40.01 The Use of Fluorescent-labeled Cetuximab for Image-guided Soft Tissue Sarcoma Surgery

Posted on January 25, 2017

N. K. Behnke1, A. C. Prince2, J. M. Warram1  1The University Of Alabama At Birmingham,Department Of Surgery,Birmingham, AL, USA 2University Of Alabama,School Of Medicine,Birmingham, Alabama, USA

BACKGROUND: Soft tissue sarcomas (STS) are a heterogeneous group of solid malignancies whose treatment includes margin-negative resection. Large tumor size and anatomic constraints make margin assessment challenging. Fluorescence-guided surgical resection can help delineate intraoperative margins; preclinical studies demonstrate improved oncologic outcomes in other malignancies using cancer-specific imaging probes.  Recent literature describes cathepsin activated probes selective for STS, but no studies using disease-specific chemotherapeutic agents conjugated to imaging probes.  This novel strategy has potential to decrease unnecessary healthy tissue resection and improve oncologic outcomes by reducing margin-positive resections.

 

Epidermal growth factor receptor (EGFR) is overexpressed in multiple subtypes of STS and is a potential target for fluorescence-guided surgery.  Recent studies show fluorescently labeled cetuximab, an FDA-approved, anti-EGFR antibody, to be safe and useful for margin assessment in head and neck cancer. Our aim was to evaluate its potential for STS, examining tumor-targeting specificity of two drug-probe conjugates, and comparing them to the described cathepsin-activated probes.  We hypothesize the drug-probe conjugates would successfully target STS, with superior tumor specificity.  We also aimed to determine the smallest tumor detectable by our imaging probe conjugate.

Methods: Athymic nude mice with subcutaneous HT1080 fibrosarcoma tumors were injected with one of five probes:  IRDye800CW fluorescent probe conjugated to either cetuximab (anti-EGFR) or DC101 (anti-VEGFR2), IRDye800CW conjugated to an isotype control (IgG), or a cathepsin-activated probe (IntegriSense 750 and Prosense 750). Fluorescence imaging was performed daily with open- and closed-field systems. Tumor-to-background ratios (TBR), signal washout times and normalized signal averages were evaluated.  On day 9, smallest resectable game evaluation was performed to assess sensitivity for detecting residual post-resection tumor

Results: At day 9 post-injection, the TBR of the cetuximab-IRDye800CW group (11.1) was significantly greater than Integrisense750 (6.88, p=0.005), the IgG-IRDye800CW control (4.44, p=0.00005), Prosense750 (2.35, p=0.00009), and DC101-IRDye800CW (1.87, p=0.00003). During in vivo imaging, cetuximab-IRDye800CW outperformed all other agents by several folds of contrast enhancement. The smallest resectable game evaluation demonstrated 1mm3 fragment detection using the cetuximab-IRDye800CW probe.

Conclusions: This study demonstrates superiority of cetuximab-IRDye800CW for disease-specific imaging in a subcutaneous animal model of STS.  The novel strategy of coupling improved margin-negative surgical resection with established chemotherapy has considerable translational significance and is an avenue for exploration with other drugs used to treat STS. 

 

30.10 Impact of Neoadjuvant Dose Escalation on Downstaging & Perioperative Mortality in Esophageal Cancer

Posted on January 25, 2017

S. Ji3, S. Thomas5,7, K. Anderson3, J. Frakes2, S. Roman4,7,8, J. A. Sosa4,6,7,8, T. Robinson2  3Duke University Medical Center,School Of Medicine,Durham, NC, USA 4Duke University Medical Center,Department Of Surgery,Durham, NC, USA 5Duke University Medical Center,Department Of Biostatistics And Bioinformatics,Durham, NC, USA 6Duke University Medical Center,Department Of Medicine,Durham, NC, USA 7Duke Cancer Institute,Durham, NC, USA 8Duke Clinical Research Institute,Durham, NC, USA 1Duke University Medical Center,Durham, NC, USA 2Moffitt Cancer Center And Research Institute,Tampa, FL, USA

Introduction:

The addition of neoadjuvant chemoradiation prior to resection of locally advanced esophageal cancer has been shown to improve disease-free and overall survival. However, the optimal radiation dose remains unknown, and conventional U.S. practice has been to use a higher dose (50.4 Gy) than that used in recent European trials (41.4 Gy). Our objective was to characterize current U.S. practice patterns and compare primary tumor and nodal down-staging, perioperative mortality, and overall survival as a function of total radiation dose. 

Methods:

We performed a retrospective analysis of adult patients with non-metastatic esophageal cancer diagnosed between 2004 and 2013 within the National Cancer Data Base treated with neoadjuvant chemoradiotherapy followed by resection. The primary outcome was overall survival. Secondary outcomes included 30- and 90-day mortality and pathologic down-staging. Univariate and multivariate analyses were used to assess the association between selected outcomes and total radiation dose (41.4, 45.0 or 50.4 Gy) after controlling for patient demographic and clinical factors. 

Results: 

A total of 5,835 patients met inclusion criteria: 154 (2.6%) received 41.4 Gy, 1,696 (29.1%) 45 Gy and 3,985 (68.3%) 50.4 Gy. Patient demographic characteristics and comorbidities were balanced among groups. The use of 41.4 and 50.4 Gy both increased substantially (2.1% to 6.3% and 45.1% to 75.4%, respectively), while use of 45 Gy decreased (52.9% to 18.3%) during the study period (p<0.001). Compared with the 41.4 Gy group, patients receiving 45 and 50.4 Gy had higher rates of nodal down-staging (49% and 48% vs. 38%, respectively; p=0.05). Survival outcomes including 30-day, 90-day and overall survival did not vary significantly by radiation dose; however, patients receiving 41.4 Gy had numerically lower rates of 30-day and 90-day (0.0% and 1.3%) mortality compared to those with 45.0 Gy (2.8% and 7.0%) or 50.4 Gy (2.7% and 6.1%; p=0.21 for 30-day; p=0.16 for 90-day mortality, respectively). 

Conclusion:

To our knowledge, this study provides the first nationally representative assessment of neoadjuvant chemoradiation dose escalation practice patterns in the treatment of locally advanced esophageal cancer in the U.S. We observed no statistically significant differences in overall or short-term survival as a function of radiation dose. Although higher radiation doses were significantly associated with improved nodal down-staging, lower dose radiation exhibited a non-significant trend towards lower 30- and 90-day mortality rates. Our study lends support to neoadjuvant approaches that balance lower elective doses (41.4 Gy) to minimize toxicity while maintaining higher doses (50.4 Gy) to gross disease to maximize locoregional control. Further research is warranted to assess the impact of neoadjuvant radiation dose escalation on locoregional disease control, perioperative complications, and overall survival. 

