bluuebunny/crossref_metadata_2025 huggingface dataset:
PS02.032: PRETREATMENT INFLAMMATORY STATUS INFLUENCES THE PROGNOSIS OF CT4B ESOPHAGEAL CARCINOMA PATIENTS UNDERGOING DEFINITIVE CHEMORADIOTHERAPY
Authors: Sugawara Kotaro , Yagi Koichi , Nishida Masato , Yamashita Hiroharu , Seto Yasuyuki
Published: September 2018

Background

The outcome of definitive chemoradiotherapy (dCRT) for patients with cT4b esophageal carcinoma (EC) remains poor. Also, few studies focused on the prognostic factors in cT4b EC patients undergoing dCRT.

Methods

80 patients undergoing dCRT for cT4b EC between 2006 and 2016 were retrospectively reviewed. All were in ECOG-PS 0–1. For evaluation of the pretreatment status, we employed demographic data, BMI, inflammatory marker (CRP), nutritional marker (Alb, prognostic nutritional index (PNI)) and tumor factors (clinical staging, pretreatment stenosis, tumor marker).

Results

There were 62 men with a mean age of 65 years (range, 41–83 years). 77 patients were squamous cell carcinoma, while 3 were adenocarcinoma. There were 12 (15%) patients with cM1 (lym) status. 36 (45.0%) patients had esophageal stenosis. 70 patients had cN + before dCRT, while 22 had cN + after dCRT. 30 patients (37.5%) had a CRP > 10 mg/l before dCRT, while 15 patients (18.8%) were in poor-nutritional status (PNI < 40). Of 80 patients, 1 patient gave up the treatment developing cerebral infarction. We analyzed survival in the 79 patients completing dCRT. Esophageal perforations were occurred in 5 (6.3%) patients. The 1- and 3-year overall survival rates were 59.8% and 38.3%, respectively. Salvage surgery was performed in 29 (36.3%) patients. R0 resection was achieved in 20 (69.0%) patients. Surgery-related death was developed in 3 patients. Pathological complete response was found in 10 (34.5%) patients. The 1- and 3-year overall survival rates of these 29 patients were 64.3% and 40.5%, respectively. Lastly, we evaluated prognostic factors in 79 patients. In univariable analysis, PNI < 40 (HR 2.43, 95% CI 1.19–4.63, P = 0.02), CRP ≥ 10 mg/l (HR 2.21, 95% CI 1.23–3.95, P = 0.01), pretreatment stenosis (HR 1.68, 95% CI 0.94–3.00, P = 0.08), cN + status after dCRT (HR 1.84, 95% CI 0.98–3.33, P = 0.06) were associated with poor prognosis. Subsequent multivariable Cox proportional hazards model revealed that CRP ≥ 10 mg/l (HR 2.00, 95% CI 1.03–3.81, P = 0.04) and cN + status after dCRT (HR 2.02, 95% CI 1.05–3.73, P = 0.03) were both independent risk factors for poor prognosis.

Conclusion

The outcome of dCRT for cT4b EC is acceptable. Pretreatment inflammatory status significantly influences the prognosis of patients undergoing dCRT.

Disclosure

All authors have declared no conflicts of interest.
PS02.041: VITAMIN D SIGNALING PATHWAYS CONFER THE SUSCEPTIBILITY OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Ji Aifang , Zhou Yang
Published: September 2018

Background

Experimental studies have determined the chemopreventive effects of vitamin D against theesophageal squamous cell carcinoma (ESCC); however, results from the epidemiological studies arenot yet well established. The current study aimed to evaluate the associations between plasmavitamin D levels and variants on vitamin D metabolic-related genes with the risks for ESCC.

Methods

A hospital-based case-control study was performed. 670 ESCC patients and 598 controls were recruited in a Northern Chinese population. The vitamin D levels in the plasma were determined with the ELISA detection kits provided by R&D Company and following the manufacturer's instructions. The coefficients of variation for the 25(OH)D levels between-assay and within-assay were less than 12.5%. Common variants on vitamin D metabolism-related genes CYP24A1, DHCR7, GC, CYP27B1, and vitamin D receptor (VDR) and theplasma 25(OH)D level were determined. The genomic DNA was extracted from the blood lymphocyte cells with the QIAamp DNA Mini Kit (Qiagen, Germany). The SNPs were genotyped using the GenomeLab SNPstream 12-plex Genotyping System (Beckman Coulter, Inc., Fullerton, CA) following the manufacturer's instructions. The unconditional logistic regression method was applied to determine the associations between the variants and vitamin D level and ESCC.

Results

we evaluated 6 common variants on genes related to vitamin D metabolism including DHCR7 (rs3829251), DBP (rs12512631 and rs115563), CYP24A1 (rs2296241), CYP27B1 (rs4646536) and VDR (rs11568820) and their association with ESCC risk. For rs2296241, rs11568820 and rs4646536, interaction analysis shows that higher the plasma 25(OH)D levels are associated with a decreased ESCC risk.For rs3829251, rs3829251 and rs1155563, the plasma 25(OH)D levels did not vary across genotypes for any of the polymorphisms. The variants rs2296241 on CYP24A1 and rs11568820 on VDR are significantly associated with ESCC cancer.

Conclusion

Vitamin D signaling pathways may participate in the ESCC development. Further studies with larger sample size are warranted to confirm the results. Intervention studies are needed to determine whether vitamin D supplementation may reduce the ESCC risk in the Chinese population.

Disclosure

All authors have declared no conflicts of interest.
PS02.052: AUTO-ANTIBODIES AGAINST TUMOR ANIGENS ARE USEFUL BIOMARKERS IN PATIENTS WITH ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Shimada Hideaki , Yajima Satoshi , Oshima Yoko , Ito Masaaki , Nanami Tatsuki , Suzuki Takashi , Funahashi Kimihiko , Otsuka Seiko , Hoshino Isamu , Nabeya Yoshihiro
Published: September 2018

Background

Serum antibodies are induced even ata the eraly phase of carcinogenesis. Serum p53 antibodies (s-p53-Abs) have been developed and approved as routine blood test for monitoring esophageal squamous cell carcinoma (SCC). Recently, we have developed new ELISA systems to detect serum anti-IgG auto-antibodies against tumor antigens in patients with esophageal (SCC). In this paper, we focused on serum auto-antibodies against p53, NY-ESO-1, Galectin-1 and RalA.

