Early Interventional Treatment of High Output Chyle Leak After Esophagectomy is Associated With Improved Survival.

OBJECTIVE: To investigate overall survival and length of stay (LOS) associated with differing management for high output (>1 L over 24 hours) leaks (HOCL) after cancer-related esophagectomy. BACKGROUND: Although infrequent, chyle leak after esophagectomy is an event that can lead to significant perioperative sequelae. Low-volume leaks appear to respond to nonoperative measures, whereas HOCLs often require invasive therapeutic interventions. METHODS: From a prospective single-institution database, we retrospectively reviewed patients treated from 2001 to 2021 who underwent esophagectomy for esophageal cancer. Within that cohort, we focused on a subgroup of patients who manifested a HOCL postoperatively. Clinicopathologic and operative characteristics were collected, including hospital LOS and survival data. RESULTS: A total of 53/2299 patients manifested a HOCL. These were mostly males (77%), with a mean age of 62 years. Of this group, 15 patients received nonoperative management, 15 patients received prompt (<72 hours from diagnosis) interventional management, and 23 received late interventional management. Patients in the late intervention group had longer LOSs compared with early intervention (slope = 9.849, 95% CI: 3.431-16.267). Late intervention (hazard ratio: 4.772, CI: 1.384-16.460) and nonoperative management (hazard ratio: 4.731, CI: 1.294-17.305) were associated with increased mortality compared with early intervention. Patients with early intervention for HOCL had an overall survival similar to patients without chyle leaks in survival analysis. CONCLUSIONS: Patients with HOCL should receive early intervention to possibly reverse the prognostic implications of this potentially detrimental complication.

Cancer of the esophagus and esophagogastric junction-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

Answer questions and earn CME/CNE New to the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual for epithelial cancers of the esophagus and esophagogastric junction are separate, temporally related cancer classifications: 1) before treatment decision (clinical); 2) after esophagectomy alone (pathologic); and 3) after preresection therapy followed by esophagectomy (postneoadjuvant pathologic). The addition of clinical and postneoadjuvant pathologic stage groupings was driven by a lack of correspondence of survival, and thus prognosis, between both clinical and postneoadjuvant pathologic cancer categories (facts about the cancer) and pathologic categories. This was revealed by a machine-learning analysis of 6-continent data from the Worldwide Esophageal Cancer Collaboration, with consensus of the AJCC Upper GI Expert Panel. Survival is markedly affected by histopathologic cell type (squamous cell carcinoma and adenocarcinoma) in clinically and pathologically staged patients, requiring separate stage grouping for each cell type. However, postneoadjuvant pathologic stage groups are identical. For the future, more refined and granular data are needed. This requires: 1) more accurate clinical staging; 2) innovative solutions to pathologic staging challenges in endoscopically resected cancers; 3) integration of genomics into staging; and 4) precision cancer care with targeted therapy. It is the responsibility of the oncology team to accurately determine and record registry data, which requires eliminating both common errors and those related to incompleteness and inconsistency. Despite the new complexity of eighth edition staging of cancers of the esophagus and esophagogastric junction, these key concepts and new directions will facilitate precision cancer care. CA Cancer J Clin 2017;67:304-317. © 2017 American Cancer Society.

Do resected colorectal cancer patients need early chest imaging? Impact of clinicopathologic characteristics on time to development of pulmonary metastases.

