Esophagectomy for End-Stage Achalasia.

Esophagectomy for achalasia is reserved for patients with end-stage disease for whom prior treatment has failed. Esophagectomy can be performed safely through a variety of techniques. Conduit options include stomach, colon, and small intestine. There are many potential complications following esophagectomy. Outcomes of esophagectomy for achalasia are good when performed in experienced surgical centers.

Development and Impact of an Institutional Enhanced Recovery Program on Opioid Use, Length of Stay, and Hospital Costs Within an Academic Medical Center: A Cohort Analysis of 7774 Patients.

BACKGROUND: Enhanced Recovery (ER) is a change management framework in which a multidisciplinary team of stakeholders utilizes evidence-based medicine to protocolize all aspects of a surgical care to allow more rapid return of function. While service-specific reports of ER adoption are common, institutional-wide adoption is complex, and reports of institution-wide ER adoption are lacking in the United States. We hypothesized that ER principles were generalizable across an institution and could be implemented across a multitude of surgical disciplines with improvements in length of stay, opioid consumption, and cost of care. METHODS: Following the establishment of a formal institutional ER program, ER was adopted in 9 distinct surgical subspecialties over 5 years at an academic medical center. We compared length of stay, opioid consumption, and total cost of care in all surgical subspecialties as a function of time using a segmented regression/interrupted time series statistical model. RESULTS: There were 7774 patients among 9 distinct surgical populations including 2155 patients in the pre-ER cohort and 5619 patients in the post-ER cohort. The introduction of an ER protocol was associated with several significant changes: a reduction in length of stay in 5 of 9 specialties; reduction in opioid consumption in 8 specialties; no change or reduction in maximum patient-reported pain scores; and reduction or no change in hospital costs in all specialties. The ER program was associated with an aggregate increase in profit over the study period. CONCLUSIONS: Institution-wide efforts to adopt ER can generate significant improvements in patient care, opioid consumption, hospital capacity, and profitability within a large academic medical center.

How Many Nodes Need to be Removed to Make Esophagectomy an Adequate Cancer Operation, and Does the Number Change When a Patient has Chemoradiotherapy Before Surgery?

INTRODUCTION AND DESIGN: Node dissection during esophagectomy is an important aspect of esophageal cancer staging. Controversy remains as to how many nodes need to be resected in order to properly stage a patient and whether the removal of more nodes carries a stage-independent survival benefit. A review of the literature performed by a group of experts in the subject may help define a minimum accepted number of lymph nodes to be resected in both primary surgery and post-induction therapy scenarios. RESULTS AND CONCLUSIONS: The existing evidence generally supports the goal of obtaining a minimum of 15 lymph nodes for pathological examination in both primary surgery and post-induction therapy scenarios.

Striving toward Improved Outcomes for Surgically Resectable Non-Small Cell Lung Cancer: the Promise and Challenges of Neoadjuvant Immunotherapy.

PURPOSE OF REVIEW: Immunotherapy has revolutionized the treatment of non-surgical stage III and stage IV non-small cell lung cancer (NSCLC). Here, we review emerging data on the safety, feasibility, and efficacy of neoadjuvant immunotherapy in the setting of earlier stage surgically resectable lung cancer. RECENT FINDINGS: Several small studies support the safety and feasibility of neoadjuvant immunotherapy, noting similar perioperative rates of morbidity and mortality compared with historical controls. Data from several phase II trials have shown high rates of major pathologic response (MPR), though it is unclear if this will correlate with a survival benefit. Phase III trials of neoadjuvant immunotherapy alone or in combination with chemotherapy are ongoing. Neoadjuvant immunotherapy offers a promising treatment modality in earlier stage NSCLC patients. Results of ongoing phase II and phase III trials will be essential in determining how to best integrate this treatment modality in the future.

Enhanced Recovery after Thoracic Surgery.