Methods

Serum samples of patients with esophageal SCC were obtained before surgery. Serum anti-IgG antibodies against several tumor antigens were analyzed by newly developed ELISA systems. Target tumor antigens were p53, NY-ESO-1, Galectin-1 and RalA. Cut-off values were fixed using mean + 3SD of values of a total of 74 healthy controls. Changing pattern of serum p53 antibodies titers was also assessed during postoperative follow-up.

Results

Positive rates of serum antibodies were 18% for p53, 31% for NY-ESO-1, 10% for Galectin-1 and 9% for RalA. Positive rates of these antibodies in healthy controls were 0%. Combination assay improved positive rates without increased false positive rates as follows; p53 + NY-ESO-1 = 40%, p53 + NY-ESO-1 + Galectin-1 = 47%, p53 + NY-ESO-1 + Galectin-1 + RalA = 51%. Although some patients with extremely-high antibody titer for p53 persistently positive even after curative surgery, changing patterns of serum titers seemed to be associated with clinical outcome.

Conclusion

Although antibody titer of s-p53-Abs seemed to be associated with tumor burden, the titer gradually decresed at the last several months of the terminal stage. Such independent changing pattern of serum autoantibodies may have adding information to conventinal serum markers. We have developed new ELISA system to detect serum autoantibodies for patients with esophageal SCC. Although the positive rates of single serum auto-antibody were still relatively low, combination assay with plural auto-antibodies may be useful.

Disclosure

All authors have declared no conflicts of interest.
PS02.058: EXTENSIVE ANALYSIS OF IMMUNECHECKPOINT RECEPTORS AND TUMOR INFILTRATING T-CELLS WITH RESPECT TO THEIR PROGNOSTIC RELEVANCE IN ESOPHAGEAL ADENOCARCINOMA
Authors: Gebauer Florian , Loeser Heike , Fuchs Hans , Leers Jessica , Schroeder Wolfgang , Quaas Alexander , Bruns Christiane
Published: September 2018

Background

Immunotherapy has grown to a rapidly advancing sphere of research on modern strategies for treatment of cancer. A well-known way of immunomodulation is the principle of immune checkpoints leading to a down-regulated immune response in tumor microenvironment. Recently, beside the PD1/PD-L1 pathway, several immunecheckpoint pathways have been found. However, almost nothing is known about the expression and the correlation as prognostic factor in esophageal adenocarcinoma.

Methods

Two tissue micro arrays (TMA) were construced, a multi-spot TMA with up to 8 spots from different tumor areas of 165 patients and a valdiation single-spot TMA of 620 patients with EAC. Immunehistochemistry analysis were performed for LAG3, Tim3, IDO, VISTA, MHC1, MHC2, CD3, CD8, CD20 and CD38 and correlated with clinico-pathological and survival data. Data were additionally correlated with molecular data like TP53 mutational and HER2-neu status.

Results

LAG3 was detectable in 13.5% of all tumors, VISTA in 40.2%, IDO in 57.9%, Tim3 in 36.3%. There was only minor intratumoral heterogeneity between the luminal and infiltration area of the tumor for all analyzed immunecheckpoints. LAG3 and VISTA expression on tumor infiltrating T-cells (TIL) was associated with superior overall-survival compared to LAG3 and VISTA negative tumors. In pT1/2 tumors, VISTA was found as excellent independent prognosticator identifiying long-term surivors in case of VISTA expression. High amount of CD3 positive TILs was also associated with a better OS than CD3 poor tumors.

Conclusion

We conducted an extensive analysis of the immunecheckpoint status and presecnce of TILs in EAC. To the best of our knowledge, this is the first report in a large patients cohort correlating the expression of LAG3, Tim3, IDO and VISTA in EAC. The prognostic impact of LAG3 and VISTA expression suggests potential promising targets for novel immune checkpoint inhibition therapies beyond the PD1/PD-L1 inhibition as it is already established in head and neck cancer and NSCLC.

Disclosure

All authors have declared no conflicts of interest.
PS02.059: ENHANCED EXPRESSION OF NT5E IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Kataoka Atsuko , Yamada Kazuhiko , Sugimoto Takayuki , Hagiwara Teruki , Nohara Kyoko , Soma Daisuke , Yamashita Satoshi , Dohi Taeko , Kawamura Yuki I
Published: September 2018

Background

Epigenetic changes such as DNA methylation are involved in the onset of ESCC. Previously, we have conducted transcriptome and methylome analyses using a paired specimen of ESCC and adjacent non-cancerous tissues and found promotor hypomethylation of NT5E with altered gene expression level in ESCC. NT5E has been known to be an extracellular nucleoside metabolism-related enzyme; however, the significance of its expression in ESCC has never been clarified. In this study, we aimed to evaluate the ESCC-related alteration of the expression of NT5E in using many cases of ESCC.

Methods

Formalin-fixed, paraffin-embedded sections of surgical specimens from 67 ESCC patients who had undergone esophagectomy or endoscopic submucosal dissection between April 2008 and December 2015 in our hospital were immunostained using anti-NT5E antibody, and classified into NT5E-negative and NE5E-positive groups. To evaluate the mRNA expression of NT5E, qRT-PCR was performed using paired normal and ESCC frozen tissue samples from 24 patients.

Results

Compared with matched normal mucosa, cancer tissues showed significantly higher NT5E mRNA expression (P < 0.05). Histologically, normal esophageal mucosa showed almost no staining of NT5E. Contrastingly, NT5E expression was clearly detected in 34 of 67 ESCC specimens (50.7%). There is no significant difference in clinicopathological factors between NT5E-positive and NT5E-negative groups.

