Predictors of Prolonged Hospital Stay After Segmentectomy.

OBJECTIVE: Segmentectomy is becoming the standard of care for small, peripheral non-small cell lung cancer. To improve perioperative management in this population, this study aims to identify factors influencing hospital length of stay after segmentectomy. METHODS: Patients who underwent segmentectomy for any indication between 01/2018-05/2023 were identified using a prospectively maintained institutional database. Multivariable logistic regression models were used to estimate associations between clinical features and prolonged (≥ 3days) hospital stay. A nomogram was designed to understand better, and possibly calculate the individual risk of prolonged hospital stays. RESULTS: In total, 533 cases were included; 337 (63%) were females. Median age was 66 years (IQR: 63-75). The median size of resected lesions was 1.6cm (IQR 1.3-2.1). Median hospital stay was 3 days (IQR: 2-4). Major adverse events occurred in 31 (5.8%) cases. The 30-day readmission rate was 5.8% (n=31). There was no 30-day mortality; 90-day mortality was <1%. Patients older than 75 years (OR=2.01, 95%CI: 1.15-3.57, P=0.02), those with FEV1 < 88% predicted (OR = 1.99, 95%CI: 1.38-2.89, P<0.001), or positive smoking history (OR=1.72, 95%CI: 1.15-2.60, P=0.01) were more likely to have prolonged hospital stays after segmentectomy. A nomogram accounting for age, sex, FEV1, body mass index, smoking history, and comorbidities was created to predict the probability of prolonged hospital stay with an AUC of 0.66. CONCLUSIONS: Older patients, those with reduced pulmonary function, current, and past smokers have elevated risk for prolonged hospital stays after segmentectomy. Validation of our nomogram could improve perioperative risk stratification in segmentectomy patients.

Complete anatomic segmentectomy shows improved oncologic outcomes compared to incomplete anatomic segmentectomy.

OBJECTIVES: To compare oncologic outcomes after segmentectomy with division of segmental bronchus, artery and vein (complete anatomic segmentectomy) versus segmentectomy with division of <3 segmental structures (incomplete anatomic segmentectomy). METHODS: We conducted a single-centre, retrospective analysis of patients undergoing segmentectomy from March 2005 to May 2020. Operative reports were audited to classify procedures as complete or incomplete anatomic segmentectomy. Patients who underwent neoadjuvant therapy or pulmonary resection beyond indicated segments were excluded. Survival was estimated with Kaplan-Meier models and compared using log-rank tests. Cox proportional hazards models were used to estimate hazard ratios (HRs) for death. Cumulative incidence functions for loco-regional recurrence were compared with Gray's test, with death considered a competing event. Cox and Fine-Gray models were used to estimate cause-specific and subdistribution HRs, respectively, for loco-regional recurrence. RESULTS: Of 390 cases, 266 (68.2%) were complete and 124 were incomplete anatomic segmentectomy. Demographics, pulmonary function, tumour size, stage and perioperative outcomes did not significantly differ between groups. Surgical margins were negative in all but 1 case. Complete anatomic segmentectomy was associated with improved lymph node dissection (5 vs 2 median nodes sampled; P < 0.001). Multivariable analysis revealed reduced incidence of loco-regional recurrence (cause-specific HR = 0.42; 95% confidence interval 0.22-0.80; subdistribution HR = 0.43; 95% confidence interval 0.23-0.81), and non-significant improvement in overall survival (HR = 0.66; 95% confidence interval: 0.43-1.00) after complete versus incomplete anatomic segmentectomy. CONCLUSIONS: This single-centre experience suggests complete anatomic segmentectomy provides superior loco-regional control and may improve survival relative to incomplete anatomic segmentectomy. We recommend surgeons perform complete anatomic segmentectomy and lymph node dissection whenever possible.

Liposomal bupivacaine intercostal block placed under direct vision reduces morphine use in thoracic surgery.