Enhanced recovery programs (ERPs) aim to reduce psychological and physiological stress related to surgery, and minimize opioid use. This article describes the tenets of enhanced recovery, the guidelines for ERP in lung surgery, and the University of Virginia experience with developing and implementing a program. The impact of these strategies on short-term patient outcomes and potential long-term benefits including influence on lung cancer-specific outcomes are reviewed. The opioid crisis is of utmost importance; this article will explore how ERPs may be a mitigating factor.

An Observational Study of the Pharmacokinetics of Surgeon-Performed Intercostal Nerve Blockade With Liposomal Bupivacaine for Posterior-Lateral Thoracotomy Analgesia.

BACKGROUND: Intercostal nerve blocks with liposomal bupivacaine are commonly used for thoracic surgery pain management. However, dose scheduling is difficult because the pharmacokinetics of a single-dose intercostal injection of liposomal bupivacaine has never been investigated. The primary aim of this study was to assess the median time to peak plasma concentration (Tmax) following a surgeon-administered, single-dose infiltration of 266 mg of liposomal bupivacaine as a posterior multilevel intercostal nerve block in patients undergoing posterolateral thoracotomy. METHODS: We chose a sample size of 15 adults for this prospective observational study. Intercostal injection of liposomal bupivacaine was considered time 0. Serum samples were taken at the following times: 5, 15, and 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours. The presence of sensory blockade, rescue pain medication, and pain level were recorded after the patient was able to answer questions. RESULTS: Forty patients were screened, and 15 patients were enrolled in the study. Median (interquartile range [IQR]) Tmax was 24 (12) hours (confidence interval [CI], 19.5-28.5 hours) with a range of 15 minutes to 48 hours. The median (IQR) peak plasma concentration (Cmax) was 0.6 (0.3) µg/mL (CI, 00.45-0.74 µg/mL) in a range of 0.3-1.2. The serum bupivacaine concentration was undetectable (<0.2 µg/mL) at 96 hours in all patients. There was significant variability in reported pain scores and rescue opioid medication across the 15 patients. More than 50% of patients had return of normal chest wall sensation at 48 hours. All patients had resolution of nerve blockade at 96 hours. No patients developed local anesthetic toxicity. CONCLUSIONS: This study of the pharmacokinetics of liposomal bupivacaine following multilevel intercostal nerve blockade demonstrates significant variability and delay in systemic absorption of the drug. Peak serum concentration occurred at 48 hours or sooner in all patients. The serum bupivacaine concentration always remained well below the described toxicity threshold (2 µg/mL) during the 96-hour study period.

What Constitutes Optimal Management of T1N0 Esophageal Adenocarcinoma?

PURPOSE AND DESIGN: Esophageal adenocarcinoma (EAC) develops as a consequence of gastroesophageal reflux disease and Barrett's esophagus (BE). While combination therapy with chemotherapy or concurrent chemoradiotherapy followed by esophagectomy improves survival in more advanced tumors, the optimal treatment strategy for early-stage EAC is undefined. Endoscopic eradication therapy, consisting of endoscopic resection and mucosal ablation, has revolutionized therapy for superficial (T1a) EAC in BE and allows for esophageal preservation in appropriate patients at low risk for lymph node metastasis (LNM). This review critically examines the literature regarding evaluation, treatment, and outcomes in patients with T1 EAC. METHODS: The literature was queried via the PubMed database to include articles published between 1990 and 2017. Search terms were generated from the key statements "Endoscopic eradication therapy results in equivalent overall survival when compared to esophagectomy for clinical T1aN0 EAC" and "Esophagectomy provides better overall survival than endoscopic eradication therapy for cT1b EAC". Abstracts were reviewed and included according to predefined selection and exclusion criteria, and were then assessed according to the GRADE system. RESULTS AND CONCLUSIONS: In patients with T1aN0 EAC, overall survival with endoscopic eradication therapy is equal to esophagectomy. Given the substantial risk of LNM in patients with submucosal (T1b) EAC, esophagectomy remains the standard of care for surgical candidates. In the case of inoperability or low-risk lesions, endoscopic resection may be considered adequate therapy. Chemotherapy and radiation can be offered as primary therapy for non-surgical candidates with lesions not amenable to endoscopic therapy, but does not have a clear role in the adjuvant setting after either endoscopic or surgical resection.