BACKGROUND AND OBJECTIVES: For patients with colorectal cancer (CRC), the lung is the most common extra-abdominal site of distant metastasis. However, practices for chest imaging after colorectal resection vary widely. We aimed to identify characteristics that may indicate a need for early follow-up imaging. METHODS: We retrospectively reviewed charts of patients who underwent CRC resection, collecting clinicopathologic details and oncologic outcomes. Patients were grouped by timing of pulmonary metastases (PM) development. Analyses were performed to investigate odds ratio (OR) of PM diagnosis within 3 months of CRC resection. RESULTS: Of 1600 patients with resected CRC, 233 (14.6%) developed PM, at a median of 15.4 months following CRC resection. Univariable analyses revealed age, receipt of systemic therapy, lymph node ratio (LNR), lymphovascular and perineural invasion, and KRAS mutation as risk factors for PM. Furthermore, multivariable regression showed neoadjuvant therapy (OR: 2.99, p < 0.001), adjuvant therapy (OR: 6.28, p < 0.001), LNR (OR: 28.91, p < 0.001), and KRAS alteration (OR: 5.19, p < 0.001) to predict PM within 3 months post-resection. CONCLUSIONS: We identified clinicopathologic characteristics that predict development of PM within 3 months after primary CRC resection. Early surveillance in such patients should be emphasized to ensure timely identification and treatment of PM.

Octreotide's role in the management of post-esophagectomy chylothorax.

The use of octreotide in managing intrathoracic chyle leak following esophagectomy has gained popularity in the adult population. While the benefits of octreotide have been confirmed in the pediatric population, there remains limited evidence to support its use in the adults post-esophagectomy. Thus, we performed a single-institution cohort study to characterize its efficacy. The study was performed using a prospective, single-center database, from which clinicopathologic characteristics were extracted of patients who had post-esophagectomy chyle leaks. Kaplan-Meier and multivariable Cox regression analyses were performed to investigate the effect of octreotide use on chest tube duration (CTD), hospital length of stay (LOS), and overall survival (OS). In our cohort, 74 patients met inclusion criteria, among whom 27 (36.5%) received octreotide. Kaplan-Meier revealed no significant effect of octreotide on CTD (P = 0.890), LOS (P = 0.740), or OS (P = 0.570). Multivariable Cox regression analyses further corroborated that octreotide had no effect on CTD (HR = 0.62, 95% confidence interval [CI]: 0.32-1.20, P = 0.155), LOS (HR = 0.64, CI: 0.34-1.21, P = 0.168), or OS (1.08, CI: 0.53-2.19, P = 0.833). Octreotide use in adult patients with chyle leak following esophagectomy lacks evidence of association with meaningful clinical outcomes. Level 1 evidence is needed prior to further consideration in this population.

Financial Toxicity in Patients With Resected Lung Cancer.

OBJECTIVES: To describe financial toxicity (FT) in patients with resected lung cancer and identify risk factors in this population. BACKGROUND: FT describes the financial burden associated with cancer care and its impact on the quality of survivorship. Few prior studies have examined FT in patients with lung cancer. METHODS: Patients who underwent lung cancer resection at our institution between January 1, 2016 and December 31, 2021, were surveyed to gather demographic information and evaluate FT using a validated questionnaire. A multivariable model was built to identify risk factors for FT. RESULTS: Of the total, 1477 patients were contacted, of whom 463 responded (31.3%). Most patients were stage I (n = 349, 75.4%) and lobectomy was performed often (n = 290, 62.8%). There were 196 patients (42.3%) who experienced FT. Upon multivariable analyses, divorced marital status [odds ratio (OR) = 3.658, 95% CI: 1.180-11.337], household income <$40,000 (OR = 2.544, 95% CI: 1.003-6.455), credit score below 739 (OR = 2.744, 95% CI: 1.326-5.679), clinical stage >I (OR = 2.053, 95% CI: 1.088-3.877), and change in work hours or work cessation (all P < 0.05) were associated with FT. Coping mechanisms, such as decreased spending on food or clothing and increased use of savings or borrowing money, were more likely to be reported by patients experiencing FT than those who did not ( P < 0.001). CONCLUSIONS: Patients undergoing lung cancer resection often experienced significant financial stress with several identifiable risk factors. FT should be considered early in the care of these patients to alleviate detrimental coping mechanisms and enhance their quality of survivorship.