Conclusion

NT5E gene and protein expression was both upregulated in ESCC; its functional significance in relation to malignancy is underinvestigation.

Disclosure

All authors have declared no conflicts of interest.
PS02.067: PREDICTIVE VALUE OF 18F-FDG PET-CT METABOLIC PARAMETERS PRIOR TO TREATMENT ON SHORT-TERM CURATIVE EFFECTS OF ESOPHAGEAL CANCER
Authors: Li Jiancheng , Sun Weijie
Published: September 2018

Background

To investigate predictive value of pre-treatment maximal standardized uptake value (SUVmax) and metabolic tumor volume (MTV) on short-term curative effects in esophageal cancer patients.

Methods

Retrospective analysis was made for 98 cases of patients with esophageal cancer treated by radiotherapy or radiotherapy combined with chemotherapy in Fujian Cancer Hospital. Before treatment, 18F-FDG PET-CT scan was performed. PET/CT images prior to treatment were read by two doctors with a high-level professional title using double-blind method. SUVmax and MTV were determined and averaged. 1–3 months after treatment, an experienced deputy director of PET/CT center and a radiotherapist evaluated the curative effect of all patients according to the Response Evaluation Criteria in Solid Tumor (RECIST).

Results

There were no significant differences of SUVmax and MTV between two groups in age, gender, cancer site, and differential extent (P > 0.05). Factors related to SUVmax were lesion length, depth of invasion, lymph node metastasis and clinical stage, while differences were statistically significant (P < 0.05). SUVmax & MTV were positively correlated with lesion length, depth of invasion, lymph node metastasis and clinical stage. The effective rate was 67.3% (66/98). SUVmax (r = -0.283, P = 0.049) and MTV(r = -0.379, P = 0.007) were negatively correlated with short-term curative effects, but the curative effect of MTV was higher than that of SUVmax.

Conclusion

There were no significant effects of clinical factors e.g. age, gender, esophageal cancer site, and differential extent on SUVmax and MTV, but length of lesion, depth of invasion, lymph node metastasis and clinical stage had significant effect on SUVmax and MTV. SUVmax and MTV prior to treatment can predict short-term curative effects of radiotherapy or radiotherapy combined with chemotherapy for esophageal cancer patients, but MTV is more predictive than SUVmax.

Disclosure

All authors have declared no conflicts of interest.
PS02.078: FEASIBILITY OF PREOPERATIVE STAGING WITH USPIO ENHANCED MRI IN PATIENTS WITH RESECTABLE ESOPHAGEAL CARCINOMA (PRECIES STUDY)
Authors: De Gouw Didi , Klarenbeek Bastiaan , Van Der Post Chella , Hermans John , Maas Marnix , Slagt Cor , Rovers Maroeska , Scheenen Tom , Rosman Camiel
Published: September 2018

Background

In operable patients suffering from esophageal cancer, the percentage of patients without metastatic lymph nodes found after neoadjuvant chemoradiotherapy (nCRT) is 69%. Extensive lymph node dissections during esophagectomy may be omitted or minimized in these patients, reducing associated morbidity. Recently, MRI with ultrasmall superparamagnetic iron oxide nanoparticles (USPIO, ferumoxtran-10) has been reintroduced to detect metastatic lymph nodes in prostate cancer. The aim of this study is to assess the feasibility of USPIO-MRI to detect loco-regional lymph node metastases in patients with esophageal cancer.

Methods

USPIO-nanoparticles are intravenously infused 24 to 36 hours before MRI. USPIO-enhanced MRI is performed before and after nCRT. After nCRT, patients are scanned under general anesthesia immediately prior to surgery in the MR system of the hybrid MITeC operation room with controlled mechanical ventilation. During controlled prolonged apneu, a four-minute iron-sensitive MRI acquisition is used to visualize suspicious esophageal lymph nodes without motion artefacts. Resected specimens, still containing USPIO, are measured ex-vivo in a preclinical 7T MR system before histopathological examination. A radiological assessment of the presence of suspicious lymph nodes in-vivo is matched to the ex-vivo nodes on preclinical MRI, providing the ground truth for the presence of metastases.

Results

Currently, three patients were included in the study of which one patient has been examined before and after nCRT. MRI under anesthesia prior to surgery with controlled mechanical ventilation was possible resulting in a clinically relevant spatial resolution to visualize possible malignant lymph nodes. Suspicious nodes were identified and could be matched using corresponding anatomical landmarks to the ex-vivo MRI, which showed good visual agreement with esophageal specimen after resection.

Conclusion

A successful method was proposed to validate USPIO-enhanced MRI to detect metastatic lymph nodes in patients with esophageal cancer. Matching ex-vivo USPIO-MRI images with histopathology results provides direct information for validation of in vivo USPIO-MRI and characteristics of loco-regional lymph nodes. Final results on the feasibility of USPIO-MRI to detect metastatic lymph nodes after nCRT are still awaited. Feasibility and preliminary values of the accuracy of the technique are the starting point for a phase two study.

Disclosure

All authors have declared no conflicts of interest.
PS02.085: ASSESSMENT OF TUMOR REGRESSION OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER NEOADJUVANT CHEMORADIOTHERAPY: COMPARISON OF 3 COMMONLY USED SCORING APPROACHES
Authors: Chao Yin-Kai , Fang Hsin-Yueh
Published: September 2018

Background

Tumor regression grade (TRG) is a measure of histopathological response of cancer to neoadjuvant chemoradiotherapy(nCRT) and is associated with outcomes. Several TRG system are used in esophageal cancer: Schneider 4 tier(0%,1∼10%,10∼50%, > 50% vital residual tumor cell[VRTC]), Chirieac 3 tier(0%,1∼50%, > 50% VRTC) and Japanese 4 tier(0%,1∼33%,33∼66%, > 66% VRTC). Although these methods are generally accepted, currently there is no common standard.