Five-Year Sustained Impact of a Thoracic Enhanced Recovery After Surgery Program.

BACKGROUND: Our thoracic enhanced recovery program (ERP) decreased the use of postoperative morphine equivalents and hospital costs 1 year after implementation at our tertiary center. The sustainability and potential increasing benefit of this program were evaluated. METHODS: From 2015 to 2021, we prospectively analyzed the outcomes of patients who underwent elective pleural, pulmonary, or mediastinal operations at our institution. Patients were separated on the basis of the incision (video-assisted thoracoscopic surgery [VATS] or thoracotomy). The ERP protocol was initiated on May 1, 2016, and includes preoperative education, carbohydrate loading, opioid-sparing analgesia, conservative fluid management, protective ventilation, and early ambulation. Outcomes of patients before (2015, pre-VATS and pre-thoracotomy) and after (May 1, 2016, to December 31, 2021, ERP-VATS and ERP-thoracotomy) ERP implementation were compared. RESULTS: The cohort included 1079 patients (pre-ERP era, n = 224 [21%]; ERP era, n = 855 [79%]). There was a median reduction of 1.5 hospital days per patient for ERP-thoracotomy and 1 hospital day per patient for ERP-VATS. Median postoperative morphine equivalents decreased in both groups (125 vs 45 mg, in ERP-thoracotomy; 84 vs 23 mg, ERP-VATS; P < .001), as did total admission cost ($32,118 vs $23,775, ERP-thoracotomy; $17,367 vs $11,560, ERP-VATS; P < .001). Median total fluid balance during the hospital stay decreased significantly. Rates of postoperative atrial fibrillation and urinary retention decreased across both subgroups. CONCLUSIONS: ERP for thoracic surgery is sustainable and has been demonstrated to improve patient outcomes, to decrease opioid use, and to lower hospital costs. Therefore, it has the potential to become the standard of care.

Impact of Opioid Use on Duration of Therapy and Overall Survival for Patients with Advanced Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICI) have significantly improved outcomes in advanced non-small cell lung cancer (NSCLC). We evaluated the effect of opioid use on outcomes in patients receiving ICI either alone or with chemotherapy. We conducted a retrospective review of 209 patients with advanced NSCLC who received an ICI at the University of Virginia between 1 February 2015 and 1 January 2020. We performed univariate and multivariate analyses to evaluate the impact of opioid use on duration of therapy (DOT) and overall survival (OS). Patients with no or low opioid use (n = 172) had a median DOT of 12.2 months (95% CI: 6.9-17.4) compared to 1.9 months (95% CI: 1.8-2.0) for those with high opioid use (n = 37, HR 0.26 95% CI: 0.17-0.40, p < 0.001). Patients with no or low opioid use had a median OS of 22.6 months (95% CI: 14.8-30.4) compared to 3.8 months (95% CI: 2.7-4.9) for those with high opioid use (HR 0.26 95% CI: 0.17-0.40 p < 0.001). High opioid use was associated with a shorter DOT and worse OS. This difference remained significant when accounting for possible confounding variables. These data warrant investigation of possible mechanistic interactions between opioids, tumor progression, and ICIs, as well as prospective evaluation of opioid-sparing pain management strategies, where possible.

Long-term Survival After Lung Cancer Resection in the National Lung Screening Trial.

