic centers in patients with higher income (P < .001). In PS matched groups, the use of MIS was associated with shorter hospital length of stay (5 days versus 6 days; P < .001), compared with open approach. However, there were no differences between the two groups in readmission rate (P = .513), or 30-/90-day mortality (P = .145/.685). In multivariable regression analysis, MIS approach was not associated with worse long-term, all-cause, survival (confidence interval: 0.91-1.09). Conclusion: The use of MIS approaches after NT increased significantly over the study period and was associated with perioperative outcomes and long-term survival comparable to those noted with the open approach.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Adult , Carcinoma, Non-Small-Cell Lung/surgery , Humans , Length of Stay , Lung Neoplasms/surgery , Minimally Invasive Surgical Procedures/adverse effects , Neoadjuvant Therapy , Propensity Score , Retrospective Studies , United StatesABSTRACT
INTRODUCTION: The COVID-19 pandemic reached New York City in early March 2020 resulting in an 11-week lockdown period to mitigate further spread. It has been well documented that cancer care was drastically affected as a result. Given New York City's early involvement, we attempted to identify any stage shift that may have occurred in the diagnoses of non-small cell lung cancer (NSCLC) at our institution as a result of these lockdowns. PATIENTS AND METHODS: We conducted a retrospective review of a prospective database of lung cancer patients at our institution from July 1, 2019 until March 31, 2021. Patients were grouped by calendar year quarter in which they received care. Basic demographics and clinical staging were compared across quarters. RESULTS: Five hundred and fifty four patients were identified that underwent treatment during the time period of interest. During the lockdown period, there was a 50% reduction in the mean number of patients seen (15 ± 3 vs. 28 ± 7, P = .004). In the quarter following easing of restrictions, there was a significant trend towards earlier stage (cStage I/II) disease. In comparison to quarters preceding the pandemic lockdown, there was a significant increase in the proportion of patients with Stage IV disease in the quarters following phased reopening (P = .026). CONCLUSION: After a transient but significant increase in Stage I/II disease with easing of restrictions there was a significant increase in patients with Stage IV disease. Extended longitudinal studies must be conducted to determine whether COVID-19 lockdowns will lead to further increases in the proportion of patients with advanced NSCLC.
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COVID-19 , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , COVID-19/epidemiology , COVID-19/prevention & control , Carcinoma, Non-Small-Cell Lung/epidemiology , Communicable Disease Control , Humans , Lung Neoplasms/epidemiology , New York City/epidemiology , Pandemics/prevention & control , SARS-CoV-2ABSTRACT
OBJECTIVE: Sublobar resection is frequently offered to patients with small, peripheral lung cancers, despite the lack of outcome data from ongoing randomized clinical trials. Sublobar resection may be a particularly attractive surgical strategy for screen-detected lung cancers, which have been suggested to be less biologically aggressive than cancers detected by other means. Using prospective data collected from patients undergoing surgery in the National Lung Screening Trial, we sought to determine whether extent of resection affected survival for patients with screen-detected lung cancer. METHODS: The National Lung Screening Trial database was queried for patients who underwent surgical resection for confirmed lung cancer. Propensity score matching analysis (lobectomy vs sublobar resection) was done (nearest neighbor, 1:1, matching with no replacement, caliper 0.2). Demographics, clinicopathologic and perioperative outcomes, and long-term survival were compared in the entire cohort and in the propensity-matched groups. Multivariable logistic regression analysis was done to identify factors associated with increased postoperative morbidity or mortality. RESULTS: We identified 1029 patients who underwent resection for lung cancer in the National Lung Screening Trial, including 821 patients (80%) who had lobectomy and 166 patients (16%) who had sublobar resection, predominantly wedge resection (n = 114, 69% of sublobar resection). Patients who underwent sublobar resection were more likely to be female (53% vs 41%, P = .004) and had smaller tumors (1.5 cm vs 2 cm, P < .001). The sublobar resection group had fewer postoperative complications (22% vs 32%, P = .010) and fewer cardiac complications (4% vs 9%, P = .033). For stage I patients undergoing sublobar resection, there was no difference in 5-year overall survival (77% for both groups, P = .89) or cancer-specific survival (83% for both groups, P = .96) compared with patients undergoing lobectomy. On multivariable