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.

Real-world Decision-making Process for Stereotactic Body Radiotherapy Versus Minimally Invasive Surgery in Early-stage Lung Cancer Patients.

OBJECTIVE: To generate a prediction model for selection of treatment modality for early-stage non-small cell lung cancer (NSCLC). SUMMARY BACKGROUND DATA: Stereotactic body radiotherapy (SBRT) and minimally invasive surgery (MIS) are used in the local treatment of early-stage NSCLC. However, selection of patients for either SBRT or MIS remains challenging, due to the multitude of factors influencing the decision-making process. METHODS: We analyzed 1291 patients with clinical stage I NSCLC treated with intended MIS or SBRT from January 2020 to July 2023. A prediction model for selection for SBRT was created based on multivariable logistic regression analysis. The receiver operating characteristic curve analysis stratified the cohort into 3 treatment-related risk categories. Post-procedural outcomes, recurrence and overall survival (OS) were investigated to assess the performance of the model. RESULTS: In total, 1116 patients underwent MIS and 175 SBRT. The prediction model included age, performance status, previous pulmonary resection, MSK-Frailty score, FEV1 and DLCO, and demonstrated an area-under-the-curve of 0.908 (95%CI, 0.876-0.938). Based on the probability scores (n=1197), patients were stratified into a low-risk (MIS, n=970 and SBRT, n=28), intermediate-risk (MIS, n=96 and SBRT, n=53) and high-risk category (MIS, n=10 and SBRT, n=40). Treatment modality was not associated with OS (HR of SBRT, 1.67 [95%CI: 0.80-3.48]; P=0.20). CONCLUSION: Clinical expertise can be translated into a robust predictive model, guiding the selection of stage I NSCLC patients for MIS versus SBRT and effectively categorizing them into three distinct risk groups. Patients in the intermediate category could benefit most from multidisciplinary evaluation.

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.

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.

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.

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.

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.

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.

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.

A More Extensive Lymphadenectomy Enhances Survival After Neoadjuvant Chemoradiotherapy in Locally Advanced Esophageal Adenocarcinoma.

OBJECTIVE: We sought to determine the extent of lymphadenectomy that optimizes staging and survival in patients with locally advanced EAC treated with neoadjuvant chemoradiotherapy followed by esophagectomy. SUMMARY OF BACKGROUND DATA: Several studies have found that a more extensive lymphadenectomy leads to better disease-specific survival in patients treated with surgery alone. Few studies, however, have investigated whether this association exists for patients treated with neoadjuvant chemoradiotherapy. METHODS: We examined our prospective database and identified patients with EAC treated with neoadjuvant chemoradiotherapy followed by esophagectomy between 1995 and 2017. Overall survival (OS) and DFS were estimated using Kaplan-Meier methods, and a multivariable Cox proportional hazards model was used to identify independent predictors of OS and DFS. The relationship between the total number of nodes removed and 5-year OS or DFS was plotted using restricted cubic spline functions. RESULTS: In total, 778 patients met the inclusion criteria. The median number of excised nodes was 21 (interquartile range, 16-27). A lower number of excised lymph nodes was independently associated with worse OS and DFS (OS: hazard ratio, 0.98; confidence interval, 0.97-1.00; P = 0.013; DFS: hazard ratio, 0.99; confidence interval, 0.98-1.00; P = 0.028). Removing 25 to 30 lymph nodes was associated with a 10% risk of missing a positive lymph node. Both OS and DFS improved with up to 20 to 25 lymph nodes removed, regardless of treatment response. CONCLUSIONS: The optimal extent of lymphadenectomy to enhance both staging and survival after chemoradiotherapy, regardless of treatment response, is approximately 25 lymph nodes.

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.

Survival After Trimodality Therapy in Patients With Locally Advanced Esophagogastric Adenocarcinoma: Does Only a Complete Pathologic Response Matter?