BACKGROUND: This study sought to evaluate the long-term survival and causes of death after surgery among patients with pathologic stage IA non-small cell lung cancer (NSCLC) in the National Lung Screening Trial (NLST). METHODS: Patients who underwent surgery and who had a diagnosis of pathologic stage IA NSCLC in the NLST were identified for analysis. The 5- and 10-year overall survival and lung cancer-specific survival, stratified by operation type, were evaluated. Among patients who underwent lobectomy, the causes of death and the cumulative incidence of lung cancer death were assessed. RESULTS: A total of 380 patients (n = 329, 86.6% lobectomy; n = 20, 5.3% segmentectomy; n = 31, 8.1% wedge resection) met inclusion criteria. Median follow-up time from the date of surgery was 7.8 years (interquartile range, 4.8-10.7 years). The 10-year overall survival rate was 58.3% (95% CI, 52.4%-63.8%) for lobectomy, 59.9% (95% CI, 33.2%-78.8%) for segmentectomy, and 45.2% (95% CI, 20.8%-66.9%) for wedge resection. The 10-year lung cancer-specific survival rate was 74.3% (95% CI, 68.6%-79.1%) for lobectomy, 81.3% (95% CI, 51.3%-93.8%) for segmentectomy, and 84.8% (95% CI, 64.0%-94.1%) for wedge resection. Lung cancer was the leading cause of death, accounting for 55.8% of deaths after lobectomy. The 10-year cumulative incidence of lung cancer death after lobectomy was 22.5% (95% CI, 18.3%-27.1%). CONCLUSIONS: The 10-year overall survival rate after lobectomy among patients with pathologic stage IA NSCLC in the NLST was 58%. Lung cancer was the leading cause of death, accounting for more than 55% of deaths.

Shortage of thoracic surgeons in the United States: Implications for treatment and survival for stage I lung cancer patients.

OBJECTIVES: To evaluate whether there is a shortage of thoracic surgeons in the United States and whether any potential shortage is impacting lung cancer treatment and outcomes. DESIGN: Using the US Area Health Resources File and Surveillance Epidemiology End Results database, we assessed the number of cardiothoracic surgeons per 100,000 people and the number of stage I non-small cell lung cancer (NSCLC) diagnoses in the US in 2010 versus 2018. Changes in the percentage of patients diagnosed with stage I NSCLC who underwent surgery and stereotactic body radiotherapy and changes in overall survival of patients with stage I NSCLC from 2010 to 2018 in the National Cancer Database were evaluated using multivariable logistic regression and Cox proportional hazards modeling. RESULTS: From 2010 to 2018, the number of cardiothoracic surgeons per 100,000 people in the US decreased by 12% (P < .001), while the number of patients diagnosed with stage I NSCLC increased by 40% (P < .001). Over the same period, the percentage of patients who underwent surgery for stage I NSCLC decreased from 81.0% to 72.3% (adjusted odds ratio, 0.59; 95% confidence interval, 0.55-0.63); this decrease was similarly seen in a subgroup of young and otherwise healthy patients. Greater decreases in the percentage of patients who underwent surgery in nonmetropolitan and underserved regions corresponded with worse improvements in survival among patients in these regions from 2010 to 2018. CONCLUSIONS: Recent declines in the US cardiothoracic surgery workforce may have led to significantly fewer patients undergoing surgery for stage I NSCLC and worsening disparities in survival between different patient populations.

MDT-BRIDGE: Neoadjuvant Durvalumab Plus Chemotherapy Followed by Either Surgery and Adjuvant Durvalumab or Chemoradiotherapy and Consolidation Durvalumab in Resectable or Borderline-resectable Stage IIB-IIIB NSCLC.