30.09 Stromal MZB1 is a Prognostic Factor of Pancreatic Cancer Resected After Chemoradiotherapy

Posted on January 25, 2017

K. Miyake1, R. Mori1, R. Matsuyama1, Y. Homma1, A. Okayama2, Y. Ota1, K. Taniguchi1, H. Hirano2, I. Endo1  2Yokohama City University,Graduate School Of Medical Life Science And Advanced Medical Research Center,Yokohama, KANAGAWA, Japan 1Yokohama City University,Department Of Gastroenterological Surgery,Yokohama, KANAGAWA, Japan

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is classified to three types following the resectability in NCCN Guidelines, namely Resectable, Borderline resectable (BR), and Unresectable. BR cases invade to surrounding major arteries and/or vein. Therefore, it is not easy to achieve R0 resection by straightforward surgery. Recently, several studies have reported that NACRT for BR-PDAC improves prognosis and resectability, and eradicates micro metastases. Furthermore, it is presumed that NACRT induces antitumor immunity, and the accumulation of tumor infiltrating lymphocytes (TILs) correlate with prognosis. In our department, we have started clinical research of NACRT for BR-PDAC from Jan 2009. In fact, we have already reported that high CD8+ TILs might be a predictive marker of long survival for these cases. However, the feature of cases with high CD8+ TILs has not been clarified. In this study, we have performed proteomic analysis to reveal the predictive marker of high accumulation of CD8+ TILs.

Methods: We studied 72 resected BR-PDAC cases with NACRT from Jan 2009 to Mar 2014. Three matched pairs of high CD8+ TILs with good prognosis and low CD8+ TILs with poor prognosis cases were selected. Shotgun proteomics was performed using the cancerous part and tumor stroma which are extracted from formalin-fixed and paraffin-embedded tissue samples. For validation of identified proteins, immunohistochemistry (IHC) was performed. 44 PDAC cases with straight forward surgery from 2006 to 2014 were evaluated for comparison. Relationships between the identified proteins and NACRT, TILs, clinical outcomes were assessed by statistical analysis.

Results: 369 proteins were identified by shotgun proteomics, and there was statistic difference of expression in 6 proteins. From these candidates, we selected one protein; Marginal zone B and B1 cell specific protein (MZB1), which is known for B lineage cell specific protein. MZB1 expression were detected in only tumor stroma, and tumor cells were negative. IHC showed high expression of stromal MZB1 in long survival cases with high CD8+ TILs as with proteomic analysis. In the NACRT group (n=72), high expression of stromal MZB1 was positively correlated with the accumulation of CD8+ TILs (|R|=0.347, p=0.002). Patients with high accumulation of stromal MZB1 (?207) had a longer overall survival (OS) than others (3 year-survival; MZB1 high : low = 60.2% : 28.6%, p=0.014). Regarding the 36 patients with high CD8+ TILs in the NACRT group, there was statistic significant relationship between high expression of stromal MZB1 and OS (3 year-survival; MZB1 high : low = 72.9% : 42.9%, p=0.003). In straight forward group (n=44), there was no significant relationships between stromal MZB1 and accumulation of CD8+ TILs, or OS.

Conclusion: MZB1 might be a predictive marker of the high CD8+ TILs and long term survival of resected BR-PDAC cases after NACRT. Furthermore, MZB1 might have a promotive effect on anti-tumor immunity.

 

30.07 Impact of Peer Support on Colorectal Cancer Patients’ Adherence to Recommended Multidisciplinary Care

Posted on January 25, 2017

A. E. Kanters1, A. M. Morris1, P. H. Abrahamse2, L. Mody3, P. A. Suwanabol1  1University Of Michigan,Department Of General Surgery,Ann Arbor, MICHIGAN, USA 2University Of Michigan,Center For Cancer Biostatistics,Ann Arbor, MI, USA 3University Of Michigan,Department Of Internal Medicine,Ann Arbor, MI, USA

Introduction:  Multidisciplinary care is critical for the successful treatment of Stage III colorectal cancer (CRC), yet postoperative receipt of chemotherapy remains unacceptably low for unclear reasons. Peer support, or exposure to others who have undergone similar diagnoses and treatment, has been proposed as a means to improve patient acceptance of and coping with cancer care. However, the specific impact of peer support on colorectal cancer patients’ attitudes toward and adherence to recommended chemotherapy is unknown. 

Methods:  We conducted a population-based survey of patients in the Detroit and Georgia Surveillance, Epidemiology and End Results regions after surgery for Stage III CRC between 2011- 2013. For this study, we assessed patient-reported exposure to any peer support, adequacy of peer support, and attitudes towards chemotherapy, and analyzed their association with receipt of postoperative chemotherapy using χ2 tests.

Results: Among 1281 patient respondents (68% response rate), 56% reported exposure to some form of peer support. Exposure to peer support was associated with younger age, higher income, and having a spouse or domestic partner (p<0.001, p=0.016 and p<0.001, respectively). Exposure to any peer support was significantly associated with receipt of adjuvant chemotherapy (p<0.001), but amount or adequacy of peer support was not (p=0.74). Respondents reported that exposure to peer support had a primarily positive impact on their attitudes (e.g., 73% indicated that it helped them know what to expect). However, the few who reported negative impact on attitudes (e.g., 11% indicated that it made them more scared or anxious about treatment) were less likely to receive chemotherapy (p=0.020). Male patients and those with lower levels of education found that peer support helped with decision making for use of chemotherapy (p=0.007 and p=0.012, respectively). 

Conclusion: Our study demonstrates that peer support is associated with overall higher rates of postoperative chemotherapy adherence, except in the rare instances of a negative peer support experience. These data suggest that a facilitated peer support program could positively influence treatment decision making and uptake of recommended multidisciplinary care. 

30.06 Hospital Minimally Invasive Surgery Utilization for Gastrointestinal Cancer

Posted on January 25, 2017

M. C. Mason1,2, H. S. Tran Cao2, S. S. Awad1,2, F. Farjah3, G. J. Chang4, C. Chai2, N. N. Massarweh1,2  1Michael E. DeBakey VA Medical Center,Houston VA Center For Innovations In Quality, Effectiveness, And Safety,Houston, TX, USA 2Baylor College Of Medicine,Michael E. DeBakey Department Of Surgery,Houston, TX, USA 3University Of Washington,Department Of Surgery And Surgical Outcomes Reseach Center,Seattle, WA, USA 4The University Of Texas MD Anderson Cancer Center,Department Of Surgical Oncology And Health Services Research,Houston, TX, USA

Introduction: Laparoscopic and robotic techniques are applied across surgical specialties. However, the extent to which these minimally invasive surgery (MIS) techniques are applied for gastrointestinal (GI) cancer resection has not been well defined and the impact of receiving care at high MIS utilizing hospitals is unclear.

Methods: Retrospective cohort study of 137,581 surgically resected esophageal, gastric, pancreatic, hepatobiliary, colon, and rectal cancer patients within the National Cancer Data Base (2010-2013). Disease-specific, reliability-adjusted MIS utilization and conversion to open rates were calculated for each hospital and used to stratify hospitals into quartiles. Among gastric, pancreatic, and colon patients for whom AC was indicated, the association between days to AC and hospital MIS utilization was examined using generalized estimating equations.  The association with risk of death was evaluated with multivariable Cox regression.

