A New Functional Threshold for Minimally Invasive Lobectomy.

OBJECTIVE: To assess the performance of a lower predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1) or diffusion capacity of the lung for carbon monoxide (DLCO) (ppoFEV1/ppoDLCO) threshold to predict cardiopulmonary complications after minimally invasive surgery (MIS) lobectomy. SUMMARY BACKGROUND DATA: Although MIS is associated with better postoperative outcomes than open surgery, MIS uses risk-assessment algorithms developed for open surgery. Moreover, several different definitions of cardiopulmonary complications are used for assessment. METHODS: All patients who underwent MIS lobectomy for clinical stage I-II lung cancer from 2018 to 2022 at our institution were considered. The performance of a ppoFEV1/ppoDLCO threshold of <45% was compared against that of the current guideline threshold of <60%. Three different definitions of cardiopulmonary complications were compared: Society of Thoracic Surgeons (STS), European Society of Thoracic Surgeons (ESTS), and Berry et al. RESULTS: In 946 patients, the ppoFEV1/ppoDLCO threshold of <45% was associated with a higher proportion correctly classified (79% [95% CI, 76%-81%] vs. 65% [95% CI, 62%-68%]; P<0.001). The complication with the biggest difference in incidence between ppoFEV1/ppoDLCO of 45%-60% and >60% was prolonged air leak (33 [13%] vs. 34 [6%]; P<0.001). The predicted probability curves for cardiopulmonary complications were higher for the STS definition than for the ESTS or Berry definitions across ppoFEV1 and ppoDLCO values. CONCLUSIONS: The ppoFEV1/ppoDLCO threshold of <45% more accurately classified patients for cardiopulmonary complications after MIS lobectomy, emphasizing the need for updated risk-assessment guidelines for MIS lobectomy to optimize additional cardiopulmonary function evaluation.

A real-world assessment of stage I lung cancer through electronic nose technology.

INTRODUCTION: Electronic nose (E-nose) technology has demonstrated excellent sensitivity and specificity in the setting of lung cancer screening. However, the performance of E-nose specifically for early-stage tumors remains unclear. Therefore, the aim of our study was to assess the diagnostic performance of E-nose technology in clinical stage I lung cancer. METHODS: This Phase-IIc trial (NCT04734145) included patients diagnosed with a single ≥50% solid stage I nodule. Exhalates were prospectively collected from January 2020 to August 2023. Blinded bioengineers analyzed the exhalates, using E-nose technology to determine the probability of malignancy. Patients were stratified into 3 risk groups (low-risk, <0.2; moderate-risk, ≥0.2 to 0.7; high-risk, ≥0.7). The primary outcome was the diagnostic performance of E-nose versus histopathology (accuracy and F1 score). The secondary outcome was the clinical performance of the E-nose versus clinicoradiological prediction models. RESULTS: Based on the predefined cut-off (<0.20), E-nose agreed with histopathological results in 86% of cases, achieving an F1 score of 92.5%, based on 86 true positives, 2 false negatives, and 12 false positives (n=100). Compared with Swensen and Brock models, E-nose would refer fewer patients with malignant nodules to observation (Low-risk: 2 vs. 9 and 11; respectively; p=0.028 and p=0.011) and more patients with malignant nodules to treatment without biopsy (High-risk: 27 vs. 19 and 6; respectively; p=0.057 and p<0.001). CONCLUSIONS: In the setting of clinical stage I lung cancer, E-nose has good agreement with histopathology. Accordingly, E-nose technology can be used in addition to imaging or as part of a "multiomics" platform.

Treatment of esophageal adenocarcinoma in patients with a history of bariatric surgery.