INTRODUCTION: In the AEGEAN trial, neoadjuvant durvalumab plus platinum-based chemotherapy (D+CT) followed by adjuvant durvalumab, versus neoadjuvant chemotherapy alone, significantly improved pathological complete response (pCR) rate and event-free survival (EFS) in patients with resectable NSCLC. In the PACIFIC trial, consolidation durvalumab significantly improved progression-free (PFS) and overall survival (OS) for patients with unresectable stage III NSCLC after chemoradiotherapy. Strong pathological and clinical outcomes with chemoimmunotherapy have generated interest in its use to enable patients with borderline-resectable NSCLC to undergo surgery. Additionally, for patients initially deemed resectable but who later become unresectable/inoperable during neoadjuvant treatment, consolidation immunotherapy after chemoradiotherapy should be explored. PATIENTS AND METHODS: MDT-BRIDGE (NCT05925530) is a multicenter, phase II, non-randomized study in ∼140 patients with EGFR/ALK wild-type, stage IIB-IIIB (N2) NSCLC. Following baseline multidisciplinary team (MDT) assessment to determine resectable/borderline-resectable status, all patients receive 2 cycles of neoadjuvant D+CT every 3 weeks, followed by MDT reassessment of resectability. Patients deemed resectable receive 1-2 additional cycles of D+CT followed by surgery (Cohort 1). Patients deemed unresectable receive standard-of-care chemoradiotherapy (Cohort 2). Cohort 1 patients who become ineligible for surgery can enter Cohort 2. Following surgery or chemoradiotherapy, patients receive adjuvant or consolidation durvalumab for 1 year. The primary endpoint is resection rate in all patients. Additional endpoints include resection rates by baseline resectable/borderline-resectable status, resection outcomes, EFS/PFS, OS, pCR rate, circulating tumor DNA dynamics pre- and post-surgery (including correlation with clinical outcomes), and safety. CONCLUSION: Enrollment began in February 2024; primary completion is anticipated in April 2026.

Segmentectomy versus lobectomy in the United States: Outcomes after resection for first primary lung cancer and treatment patterns for second primary lung cancers.

OBJECTIVE: The study objective was to identify whether the results of JCOG0802 could be generalized to US clinical settings. METHODS: Patients diagnosed with clinical stage IA (≤2 cm) non-small cell lung cancer who underwent segmentectomy versus lobectomy (2004-2017) in the National Cancer Database were identified. Overall survival of patients in the National Cancer Database was assessed using propensity score-matched analysis. A separate analysis of the Surveillance Epidemiology End Results database was conducted to evaluate treatment patterns of second primary lung cancers among patients who underwent segmentectomy versus lobectomy for a first primary lung cancer. RESULTS: Of the 23,286 patients in the National Cancer Database meeting inclusion criteria, 1397 (6.0%) underwent segmentectomy and 21,889 (94.0%) underwent lobectomy. In a propensity score-matched analysis of all patients in the study cohort, there were no significant differences in overall survival between patients undergoing segmentectomy versus lobectomy (5-year overall survival: 79.9% [95% CI, 76.7%-82.0%] vs 81.8% [95% CI, 78.7%-84.4%], log-rank: P = .72). In subgroup analyses by tumor grade and histologic subtype, segmentectomy was associated with similar overall survival compared with lobectomy in all subgroups evaluated. In a propensity score-matched analysis of patients in the Surveillance Epidemiology End Results database, there were no significant differences in treatment patterns of second primary lung cancers between patients who underwent segmentectomy and patients who underwent lobectomy for their first primary lung cancer. CONCLUSIONS: In this national analysis of US patients diagnosed with stage IA (≤2 cm) non-small cell lung cancer, there were no significant differences in overall survival between segmentectomy and lobectomy in the overall cohort or in subgroup analyses by tumor grade or histologic subtype.

The Society of Thoracic Surgeons Expert Consensus Document on the Management of Pleural Drains After Pulmonary Lobectomy: Expert Consensus Document.

The Society of Thoracic Surgeons Workforce on Evidence-Based Surgery provides this document on management of pleural drains after pulmonary lobectomy. The goal of this consensus document is to provide guidance regarding pleural drains in 5 specific areas: (1) choice of drain, including size, type, and number; (2) management, including use of suction vs water seal and criteria for removal; (3) imaging recommendations, including the use of daily and postpull chest roentgenograms; (4) use of digital drainage systems; and (5) management of prolonged air leak. To formulate the consensus statements, a task force of 15 general thoracic surgeons was invited to review the existing literature on this topic. Consensus was obtained using a modified Delphi method consisting of 2 rounds of voting until 75% agreement on the statements was reached. A total of 13 consensus statements are provided to encourage standardization and stimulate additional research in this important area.