logistic regression analysis, sublobar resection was the only factor associated with lower postoperative morbidity/mortality (odds ratio, 0.63; 95% confidence interval, 0.40-0.98). To compare surgical strategies in balanced patient populations, we propensity matched 127 patients from each group undergoing sublobar resection and lobectomy. There were no differences in demographics or clinical and tumor characteristics among matched groups. There was again no difference in 5-year overall survival (71% vs 65%, P = .40) or cancer-specific survival (75% vs 73%, P = .89) for patients undergoing lobectomy and sublobar resection, respectively. CONCLUSIONS: For patients with screen-detected lung cancer, sublobar resection confers survival similar to lobectomy. By decreasing perioperative complications and potentially preserving lung function, sublobar resection may provide distinct advantages in a screened patient cohort.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/surgery , Female , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Male , Neoplasm Staging , Pneumonectomy/adverse effects , Prospective Studies , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Routine mutation profiling for resected lung cancers is not widespread despite an increasing array of targeted therapies. We report the incidence of epidermal growth factor receptor mutations (EGFRmu+) in resected lung adenocarcinomas and their outcomes at a large North American cancer center to characterize this population now eligible for targeted adjuvant therapy. METHODS: Among 1036 pulmonary resections performed between 2015 and 2019, 647 patients (62%) had adenocarcinomas that underwent molecular profiling by next-generation sequencing. Clinical and pathologic characteristics, along with survival, were analyzed. RESULTS: EGFRmu+ were identified in 238 patients (37%). Patients with EGFRmu+ were more likely to be Asian than those with EGFR wild-type (79/238 [33%] vs 37/409 [9%], respectively; P < .001) and more likely to be never-smokers (115/238 [48%] vs 73/409 [18%], P < .001). However, most patients with EGFRmu+ in our cohort were White (45%) and had a history of smoking (52%). A statistically nonsignificant trend was observed toward improved 3-year overall survival for pathologic stage IB to III cancers with EGFRmu+ (91% vs 77%, P = .09). Patients with pathologic stage IB lung cancers with EGFRmu+ had a 97% rate of 3-year disease-free survival, with only 1 recurrence in the first 3 years of follow-up. EGFR mutation subtype was not associated with survival differences. CONCLUSIONS: Although Asians and never-smokers comprised a disproportionately large group of patients with lung adenocarcinomas with EGFRmu+, most EGFR mutations within our cohort were found in patients who were White or with a smoking history, supporting a routine rather than selective approach to mutation profiling. Patients with surgically resected stage IA and IB lung adenocarcinomas enjoy excellent survival regardless of their mutational status.
Subject(s)
Adenocarcinoma of Lung , Adenocarcinoma , Lung Neoplasms , Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Adenocarcinoma/surgery , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/surgery , ErbB Receptors/genetics , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/surgery , Mutation , Neoplasm StagingSubject(s)
Mediastinum/diagnostic imaging , Pneumonectomy/adverse effects , Postoperative Complications/etiology , Thoracotomy/methods , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/surgery , Male , Mediastinum/surgery , Middle Aged , Postoperative Complications/diagnosis , Postoperative Complications/surgery , Reoperation , Syndrome , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Previous phase 2 trials of neoadjuvant anti-PD-1 or anti-PD-L1 monotherapy in patients with early-stage non-small-cell lung cancer have reported major pathological response rates in the range of 15-45%. Evidence suggests that stereotactic body radiotherapy might be a potent immunomodulator in advanced non-small-cell lung cancer (NSCLC). In this trial, we aimed to evaluate the use of stereotactic body radiotherapy in patients with early-stage NSCLC as an immunomodulator to enhance the anti-tumour immune response associated with the anti-PD-L1 antibody durvalumab. METHODS: We did a single-centre, open-label, randomised, controlled, phase 2 trial, comparing neoadjuvant durvalumab alone with neoadjuvant durvalumab plus stereotactic radiotherapy in patients with early-stage NSCLC, at NewYork-Presbyterian and Weill Cornell Medical Center (New York, NY, USA). We enrolled patients with potentially resectable early-stage NSCLC (clinical stages I-IIIA as per the 7th edition of the American Joint Committee on Cancer) who were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients were randomly assigned (1:1) to either neoadjuvant durvalumab monotherapy or neoadjuvant durvalumab plus stereotactic body radiotherapy (8 Gy × 3 fractions), using permuted blocks