BACKGROUND: The relationship among obesity, bariatric surgery, and esophageal adenocarcinoma (EAC) is complex, given that some bariatric procedures are thought to be associated with increased incidence of reflux and Barrett's esophagus. Previous bariatric surgery may complicate the use of the stomach as a conduit for esophagectomy. In this study, we presented our experience with patients who developed EAC after bariatric surgery and described the challenges encountered and the techniques used. METHODS: We conducted a retrospective review of our institutional database to identify all patients at our institution who were treated for EAC after previously undergoing bariatric surgery. RESULTS: In total, 19 patients underwent resection with curative intent for EAC after bariatric surgery, including 10 patients who underwent sleeve gastrectomy. The median age at diagnosis of EAC was 63 years; patients who underwent sleeve gastrectomy were younger (median age, 56 years). The median time from bariatric surgery to EAC was 7 years. Most patients had a body mass index (BMI) score of >30 kg/m2 at the time of diagnosis of EAC; approximately 40% had class III obesity (BMI score > 40 kg/m2). Six patients (32%) had known Barrett's esophagus before undergoing a reflux-increasing bariatric procedure. Sleeve gastrectomy patients underwent esophagectomy with gastric conduit, colonic interposition, or esophagojejunostomy. Only 1 patient had an anastomotic leak (after esophagojejunostomy). CONCLUSION: Endoscopy should be required both before (for treatment selection) and after all bariatric surgical procedures. Resection of EAC after bariatric surgery requires a highly individualized approach but is safe and feasible.

Lung resection after initial nonoperative treatment for non-small cell lung cancer.

OBJECTIVES: The study objectives were to assess the outcomes of lung resection in patients with non-small cell lung cancer previously treated with nonoperative treatment and to identify prognostic factors associated with survival. METHODS: Patients who underwent surgery (2010-2022) after initial nonoperative treatment at a single institution were identified from a prospectively maintained database. Exclusion criteria included metachronous cancer, planned neoadjuvant therapy, and surgery for diagnostic or palliative indications. Cox models were constructed for overall survival and event-free survival. Survival of patients with stage IV disease was compared with survival of a nonstudy cohort who did not undergo surgery. RESULTS: In total, 120 patients met the inclusion criteria. Initial clinical stage was early stage in 16%, locoregionally advanced in 25%, and metastatic in 59% of patients. The indication for surgery was recurrence in 18%, local persistent disease in 23%, oligoprogression in 22%, and local control of oligometastatic disease in 38% of patients. Grade 3 or greater complications occurred in 5% of patients; 90-day mortality was 3%. Three-year event-free survival and overall survival were 39% and 73%, respectively. Male sex and lymphovascular invasion were associated with shorter event-free survival and overall survival; younger age and prior radiation therapy were associated with shorter overall survival. Patients with stage IV disease who received salvage lung resection had better overall survival than similar patients who received subsequent systemic therapy and no surgery. CONCLUSIONS: In this selected, heterogeneous population, lung resection after initial nonoperative treatment for non-small cell lung cancer was safe. Surgery as local consolidative therapy was associated with encouraging outcomes and should be considered for these patients.

Biologic versus synthetic prosthesis for chest wall reconstruction: a matched analysis.

OBJECTIVES: The aim of this study was to compare postoperative outcomes between biologic and synthetic reconstructions after chest wall resection in a matched cohort. METHODS: All patients who underwent reconstruction after full-thickness chest wall resection from 2000 to 2022 were reviewed and stratified by prosthesis type (biologic or synthetic). Biologic prostheses were of biologic origin or were fully absorbable and incorporable. Integer matching was performed to reduce confounding. The study end point was surgical site complications requiring reoperation. Multivariable analysis was performed to identify associated risk factors. RESULTS: In total, 438 patients underwent prosthetic chest wall reconstruction (unmatched: biologic, n = 49; synthetic, n = 389; matched: biologic, n = 46; synthetic, n = 46). After matching, the median (interquartile range) defect size was 83 cm2 (50-142) for the biologic group and 90 cm2 (48-146) for the synthetic group (P = 0.97). Myocutaneous flaps were used in 33% of biologic reconstructions (n = 15) and 33% of synthetic reconstructions (n = 15) in the matched cohort (P = 0.99). The incidence of surgical site complications requiring reoperation was not significantly different between biologic and synthetic reconstructions in the unmatched (3 [6%] vs 29 [7%]; P = 0.99) and matched (2 [4%] vs 4 [9%]; P = 0.68) cohorts. On the multivariable analysis, operative time [adjusted odds ratio (aOR) = 1.01, 95% confidence interval (CI), 1.00-1.01; P = 0.006] and operative blood loss (aOR = 1.00, 95% CI, 1.00-1.00]; P = 0.012) were associated with higher rates of surgical site complications requiring reoperation; microvascular free flaps (aOR = 0.03, 95% CI, 0.00-0.42; P = 0.024) were associated with lower rates. CONCLUSIONS: The incidence of surgical site complications requiring reoperation was not significantly different between biologic and synthetic prostheses in chest wall reconstructions.