Delayed esophageal anastomotic complication and ramucirumab therapy: A case report.

Current NCCN guidelines for second-line therapy in recurrent or metastatic esophago-gastric cancers recommend the use of VEGF inhibitors such as ramucirumab. VEGF inhibitors have been shown to be associated with gastrointestinal perforation in clinical trials and late colorectal anastomotic leaks in a few case reports. Here, we present a case of late esophageal anastomotic leak in a patient receiving ramucirumab. Case information was obtained from our institution's electronic medical records. The patient was found to have T4N1M0, poorly differentiated invasive adenocarcinoma and subsequently received neoadjuvant chemoradiation followed by hybrid Ivor-Lewis esophagectomy 6 weeks later. He recovered well with no leak or perioperative complications. The patient had disease progression 9 months postoperatively on CT and PET imaging. Sixteen months after surgery he began paclitaxel and ramucirumab and 16 weeks after ramucirumab initiation, he was found to have an esophago-pulmonary fistula in the region of the anastomosis. Biopsies were negative for recurrence at the anastomosis. He died one week later from progressive pneumonia despite stenting. In conclusion, this is the only known report of delayed esophageal anastomotic complication associated with ramucirumab. VEGF inhibitor therapies such as bevacizumab have been associated with late (greater than 3 months postoperative) colorectal anastomotic complications including fistulas and leaks. Risk factors that have been associated are perioperative radiotherapy and history of early postoperative leak. These findings raise concern whether VEGF inhibitor therapy should be used in post-esophagectomy patients with recurrence if these rare but catastrophic events are likely to be terminal.

Malignant undifferentiated and rhabdoid tumors of the gastroesophageal junction and esophagus with SMARCA4 loss: a case series.

Undifferentiated SMARCA4-deficient carcinoma of the esophagus and gastroesophageal junction is a rare, highly aggressive, and diagnostically challenging malignancy. Here we present a case series of high-grade undifferentiated malignant neoplasms of the esophagus and gastroesophageal junction that share SMARCA4 loss by immunohistochemistry and demonstrate a rhabdoid phenotype. Five cases are presented, including 4 men and 1 woman with an age range of 48-79 years. Interestingly, only one case showed intestinal metaplasia (Barrett's esophagus) and no cases demonstrated glandular dysplasia or glandular differentiation. In all, the lesional cells were immunoreactive with antibodies to keratins (3/5), CD34 (2/4), and CD138 (4/5). SMARCA4 expression was diffusely lost in all cases, whereas SMARCB1 expression was intact. OncoScan™ assay demonstrated loss of SMARCA4 in all cases analyzed. Additional OncoScan™ findings included abnormalities of CDKN2A in 2 of 3 cases, abnormalities of TP53 in 2 of 3 cases, and abnormalities of PTPRD in 2 of 3 cases, among other abnormalities.

Pafolacianine for intraoperative molecular imaging of cancer in the lung: The ELUCIDATE trial.