Background: Thoracic epidural analgesia (TEA) and liposomal bupivacaine (LB) are two methods used for postoperative pain control after thoracic surgery. Some studies have compared LB to standard bupivacaine. However, data comparing the outcomes of LB to TEA after minimally invasive lung resection is limited. Therefore, the objective of our study was to compare postoperative pain, opioid usage, and outcomes between patients who received TEA vs. LB. Methods: We conducted a retrospective chart review of patients who underwent minimally invasive lung resections over an 8-month period. Intraoperatively, patients received either LB under direct vision or a TEA. Pain scores were obtained in the post-anesthesia care unit (PACU) and at 12, 24, and 48 hours postoperatively. Morphine milligram equivalents (MMEs) were calculated at 24 and 48 hours postoperatively. Postoperative outcomes were then compared between groups. Results: In total, 391 patients underwent minimally invasive lung resection: 236 (60%) wedge resections, 51 (13%) segmentectomies, and 104 (27%) lobectomies. Of these, 326 (83%) received LB intraoperatively. Fewer patients in the LB group experienced postoperative complications (18% vs. 34%, P=0.004). LB patients also had lower median pain scores at 24 (P=0.03) and 48 hours (P=0.001) postoperatively. There was no difference in MMEs at 24 hours (P=0.49). However, at 48 hours, patients who received LB required less narcotics (P=0.02). Median hospital length of stay (LOS) was significantly shorter in patients who received LB (2 vs. 4 days, P<0.001). On multivariable analysis, increasing age, postoperative complications, and use of TEA were independently associated with a longer hospital LOS. Conclusions: Compared to TEA, LB intercostal block placed under direct vision reduced morphine use 48 hours after thoracic surgery. It was also associated with fewer postoperative complications and shorter median hospital LOS. LB is a good alternative to TEA for pain management after minimally invasive lung resection.

Clinical Outcomes of Resected Pure Ground-Glass, Heterogeneous Ground-Glass, and Part-Solid Pulmonary Nodules.

Background: Increased (but not definitively solid) density within pure ground-glass nodules (pGGNs) may indicate invasive adenocarcinoma and need for resection rather than surveillance. Objective: To compare clinical outcomes between resected pGGNs, heterogeneous ground-glass nodules (GGNs), and part-solid nodules (PSNs). Methods: This retrospective study included 469 patients (median age, 68 years [IQR, 11 years]; 335 female, 134 male) who underwent resection between January 2012 and December 2020 of lung adenocarcinoma appearing as a subsolid nodule on CT. Two radiologists using lung windows independently classified each nodule as a pGGN, heterogeneous GGN, or PSN, resolving discrepancies through discussion. Heterogeneous GGN was defined as a GGN with internal increased density not quite as dense as pulmonary vessels; PSN had an internal solid component as dense as pulmonary vessels. Outcomes included pathologic diagnosis of invasive adenocarcinoma, 5-year recurrence rates (locoregional or distant), and recurrence-free survival (RFS) and overall survival (OS) through 7 years analyzed by Kaplan-Meier and Cox proportional hazards regression analyses, censoring patients with incomplete follow-up. Results: Interobserver agreement for nodule type, expressed as kappa, was 0.69. Using consensus assessments, 59 nodules were pGGNs, 109 were heterogeneous GGNs, and 301 were PSNs. Frequency of invasive adenocarcinoma was 39.0% in pGGNs, 67.9% in heterogeneous GGNs, and 75.7% in PSNs (pGGN vs heterogeneous GGN: P<.001; pGGN vs PSN: P<.001; heterogeneous GGN vs PSN: P=.28). The 5-year recurrence rate was 0.0% in pGGNs, 6.3% in heterogeneous GGNs, and 10.8% in PSNs (pGGN vs heterogeneous GGN: P=.06; pGGN vs PSN: P=.02; heterogeneous GGN vs PSN: P=.18). At 7 years, RFS was 97.7% in pGGNs, 82.0% in heterogeneous GGNs, and 79.4% in PSNs (pGGN vs heterogeneous GGN: P=.02; pGGN vs PSN: P=.006; heterogeneous GGN v PSN: P=.40); OS was 98.0% in pGGNs, 84.6% in heterogeneous GGNs, and 82.9% in PSNs (pGGN vs heterogeneous GGN: P=.04; pGGN vs PSN: P=.01; heterogeneous GGN vs PSN: P=.50). Conclusion: Resected pGGNs had excellent clinical outcomes. Heterogeneous GGNs had relatively worse outcomes, more closely resembling outcomes for PSNs. Clinical Impact: The findings support surveillance for truly homogeneous pGGNs, versus resection for GGNs exhibiting internal increased density, even if not a true solid component.

