The Emerging Role of Immunotherapy in Resectable Non-Small Cell Lung Cancer.

BACKGROUND: Despite surgical resection, long-term survival of patients with resectable non-small cell lung cancer (NSCLC) remains poor. Adjuvant chemotherapy, the standard of care for locally advanced NSCLC, provides a marginal 5.4% benefit in survival. Immune checkpoint inhibitors (ICIs) have shown a significant survival benefit in some patients with advanced NSCLC and are being evaluated for perioperative use in resectable NSCLC. METHODS: We conducted a literature search using the PubMed online database to identify clinical trials of immunotherapy in resectable NSCLC and studies analyzing biomarkers and immune priming strategies. RESULTS: Building on previous phase I and II trials, randomized phase III trials have shown efficacy of neoadjuvant nivolumab, perioperative pembrolizumab, adjuvant atezolizumab, and adjuvant pembrolizumab in the treatment of NSCLC with improvement of event-free/disease-free survival of 24% to 42%, leading to United States Food and Drug Administration approval of these drugs in the treatment of resectable NSCLC. Three additional phase III trials have also recently reported the use of immunotherapy both before and after surgery, with pathologic complete response rates of 17% to 25%, significantly better than chemotherapy alone. Perioperative ICI therapy has comparable perioperative morbidity to chemotherapy alone and does not impair surgical outcomes. CONCLUSIONS: Perioperative immunotherapy, in combination with chemotherapy, is safe and improves outcomes in patients with resectable NSCLC. Questions regarding patient selection, the need for adjuvant ICI therapy after neoadjuvant chemoimmunotherapy, and the duration of perioperative immunotherapy remain to be answered by future trials.

The Society of Thoracic Surgeons/American Society for Radiation Oncology Updated Clinical Practice Guidelines on Multimodality Therapy for Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction.

Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.

The Society of Thoracic Surgeons/American Society for Radiation Oncology Updated Clinical Practice Guidelines on Multimodality Therapy for Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction.

Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.

Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer.

BACKGROUND: Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative regimens may combine benefits of both to improve long-term outcomes. METHODS: We randomly assigned patients with resectable NSCLC (stage II to IIIB [N2 node stage] according to the eighth edition of the AJCC Cancer Staging Manual) to receive platinum-based chemotherapy plus durvalumab or placebo administered intravenously every 3 weeks for 4 cycles before surgery, followed by adjuvant durvalumab or placebo intravenously every 4 weeks for 12 cycles. Randomization was stratified according to disease stage (II or III) and programmed death ligand 1 (PD-L1) expression (≥1% or <1%). Primary end points were event-free survival (defined as the time to the earliest occurrence of progressive disease that precluded surgery or prevented completion of surgery, disease recurrence [assessed in a blinded fashion by independent central review], or death from any cause) and pathological complete response (evaluated centrally). RESULTS: A total of 802 patients were randomly assigned to receive durvalumab (400 patients) or placebo (402 patients). The duration of event-free survival was significantly longer with durvalumab than with placebo; the stratified hazard ratio for disease progression, recurrence, or death was 0.68 (95% confidence interval [CI], 0.53 to 0.88; P = 0.004) at the first interim analysis. At the 12-month landmark analysis, event-free survival was observed in 73.4% of the patients who received durvalumab (95% CI, 67.9 to 78.1), as compared with 64.5% of the patients who received placebo (95% CI, 58.8 to 69.6). The incidence of pathological complete response was significantly greater with durvalumab than with placebo (17.2% vs. 4.3% at the final analysis; difference, 13.0 percentage points; 95% CI, 8.7 to 17.6; P<0.001 at interim analysis of data from 402 patients). Event-free survival and pathological complete response benefit were observed regardless of stage and PD-L1 expression. Adverse events of maximum grade 3 or 4 occurred in 42.4% of patients with durvalumab and in 43.2% with placebo. Data from 62 patients with documented EGFR or ALK alterations were excluded from the efficacy analyses in the modified intention-to-treat population. CONCLUSIONS: In patients with resectable NSCLC, perioperative durvalumab plus neoadjuvant chemotherapy was associated with significantly greater event-free survival and pathological complete response than neoadjuvant chemotherapy alone, with a safety profile that was consistent with the individual agents. (Funded by AstraZeneca; AEGEAN ClinicalTrials.gov number, NCT03800134.).