Superior sulcus non-small cell lung cancers (Pancoast tumors): Current outcomes after multidisciplinary management.

OBJECTIVE: Despite neoadjuvant chemoradiotherapy, Pancoast tumors still present surgical and oncologic challenges. To optimize outcomes, we used a multidisciplinary care paradigm with medical and radiation oncology, and involvement of spine neurosurgery for most T3 and all T4 tumors. Spine neurosurgery permitted resection of transverse process for T3 and vertebral body resection for T4 tumors. METHODS: Retrospective analysis of single institution, prospective database of patients undergoing resection for cT3 4M0 Pancoast tumors. Patients were grouped as cT3 with combined resection with spine neurosurgery (T3 Neuro), cT3 without spine neurosurgery (T3 NoNeuro), and cT4. Overall survival, progression-free survival were analyzed by Kaplan-Meier and compared between groups using log-rank test. Cumulative incidence of local-regional and distant recurrence were compared using Gray test. P value <.05 was considered significant. RESULTS: From 2000 to 2021, 155 patients underwent surgery: median age was 58 years, and 81 were (52%) men. Most patients received neoadjuvant platinum-based neoadjuvant chemoradiotherapy (n = 127 [82%]). Operations were 48 cT3 Neuro, 41 cT3 NoNeuro, 66 cT4. R0 resection was achieved in 49 (94%) cT3 NoNeuro, 35 (85%) cT3 Neuro, and 57 (86%) cT4 patients (P = .4). Complete or major pathologic response occurred in 71 (55%) patients. Lower local-regional cumulative incidence was seen in cT3 Neuro versus cT3 NoNeuro (P = .05) and after major pathologic response. Overall survival and progression-free survival were associated with complete response, pathologic stage, and nodal status but not cT category. CONCLUSIONS: This treatment paradigm was associated with a high frequency of R0 resection, complete response, and major pathologic response. cT3 and cT4 tumors had similar outcomes. Novel therapies are needed to improve complete response.

Prognostic value of circumferential radial margin involvement in esophagectomy for esophageal cancer: a case series.

BACKGROUND: Residual tumor at the proximal or distal margin after esophagectomy is associated with worse survival outcomes; however, the significance of the circumferential resection margin (CRM) remains controversial. In this study, we sought to evaluate the prognostic significance of the CRM in patients with esophageal cancer undergoing resection. MATERIALS AND METHODS: We identified patients who underwent esophagectomy for pathologic T3 esophageal cancer from 2000 to 2019. Patients were divided into three groups: CRM- (residual tumor >1 mm from the CRM), CRM-close (residual tumor >0 to 1 mm from the CRM), and CRM+ (residual tumor at the surgical CRM). CRM was also categorized and analyzed per the Royal College of Pathologists (RCP) and College of American Pathologists (CAP) classifications. RESULTS: Of the 519 patients included, 351 (68%) had CRM-, 132 (25%) had CRM-close, and 36 (7%) had CRM+. CRM+ was associated with shorter disease-free survival [DFS; CRM+ vs. CRM-: hazard ratio (HR), 1.53 [95% CI, 1.03-2.28]; P =0.034] and overall survival (OS; CRM+ vs. CRM-: HR, 1.97 [95% CI, 1.32-2.95]; P <0.001). Survival was not significantly different between CRM-close and CRM-. After adjustment for potential confounders, CAP+ was associated with poor oncologic outcomes (CAP+ vs. CAP-: DFS: HR, 1.47 [95% CI, 1.00-2.17]; P =0.050; OS: HR, 1.93 [95% CI, 1.30-2.86]; P =0.001); RCP+ was not (RCP+ vs. RCP-: DFS: HR, 1.21 [95% CI, 0.97-1.52]; P =0.10; OS: HR, 1.21 [95% CI, 0.96-1.54]; P =0.11). CONCLUSION: CRM status has critical prognostic significance for patients undergoing esophagectomy: CRM+ was associated with worse outcomes, and outcomes between CRM-close and CRM- were similar.

A Prospective Clinical Trial to Evaluate Mesothelin as a Biomarker for the Clinical Management of Patients With Esophageal Adenocarcinoma.