Methods

We compared the application of three major systems for assessment of tumor regression. Hematoxylin and eosin–stained slides from 370 resection specimens of esophageal squamous cell carcinoma following nCRT were independently reviewed by two pathologists. Primary endpoints included (1) interobserver agreement (2) prognostic discrimination

Results

Interobserver agreement was excellent for all three sutem while the Chirieac 3 tier system showed the best kappa value(0.93). All models had similar discriminatory and stratification power, and they predicted survival (P < 0.0001) on univariate analysis. While Chirieac system remained a significant predictor for overall survival independent of yp-stage and margin status in multivariate analysis.

Conclusion

A simple 3-tiered system with the estimation of VRTC(0%,1∼50%, > 50%) is most reproducible for the evaluation of histological response and together with yp-stage and margin status as independent predictors for survival.

Disclosure

All authors have declared no conflicts of interest.
PS02.088: COMPARATIVE STUDY OF CT AND PATHOLOGICAL DIAGNOSIS TOWARD MEDIASTINAL LYMPH NODE METASTASIS IN ESOPHAGEAL CARCINOMA
Authors: Li Jiancheng , Chen Shanshan
Published: September 2018

Background

To investigate the diagnostic criteria of mediastinal lymph node metastasis (MLNM) in special site, which were less than 1cm, in esophageal carcinoma (EC) by comparing the lymph node size measured by CT and obtained by postoperative pathological examination.

Methods

A total of 305 EC patients were selected, scanned the location, short diameter, and number of MLNs one week before surgery, and then compared with their pathological findings.

Results

the ROC curve analysis revealed that the best short diameters of MLNM in the thoracic cavity, supraclavicular fossa (located among the clavicle, sternocleidomastoid, and omohyoid muscle), tracheoesophageal groove that can be diagnosed by CT were 8mm, 5mm, and 6mm, respectively; compared with those with the short diameter as 10mm, the sensitivity was increased significantly, the specificity and accuracy were little changed, while the Youden's index was increased significantly.

Conclusion

It is reasonable to reduce the CT diagnostic criteria of the short diameter of positive lymph nodes in some special site such as supraclavicular fossa and tracheoesophageal groove.

Disclosure

All authors have declared no conflicts of interest.
PS02.091: ENDOSCOPIC FINDINGS OF SMALL ESOPHAGEAL SQUAMOUS CELL CARCINOMA DEPTH OF INVASION OF SM2
Authors: Nakano Kaoru , Ishiyama Akiyoshi , Namikawa Ken , Yamamoto Yasunori , Akazawa Naoki , Fujisaki Jyunko
Published: September 2018

Background

Among superficial esophageal squamous cell carcinomas (SESCCs), cases with invasion of deeper submucosal layer (clinical SM2) were not be indication for treatment with endoscopic resection (ER). We occasionally have selected ER for cSM2 SESCC in patients with small lesions or who are in poor general condition. The result of the report of clinical research (JCOG0508) proved non-inferiority of three year overall survival in stage pT1b cases with treated by of ER plus chemoradiotherapy compared to surgical resection. Accurate prediction of invasion depth of SM2 will be possible to resect by ER with negative vertical margins and to decrease radiation dose. In this study, we compared the efficacy of endoscopic modality for predicting SM2 invasion in patients with small SESCCs.

Methods

We enrolled 13 patients with SESCC, pathologically diagnosed SM2, and lesions smaller than 15mm who had undergone ESD with en-bloc resection at our hospital between April 2005 and March 2017. We compared accuracy rates of diagnosis before ESD for invasion depth in each modality. Especially with WLI, we defined several findings suspected to indicate SM2 invasion of tumor (hereinafter called ‘SM2 sign’). We evaluated whether ‘SM2 signs’ were present or absent for each lesion.

Results

The median size was 10mm. Macroscopic types elevated in three cases, flat in one and depressed in nine. The only flat type case was detected after iodine staining, and its predicted invasion depth was intra-mucosal layer. Among three elevated type lesions the accuracy of WLI and ME-NBI SM2 was 33% and 33%, respectively. EUS was underdiagnosed. ‘SMT-like elevation’, ‘elevate taller than 2mm’ and ‘intense redness’ were observed in two, one and one case, respectively. Among nine depressed type lesions, the accuracy of WLI, ME-NBI and EUS was 22%, 11%, and 25%, respectively. ‘Deep depression’ ‘uneven mucosa of depressed area’ and ‘marginal elevation’ were observed in zero, five and six cases, respectively. At least one finding of SM2 sign was observed in 77%.

Conclusion

We can increase in the accuracy rate of SM2 invasion for small SESCCs when focusing on SM2 sign with WLI before ER.

Disclosure

All authors have declared no conflicts of interest.
PS02.092: HER2 EXPRESSION AND GENE AMPLIFICATION CORRELATES WITH BETTER SURVIVAL IN ESOPHAGEAL ADENOCARCINOMA
Authors: Loeser Heike , Plum Patrick , Zander Thomas , Kraemer Max , Alakus Hakan , Buettner Reinhard , Bruns Christiane , Gebauer Florian , Quaas Alexander
Published: September 2018

Background

Targeting Her2 is highly established in cancers of the upper gastrointestinal tract, since clinical studies showed a survival benefit in Her2-positive gastric cancer. To date there is conflicting data concerning the impact of Her2 expression and gene amplification in esophageal adenocarcinoma (EAC), as most studies do not differ between cancers of the esophagus, gastroesophageal junction and stomach. The aim of this study was to analyze the expression and gene amplification of Her2 in EAC in correlation to clinical and pathological data to verify the prognostic impact.

Methods

We analyzed 506 patients with esophageal adenocarcinomas that underwent thoraco-abdominal esophagectomy between 1997 and 2013 using a tissue micro array (TMA) for the expression of Her2 by immunohistochemistry (IHC) according to the guidelines. Fluorescence-in-situ-hybridization (FISH) was performed for IHC score 2. The Her2-status was correlated with clinical and pathological data.