Meta-Analysis of Rates and Risk Factors for Local Recurrence in Surgically Resected Patients With NSCLC and Differences Between Asian and Non-Asian Populations.

Introduction: Postoperative radiotherapy (PORT) reduces local failure in patients with NSCLC, without a clear overall survival benefit. It is unknown whether the subsets of patients benefit. Two recent large randomized controlled trials, PORT-C (People's Republic of China) and Lung ART (Europe), reported widely different locoregional recurrence (LR) rates in the control arms, at 18.3% and 28.1% (46% of which were mediastinal recurrences), respectively. We performed a meta-analysis of patients with pathologic (p) N0 to N2 disease to evaluate the risk factors for LR and to explore possible differences in recurrence risk between Asian population (AP) and non-Asian population (NAP). Methods: We identified all original studies of curative NSCLC surgical resection which reported risk of LR between January 1, 2000, and January 10, 2021, excluding studies with less than 10 LR, patients with metastatic disease, or any neoadjuvant therapy. A total of 87 studies were identified with pN0 to N2 disease; of these, 56 were of high quality (HQ) on the basis of the Newcastle-Ottawa Scale. For each risk factor, we derived pooled relative risk (RR) and 5-year rate estimates using random-effects models. Results: Overall, the three significant highest pooled RRs (95% confidence intervals) for LR were pN2 versus pN0 (3.01, 1.39-6.55), lymphovascular invasion (1.92, 1.58-2.33), and advanced pT3-4 stage versus pT1 (1.86, 1.53-2.25). For HQ studies, the highest RRs for LR were lymphovascular invasion (1.94, 1.57-2.40), sublobar versus lobar resection (1.86, 1.46-2.36), and pN1 versus pN0 (1.84, 1.37-2.47), but pN2 versus pN0 was no longer significant (3.0, 0.57-15.61), on the basis of only two eligible studies. The RRs for LR were consistent for most factors in AP and NAP, although the RR for male versus female sex was higher in AP (1.44, 1.21-1.72) than in NAP (1.09, 0.99-1.19). Where reported, the pooled rate of LR at 5 years was lower in AP (12.0%) than in NAP (22.7%), despite similar overall 5-year recurrence rates (both LR and distal) in both populations: 38.0% in AP and 37.3% in NAP. Nevertheless, a lower 5-year mortality rate was noted in AP (24.3%) than in NAP (45.9%). Conclusions: There is little high-quality evidence to support the hypothesis that pN2 disease is a risk factor for LR, but LR seems to be lower in Asians. Prospective evaluation of LR factors and rates may be necessary before further prospective evaluation of PORT, because it may not depend on nodal status alone. Recurrence rates may differ in Asians. The impact of mutational status and modern treatment including targeted therapies and immune checkpoint inhibitors is inadequately studied.

Immune Phenotype and Postoperative Complications After Elective Surgery.