Results: While disease-specific MIS use increased significantly (42.0-68.3% increase; trend test, p<0.001 for all but hepatobiliary [p=0.007]), most hospitals remained low MIS-utilizers. High MIS utilization is associated with increased lymph nodes examined (p<0.001 for all) and shorter LOS (p<0.001 for all). Among colon and rectal patients, mortality at 30 days (colon—0.7% lowest MIS quartile vs 0.4% highest quartile; trend test, p<0.001; rectal—1.1% vs 0.8%; trend test, p=0.018) and 90 days (colon—2.6% vs 2.0%; trend test, p=0.002; rectal—2.4% vs 1.6%; trend test, p=0.002) was lower at higher MIS utilizing hospitals. Except for colon, case volume was highest at hospitals in the lowest and highest conversion to open quartiles. However, hospital conversion rates were not clearly associated with worse perioperative outcomes. For gastric cancer, each 10% increase in hospital MIS utilization is associated with 3.3[95% CI, 1.2-5.3] fewer days to AC initiation. While this association was not observed for pancreatic or colon patients overall, time-to-AC was decreased by 3.3[0.7-5.8] days for gastric and 1.1 [0.3-2.0] days for colon patients who had open resection.  Relative to the lowest quartile hospitals, care at higher MIS utilizing hospitals was associated with a lower risk of death for colon (Q2–Hazard Ratio 0.96[0.89-1.02]; Q3–HR 0.91[0.86-0.98]; Q4–HR 0.87[0.82-0.93]) and rectal cancer patients (Q2–Hazard Ratio 0.89[0.76-1.05]; Q3–HR 0.84[0.72-0.97]; Q4–HR 0.86[0.74-0.98]).

Conclusions: Although MIS use for GI cancer has increased, most hospitals remain low utilizers. Shorter LOS at high utilizing hospitals and the lack of a clear association between hospital conversion rates and perioperative outcomes potentially reflect the real world effectiveness of MIS.  As data regarding MIS for GI cancer resection evolve, MIS utilization may help identify hospitals with infrastructure and care processes that can be used to facilitate multimodality cancer care.

30.05 Postoperative Outcomes From Rectal Cancer Resection in the U.S.: Still Room For Improvement

Posted on January 25, 2017

L. Gregorian1, E. Vo1, L. Haubert1,2, E. Choi1,2, S. S. Awad1,3, A. Artinyan1,2  1Baylor College Of Medicine,Houston, TX, USA 2Baylor St. Lukes Medical Center,Houston, TX, USA 3Michael E. DeBakey Veterans Affairs Medical Center,Houston, TX, USA

Introduction:
Colorectal cancer is a leading cause of cancer death in the US. We have previously described changes in cancer-specific rectal cancer treatment and long-term survival over the last 4 decades. The aim of our current study was to describe changes in early postoperative outcomes after curative-intent surgery for rectal cancer in the US. We hypothesized that postoperative outcomes such as length of stay (LOS), mortality, and postoperative complications have improved over time.

Methods:
The National Inpatient Sample and the Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality data were queried in 5 year intervals from 1993-2013 for patients with rectal adenocarcinoma, older than 18 years of age, who had undergone curative-intent surgery (n=16,419). Baseline characteristics (age, gender, type of operation) and postoperative outcomes (LOS, inpatient mortality, discharge disposition, and postoperative complications) were described. Clinical/demographic characteristics and postoperative outcomes were compared by discharge year. Continuous variables were compared using the 1-way analysis of variance (ANOVA) or non-parametric tests, and categorical variables were compared using the chi-square test.

Results:
The mean age of the entire population was 65.6±13.1 years. 58.7% of patients were male and median LOS was 8 (IQR 4-11) days. Mean age of diagnosis has decreased with time (68.3±12.1 in 1993 to 62.6±13.0 years in 2013, p<0.001). The proportion of male patients has increased in the same time period (56% to 62%, p<0.001). As in our prior study, sphincter-preserving operations increased significantly over time (51% in 1993 to 60.5% in 2013, p<0.001). During the same time period, perioperative hemorrhage and inpatient mortality decreased from 3.6% to 1.6% (p<0.001) and 1.9% to 0.7% (p<0.001), respectively. There was no clinically significant change in the surgical site infection (SSI) rate (4.3% to 4.6%, p<0.001), whereas anastomotic leak and digestive complications increased over time (9.8% to 12.7%, p<0.001). Median LOS decreased significantly from 10 (IQR 7-13) to 6 (IQR 4-9) days (p<0.001). However, non-home discharges and home-health use increased from 8.3% to 11.4% and 23.5% to 42.7%, respectively (p<0.001).

Conclusion:
The treatment of rectal cancer continues to evolve, with a greater emphasis on sphincter-preserving surgery, as well as decreases in perioperative hemorrhage and inpatient mortality. However, the rate of SSIs has not changed meaningfully and the risk of anastomotic and other digestive complications has increased, potentially secondary to anatomically lower pelvic anastomoses. Although LOS has decreased, there has been an increase in transitional care and home-health service needs. A shift toward organ-preserving strategies is likely necessary to further improve post-operative outcomes from rectal cancer surgery.

30.04 Age is an Important Risk Stratifier for Lymph Node Metastasis in Patients with Thin Melanoma

Posted on January 25, 2017

A. J. Sinnamon1, M. G. Neuwirth1, R. L. Hoffman1, D. E. Elder2, X. Xu2, R. R. Kelz1, R. E. Roses1, D. L. Fraker1, G. C. Karakousis1  2Hospital Of The University Of Pennsylvania,Department Of Pathology,Philadelphia, PA, USA 1Hospital Of The Univerity Of Pennsylvania,Endocrine And Oncologic Surgery,Philadelphia, PA, USA

Introduction:
While the association of age with nodal metastases and outcomes in patients with melanoma has been recognized and variably reported upon, the influence of age on nodal positivity in patients with thin melanoma has been less well studied, limited by few events in institutional experiences.  Using a large national dataset we study the association of age and nodal positivity in thin melanoma and its implications on current recommendations for sentinel lymph node biopsy in this patient population.

Methods:
Patients with clinical stage I 0.50-1.0mm thin melanoma diagnosed from 2010-2013 who underwent wide excision and had any LNs pathologically evaluated were identified using the National Cancer Data Base (NCDB). Nodes were defined as either positive or negative based on presence of any metastatic disease. Age was categorized as <40 years, 40-64 years, and ≥65 years. Clinicopathologic factors associated with LN positivity were identified using chi-square or Fisher exact method as indicated. Multivariable logistic regression was performed to identify predictors of LN positivity.

Results:
From 2010-2013, 8772 patients underwent wide excision and had evaluation of regional LNs. Of these, 333 were found to have nodal spread, for an overall positivity rate of 3.8%. Median age was 56y (IQR 46-67y) in those with negative LNs and 52y (IQR 41-61y) with LN disease (p<0.001). By multivariable analysis, age≥65 years, thickness≥0.76mm, increasing Clark level, mitoses, ulceration, and acral lentiginous or epithelioid histology were independently associated with LN positivity. Age was found to reliably stratify patients for LN positivity among other high risk features, namely tumor depth, mitogenicity, and ulceration status (figure).  Patients <40yo with T1a tumors<0.76mm (who would not generally be recommended SLN biopsy) had LN positivity rate of 5.56% (18/324 patients); conversely, patients ≥65yo with T1b tumors ≥0.76mm (who would generally be recommended for SLN biopsy) demonstrated LN positivity rate of 3.87% (37/956).  This pattern remained unchanged if including Clark level IV/V as a worrisome feature in addition to mitogenicity and ulceration.

Conclusion:

Current guidelines for SLN biopsy in patients with thin melanoma focused on tumor variables may be too restrictive in young patients and overly permissive among patients ≥65 years using a 5 percent threshold for LN positivity; patient’s age should be an important factor when counseling these patients for lymph node evaluation.