OBJECTIVE: To investigate the utility of serum soluble mesothelin-related peptide (SMRP) and tumor mesothelin expression in the management of esophageal adenocarcinoma (ADC). BACKGROUND: Clinical management of esophageal ADC is limited by a lack of accurate evaluation of tumor burden, treatment response, and disease recurrence. Our retrospective data showed that tumor mesothelin and its serum correlate, SMRP, are overexpressed and associated with poor outcomes in patients with esophageal ADC. METHODS: Serum SMRP and tumoral mesothelin expression from 101 patients with locally advanced esophageal ADC were analyzed before induction chemoradiation (pretreatment) and at the time of resection (posttreatment), as a biomarker for treatment response, disease recurrence, and overall survival (OS). RESULTS: Pre and posttreatment serum SMRP was ≥1 nM in 49% and 53%, and pre and post-treatment tumor mesothelin expression was >25% in 35% and 46% of patients, respectively. Pretreatment serum SMRP was not significantly associated with tumor stage ( P = 0.9), treatment response (radiologic response, P = 0.4; pathologic response, P = 0.7), or recurrence ( P =0.229). Pretreatment tumor mesothelin expression was associated with OS (hazard ratio: 2.08; 95% CI: 1.14-3.79; P = 0.017) but had no statistically significant association with recurrence ( P = 0.9). Three-year OS of patients with pretreatment tumor mesothelin expression of ≤25% was 78% (95% CI: 68%-89%), compared with 49% (95% CI: 35%-70%) among those with >25%. CONCLUSIONS: Pretreatment tumor mesothelin expression is prognostic of OS for patients with locally advanced esophageal ADC, whereas serum SMRP is not a reliable biomarker for monitoring treatment response or recurrence.

The contribution of microvascular free flaps and pedicled flaps to successful chest wall surgery.

OBJECTIVE: Pedicled flaps (PFs) have historically served as the preferred option for reconstruction of large chest wall defects. More recently, the indications for microvascular-free flaps (MVFFs) have increased, particularly for defects in which PFs are inadequate or unavailable. We sought to compare oncologic and surgical outcomes between MVFFs and PFs in reconstructions of full-thickness chest wall defects. METHODS: We retrospectively identified all patients who underwent chest wall resection at our institution from 2000 to 2022. Patients were stratified by flap reconstruction. End points were defect size, rate of complete resection, rate of local recurrence, and postoperative outcomes. Multivariable analysis was performed to identify factors associated with complications at 30 days. RESULTS: In total, 536 patients underwent chest wall resection, of whom 133 had flap reconstruction (MVFF, n = 28; PF, n = 105). The median (interquartile range) covered defect size was 172 cm2 (100-216 cm2) for patients receiving MVFF versus 109 cm2 (75-148 cm2) for patients receiving PF (P = .004). The rate of R0 resection was high in both groups (MVFF, 93% [n = 26]; PF, 86% [n = 90]; P = .5). The rate of local recurrence was 4% in MVFF patients (n = 1) versus 12% in PF patients (n = 13, P = .3). Postoperative complications were not statistically different between groups (odds ratio for PF, 1.37; 95% confidence interval, 0.39-5.14]; P = .6). Operative time >400 minutes was associated with 30-day complications (odds ratio, 3.22; 95% confidence interval, 1.10-9.93; P = .033). CONCLUSIONS: Patients with MVFFs had larger defects, a high rate of complete resection, and a low rate of local recurrence. MVFFs are a valid option for chest wall reconstructions.

Waiting to Operate: The Risk of Salvage Esophagectomy.