OBJECTIVES: To characterize and quantify accumulating immunologic alterations, pre and postoperatively in patients undergoing elective surgical procedures. BACKGROUND: Elective surgery is an anticipatable, controlled human injury. Although the human response to injury is generally stereotyped, individual variability exists. This makes surgical outcomes less predictable, even after standardized procedures, and may provoke complications in patients unable to compensate for their injury. One potential source of variation is found in immune cell maturation, with phenotypic changes dependent on an individual's unique, lifelong response to environmental antigens. METHODS: We enrolled 248 patients in a prospective trial facilitating comprehensive biospecimen and clinical data collection in patients scheduled to undergo elective surgery. Peripheral blood was collected preoperatively, and immediately on return to the postanesthesia care unit. Postoperative complications that occurred within 30 days after surgery were captured. RESULTS: As this was an elective surgical cohort, outcomes were generally favorable. With a median follow-up of 6 months, the overall survival at 30 days was 100%. However, 20.5% of the cohort experienced a postoperative complication (infection, readmission, or system dysfunction). We identified substantial heterogeneity of immune senescence and terminal differentiation phenotypes in surgical patients. More importantly, phenotypes indicating increased T-cell maturation and senescence were associated with postoperative complications and were evident preoperatively. CONCLUSIONS: The baseline immune repertoire may define an immune signature of resilience to surgical injury and help predict risk for surgical complications.

The Impact of Adjuvant Hemithoracic Radiation on Outcomes in Patients With Stage I-III Malignant Pleural Mesothelioma: A Dual Registry Analysis.

BACKGROUND: The outcomes associated with receipt of adjuvant radiation in patients after surgery for MPM are poorly understood. OBJECTIVE: The objective of this study was to use 2 registries to compare the outcomes of patients receiving adjuvant radiation or no radiation after definitive surgery for pathologic stage I-III MPM. METHODS: Patients with resected pathologic stage I-III MPM were identified from the Duke University registry (1996-2016) and National Cancer Database (NCDB) (2004-2015). The primary outcome was overall survival. Propensity score-matched and landmark subgroup analyses were performed. RESULTS: A total of 212 institutional and 1615 NCDB patients met criteria. In both cohorts, patients who underwent radiation were more likely to have margin-negative resection and more advanced pathologic stage. At a landmark time of 4.4 and 4.7 months from surgery, Duke [hazard ratio (HR) 1.14; 95% confidence interval (CI) 0.62-2.11] and NCDB patients (HR 0.97; 95% CI 0.81-1.17) who received adjuvant radiation did not experience improved survival compared to those who did not receive radiation in multivariable analysis. Duke patients who received radiation had similar incidence of recurrence and time to both overall recurrence and ipsilateral recurrence (HR 0.87; 95% CI 0.43-1.77) compared to those who did not. Duke patients experienced 100 grade 1/2, 21 grade 3/4, and one grade 5 toxicity events during radiation. CONCLUSIONS: In this dual registry analysis of patients with resected stage I-III MPM, the receipt of adjuvant hemithoracic radiation was not associated with improved survival compared to no radiation.

The Effect of Center Esophagectomy Volume on Outcomes in Clinical Stage I to III Esophageal Cancer.

OBJECTIVE: To determine the threshold annualized esophagectomy volume that is associated with improved survival, oncologic resection, and postoperative outcomes. BACKGROUND: Esophagectomy at high-volume centers is associated with improved outcomes; however, the definition of high-volume remains debated. METHODS: The 2004 to 2016 National Cancer Database was queried for patients with clinical stage I to III esophageal cancer undergoing esophagectomy. Center esophagectomy volume was modeled as a continuous variable using restricted cubic splines. Maximally selected ranks were used to identify an inflection point of center volume and survival. Survival was compared using multivariable Cox proportional hazards methods. Multivariable logistic regression was used to examine secondary outcomes. RESULTS: Overall, 13,493 patients met study criteria. Median center esophagectomy volume was 8.2 (interquartile range: 3.2-17.2) cases per year. On restricted cubic splines, inflection points were identified at 9 and 30 cases per year. A multivariable Cox model was constructed modeling annualized center surgical volume as a continuous variable using 3 linear splines and inflection points at 9 and 30 cases per year. On multivariable analysis, increasing center volume up to 9 cases per year was associated with a substantial survival benefit (hazard ratio: 0.97, 95% confidence interval, 0.95-0.98, P ≤0.001). On multivariable logistic regression, factors associated with undergoing surgery at a high-volume center (>9 cases per year) included private insurance, care at an academic center, completion of high school education, and greater travel distance. CONCLUSIONS: This National Cancer Database study utilizing multivariable analysis and restricted cubic splines suggests the threshold definition of a high-volume esophagectomy center as one that performs at least 10 operations a year.