30.03 Impact of Time to Surgery in Patients with Clinical Stage I-II Pancreatic Adenocarcinoma

Posted on January 25, 2017

D. S. Swords1, C. Zhang2, A. P. Presson2, M. A. Firpo1, S. J. Mulvihill1, C. L. Scaife1  1University Of Utah,Department Of Surgery,Salt Lake City, UT, USA 2University Of Utah,Study Design And Biostatistics Center,Salt Lake City, UT, USA

Introduction:  Timeliness is a domain of healthcare quality, and wait times for cancer surgery have increased in recent years. Time to surgery (TTS) from diagnosis in pancreatic adenocarcinoma (PDAC) may be delayed due to the need for biliary decompression, multi-disciplinary review, or medical optimization. Existing data on the clinical impact of TTS have been conflicting.

Methods:  The National Cancer Database was reviewed from 2004-2012 for patients undergoing upfront resection of clinical Stage I-II PDAC with data on TTS. TTS was defined as time from diagnosis to resection. Patients with TTS of 0 or > 120 days and those that received neoadjuvant therapy were excluded. Patients with unknown clinical stage were excluded if pathologic stage was III-IV. Overall survival (OS) began at time of surgery and was the primary outcome. Multivariable Cox regression with TTS modeled as a restricted cubic spline was used to evaluate the relationship between TTS and mortality in order to define TTS groups. OS was evaluated with unadjusted Kaplan-Meier analysis and multivariate Cox regression analysis. Secondary outcomes were rates of positive margins, nodal positivity, and upstaging from clinical to pathologic stage; they were examined using logistic regression models adjusted for demographic and clinical characteristics.

Results: There were 15,945 patients available for analysis. Patients with TTS ≤ 2 weeks had the highest risk of mortality with a gradual decrease to 40 days, and then a gradual increase to 120 days. We thus defined TTS as: short (1-14 days, N=5,465), medium (15-42 days, N=8,241), and long (43-120 days, N=2,239). Adjusted odds of positive margins, nodal positivity, and upstaging were not significantly different between TTS groups. On unadjusted survival analysis, short TTS patients had slightly worse survival than medium and long (P<0.001, Log-rank). Survival differences between TTS groups were most pronounced in Stage I patients; long TTS  had superior survival to medium TTS, which was superior to short TTS (P<0.001 for both, Log-rank, Figure). On multivariate Cox proportional hazard analysis, short vs. medium TTS was associated with modestly increased hazards of mortality (Hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.02-1.11, P=0.003) but long vs. medium was not (HR 0.95, 95% CI 0.9-1.01, P=0.12).

Conclusion: Moderately longer TTS was not associated with worse outcomes and short TTS was associated with higher mortality, especially in Stage I disease. These findings should reassure patients and providers that reasonable delays are likely safe. However, we could not account for patients who initially were planned for resection but progressed on repeat imaging or who were unresectable on exploration.

30.02 Disparities in Managing Emotions when Facing Breast Cancer: Results of Couples Distress Screening

Posted on January 25, 2017

S. Dumitra1, V. Jones1, C. Vito1, J. Rodriguez1, C. Bitz1, E. Polamero2, M. Loscalzo2, R. Obenchain2, L. Kruper1, S. G. Warner1  1City Of Hope National Medical Center,Department Of Surgery,Duarte, CA, USA 2City Of Hope National Medical Center,Department Of Populational Sciences,Duarte, CA, USA

Introduction: Distress screening and referral is now required for cancer center accreditation. Understanding patient and caregiver stress is critical to successful cancer care. This study examines the perceived emotional impact of breast cancer on both patients and partners.

Methods: From March 2011 to February 2016, patients and partners underwent an electronic 48-point distress screen during their initial surgical clinic visit. Distress was measured via self-reported concerns on a five-point Likert scale. Respondents were also asked about preferred interventions. Patient and partner ability to manage emotions was assessed in relation to education, ethnicity, fatigue, anxiety and depression using ordered logistic regression.

Results: Of the 665 individuals screened, 51.7% (n=344) were patients while 48.3% (n=321) were partners. Patients were more distressed than partners regarding fatigue, anxiety, depression, and worrying about the future (p<0.005). Partners requested information regarding “managing emotions” less often than patients (19.7% vs. 46.3%).  In the univariate analysis for managing emotions, being partner was protective against self-reported distress (OR 0.49 (95%CI 0.34–0.70), p<0.000) as was holding an advanced degree (OR 0.36 (95%CI 0.14–0.93),p=0.035). In the multivariate ordered logistic regression, having at least some college remained protective against difficulty in managing emotions, while being a partner was not(OR 0.93 (95%C I0.62–1.39, p=0.789). Financial concerns, anxiety, depression, and worrying about the future remained significantly associated with increased difficulty in managing emotions (Table 1). After correcting for known variables, partners were found to ask for information or help less than patients(OR 0.28 (95%CI 0.17–0.48), p<0.000).

Conclusion: While partners have similar concerns as patients, they do not seek information or help in managing emotions. Both patients and partners with less education and increased financial distress were more likely to report difficulty managing emotions. This study identifies groups who would benefit from supportive measures even in the absence of a request for help.

30.01 Can Medicaid Expansion Decrease Disparity in Surgical Cancer Care at High Quality Hospitals?

Posted on January 25, 2017

D. Xiao1,2,3, C. Zheng1,2,3, M. Jindal1,2,3, C. Ihemelandu1,2,3, L. Johnson1,2,3, T. DeLeire2,3, N. Shara1,2,3, W. Al-Refaie1,2,3  1MedStar Georgetown University Hospital,Washington, DC, USA 2MedStar Georgetown Surgical Outcomes Research Center,Washington, DC, USA 3Georgetown University Medical Center,Washington, DC, USA

Introduction:  Skepticism on Medicaid program’s ability to provide quality care has contributed to the debate on Affordable Care Act’s (ACA) Medicaid expansion. It is unknown whether Medicaid expansion can improve access to high-quality surgical cancer care for poor Americans. To address this gap, we examined the effects of the largest pre-ACA expansion in Medicaid eligibility, which occurred in New York in 2001. We hypothesized that this policy decreased disparity in access to surgical cancer care at high-quality hospitals (HQH) by insurance type and by race.

Methods:  We identified 67,685 non-elderly adults 18-64 years old from the 1997-2006 New York State Inpatient Database who underwent one of nine major cancer resections. HQHs were defined as either high-volume hospitals (HVH, assigned yearly as hospitals of highest procedure volumes that treated 1/3 of all patients) or low-mortality hospitals (LMHs), whose observed-to-expected mortality ratio were < 0.7. Analysis examining access to HVH was restricted only to patients of procedures with strong volume-outcome relationship (esophagus, liver, stomach, pancreas, and urinary bladder; N=10,737).   

Disparity was defined as the model-adjusted difference in percentage of patients operated at HQH by insurance type (Medicaid/uninsured vs privately insured) or by race (blacks vs whites). Consistent with published literature, we combined Medicaid and uninsured patients to capture changes in access to care due to newly gained Medicaid coverage by an otherwise uninsured patient. Covariates included age, sex, procedure type and emergency admission. Levels of disparity were calculated quarterly for each pair of comparison, then regressed using interrupted time series to evaluate the impact of Medicaid expansion.