High-Risk Features of Esophageal Adenocarcinoma Following Neoadjuvant Chemoradiation: Patients for Whom Surgery Should Not Be Delayed.

OBJECTIVE: Clinical predictors of pathological complete response have not reliably identified patients for whom an organ-sparing approach following neoadjuvant chemoradiation be undertaken for esophageal cancer patients. We sought to identify high-risk predictors of residual carcinoma that may preclude patients from a selective surgical approach. BACKGROUND: Patients treated with neoadjuvant chemoradiation followed by esophagectomy for esophageal adenocarcinoma were identified. PATIENTS AND METHODS: Correlation between clinical and pathologic complete responses were examined. Regression models and recursive partitioning were utilized to identify features associated with residual carcinoma. External validation of these high-risk factors was performed on a data set from an independent institution. RESULTS: A total of 326 patients were identified, in whom clinical complete response was noted in 104/326 (32%). Pathologic complete response was noted in only 33/104 (32%) of these clinical complete responders. Multivariable analysis identified that the presence of stricture ( P =0.011), positive biopsy ( P =0.010), and signet ring cell histology ( P =0.019) were associated with residual cancer. Recursive partitioning corroborated a 94% probability of residual disease, or greater, for each of these features. The positive predictive value was >90% for these characteristics. A SUV max >5.4 at the esophageal primary in the absence of esophagitis was also a high-risk factor for residual carcinoma. External validation confirmed these high-risk factors to be implicated in the finding of residual carcinoma. CONCLUSIONS: Clinical parameters of response are poor predictors of complete pathologic response leading to challenges in selecting candidates for active surveillance. However, we characterize several high-risk features for residual carcinoma which indicate that esophagectomy should not be delayed.

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.

Chemoradiotherapy Followed by Active Surveillance Versus Standard Esophagectomy for Esophageal Cancer: A Systematic Review and Individual Patient Data Meta-analysis.

OBJECTIVE: To compare overall survival of patients with a cCR undergoing active surveillance versus standard esophagectomy. SUMMARY OF BACKGROUND DATA: One-third of patients with esophageal cancer have a pathologically complete response in the resection specimen after neoadjuvant chemoradiotherapy. Active surveillance may be of benefit in patients with cCR, determined with diagnostics during response evaluations after chemoradiotherapy. METHODS: A systematic review and meta-analysis was performed comparing overall survival between patients with cCR after chemoradiotherapy undergoing active surveillance versus standard esophagectomy. Authors were contacted to supply individual patient data. Overall and progression-free survival were compared using random effects meta-analysis of randomized or propensity score matched data. Locoregional recurrence rate was assessed. The study-protocol was registered (PROSPERO: CRD42020167070). RESULTS: Seven studies were identified comprising 788 patients, of which after randomization or propensity score matching yielded 196 active surveillance and 257 standard esophagectomy patients. All authors provided individual patient data. The risk of all-cause mortality for active surveillance was 1.08 [95% confidence interval (CI): 0.62-1.87, P = 0.75] after intention-to-treat analysis and 0.93 (95% CI: 0.56-1.54, P = 0.75) after per-protocol analysis. The risk of progression or all-cause mortality for active surveillance was 1.14 (95% CI: 0.83-1.58, P = 0.36). Five-year locoregional recurrence rate during active surveillance was 40% (95% CI: 26%-59%). 95% of active surveillance patients undergoing postponed esophagectomy for locoregional recurrence had radical resection. CONCLUSIONS: Overall survival was comparable in patients with cCR after chemoradiotherapy undergoing active surveillance or standard esophagectomy. Diagnostic follow-up is mandatory in active surveillance and postponed esophagectomy should be offered to operable patients in case of locoregional recurrence.

Robotic Techniques in Esophagogastric Cancer Surgery: An Assessment of Short- and Long-Term Clinical Outcomes.

