113 Background: Knowledge of pathologic complete tumor response (pCR) and the used neoadjuvant chemoradiotherapy (nCRT) schedule on the distribution of recurrent disease is important in the treatment of esophageal cancer (EC) patients. We assessed the effect of both pCR and different nCRT schedules on the pattern of first tumor recurrences in EC. Methods: The study was performed in two different centers in patients with T1N+/T2-4aN0-3/M0 EC. Patients were treated with nCRT according to the CROSS (carboplatin/paclitaxel/41.4Gy : n=134) and Cis/5FU schedule (Cisplatin/5-fluorouracil/45-50.4Gy : n=88) followed by surgery. First we determined the effect of pCR on tumor recurrence distribution (local, distant or combined) and site-specific recurrences in the CROSS group. After propensity matching on clinical T-stage, clinical N-stage and histology (n=63), we determined the effect of both nCRT schedules on the distribution of tumor recurrence and site specific recurrences. Results: The median follow-up after pCR (n=24) was significant longer ( P=0.001) than in non-complete responders (pNCR); 45.5 (IQR 20.3-69.5) and 20.0 months (12.0-42.3), respectively. The pattern of recurrence also differed significantly ( P=0.001), with 0 (0.0%) and 7 (6.4%) locoregional, 5 (20.8%) and 36 (32.7%) distant, and 0 (0.0%) and 21 (19.1%) local and distant recurrence between the pCR and pNCR group, respectively. Patients with a pCR had significant less local and distant recurrences. With equal median time to recurrence, the distribution of metastases in the matched groups differed only in the numbers of lung metastases ( P=0.029), with 15 (23.8%) and 6 (9.5%), respectively. Conclusions: Patients with a pCR have less local and distant recurrences. With equal time to first recurrence, the nCRT schedule itself had only a minor influence on the distribution of recurrences.

93 Background: 18-F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is currently the imaging method of choice in assessing response of neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (EC) patients. PET/CT derived texture analysis is potentially more useful than common PET/CT measurements in response assessment and might also be of predictive value in different cancer types. The aim of this study was to develop a model to predict response to nCRT in EC based on pretreatment FDG-PET derived textural features in combination with clinical parameters. Methods: We reviewed 80 locally advanced EC patients who underwent pretreatment FDG-PET/CT and radiation planning CT scans between 2009 and 2015. Patients received nCRT according to the CROSS regimen (carboplatin/paclitaxel/41.4Gy) followed by esophagectomy. We analyzed 7 clinical, 16 geometry-based, and 87 different texture features derived from pretreatment FDG-PET images of the radiotherapy gross tumor volume. Ordinal logistic regression analysis was performed to construct a prediction model for treatment response, which was pathologically classified in complete, partial and no response on the Mandard tumor regression grade (1 vs. 2-3 vs. 4-5). The performance of this model was estimated by comparison with clinical outcome. Results: Pathologic examination revealed 16 (20.0%) complete, 46 (57.5%) partial, and 18 (22.5%) non- responders. Response analysis yielded the following independent predictive textural features: SUVmin, small zone low gray level emphasis, and contrast; and the independent predictive clinical parameters: nodal stage, endoscopic tumor length, and gender. The model has a sensitivity/specificity, positive/negative predictive value, and accuracy of 69%/97%, 85%/93%, and 91% for the prediction of complete response and 61%/79%, 46%/88%, and 75% for non-response, respectively. Conclusions: The prediction model constructed in this study, shows a good overall performance level in predicting response to nCRT in EC patients, but requires further external validation and refinement before it can be used for clinical decision making.

25 Background: The optimal sequence of endoscopic ultrasonography (EUS) and positron emission tomography with computed tomography (PET/CT) in esophageal cancer (EC) is a matter of debate. The use of EUS with fine needle aspiration (FNA) after PET/CT seems to increase the efficacy of curative intended neoadjuvant or definitive chemoradiotherapy. Retrospectively, we assessed the impact of EUS in the PET/CT upfront model on the treatment decision making in EC patients. Methods: In the period 2009 to 2015, 298 EC patients were staged with hybrid PET/CT or PET with CT, and EUS if applicable, in a non-specific order to assess curability (T1-4a,N0-3M0). We determined the feasibility of EUS and whether the initial or additional EUS changed the primary decision suspicious incurable (T4b and M+) into curable disease or added extra nodal information leading to up/downstaging or exhibit suspected nodes at different lymph node stations. In addition, we assessed if EUS changed the radiation area (i.e. lymph nodes > 3.5 cm from the defined radiation target volumes) in the PET/CT “upfront model”. Results: EUS was complete in 185 (62.1%) and incomplete due to stricture from a relative obstructing tumor in 59 (19.8%) patients. Fifty-four patients (18.1%) did not receive EUS because of stenosis (n = 46; 15.4%), patient dependent reasons (n = 4; 1.3%) or other reasons (n = 4; 1.3%). EUS after hybrid PET/CT or PET with CT (n = 244) gave additional information in 166 patients (68.0%); it changed the curability in 4 (1.6%), lead to nodal up and downstaging in respectively, 81 (33.2%) and 27 (11.1%) patients, changed the number of or lymph node station of suspected lymph nodes in an additional 58 patients (n = 23.8%), and FNA gave additional information in 34 (13.9%) patients. EUS after PET/CT ”upfront” changed the treatment plan in 90 patients (36.9%), including alteration in the radiation field (86; 35.2%) and curability (4; 1.6%). Conclusions: EUS gave additional information after PET/CT “up front” and altered the radiation field in about one third of the EC patients, suggesting a better yield of “EUS on indication” after PET/CT upfront.

111 Background: Although essential in treatment decision making, clinical nodal (cN) staging in esophageal cancer (EC) remains difficult. We assessed the rate of nodal up- and downstaging and its prognostic value on 5-year disease-free survival (DFS) in EC patients treated with surgery-alone or with neoadjuvant chemoradiotherapy (nCRT). Methods: For this retrospective study, we included 395 EC patients who underwent a curative esophagectomy with or without nCRT between 2000 and 2015. The surgery-alone and nCRT group were matched on clinical T-stage (cT), cN-stage, and histopathological type using propensity score matching ( n=270). Staging consisted of PET with CT, or PET/CT, and endoscopic ultrasonography (n = 235). We compared cN and pathological N-stage (pN) and scored correct, down- and upstaging. The prognostic value of nodal up- and downstaging and localization of node metastases on 5-year DFS were assessed with multivariate Cox regression analysis (factors with a P-value <0.1 on univariate analysis). Results: Nodal upstaging (43.0% vs. 16.3%), correct staging (31.9% vs. 28.1%) and downstaging (25.2% vs. 55.6%) differed between the surgery-alone and nCRT group ( P<0.001). Nodal upstaging was commonly present in adenocarcinoma and cT3-4a tumors. Independent prognostic factors for DFS were pN ( P=0.002) and lymph-angioinvasion ( P=0.016) in the surgery and cN metastasis under the diaphragm ( P=0.012) and lymph node ratio ( P=0.034) in the nCRT group. Conclusions: In esophageal cancer, clinical lymph node staging is still insufficient with >25% nodal downstaging. This inaccuracy might impede assessment of true nodal response to nCRT, affording dubious decisions for a ‘wait-and-see’ strategy.