Empiric flap coverage for the pneumonectomy stump: How protective is it? A single-institution cohort study.

OBJECTIVE: To evaluate the impact of empiric tissue flaps on bronchopleural fistula (BPF) rates after pneumonectomy. METHODS: Patients who underwent pneumonectomy between January 2001 and December 2019 were included. Primary end point was development of BPF. Secondary end points were impact of flap type on BPF rates, time to BPF development, and perioperative mortality. RESULTS: During the study period, 383 pneumonectomies were performed; 93 were extrapleural pneumonectomy. Most pneumonectomy cases had empiric flap coverage, with greater use in right-sided operations (right: 97%, 154/159; left: 80%, 179/224, P < .001). Empiric flaps harvested included intercostal, latissimus dorsi, serratus anterior, omentum, pectoralis major, pericardial fat/thymus, pericardium, and pleura. BPF occurred in 10.4% of the entire cohort but decreased to 6.6% when extrapleural pneumonectomy cases were excluded; 90% (36/40) of BPFs occurred on the right side (P < .001). Median time to develop BPF was 63 days, and 90-day mortality was greater in patients with BPF (12.5% BPF vs 7.4% non-BPF, P < .0001). Intercostal muscle had the lowest rate of BPF (4.5%), even in right-sided operations (8.7%). In contrast, larger muscle flaps such as latissimus dorsi (21%) and serratus anterior (33%) had greater rates of BPF, but the sample size was small in these cohorts. CONCLUSIONS: Empiric bronchial stump coverage should be performed in all right pneumonectomy cases due to greater risk of BPF. In our series, intercostal muscle flaps had low BPF rates, even in right-sided operations. Coverage of the left pneumonectomy stump is unnecessary due to low incidence of BPF in these cases.

Predicting outcomes in esophageal adenocarcinoma following neoadjuvant chemoradiation: Interactions between tumor response and survival.

OBJECTIVES: The prognostic value of tumor regression scores (TRS) in patients with esophageal adenocarcinoma (EAC) who underwent neoadjuvant chemoradiation remains unclear. We sought to investigate the prognostic value of pathologic and metabolic treatment response among EAC patients undergoing neoadjuvant chemoradiation. METHODS: Patients who underwent esophagectomy for EAC after neoadjuvant CROSS protocol between 2016 and 2020 were evaluated. TRS was grouped according to the modified Ryan score; metabolic response, according to the PERCIST criteria. Variables from endoscopic ultrasound, endoscopic biopsies, and positron emission tomography (primary and regional lymph node standardized uptake values [SUVs]) were collected. RESULTS: The study population comprised 277 patients. A TRS of 0 (complete response) was identified in 66 patients (23.8%). Seventy-eight patients (28.1%) had TRS 1 (partial response), 97 (35%) had TRS 2 (poor response), and 36 (13%) had TRS 3 (no response). On survival analysis for overall survival (OS), patients with TRS 0 had longer survival compared to those with TRS 1, 2, or 3 (P = .010, P < .001, and P = .005, respectively). On multivariable logistic regression, the presence of signet ring cell features on endoscopic biopsy (odds ratio [OR], 7.54; P = .012) and greater SUV uptake at regional lymph nodes (OR, 1.42; P = .007) were significantly associated with residual tumor at pathology (TRS 1, 2, or 3). On multivariate Cox regression for predictors of OS, higher SUVmax at the most metabolically active nodal station (hazard ratio [HR], 1.08; P = .005) was independently associated with decreased OS, whereas pathologic complete response (HR, 0.61; P = .021) was independently associated with higher OS. CONCLUSIONS: Patients with pathologic complete response had prolonged OS, whereas no difference in survival was detected among other TRS categories. At initial staging, the presence of signet ring cells and greater SUV uptake at regional lymph nodes predicted residual disease at pathology and shorter OS, suggesting the need for new treatment strategies for these patients.

