Surgery For Esophageal Adenocarcinoma Research Articles

434. INCREASING TUMOUR INFILTRATING LYMPHOCYTES THROUGH EXERCISE ALONE—A PILOT RCT IN ESOPHAGEAL ADENOCARCINOMA

Abstract Background The immune system is highly responsive and positively adapts to exercise. A single bout of exercise results in the mobilisation of highly functional effector CD8+ T cells and NK-cells into the circulation. Murine cancer models have shown that exercise reduces tumour burden by increasing the frequency of tumour-infiltrating lymphocytes (TILs). There are no studies assessing the impact of an exercise programme on the levels of TILs in patients’ solid tumours in any cancer. Methods We recently completed a 16-week randomised prehabilitation exercise program (NCT02950324) in esophageal cancer patients before esophagogastric cancer resection. Exercise training was a low-to-moderate intensity twice supervised, thrice home-based weekly program. Tumour specimens obtained at the time of resection were formalin fixed paraffin embedded (FFPE) for multispectral immunohistochemical analysis. Tumour tissues were stained with primary antibodies for CD68, CD57, CD8, CD4, FoxP3, Granzyme B, PDL1 and pancytokeratin. Cell populations and spatial relationships were analysed using the Phenoimager HT (Akoya Biosciences) and QuPath. Results Although our exercise program was ~33% of the physical activity guidelines for cancer patients, physical fitness and well-being were maintained rather than significantly reduced in the intervention group compared to the control group. Multispectral analysis observed that 3.2% ± 1.1% of cells in the tumours were CD8+ T cells compared to 1.4% ± 0.5% in the control group (p < 0.001). Furthermore, we observed positive associations between increased frequencies of CD8 + TILs (Fig 1C: r = 0.562, p = 0.016), Granzyme B+/CD8 + TILs (r = 0.637, p = 0.003) and larger increases in exercise induced aerobic capacity. This data suggests that the more exercise can increase aerobic fitness, the greater the likelihood of increasing functional TILs. Conclusion New approaches to improve outcomes following surgery for esophageal adenocarcinoma are required. One such approach is immunotherapy. However, immunotherapy is relatively ineffective in esophageal adenocarcinoma due to the lack of CD8+ T cells and NK cells in the tumours. Increasing TILs through exercise programmes that are designed to focus on maintaining or improving aerobic capacity may improve patients’ response to immunotherapy and positively impact prognosis and survival.

Pathologic Lymph Node Regression After Neoadjuvant Chemotherapy Predicts Recurrence and Survival in Esophageal Adenocarcinoma: A Multicenter Study in the United Kingdom.

There is limited evidence regarding the prognostic effects of pathologic lymph node (LN) regression after neoadjuvant chemotherapy for esophageal adenocarcinoma, and a definition of LN response is lacking. This study aimed to evaluate how LN regression influences survival after surgery for esophageal adenocarcinoma. Multicenter cohort study of patients with esophageal adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection at five high-volume centers in the United Kingdom. LNs retrieved at esophagectomy were examined for chemotherapy response and given a LN regression score (LNRS)-LNRS 1, complete response; 2, <10% residual tumor; 3, 10%-50% residual tumor; 4, >50% residual tumor; and 5, no response. Survival analysis was performed using Cox regression adjusting for confounders including primary tumor regression. The discriminatory ability of different LN response classifications to predict survival was evaluated using Akaike information criterion and Harrell C-index. In total, 17,930 LNs from 763 patients were examined. LN response classified as complete LN response (LNRS 1 ≥1 LN, no residual tumor in any LN; n = 62, 8.1%), partial LN response (LNRS 1-3 ≥1 LN, residual tumor ≥1 LN; n = 155, 20.3%), poor/no LN response (LNRS 4-5; n = 303, 39.7%), or LN negative (no tumor/regression; n = 243, 31.8%) demonstrated superior discriminatory ability. Mortality was reduced in patients with complete LN response (hazard ratio [HR], 0.35; 95% CI, 0.22 to 0.56), partial LN response (HR, 0.72; 95% CI, 0.57 to 0.93) or negative LNs (HR, 0.32; 95% CI, 0.25 to 0.42) compared with those with poor/no LN response. Primary tumor regression and LN regression were discordant in 165 patients (21.9%). Pathologic LN regression after neoadjuvant chemotherapy was a strong prognostic factor and provides important information beyond pathologic TNM staging and primary tumor regression grading. LN regression should be included as standard in the pathologic reporting of esophagectomy specimens.

