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OBJECTIVE: To evaluate whether pathologic complete response (pCR) exclusively defines major pathologic response to treatment with improved survival. SUMMARY BACKGROUND DATA: pCR following trimodality therapy for esophagogastric adenocarcinoma 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 adenocarcinoma between 1995 and 2017. Overall survival (OS) was examined by percentage treatment response (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, 0.4–210.6); median OS was 48.3 months (95% CI, 42.2–58.8). Absence of residual nodal disease was independently associated with improved survival (P

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.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.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.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.

Standard-of-care for resectable gastric/gastroesophageal junction cancer includes surgery and neoadjuvant-adjuvant 5-fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) chemotherapy. Early-phase clinical studies support further clinical development of the immune checkpoint inhibitor (ICI); durvalumab, an anti-PD-L1 antibody, in patients with gastric/gastroesophageal junction cancer. Accumulating evidence indicates that ICIs combined with FLOT chemotherapy improve clinical outcomes in patients with advanced or metastatic cancer. We describe the rationale for and the design of MATTERHORN, a randomized, double-blind, placebo-controlled, phase III study investigating the efficacy and safety of neoadjuvant-adjuvant durvalumab and FLOT chemotherapy followed by adjuvant durvalumab monotherapy in patients with resectable gastric/gastroesophageal junction cancer. The planned sample size is 900 patients, the primary end point is event-free survival and safety and tolerability will be evaluated. Clinical trial registration: NCT04592913 (ClinicalTrials.gov). ispartof: FUTURE ONCOLOGY vol:18 issue:20 pages:2465-2473 ispartof: location:England status: published

Concordance between copy-number inferred from next generation sequencing and protein overexpression by IHC or gene amplification by FISH.

Text legends for Supplementary Figures S1-S4.

The incidence of esophagogastric cancer is rapidly rising, but only a minority of patients derive durable benefit from current therapies. Chemotherapy as well as anti-HER2 and PD-1 antibodies are standard treatments. To identify predictive biomarkers of drug sensitivity and mechanisms of resistance, we implemented prospective tumor sequencing of patients with metastatic esophagogastric cancer. There was no association between homologous recombination deficiency defects and response to platinum-based chemotherapy. Patients with microsatellite instability–high tumors were intrinsically resistant to chemotherapy but more likely to achieve durable responses to immunotherapy. The single Epstein–Barr virus–positive patient achieved a durable, complete response to immunotherapy. The level of ERBB2 amplification as determined by sequencing was predictive of trastuzumab benefit. Selection for a tumor subclone lacking ERBB2 amplification, deletion of ERBB2 exon 16, and comutations in the receptor tyrosine kinase, RAS, and PI3K pathways were associated with intrinsic and/or acquired trastuzumab resistance. Prospective genomic profiling can identify patients most likely to derive durable benefit to immunotherapy and trastuzumab and guide strategies to overcome drug resistance.Significance: Clinical application of multiplex sequencing can identify biomarkers of treatment response to contemporary systemic therapies in metastatic esophagogastric cancer. This large prospective analysis sheds light on the biological complexity and the dynamic nature of therapeutic resistance in metastatic esophagogastric cancers. Cancer Discov; 8(1); 49–58. ©2017 AACR.See related commentary by Sundar and Tan, p. 14.See related article by Pectasides et al., p. 37.This article is highlighted in the In This Issue feature, p. 1

Supplementary Table 1: Comprehensive clinical data and sample IDs. Supplementary Table 2: Summary of baseline patient and sample characteristics. Supplementary Table 3: List of somatic mutations identified in all samples. Supplementary Table 4: Detailed data for assesment of ERBB2 amplification. Supplementary Table 5: Genes included on MSK-IMPACT platform

Supplementary Figures

Supplementary Data from The Role of the TP53 Pathway in Predicting Response to Neoadjuvant Therapy in Esophageal Adenocarcinoma