OBJECTIVE: To assess postoperative morbidity, disease-free survival (DFS), and overall survival (OS) in patients treated with salvage esophagectomy (SE). BACKGROUND DATA: A shift toward a "surgery as needed" approach for esophageal cancer has emerged, potentially resulting in delayed esophagectomy. METHODS: We identified patients with clinical stage I-III esophageal adenocarcinoma or squamous cell carcinoma who underwent chemoradiation followed by esophagectomy from 2001 to 2019. SE was defined as esophagectomy performed >90 days after chemoradiation ("for time") and esophagectomy performed for recurrence after curative-intent chemoradiation ("for recurrence"). The odds of postoperative serious complications were assessed by multivariable logistic regression. The relationship between SE and OS and DFS were quantified using Cox regression models. RESULTS: Of 1137 patients identified, 173 (15%) underwent SE. Of those, 61 (35%) underwent SE for recurrence, and 112 (65%) underwent SE for time. The odds of experiencing any serious complication [odds ratio, 2.10 (95% CI, 1.37-3.20); P =0.001] or serious pulmonary complication [odds ratio, 2.11 (95% CI, 1.31-3.42); P =0.002] were 2-fold higher for SE patients; SE patients had a 1.5-fold higher hazard of death [hazard ratio, 1.56 (95% CI, 1.25-1.94); P <0.0001] and postoperative recurrence [hazard ratio, 1.43 (95% CI, 1.16-1.77); P =0.001]. Five-year OS for nonsalvage esophagectomy was 45% [(95% CI, 41.6%-48.6%) versus 26.5% (95% CI, 20.2%-34.8%) for SE (log-rank P <0.001)]. Five-year OS for SE for time was 27.1% [(95% CI, 19.5%-37.5%) versus 25.2% (95% CI, 15.3%-41.5%) for SE for recurrence ( P =0.611)]. CONCLUSIONS: SE is associated with a higher risk of serious postoperative complications and shorter DFS and OS.

Clinicopathologic outcomes of preoperative targeted therapy in patients with clinical stage I to III non-small cell lung cancer.

OBJECTIVE: Targeted therapy improves outcomes in patients with advanced-stage non-small cell lung cancer (NSCLC) and in the adjuvant setting, but data on its use before surgery are limited. We sought to investigate the safety and feasibility of preoperative targeted therapy in patients with operable NSCLC. METHODS: We retrospectively reviewed 51 patients with clinical stage I to III NSCLC who received targeted therapy, alone or in combination with chemotherapy, before surgical resection with curative intent, treated from 2004 to 2021. The primary outcome was the safety and feasibility of preoperative targeted therapy; secondary outcomes included objective response rate, major pathologic response (defined as ≤10% viable tumor) rate, recurrence-free survival (RFS), and overall survival. RESULTS: Of the 51 patients included, 46 had an activating epidermal growth factor receptor gene alteration and 5 had an anaplastic lymphoma kinase fusion. Overall, 37 of 46 evaluable patients experienced at least 1 adverse event before surgery; however, only 3 patients experienced a grade 3 or 4 event. The objective response rate was 38% (17/45) for all evaluable patients and 44% (14/32) for patients with clinical stage II or III disease. The major pathologic response rate was 20% (9/44); 2 patients had a complete pathologic response. Median RFS was 3.8 years (95% CI, 2.8 to not reached). Targeted therapy alone was associated with better RFS than combination therapy (P = .009) in patients with clinical stage II or III disease. CONCLUSIONS: Preoperative targeted therapy was well tolerated and associated with good outcomes, with or without induction chemotherapy. In addition, radiographic response and pathologic response were strongly correlated.

Incidence and management of esophageal cancer recurrence to regional lymph nodes after curative esophagectomy.

Up to 50% of patients treated with curative esophagectomy for esophageal cancer will develop recurrence, contributing to the dismal survival associated with this disease. Regional recurrence may represent disease that is not yet widely metastatic and may therefore be amenable to more-aggressive treatment. We sought to assess all patients treated with curative esophagectomy for esophageal cancer who developed regional recurrence. We retrospectively identified all patients who underwent esophagectomy for esophageal adenocarcinoma and esophageal squamous cell carcinoma at a single institution from January 2000 to August 2019. In total, 1626 patients were included in the study cohort. As of June 2022, 595 patients had disease recurrence, which was distant or systemic in 435 patients (27%), regional in 125 (7.7%) and local in 35 (2.2%). On multivariable analysis, neoadjuvant chemoradiation with a total radiation dose <45 Gy (hazard ratio [HR], 3.5 [95% CI, 1.7-7.3]; P = .001), pathologic node-positive disease (HR, 1.9 [95% CI, 1.3-3.0]; P = .003) and lymphovascular invasion (HR, 1.6 [95% CI, 1.0-2.5]; P = .049) were predictors of isolated nodal recurrence, whereas increasing age (HR, 0.97 [95% CI, 0.96-0.99]; P = .001) and increasing number of excised lymph nodes (HR, 0.98 [95% CI, 0.95-1.00]; P = .021) were independently associated with decreased risk of regional recurrence. Patients treated with a combination of local and systemic therapies had better survival outcomes than patients treated with systemic therapy alone (P < .001). In patients with recurrence of esophageal cancer limited to regional lymph nodes, salvage treatment may be possible. Higher radiation doses and more-extensive lymphadenectomy may reduce the risk of regional recurrence.