Changes in Perioperative Platelet Lymphocyte Ratio Predict Survival in Oesophago-Gastric Adenocarcinoma.

Platelet to lymphocyte ratio (PLR) is associated with survival in oesophageal cancer. We explored whether PLR changes during different stages of treatment correlate with survival outcomes. A retrospective single-centre study was performed. Consecutive patients who received neoadjuvant chemotherapy followed by surgery for oesophageal adenocarcinoma were identified. Changes in PLR were calculated during two time periods: the first spanning the neoadjuvant period (T1); the second the perioperative period (T2). Differences in PLR were calculated for clinicopathological variables during both T1 and T2 and for variables with regards to their association with median overall survival (OS). Variables found to be significant on univariate analysis were included in a multivariate Cox regression model. Using ROC analysis, optimal cut-offs for PLR changes were identified and plotted on a Kaplan-Meir curve. Of the 370 patients identified, 110 (29.7%) were included in the analysis. During T1 a positive correlation was noted between higher positive lymph node ratio and PLR change. During T2, PLR change was positively higher in patients who suffered major postoperative complications. Median survival for the cohort as a wholewas 42.3 months and 5-year OS was 57.3%. Survival at 5 years was associated with lower PLR changes during T2.On univaraite analysis, median OS was significantly less for patients with a tumour size > 3 cm, poor differentiation and change inPLR ≥ 43.4 during T2. The latter two variables remained significant on multivariate analysis. Using the same PLR threshold, the survival curve comparing changes in PLR duringT2 remained statistically significant. Perioperative PLR changes are highly prognostic of survival outcomes in patients treated for oesophageal adenocarcinoma.

Completion of FLOT Therapy, Regardless of Tumor Regression, Significantly Improves Overall Survival in Patients with Esophageal Adenocarcinoma.

Simple SummaryMultimodal therapy concepts, including surgery and systemic therapy, are the mainstay in the treatment of esophageal adenocarcinoma. Despite the technical advances in the surgical field and the widespread use of chemoradiation therapy, the prognosis and overall survival for esophageal cancer remains poor. Therapy with a continuous infusion of 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT protocol) has been shown to improve the overall survival for patients with esophageal adenocarcinoma. However, uncertainty exists as to whether patients with poor tumor responses should complete the chemotherapy following surgery. The aim of our study was to analyze the effect of neoadjuvant and adjuvant FLOT therapy on the outcomes of patients following an esophagectomy for adenocarcinoma, with the focus on the tumor regression grading and the completion of the systemic therapy. We showed that the completion of the systemic therapy, regardless of the tumor regression grading, improved the outcomes of patients with esophageal adenocarcinoma. Subgroup analyses further showed that complications from chemotherapy reduced the overall survival, while surgical complications did not.Esophageal cancer is the eighth most common cancer worldwide, with poor prognosis and high mortality. The combination of surgery and systemic therapy provide the best chances for long-term survival. The purpose of this study was to analyze the impact of the FLOT protocol on the overall survival of patients following surgery for esophageal adenocarcinoma, with a focus on the patients who did not benefit in terms of pathological remission from the neoadjuvant therapy. A retrospective analysis of all the patients who underwent esophagectomies from 2012 to 2017 for locally advanced adenocarcinomas of the esophagus at a tertiary medical center was performed. The results show that the completion of systemic therapy, regardless of the tumor regression grading, had a significant positive impact on the overall survival. The patients with complete regression and complete systemic therapy showed the best outcomes. Anastomotic insufficiency did not negatively impact the long-term survival, while complications of the systemic therapy led to significantly reduced overall survival. We conclude that adjuvant systemic therapy should, when possible, always be completed, regardless of the tumor regression, following an esophagectomy.