A Multidimensional Bioinformatic Platform for the Study of Human Response to Surgery.

OBJECTIVE: To design and establish a prospective biospecimen repository that integrates multi-omics assays with clinical data to study mechanisms of controlled injury and healing. BACKGROUND: Elective surgery is an opportunity to understand both the systemic and focal responses accompanying controlled and well-characterized injury to the human body. The overarching goal of this ongoing project is to define stereotypical responses to surgical injury, with the translational purpose of identifying targetable pathways involved in healing and resilience, and variations indicative of aberrant peri-operative outcomes. METHODS: Clinical data from the electronic medical record combined with large-scale biological data sets derived from blood, urine, fecal matter, and tissue samples are collected prospectively through the peri-operative period on patients undergoing 14 surgeries chosen to represent a range of injury locations and intensities. Specimens are subjected to genomic, transcriptomic, proteomic, and metabolomic assays to describe their genetic, metabolic, immunologic, and microbiome profiles, providing a multidimensional landscape of the human response to injury. RESULTS: The highly multiplexed data generated includes changes in over 28,000 mRNA transcripts, 100 plasma metabolites, 200 urine metabolites, and 400 proteins over the longitudinal course of surgery and recovery. In our initial pilot dataset, we demonstrate the feasibility of collecting high quality multi-omic data at pre- and postoperative time points and are already seeing evidence of physiologic perturbation between timepoints. CONCLUSIONS: This repository allows for longitudinal, state-of-the-art geno-mic, transcriptomic, proteomic, metabolomic, immunologic, and clinical data collection and provides a rich and stable infrastructure on which to fuel further biomedical discovery.

The Impact of Adjuvant Therapy on Survival After Esophagectomy for Node-negative Esophageal Adenocarcinoma.

OBJECTIVE: Determine whether adjuvant chemotherapy is associated with a survival benefit in high risk T2-4a, pathologically node-negative distal esophageal adenocarcinoma. SUMMARY OF BACKGROUND DATA: There is minimal literature to substantiate the NCCN guidelines recommending adjuvant therapy for patients with distal esophageal adenocarcinoma and no pathologic evidence of nodal disease. METHODS: The National Cancer Database was used to identify adult patients with pT2-4aN0M0 esophageal adenocarcinoma who underwent definitive surgery (2004-2015) and had characteristics considered high risk by the NCCN. Patients were stratified by receipt of adjuvant chemotherapy with or without radiation. The primary outcome was overall survival, which was evaluated using Kaplan-Meier and multivariable Cox Proportional Hazards models. A 1:1 propensity score-matched analysis was also performed to compare survival between the groups. RESULTS: Four hundred three patients met study criteria: 313 (78%) without adjuvant therapy and 90 who received adjuvant chemotherapy with or without radiation (22%). In both unadjusted and multivariable analysis, adjuvant chemotherapy with or without radiation was not associated with a significant survival benefit compared to no adjuvant therapy. In a subgroup analysis of 335 patients without high risk features by NCCN criteria, adjuvant chemotherapy was not independently associated with a survival benefit. CONCLUSION: In this analysis, adjuvant chemotherapy with or without radiation was not associated with a significant survival benefit in completely resected, pathologically node-negative distal esophageal adenocarcinoma, independent of presence of high risk characteristics. The risks and benefits of adjuvant therapy should be weighed before offering it to patients with completely resected pT2-4aN0M0 esophageal adenocarcinoma.

The Relationship Between Lymph Node Ratio and Survival Benefit With Adjuvant Chemotherapy in Node-positive Esophageal Adenocarcinoma.