OBJECTIVE: To evaluate whether pCR exclusively defines major pathologic response to treatment with improved survival. SUMMARY BACKGROUND DATA: pCR after trimodality therapy for EAC is infrequent but associated with improved prognosis. Yet most clinical trials and correlative studies designate pCR as the primary endpoint. METHODS: We analyzed our prospectively maintained database for patients who underwent trimodality therapy for locally advanced esophageal adeno-carcinoma between 1995 and 2017. Overall survival (OS) was examined by percentage TR in the primary tumor bed and pathologic nodal stage (ypN0) using Kaplan-Meier plots. Optimal thresholds of TR for differentiating patients in terms of OS were investigated with descriptive plots using restricted cubic spline functions; associations were quantified using Cox multivariable analysis. RESULTS: Among 788 patients, median follow-up was 37.5 months (range, 0.4210.6); median OS was 48.3 months (95% CI, 42.2-58.8). Absence of residual nodal disease was independently associated with improved survival ( P < 0.001). Survival curves for 90% to 99% TR and 100% TR were similar, and a change in probability of improved OS was observed at 90% TR. On multivariable analysis, combining 90% to 99% and 100% TR was independently associated with improved OS, compared with 50% to 89% and <50% TR. CONCLUSIONS: ypN0 status is the strongest indicator of major pathologic response to trimodality therapy, in addition to >90% TR in the primary tumor bed. These findings may allow the definition of major pathologic response to be expanded, from pCR to > 90% TR and ypN0. This has meaningful implications for future clinical trials and correlative studies.

Outcomes After Multidisciplinary Management of Primary Mediastinal Germ Cell Tumors.

OBJECTIVE: We examined management strategies, overall survival (OS), and progression-free survival (PFS) among patients with PMNSGCTs undergoing resection and multidisciplinary management at a high-volume institution. SUMMARY OF BACKGROUND DATA: Outcomes after resection of PMNSGCTs are not well-characterized, with limited data on factors associated with survival. METHODS: We reviewed patients with PMNSGCT who underwent resection between 1980 and 2019. Median follow-up was 3.4 years. Preoperative therapy (including use of bleomycin), surgical management, recurrence, and survival were examined. Factors associated with survival were analyzed using Cox regression. RESULTS: In total, 113 patients were included [median age, 28 years (range, 16-65)]. Preoperative serum tumor markers (STMs) normalized/decreased in 74% of patients. Pathology included necrosis only (25%), teratoma +/- necrosis (20%), viable nonteratomatous germ cell tumor +/- teratoma (41%), and secondary somatic-type malignancy +/- teratoma (20%). Bleomycin chemotherapy was not associated with pulmonary complications or 90-day mortality. Patients receiving second-line chemotherapy followed by resection had significantly worse OS and PFS than patients receiving first-line chemotherapy followed by resection. On multivariable analysis, R1/R2 resection (HR, 3.92; P < 0.001) and increasing postoperative STMs (HR, 4.98; P < 0.001) were associated with shorter PFS; necrosis on pathology (HR, 0.42, P = 0.043) was associated with longer PFS. CONCLUSIONS: In patients with PMNSGCT undergoing resection, completeness of resection, postoperative pathology, and postoperative STMs were associated with PFS. Induction bleomycin was not associated with pulmonary complications or mortality in patients undergoing resection. Patients undergoing second-line chemotherapy followed by resection have a poor prognosis, with long-term survival of 22%.

Use of vasopressors during esophagectomy is not associated with increased risk of anastomotic leak.

Vasopressor use during esophagectomy has been reported to increase the risk of postoperative anastomotic leak and associated morbidity. We sought to assess the association between vasopressor use and fluid (crystalloid and colloid) administration and anastomotic leak following open esophagectomy. Patients who underwent open Ivor Lewis esophagectomy were identified from a prospective institutional database. The primary outcome was postoperative anastomotic leak (any grade) and analyzed using logistic regression models. Postoperative anastomotic leak developed in 52 of 327 consecutive patients (16%) and was not significantly associated with vasopressor use or fluid administered in either univariable or multivariable analyses. Increasing body mass index was the only significant characteristic of both univariable (P = 0.004) and multivariable analyses associated with anastomotic leak (odds ratio, 1.05; 95% confidence interval, 1.01-1.09; P = 0.007). Of the 52 patients that developed an anastomotic leak, 12 (23%) were grade 1, 21 (40%) were grade 2 and 19 (37%) were grade 3. In our cohort, only body mass index, and not intraoperative vasopressor use and fluid administration, was significantly associated with increased odds of postoperative anastomotic leak following open Ivor Lewis esophagectomy.

Unique Considerations for Females Undergoing Esophagectomy.