Adjuvant therapy following neoadjuvant chemotherapy and surgery for oesophageal adenocarcinoma in patients with clear resection margins

Background The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy (NAC) and surgery is contentious. In UK practice, surgical resection margin status is often used to classify patients into receiving adjuvant treatment. This study aimed to assess any survival benefit of adjuvant therapy in patients with clear resection margins. Methods This was a retrospective collaborative cohort study combining two prospectively collected UK institutional databases of patients with oesophageal adenocarcinoma. Multivariable Cox regression and propensity matched analyses were used to compare overall and recurrence-free survival according to the adjuvant treatment. Results Of 374 patients with clear resection margins, 221 patients (59%) had no adjuvant treatment, 137 patients (37%) had adjuvant chemotherapy and 16 patients (4%) had adjuvant chemoradiotherapy. For patients who had received NAC (290, 76%), when adjuvant chemotherapy was compared to no adjuvant treatment, hazard ratios (HRs) favoured adjuvant chemotherapy but did not reach independent significance (overall survival [OS] HR 0.65 95% confidence interval [CI] 0.40–1.06; p .0.087). Responders to NAC (Mandard 1–3) were seemingly more likely to demonstrate a survival benefit from adjuvant chemotherapy (HR 0.42 95% CI 0.15–1.11; p .1.081). Conclusions Although no independent survival benefit was observed, the point estimates favoured adjuvant treatment, predominantly in patients with chemo-responsive tumours.

Longitudinal tracking of 97 esophageal adenocarcinomas using liquid biopsy sampling

The incidence of esophageal adenocarcinoma (EAC) is rapidly rising and has a 5-year survival rate of <20%. Beyond TNM (tumor-node-metastasis) staging, no reliable risk stratification tools exist and no large-scale studies have profiled circulating tumor DNA (ctDNA) at relapse in EAC. Here we analyze the prognostic potential of ctDNA dynamics in EAC, taking into account clonal hematopoiesis with indeterminate potential (CHIP). A total of 245 samples from 97 patients treated with neoadjuvant chemotherapy and surgery were identified from the prospective national UK Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium data set. A pan-cancer ctDNA panel comprising 77 genes was used. Plasma and peripheral blood cell samples were sequenced to a mean depth of 7082× (range 2196-28524) and ctDNA results correlated with survival. Characteristics of the 97 patients identified were as follows: 83/97 (86%) male, median age 68 years (SD 9.5 years), 100% cT3/T4, 75% cN+. EAC-specific drivers had higher variant allele fractions than passenger mutations. Using stringent quality criteria 16/79 (20%) were ctDNA positive following resection; recurrence was observed in 12/16 (75%) of these. As much as 78/97 (80%) had CHIP analyses that enabled filtering for CHIP variants, which were found in 18/78 (23%) of cases. When CHIP was excluded, 10/63 (16%) patients were ctDNA positive and 9/10 of these (90%) recurred. With correction for CHIP, median cancer-specific survival for ctDNA-positive patients was 10.0 months versus 29.9 months for ctDNA-negative patients (hazard ratio 5.55, 95% confidence interval 2.42-12.71; P= 0.0003). Similar outcomes were observed for disease-free survival. We demonstrate in a large, national, prospectively collected data set that ctDNA in plasma following surgery for EAC is prognostic for relapse. Inclusion of peripheral blood cell samples can reduce or eliminate false positives from CHIP. In future, post-operative ctDNA could be used to risk stratify patients into high- and low-risk groups for intensification or de-escalation of adjuvant chemotherapy.

Lymphadenectomy and Survival After Neoadjuvant Chemoradiation for Esophageal Adenocarcinoma: Is More Better?

PurposeThe purpose of this study was to assess the impact of number of lymph nodes examined on survival in patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiation. MethodsThe National Cancer Database was queried for patients who underwent neoadjuvant chemoradiation followed by surgery for esophageal adenocarcinoma. Propensity scores were created predicting the odds of undergoing resection of ≥ 25 nodes. Patients were matched on propensity score. Overall survival analyses were performed using the Kaplan-Meier method. Sensitivity analyses were performed using various nodal cutoffs. ResultsIn total, 3953 patients who underwent neoadjuvant chemoradiation were identified. The median number of resected nodes was 14 nodes (IQR, 8–20 nodes). Resection of ≥ 15 (vs. < 15 nodes: 32 vs. 26 months; p < 0.001), ≥ 20 (vs. < 20 nodes: 36 vs. 28 months; p = 0.001), and ≥ 25 (vs. < 25 nodes: 37 vs. 29 months; p = 0.015) nodes was associated with higher median survival, but resection of ≥ 30 nodes was not (vs. < 30 nodes: 41 vs. 33 months; p = 0.367). Resection of ≥ 25 lymph nodes remained predictive for improved survival on subset analysis in patients with negative nodes and who underwent treatment at high-volume centers. ConclusionsAfter neoadjuvant chemoradiation, resection of 25 or more lymph nodes was associated with longer median survival. Prospective trials are warranted to determine the optimal nodal yield after neoadjuvant chemoradiation.