BACKGROUND: We hypothesized that the ratio of positive lymph nodes to total assessed lymph nodes (LNR) is an indicator of cancer burden in esophageal adenocarcinoma and may identify patients who may most benefit from AC. OBJECTIVE: The aim of this study was to discern whether there is a threshold LNR above which AC is associated with a survival benefit in this population. METHODS: The 2004-2015 National Cancer Database was queried for patients who underwent upfront, complete resection of pT1-4N1-3M0 esophageal adenocarcinoma. The primary outcome, overall survival, was examined using multivariable Cox proportional hazards models employing an interaction term between LNR and AC. RESULTS: A total of 1733 patients were included: 811 (47%) did not receive AC whereas 922 (53%) did. The median LNR was 20% (interquartile range 9-40). In a multivariable Cox model, the interaction term between LNR and receipt of AC was significant (P = 0.01). A plot of the interaction demonstrated that AC was associated with improved survival beyond a LNR of about 10%-12%. In a sensitivity analysis, the receipt of AC was not associated with improved survival in patients with LNR <12% (hazard ratio 1.02; 95% confidence interval 0.72-1.44) but was associated with improved survival in those with LNR ≥12% (hazard ratio 0.65; 95% confidence interval 0.50-0.79). CONCLUSIONS: In this study of patients with upfront, complete resection of node-positive esophageal adenocarcinoma, AC was associated with improved survival for LNR ≥12%. LNR may be used as an adjunct in multidisciplinary decision-making about adjuvant therapies in this patient population.

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer.

OBJECTIVES: Pembrolizumab is a programmed death receptor-1 masking antibody approved for metastatic non-small cell lung cancer. This Phase 2 study (NCT02818920) of neoadjuvant pembrolizumab in non-small cell lung cancer had a primary end point of safety and secondary end points of efficacy and correlative science. METHODS: Patients with untreated clinical stage IB to IIIA non-small cell lung cancer were enrolled. Two cycles of pembrolizumab (200 mg) were administered before surgery. Standard adjuvant chemotherapy and radiation were encouraged but not required. Four cycles of adjuvant pembrolizumab were provided. RESULTS: Of 35 patients enrolled, 30 received neoadjuvant pembrolizumab and 25 underwent lung resection. Only 1 patient had a delay before surgery attributed to pembrolizumab; this was due to thyroiditis. All patients underwent anatomic resection and mediastinal lymph node dissection; the majority (18/25%, 72%) of patients underwent lobectomy. Of the 25 patients, 23 had an initial minimally invasive approach (92%); 5 of these were converted to thoracotomy (21.7%). R0 resection was achieved in 22 patients (88%), and major pathologic response was observed in 7 of 25 patients (28%). The most common postoperative adverse event was atrial fibrillation, affecting 6 of 25 patients (24%). Median chest tube duration and length of stay were 3 and 4 days, respectively. One patient required readmission to the hospital within 30 days. There was no mortality within 90 days of surgery. CONCLUSIONS: In this study, pembrolizumab was safe and well tolerated in the neoadjuvant setting, and its use was not associated with excess surgical morbidity or mortality. Minimally invasive approaches are feasible in this patient population, but may be more challenging than in cases without neoadjuvant immunotherapy. Pathologic response was higher than typically observed with standard neoadjuvant chemotherapy.

Impact of Time to Endoscopic Resection on Outcomes for Stage I Esophageal Adenocarcinoma.