OBJECTIVE: To improve understanding of sex differences in clinicopathologic characteristics, treatment and outcomes between male and female patients undergoing esophagectomy for esophageal cancer. SUMMARY BACKGROUND DATA: Esophageal cancer is a male predominant disease, and sex has not been considered in previous studies as an important factor in diagnosis or management. Sex differences in demographics, clinicopathologic characteristics, and postoperative outcomes remain largely undefined. METHODS: Retrospective review of 1958 patients (21% female) with esophageal cancer who underwent esophagectomy at a single institution between 1995 and 2017. RESULTS: Most patients had adenocarcinoma (83%); however, the rate of squamous cell carcinoma was significantly higher in females (35% vs 11%, respectively; P < .0001). Females had a lower rate of smoking (62 vs 73%) and heavy alcohol use (12 vs 19%) but a higher rate of previous mediastinal radiation (8.4 vs 1.8%) (P < 0.001). Postoperative mortality and overall survival (OS) were similar between sexes. However, subanalysis of patients with locoregional disease (clinical stage II/III) demonstrated that females received neoadjuvant therapy less frequently than males and had worse OS (median OS 2.56 yrs vs 2.08; P = 0.034). This difference remained significant on adjusted analysis (HR 1.24, 95% CI 1.06-1.46). CONCLUSIONS: Female patients had higher incidence of squamous cell carcinoma despite lower prevalence of behavioral risk factors. Among patients with locoregional disease, undertreatment in females may reflect treatment bias and history of previous mediastinal radiation. Esophageal cancer in females should be considered a unique entity as compared with the presentation and treatment of males.

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.

Does pyloric drainage have a role in the era of minimally invasive esophagectomy?

INTRODUCTION: Pyloric drainage during minimally invasive esophagectomy (MIE) may be more technically challenging than with an open approach. Alternatives to classic surgical drainage have increased in popularity; however, data are lacking to demonstrate whether one technique is superior in MIE. The purpose of this study was to compare post-operative outcomes after MIE between different pyloric drainage methods. METHODS: We performed a retrospective review of a prospectively maintained database of patients undergoing MIE at a single academic institution. Patients were divided into three groups for analysis: no drainage, intrapyloric Botulinum Toxin injection, and surgical drainage (pyloroplasty or pyloromyotomy). The primary outcome was any complication within 90 days of surgery; secondary outcomes included reported symptoms and need for pyloric dilation at 6 and 12 months post-operatively. Comparisons among groups were conducted using the Kruskal Wallis and Chi Square tests. RESULTS: There were 283 MIE performed between 2011 and 2017; of these, 126 (45%) had drainage (53 Botulinum injection and 73 surgical). No significant difference in the rate of post-operative complications, pneumonia, or anastomotic leak was observed between groups. At 6 and 12 months, patients that received Botulinum injection and surgical drainage had significantly more symptoms than no drainage (p < 0.0001) and higher need for pyloric dilation at 6 months (p = 0.007). CONCLUSIONS: Pyloric drainage was not significantly associated with lower post-operative complications or long-term symptoms. While Botulinum injection appears safe post-operatively, it was associated with increased morbidity long-term. Pyloric drainage in MIE may be unnecessary.

Long-term Survival Based on the Surgical Approach to Lobectomy For Clinical Stage I Nonsmall Cell Lung Cancer: Comparison of Robotic, Video-assisted Thoracic Surgery, and Thoracotomy Lobectomy.

OBJECTIVE: To compare the long-term outcomes among robotic, video-assisted thoracic surgery (VATS), and open lobectomy in stage I nonsmall cell lung cancer (NSCLC). BACKGROUND: Survival comparisons between robotic, VATS, and open lobectomy in NSCLC have not yet been reported. Some studies have suggested that survival after VATS is superior, for unclear reasons. METHODS: Three cohorts (robotic, VATS, and open) of clinical stage I NSCLC patients were matched by propensity score and compared to assess overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analyses were performed to identify factors associated with the outcomes. RESULTS: From January 2002 to December 2012, 470 unique patients (172 robotic, 141 VATS, and 157 open) were included in the analysis. The robotic approach harvested a higher number of median stations of lymph nodes (5 for robotic vs 3 for VATS vs 4 for open; P < 0.001). Patients undergoing minimally invasive approaches had shorter median length of hospital stay (4 d for robotic vs 4 d for VATS vs 5 d for open; P < 0.001). The 5-year OS for the robotic, VATS, and open matched groups were 77.6%, 73.5%, and 77.9%, respectively, without a statistically significant difference; corresponding 5-year DFS were 72.7%, 65.5%, and 69.0%, respectively, with a statistically significant difference between the robotic and VATS groups (P = 0.047). However, multivariate analysis found that surgical approach was not independently associated with shorter OS and DFS. CONCLUSIONS: Minimally invasive approaches to lobectomy for clinical stage I NSCLC result in similar long-term survival as thoracotomy. Use of VATS and robotics is associated with shorter length of stay, and the robotic approach resulted in greater lymph node assessment.