Results: Overall, 15.0% of our study cohort were Medicaid/self-pay and 12.1% were blacks. The disparity in access to HVH by insurance type was reduced by 0.61 percentage points per quarter following the expansion (p=0.003) (Figure). Meanwhile, the Medicaid/uninsured beneficiaries had similar access to LMH as the privately insured; no significant change was detected around the expansion. Conversely, racial disparity has increased by 0.86 percentage points per quarter (p<0.001) in access to HVH (Figure) and by 0.48 percentage points per quarter (p=0.005) in access to LMH after the expansion.

Conclusions: The pre-ACA Medicaid expansion reduced the disparity in access to surgical cancer care at HQH by insurance type. However, it was associated with an increased racial gap in access to HQH for surgical cancer care. Further investigations are needed to explore whether Medicaid expansion may aggravate racial disparity in surgical cancer care.

29.10 Does High Expression of Tumor Suppressive MicroRNA Prolong Survival of Breast Cancer?

Posted on January 25, 2017

T. Kawaguchi1, L. Yan2, Q. Qi2, S. Liu2, J. Young1, K. Takabe1  1Roswell Park Cancer Institute,Breast Surgery, Department Of Surgical Oncology,,Buffalo, NY, USA 2Roswell Park Cancer Institute,Department Of Biostatistics & Bioinformatics,Buffalo, NY, USA

Introduction:
MicroRNAs (miRNAs) are noncoding RNAs with 19-25 nucleotides that exert its function by either degradation of coding mRNA or inhibition of mRNA translation. Dysregulations of miRNAs have been reported to play critical roles in carcinogenesis and progression of various types of cancer including breast cancer (BrCa). Some miRNAs, such as miR-31, miR-126, miR-146b, miR-206, miR-335, have been reported as tumor suppressive miRNAs targeting oncogenes. However, clinical relevance of those reports has not yet been validated using common large cohort, which provides sufficient statistical power with proved high quality genetic samples. In this study we took advantage of the high-throughput data from The Cancer Genome Atlas (TCGA) as a validation cohort to evaluate the clinical relevance of well-known nine suppressive miRNAs. 

Methods:
All data were obtained from The Cancer Genome Atlas (TCGA). Expression of five suppressive miRNAs in BrCa, miR-31, miR-126, miR-146b, miR-206, miR-335, were retrieved from the GDC data portal and were analyzed using microRNA-Seq dataset. Overall survival was compared using the Cox proportional hazard model between the high and low expression groups determined by each miRNA-specific thresholds.

Results:
Among the 1097 patient breast cancer samples logged in TCGA, 1053 samples were found to contain both microRNA-seq datasets and survival data. High expression levels of miR-31 and miR-146b demonstrated significantly better survival (p = 0.032 and p = 0.025, respectively), while high expression levels of miR-206 tend to show worse prognosis (p = 0.091). The other miRNAs of interest, miR-126 and miR-335 have no significant difference between high and low expression groups. All of the miRNAs examined did not show any significant difference between high and low expression groups in clinicopathological factors such as staging, tumor size (T category), nodal metastasis (N category), distant metastasis (M category), and intrinsic subtype (ER, PR, and HER2 status), except for miR-126 that demonstrated significant association with PR and HER2 status (p = 0.003 and p < 0.001, respectively).

Conclusion:
Utilizing a big data (TCGA) with sufficient statistical power, we found that high expression of miR-31 and miR-146b was significantly associated with better overall survival. This is in agreement with previous reports that demonstrated their tumor suppressive role in BrCa. Conversely, expression of miR-126 and miR-335 did not show any survival impact, and high expression of miR-206 demonstrated a trend to worse prognosis against the previous reports. We conclude that it is essential to validate the survival impact of reported miRNAs using a large publically available data base such as TCGA.
 

29.08 Outcome in Real-World Practice for Elderly Patients with Early Breast Cancer

Posted on January 25, 2017

Q. D. Chu1, P. Peddi1, M. Zhou2, K. Medeiros2, X. Wu2  1Louisiana State University Health Sciences Center,Surgery,Shreveport, LA, USA 2Louisiana State University Health Sciences Center,Biostatistics,New Orleans, LA, USA

Introduction: Clinical trials demonstrated the efficacy of omitting radiation therapy (RT) for women ≥ 70 years old, hormone receptor positive (HR+) T1 breast cancer who underwent breast-conserving therapy cancer treated with anti-hormonal therapy. Whether such results also apply to real-world population is unknown. We report the survival outcomes of patients who received adjuvant RT versus those who did not using a large national clinical oncology database.

Methods: Using the National Cancer Data Base, representing about 70% of newly diagnosed cancer cases nationwide, we evaluated a cohort of 66,763 women diagnosed with breast cancer in 2004 -2012 and meeting the following criteria: age ≥ 70 years, pathologic stage I, HR+, negative margins, and receipt of anti-hormonal therapy. Patients were stratified into two groups: (1) RT and (2) no RT. Propensity score matching was used to compensate for differences in baseline characteristics. Univariate and multivariable survival analysis with Cox proportional hazards models were employed to determine the impact of radiation therapy on the overall survival (OS). 

Results:After matching, 23,276 cases were analyzed. The 5-year OS was 85.9% for RT group and 78.3% for no RT group (HR=1.59; P<0.0001). The median survival time was 114.07 months for RT and 103.56 months for no RT. Significant adjusted predictors (P<0.01) of poor OS were lack of radiation, advanced age, facility type, facility location, and high comorbidity score.

Conclusion:Patients who received RT had better survival outcomes than those who did not, revealing discordance between results of randomized trials and real-world setting.

 

29.07 Clinical Fate of T0N1 Squamous Cell Carcinoma of the Esophagus

Posted on January 25, 2017

R. Shridhar2, j. Huston1, S. Kucera1, K. Meredith1  1Florida State University College Of Medicine/Sarasota Memorial Health Care System,Gastrointestinal Oncology,Sarasota, FL, USA 2University Of Central Florida,Radiation Oncology,Orlando, FLORIDA, USA

Introduction: The long-term survival for patients with locally advanced esophageal SCC remains poor despite improvements in multi-modality care. Neoadjuvant chemoradiation(NCR) followed by surgical resection remains piviotal in the management of patients with locally advanced SCC.  Response to NCR is predictive of overall survival.  However the outcomes of patients whose primary tumor exhibits a complete response with residual regional nodal disease (T0N1) remains unclear as well as the role for adjuvant therapy. 

Methods: Utilizing the National Cancer Database we identified patients with SCC of the esophagus who underwent NCR followed by esophagectomy. Outcomes of patients with pathologic T0N1 were then compared.  Baseline univariate comparisons of patient characteristics were made for continuous variables using both the Mann-Whitney U and Kruskal Wallis tests as appropriate. Pearson’s Chi-square test was used to compare categorical variables. Survival was evaluated on the basis of time from date of diagnosis to date of death or censoring. Unadjusted survival analyses were performed using the Kaplan-Meier method comparing survival curves with the log-rank test. All statistical tests were two-sided and α (type I) error <0.05 was considered statistically significant.