Translating Telemedicine to Thoracic Surgical Oncological Care: Performance Analysis and Patient Perceptions During the COVID-19 Pandemic.

OBJECTIVE: The objective is to determine how the COVID-19 pandemic affected care for patients undergoing thoracic surgery for cancer. BACKGROUND: The COVID-19 pandemic accelerated the adoption of telemedicine. METHODS: Characteristics and outcomes of new patients seen between March 1 and June 30, 2019, and the same period in 2020 were compared. Patients who did not undergo surgery were excluded. Patients who had a telemedicine visit (new and established) in the 2020 period were asked to complete a survey. RESULTS: In total, 624 new patients were seen in 2019 versus 299 in 2020 (52% reduction); 45% of patients (n=136) in 2020 were seen via telemedicine. There was no statistically significant difference in time to surgery, pathological upstaging, or postsurgical complications between 2019 and 2020. In total, 1085 patients (new and established) had a telemedicine visit in 2020; 239 (22%) completed the survey. A majority replied that telemedicine was equivalent to in-person care (77%), did not impair care quality (84%), resulted in less stress (69%) and shorter waits (86%), was more convenient (92%), saved money and commuting time (93%), and expanded who could attend visits (91%). Some patients regretted the loss of human interaction (71%). Most would opt for telemedicine after the pandemic (60%), although some would prefer in-person format for initial visits (55%) and visits with complex discussions (49%). Only 21% were uncomfortable with the telemedicine technology. CONCLUSIONS: Telemedicine enabled cancer care to continue during the COVID-19 pandemic without delays in surgery, cancer progression, or worsened postoperative morbidity and was generally well received.

Distinct Differences in Gastroesophageal Junction and Gastric Adenocarcinoma in 2194 Patients: In Memory of Rebecca A. Carr, February 24, 1988-January 19, 2021.

OBJECTIVE: We sought to compare gastroesophageal junction (GEJ) cancer and gastric cancer (GC) and identify clinicopathological and oncological differences. SUMMARY BACKGROUND DATA: GEJ cancer and GC are frequently studied together. Although the treatment approach for each often differs, clinico-pathological and oncological differences between the 2 have not been fully evaluated. METHODS: We retrospectively identified patients with GEJ cancer or GC who underwent R0 resection at our center between January 2000 and December 2016. Clinicopathological characteristics, disease-specific survival (DSS), and site of first recurrence were compared. RESULTS: In total, 2194 patients were analyzed: 1060 (48.3%) with GEJ cancer and 1134 (51.7%) with GC. Patients with GEJ cancer were younger (64 vs 66 years; P < 0.001), more often received neoadjuvant treatment (70.9% vs 30.2%; P < 0.001), and had lower pathological T and N status. Five-year DSS was 62.2% in patients with GEJ cancer and 74.6% in patients with GC ( P < 0.001). After adjustment for clinicopathological factors, DSS remained worse in patients with GEJ cancer (hazard ratio, 1.78; 95% confidence interval, 1.40-2.26; P < 0.001). The cumulative incidence of recurrence was approximately 10% higher in patients with GEJ cancer ( P < 0.001). The site of first recurrence was more likely to be hematogenous in patients with GEJ cancer (60.1% vs 31.4%; P < 0.001) and peritoneal in patients with GC (52.9% vs 12.5%; P < 0.001). CONCLUSIONS: GEJ adenocarcinoma is more aggressive, with a higher incidence of recurrence and worse DSS, compared with gastric adenocarcinoma. Distinct differences between GEJ cancer and GC, especially in patterns of recurrence, may affect evaluation of optimal treatment strategies.

Induction FOLFOX and PET-Directed Chemoradiation for Locally Advanced Esophageal Adenocarcinoma.