Results

Her2-positivity was found in 11.7% (n = 59) of all EAC (IHC score 3 + or IHC score 2 + with amplification) and demonstrated a significant better overall-survival (OS) in correlation to Her2-negative tumors (median OS 55.0 vs. 22.7 months, P < 0.0001) (Figure below). Overexpression of Her2 was associated with lower tumor stages (pT1/pT2, P = 0.038), absence of lymph node metastases (pN0/pN + , P = 0.030) and was significantly associated with tubular and/or papillary tumor growth pattern (P = 0.029).

Conclusion

We demonstrated a positive prognostic impact of Her2 expression and gene amplification in a large cohort of EAC, contrary to other solid malignancies including gastric cancer, but according to a large study of EAC from 2012. Her2-positive tumors significantly have a tubular and/or papillary tumor growth pattern, indicating a marker of differentiation in EAC.

Disclosure

All authors have declared no conflicts of interest.
PS02.097: PROGNOSTIC IMPACT OF LYMPH NODE METASTASIS STATIONS IN PN1 STAGE ESOPHAGEAL SQUAMOUS CARCINOMA PATIENTS
Authors: Tang Peng , Ma Zhao , Yu Zhentao
Published: September 2018

Background

Although numerically based lymph node staging system of UICC/AJCC of esophageal squamous cell carcinoma (ESCC) offers excellent prognostic performance, it doesn’t offer information on the anatomical extent of disease. The aim was to evaluate prognostic impact of lymph node metastasis (LNM) stations and regions in pN1 stage patients.

Methods

Among patients with ESCC undergone esophagectomy classified as R0 from January 2005 to December 2010, 185 patients diagnosed as pN1 were selected for analysis with univariate and multivariate Cox regression analysis.

Results

The most common metastasis areas in pN1 patients were middle and lower thoracic paraesophageal LN (28.6%), left gastric artery LN (27.6%) and paracardial LN (24.3%). Non- middle and lower paraesophageal LNM (P = 0.049), subcarinal LNM (P = 0.041) and multiple left gastric artery LNM (P = 0.010) were independent risk factors for worse survival. The median survival of the N1 (JES) group was significantly better than the N2 (JES) (40.1 months vs. 22.4 months, P = 0.012). However, no significant difference was found in median survival rate among intra-thoracic LNM, upper-abdominal LNM and both LNM.

Conclusion

Paraesophageal LNM, subcarinal LNM and left gastric artery LNM are predictive factors for survival and should be swept routinely in pN1 stage ESCC patients. On the basis of UICC/AJCC lymph node Classification system, anatomical lymphatic spread pattern analysis could further improve prognosis prediction.

Disclosure

All authors have declared no conflicts of interest.
PS02.099: EFFORTS IN PROPHYLAXIS OF FEBRILE NEUTROPENIA IN DCF THERAPY FOR ESOPHAGEAL CANCER
Authors: Okamoto Koichi , Ninomiya Itasu , Ohta Tetsuo , Fushida Sachio , Oyama Katsunobu , Kinoshita Jun
Published: September 2018

Background

DCF therapy (5-FU + CDDP + Docetaxel) for esophageal cancer is known to have strong anti-tumor effect but the incidence of bone marrow suppression (BMS) and febrile neutropenia (FN) after DCF therapy has been frequent and patients is often forced to reduce the dose of anti-cancer drug or discontinue of chemotherapy. We clarified the influence of prophylactic administration of a long-acting G-CSF, pegfilgrastim, in DCF therapy for esophageal cancer on the incidence of adverse events and anti-tumor effect.

Methods

From March, 2011 to July, 2017, 87 patients underwent DCF therapy (Docetaxel 60mg/m2 D1, CDDP 60mg/m2 D1, 5-FU 800mg/m2 D1–5) for esophageal squamous cell carcinoma above cStage II (33 patients administered pegfilgrastim, P group; 54 patients without pegfilgrastim, N group). We investigated the influence of pegfilgrastim on the incidence of adverse events in both groups according to CTCAE v4.0 grading system. And we investigated anti-tumor effects assessed by image examination in all patients and 47 surgically resected specimens.

Results

The incidence of leukocytopenia and neutropenia in P group were significantly lower than that in N group (15.2% vs 57.4%, P < 0.001; 21.2% vs 64.8%, P < 0.001, respectively). The incidence of FN in P group tended to be lower than that in N group (9.1% vs 20.4%, P = 0.233). Significantly more patients in N group suffered dose reduction or discontinuation of chemotherapy due to BMS or FN (30.3% vs 72.2%, P < 0.001). Relative dose intensity of 5-FU in P group was significantly higher than that in N group (95.6% vs 82.5%, P = < 0.001). In endoscopically evaluated response after 2 courses of DCF therapy, the reductive effects in the patients in P group significantly better than in those in N group (PR < ; 78.1% vs 44.0%, P = 0.002). The overall response rate was also significantly better in the patients in P group than in those in N group (PR < ; 60.6% vs 35.2%, P = 0.021). Histopathological responses in surgically resected tumor in P group tended to be better than N group (Grade 1b < ; 47.1% vs 33.3%, P = 0.352).

Conclusion

DCF chemotherapy with prophylactic administration of pegfilgrastim may be an option for safe and effective chemotherapy for advanced esophageal cancer.

Disclosure

All authors have declared no conflicts of interest.
PS02.103: THE PATTERN OF RESIDUAL TUMOR AFTER NEOADJUVANT CHEMOTHERAPY FOR ADVANCED ESOPHAGEAL CANCER AND ITS CLINICAL SIGNIFICANCE
Authors: Hashimoto Tadayoshi , Makino Tomoki , Yamasaki Makoto , Tanaka Koji , Miyazaki Yasuyuki , Takahashi Tsuyoshi , Kurokawa Yukinori , Nakajima Kiyokazu , Mori Masaki , Doki Yuichiro
Published: September 2018

Background

Although neoadjuvant chemotherapy (NAC) has recently became a standard treatment for locally-advanced esophageal squamous cell carcinoma (ESCC), residual pattern of cancer cells in resected specimen after NAC has not been clarified yet.