Results:We identified 1,743 patients with SCC of the esophagus with a median age of 61 (25 – 83) years.  There were 1204 (69.1%) males and 539 (30.9%) females. The location was 639 (36.7%) middle, 845 (48.5%) lower, and 173 (9.9%) gastroesophageal junction.   R0 resections were achieved in 1594 (95.2%) patients and this correlated to improved survival, median survival 55.4 (RO) and 24.4 (R1) months respectively, p,0.001. The median nodes harvested were 10 (0-99) and did not correlate to an increase in survival as more nodes were resected. Complete response (pCR) was achieved in 375 (34.9%), partial response (pPR) 356 (33.2 %) and non response (pNR)297 (27.7%).  There were 45 (4.2%) patients deemed as pathologic T0N1.  The median survival of patients with pCR was 72.6 months compared to 26.3 months in the T0N1 patients p<0.001. T0N1 patients did not demonstrate an improved survival over T1-4 N1 patients who had a median survival of 21.8 months p=0.7. Adjuvant chemotherapy in T0N1 did not provide a benefit in survival, median survival adjuvant versus no adjuvant 33 vs 26.6 months respectively, p=0.7. Similarly adjuvant therapy in all node positive patients did not demonstrate significant benefit in survival p=0.1.

Conclusion:Patients with squamous cell carcinoma of the esophagus who exhibit a pathologic T0N1 after neoadjuvant chemoradiation have oncologic fates similar to node positive patients.  Patients with complete pathologic response of the primary tumor and regional lymph nodes continue to demonstrate significant survival benefits over all remaining pathologic cohorts.  Adjuvant therapy failed to improve survival in T0N1 or any node positive SCC esophageal patients.

 

29.06 Impact of Lymph Node Ratio in Selecting Patients with Resected Gastric Cancer for Adjuvant Therapy

Posted on January 25, 2017

Y. Kim1, M. H. Squires2, G. A. Poultsides3, R. C. Fields4, S. M. Weber5, K. I. Votanopoulos6, D. Kooby2, D. J. Worhunsky3, L. X. Jin4, W. G. Hawkins4, A. W. Acher5, C. S. Cho5, N. Saunders7, E. A. Levine6, C. R. Schmidt7, S. K. Maithel2, T. M. Pawlik1,7  1Johns Hopkins University School Of Medicine,Baltimore, MD, USA 2Emory University School Of Medicine,Atlanta, GA, USA 3Stanford University,Palo Alto, CA, USA 4Washington University,St. Louis, MO, USA 5University Of Wisconsin,Madison, WI, USA 6Wake Forest University School Of Medicine,Winston-Salem, NC, USA 7Ohio State University,Columbus, OH, USA

Introduction:  The impact of adjuvant chemotherapy (CTx) and chemo-radiation therapy (cXRT) in the treatment of resectable gastric cancer remains varied.  We sought to define the clinical impact of lymph node ratio (LNR) on the relative benefit of adjuvant CTx or cXRT among patients having undergone curative-intent resection for gastric cancer.

Methods:  Using the multi-institutional U.S. Gastric Cancer Collaborative database, 769 patients with gastric adenocarcinoma who underwent curative-intent resection between 2000 and 2012 were identified. Patients with metastasis or an R2 margin were excluded. The impact of LNR on disease-free survival (DFS) among patients who received CTx or cXRT was evaluated.

Results: Median patient age was 65 years and the majority of patients were male (55.8%).  The majority of patients underwent either subtotal (40.9%) or total gastrectomy (41.4%), with the remainder undergoing distal gastrectomy or wedge resection (17.7%). On pathology, median tumor size was 4 cm; more patients had a T3 (33.5%) or T4 (28.7%) lesion and lymph node metastasis (60.6%).  Margin status was R0 in 92.2% of patients.  A total of 361 (46.9%) patients underwent surgery alone, 257 (33.4%) patients received 5-FU based cXRT, whereas the remaining 151 (19.6%) received CTx. Recurrence occurred in 236 (30.7%) patients.  At a median follow-up of 17.2 months, median disease-free survival (DFS) was 29.0 months and 5-year DFS was 34.7%. According to LNR categories, 5-year DFS for patients with LNR of 0, 0.1-0.10, >0.10-0.25, >0.25 were 52.2%, 40.0%, 43.0% and 13.9%, respectively. Factors associated with worse DFS included age (hazard ratio [HR] 1.01), tumor size (HR 1.08), tumor grade (moderate/poor: HR 1.27), GE junction (HR 1.87), T-stage (3-4: HR 2.66), and LNR (>0.25: HR 2.18) (all P<0.05). In contrast, receipt of adjuvant cXRT was associated with an improved DFS in the multivariable model (vs. surgery alone: HR 0.57; vs. CTx: HR 0.45, both P<0.001). The benefit of cXRT for resected gastric cancer was noted only among patients with LNR >0.25 (vs. surgery alone: HR 0.39; vs. CTx: HR 0.44, both P<0.001).  In contrast, there was no noted DFS benefit of CTx or cXRT among patients with LNR ≤0.25 (all P>0.05) (Figure).

Conclusion: Adjuvant CTx or cXRT were utilized in over one-half of patients undergoing curative-intent resection for gastric cancer. LNR may be a useful tool to select patients for adjuvant cXRT, as the benefit of cXRT therapy was isolated to patients with higher degrees of lymphatic spread (i.e., LNR >0.25).

 

29.05 Failure to Rescue Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Posted on January 25, 2017

K. Li1, A. A Mokdad1, M. Augustine1, S. Wang1, M. Porembka1, A. Yopp1, R. Minter1, J. Mansour1, M. Choti1, P. Polanco1  1University Of Texas Southwestern Medical Center,Division Of Surgical Oncology,Dallas, TX, USA

Introduction: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been shown to significantly improve the survival of selected patients with peritoneal carcinomatosis (PC). However, this invasive procedure can result in significant morbidity and mortality. Using a national cohort of patients, this study aims to identify perioperative patient characteristics predictive of failure to rescue (FTR)–mortality following postoperative complications from CRS/HIPEC.

Methods: Patients who underwent CRS/HIPEC between 2005 and 2013 were identified in the American College of Surgeons National Surgical Quality Improvement Program dataset (NSQIP). Patients who suffered any post-operative complication were identified. Major complications were defined as those corresponding to Clavien-Dindo grade III or IV. Failure to rescue (FTR) was defined as 30-day mortality in the setting of a treatable complication. Patients who suffered FTR were compared against those who survived a complication (non-FTR) using patient characteristics, pre-operative clinical information, types of resections, and severity of complication. Univariable comparisons were conducted using the Wilcoxon rank-sum test for continuous variables and the Fischer’s exact test for categorical variables. Predictors of FTR were identified using a multi-variable logistic regression model.

Results: From the NSQIP database, 915 eligible CRS/HIPEC cases were identified in the study period. Overall, 382 patients (42%) developed postoperative complications and constituted our study population. A total of 88 (10%) patients suffered one or more major complications. Seventeen patients died following a complication, amounting to an FTR rate of 4%. Patients’ age, gender, and race were similar between FTR and non-FTR groups. Colorectal cancer was the most common diagnosis in the FTR and non-FTR groups (35% vs 25%, respectively). The rates of multi-visceral resections were also similar (88% vs 86%, p=1.00). FTR patients were more likely than non-FTR patients to have dependent functional status (18% vs 2%, p=0.01), have ASA class 4 status (29% vs 8%, p=0.01), develop three or more complications (65% vs 24%, p<0.01), and suffer a major complication (94% vs 20%, p<0.01). Independent predictors of FTR were as follows: having a major complication (odds ratio [OR] 66.0, 95% confidence interval [CI] 8.4-516.6), dependent functional status (OR 5.9, 95%CI 0.8-41.9), and ASA class 4 (OR 13.4, 95%CI 1.2-146.8). Procedure type and diagnosis were not predictive of FTR.

