Jaroszewski, Dawn E.

e15567 Background: Esophageal adenocarcinoma (EAC) prognosis is poor and there is a need to identify patients that benefit most from neoadjuvant therapy. To examine the association of various biomarkers with clinical outcomes in neoadjuvant treatment of EAC, we retrospectively evaluated the biomarker expression (TS, ERCC1, TOPO1, PD-L1, PD-1) in patient matched formalin-fixed paraffin-embedded (FFPE) tumor samples. Methods: Immunohistochemistry of TS (TS106/4H4B1) , ERCC1 (Ab. 8F1), TOPO1 (1D6), PD-L1 (both 22c3 and SP142), PD-1 (NAT105), and chromogenic in-situ hybridization (CISH) of Her2 were performed on FFPE samples from 35 patients across 2 institutions at time of EAC diagnosis and after treatment when available. Retrospective clinical data and survival (5/2006-1/2016) was analyzed with a mean follow up of 110 months (range 22-306). Results: Overexpression (pre/post-treatment) of TS (60%/54%), ERCC1 (69%/16%), TOPO1 (74%/50%), PD-1 (54%/63%), PD-L1 (SP142) (2.9%/4%), PD-L1 (22c3) (0%/4%) and amplification of Her2 (18%/23%) were observed. Pretreatment observed PD-L1 levels were lower in our study (3%) when compared to other studies in EAC specimens (35%). Immunohistochemistry and changes observed after chemoradiation are reviewed in Table. No markers had significant correlation with prognosis however TS negative expression showed a non-significant (p=0.15) trend towards improved survival. Conclusions: Analyzing biomarkers in our neoadjuvant EAC cohort demonstrated a lower than expected PD-L1 positivity. In the largest cohort, to our knowledge, of patient matched FFPE tumor samples, we did not observe a statistically significant association between TS, ERCC1, TOPO1, PD-L1, or PD-1 with improved clinical outcomes. [Table: see text]

e15563 Background: Expression of thymidylate synthase (TS), a target of fluoropyrimidine-based (5-FU) chemotherapy, has prognostic value in colorectal adenocarcinoma. Its value as a biomarker in treatment of esophageal adenocarcinoma (EAC) is unknown. With widespread adoption of CROSS trial protocol for treatment of EAC, 5-FU is frequently omitted from regimens. We retrospectively analyzed the association between TS protein expression and clinical outcomes in EAC. Methods: TS expression levels were measured by immunohistochemistry in formalin-fixed paraffin-embedded specimens from 35 primary EAC patients from 2 institutions (range 5/2006-1/2016); at time of diagnosis and surgical resection (33 neoadjuvant chemoradiation and 2 surgery alone). TS expression higher than 1+, 5% was read as positive. Mean follow up was 1323 days (range 263-3677). TS expression correlated with treatment response and survival in patients treated with and without 5-FU therapy (log-rank test, Kaplan-Meier method). Results: In the cohort of 35 patients, 21 patients (60%) had pretreatment positive TS expression. Overall survival (OS) for TS negative patients was 1216 days versus 974 days for TS positive (p = 0.15). In the 23 patients treated with 5-FU, TS-negative patients had a trend towards longer overall survival compared to TS-positive patients, mean OS (1272 days versus 743 days, p = 0.08). In the group of 12 patients not treated with 5-FU, 2 patients showed negative TS staining. Neoadjuvant chemoradiation was performed in 33/35 patients. Downstaging was observed in 69% (9/13) of patients with negative pre-treatment TS levels versus 55% (11/20) in pre-treatment TS positive patients (p = 0.48). In 23 patients treated with 5FU, 9/12 (75%) were downstaged in the TS-negative cohort versus 6/11 (45%) in the TS-positive cohort (p = 0.21). In the 5FU treatment group, complete response was seen in 2 patients with negative TS staining. Conclusions: Low TS expression in EAC patients trended towards improved survival and tumor downstaging, particularly in patients treated with neoadjuvant 5-FU and platinum based therapy. Prospective data and greater patient numbers may be necessary to demonstrate statistical significance.