Methods

A total of 120 patients with cT3 or T4 ESCC who underwent curative esophagectomy after NAC and achieved grade2 as histological efficacy between 2000–2016 were analyzed. We classified the pattern of residual tumor into 4 categories; Type 1: Shallow remnant (between mucosa and submucosa), Type 2: Central remnant (between submucosa and muscularis propria), Type 3: Deep remnant (between muscularis propria and adventitia), and Type 4: diffuse remnant (between mucosa/submucosa and muscularis propria/adventitia) and examined its relationship with clinicopathological factors and prognosis.

Results

The tumor remnant type was categorized as follows; Type 1/Type 2/Type 3/Type 4: = 49/33/9/29 cases. Forty-five cases had no residual cancer cells in the mucosal layer. The positivity rate of lymphatic invasion was similar between 4 categories, while the positivity of venous invasion was significantly higher in Type 3 and 4 as compared to Type 1 or 2 (P = 0.04). Regarding the pattern of recurrence, lymph node recurrence was more common in Type 1 (69%) and Type 2 (83%) compared to Type 3 (50%) or Type 4 (38%) (P = 0.29). Notably, more patients with Type 3 or 4 developed pleural dissemination or distant metastasis as compared with those with Type 1 or 2 [pleural dissemination: Type 1/2/3/4: 0%/0%/50%/38% (P = 0.029), distant metastasis: Type 1/2/3/4: 31%/13%/50%/88%, (P = 0.11)]. No significant difference in 2-year recurrence-free survival rate was identified among 4 categories (Type 1/2/3/4: 65.9%/78.0%/74.1%/71.8%, P = 0.757).

Conclusion

The most common pattern of residual tumor after NAC for advanced ESCC was shallow remnant although approximately forty percent of cases inversely showed tumor disappearance at least in mucosal layer. Lymph node metastases was the predominant pattern of disease recurrence in patients with the shallow and middle remnant type while deep and diffuse remnant pattern were significantly associated with pleural dissemination and distant metastasis.

Disclosure

All authors have declared no conflicts of interest.
PS02.106: THE IMPACT OF HISTOPATHOLOGICAL LYMPH NODE METASTASES AFTER PREOPERATIVE CHEMO-RADIOTHERAPY ON THE PROGNOSIS IN ESOPHAGEAL CANCER PATIENTS
Authors: Murakami Kentaro
Published: September 2018

Background

Esophageal cancer does not have a good prognosis despite being resectable. A recent randomized controlled trial (the Dutch CROSS study) showed the superiority of preoperative chemo-radiotherapy over surgery alone with regard to the five-year survival. At present, this therapeutic approach is regarded as the standard care in the United States and Europe. However, the prognosis in cases where part of the tumor remains is poor, so additional adjuvant therapy is required. The impact of the histopathological lymph node metastases status after preoperative chemo-radiotherapy on the prognosis is unknown, and is which patients require additional adjuvant therapy to manage lymph node metastases.

Methods

Esophageal cancer patients with more than five lymph node metastases or lymph node metastases spreading into three fields have a poor prognosis, despite their tumor being resectable. We therefore performed neoadjuvant chemo-radiotherapy in these patients in 1998 (NACRT group). We also performed chemo-radiotherapy for initially unresectable locally advanced esophageal cancer invading adjacent organs and curative surgery for the above-mentioned patients in whom the invasion had disappeared after chemo-radiotherapy (conversion group). The chemo-radiotherapy regimen was the same for both groups and consisted of radiotherapy 40 Gy/20 fr and chemotherapy with 5-FU (500 mg/m2 days 0–4) and CDDP (15 mg/m2 days 1–5). We then examined the impact of the histopathological lymph node metastasis status after preoperative chemo-radiotherapy on the prognosis in our institute.

Results

Patients with three or more histopathological lymph node metastases had a significantly poorer prognosis than those with fewer metastases in both groups. In the NACRT group, the 5-year survival rate was 35.5% vs. 36.1% (number of lymph node metastases 0 vs. ≥ 1; P = 0.889), 34.0% vs. 36.7% (0–1 vs. ≥ 2; P = 0.678), and 47.1% vs. 0% (0–2 vs. ≥ 3; P = 0.003). In conversion group, it was 40.4% vs. 43.6% (number of lymph node metastases 0 vs. ≥ 1; P = 0.841), 45.6% vs. 33.6% (0–1 vs. ≥ 2; P = 0.106), and 49.5% vs. 20.0% (0–2 vs. ≥ 3; P = 0.025).

Conclusion

Patients with three or more histopathological lymph node metastases after preoperative chemo-radiotherapy had a significantly poorer prognosis than those with fewer metastases and required additional adjuvant therapy.

Disclosure

All authors have declared no conflicts of interest.
PS02.109: CLINICAL SIGNIFICANCE OF NEOADJUVANT CHEMOTHERAPY IN ESOPHAGEAL CANCER PATIENTS WITH SEVERE DYSPHAGIA
Authors: Kosugi Shin-Ichi , Nemoto Mariko , Ichikawa Hiroshi , Muneoka Yusuke , Kano Yosuke , Hanyu Takaaki , Ishikawa Takashi , Wakai Toshifumi
Published: September 2018

Background

Neoadjuvant chemotherapy (NAC) followed by curative resection is a standard treatment for resectable locally advanced esophageal cancer. However, clinical significance of NAC for patients with severe dysphasia due to esophageal stenosis was not fully validated.

Methods

Fifty patients with resectable locally advanced esophageal cancer who received cisplatin and 5-fluorouracil followed by curative resection between 2006 and 2005 in our institution were retrospectively reviewed. Twenty-one patients required nutritional support due to severe dysphasia before or during NAC (Group A) and the remaining 29 patients had no dysphagia (Group B). Clinicopathological characteristics, nutritional status, treatment-related adverse events, and survival were compared between the two groups.