OBJECTIVE: The study objective was to determine the clinical utility of pafolacianine, a folate receptor-targeted fluorescent agent, in revealing by intraoperative molecular imaging folate receptor α positive cancers in the lung and narrow surgical margins that may otherwise be undetected with conventional visualization. METHODS: In this Phase 3, 12-center trial, 112 patients with suspected or biopsy-confirmed cancer in the lung scheduled for sublobar pulmonary resection were administered intravenous pafolacianine within 24 hours before surgery. Participants were randomly assigned to surgery with or without intraoperative molecular imaging (10:1 ratio). The primary end point was the proportion of participants with a clinically significant event, reflecting a meaningful change in the surgical operation. RESULTS: No drug-related serious adverse events occurred. One or more clinically significant event occurred in 53% of evaluated participants compared with a prespecified limit of 10% (P < .0001). In 38 participants, at least 1 event was a margin 10 mm or less from the resected primary nodule (38%, 95% confidence interval, 28.5-48.3), 32 being confirmed by histopathology. In 19 subjects (19%, 95% confidence interval, 11.8-28.1), intraoperative molecular imaging located the primary nodule that the surgeon could not locate with white light and palpation. Intraoperative molecular imaging revealed 10 occult synchronous malignant lesions in 8 subjects (8%, 95% confidence interval, 3.5-15.2) undetected using white light. Most (73%) intraoperative molecular imaging-discovered synchronous malignant lesions were outside the planned resection field. A change in the overall scope of surgical procedure occurred for 29 of the subjects (22 increase, 7 decrease). CONCLUSIONS: Intraoperative molecular imaging with pafolacianine improves surgical outcomes by identifying occult tumors and close surgical margins.

Induction chemoimmunotherapy with surgery versus concurrent chemoradiation followed by immunotherapy for stage III-N2 non-small cell lung cancer.

OBJECTIVE: Despite the growing relevance of immunotherapy for non-small cell lung cancer (NSCLC), there is limited consensus on the optimal treatment strategy for locally advanced NSCLC. This study evaluated the overall survival of patients with stage III-N2 NSCLC undergoing induction chemoimmunotherapy with surgery (CT/IO+Surgery) and definitive concurrent chemoradiation followed by immunotherapy (cCRT+IO). METHODS: Patients with cT1-3, N2, M0 NSCLC in the National Cancer Database (2013 to 2019) were included and stratified by treatment regimen: CT/IO+Surgery or cCRT+IO. Overall survival was evaluated using Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching on 10 prognostic variables. RESULTS: Of the 3382 patients who met the study eligibility criteria, 3289 (97.3%) received cCRT+IO and 93 (2.8%) received CT/IO+Surgery. The 3-year overall survival of the entire cohort was 58.2% (95% CI, 56.2% to 60.1%). Multivariable-adjusted Cox proportional hazards modeling demonstrated better survival after CT/IO+Surgery than after cCRT+IO (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.32 to 0.84; P = .007). In a 3:1 variable ratio propensity score-matched analysis of 223 patients who received cCRT+IO and 76 patients who received CT/IO+Surgery, 3-year overall survival was 63.2% (95% CI, 55.9% to 70.2%) after cCRT+IO and 77.2% (95% CI, 64.6% to 85.7%) after CT/IO+Surgery (P = .029). CONCLUSIONS: In this national analysis, multimodal treatment including immunotherapy was associated with a 3-year overall survival rate of 58.2% for all patients with stage III-N2 NSCLC and 77.2% for patients who underwent chemoimmunotherapy followed by surgery. These results should be considered hypothesis-generating and demonstrate the importance of developing a randomized trial to evaluate the role of surgery versus chemoradiation for locally advanced NSCLC in the modern immunotherapy era.

A National Survey of Surgeons Evaluating the Accuracy of Mediastinal Lymph Node Identification.