Multimodal treatment including surgery for esophageal adenocarcinoma with liver oligo-metastases: a pathological complete response but early brain metastasis.

Survival of patients with stage IV esophageal adenocarcinoma is exceedingly poor, with less than 5% surviving 5years. Current National Comprehensive Cancer Network guidelines recommend only palliative and supportive measures for patients with metastatic esophageal cancer. Treatment for stage IV disease is chemotherapy in selected patients, while the role of radiation therapy and surgical resection remain controversial. We report herein a young patient with esophageal adenocarcinoma and synchronous liver metastasis who underwent induction chemotherapy with encouraging downstaging, then two-field esophageal resection with left liver lobectomy. Despite a complete response of esophageal and residual liver lesions, early progression with isolated brain metastasis occurred 2months after discharge. Our case highlights that despite progress in perioperative chemotherapy, the role of surgery remains uncertain for patients with esophageal cancer and synchronous M1 disease who exhibit excellent response to neoadjuvant treatment.

Machine learning to predict early recurrence after oesophageal cancer surgery.

BackgroundEarly cancer recurrence after oesophagectomy is a common problem, with an incidence of 20–30 per cent despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. This study aimed to develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multinational cohort and machine learning approaches.MethodsConsecutive patients who underwent oesophagectomy for adenocarcinoma and had neoadjuvant treatment in one Dutch and six UK oesophagogastric units were analysed. Using clinical characteristics and postoperative histopathology, models were generated using elastic net regression (ELR) and the machine learning methods random forest (RF) and extreme gradient boosting (XGB). Finally, a combined (ensemble) model of these was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model.ResultsA total of 812 patients were included. The recurrence rate at less than 1 year was 29·1 per cent. All of the models demonstrated good discrimination. Internally validated areas under the receiver operating characteristic (ROC) curve (AUCs) were similar, with the ensemble model performing best (AUC 0·791 for ELR, 0·801 for RF, 0·804 for XGB, 0·805 for ensemble). Performance was similar when internal–external validation was used (validation across sites, AUC 0·804 for ensemble). In the final model, the most important variables were number of positive lymph nodes (25·7 per cent) and lymphovascular invasion (16·9 per cent).ConclusionThe model derived using machine learning approaches and an international data set provided excellent performance in quantifying the risk of early recurrence after surgery, and will be useful in prognostication for clinicians and patients.

Surgery for Esophageal Adenocarcinoma: Three field open McKeown procedure has a role in assessment and treatment of extensive locally advanced esophageal adenocarcinoma with a favorable clinical and pathological outcome.

Esophageal adenocarcinoma has seen an increased incidence due to gastroesophageal reflux disease , smoking and obesity. There are no established guidelines for screening of esophageal cancer and many patients present late in their disease process. Most early stage adenocarcinoma of the esophagus is treated with neoadjuvant chemotherapy and radiation follow by surgical resection in suitable operative candidates. We describe a case of locally advanced esophageal cancer, where the patient had a relatively insignificant response to neoadjuvant chemotherapy and radiation, who was then treated by open direct resection of the esophagus and proximal stomach (three field McKeown approach) with lymphadenectomy. The patient did well after surgery apart from pneumonia and increased secretions that required tracheostomy. There were no surgical complications such as anstomotic leak or chylothorax. Pathology showed T2N0 disease.

The Prognostic Role of Pre-operative Positron Emission Tomography-Computed Tomography and Endoscopic Ultrasound Parameters in Oesophageal Adenocarcinoma.