Change in chemotherapy during concurrent radiation followed by surgery after a suboptimal positron emission tomography response to induction chemotherapy improves outcomes for locally advanced esophageal adenocarcinoma.

BACKGROUND: A positron emission tomography (PET) scan after induction chemotherapy before preoperative chemoradiation and surgery for esophageal adenocarcinoma predicts outcomes. Some patients with progression on PET after induction chemotherapy had long-term overall survival (OS) when they were changed to alternative chemotherapy during radiation. METHODS: This study retrospectively reviewed esophageal adenocarcinoma patients who received induction chemotherapy and chemoradiation before planned surgery; all had undergone a PET scan before and after induction chemotherapy. RESULTS: There were 201 patients, and 113 (56%) were PET responders (≥35% decrease in the maximum standardized uptake value of the tumor). All PET responders received the same chemotherapy during radiation, whereas 38 of the 88 PET nonresponders (43%) changed chemotherapy. Among the 152 patients who underwent surgery, the pathologic complete response rate was 15% for PET responders and 3% for PET nonresponders who did not change chemotherapy (P = .046). The median progression-free survival (PFS; 18.9 vs 10.0 months, P < 0.01) and OS (37 vs 25.3 months, P = .02) were significantly better for PET responders versus PET nonresponders who did not change chemotherapy. The median PFS for PET nonresponders who changed chemotherapy was 17.9 months, and it was superior to the median PFS for PET nonresponders who did not change chemotherapy (P = .01). For PET nonresponders, the 5-year OS rates were 37% for those who changed chemotherapy and 25% for those who did not change chemotherapy (P = .18). CONCLUSIONS: A PET scan after induction chemotherapy predicts outcomes for locally advanced esophageal adenocarcinoma patients who undergo chemoradiation and surgery. The median PFS is improved, and trends toward improved OS appear possible in PET nonresponders who change chemotherapy during radiation. The fully accrued Cancer and Leukemia Group B 80803 study (NCT01333033) is evaluating this strategy. Cancer 2016;122:2083-90. © 2016 American Cancer Society.

The Prognostic Impact of a Positive Vascular Margin on pT3 Clear Cell Renal Cell Carcinoma.

PURPOSE: We examined the impact of positive vascular margins in patients with pT3 clear cell renal cell carcinoma. MATERIALS AND METHODS: After excluding patients with nonvascular positive margins, metastasis, lymph node involvement, neoadjuvant therapy or nonclear cell histology, we identified 224 patients with venous tumor invasion through our institutional database from 1999 to 2013. Kaplan-Meier analysis and log rank tests were used to evaluate whether positive vascular margins were associated with progression-free survival or cancer specific survival. RESULTS: There were 41 patients (18%) with a positive vascular margin. Margin status was directly related to the level of invasion (p <0.0001). Compared to the negative vascular margin group the positive group had a significantly worse progression-free survival (p=0.01) but not cancer specific survival (p=0.3). Similarly the level of vascular thrombus invasion was significantly associated with worse progression-free survival (p=0.02) but not cancer specific survival (p=0.4). The 3-year progression-free survival was worst with inferior vena cava invasion and best with segmental/muscular venous branch invasion (54%, 95% CI 34-70 vs 76%, 95% CI 64-85). Among patients with only main renal vein thrombus, vascular margin status was not associated with progression-free survival (p=0.5) or cancer specific survival (p=0.2). CONCLUSIONS: In patients with pT3N0/XM0 clear cell renal cell carcinoma positive vascular margins are associated with risk of disease progression. However, the risk of relapse associated with positive vascular margins is driven by the extent of vascular thrombus invasion. These findings suggest that the clinical significance of vascular margin status as currently defined in pT3 clear cell renal cell carcinoma is minimal.