AbstractPatients with pectus excavatum (PE) frequently present with complaints of exercise intolerance and cardiopulmonary symptoms. There continues to be controversy regarding the physiologic benefits of repair. The aim of this review is to summarize and discuss recent data regarding the cardiopulmonary effects of PE deformity and the evidence for improvement obtained after surgical repair including (1) a greater efficiency of breathing (chest wall mechanics), (2) improvement in pulmonary restrictive deficits, (3) an increase in cardiac chamber size and output, with improved cardiac strain and strain rate, and (4) improvement in exercise capacity.

Objective Patients in acute cardiogenic shock are the most challenging patients to manage. Unless a mechanical circulatory assist device is placed, maintaining end-organ function can be difficult. Transporting cardiogenic shock patients to tertiary care centers for higher level care also is difficult. The Mayo Clinic Arizona uses a SWAT team approach to deploy a specialized medical or surgical multidisciplinary team to implant mechanical circulatory assist devices at referring hospitals and transport patients back to Mayo Clinic Arizona. Results The cardiac transport team at Mayo Clinic Arizona got 23 referrals from 15 local community hospitals from February 2006 to September 2009. The medical team deployed for transfers of 6 patients, 3 of whom survived to hospital discharge. The surgical transport team deployed for transfers of 17 patients (6 with left ventricular assist devices, 2 with right ventricular assist devices, 5 with biventricular assist devices, and 4 with extracorporeal membrane oxygenation), of whom 8 survived to hospital discharge. Ten of the 17 referrals (59%) required a surgeon to place a mechanical circulatory assist device at the referring hospital. Conclusion The SWAT team approach allows cardiogenic shock patients to be stabilized at the referring hospital by heart failure and cardiac surgical specialists. If necessary, a surgeon from Mayo Clinic Arizona places a mechanical circulatory assist device at the referring hospital to stabilize the patient. Doing so allows safe transport back to the tertiary care center for higher level care and possible transplant evaluation with placement of a long-term durable device.

179 Background: GISTs arise from interstitial cells of Cajal anywhere within the gastrointestinal tract, but those of the esophagus and GEJ are exceedingly rare ( < 1% of cases). Our aim was to characterize clinicopathological features and outcomes of esophageal and GEJ GISTs and compare survival with a population-based registry (SEER). Methods: 28 cases were identified using the Mayo Clinic Cancer Registry from 1997 to 2016, and 378 cases from the SEER 18 registry from 2000 to 2013. Mayo cases were re-reviewed by Mayo pathologists. We analyzed patient characteristics, tumor location, TNM staging, mitotic index, molecular diagnostics, IHC staining, and histomorphology. JMP software was used to calculate time to recurrence (TTR) and overall survival (OS) utilizing Kaplan-Meier and log-rank. Results: At Mayo, 60% of tumors arose in the distal esophagus. Mean tumor size was 5.73 cm. 42% of cases were low grade. None had nodal involvement. Five cases were metastatic at diagnosis, all to the liver. 86.7% had spindle cell morphology. IHC staining was positive for KIT in 92%, followed by CD34 (52%), DOG-1 (24%), and actin (16%). Mutational analysis was done on 10 cases and KIT mutation was found in 8 cases; 2 were wild-type. Two-thirds of patients underwent surgery, mostly esophagectomy. 14 patients received adjuvant imatinib. Median time to diagnosis from symptom onset was 2 months; median time to surgery from diagnosis was 1 month. Of 10 patients with complete follow-up, 2 had recurrences: 1at the anastomotic site and 1 in the liver. Median TTR from surgery was 36.5 months. Median follow-up time was 31.5 months. Median OS from diagnosis for the Mayo cohort was 129.5 months (95% CI 55.7-x). SEER cohort median OS was 81 months (95% CI 63-101), and females had superior OS compared to males (HR 0.67; 95% CI 0.48-0.93, p = 0.016). Conclusions: Patients undergoing surgical resection for esophageal and GEJ GISTs had a favorable prognosis, but recurrences occurred. The superior OS seen in the Mayo cohort suggests early resection and adjuvant imatinib may improve outcomes.