OBJECTIVE: To compare the efficacy and safety of induction FOLFOX followed by PET-directed nCRT, induction CP followed by PET-directed nCRT, and nCRT with CP alone in patients with EAC. SUMMARY OF BACKGROUND DATA: nCRT with CP is a standard treatment for locally advanced EAC. The results of cancer and leukemia group B 80803 support the use of induction chemotherapy followed by PET-directed chemo-radiation therapy. METHODS: We retrospectively identified all patients with EAC who underwent the treatments above followed by esophagectomy. We assessed incidences of pathologic complete response (pCR), near-pCR (ypN0 with ≥90% response), and surgical complications between treatment groups using Fisher exact test and logistic regression; disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and evaluated using the log-rank test and extended Cox regression. RESULTS: In total, 451 patients were included: 309 (69%) received induction chemotherapy before nCRT (FOLFOX, n = 70; CP, n = 239); 142 (31%) received nCRT with CP. Rates of pCR (33% vs. 16%, P = 0.004), near-pCR (57% vs. 33%, P < 0.001), and 2-year DFS (68% vs. 50%, P = 0.01) were higher in the induction FOLFOX group than in the induction CP group. Similarly, the rate of near-pCR (57% vs. 42%, P = 0.04) and 2-year DFS (68% vs. 44%, P < 0.001) were significantly higher in the FOLFOX group than in the no-induction group. CONCLUSIONS: Induction FOLFOX followed by PET-directed nCRT may result in better histopathologic response rates and DFS than either induction CP plus PET-directed nCRT or nCRT with CP alone.

Operative Time is Associated With Postoperative Complications After Pulmonary Lobectomy.

OBJECTIVE: To investigate the association between operative time and postoperative outcomes. BACKGROUND: The association between operative time and morbidity after pulmonary lobectomy has not been characterized fully. METHODS: Patients who underwent pulmonary lobectomy for primary lung cancer at our institution from 2010 to 2018 were reviewed. Exclusion criteria included clinical stage ≥IIb disease, conversion to thoracotomy, and previous ipsilateral lung treatment. Operative time was measured from incision to closure. Relationships between operative time and outcomes were quantified using multivariable mixed-effects models with surgeon-level random effects. RESULTS: In total, 1651 patients were included. The median age was 68 years (interquartile range, 61-74), and 63% of patients were women. Median operative time was 3.2 hours (interquartile range, 2.7-3.8) for all cases, 3.0 hours for open procedures, 3.3 hours for video-assisted thoracoscopies, and 3.3 hours for robotic procedures ( P =0.0002). Overall, 488 patients (30%) experienced a complication; 77 patients (5%) had a major complication (grade ≥3), and 5 patients (0.3%) died within 30 days of discharge. On multivariable analysis, operative time was associated with higher odds of any complication [odds ratio per hour, 1.37; 95% confidence interval (CI), 1.20-1.57; P <0.0001] and major complication (odds ratio per hour, 1.41; 95% CI, 1.21-1.64; P <0.0001). Operative time was also associated with longer hospital length of stay (ß, 1.09; 95% CI, 1.04-1.14; P =0.001). CONCLUSIONS: Longer operative time was associated with worse outcomes in patients who underwent lobectomy. Operative time is a potential risk factor to consider in the perioperative phase.

Brief Report: Contralateral Lobectomy for Second Primary NSCLC: Perioperative and Long-Term Outcomes.

Introduction: Anatomical resection-often by lobectomy-is the standard of care for patients with early stage NSCLC. With increased diagnosis, survival, and prevalence of persons with early stage NSCLC, the incidence of second primary NSCLC, and consequently, the need for contralateral lobectomy for a metachronous cancer, is increasing. Perioperative outcomes after contralateral lobectomy are unknown. Methods: Among patients who underwent contralateral lobectomy for second primary NSCLC during 1995 to 2020, we evaluated 90-day mortality and major morbidity (Clavien-Dindo grades 3-5) rates and their association with clinicopathologic variables, including the year of contralateral lobectomy and duration between lobectomies. Results: A total of 98 patients underwent contralateral lobectomy for second primary NSCLC; 51 during an early time period (1995-2009) and 47 from a late time period (2010-2020). There were five mortalities and 23 patients with major morbidities after contralateral lobectomy; both rates decreased in 2010 to 2020 compared with 1995 to 2009 (mortality 10%-0%, major morbidity 35%-11%). Major morbidity was associated with an interval of less than 1 year between lobectomies, a diffusing capacity of the lung for carbon monoxide <80%, and right lower lobe resections. Mortality was associated with squamous cell carcinoma. Patients who underwent contralateral lobectomy for stage I NSCLC had 74% (95% confidence interval: 64%-85%) 3-year overall survival and 15% (95% confidence interval: 6.5%-24%) 3-year lung cancer cumulative incidence of death. Conclusions: Contralateral lobectomy for second primary early stage NSCLC was associated with poor outcomes before 2010. Since 2010, perioperative and long-term outcomes of contralateral lobectomy have been comparable with reported outcomes after unilateral lobectomy.