Analysis of recurrence in lung adenocarcinoma with spread through air spaces.

OBJECTIVES: Spread through air spaces is defined as tumor cells in air spaces away from the edge of tumor in lung carcinoma. It is associated with higher locoregional recurrence and lower survival in lung adenocarcinoma. The features of spread through air spaces portending worse outcomes are still under investigation. We reviewed our lung cancer experience to define potential factors related to spread through air spaces that influence recurrence and survival. METHODS: Between January 2010 and December 2017, we identified 968 patients who underwent resection for T1-3N0M0 lung adenocarcinoma. Of these, histologic examination was possible in 787 patients. We examined the presence of spread through air spaces, spread through air spaces characteristics (micropapillary, solid nest, or single cell), average density (number per slide), and farthest distance from tumor at which spread through air spaces was detected, or maximal spread distance. Overall survival and recurrence-free survival were estimated using Kaplan-Meier curves, and differences between spread through air spaces positive versus spread through air spaces negative groups were assessed using the log-rank test. RESULTS: Spread through air spaces was present in 389 of 787 of the reviewed cases (49.4%). Overall survival and recurrence-free survival were significantly lower in the spread through air spaces positive group over 10 years (P < .0001). The incidences of locoregional and distant recurrence were nearly doubled over 10 years in the spread through air spaces positive group compared with the spread through air spaces negative group (P = .002 and <.0001, respectively). In a multivariable Cox regression model adjusted for spread through air spaces characteristics, distance, and tumor size, lobar resection did not confer survival advantage in patients with spread through air spaces (hazard ratio of sublobar resection with respect to lobar resection, 1.44; 95% confidence interval, 0.98-2.11; P = .067). In the spread through air spaces positive group, spread through air spaces density was 2.7 ± 1.4 clusters per slide and the maximal spread distance was 2.2 ± 1.7 mm from the tumor edge. There was no observed correlation between spread through air spaces density or maximal spread distance and overall survival or recurrence. CONCLUSIONS: We show increased distant recurrence in spread through air spaces positive lung adenocarcinoma. Quantifiable measures of spread through air spaces do not appear to correlate with recurrence or survival metrics.

Plain language summary of the CheckMate 816 study results: nivolumab plus chemotherapy given before surgery for non-small-cell lung cancer.

WHAT IS THIS SUMMARY ABOUT?: In this article, we summarize results from the ongoing phase 3 CheckMate 816 clinical study that were published in The New England Journal of Medicine in 2022. The goal of CheckMate 816 was to find out if nivolumab, an immunotherapy that activates a person's immune system (the body's natural defense system) to fight cancer, plus chemotherapy works better than chemotherapy alone when given before surgery in people with non-small-cell lung cancer (NSCLC) that can be removed surgically (resectable NSCLC). WHAT HAPPENED IN THE STUDY?: Adults who had not previously taken medications to treat NSCLC and whose cancer could be removed with surgery were included in CheckMate 816. During this study, a computer randomly assigned the treatment each person would receive before surgery for NSCLC. In total, 179 people were randomly assigned to receive nivolumab plus chemotherapy, and 179 people were randomly assigned to receive chemotherapy alone. The researchers assessed whether people who received nivolumab plus chemotherapy lived longer without the cancer geting worse or coming back and whether there were any cancer cells left in the tumor and lymph nodes removed by surgery. The researchers also assessed how adding nivolumab to chemotherapy affected the timing and outcomes of surgery and whether the combination of these drugs was safe. WHAT WERE THE RESULTS?: Researchers found that people who took nivolumab plus chemotherapy lived longer without the cancer getting worse or coming back compared with those who took chemotherapy alone. More people in the nivolumab plus chemotherapy group had no cancer cells left in the tumor and lymph nodes removed by surgery. Most people went on to have surgery in both treatment groups; the people who took nivolumab plus chemotherapy instead of chemotherapy alone had less extensive surgeries and were more likely to have good outcomes after less extensive surgeries. Adding nivolumab to chemotherapy did not lead to an increase in the rate of side effects compared with chemotherapy alone, and side effects were generally mild and manageable. WHAT DO THE RESULTS OF THE STUDY MEAN?: Results from CheckMate 816 support the benefit of using nivolumab plus chemotherapy before surgery for people with resectable NSCLC. Clinical Trial Registration: NCT02998528 (ClinicalTrials.gov).