Background: To evaluate the prognostic role of Positron Emission Tomography/Computed Tomography (PET/CT) and Endoscopic Ultrasound (EUS) performed before neoadjuvant chemotherapy (NAC) and surgery for oesophageal adenocarcinoma (OAC) patients, focusing on lymph node (LN) assessment. Methods: OAC patients treated in a single tertiary center during January 2008 until December 2014 were retrospectively studied. All patients had PET/CT and EUS before NAC and oesophagectomy. PET-FDG-avid local LNs and maximum standardized uptake value (SUVmax) of the primary tumour, EUS positive LNs and EUS tumour length were recorded. Univariate, multivariate and survival analyses were performed. Results: Following exclusions 151consecutive patients met the inclusion criteria, (median age 62 years). PET/CT and EUS sensitivity for local LNs metastasis was 39.2% and 88.6%, with specificities of 83.33% and 19.15% respectively. No overall survival (OS) difference was found between patients with PET/CT FDG-avid LNs and those with negative LNs (p=0.347). SUVmax uptake was divided into high and low (median cut-off value: 10) with no significant difference in OS between groups (p=0.141). EUS tumour length was not prognostic (OS, p=0.455). Conclusions: Initial LN staging in OA is inaccurate. Although PET/CT and EUS assessments may be complimentary, none independently predicted survival.

FA03.05: NEOADJUVANT CHEMOTHERAPY OR CHEMORADIOTHERAPY FOR ADENOCARCINOMA OF THE ESOPHAGUS

Abstract Background Multimodality treatment of patients with esophageal adenocarcinoma (EAC) improve survival, but the optimal treatment strategy remains undetermined. The aim of this study was to compare outcomes in patients undergoing neoadjuvant chemotherapy (nCT) and neoadjuvant chemoradiotherapy (nCRT) for EAC. Methods Patients who underwent nCT or nCRT followed by surgery for EAC were identified from a prospective database (2000–2017) and included in this study. After propensity score matching, we compared the impact of the treatments on postoperative complications, in-hospital mortality, pathological outcomes and survival rates. Results Of the 396 eligible patients, 262 patients were analysed following propensity score matching. This resulted in 131 patients in the nCT group versus 131 patients in the nCRT group. There were no significant differences between the nCT and nCRT groups for overall complications (59% vs 57%, P = 0.802) or in-hospital mortality (2% vs 0%, P = 0.156). Patients who had nCRT had more R0 resections (93% vs. 83%, P = 0.013), and a higher pathological complete response rate (15% vs. 5%, P &lt; 0.001). The pattern of recurrence was similar (P = 0.753) and there were no differences in 5-year disease-free survival rates (nCT vs nCRT; 39% vs 39%, P = 0.879) or 5-year overall survival rates (nCT vs nCRT; 44% vs 33%, P = 0.645). Conclusion In this study no differences between nCT and nCRT were seen in postoperative complications and in-hospital mortality in patients treated for EAC. Inspite of improved complete resection and pathological response there was no difference in the overall survival between the treatment modalities. Disclosure All authors have declared no conflicts of interest.

Neoadjuvant chemotherapy or chemoradiotherapy for adenocarcinoma of the esophagus.

The optimal treatment strategy for patients with esophageal adenocarcinoma (EAC) remains undetermined. This study compared outcomes in patients undergoing neoadjuvant chemotherapy (nCT) and neoadjuvant chemoradiotherapy (nCRT) for EAC. Patients who underwent nCT or nCRT followed by surgery for EAC were identified from a prospective database (2000-2017) and included. After propensity score matching, the impact of the treatments on postoperative complications, in-hospital mortality, pathological outcomes, and survival rates were compared. Of the 396 eligible patients, 262 patients were analysed following matching with 131 patients in both groups. There were no significant differences between the nCT and nCRT groups for overall complications (59% vs 57%, P = 0.802) or in-hospital mortality (2% vs 0%, P = 0.156). Patients who had nCRT had more R0 resections (93% vs 83%, P = 0.013), and higher pathological complete response rates (15% vs 5%, P < 0.001). No differences in 5-year overall survival rates (nCT vs nCRT; 44% vs 33%, P = 0.645) were found. In this study no differences between nCT and nCRT were seen in postoperative complications and in-hospital mortality in patients treated for EAC. Inspite of improved complete resection and pathological response there was no difference in the overall survival between the treatment modalities.

Impact of visceral obesity and metabolic syndrome on the postoperative immune, inflammatory, and endocrine response following surgery for esophageal adenocarcinoma.