Purpose:The majority of broad-panel tumor genomic profiling has used a gene-centric approach, although much of that data is unused in clinical decision making. We hypothesized that a pathway-centric approach using next-generation sequencing (NGS), combined with conventional clinicopathologic features, may better predict disease-free survival (DFS) in early stage lung adenocarcinoma.Experimental Design:Utilizing our prospectively maintained database, we analyzed 492 patients with primary, untreated, completely surgically resected lung adenocarcinoma. Ten canonical pathways were analyzed using broad-panel NGS. The correlations of DFS and number (and type) of pathway (NPA) were analyzed using the Kaplan–Meier method and log-rank test. Associations between altered pathways and clinicopathologic variables, as well as identification of actionable therapeutic strategies were explored.Results:Median NPA for the cohort was two (range, 0–5). Smoking status, solid morphologic appearance on preoperative CT, maximal standardized uptake value, pathologic tumor size, aggressive histologic subtype, lymphovascular invasion, visceral pleural invasion, and positive lymph nodes were significantly associated with NPA (P < 0.05). Of 543 actionable genetic alterations identified, 455 (84%) were within the RTK/RAS pathway. A total of 86 tumors had actionable therapeutic genomic alterations in >1 pathway. On multivariable analysis, higher NPA was significantly associated with worse DFS (HR, 1.31; P = 0.014).Conclusions:NPA and specific pathway alterations are associated with clinicopathologic features in patients with surgically resected lung adenocarcinoma. Cell cycle, Hippo, TGFβ, and p53 pathway alterations are associated with poor DFS. Finally, NPA is an independent risk factor for poor DFS in our cohort.See related commentary by Blakely, p. 7269

Purpose:In patients with locally advanced esophageal adenocarcinoma, response to neoadjuvant therapy strongly predicts survival, but robust molecular predictors of response have been lacking. We therefore sought to discover meaningful predictors of response in these patients.Experimental Design:We retrospectively identified all patients with adenocarcinoma of the lower esophagus or gastroesophageal junction who (i) were treated with multimodality therapy with curative intent at our institution from 2014 through 2020 and (ii) underwent prospective sequencing by Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets. Clinicopathologic and genomic data were analyzed to identify potential genomic features, somatic alterations, and oncogenic pathways associated with treatment response.Results:In total, 237 patients were included. MDM2 amplification was independently associated with poor response to neoadjuvant therapy [OR, 0.10 (95% confidence interval, 0.01–0.55); P = 0.032], when accounting for significant clinicopathologic variables, including clinical stage, tumor grade, and chemotherapy regimen. Moreover, TP53 pathway alterations, grouped according to inferred severity of TP53 dysfunction, were significantly associated with response to neoadjuvant therapy (P = 0.004, q = 0.07). Patients with MDM2 amplifications or truncating biallelic TP53 mutations had similar outcomes in terms of poor responses to neoadjuvant therapy and, consequently, shorter progression-free survival, compared with patients with TP53 pathway wild-type tumors. Thus, worsening TP53 dysfunction was directly correlated with worse outcomes.Conclusions:MDM2 amplification and TP53 status are associated with response to therapy in patients with esophageal adenocarcinoma. Given the dearth of actionable targets in esophageal adenocarcinoma, MDM2 inhibition, in combination with cytotoxic chemotherapy, may represent an important therapeutic strategy to overcome treatment resistance and improve outcomes in these patients.

Purpose:To delineate recurrent oncogenic driver alterations and dysregulated pathways in esophageal adenocarcinoma and to assess their prognostic value.Experimental Design:We analyzed a large cohort of patients with lower esophageal and junctional adenocarcinoma, prospectively sequenced by MSK-IMPACT with high-quality clinical annotation. Patients were subdivided according to treatment intent, curative versus palliative, which closely mirrored clinical staging. Genomic features, alterations, and pathways were examined for association with overall survival using Cox proportional hazard models, adjusted for relevant clinicopathologic factors knowable at the time of diagnosis.Results:Analysis of 487 patients revealed 16 oncogenic driver alterations, mostly amplifications, present in ≥5% of patients. Patients in the palliative-intent cohort, compared with those in the curative-intent cohort, were more likely to have metastatic disease, ERBB2 amplifications, Cell-cycle and RTK–RAS pathway alterations, as well as a higher fraction of genome altered and rate of whole-genome doubling. In multivariable analyses, CDKN2A alterations, SMAD4 alterations, KRAS amplifications, Cell-cycle and TGFβ pathways, and overall number of oncogenic drivers were independently associated with worse overall survival. ERBB2 amplification was associated with improved survival, presumably due to trastuzumab therapy.Conclusions:Our study suggests that higher levels of genomic instability are associated with more advanced disease in esophageal adenocarcinoma. Furthermore, CDKN2A, KRAS, and SMAD4 represent prognostic biomarkers, given their strong association with poor survival.