Conclusion: Morbidity associated with CRS/HIPEC is comparable to other complex surgical procedures and has an acceptable low rate of death in this national cohort of patients. Dependent functional status and ASA class 4 are patient factors predictive of FTR. These patients have a prohibitively high risk of 30-day mortality following postoperative complications and should be considered ineligible for CRS/HIPEC.

29.04 Clinicopathologic Score Predicting Lymph Node Metastasis in T1 Gastric Cancer

Posted on January 25, 2017

T. B. Tran1, D. J. Worhunsky1, M. H. Squires2, L. X. Jin3, G. Spolverato4, K. I. Votanopoulos7, C. S. Cho5, S. M. Weber5, C. Schmidt6, E. A. Levine7, R. C. Fields3, T. Pawlik4,6, S. Maithel2, J. A. Norton1, G. A. Poultsides1  2Emory University,Atlanta, GA, USA 3Washington University In St. Louis,St. Louis, MO, USA 4John Hopkins Hospital,Baltimore, MD, USA 5University Of Wisconsin,Madison, WI, USA 6The Ohio State University,Columbus, OH, USA 7Wake Forest University,Winston-Salem, NC, USA 1Stanford University,Palo Alto, CA, USA

Introduction:  While gastrectomy with D2 lymphadenectomy is considered the standard treatment for invasive gastric adenocarcinoma, endoscopic resection (ER) has been described by Asian authors in select patients with T1 gastric cancer. Accurate preoperative prediction of lymph node (LN) metastasis in this setting is critical, since ER omits LN harvest. The objective of this study is to identify preoperative predictors of LN metastasis in US patients with T1 gastric cancer.

Methods:  Patients who underwent surgical resection for T1 gastric cancer (T1a: into lamina propria or muscularis mucosa, and T1b:  into submucosa) between 2000 and 2012 in 7 US academic institutions were identified. Clinicopathologic predictors of LN metastasis were determined using univariate and multivariate logistic regression. A preoperative score was created assigning points based on each variable’s beta-coefficient.

Results: Among 965 patients with gastric cancer undergoing surgical resection, 198 patients (20.5%) had T1 disease confirmed on final pathology.  Of those, 40 patients (20%) had LN metastasis. Independent predictors of LN involvement on multivariate analysis were poor differentiation (OR 4.5, P=0.002, beta 1.5), T1b stage (OR=4.5, P=0.02, beta 1.5), lymphovascular invasion (OR 2.8, P=0.049, beta 1.4), and tumor size > 2 cm (OR 2.8, P=0.026, beta 1.0). A clinicopathologic risk score predicting LN metastasis was created, assigning 3 points for the first 3 variables and 2 points for the last variable. The performance of the score was evaluated with an ROC curve (Figure) showing excellent discrimination (AUC = 0.79) and 100% sensitivity in detecting LN metastasis in patients with a score of 3 or less.

Conclusion: In this cohort of US patients with T1 gastric adenocarcinoma, lack of LN involvement could be predicted if none or one of the following unfavorable factors is present (T1b, poor differentiation, lymphovascular invasion, size > 2 cm). For these patients, endoscopic resection may be a potential treatment option provided it could be achieved with negative margins. 

 

29.03 Trends in major abdominal surgery for cancer in octogenarians

Posted on January 25, 2017

M. G. Neuwirth1, A. J. Sinnamon1, D. L. Fraker1, R. R. Kelz1, R. E. Roses1, G. C. Karakousis1  1Hospital Of The University Of Pennsylvania,Department Of Surgery,Philadelphia, PA, USA

Introduction: While there is the general perception as the population ages that we are operating on older patients for cancer, there is little data on trends in major resections for cancer in this population when adjusted for cancer incidence and short-term outcomes in this group.

Methods: The Nationwide Inpatient Sample was used to estimate the national trends of major abdominal resections for cancer in octogenarians from 2000 through 2011 including pancreatic resections, total gastrectomies, hepatectomies, and total colectomies.  Partial resections of the stomach, colon and liver lobes were excluded in order to target a subset of elderly patients undergoing comparably morbid procedures.  Rates of resections performed per year were incidence-adjusted to the US incidence among octogenarians for each cancer type as determined by the SEER registry.  Joinpoint regression was used to calculate annual percentage change (APC) and average annual percentage change (AAPC) when evaluating trends over time.

Results:Over the study period, an estimated 17,002 major abdominal organ resections for cancer were performed in patients 80 or older in the U.S, 44.2% were pancreatic resections, with 27.9% total gastrectomies, 18.2% total colectomies 9.5% and major liver resections.   The estimated number of resections per year in the elderly increased substantially over time from 732 in 2000 to 1848 in 2011 (APC=8.0%, p<.01) along with an increase in Elixhauser comorbidities in this group from a mean of 2.3 in 2000 to 3.4 in 2011 (APC=3.5, p<.001).  However, inpatient mortality during this time decreased in octogenarians from 23.5% to 18.1% (AAPC=-1.8, p<.001) with the most significant decrease over the latest 5 years of 2007 to 2011 (APC =-6.97, p<.001).  Pancreatic resections increased at the fastest rate in elderly patients, APC=11.3, p<.001, fatality rates decreased from 15.6 to 7.8% (APC= -6.2, p<.001).  Major liver resections and total with incidence of pancreatic cancers in this age group increasing by 21.2% and colectomies increased slightly (APC=4.28, p=.1 and APC=3.37 p<.001 respectively).  Total gastrectomies for cancer decreased over time in this population, although the trend was not significant (APC=-.5, p=.8), and fatality rates also decreased during this time from 17.1 to 12.6%, with a significant decrease over time from 2004 to 2011 (APC=-8.0, p<.001). 

Conclusion:Major abdominal resections for cancer are increasing over time in octogenarians at a disproportionally higher rate than respective increases in incidences of cancer diagnoses, and with a concurrent significant decrease in 30-day in-patient mortality rates. This pattern may suggest a shifting selection criterion for elderly surgical patients with time.

29.02 Preoperative Enteral Access is not Requite Prior to Multimodality Treatment of Esophageal Cancer

Posted on January 25, 2017

T. K. Jenkins4, A. N. Lopez4, G. A. Sarosi1,2, K. Ben-David3, R. M. Thomas1,2  1University Of Florida,Department Of Surgery,Gainesville, FL, USA 2North Florida/South Georgia Veterans Health System,Department Of Surgery,Gainesville, FL, USA 3Mount Sinai Medical Center,Department Of Surgery,Miami Beach, FL, USA 4University Of Florida,College Of Medicine,Gainesville, FL, USA

Introduction:  While prior research has shown that preoperative (preop) enteral access is feasible and safe in patients to support their nutrition prior to esophagectomy, controversy exists regarding its necessity, as subjective dysphagia is a poor indicator of need for enteral access. We hypothesized that patients who underwent preop enteral access prior to esophagectomy for cancer fared no better than those who had surgical enteral access performed at the time of esophagectomy.

Methods: An IRB approved retrospective database of patients undergoing esophagectomy for esophageal malignancy from 2007-2014 was established. Clinicopathologic factors were recorded including preop enteral access, weight change, nutritional labs, preop cancer stage, operative details, and perioperative complications.