165 Background: Distant metastases are common in primary esophageal cancer, but data conflict regarding the rates of brain metastases (BM) ranging from 0% to 13%. We sought to investigate whether the incidence of BM from esophageal malignancies is increasing in the modern era. Methods: After IRB approval, a single institution retrospective review identified 583 patients (pts) treated between 1/1997 and 1/2016 for stage I-IV cancer of the esophagus/esophagogastric junction with at least 3 months follow-up. Data collected included demographic information, primary diagnosis date and staging, histologic subtype, treatment regimens for primary and BM, date of BM diagnosis, status of neurologic symptoms and extracranial disease at BM diagnosis, and date of death. Data were analyzed by Fischer’s exact test and Kaplan-Meier analysis. Results: The overall cohort was comprised of 495 pts (85%) with adenocarcinoma and 82 pts (14%) with squamous cell carcinoma. 492 pts (84%) were male; the median age was 68 years (range 26-90). BM were identified in 22 pts (3.8%) with a median latency of 11 months from the primary diagnosis. Of the pts with BM, the primary histology was adenocarcinoma in 21 pts and squamous cell carcinoma in 1 pt ( P = 0.3). BM developed in 12 pts who were initially treated for locally advanced disease and in 10 pts who presented with distant metastases. Diagnosis of BM was at the time of initial presentation in 4 of these 10 stage IV pts. A solitary BM was identified in 9 pts. Initial treatments of BM were surgical resection followed by stereotactic radiosurgery (SRS; n = 5); surgical resection followed by whole brain radiotherapy (WBRT; n = 1); WBRT alone (n = 13); SRS alone (n = 3). Overall survival (OS) following diagnosis of BM was 18% at 1 year with a median of 4 months. OS was superior for pts who had surgical resection as initial treatment of BM compared to pts treated with WBRT or SRS alone (1-year OS 67 vs. 0%; median OS 13.5 vs. 3 months; P = 0.003). Conclusions: The incidence of BM is low in esophageal cancer with no statistically significant increased rate of BM developing in patients with adenocarcinoma compared with squamous cell carcinoma. Outcomes were poor overall for pts who developed BM, but pts who were appropriate for neurosurgical resection had improved survival.

134 Background: Brain metastasis (BM) is an uncommon site of failure in patients (pts) with esophageal cancer (EC) with reported rates between 1-6%. EC pts are living longer with the wider adoption of trimodality therapy and, as with other malignancies, this may change the patterns of failure. We evaluated the incidence and outcomes of BM in EC at Mayo Clinic in Arizona. Methods: A retrospective review identified pts who developed BM from cancer of the esophagus or gastroesophageal junction. A total of 321 patients treated for stage I-IV EC (adenocarcinoma, n = 273; squamous, n = 46; small cell, n = 2) were identified between 1997 and 2012. Fisher’s exact test was used for comparisons. Actuarial survival was calculated using Kaplan-Meier analysis. Results: BM developed in 13 pts (4%), all of whom had adenocarcinoma. Nine pts initially presented with T3 and/or node-positive disease. Four pts presented with metastatic disease to other sites, but only 1 of this group was diagnosed with BM at initial presentation. The median time from initial diagnosis to BM detection was 12 months (range 0-40). All pts were symptomatic at diagnosis. BM was solitary in 6 pts, multiple in 6 pts, and unknown in 1 pt. The posterior fossa was involved in 9 pts. The brain represented the first site of failure in 9 pts. Treatment included surgical resection (n = 5), stereotactic radiosurgery (n = 4), and whole brain radiotherapy (n = 9). Median overall survival was 24 months from initial diagnosis and 5 months from BM detection. Among pts with adenocarcinoma, 3/119 (2.5%) were diagnosed between 1997-2006 compared to 10/154 (6.5%) between 2007-2012 (P = 0.1). Conclusions: The brain remains an uncommon site of failure among pts with EC. A recent series reported an incidence of BM in 13% of pts, raising the possibility of a changing failure pattern. In our series, BM was detected in only 4% of pts. Our study is suggestive of a trend towards increased incidence of BM in more recent years, although it did not reach statistical significance and could be a consequence of the retrospective nature of the study. Both series found BM limited only to pts with adenocarcinoma, and a possible association has been reported between HER-2 overexpression and BM in EC. Therefore, BM in EC may be an interesting area for future study.