Alterations in esophageal adenocarcinoma in the TCGA dataset, and mapping of alterations onto the RTK-RAS and Cell Cycle pathways.

Supplementary Tables

Supplementary Figure from The Role of the TP53 Pathway in Predicting Response to Neoadjuvant Therapy in Esophageal Adenocarcinoma

Supplementary Tables 1 and 2

Online supplement

Purpose:KRASG12C is the most common KRAS mutation in primary lung adenocarcinoma. Phase I clinical trials have demonstrated encouraging clinical activity of KRASG12C inhibitors in the metastatic setting. We investigated disease-free survival (DFS) and tumor genomic features in patients with surgically resected KRASG12C-mutant lung adenocarcinoma.Experimental Design:Patients who underwent resection of stage I–III lung adenocarcinoma and next-generation sequencing (NGS) were evaluated. Exclusion criteria were receipt of induction therapy, incomplete resection, and low-quality NGS. Mutations were classified as KRAS wild-type (KRASwt), G12C (KRASG12C), or non-G12C (KRASother). DFS was compared between groups using the log-rank test; factors associated with DFS were assessed using Cox regression. Mutual exclusivity and cooccurrence, tumor clonality, and mutational signatures were assessed.Results:In total, 604 patients were included: 374 KRASwt (62%), 95 KRASG12C (16%), and 135 KRASother (22%). Three-year DFS was not different between KRAS-mutant and KRASwt tumors. However, 3-year DFS was worse in patients with KRASG12C than KRASother tumors (log-rank P = 0.029). KRASG12C tumors had more lymphovascular invasion (51% vs. 37%; P = 0.032) and higher tumor mutation burden [median (interquartile range), 7.0 (5.3–10.8) vs. 6.1 (3.5–9.7); P = 0.021], compared with KRASother tumors. KRASG12C mutation was independently associated with worse DFS on multivariable analysis. Our DFS findings were externally validated in an independent The Cancer Genome Atlas cohort.Conclusions:KRASG12C mutations are associated with worse DFS after complete resection of stage I–III lung adenocarcinoma. These tumors harbor more aggressive clinicopathologic and genomic features than other KRAS-mutant tumors. We identified a high-risk group for whom KRASG12C inhibitors may be investigated to improve survival.

Every effort must be made by the leaders in our field, as well as by every individual cardiothoracic surgeon, to assure equal opportunity for all cardiothoracic surgeons, regardless of race, gender or any other sociodemographic source of bias. Every effort must be made by every surgeon, not just those in particular leadership roles. Opportunities for advancement must be equal in multiple domains, including clinical practice, patient referral, clinical leadership, academic leadership, institutional leadership and leadership in professional medical and surgical societies. Such actions to minimize bias and promote inclusivity will also ensure that cardiothoracic surgical care is provided by a workforce that represents the diversity of patients whom we serve. In the final analysis, it is an absolute fact that gender differences in payments to cardiothoracic surgeons are absolutely unacceptable and cannot be tolerated.