BACKGROUND: Robotic esophagogastric cancer surgery is gaining widespread adoption. This population-based cohort study aimed to compare rates of textbook outcomes (TOs) and survival from robotic minimally invasive techniques for esophagogastric cancer. METHODS: Data from the United States National Cancer Database (NCDB) (2010-2017) were used to identify patients with non-metastatic esophageal or gastric cancer receiving open surgery (to the esophagus, n = 11,442; stomach, n = 22,183), laparoscopic surgery (to the esophagus [LAMIE], n = 4827; stomach [LAMIG], n = 6359), or robotic surgery (to the esophagus [RAMIE], n = 1657; stomach [RAMIG], n = 1718). The study defined TOs as 15 or more lymph nodes examined, margin-negative resections, hospital stay less than 21 days, no 30-day readmissions, and no 90-day mortalities. Multivariable logistic regression and Cox analyses were used to account for treatment selection bias. RESULTS: Patients receiving robotic surgery were more commonly treated in high-volume academic centers with advanced clinical T and N stage disease. From 2010 to 2017, TO rates increased for esophageal and gastric cancer treated via all surgical techniques. Compared with open surgery, significantly higher TO rates were associated with RAMIE (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.27-1.58) and RAMIG (OR 1.30; 95% CI 1.17-1.45). For esophagectomy, long-term survival was associated with both TO (hazard ratio [HR 0.64, 95% CI 0.60-0.67) and RAMIE (HR 0.92; 95% CI 0.84-1.00). For gastrectomy, long-term survival was associated with TO (HR 0.58; 95% CI 0.56-0.60) and both LAMIG (HR 0.89; 95% CI 0.85-0.94) and RAMIG (HR 0.88; 95% CI 0.81-0.96). Subset analysis in high-volume centers confirmed similar findings. CONCLUSION: Despite potentially adverse learning curve effects and more advanced tumor stages captured during the study period, both RAMIE and RAMIG performed in mostly high-volume centers were associated with improved TO and long-term survival. Therefore, consideration for wider adoption but a well-designed phase 3 randomized controlled trial (RCT) is required for a full evaluation of the benefits conferred by robotic techniques for esophageal and gastric cancers.

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 Role of Surgery in the Treatment of Melanoma Pulmonary Metastases in the Modern Era.

INTRODUCTION: The lung represents a frequent site of spread for metastatic melanoma, which has historically been managed with surgical resection achieving promising outcomes. We hypothesized that the role of surgery in the management of melanoma pulmonary metastases (MPM) is evolving among the development of less invasive diagnostic and novel systemic therapeutic strategies. MATERIALS AND METHODS: A single-center thoracic surgery database was reviewed and patients who underwent surgical resection of MPM between 1998 and 2019 were identified. Demographic, clinicopathologic, and surgical data were collected and analyzed, as were the annual volumes and indications for surgical resection. A Cochran-Armitage test was used to assess the trend in surgical indication. RESULTS: Three hundred and seventy seven surgical procedures for MPM were performed during the years of study in the care of 347 patients. Patients were predominantly male, with a mean age of 59.3 y. The mean number of annual resections was 17 and while this number initially increased from six in 1998 to a peak of 39 cases in 2008, a decline was subsequently observed. Diagnostic resection decreased from 22% in 1998-1999 to 5% at the peak of procedures in 2008-2009 and to 0 in 2018-2019 (P = 0.02). Curative resection increased from 44% in 1998-1999 to 73% in 2008-2009 (P < 0.001) and remained the dominant reason for surgery in later years. CONCLUSIONS: Surgical indications in the management of MPM have transformed in conjunction with systemic modalities, and the volume of resections has decreased in the modern era. Despite innovations in systemic management and shifting goals of operative interventions, surgeons continue to play a vital role in caring for these patients with an advanced disease.

Targeting cancer stem cells with a pan-BCL-2 inhibitor in preclinical and clinical settings in patients with gastroesophageal carcinoma.