Results

Seventeen patients received enteral feeding with transnasal tube and the remaining 4 patients (19%) received parenteral nutrition alone in group A. There were no significant differences in tumor characteristics between the two groups. Serum albumin levels of group A and B before NAC were 3.8 and 4.3 g/dL (P = 0.02), and those after NAC were 3.6 and 4.0 g/dL, respectively (P < 0.01). NAC completion rates of group A and B were 86% and 83% (P = 0.78) and grade 3 or higher leukocytopenia developed in 33% and 10%, respectively (P = 0.07). Postoperative pneumonia of grade 2 or higher according to the Clavien-Dindo classification occurred in 48% and 28%, respectively (P = 0.23). Five-year overall survival rates of group A and B were 45% and 71%, respectively (P = 0.04).

Conclusion

NAC could be safely completed in patients with severe dysphagia; however, those were likely to have treatment-related adverse events and poorer survival.

Disclosure

All authors have declared no conflicts of interest.
PS02.118: THE RESEARCH ABOUT SITE AND RISK FACTORS OF THE RECURRENCE AND METASTASIS AFTER POSTOPERATIVE RADIOTHERAPY IN ESOPHAGEAL
Authors: Li Jiancheng , Lin Yina
Published: September 2018

Background

To explore the risk factors of recurrence of postoperative esophageal cancer after radiotherapy, and analyze the regional and temporal regularity of this kind of recurrence.

Methods

Retrospective analysis the198 patients from Fujian Provincial Tumor Hospital Radiotherapy Department between January 2000 and December 2015 were collected of esophageal cancer after surgery, were treated with adjuvant postoperative radiotherapy, 198 patients were followed up for recurrence, To study the relationship between the observed indexes and the recurrence of esophageal cancer after radiotherapy. The recurrence site was divided into local recurrence and distant metastasis, and analysis of the relationship between the recurrence site and time, so as to take different treatment modalities for patients with different time periods.

Results

In 198 patients with recurrence and metastasis, 166 (84%) were found within 2 years.The patients whose metastasis and recurrence in 2 years, 43 cases (26%)had recurrence in the irradiation field, 85 cases (51%) had metastasis outside the irradiation field, 38 cases (23%) were both in and outside of the field. In 88 cases of recurrence within six months of the patients, only 18 cases (20%) recurrenced in the field, the recurrence rate was significantly lower than that of the outside the field. Multi-factor analysis results show that the lymph node metastasis and the start time of radiotherapy are the main risk factors affecting the recurrence, The postoperative pathological diagnosis in the control of N0, the risk of recurrence of N3 is 1.673 times of N0 (P = 0.036, HR = 1.673, 95%CI = 1.033 to 2.711); Less than 30 day recurrence risk is 2.482 times (P = 0.003, HR = 2.482, 95%CI = 1.364 to 4.520), more than 60 day recurrence risk is 1.42 times (P = 0.039, HR 1.42, 95%CI 1.019 to 1.979).

Conclusion

After radiotherapy after esophagectomy, 84% recurrence within 2 years, so should be closely followed up 2 years after the treatment, postoperative radiotherapy only control the radiation within the field of the recurrence rate within the next six months. Lymph node metastasis, radiation therapy, the start time is a risk factor for esophageal predicting recurrence after radiotherapy after surgery.

Disclosure

All authors have declared no conflicts of interest.
PS02.123: LYMPH NODE METASTASIS STATUS AFTER DIFFERENT STRATEGIES OF NEO-ADJUVANT THERAPIES FOR THE ESOPHAGEAL SQUAMOUS CELLS CARCINOMAS
Authors: Gong Lei , Tang Peng , Jiang Hongjing , Shang Xiaobin , Zhang Hongdian , Yu Zhentao
Published: September 2018

Background

Lymph node status is an essential prognostic factor for the long term survival of esophageal cancer patients. The impact of neo-adjuvant therpay on lymph node status remains unconcern, especially for squamous cells carcinomas. The study objectives were to retrospective analyzed the impact on the numbers and stations of metastasis of lymph nodes after the neo-adjuvant therapy.

Methods

Patients undergoing esophagectomy for thoracic esophageal squamous cell carcinoma at Tianjin Medical University Cancer Institute and Hospital from 2013 to 2017 were included in this study. Group 1 included the patients who were treated with surgery only (N = 120). Group 2 included the patients who received the neo-adjuvant chemoradiation (n = 77). Group 3 included the patients who received the neo-adjuvant chemotherapy (n = 117).

Results

In group 2, the pathological complete response (pCR) rate was 45.61%, partial response (PR) rate was 22.8%, and stable disease (SD) rate was 22.39%. In group 3, the pCR rate was 12.7%, PR rate was 27.8%, and SD rate was 59.5%. The lymph node metastasis rate at upper mediastinum was 22.39% in group 1, 17.54% in group 2, 35.90% in group 3. The lymph node metastasis rate at middle mediastinum was 19.40% in group 1, 1.75% in group 17.54% in group 3. There were no significant differences at other part of station.

Conclusion

There is still no standardized guideline for the treatment of esophageal squamous cells carcinomas. In our study, we retrospectively compared the effects of neo-adjuvant chemoradiation and chemotherapy on the status of lymph node metastasis. It is showed that there were less lymph node metastasis after the the neo-adjuvant therapy compared with the surgery alone group. But the group 2 had better pCR rates than the group 3. And after the chemoradiation, it also showed less lymph node metastasis on the upper and middle mediastinum. From the results of our study, we may draw a conclusion that neo-adjuvant chemoradiation would be a better choice for those patients who had multiple stations of lymph node metastasis. But we still need the prospective studies to verify our hypothesis.