The Memorial Sloan Kettering Cancer Center (MSK) nomogram combined both gastroesophageal junction (GEJ) and gastric cancer patients and was created in an era from patients who generally did not receive neoadjuvant chemotherapy. We sought to reevaluate the MSK nomogram in the era of multidisciplinary treatment for GEJ and gastric cancer.Using data on patients who underwent R0 resection for GEJ or gastric cancer between 2002 and 2016, the C-index of prediction for disease-specific survival (DSS) was compared between the MSK nomogram and the American Joint Committee on Cancer (AJCC) 8th edition staging system after segregating patients by tumor location (GEJ or gastric cancer) and neoadjuvant treatment. A new nomogram was created for the group for which both systems poorly predicted prognosis.During the study period, 886 patients (645 gastric and 241 GEJ cancer) underwent up-front surgery, and 999 patients (323 gastric and 676 GEJ) received neoadjuvant treatment. Compared with the AJCC staging system, the MSK nomogram demonstrated a comparable C-index in gastric cancer patients undergoing up-front surgery (0.786 vs 0.753) and a better C-index in gastric cancer patients receiving neoadjuvant treatment (0.796 vs 0.698). In GEJ cancer patients receiving neoadjuvant chemotherapy, neither the MSK nomogram nor the AJCC staging system performed well (C-indices 0.647 and 0.646). A new GEJ nomogram was created based on multivariable Cox regression analysis and was validated with a C-index of 0.718.The MSK gastric cancer nomogram's predictive accuracy remains high. We developed a new GEJ nomogram that can effectively predict DSS in patients receiving neoadjuvant treatment.

Purpose: In patients with locally advanced esophageal adenocarcinoma, response to neoadjuvant therapy strongly predicts survival, but robust molecular predictors of response have been lacking. We therefore sought to discover meaningful predictors of response in these patients. Experimental Design: We retrospectively identified all patients with adenocarcinoma of the lower esophagus or gastroesophageal junction who (i) were treated with multimodality therapy with curative intent at our institution from 2014 through 2020 and (ii) underwent prospective sequencing by Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets. Clinicopathologic and genomic data were analyzed to identify potential genomic features, somatic alterations, and oncogenic pathways associated with treatment response. Results: In total, 237 patients were included. MDM2 amplification was independently associated with poor response to neoadjuvant therapy [OR, 0.10 (95% confidence interval, 0.01–0.55); P = 0.032], when accounting for significant clinicopathologic variables, including clinical stage, tumor grade, and chemotherapy regimen. Moreover, TP53 pathway alterations, grouped according to inferred severity of TP53 dysfunction, were significantly associated with response to neoadjuvant therapy (P = 0.004, q = 0.07). Patients with MDM2 amplifications or truncating biallelic TP53 mutations had similar outcomes in terms of poor responses to neoadjuvant therapy and, consequently, shorter progression-free survival, compared with patients with TP53 pathway wild-type tumors. Thus, worsening TP53 dysfunction was directly correlated with worse outcomes. Conclusions: MDM2 amplification and TP53 status are associated with response to therapy in patients with esophageal adenocarcinoma. Given the dearth of actionable targets in esophageal adenocarcinoma, MDM2 inhibition, in combination with cytotoxic chemotherapy, may represent an important therapeutic strategy to overcome treatment resistance and improve outcomes in these patients.

Esophagectomy for achalasia is reserved for patients with end-stage disease for whom prior treatment has failed. Esophagectomy can be performed safely through a variety of techniques. Conduit options include stomach, colon, and small intestine. There are many potential complications following esophagectomy. Outcomes of esophagectomy for achalasia are good when performed in experienced surgical centers.