Sublobar resections for lung cancer: Finally, some answers and some more questions?

The Lung Cancer Study Group Trial, published in 1995, set the tone for lobectomy as the standard of care for early-stage nonsmall cell lung cancer. Twenty-seven years and two randomized trials later, does the thoracic oncology community have clarity regarding the choice type of resection, or more questions?

When a segmentectomy is not a segmentectomy: Quality assurance audit and evaluation of required elements for an anatomic segmentectomy.

OBJECTIVE: The advent of lung cancer screening and detection of smaller nodules amplifies the need to clarify the oncological quality of sublobar resections. Furthermore, studies comparing sublobar resections to lobectomies offer conflicting conclusions. We hypothesize that this is driven, in part, by inconsistency in reporting; that is, variable interpretation of what constitutes an operative segment. Without an established standard, 2 very different operations may be reported as segmental resections, leaving the data on sublobar approaches subject to interpretative variability. METHODS: A retrospective audit was performed on all segmental resections from May 2016 to December 2019 at Brigham and Women's Hospital. Pathology and operative reports were reviewed, with particular attention to the dissection of the component artery, vein, and bronchus. Resections with dissection and division of at least 1 major vascular structure (the segmental artery or vein), as well as the segmental bronchus, met operative criteria for anatomic segmentectomy. Surgical quality metrics were compared between the 2 groups. RESULTS: There were 271 segmental resections: 219 (80.8%) were anatomic segmentectomies and 52 (19.2%) were nonanatomic segmentectomies. For the entire cohort, nonanatomic segmentectomies had smaller margins (1.0 vs 1.5 cm; P = .02), fewer lymph nodes (2.0 vs 6.0; P < .001), and fewer mediastinal lymph node stations sampled (1.0 vs 2.0; P < .001). Similarly, there were smaller margins (1.5 vs 1.8 cm; P = .03), fewer lymph nodes (2.0 vs 6.0; P < .001), and fewer mediastinal lymph node stations sampled (1.0 vs 2.0; P < .001) in nonanatomic segmentectomies for non-small cell lung cancer. CONCLUSIONS: Nearly 20% of reported segmentectomies may not meet criteria for true segmental resection. Therefore, prior studies may need further scrutiny to clarify outcomes and results. Establishing a professional standard may help mitigate ambiguity in published data on this subject.

Hyperthermic intraoperative chemotherapy (HIOC) for Stage IVa thymic malignancy may improve 5-year disease-free survival.

BACKGROUND AND OBJECTIVES: Stage IVa thymic malignancy has limited treatments. This study evaluated whether hyperthermic intraoperative chemotherapy (HIOC) after radical resection of Stage IVa thymic malignancy improves survival. METHODS: All patients who underwent resection, with or without HIOC, for Stage IVa thymic malignancy at a single center from 1990 to 2021 were reviewed. RESULTS: Thirty-four patients were identified; 22 surgery-only versus 12 surgery and HIOC (60 min cisplatin regimen 175 mg/m2 ). Demographics and comorbidities were similar between groups. Three patients in each group were carcinomas; remainder were thymomas. Thirty-two patients underwent attempted macroscopic complete resection; 22 operations succeeded, 68.8%. Significant complications were similar between groups, 18.2% surgery-only versus 25.0% HIOC, p = 0.68. Median time to recurrence trended longer for HIOC patients (42.9 vs. 32.9 months in surgery-only, p = 0.77). Overall survival, 5-year, was similar (75.8% HIOC vs. 76.2% surgery-only, p = 0.91). On stratified analysis, thymoma patients with macroscopic complete resection and HIOC experienced similar 5-year Overall (80.0% vs. 100.0% surgery-only, p = 0.157) but longer trending 5-year disease-free (85.7% vs. 40.0%, p = 0.18) and 5-year locoregional recurrence-free survival (85.7% vs. 68.6%, p = 0.75). CONCLUSIONS: This retrospective cohort study treating Stage IVa thymic malignancy with radical pleurectomy, with or without HIOC, found addition of HIOC-signaled delayed recurrence and improved disease-free survival.