Results: One hundred fifty-six patients were identified, of which 99 (63.5%) received preop chemoradiation (cXRT) prior to esophagectomy. Since preop cXRT can influence perioperative nutrition, this group comprised the study cohort. Fifty (50.5%) underwent preop enteral access [esophageal stent (1), gastrostomy (14), jejunostomy (32), nasoenteric (1), combination (2); “access group”] prior to cXRT followed by esophagectomy and feeding jejunostomy unless it was pre-existing. There was no difference in demographics, preop tumor staging, or operative details between the access and non-access groups. No difference was noted between access and non-access groups in subjective dysphagia [n=43 (86%) vs 37 (75.5%), respectively; p=0.2)] or mean preop serum albumin (gm/dl) [3.9 (range 3.1-4.5) vs 4 (range 3.3-6.4), respectively; p=0.2]. To account for potential cXRT delays, there was no difference in median time from diagnosis to surgery in the access vs non-access groups (126d vs 126d, p=0.5). Comparing weight loss 6mo preop to surgery, the access group had a mean 5.2% weight loss (range -29.4 – +6.6%) vs 4.5% reduction (range -19.4% – +68.2%) in the non-access group (p=0.8). Additionally, mean weight loss 6mo preop to 6mo postop was similar in the access vs non-access groups [-11.2% (range -44% – +5.3%) vs -15.4% (range -34.1% – -1.4%), respectively p=0.1].  Complication rates between access and non-access groups (64% vs 51%, respectively; p=0.2) were likewise similar.  In patients with reported dysphagia, there was no difference in weight change 6mo preop to 6mo postop in the access vs non-access group (-11% vs -15.2%, p=0.1; respectively).

Conclusions: Despite the bias of establishing enteral access prior to preop cXRT for esophageal malignancy in candidates for esophagectomy, there was no difference in weight change, preop albumin, or complication rates in patients who had preop enteral access versus those who did not. Patients with esophageal malignancy should therefore proceed directly to appropriate neoadjuvant and surgical therapy with enteral access performed at the time of definitive resection or reserved for those with obstruction confirmed on endoscopy.

29.01 Prognostic impact of pancreastatin following chemoembolization for neuroendocrine tumors

Posted on January 25, 2017

D. S. Strosberg1, J. Onesti4, N. Saunders3, G. Davidson1, M. Shah5, M. Dillhoff1, C. Schmidt1, M. Bloomston2, L. A. Shirley1  1The Ohio State University Wexner Medical Center,Surgical Oncology,Columbus, OH, USA 221st Century Oncology,Fort Meyers, FL, USA 3Emory University School Of Medicine,Atlanta, GA, USA 4Mercy Health Grand Rapids,Grand Rapids, MI, USA 5The Ohio State University Wexner Medical Center,Medical Oncology,Columbus, OH, USA

Introduction: Transarterial chemoembolization (TACE) is a viable treatment option for patients with metastatic neuroendocrine tumors (NETs) to control tumor progression and palliate symptoms of hormone excess.  Pancreastatin, a split product of chromogranin, has been shown to correlate with survival in patients with NETs. The objective of this study was to investigate the prognostic impact of pancreastatin levels in patients with metastatic NETs treated with TACE.

Methods: Patients with metastatic NET treated with TACE at a single institution from 2000 to 2013 were analyzed. Clinical variables were analyzed with Chi-square, Fisher Exact, or independent T-test as appropriate.  Kaplan-Meier curves for overall survival (OS) were analyzed using log-rank testing for curve differences.

Results: 188 patients underwent TACE for metastatic NETs during the study period.  An initial pancreastatin level greater than 5000 pg/mL correlated with worse OS from time of first TACE (Median OS 58.5 months vs 22.1 months, p<0.001). A decrease in pancreastatin levels by 50% or more after TACE treatment correlated with improved OS (Median OS 53.8 months vs 29.9 months, p=0.032). Patients with carcinoid syndrome were more likely to have a subsequent increase in pancreastatin after initial drop post-TACE (percent of patient with increase 78.1% vs 55.2%, p=0.002). Patients who had an increase in pancreastatin levels after initial drop post-TACE were also more likely to have liver progression on axial imaging (70.7% vs 40.7%, p=0.005) as well as more likely to need repeat TACE (21.1% vs 6.7%, p=0.009).

Conclusion: For patients with liver metastases from NET, measurement of pancreastatin levels can be useful in several steps during potential TACE treatment.  Extreme high levels prior to TACE can predict poor outcomes, significant drops in pancreastatin after TACE correlate with improved survival, and a rise in levels after initial drop may predict progressive liver disease requiring repeat TACE.  As such, pancreastatin levels should be measured throughout the TACE treatment period.

 

25.09 Modifications to T Cell Receptor Enhance Anti-Tumor Activity Against Metastatic Melanoma

Posted on January 25, 2017

E. H. Wood1, K. Calabrese2, D. Murray2, K. Foley2, K. Nagato2, M. Nishimura1,2  1Loyola University Medical Center,Surgery,Maywood, ILLINOIS, USA 2Loyola University Chicago,Oncology Institute,Chicago, IL, USA

Introduction:
Adoptive cell transfer of T cells engineered to express receptors with specific anti-tumor effects has shown great promise in the treatment of metastatic melanoma. However, exogenously introduced T cell receptors (TCR) must compete with endogenous receptors for surface expression resulting in blunted anti-tumor activity. Our goal is to create TCR modifications that will enhance receptor pairing resulting in increased surface expression and improved tumor recognition.  

Methods:
Using TCR 1383I, a receptor against the melanoma antigen tyrosinase, the following modifications were made: codon optimization, introduction of a disulfide bridge into the constant region, introduction of a cytoplasmic leucine zipper, and murinization of the constant regions. These modifications have all been demonstrated in the literature to improve receptor pairing; however, they have never been tested side by side in the same TCR. Peripheral blood lymphocytes were transduced with each modification. Surface expression and peptide recognition were studied using multicolor flow cytometry, alanine scanning, and intracellular and extracellular cytokine release assays (IFN-γ  TNF-α , IL-2, IL-4, IL-22, IL-17A, and CD107a).

Results:
While the disulfide bridge and codon optimized TCRs demonstrated enhanced surface expression compared to the wild type receptor, there was no improvement in peptide recognition and anti-tumor effects. Only the murinized TCR significantly improved receptor pairing and surface expression. This receptor dramatically increased antigenic peptide recognition, and also altered the complement of cytokines produced by the lymphocytes. T cells expressing the murinized TCR not only secreted more cytokine but exhibited increased polyfunctionality compared to all other modifications and wild type. We utilized alanine scanning to delineate the interaction between the tyrosinase peptide and each TCR modification. The disulfide bridge, codon optimized, and leucine zipper modified TCRs demonstrated the same peptide recognition patterns as the wild type receptor, however the murinized receptor appeared to be less restricted. 

Conclusion:
TCR modifications were created in an attempt to enhance receptor pairing and T cell functionality. In the context of TCR 1383I, only the murinized modification consistently improved pairing, T cell surface expression, and anti-tumor functionality. TCRs require a CD3 coreceptor to initiate its signaling cascade and murine TCRs have been shown to have higher affinity for CD3 allowing our target TCR to outcompete endogenous receptor expression. The modification may have also created a conformational change allowing better recognition of target antigens. Future studies are needed to assess peptide-TCR interactions on a molecular level, to examine cross-reactivity against other peptides, and to establish an in vivo model.
 

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