Background This study evaluates the safety and feasibility of combined resection for patients with synchronous pulmonary and esophageal cancer. Methods Patients undergoing esophagectomy between 1997 and 2019 were identified from prospectively collected databases at three tertiary referral centers, and those with combined anatomic lung resection at the same setting were identified. This cohort was then matched in a 1:3 ratio to esophagectomy alone cases, based on age, sex, pathologic stage, neoadjuvant therapy, and surgical procedure. Demographic data, peri-operative data, post-operative complications were compared. Statistical analysis included unpaired t-test, Fisher’s exact or chi-squared test and Gehan-Breslow analysis. Results Of 4729 esophagectomies, combined anatomic lung resection was performed in 18 patients with discrete pulmonary lesions. Matching yielded 49 patients who underwent esophagectomy only and was statistically similar compared to patients undergoing combined resections. Ivor Lewis esophagectomy and lobectomy were the most frequent procedures. Combined resections did not have a higher overall complication rate than esophagectomy alone, rather these patients had fewer overall complications (56% vs 84%; p=0.02). Specifically, there was not difference in anastomotic leak (17% vs. 18%) or pulmonary complications (39% vs. 33%) between combined resection and esophagectomy alone. No post-operative mortality was identified, and median overall survival was 4.1 years versus 6.5 years (p=0.10). Conclusions Patients with synchronous localized lung and esophageal cancer, although rare, should not be biased towards non-surgical therapy, as the morbidity associated with combined esophagectomy and anatomic lung resection does not differ significantly from esophagectomy alone in this highly selected group of patients.

BackgroundPostoperative atrial fibrillation may identify patients at risk of subsequent atrial fibrillation, with its greater risk of stroke. This study hypothesized that N-acetylcysteine mitigates inflammation and oxidative stress to reduce the incidence of postoperative atrial fibrillation.MethodsIn this double-blind, placebo-controlled trial, patients at high risk of postoperative atrial fibrillation scheduled to undergo major thoracic surgery were randomized to N-acetylcysteine plus amiodarone or placebo plus amiodarone. On arrival to the postanesthesia care unit, N-acetylcysteine or placebo intravenous bolus (50 mg/kg) and then continuous infusion (100 mg/kg over the course of 48 h) was administered plus intravenous amiodarone (bolus of 150 mg and then continuous infusion of 2 g over the course of 48 h). The primary outcome was sustained atrial fibrillation longer than 30 s by telemetry (first 72 h) or symptoms requiring intervention and confirmed by electrocardiography within 7 days of surgery. Systemic markers of inflammation (interleukin-6, interleukin-8, tumor necrosis factor α, C-reactive protein) and oxidative stress (F2-isoprostane prostaglandin F2α; isofuran) were assessed immediately after surgery and on postoperative day 2. Patients were telephoned monthly to assess the occurrence of atrial fibrillation in the first year.ResultsAmong 154 patients included, postoperative atrial fibrillation occurred in 15 of 78 who received N-acetylcysteine (19%) and 13 of 76 who received placebo (17%; odds ratio, 1.24; 95.1% CI, 0.53 to 2.88; P = 0.615). The trial was stopped at the interim analysis because of futility. Of the 28 patients with postoperative atrial fibrillation, 3 (11%) were discharged in atrial fibrillation. Regardless of treatment at 1 yr, 7 of 28 patients with postoperative atrial fibrillation (25%) had recurrent episodes of atrial fibrillation. Inflammatory and oxidative stress markers were similar between groups.ConclusionsDual therapy comprising N-acetylcysteine plus amiodarone did not reduce the incidence of postoperative atrial fibrillation or markers of inflammation and oxidative stress early after major thoracic surgery, compared with amiodarone alone. Recurrent atrial fibrillation episodes are common among patients with postoperative atrial fibrillation within 1 yr of major thoracic surgery.Editor’s PerspectiveWhat We Already Know about This TopicWhat This Article Tells Us That Is New

Background Women in Thoracic Surgery (WTS) has previously reported on the status of women in cardiothoracic (CT) surgery. We sought to provide a 10-year update on women in CT surgery. Methods An anonymous research electronic data capture survey link was emailed to female diplomats of the American Board of Thoracic Surgery. Survey questions queried respondents regarding demographics, training, accolades, practice details, and career satisfaction. The survey link was open for 30 days. Results were compared with The Society of Thoracic Surgeons 2019 workforce survey. Descriptive analyses were performed using frequency and proportions. Comparisons were performed using Student's t tests, Fisher's exact tests, and χ2 tests. Results Of 354 female diplomats, 309 were contacted and 176 (57%) responded. The majority of respondents were aged 36 to 50 years (59%), white (67.4%), and had graduated from traditional-track programs (91.4%). Most respondents reported practicing in an urban (64%) and academic setting (73.1%). 36.4% and 23.9% reported a general thoracic and adult cardiac practice (22.7% mixed practice, 9.6% congenital). Fifty percent of respondents reported salaries between $400,000 and $700,000 annually; 37.7% reported salaries less than 90% of their male colleagues; 21.6% of respondents in academia are full professor; 53.4% reported having a leadership role. Whereas 74.1% would pursue a career in CT surgery again, only 27.3% agreed that CT surgery is a healthy and positive environment for women. Conclusions The number of women in CT surgery has steadily increased. Although women are rising in academic rank and into leadership positions, salary disparities and the CT surgery work environment remain important issues in achieving a diverse work force.