OBJECTIVE: Gastro-oesophageal cancers (GEC) are resistant to therapy and lead to poor prognosis. The cancer stem cells (CSCs) and antiapoptotic pathways often confer therapy resistance. We sought to elucidate the antitumour action of a BCL-2 inhibitor, AT101 in GEC in vitro, in vivo and in a clinical trial. METHODS: Extensive preclinical studies in vitro and in vivo were carried out to establish the mechanism action of AT101 on targeting CSCs and antiapoptotic proteins. A pilot clinical trial in patients with GEC was completed with AT-101 added to standard chemoradiation. RESULTS: Overexpression of BCL-2 and MCL-1 was noted in gastric cancer tissues (GC). AT-101 induced apoptosis, reduced proliferation and tumour sphere formation in MCL-1/BCL-2 high GC cells. Interestingly, AT101 dramatically downregulated genes (YAP-1/Sox9) that control CSCs in GEC cell lines regardless of BCL-2/MCL-1 expression. Addition of docetaxel to AT-101 amplified its antiproliferation and induced apoptosis effects. In vivo studies confirmed the combination of AT101 and docetaxel demonstrated stronger antitumour activity accompanied with significant decrease of CSCs biomarkers (YAP1/SOX9). In a pilot clinical trial, 13 patients with oesophageal cancer (EC) received AT101 orally concurrently with chemoradiation. We observed dramatic clinical complete responses and encouraging overall survival in these patients. Clinical specimen analyses revealed that AT-101 dramatically reduced the expression of CSCs genes in treated EC specimens indicating antitumour activity of AT101 relies more on its anti-CSCs activity. CONCLUSIONS: Our preclinical and clinical data suggest that AT-101 overcomes resistance by targeting CSCs pathways suggesting a novel mechanism of action of AT101 in patients with GEC.

Frequency and Implications of Paratracheal Lymph Node Metastases in Resectable Esophageal or Gastroesophageal Junction Adenocarcinoma.

OBJECTIVE: We aimed to evaluate the frequency of paratracheal lymph nodes (LN) metastases and their prognostic influence. SUMMARY BACKGROUND DATA: Paratracheal LNs are considered regional nodes in the esophageal cancer classification, but their metastatic rate and influence on survival remain unclear. METHODS: One thousand one hundred ninety-nine patients with resectable esophageal or gastroesophageal junction adenocarcinoma (EAC) (January 2002 and December 2016) in our Gastrointestinal Medical Oncology Database were analyzed. Paratracheal LNs were defined as1R, 1L, 2R, 2L, 4R, and 4L, according to the 8th American Joint Committee on Cancer classification. RESULTS: Of 1199 patients, 73 (6.1%) had positive paratracheal LNs at diagnosis. The median overall survival (OS) of 73 patients with initial paratracheal LN involvement was 2.10 years (range 0.01-10.1, 5-yrs OS 24.2%). Of 1071 patients who were eligible for recurrence evaluation, 70 patients (6.5%) developed paratracheal LN metastases as the first recurrence. The median time to recurrence was 1.28 years (range 0.28-5.96 yrs) and the median OS following recurrence was only 0.95 year (range 0.03-7.88). OS in 35 patients who had only paratracheal LN recurrence was significantly longer than in patients who had other recurrences (median OS 2.26 vs 0.51 yrs, 5-yrs OS; 26.8% vs 0%, P < 0.0001). Higher T stage (T3/T4) was an independently risk factor for paratracheal LN recurrence (odds ratio 5.10, 95% confidence interval 1.46-17.89). We segregated patients in 3 groups based on the distance of tumor's proximal edge to esophagogastric junction (low; ≤2 cm, medium; 2.0-7.0 cm, and high; >7.0 cm). Paratracheal LN metastases were more frequent with the proximal tumors (low, 4.2%; medium, 12.0%; high, 30.3%; Cochran-Armitage Trend test, P < 0.001). CONCLUSION: Paratracheal LN metastases were associated with a shorter survival in resectable EAC patients. Alternate approaches to prolong survival of this group of patients are warranted.

