Comparison of robotic-assisted minimally invasive esophagectomy versus minimally invasive esophagectomy: A propensity-matched study from a single high-volume institution.

OBJECTIVE: Robotic-assisted minimally invasive esophagectomy accounts for a growing proportion of esophagectomies, potentially due to improved technical capabilities simplifying the challenging aspects of standard minimally invasive esophagectomy. However, there is limited evidence directly comparing both operations. The objective is to evaluate the short-term and long-term outcomes of robotic-assisted minimally invasive esophagectomy in comparison with the minimally invasive esophagectomy approach for patients with esophageal cancer over a 7-year period at a high-volume center. The primary end points of this study were overall survival and disease-free survival. Secondary end points included operation-specific morbidity, lymph node yield, readmission status, and in-hospital, 30-day, and 90-day mortality. METHODS: Patients who underwent robotic-assisted minimally invasive esophagectomy or standard minimally invasive esophagectomy over a 7-year period were identified from a prospectively maintained database. Inclusion criteria were patients with stage I to III disease, operations performed past the learning curve, and no evidence of scleroderma or cirrhosis. A 1:3 propensity match (robotic-assisted minimally invasive esophagectomy:minimally invasive esophagectomy) for multiple clinical covariates was performed to identify the final study cohort. Perioperative outcomes were compared between the 2 operations. RESULTS: A total of 734 patients undergoing minimally invasive esophagectomy (n = 630) or robotic-assisted minimally invasive esophagectomy (n = 104) for esophageal cancer were identified. After exclusions and matching, a total cohort of 246 patients undergoing robotic-assisted minimally invasive esophagectomy (n = 65) or minimally invasive esophagectomy (n = 181) were identified. There was no difference in overall survival (P = .69) or disease-free survival (P = .70). There were no significant differences in rates of major morbidity: pneumonia (17% vs 17%, P = .34), chylothorax (8% vs 9%, P = .95), recurrent laryngeal nerve injury (0% vs 1.5%, P = 1), anastomotic leak (5% vs 4%, P = .49), intraoperative complications (9% vs 8%, P = .73), or complete resection rates (99% vs 96%, P = .68). There was no difference in in-hospital (P = .89), 30-day (P = .66) or 90-day mortality (P = .73) between both cohorts. The robotic-assisted minimally invasive esophagectomy cohort yielded a higher median lymph node harvest in comparison with the minimally invasive esophagectomy cohort (32 vs 29, P = .02). CONCLUSIONS: Robotic-assisted minimally invasive esophagectomy may improve lymphadenectomy in patients undergoing esophagectomy for cancer. Minimally invasive esophagectomy and robotic-assisted minimally invasive esophagectomy are otherwise associated with similar mortality, morbidity, and perioperative outcomes. Further prospective study is required to investigate whether improved lymph node resection may translate to improved oncologic outcomes.

Intrapleural interleukin-2-expressing oncolytic virotherapy enhances acute antitumor effects and T-cell receptor diversity in malignant pleural disease.

OBJECTIVE: The mainstay of treatment for patients with malignant pleural disease is fluid drainage and systemic therapy. A tumor-specific oncolytic virus or T-cell-activating interleukin-2 immunotherapy may provide an opportunity for local control. We previously developed a vaccinia virus-expressing interleukin-2, an oncolytic virus that mediated tumor regression in preclinical peritoneal tumor models with expansion of tumor-infiltrating lymphocytes. We evaluated the antitumor efficacy and immune modulatory effects of vaccinia virus-expressing interleukin-2 in malignant pleural disease. METHODS: A murine model of malignant pleural disease was established with percutaneous intrapleural deposition of the Lewis lung carcinoma cell line and monitored with bioluminescent imaging. After intrapleural or systemic administration of vaccinia viruses (vaccinia virus yellow fluorescent protein control, vaccinia virus-expressing interleukin-2), systemic anti-programmed cell death-1 antibody, or combination therapy (vaccinia virus-expressing interleukin-2 and anti-programmed cell death-1), tumor mass, immune cell infiltration, T-cell receptor diversity, and survival were assessed. RESULTS: Intrapleural vaccinia virus resulted in significant tumor regression compared with phosphate-buffered saline control (P < .05). Inclusion of the interleukin-2 transgene further increased intratumoral CD8+ T cells (P < .01) and programmed cell death-1 expression on CD8+ tumor-infiltrating lymphocytes (P < .001). Intrapleural vaccinia virus-expressing interleukin-2 was superior to systemic vaccinia virus-expressing interleukin-2, with reduced tumor burden (P < .0001) and improved survival (P < .05). Intrapleural vaccinia virus-expressing interleukin-2 alone or combined treatment with systemic anti-programmed cell death-1 reduced tumor burden (P < .01), improved survival (P < .01), and increased intratumoral αß T-cell receptor diversity (P < .05) compared with systemic anti-programmed cell death-1 monotherapy. CONCLUSIONS: Intrapleural vaccinia virus-expressing interleukin-2 reduced tumor burden and enhanced survival in a murine malignant pleural disease model. Increased CD8+ tumor-infiltrating lymphocytes and αß T-cell receptor diversity are associated with enhanced response. Clinical trials will enable assessment of intrapleural vaccinia virus-expressing interleukin-2 therapy in patients with malignant pleural disease.