Background: Laparoscopic anti-reflux surgery, including hiatus hernia repair, is a common operation performed by both general and thoracic surgeons and an important learning objective for surgical trainees. This study aimed to design a competency assessment instrument for laparoscopic anti-reflux surgery. Method: A comprehensive competency assessment instrument was designed by a process of logical analysis by 4 expert thoracic surgeons with an interest in foregut surgery, and then reviewed informally by a panel of experts. The instrument was then further assessed and refined using a modified Delphi process. The Delphi questionnaire was distributed to all members of the Fellowship Training Committee of the American Foregut Society (n = 21). Results: A first draft of the competency assessment instrument included 32 steps in 4 categories. The first round of the Delphi review was completed by 14 respondents (response rate 66.7%). A total of 3 rounds of Delphi review were performed. Ultimately, 25 items were retained from the original instrument and 1 modified and 4 new items were added. The final instrument has 30 steps in 4 categories. Conclusions: An international and inter-specialty consensus was established on the key components of assessing competence to perform anti-reflux surgery. The resulting instrument could be used to guide competency based assessments of general and thoracic surgeons and trainees.

e16038Background: Esophageal cancer primarily affects older adults, who are at highest risk for poor nutritional status due to medical comorbidities, physiological changes of aging and geriatric is...

PURPOSEComprehensive genomic profiling has defined key oncogenic drivers and distinct molecular subtypes in esophagogastric cancer; however, the number of clinically actionable alterations remains limited. To establish preclinical models for testing genomically driven therapeutic strategies, we generated and characterized a large collection of esophagogastric cancer patient–derived xenografts (PDXs).MATERIALS AND METHODSWe established a biobank of 98 esophagogastric cancer PDX models derived from primary tumors and metastases. Clinicopathologic features of each PDX and the corresponding patient sample were annotated, including stage at diagnosis, treatment history, histology, and biomarker profile. To identify oncogenic DNA alterations, we analyzed and compared targeted sequencing performed on PDX and parent tumor pairs. We conducted xenotrials in genomically defined models with oncogenic drivers.RESULTSFrom April 2010 to June 2019, we implanted 276 patient tumors, of which 98 successfully engrafted (35.5%). This collection is enriched for PDXs derived from patients with human epidermal growth factor receptor 2–positive esophagogastric adenocarcinoma (62 models, 63%), the majority of which were refractory to standard therapies including trastuzumab. Factors positively correlating with engraftment included advanced stage, metastatic origin, intestinal-type histology, and human epidermal growth factor receptor 2–positivity. Mutations in TP53 and alterations in receptor tyrosine kinases ( ERBB2 and EGFR), RAS/PI3K pathway genes, cell-cycle mediators ( CDKN2A and CCNE1), and CDH1 were the predominant oncogenic drivers, recapitulating clinical tumor sequencing. We observed antitumor activity with rational combination strategies in models established from treatment-refractory disease.CONCLUSIONThe Memorial Sloan Kettering Cancer Center PDX collection recapitulates the heterogeneity of esophagogastric cancer and is a powerful resource to investigate mechanisms driving tumor progression, identify predictive biomarkers, and develop therapeutic strategies for molecularly defined subsets of esophagogastric cancer.