with varied sizes and no stratification for clinical or molecular variables. Patients, treating physicians, and all study personnel were unmasked to treatment assignment after all patients were randomly assigned. All patients received two cycles of durvalumab 3 weeks apart at a dose of 1·12 g by intravenous infusion over 60 min. Those in the durvalumab plus radiotherapy group also received three consecutive daily fractions of 8 Gy stereotactic body radiotherapy delivered to the primary tumour immediately before the first cycle of durvalumab. Patients without systemic disease progression proceeded to surgical resection. The primary endpoint was major pathological response in the primary tumour. All analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrial.gov, NCT02904954, and is ongoing but closed to accrual. FINDINGS: Between Jan 25, 2017, and Sept 15, 2020, 96 patients were screened and 60 were enrolled and randomly assigned to either the durvalumab monotherapy group (n=30) or the durvalumab plus radiotherapy group (n=30). 26 (87%) of 30 patients in each group had their tumours surgically resected. Major pathological response was observed in two (6·7% [95% CI 0·8-22·1]) of 30 patients in the durvalumab monotherapy group and 16 (53·3% [34·3-71·7]) of 30 patients in the durvalumab plus radiotherapy group. The difference in the major pathological response rates between both groups was significant (crude odds ratio 16·0 [95% CI 3·2-79·6]; p<0·0001). In the 16 patients in the dual therapy group with a major pathological response, eight (50%) had a complete pathological response. The second cycle of durvalumab was withheld in three (10%) of 30 patients in the dual therapy group due to immune-related adverse events (grade 3 hepatitis, grade 2 pancreatitis, and grade 3 fatigue and thrombocytopaenia). Grade 3-4 adverse events occurred in five (17%) of 30 patients in the durvalumab monotherapy group and six (20%) of 30 patients in the durvalumab plus radiotherapy group. The most frequent grade 3-4 events were hyponatraemia (three [10%] patients in the durvalumab monotherapy group) and hyperlipasaemia (three [10%] patients in the durvalumab plus radiotherapy group). Two patients in each group had serious adverse events (pulmonary embolism [n=1] and stroke [n=1] in the durvalumab monotherapy group, and pancreatitis [n=1] and fatigue [n=1] in the durvalumab plus radiotherapy group). No treatment-related deaths or deaths within 30 days of surgery were reported. INTERPRETATION: Neoadjuvant durvalumab combined with stereotactic body radiotherapy is well tolerated, safe, and associated with a high major pathological response rate. This neoadjuvant strategy should be validated in a larger trial. FUNDING: AstraZeneca.
Subject(s)
Antibodies, Monoclonal/administration & dosage , B7-H1 Antigen/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Adolescent , Adult , Aged , Antibodies, Monoclonal/adverse effects , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy/adverse effects , Neoplasm Staging , Radiosurgery/methods , Young AdultABSTRACT
BACKGROUND: Percutaneous image-guided thermal ablation has an increasing role in the treatment of primary and metastatic lung tumors. Achieving acceptable clinical outcomes requires better tools for pre-procedure prediction of ablation zone size and shape. METHODS: This was a prospective, non-randomized, single-arm, multicenter study conducted by Medtronic (ClinicalTrials.gov ID: NCT02323854). Subjects scheduled for resection of metastatic or primary lung nodules underwent preoperative percutaneous microwave ablation. Ablation zones as measured via CT imaging following ablation immediately and before resection surgically versus predicted ablation zones as prescribed by the investigational system software were compared. This CT scan occurred after the ablation was finished but the antenna still in position. Time (minutes) from antenna placement to removal was 23.7±13.1 (n=14); median: 21.0 (range, 6.0 to 48.0). The definition of the secondary endpoint of complete ablation was 100% non-viable tumor cells based on nicotinamide adenine dinucleotide hydrogen (NADH) staining. Safety endpoints were type, incidence, and severity of adverse events. RESULTS: Fifteen patients (mean age 58.9 years; 67% male; 33% female) were enrolled in the study, 33.3% (5/15) with previous thoracic surgery, 73% (11/15) with metastasis, and 27% (4/15) with primary lung tumors. All underwent percutaneous microwave ablation followed by surgical resection the same day. Complete ablation was detected in 54.4% (6/11), incomplete ablation in 36.4% (4/11), and delayed necrosis in 9.1% (1/11). There were no device-related adverse events. Ablation zone volume was overestimated in all patients. CONCLUSIONS: Histological complete ablation was observed in 55% of subjects. CT scanning less than an hour after ablation and tissue shrinkage may account for the smaller zone of ablation observed compared to predicted by the investigational system software.