BACKGROUND: Endoscopic resection (ER) is the preferred treatment for superficial esophageal cancer; however, a safe time frame for performing ER has not been established. This study evaluated the period in which ER can be performed for patients with stage I esophageal adenocarcinoma without compromising outcomes. METHODS: The 2004-2015 National Cancer Database was used to identify patients with cT1 N0 M0 esophageal adenocarcinoma who underwent upfront ER. The primary outcome was overall survival, which was evaluated using Kaplan-Meier and multivariable Cox proportional hazards methods. The secondary outcome was rate of margin-positive resection, which was evaluated using a multivariable logistic regression. RESULTS: A total of 983 patients met study criteria. The median time from diagnosis to ER was 34 days (interquartile range, 5-70 days). Patients in the highest quartile of time to ER were more likely to be treated at a high-volume center and at a center different from that of diagnosis compared with those in the lowest quartile. Increasing time to ER was not independently associated with survival (adjusted hazard ratio per 10 days, 1.02; 95% confidence interval, 0.98-1.05; P = .32) or margin-positive resection (odds ratio per 10 days 1.01; 95% confidence interval, 0.96-1.06; P = .60). CONCLUSIONS: In this National Cancer Database analysis, increasing time to endoscopic resection, up to 180 days from diagnosis, was not associated with worsened survival or increased odds of margin-positive resection in patients with cT1 N0 M0 esophageal adenocarcinoma. Given these findings, patients may be afforded time to be seen in specialty centers without risk of tumor progression.

Tumor Size, Histology, and Survival After Stereotactic Ablative Radiotherapy and Sublobar Resection in Node-negative Non-small Cell Lung Cancer.

BACKGROUND: Although SABR is increasingly emerging as an alternative to surgery for node-negative non-small cell lung cancer, there is poor understanding of patients who may most benefit SABR compared to surgery. OBJECTIVE: This study examined the relationship between tumor size and the comparative outcomes of SABR and sublobar resection in patients with node-negative non-small cell lung cancer. RESULTS: A total of 59,949 patients met study criteria: 19,888 (33%) underwent SABR, 33,052 (55%) wedge resection, and 7009 (12%) segmental resection. In multivariable regression, a significant 3-way interaction was found between histology, tumor size, and type of treatment. After stratification by histology, a significant interaction between tumor size and treatment was preserved for patients with adenocarcinoma and squamous cell carcinoma. Sublobar resection was associated with greater survival compared to SABR for tumor sizes greater than 6 and 8 mm for patients with adenocarcinoma and squamous cell carcinoma, respectively. SABR was associated with similar survival compared to sublobar resection for patients with papillary and large cell histology. CONCLUSIONS: In this National Cancer Database analysis, sublobar resection was associated with greater survival compared to SABR for lesions >6or 8 mm in patients with adenocarcinoma or squamous cell carcinoma; however, SABR was associated with similar survival compared to sublobar resection in patients with aggressive tumors including papillary and large cell histology. Histologic diagnosis in patients with even small tumors may enable better treatment selection in those who cannot tolerate lobectomy.

Design and Rationale for a Phase III, Double-Blind, Placebo-Controlled Study of Neoadjuvant Durvalumab + Chemotherapy Followed by Adjuvant Durvalumab for the Treatment of Patients With Resectable Stages II and III non-small-cell Lung Cancer: The AEGEAN Trial.

For patients with resectable, early-stage non-small-cell lung cancer (NSCLC), surgery is the primary treatment; however, 5-year survival rates remain poor. Postoperative adjuvant platinum-doublet chemotherapy is associated with a statistically significant but modest improvement in survival of ∼5% at 5 years and is widely accepted as standard of care in patients with resectable, Stage II-III NSCLC. Neoadjuvant chemotherapy has been associated with similar improvements in overall survival to adjuvant therapy in this setting. Durvalumab, a high-affinity PD-L1 inhibitor, has become the standard of care for patients with unresectable, Stage III NSCLC following chemoradiotherapy based on improved progression-free and overall survival in the phase III PACIFIC trial. AEGEAN is a phase III, double-blind, placebo-controlled, international study that will assess pathological and clinical outcomes of durvalumab plus chemotherapy prior to surgery, followed by durvalumab monotherapy after surgery in adults with resectable, Stage II-III NSCLC. Approximately 800 patients will be randomized (1:1) to receive durvalumab or placebo every 3 weeks (q3w) alongside platinum-based chemotherapy (≤4 cycles) prior to surgery, followed by durvalumab or placebo monotherapy q4w, for an additional 12 cycles post surgery, stratified by disease stage (IASLC 8th Edition, Stage II vs. Stage III) and PD-L1 tumor cell expression levels (<1% vs. ≥1%). Primary endpoints include pathological complete response and event-free survival for patients with wild-type EGFR and ALK. Key secondary efficacy endpoints include major pathologic response, disease-free survival and overall survival.