Visceral obesity and metabolic syndrome (MetSyn) represent a constellation of inflammation, insulin resistance, and hyperglycemia and are established risk factors for gastrointestinal cancer. However, their impact on the immune and inflammatory response after major upper gastrointestinal oncologic surgery is unknown. In 125 consecutive patients who underwent esophagectomy, C-reactive protein (CRP) and CRP:albumin levels were recorded preoperatively and on days 1, 3, 7, and 14 postoperatively. In a subset of 30 patients, circulating levels of IL-6, IL-8, IL-10, IL-12p70, IFN-γ, TNF-α, TGF-β, and cortisol were measured. Incidences of postoperative complications were prospectively recorded. In the study cohort, 51% of patients were viscerally obese, 40.7% had MetSyn, and 33.6% were hyperglycemic. Viscerally obese and MetSyn-positive patients demonstrated greater postoperative CRP levels and CRP:albumin levels on day 7 and day 14 compared with nonobese and MetSyn-negative patients (P < 0.05). Higher postoperative circulating levels of cortisol were observed in the viscerally obese and hyperglycemic patients compared to nonobese and normoglycemic patients. No association was observed between visceral obesity, MetSyn or hyperglycemia, and postoperative cytokine profile. Viscerally obese patients had an increased overall incidence of postoperative complications compared to nonobese patients (67.2% vs. 47.5%, P = 0.031) on univariate but not multivariate analysis (P = 0.078) and visceral obesity was not associated with an increased incidence of specific complications. Visceral obesity, MetSyn, and hyperglycemia are prevalent in patients undergoing major upper gastrointestinal resection and are associated with an exaggerated acute-phase inflammatory response postoperatively. Further research is warranted to determine whether this association is directly causal.

Predictors of survival after trimodality therapy for esophageal adenocarcinoma: Analysis from the National Cancer Database.

116 Background: Trimodality therapy with neoadjuvant chemoradiation followed by surgery has been shown to improve survival compared to surgery alone for the treatment of locally advanced esophageal cancer, but there is considerable variation in survival in this population. We sought to analyze factors associated with survival after trimodality therapy in esophageal adenocarcinoma. Methods: We identified 4,679 patients from the National Cancer Database (NCDB) who received chemotherapy and radiation prior to surgery for esophageal adenocarcinoma from 2006-2013. Patients with stage IV disease and unknown pathological nodal status were excluded. We performed a multivariate analysis using a Cox proportional hazards model to identify independent predictors of overall survival. Results: On multivariate analysis, pathologic characteristics associated with decreased overall survival included stage, lymphovascular invasion, and positive surgical margins. Insurance status, age, and comorbidity index were also associated with decreased survival. We found that patients treated at academic programs (HR 0.85, CI 0.78-0.92, p=0.0001) and those who received additional adjuvant chemotherapy had improved survival (HR 0.86, CI 0.75-1.00, p=0.0452), but the vast majority of patients receiving trimodality therapy (4,306; 92.0%) did not receive adjuvant chemotherapy. Patients who received adjuvant chemotherapy were more likely to have private insurance (69 vs. 53%, p&lt;0.0001). Compared to private insurance, Medicaid (HR 1.43, CI 1.20-1.70, p&lt;0.0001), Medicare (HR 1.21, CI 1.07-1.36, p=0.0026), or having no insurance (HR 1.49, CI 1.16-1.90, p=0.0015) were all negative predictors of overall survival. Conclusions: There is wide variation in survival following trimodality therapy for esophageal adenocarcinoma. Both tumor characteristics and patient characteristics play a role. Adjuvant chemotherapy appears to be associated with improved survival, but only a minority of patients receive adjuvant chemotherapy in this setting. Insurance status and treatment setting are independent predictors of overall survival after trimodality therapy and may indicate treatment disparities.

The prognostic significance of perineural invasion in patients with esophageal adenocarcinoma treated with neoadjuvant chemoradiotherapy.