Disclosure

All authors have declared no conflicts of interest.
PS02.124: NOVEL APPROACHES AND CONSIDERATIONS FOR IMMUNOTHERAPY IN OBESITY-ASSOCIATED OESOPHAGEAL ADENOCARCINOMA
Authors: Conroy Melissa , Galvin Karen , Dunne Margaret , Reynolds John , Lysaght Joanne
Published: September 2018

Background

Immunotherapies are transforming cancer treatment for inoperable and advanced disease. However, the incidence of obesity-associated cancers, including oesophageal adenocarcinoma (OAC) continue to increase. Treatment with immune-based therapies present a unique challenge for immunologists, as they need to enhance anti-tumour immunity without exacerbating pre-existing carcinogenic inflammation. Therefore, we examined the effect of PD-1 blockade in omentum and liver of OAC patients, sites of activated inflammatory T cells, which play a key role in obesity-associated inflammation. In addition, we examined novel ways to reduce the infiltration of inflammatory T cells to these sites in a bid to reduce adipose tissue inflammation.

Methods

Blood, omentum and liver samples were obtained from consenting OAC patients and treated with anti-PD-1 antibody. CD4+ and CD8+ T cell activation, cytokine expression and cytotoxic potential were assessed by flow cytometry. To identify potential chemokine pathways to alter T cell trafficking to the omentum and liver, chemokine receptor expression was examined, along with levels of secreted chemokines using flow cytometry and ELISAs. Pre-treatment of T cells with chemokine receptor antagonists was performed prior to chemotaxis assays using an in vitro transwell system.

Results

In addition to OAC tumour, omentum and liver were found to be enriched with substantial populations of PD-1 expressing T cells. Treatment of omental and hepatic T cells with anti-PD-1 did not enhance inflammatory cytokine expression or proliferation, but transiently increased CD107a expression by CD8+ T cells. MIP-1α, MIP-1β and IP-10 mediate T cell trafficking to the omentum and liver in OAC. OAC-derived T cells preferentially migrate to the adipose and liver tissue conditioned media of obese OAC patients and this can be significantly reduced using a MIP-1α receptor antagonist.

Conclusion

This study provides evidence that anti-PD-1 treatment is unlikely to exacerbate pre-existing T cell-mediated inflammation outside the tumour in obesity-associated cancers. Furthermore, novel CCR1 antagonists may be used to attenuate pathological inflammation in obesity. This dual targeting approach aims to enhance anti-tumour immunity through the use of immune checkpoint inhibitors, and has identified a novel immunotherapeutic approach to reduce obesity-associated inflammation by targeting key chemokine pathways. In vivo testing is required to determine the efficacy of this approach.

Disclosure

All authors have declared no conflicts of interest.
PS02.133: THE EFFICACY AND SAFETY OF S-1 MONOTHERAPY FOR RECURRENT OR METASTATIC ESOPHAGEAL SQUAMOUS CELL CARCINOMA REFRACTORY OR INTOLERABLE TO PLATINUM PLUS 5-FU
Authors: Ito Takahiko , Honma Yoshitaka , Miyamoto Takahiro , Hirano Hidekazu , Shoji Hirokazu , Okita Natsuko , Iwasa Satoru , Takashima Atsuo , Kato Ken , Boku Narikazu
Published: September 2018

Background

Platinum plus 5-fluorouracil (FP) is recognized as the standard regimen of palliative chemotherapy for recurrent or metastatic esophageal squamous cell carcinoma (ESCC). Although taxane is widely selected for 2nd line regimen, other options are very limited. In Japan, S-1 is available for esophageal cancer. In this retrospective study, we evaluated the efficacy of S-1 monotherapy for recurrent or metastatic (advanced) ESCC refractory or intolerable to FP.

Methods

The subjects of this study were 11 patients with advanced ESCC who received S-1 after failure of FP. The endpoints evaluating efficacy were overall survival (OS), progression free survival (PFS), and overall response rate (ORR) in patients with target lesions (TLs).

Results

The characteristics of the subjects were: median age 69 years, PS (0/1) 5/6, number of prior chemotherapy regimens (1/2/3 ≥ ) 4/4/3. 9 patients were refractory and 2 were intolerant to prior FP. 9 patients had good control of the primary lesions. Only 2 patients received post-S-1 therapy. The median OS and PFS were 11.7and 3.0 months. Two of 9 patients with TLs, one refractory and the other intolerant to prior FP, achieved partial response (PR) while the remaining 7 patients showed progressive disease (ORR 22%). The other 2 patients without TLs showed nonCR/nonPD. Common treatment-related adverse events included grade 3 leukopenia for 1 patients (9.1%), but there were no serious cases.

Conclusion

ORR of 22% suggests modest activity of S-1 for advanced ESCC refractory or intolerable to platinum plus 5-FU (FP). However, more than half of the patients showed progressive disease. Future study exploring optimal patient selection for S-1 is warranted.

Disclosure

All authors have declared no conflicts of interest.
PS02.136: SURGICAL INTERVENTION FOR RECURRENT CANCER OF THE ESOPHAGUS
Authors: Muhinga Morris
Published: September 2018

Background

CASE REPORT ON SUCCESFUL SURGICAL INTERVENTION FOR RECURRENT CA OESOPHAGUS

45 year old female diagnosed with cancer of the oesophagus in 2013, CT Scan showed operable tumour. Patient underwent Ivor Lewis oesophagectomy. Histopatholgy showed pT2N0Mx(Stage IIA). Patient was followed up and was noted to be loosing weight in April 2016, upper GI Endoscopy showed recurrence of the tumour, at the intrathoracic stomach level.CT Scan revealed a tumour involving the stomach but no pulmonary nodules. In Multidisciplinary discussion it was agreed to offer patient surgical resection. At surgery the intrathoracic stomach was mobilised and resection done. Formal laparotomy was performed and the transverse colon prepared for colonic interposition at the cervical region. At the time of surgery the patient's weight was 38 kg, this increased to 45kg within the first 6 months after surgery. Patient underwent adjuvant chemotherapy and is doing well 2 years after the second surgery.

Methods

this is a case report.

Results

case report.

Conclusion

recurrence after esophagectomy is high and some patients can benefit from redo surgery.

Disclosure

All authors have declared no conflicts of interest.