Patterns and influence of nodal metastases after neoadjuvant chemoradiation and R0 resection in esophageal adenocarcinoma.

OBJECTIVE: Little is known about the pattern of nodal metastases in patients with esophageal adenocarcinoma who have received neoadjuvant chemoradiation and undergone surgery. We sought to assess this pattern and evaluate its association with prognosis. METHODS: All patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiation and R0 esophagectomy between 2010 and 2018 at our institution were included (n = 537). The primary objective was to evaluate the association of sites of lymph node metastases with disease-free survival. The number of nodal stations and individual sites of nodal metastases were evaluated first in univariable then in separate multivariable Cox regression models adjusted for clinical factors. RESULTS: Of 537 patients, 193 (36%) had pathologic nodal metastases at the time of surgery; 153 (28%) had single-station disease, 32 (6.0%) had 2-station disease, and 8 (1.5%) had 3-station disease. The majority of patients with multiple positive nodal stations had positive nodes in the paraesophageal (93%) and/or left gastric stations (60%). Multivariable models controlling for clinical factors showed that an increasing number of positive nodal stations (hazard ratio, 1.59; 95% CI, 1.35-1.84; P < .01)-in particular, the subcarinal (hazard ratio, 2.78; 95% CI, 1.54-5.03; P < .01) and paraesophageal stations (hazard ratio, 2.0; 95% CI, 1.58-2.54; P < .01)-was associated with increased risk of recurrence. CONCLUSIONS: One-third of patients who have undergone R0 resection for esophageal adenocarcinoma following induction chemoradiation therapy have metastatic lymph nodes. An increasing number of nodal stations, particularly paraesophageal and subcarinal metastases, were associated with increased risk of recurrence.

Propensity-matched Analysis Demonstrates Long-term Risk of Respiratory and Cardiac Mortality After Pneumonectomy Compared With Lobectomy for Lung Cancer.

OBJECTIVE: We sought to quantify and characterize long-term consequences of pneumonectomy, with particular attention to nononcologic mortality. SUMMARY OF BACKGROUND DATA: Pneumonectomy is associated with profound changes in cardiopulmonary physiology. Studies of long-term outcomes after pneumonectomy typically report generalized measures, such as disease-free and overall survival. METHODS: Patients undergoing lobectomy or pneumonectomy for lung cancer at our institution from 2000 to 2018 were reviewed. Propensity-score matching was performed for 12 clinicopathologic factors. Ninety-day complications and deaths were compared. Five-year cumulative incidence of oncologic and nononcologic mortality were compared using competing risks approaches. RESULTS: From 3339 lobectomy and 355 pneumonectomy patients identified, we derived 318 matched pairs. At 90 days, rates of overall complications were similar (46% for pneumonectomy vs 43% for lobectomy; P = 0.40), but rates of major complications (21% vs 13%; P = 0.005) and deaths (6.9% vs 1.9%; P = 0.002) were higher the pneumonectomy cohort. The cumulative incidence of oncologic mortality was not significantly different between cohorts (P = 0.9584). However, the cumulative incidence of nononcologic mortality was substantially higher in the pneumonectomy cohort for both date of surgery and 1-year landmark analyses (P < 0.0001 and P = 0.0002, respectively). Forty-five pneumonectomy patients (18%) died of nononcologic causes 1-5 years after surgery; pneumonia (n = 21) and myocardial infarction (n = 10) were the most common causes. In pneumonectomy patients, preexisting cardiac comorbidity and low diffusion capacity of the lungs for carbon monoxide were predictive of nononcologic mortality. CONCLUSIONS: Compared to lobectomy, excess mortality after pneumonectomy extends beyond 1 year and is driven primarily by nononcologic causes. Pneumonectomy patients require lifelong monitoring and may benefit from expeditious assessment and intervention at the initial signs of illness.