146 Background: Perineural invasion (PNI) is the process of neoplastic invasion of nerves. PNI has been reported as a prognostic indicator in malignancies of the pancreas, stomach, colon, rectum, prostate, head and neck, and biliary tract. However, studies examining the prognostic significance of PNI in esophageal cancer have shown inconsistent results. Analyses in patients with esophageal adenocarcinoma (EAC) have alternatively shown PNI to be a significant and a nonsignificant predictor of OS and DFS in both univariate and multivariate analysis. The majority of these studies analyzed patients who had not received any preoperative therapy. We sought to identify the prognostic significance of PNI in patients with EAC treated with neoadjuvant chemoradiotherapy (nCRT). Methods: We performed a retrospective analysis of 108 patients treated with nCRT and surgery for EAC at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute from 1996-2015. The final analysis identified 73 patients with data on PNI. We evaluated the association of PNI with disease-free survival (DFS), loco-regional progression-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) using log-rank and Cox proportional hazard modeling. Results: Of 73 patients, 17 patients (23%) had PNI and 56 patients (77%) did not have PNI at the time of surgery. The median follow-up was 15.3 months (range 5.8 to 179.3 months). The median DFS was 12.4 months for PNI+ and 36.4 months for PNI- (p = 0.042). The median LRFS was 48.2 months for PNI+ and median not reached for PNI- (p = 0.003). We did not detect a significant association between the presence of PNI and worse OS or DMFS. In a multivariate model including age, sex, gastric involvement, biopsy grade, presence of pathologic complete response, and pathologic N stage, PNI remained a significant independent predictor of LRFS (HR 0.37, 95% CI 0.14 to 1, p = 0.05). Conclusions: In patients with esophageal adenocarcinoma treated with neoadjuvant chemoradiotherapy, PNI discovered at the time of surgery is significantly associated with worse DFS and LRFS.

An analysis of treatment timing parameters for patients receiving neoadjuvant chemoradiation followed by surgery for esophageal adenocarcinoma: a National Cancer Data Base study

An analysis of treatment timing parameters for patients receiving neoadjuvant chemoradiation followed by surgery for esophageal adenocarcinoma: a National Cancer Data Base study

41. The influence of delaying surgery for esophageal adenocarcinoma after neoadjuvant chemoradiotherapy on postoperative outcome

41. The influence of delaying surgery for esophageal adenocarcinoma after neoadjuvant chemoradiotherapy on postoperative outcome

Long-term monitoring of serum p53 antibody after neoadjuvant chemotherapy and surgery for esophageal adenocarcinoma: report of a case

We monitored serum p53 antibody (s-p53-Ab) titers in a 76-year-old man with esophageal adenocarcinoma, clinical stage III (T2N2M0), for over 4 years, including during the perioperative period and throughout follow-up after surgery. Screening tests for CA19-9 (205 IU/ml) and s-p53-Abs (381 U/ml) were positive before treatment. After neoadjuvant chemotherapy with 5-FU and cisplatin, CA19-9 decreased to the normal range, but the s-p53-Ab titer remained positive (224 U/ml). Pathological findings of surgically resected specimens showed stage T1b disease and no lymph node metastases. After surgery, s-p53-Ab titers consistently decreased, with no disease recurrence. Although the s-p53-Ab titer remained positive even after 4 years, it decreased to 8.66, 3.59, 2.38, and 1.92 U/ml, 1, 2, 3, and 4 years after surgery, respectively. Thus, monitoring perioperative changes in s-p53-Ab titers proved useful for detecting the presence of residual cancer cells in a patient with superficial esophageal adenocarcinoma.

Neoadjuvant chemoradiotherapy followed by surgery for esophageal adenocarcinoma: Significance of microscopically positive circumferential radial margins

The incidence and consequence of an isolated involved circumferential radial margin (CRM) after resection for esophageal adenocarcinoma in the setting of neoadjuvant chemoradiotherapy (CRT) has not been reported. We aimed to determine the frequency and significance of a close (<1 mm) or involved CRM in patients undergoing esophagectomy after CRT. We retrospectively analyzed the data from patients undergoing resection from 1997 to 2008 for esophageal adenocarcinoma after neoadjuvant CRT. A positive CRM was defined as microscopic tumor at or less than 1 mm of the radial margin. An R1 resection was tumor at the radial margin. Only patients with ypT3 or greater tumors were included. R2 resections were excluded. Statistical comparisons were performed using Cox regression and Kaplan-Meier analyses. A total of 160 patients met the inclusion criteria, 42 (26%) had a positive CRM. The median survival did not significantly differ between the CRM-negative and -positive groups (28 vs 50 months, P = .84). A propensity score matching analysis also failed to find a significant difference in outcomes. When analyzed by tumor present at the margin (R1), R0 patients had a longer median survival compared with R1 patients (28 vs 8 months, P = .01). This difference, however, was not seen on propensity score matching. Resections of locally advanced esophageal adenocarcinoma with residual transmural viable tumor after CRT frequently showed involvement of the radial margin with tumor either close to or at the margin. Tumor close (<1 mm) to the radial margin did not result in a significant decrease in overall or disease-free survival or increase in local recurrence.