BACKGROUND: The Commission on Cancer implemented Standard 5.8 in 2021, which requires removal of 3 mediastinal nodes and 1 hilar node with lung cancer resection. We conducted a national survey to assess whether surgeons who treat lung cancer in different clinical settings correctly identify mediastinal lymph node stations. METHODS: Cardiac or thoracic surgeons expressing interest in lung cancer surgery on the Cardiothoracic Surgery Network were asked to complete a 7-question survey assessing their knowledge of lymph node anatomy. General surgeons whose practice includes thoracic surgery were invited through American College of Surgeon's Cancer Research Program. Results were analyzed using Pearson's chi-square test. Multivariable linear regression was used to identify predictors of a higher score on the survey. RESULTS: Of the 280 surgeons that responded, 86.8% were male and 13.2% were female; the median age was 50 years. Of these surgeons, 211 (75.4%) were thoracic, 59 (21.1%) were cardiac, and 10 (3.6%) were general surgeons. Surgeons were most likely to correctly identify lymph node stations 8R and 9R and least likely to correctly identify the midline pretracheal node just superior to the carina (4R). Surgeons whose practice involved a greater percentage of thoracic surgery patients and surgeons who performed a greater number of lobectomies scored higher on the lymph node assessment. CONCLUSION: Knowledge of mediastinal node anatomy among surgeons who perform thoracic surgery is generally high, but varies by clinical setting. Efforts are under way to better educate lung cancer surgeons on nodal anatomy, and to increase adoption of Standard 5.8.

Carcinoembryonic Antigen-Related Cell Adhesion Molecule Type 5 Receptor-Targeted Fluorescent Intraoperative Molecular Imaging Tracer for Lung Cancer: A Nonrandomized Controlled Trial.

Importance: Localization of subcentimeter ground glass opacities during minimally invasive thoracoscopic lung cancer resections is a significant challenge in thoracic oncology. Intraoperative molecular imaging has emerged as a potential solution, but the availability of suitable fluorescence agents is a limiting factor. Objective: To evaluate the suitability of SGM-101, a carcinoembryonic antigen-related cell adhesion molecule type 5 (CEACAM5) receptor-targeted near-infrared fluorochrome, for molecular imaging-guided lung cancer resections, because glycoprotein is expressed in more than 80% of adenocarcinomas. Design, Setting, and Participants: For this nonrandomized, proof-of-principal, phase 1 controlled trial, patients were divided into 2 groups between August 1, 2020, and January 31, 2022. Patients with known CEACAM5-positive gastrointestinal tumors suggestive of lung metastasis were selected as proof-of-principle positive controls. The investigative group included patients with lung nodules suggestive of primary lung malignant neoplasms. Patients 18 years or older without significant comorbidities that precluded surgical exploration with suspicious pulmonary nodules requiring surgical biopsy were included in the study. Interventions: SGM-101 (10 mg) was infused up to 5 days before index operation, and pulmonary nodules were imaged using a near-infrared camera system with a dedicated thoracoscope. Main Outcomes and Measures: SGM-101 localization to pulmonary nodules and its correlation with CEACAM5 glycoprotein expression by the tumor as quantified by tumor and normal pulmonary parenchymal fluorescence. Results: Ten patients (5 per group; 5 male and 5 female; median [IQR] age, 66 [58-69] years) with 14 total lesions (median [range] lesion size, 0.91 [0.90-2.00] cm) were enrolled in the study. In the control group of 4 patients (1 patient did not undergo surgical resection because of abnormal preoperative cardiac clearance findings that were not deemed related to SGM-101 infusion), the mean (SD) lesion size was 1.33 (0.48) cm, 2 patients had elevated serum CEA markers, and 2 patients had normal serum CEA levels. Of the 4 patients who underwent surgical intervention, those with 2+ and 3+ tissue CEACAM5 expression had excellent tumor fluorescence, with a mean (SD) tumor to background ratio of 3.11 (0.45). In the patient cohort, the mean (SD) lesion size was 0.68 (0.22) cm, and no elevations in serum CEA levels were found. Lack of SGM-101 fluorescence was associated with benign lesions and with lack of CEACAM5 staining. Conclusions and Relevance: This in-human proof-of-principle nonrandomized controlled trial demonstrated SGM-101 localization to CEACAM5-positive tumors with the detection of real-time near-infrared fluorescence in situ, ex vivo, and by immunofluorescence microscopy. These findings suggest that SGM-101 is a safe, receptor-specific, and feasible intraoperative molecular imaging fluorochrome that should be further evaluated in randomized clinical trials. Trial Registration: ClinicalTrials.gov identifier: NCT04315467.