Ivor Lewis Esophagectomy and the Care of Humphrey Bogart's Midesophageal Cancer.

In 1945, the Welsh surgeon Ivor Lewis first reported performing the resection of a midesophageal tumor through a combined approach involving the abdomen and right chest. Although his technique was initially rebuffed by the preeminent esophageal surgeons of the time, it quickly became the standard approach for cancers of the midesophagus. Here we review the development and early dissemination of Lewis' operation using the case of the American actor Humphrey Bogart, who underwent an Ivor Lewis esophagectomy for esophageal cancer in 1956.

Impact of lymphadenectomy extent on immunotherapy efficacy in postresectional recurred non-small cell lung cancer: a multi-institutional retrospective cohort study.

BACKGROUND: Lymph node (LN) dissection is a common procedure for non-small cell lung cancer (NSCLC) to ascertain disease severity and treatment options. However, murine studies have indicated that excising tumor-draining LNs diminished immunotherapy effectiveness, though its applicability to clinical patients remains uncertain. Hence, the authors aim to illustrate the immunological implications of LN dissection by analyzing the impact of dissected LN (DLN) count on immunotherapy efficacy, and to propose a novel 'immunotherapy-driven' LN dissection strategy. MATERIALS AND METHODS: The authors conducted a retrospective analysis of NSCLC patients underwent anti-PD-1 immunotherapy for recurrence between 2018 and 2020, assessing outcomes based on DLN count stratification. RESULTS: A total of 144 patients were included, of whom 59 had a DLN count less than or equal to 16 (median, IQR: 11, 7-13); 66 had a DLN count greater than 16 (median, IQR: 23, 19-29). With a median follow-up time of 14.3 months (95% CI: 11.0-17.6), the overall median progression-free survival (PFS) was 7.9 (95% CI: 4.1-11.7) months, 11.7 (95% CI: 7.9-15.6) months in the combination therapy subgroup, and 4.8 (95% CI: 3.1-6.4) months in the immunotherapy alone subgroup, respectively. In multivariable Cox analysis, DLN count less than or equal to 16 is associated with an improved PFS in all cohorts [primary cohort: HR=0.26 (95% CI: 0.07-0.89), P =0.03]; [validation cohort: HR=0.46 (95% CI: 0.22-0.96), P =0.04]; [entire cohort: HR=0.53 (95% CI: 0.32-0.89), P =0.02]. The prognostic benefit of DLN count less than or equal to 16 was more significant in immunotherapy alone, no adjuvant treatment, pN1, female, and squamous carcinoma subgroups. A higher level of CD8+ central memory T cell (Tcm) within LNs was associated with improved PFS (HR: 0.235, 95% CI: 0.065-0.845, P =0.027). CONCLUSIONS: An elevated DLN count (cutoff: 16) was associated with poorer immunotherapy efficacy in recurrent NSCLC, especially pronounced in the immunotherapy alone subgroup. CD8+Tcm proportions in LNs may also impact immunotherapy efficacy. Therefore, for patients planned for adjuvant immunotherapy, a precise rather than expanded lymphadenectomy strategy to preserve immune-depending LNs is recommended.

The American Association for Thoracic Surgery (AATS) 2023 Expert Consensus Document: Staging and multidisciplinary management of patients with early-stage non-small cell lung cancer.

Novel targeted therapy and immunotherapy drugs have recently been approved for use in patients with surgically resectable lung cancer. Accurate staging, early molecular testing, and knowledge of recent trials are critical to optimize oncologic outcomes in these patients.

Esophageal and Esophagogastric Junction Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Cancers originating in the esophagus or esophagogastric junction constitute a major global health problem. Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. In contrast to esophageal adenocarcinoma, which usually affects the lower esophagus, esophageal SCC is more likely to localize at or higher than the tracheal bifurcation. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability status, and the expression of programmed death-ligand 1, has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, ipilimumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with locally advanced esophageal or esophagogastric junction cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on the management of recurrent or metastatic disease.

Utilization Trends and Volume-outcomes Relationship of Endoscopic Resection for Early Stage Esophageal Cancer.

OBJECTIVES: We describe utilization trends and center volume-outcomes relationship of ER of early stage esophageal cancer using a large hospitalbased registry. SUMMARY OF BACKGROUND DATA: ER is increasingly accepted as the preferred treatment for early stage esophageal cancer, however its utilization and the center volume-outcomes relationship in the United States is unknown. METHODS: The National Cancer Database was used to identify patients with cT1N0M0 esophageal cancer treated with ER or esophagectomy between 2004 and 2015. Relative frequencies were plotted over time. Restricted cubic splines and maximally selected rank statistics were used to identify an inflection point of center volume and survival. RESULTS: A total of 1136 patients underwent ER and 2829 patients underwent esophagectomy during the study period. Overall utilization of ER, and relative use compared to esophagectomy, increased throughout the study period. Median annualized center ER volume was 1.9 cases per year (interquartile range 0.5-5.8). Multivariable Cox regression showed increasing annualized center volume by 1 case per year was associated with improved survival. Postoperative 30- or 90-day mortality, 30-day readmission, and pathologic T upstaging rates were similar irrespective of center volume. CONCLUSIONS: Utilization of ER compared to esophagectomy for stage I esophageal cancer has increased over the past decade, though many individual centers perform fewer than 1 case annually. increasing annualized center volume by one procedure per year was associated with improved survival. increased volume beyond this was not associated with survival benefit. Referral to higher volume centers for treatment of superficial esophageal cancer should be considered.

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.

Multi-institutional Care in Clinical Stage II and III Esophageal Cancer.

BACKGROUND: Management of clinical stage II or III esophageal cancer requires multidisciplinary care. Multi-institutional care has been associated with worse survival in other malignant diseases. This study aimed to determine the impact of multi-institutional care on survival in patients with stage II or III esophageal cancer. METHODS: The 2004 to 2016 National Cancer Database was queried for patients with clinical stage II or III esophageal cancer who received neoadjuvant chemotherapy with or without radiation therapy followed by surgical resection. Patients were stratified into 2 groups: multi-institutional or single-institution care. Survival between groups was compared using Kaplan-Meier and multivariable Cox proportional hazards methods. Multivariable logistic regression was performed to identify factors associated with multi-institutional care. RESULTS: Overall, 11 399 patients met study criteria: 6569 (57.6%) received multi-institutional care and 4,830 (42.4%) received care at a single institution. In a multivariable analysis, factors associated with multi-institutional care were later year of diagnosis, greater distance from treating facility, residence in an urban or rural setting (vs metro), and residence in states without Medicaid expansion. Care at a single institution was associated with Black race, lack of insurance, and treatment at higher-volume or academic centers. Despite these differences, patients who received multi-institutional care had survival comparable to that in patients who received care at a single institution (HR, 0.97; 95% CI, 0.92-1.03; P = .30). CONCLUSIONS: In this National Cancer Database analysis, multi-institutional care was not associated with inferior overall survival. As complex cancer care becomes more regionalized, patients may consider receiving part of their cancer care closer to home, whereas traveling to surgical centers of excellence should be encouraged.

Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.

Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.

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.

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.

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.

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.