Esophagectomy or Total Gastrectomy for Siewert 2 Gastroesophageal Junction (GEJ) Adenocarcinoma? A Registry-Based Analysis.

BACKGROUNDS: Due to a lack of randomized and large studies, the optimal surgical approach for Siewert 2 gastroesophageal junctional (GEJ) adenocarcinoma remains unknown. This population-based cohort study aimed to compare survival between esophagectomy and total gastrectomy for the treatment of Siewert 2 GEJ adenocarcinoma. METHODS: Data from the National Cancer Database (NCDB) from 2010 to 2016 was used to identify patients with non-metastatic Siewert 2 GEJ adenocarcinoma who received either esophagectomy (n = 999) or total gastrectomy (n = 8595). Propensity score-matching (PSM) and multivariable analyses were used to account for treatment selection bias. RESULTS: Comparison of the unmatched cohort's baseline demographics showed that the patients who received esophagectomy were younger, had a lower burden of medical comorbidities, and had fewer clinical positive lymph nodes. The patients in the unmatched cohort who received gastrectomy had a significantly shorter overall survival than those who received esophagectomy (median, 47 vs. 68 months [p < 0.001]; 5-year survival, 45 % vs. 53 %). After matching, gastrectomy was associated with significantly reduced survival compared with esophagectomy (median, 51 vs. 68 months [p < 0.001]; 5-year survival, 47 % vs. 53 %), which remained in the adjusted analyses (hazard ratio [HR], 1.22; 95 % confidence interval [CI], 1.09-1.35; p < 0.001). CONCLUSIONS: In this large-scale population study with propensity-matching to adjust for confounders, esophagectomy was prognostically superior to gastrectomy for the treatment of Siewert 2 GEJ adenocarcinoma despite comparable lymph node harvest, length of stay, and 90-day mortality. Adequately powered randomized controlled trials with robust surgical quality assurance are the next step in evaluating the prognostic outcomes of these surgical strategies for GEJ cancer.

Simultaneous versus staged resections for bilateral pulmonary metastases.

BACKGROUND: For patients with bilateral pulmonary metastases, staged resections have historically been the preferred surgical intervention. During the spring of 2020, the COVID-19 pandemic made patient travel to the hospital challenging and necessitated reduction in operative volume so that resources could be conserved. We report our experience with synchronous bilateral metastasectomies for the treatment of disease in both lungs. METHODS: Patients with bilateral pulmonary metastases who underwent simultaneous bilateral resections were compared with a cohort of patients who underwent staged resections. We used nearest-neighbor propensity score (1:1) matching to adjust for confounders. Perioperative outcomes were compared between groups using paired statistical analysis techniques. RESULTS: Between 1998 and 2020, 36 patients underwent bilateral simultaneous metastasectomies. We matched 31 pairs of patients. The length of stay was significantly shorter in patients undergoing simultaneous resection (median 3 vs. 8 days, p < .001) and operative time was shorter (156 vs. 235.5 min, p < .001) when compared to the sum of both procedures in the staged group. The groups did not significantly differ with regard to postoperative complications. CONCLUSION: In a carefully selected patient population, simultaneous bilateral metastasectomy is a safe option. A single procedure confers benefits for both the patient as well as the hospital resource system.

Pulmonary resection for tissue harvest in adoptive tumor-infiltrating lymphocyte therapy: Safety and feasibility.