Perioperative Esophagectomy Outcomes in Older Esophageal Cancer Patients in Two Different Time Eras.

To investigate perioperative outcomes of esophagectomies by age groups. Retrospective analysis of esophageal cancer patients undergoing esophagectomy from 2005 to 2020 at a single academic institution. Baseline characteristics and outcomes were analyzed by 3 age groups: <70, 70-79, and ≥80 years-old. Sub-analysis was done for 2 time periods: 2005-2012 and 2013-2020. Of 1135 patients, 789 patients were <70, 294 were 70-79, and 52 were ≥80 years-old. Tumor characteristics, and operative technique were similar, except positive longitudinal margins rates (all <3%) (P = 0.008). Older adults experienced increased complications (53.6% vs 69.7% vs 65.4% respectively; P < 0.001) attributable to grade II complications (41.4% vs 62.2% vs 63.5% respectively; P < 0.001). Hospital length of stay (LOS) and rehabilitation requirements were higher in older adults (both P < 0.05). 30-day readmissions, reoperation, and 30-day mortality rates (all <2%) showed no association with age group. Overall complications, LOS, discharge disposition and re-operative rates improved from 2005 to 2012 to 2013-2020 for all (P < 0.05). Increasing age was an independent risk factor for cardiovascular complications (OR 1.7, 95% CI 1.23-2.46 for ages 70-79 and OR 2.7, 95% CI 1.37-5.10 for ages ≥80 ), inpatient rehabilitation (OR 3.3, 95% CI 2.26-5.05 for ages 70-79 and OR 12.1 95% CI 5.83-25.04 for ages ≥80), and prolonged LOS (OR 1.64 95% CI 1.16-2.31 for ages 70-79 and OR 3.6 95% CI 1.71-7.67 for ≥80. After adjusting for time period, older age remained associated with complications (P < 0.05). Highly selected older adults at a large volume esophagectomy center can undergoesophagectomy with increased minor complication and rehabilitation needs.

Report on lung cancer surgery during COVID-19 pandemic at a high volume US institution.

Background: The impact of COVID-19 has been felt in every field of medicine. We sought to understand how lung cancer surgery was affected at a high volume institution. We hypothesized that patients would wait longer for surgery, have more advanced tumors, and experience more complications during the COVID-19 crisis. Methods: A retrospective review was conducted, comparing pathologically confirmed non-small cell lung cancer (NSCLC) surgical cases performed in 2019 to cases performed from March to May 2020, during the height of the COVID-19 crisis. Clinical and pathologic stage, tumor size, time to surgery, follow up time, and complications were evaluated. Results: A total of 375 cases were performed in 2019 vs. 58 cases in March to May 2020. Overall, there were no differences in the distribution of clinical stages or in the distribution of median wait times to surgery between groups (COVID-19 16.5 days vs. pre-COVID-19 17 days, P=0.54), nor were there differences when subdivided into Stage I-II and Stage III-IV. Case volume was lowest in April 2020 with 6 cases vs. 37 in April 2019, P<0.01. Tumor size was clinically larger in the COVID-19 group (median 2.1 vs. 1.9 cm, P=0.05) but not at final pathology. No differences in complications were observed between groups (COVID-19 31.0% vs. pre-COVID-19 30.9%, P=1.00). No patients from the COVID-19 group tested positive for the disease during their hospital stay or by the median 15 days to first follow-up. Conclusions: Surgical wait time, pathologic tumor size, and complications were not different among patients undergoing surgery before vs. during the pandemic. Importantly, no patients became infected as a result of their hospital stay. The significant decrease in surgical cases is concerning for untreated cancers that may progress without proper treatment.