110 Background: Anastomotic leaks can occur after esophagectomy and optimal management after minimally invasive esophagectomy (MIE) is not well defined. We reviewed endoscopic management of leaks after MIE in patients undergoing trimodality therapy at Mayo Clinic Arizona. Methods: Records of patients undergoing MIE from November, 2006 to February, 2015 were reviewed after appropriate IRB approval. Results: 148 patients underwent MIE including 136 (91.8%) thoracic and 12 (8.1%) cervical anastomoses. Clinically significant anastomotic leaks were observed in 13 (8.8%) patients with 2 (16%) cervical and 11 (8%) thoracic anastomosis at a median of 6.1 days (0-14). 11 (11%) patients treated with neoadjuvant chemoradiotherapy experienced esophageal leak and 2 who did not receive chemoradiotherapy (4%). For treatment of anastomotic leaks, 10 patients underwent VATS with pleural space irrigation and chest tube replacement, and 11 patients underwent stent deployment at the anastomosis for repair. Stents were placed such that the fistula/leak was in the fully covered portion with the greater portion of the stent residing in the esophageal remnant. Stents were removed at a mean of 54 days (28-114). In 2 patients, overgrowth into the stent body required stent-in-stent placement (fully covered) with removal of both stents. Stents were successful at sealing all leaks. Conclusions: Leaks after MIE represent a small, but significant, morbidity in MIE. The majority can be managed by endoscopic stent placement. Stenting is an effective management tool for postoperative leaks in locally advanced esophageal malignancies.

158 Background: Esophageal cancer patients (pts) require multidisciplinary management involving thoracic and general surgeons, medical and radiation oncologists, gastroenterologists and psychiatrists. Pts navigate complex medical discussions and endure challenges to nutrition, body image, swallowing mechanics, energy level and weight, mood, and performance status. Coordination of care is complicated by multiple sites of pt entry, complex scheduling requirements, and incomplete information at multidisciplinary consultation. A nurse navigator to coordinate the patient experience may optimize treatment and improve outcomes, quality of life and patient satisfaction. Methods: The nurse navigator evaluates all pt records prior to initial appointment and coordinates scheduling, records acquisition, testing and specialty appointments. The nurse navigator serves as a liaison with pts throughout the course of care and provides a patient navigation book (PNB) as a central source for patient-directed information and record keeping. Benchmarks compared before and after creation of the nurse navigator position include: (1) time from appointment request to multidisciplinary evaluation and start of treatment; (2) completeness of medical records and data (scans, pathology slides); (3) patient awareness of support services for themselves and caregivers; (4) utilization of the PNB; (5) number and frequency of interim hospitalizations and emergency room visits; (6) patient, caregiver, and physician satisfaction. Results: From January to July 2012, 27 gastroesophageal cancer pts have been followed by the nurse navigator. Most of these patients remain on active treatment, hence benchmark analysis is ongoing. Metrics thus far suggest improvement in time to treatment start and awareness of patient resources, use of the PNB and patient satisfaction. Conclusions: Esophageal cancer pts undergo complex and toxic multimodality therapy with curative intent. A dedicated nurse navigator may improve the patient experience, optimize adherence to guideline based therapy and appropriate timeframes and provide continuity to pts undergoing multidisciplinary treatment.