Complications after Ravitch versus Nuss repair of pectus excavatum: A Society of Thoracic Surgeons (STS) General Thoracic Surgery Database analysis.

BACKGROUND: There are conflicting reports in the literature comparing outcomes after open Ravitch and minimally invasive Nuss procedures for pectus excavatum repair, and there is relatively little data available comparing the outcomes of these procedures performed by thoracic surgeons. METHODS: The 2010 to 2018 Society of Thoracic Surgeons General Thoracic Surgery Database was queried for patients age 12 or greater undergoing open or minimally invasive repair of pectus excavatum. Patients were stratified by operative approach. Multivariable logistic regression was performed with a composite outcome of 30-day complications. RESULTS: A total of 1,767 patients met inclusion criteria, including 1,017 and 750 patients who underwent minimally invasive pectus repair and open repair, respectively. Open repair patients were more likely to be American Society of Anesthesiologists (ASA) class III or greater (24% vs 14%; P < .001), have a history of prior cardiothoracic surgery (26% vs 14%; P < .001), and require longer operations (median 268 vs 185 minutes; P < .001). Open repair patients were more likely to require greater than 6 days of hospitalization (18% vs 7%; P < .001), undergo transfusion (7% vs 2%; P < .001), and be readmitted (8% vs 5%; P = .004). After adjustment, open repair was not associated with an increased risk of a composite of postoperative complications (odds ratio 0.99, 95% confidence interval 0.67-1.46). This finding persisted after propensity score matching (odds ratio 1.11, 95% confidence interval 0.74-1.67). CONCLUSION: Pectus excavatum repair procedure type was not associated with the risk of postoperative complications after adjustment. Further investigation is necessary to determine the impact of pectus excavatum repair type on recurrence and patient reported outcomes, including satisfaction, quality of life, and pain control.

The Effect of Tumor Size and Histologic Findings on Outcomes After Segmentectomy vs Lobectomy for Clinically Node-Negative Non-Small Cell Lung Cancer.

BACKGROUND: The interaction between tumor size and the comparative prognosis of lobar and sublobar resection has been defined poorly. RESEARCH QUESTION: The purpose of this study was to characterize the relationship between tumor size and the receipt of segmentectomy or lobectomy in association with overall survival in patients with clinically node-negative non-small cell lung cancer (NSCLC). STUDY DESIGN AND METHODS: The 2004-2015 National Cancer Database (NCDB) was queried for patients with cT1-3N0M0 NSCLC who underwent segmentectomy or lobectomy without neoadjuvant therapy or missing survival data. The primary outcome was overall survival, which was evaluated using multivariate Cox proportional hazards including an interaction term between tumor size and type of surgery. RESULTS: A total of 143,040 patients were included: 135,446 (95%) underwent lobectomy and 7594 (5%) underwent segmentectomy. In multivariate Cox regression, a significant three-way interaction was found among tumor size, histologic results, and type of surgery (P < .001). When patients were stratified by histologic results, lobectomy was associated with significantly improved survival compared with segmentectomy beyond a tumor size of approximately 10 mm for adenocarcinoma and 15 mm for squamous cell carcinoma that was recapitulated in subgroup analyses. No interaction between tumor size and type of surgery was found for patients with neuroendocrine tumors. INTERPRETATION: In this NCDB study of patients with node-negative NSCLC, we found different tumor size thresholds, based on histologic results, that identified populations of patients who least and most benefitted from lobectomy compared with segmentectomy.