BACKGROUND AND OBJECTIVES: Adoptive T-cell therapies (ACTs) using expansion of tumor-infiltrating lymphocyte (TIL) populations are of great interest for advanced malignancies, with promising response rates in trial settings. However, postoperative outcomes following pulmonary TIL harvest have not been widely documented, and surgeons may be hesitant to operate in the setting of widespread disease. METHODS: Patients who underwent pulmonary TIL harvest were identified, and postoperative outcomes were studied, including pulmonary, cardiovascular, infectious, and wound complications. RESULTS: 83 patients met inclusion criteria. Pulmonary TIL harvest was undertaken primarily via a thoracoscopy with a median operative blood loss and duration of 30 ml and 65 min, respectively. The median length of stay was 2 days. Postoperative events were rare, occurring in only five (6%) patients, including two discharged with a chest tube, one discharged with oxygen, one episode of urinary retention, and one blood transfusion. No reoperations occurred. The median time from TIL harvest to ACT infusion was 37 days. CONCLUSIONS: Pulmonary TIL harvest is safe and feasible, without major postoperative events in our cohort. All patients were able to receive intended ACT infusion without delays. Therefore, thoracic surgeons should actively participate in ongoing ACT trials and aggressively seek to enroll patients on these protocols.

Total Lesion Glycolysis Assessment Identifies a Patient Fraction With a High Cure Rate Among Esophageal Adenocarcinoma Patients Treated With Definitive Chemoradiation.

OBJECTIVE: We aimed to determine whether tumor metabolism could be prognostic of cure in L-EAC patients who receive definitive chemoradiation. SUMMARY BACKGROUND DATA: Patients with inoperable localized esophageal adenocarcinoma (L-EAC) often receive definitive chemoradiation; however, biomarkers and/or imaging variables to prognosticate cure are missing. METHODS: Two hundred sixty-six patients with L-EAC who had chemoradiation but not surgery were analyzed from the prospectively maintained EAC databases in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center (Texas, USA) between March 2002 and April 2015. Maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG) from the positron emission tomography data were evaluated. RESULTS: Of 266 patients, 253 (95%) were men; the median age was 67 years (range 20-91 yrs) and 153 had poorly differentiated L-EAC. The median SUVmax was 10.3 (range 0-87) and the median TLG was 85.7 (range 0-3227). Both SUVmax and TLG were higher among those with: tumors >5 cm in length, high clinical stage, and high tumor and node categories by TNM staging (all P < 0.0001). Of 234 patients evaluable for cure, 60 (25.6%) achieved cure. In the multivariable logistic regression model, low TLG (but not low SUVmax) was associated with cure (continuous TLG value: odds ratio 0.70, 95% confidence interval (CI) 0.54-0.92). TLG was quantified into 4 quartile categorical variables; first quartile (Q1; <32), second quartile (Q2; 32.0-85.6), third quartile (Q3; 85.6-228.4), and fourth quartile (Q4; >228.4); the cure rate was only 10.3% in Q4 and 5.1% in Q3 but increased to 28.8% in Q2, and 58.6% in Q1. The cross-validation resulted in an average accuracy of prediction score of 0.81 (95% CI, 0.75-0.86). CONCLUSIONS: In this cross-validated model, 59% of patients in the 1st quartile were cured following definitive chemoradiation. Baseline TLG could be pursued as one of the tools for esophageal preservation.

18F-fluorodeoxyglucose positron emission tomography correlates with tumor immunometabolic phenotypes in resected lung cancer.