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OBJECTIVES: Oesophagectomy following induction chemoradiation therapy (CRT) is technically challenging. To date, little data exist to describe the feasibility of a robotic approach in this setting. In this study, we assessed national trends and outcomes of robotic oesophagectomy following induction CRT compared to the traditional open approach. METHODS: The National Cancer Database was queried for patients who underwent oesophagectomy following induction CRT (2010-2014). Trends of robotic utilization were assessed by a Mantel-Haenszel test of trend. Propensity matching controlled for differences in age, gender, comorbidity, stage, histology and tumour location between the robotic and open groups. Overall survival was estimated by Kaplan-Meier analysis and compared by a log-rank test. RESULTS: Oesophagectomy following induction CRT was performed in 6958 patients. Of them, 555 patients (8%) underwent robotic surgery (5% converted to an open approach). Between 2010 and 2014, utilization of a robotic approach increased from 3% to 11% (Mantel-Haenszel, P < 0.001) and the number of hospitals performing at least 1 robotic oesophagectomy increased from 23 to 57. Compared to the traditional open approach, robotic oesophagectomy was used more frequently at academic hospitals (76% vs 60%, P < 0.001), and in patients living in metropolitan areas (85% vs 77%, P < 0.001) and those living in the Midwest (41% vs 33%, P < 0.001). In the matched groups, a robotic approach was associated with shorter median hospital stay (9 vs 10 days, P = 0.004) and dissection of more lymph nodes (median, 16 vs 12, P < 0.001). However, there were no differences in rates of positive margin resection (5% for both groups, P = 0.95), 30-day readmissions (5% vs 7%, P = 0.18), 30-day mortality (2.5% vs 4%, P = 0.79), 90-day mortality (9% vs 8.5%, P = 0.89) or 5-year overall survival (42% vs 39%, P = 0.19) between patients undergoing robotic and open surgery, respectively. CONCLUSIONS: Robotic oesophagectomy after induction CRT is feasible and associated with shorter hospitalization compared to an open approach, and does not compromise the adequacy of oncological resection, perioperative outcomes or long-term survival.
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OBJECTIVE: Surgery may be underused for stage IIIA non-small cell lung cancer. Although an argument can be made for definitive chemoradiation for N2/3 mediastinal nodal disease, the role of a nonsurgical strategy is less clear in patients with cT3N1M0 stage IIIA given a lack of randomized data. We sought to determine the outcomes of patients with cT3N1M0 by treatment type from the National Cancer Database. METHODS: The National Cancer Database (2004-2014) was queried for patients with cT3N1M0 non-small cell lung cancer, known treatment modalities, and sequence. Comparisons between groups were performed using Mann-Whitney and chi-square tests. Cox regression was performed to identify predictors of overall survival. Propensity score matching analysis was performed to compare overall survival in surgery versus definitive chemoradiation. RESULTS: We identified 1937 patients undergoing surgery (1518 up-front and 419 after neoadjuvant treatment) and 1844 patients undergoing definitive chemoradiation. Among patients undergoing surgery without prior treatment, 19% were overstaged and were found to have pN0, whereas 9.6% had pN2/3. Median overall survival was 33.1 months in the surgery group (± adjuvant/neoadjuvant) versus 18 months in definitive chemoradiation. To compare outcomes in balanced groups, we propensity matched 1081 pairs of patients. Median overall survival was 31.1 months in the surgery group compared with 19.1 months in the definitive chemoradiation group (P < .001). By multivariable analysis, surgery (hazard ratio, 0.65; confidence interval, 0.59-0.73), female sex (hazard ratio, 0.88; confidence interval, 0.79-0.98), age (hazard ratio, 1.02; confidence interval, 1.01-1.03), squamous histology (hazard ratio, 1.22; confidence interval, 1.07-1.38), and Charlson score of 2 (hazard ratio, 1.31; confidence interval, 1.11-1.54) were predictors of survival. CONCLUSIONS: In the National Cancer Database, approximately half of patients with clinical T3N1M0 were treated with definitive chemoradiation rather than surgery. This practice should be avoided in operable patients, because surgical resection is associated with better survival.