ispartof: JOURNAL OF THORACIC DISEASE vol:15 issue:1 pages:204-213 ispartof: location:China status: published

Background Unintentional weight loss and malnutrition are associated with poorer prognosis in patients with cancer. Risk of cancer‐associated malnutrition is highest among patients with esophageal cancer (EC) and has been repeatedly shown to be an independent risk factor for worse survival in these patients. Implementation of nutrition protocols may reduce postoperative weight loss and enhance recovery in these patients. Methods We retrospectively identified all patients who underwent Ivor Lewis esophagectomy for EC from January 2015 to August 2019 from a prospectively collected institutional database. Patients who underwent surgery after the implementation of this protocol (September 2017–August 2019) were compared with patients who underwent resection before protocol implementation (January 2015–July 2017). Patients undergoing surgery during the month of protocol initiation were excluded. Results Of the 404 patients included in our study, 217 were in the preprotocol group, and 187 were in the postprotocol group. Compared with the preprotocol group, there were significant reductions in length of hospital stay (p

We present the case of a patient who developed esophageal adenocarcinoma after a previous laparoscopic sleeve gastrectomy. Bariatric surgery has emerged as the most effective treatment option for weight loss and obesity-related diseases; however, sleeve gastrectomy promotes gastroesophageal reflux and leads to Barrett’s esophagus in a substantial portion of patients. The natural history of Barrett’s esophagus in these patients is unknown, and active surveillance is recommended until the incidence of dysplasia and adenocarcinoma in this population is clarified. Management options for these patients include conversion to Roux-en-Y gastric bypass. Although esophagectomy in patients who have previously undergone sleeve gastrectomy may require an alternative conduit, the remnant stomach can be used in carefully selected patients. Here, we review the different weight loss procedures, their effect on gastroesophageal reflux disease and Barrett’s esophagus, and the treatment options for patients with esophageal cancer after sleeve gastrectomy. We report the use of preoperative coil embolization as a means of vascular preconditioning before successful use of a gastric conduit.

BACKGROUND: More than half of patients treated with esophagectomy for esophageal cancer experience recurrence. Oligometastasis, a proposed intermediate state of isolated local or solid-organ recurrence that occurs before widespread systemic disease, is a potential target for aggressive local intervention. We investigated presentation and prognosis between solid-organ recurrence sites. METHODS: Patients with isolated solid-organ recurrence at the liver, lung, or brain who underwent R0 esophagectomy from 1995 to 2016 were identified. Clinicopathologic characteristics and outcomes were compared between sites of recurrence. Overall survival was quantified using the Kaplan-Meier approach and Cox proportional hazards models. RESULTS: In total, 104 patients were included (site: brain, 37; lung, 27; liver, 40). Eighty percent of liver, 51% of brain, and 44% of lung oligometastases occurred in the first 12 months after esophagectomy. Despite the limited use of aggressive therapy, patients with lung oligometastasis had significantly longer median overall survival (2.41 years; 95% confidence interval [CI], 1.58–3.31) than patients with brain (0.95 years; 95% CI, 0.62–1.49) or liver (0.95 years; 95% CI, 0.82–1.41) oligometastasis (p

Background Minimally invasive (MIS) esophagectomy is the preferred approach for surgical resection of the esophagus in many centers. This video demonstrates our approach to MIS Ivor Lewis esophagectomy. Operation MIS Ivor Lewis esophagectomy begins with the abdominal portion of the case and ends in the chest. The abdominal portion involves lymphadenectomy of the celiac trunk and division of the left gastric pedicle, mobilization of the greater curvature, transhiatal dissection, creation of the conduit and feeding tube placement. The thoracic portion involves division of the pleura and azygous vein, circumferential mobilization of the esophagus, division of the esophagus, gastric pullup, division of the specimen with pathologic assessment of margins, mediastinal lymphadenectomy, assessment of conduit perfusion, and anastomosis. Conclusions MIS Ivor Lewis esophagectomy allows for significant reduction in the morbidity associated with open resection, while offering equivalent oncological outcomes. This article is a video atlas that describes the steps of this operation.