Enhanced tumor glycolytic activity is a mechanism by which tumors induce an immunosuppressive environment to resist adoptive T cell therapy; therefore, methods of assessing intratumoral glycolytic activity are of considerable clinical interest. In this study, we characterized the relationships among tumor 18F-fluorodeoxyglucose (FDG) retention, tumor metabolic and immune phenotypes, and survival in patients with resected non-small cell lung cancer (NSCLC). We retrospectively analyzed tumor preoperative positron emission tomography (PET) 18F-FDG uptake in 59 resected NSCLCs and investigated correlations between PET parameters (SUVMax, SUVTotal, SUVMean, TLG), tumor expression of glycolysis- and immune-related genes, and tumor-associated immune cell densities that were quantified by immunohistochemistry. Tumor glycolysis-associated immune gene signatures were analyzed for associations with survival outcomes. We found that each 18F-FDG PET parameter was positively correlated with tumor expression of glycolysis-related genes. Elevated 18F-FDG SUVMax was more discriminatory of glycolysis-associated changes in tumor immune phenotypes than other 18F-FDG PET parameters. Increased SUVMax was associated with multiple immune factors characteristic of an immunosuppressive and poorly immune infiltrated tumor microenvironment, including elevated PD-L1 expression, reduced CD57+ cell density, and increased T cell exhaustion gene signature. Elevated SUVMax identified immune-related transcriptomic signatures that were associated with enhanced tumor glycolytic gene expression and poor clinical outcomes. Our results suggest that 18F-FDG SUVMax has potential value as a noninvasive, clinical indicator of tumor immunometabolic phenotypes in patients with resectable NSCLC and warrants investigation as a potential predictor of therapeutic response to immune-based treatment strategies.

Cancer associated macrophage-like cells and prognosis of esophageal cancer after chemoradiation therapy.

BACKGROUND: Cancer Associated Macrophage-Like cells (CAMLs) are polynucleated circulating stromal cells found in the bloodstream of numerous solid-tumor malignancies. Variations within CAML size have been associated with poorer progression free survival (PFS) and overall survival (OS) in a variety of cancers; however, no study has evaluated their clinical significance in esophageal cancer (EC). METHODS: To examine this significance, we ran a 2 year prospective pilot study consisting of newly diagnosed stage I-III EC patients (n = 32) receiving chemoradiotherapy (CRT). CAML sizes were sequentially monitored prior to CRT (BL), ~ 2 weeks into treatment (T1), and at the first available sample after the completion of CRT (T2). RESULTS: We found CAMLs in 88% (n = 28/32) of all patient samples throughout the trial, with a sensitivity of 76% (n = 22/29) in pre-treatment screening samples. Improved 2 year PFS and OS was found in patients with CAMLs < 50 µm by the completion of CRT over patients with CAMLs ≥ 50 µm; PFS (HR = 12.0, 95% CI = 2.7-54.1, p = 0.004) and OS (HR = 9.0, 95%CI = 1.9-43.5, p = 0.019). CONCLUSIONS: Tracking CAML sizes throughout CRT as a minimally invasive biomarker may serve as a prognostic tool in mapping EC progression, and further studies are warranted to determine if presence of these cells prior to treatment suggest diagnostic value for at-risk populations.

Importance of resection for locoregional disease control in Masaoka stage IVA thymic neoplasms.

BACKGROUND AND OBJECTIVES: It is unclear if a specific strategy for simultaneous treatment of primary thymic neoplasms and pleural metastases confers benefit for Masaoka stage IVA disease. We reviewed our experience with thymic neoplasms with concurrent pleural metastases to identify factors influencing outcomes. METHODS: Records of patients who presented with stage IVA thymic neoplasms from 2000 to 2018 were assessed. Multivariate Cox proportional hazards analyses were completed to determine predictors of progression-free and overall survival. RESULTS: Forty-eight patients were identified, including 34 (71%) who underwent surgery. Median overall and progression-free survival were 123 and 21 months, respectively. The extent of resection varied, and was most commonly thymectomy plus partial pleurectomy (22, 65%). Median progression-free survival for patients who underwent surgical resection versus those who had not was 24 versus 12 months (P = .018). Following surgical resection, mediastinal recurrence was uncommon (2, 6%, vs 7, 50% nonoperatively). Five-year survival rates in these groups were suggestive of possible benefit to surgery (87% vs 68%). CONCLUSIONS: Thymic neoplasms with pleural dissemination represents a treatment challenge. As part of a multidisciplinary approach, surgery appears to be associated with more favorable long-term results, although selection bias may account for some of the survival differences observed.