Salvage surgery for local recurrence after sublobar surgery in Stages I and II non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: To examine if patients undergoing salvage surgery for local recurrence following sublobar resection (SLR) have similar perioperative complications and overall survival (OS) compared to lobectomy patients for early stage non-small cell lung cancer (NSCLC). METHODS: Patients undergoing lobectomy and SLR (segmentectomy or wedge resection) for Stages I and II NSCLC from 2010 to 2016 were reviewed. Lobectomy patients and those who underwent salvage surgery for local recurrence after SLR were compared. Salvage surgeries were curative-intent resections for recurrence. RESULTS: Cases included 634 lobectomies and 986 SLR. Fifty-nine SLR patients (6.0%) recurred at a local site compared to 11 lobectomy patients (1.7%; p < 0.001). Twenty-three locally recurrent SLR patients (39.0%) went on to salvage surgery. Peri-operative complications after salvage surgeries were similar to lobectomies (34.8% 8/23 vs. 34.7% 220/634, p = 1.00). OS at 5 years for salvage surgery patients was similar to lobectomy patients (79.6% 13/23 vs. 70.6% 227/634, p = 0.23). OS for patients who underwent salvage surgery was significantly better than those who did not have salvage surgery for recurrence (79.6% vs. 53.0%, p = 0.02). CONCLUSIONS: Patients who undergo salvage surgery for local recurrence after SLR had similar perioperative complications and OS compared to lobectomy patients but less than half underwent salvage surgery.

Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer.

BACKGROUND: Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non-small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings. METHODS: In this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients. RESULTS: The median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P = 0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-plus-chemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group. CONCLUSIONS: In patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.).

Long-term Outcomes Following Esophagectomy in Older and Younger Adults with Esophageal Cancer.

BACKGROUND: Patterns of overall and disease-free survival after esophagectomy for esophageal cancer in older adults have not been carefully studied. METHODS: Retrospective analysis of all patients with esophageal cancer undergoing esophagectomy from 2005 to 2020 at our institution was performed. Differences in outcomes were stratified by age groups, < 75 and ≥ 75 years old, and two time periods, 2005-2012 and 2013-2020. RESULTS: A total of 1135 patients were included: 979 (86.3%) patients were < 75 (86.3%), and 156 (13.7%) were ≥ 75 years old. Younger patients had fewer comorbidities, better nutritional status, and were more likely to receive neoadjuvant and adjuvant therapy (all p < 0.05). However, tumor stage and operative approach were similar, except for increased performance of the McKeown technique in younger patients (p = 0.02). Perioperatively, younger patients experienced fewer overall and grade II complications (both p < 0.05). They had better overall survival (log-rank p-value < 0.001) and median survival, 62.2 vs. 21.5 months (p < 0.05). When stratified by pathologic stage, survival was similar for yp0 and pathologic stage II disease (both log-rank p-value > 0.05). Multivariable Cox models showed older age (≥ 75 years old) had increased hazard for reduced overall survival (HR 2.04 95% CI 1.5-2.8; p < 0.001) but not disease-free survival (HR 1.1 95% CI 0.78-1.6; p = 0.54). Over time, baseline characteristics remained largely similar, while stage became more advanced with a rise in neoadjuvant use and increased performance of minimally invasive esophagectomy (all p < 0.05). While overall complication rates improved (p < 0.05), overall and recurrence-free survival did not. Overall survival was better in younger patients during both time periods (both log-rank p < 0.05). CONCLUSIONS: Despite similar disease-free survival rates, long-term survival was decreased in older adults as compared to younger patients. This may be related to unmeasured factors including frailty, long-term complications after surgery, and competing causes of death. However, our results suggest that survival is similar in those with complete pathologic responses.