Early Distant Recurrence in Patients With Resected Stage I Lung Cancer: A Case Series of "Blast Metastasis".

BACKGROUND: The standard of care in the management of stage I non-small-cell lung cancer (NSCLC) has been anatomic lung resection with multistation lymph node sampling of ≥ 10 lymph nodes. The 5-year survival for NSCLC has ranged from 73% to 93% (for stage IB and stage IA, respectively) and will be more favorable for patients with fewer comorbidities and those with a higher state of premorbid functioning and who undergo surgical resection. Despite the positive prognosis for operable stage I NSCLC, a subset of patients will develop metastatic disease within as few as 12 months after resection. Using an institutional database, we have presented the data from 68 patients who had developed distant metastatic recurrence after resection of pathologic stage I NSCLC within 1 year after surgery. PATIENTS AND METHODS: A retrospective study was conducted of a prospectively maintained intuitional database. The final cohort included patients with pathologic stage I NSCLC who had undergone anatomic resection but had subsequently presented with multiple sites of distant recurrence within 1 year. The study period extended from 2003 to 2020. Patients with broad local recurrence or recurrence at a single distant site were excluded. Kaplan-Meier analysis was used to estimate the 5-year survival. RESULTS: A total of 2827 patients had undergone surgical resection for stage I NSCLC during the 17-year period and 68 met the criteria for inclusion. Most of the patients (n = 48) were smokers, and the dominant histologic type was adenocarcinoma (n = 37). After recurrence, 22 patients (33%) had undergone chemoradiotherapy and 19 (28%) had received chemotherapy alone. The mean and median overall survival were 23.7 and 14 months, respectively. The 5-year survival from recurrence and surgery were both 13.2%. CONCLUSIONS: Limited data are available on the risk factors for early metastasis after resected stage I NSCLC. The results from our cohort have demonstrated poor survival after recurrence. These data might be the basis for determining a phenotype for patients prone to early widespread metastasis despite seemingly curative surgical resection.

Node-Positive Segmentectomy for Non-Small-Cell Lung Cancer: Risk Factors and Outcomes.

BACKGROUND: Segmentectomy for well-selected early stage non-small-cell lung carcinoma (NSCLC) has been shown to have similar oncologic outcomes and survival to lobectomy. However, these data are based on the presumption that the disease is node negative. Few data exist regarding the risk factors for and the outcomes of patients with disease treated with segmentectomy that is found to be node positive. We sought to determine the risk factors for and outcomes of clinical stage I NSCLC patients who are treated with segmentectomy but are determined to be node positive. PATIENTS AND METHODS: We queried patients with clinical stage I NSCLC ≤ 3 cm within the National Cancer Data Base between 2004 and 2014 who were treated with segmentectomy or lobectomy and found to have positive nodes. Kaplan-Meier curves with log-rank tests were used to compare overall survival (OS) between segmentectomy and lobectomy. For comparison only, segmentectomy patients with pathologically node-negative disease were identified to determine predictors of node positivity after segmentectomy via multivariable logistic regression. RESULTS: A total of 4556 patients with node-positive disease were identified, comprising 115 segmentectomy patients and 4441 lobectomy patients. Multivariable analysis identified increasing tumor size, squamous-cell histology, and increasing number lymph nodes sampled as significant predictors of node positivity after segmentectomy. There was no difference in OS between segmentectomy and lobectomy, with 3-year OS rates of 66.3% and 68.1%, respectively (P = .723). CONCLUSION: There are discrete risk factors for discovering positive nodes after segmentectomy. Segmentectomy is associated with similar OS compared to lobectomy for clinical stage I NSCLC found to be node positive.