bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarker studies in a phase I trial of DKN-01 in advanced esophageal cancer.
Authors: Strickler John H. , Kagey Michael , Sirard Cynthia A. , Duda Gabriel Dan , Almenara Jorge , Powers Celeste N. , Bendell Johanna C. 
Published: March 2017

161 Background: DKK1 is a modulator of Wnt signaling that is frequently overexpressed in tumors and such expression has been associated with worse survival. Preclinical studies have shown that DKK1 can promote tumor growth by increasing angiogenesis and contributing to an immunosuppressive tumor microenvironment. DKN-01 is a humanized IgG4 monoclonal antibody against DKK1 that has shown encouraging efficacy signals in patients (pts) with advanced esophageal (EC) or esophagogastric junction (EGJ) cancer when administered in combination with paclitaxel. Correlative studies are evaluating DKK1 expression and genetics in archived tumor specimens and baseline and on-treatment plasma levels of angiogenesis and inflammation biomarkers as predictors of response. Methods: Formalin fixed paraffin embedded (FFPE) archived tumor tissue was evaluated for DKK1 expression by immunohistochemistry (IHC) and scored for fraction of positive cells, intensity, and localization of DKK1. Genetics were collected if known and/or performed using an Archer VariantPlex Solid Tumor Panel covering 67 genes. Plasma samples, pre- and on DKN-01 treatment were evaluated by multiplexed array for angiogenesis (bFGF, PIGF/PGF, sFLT1/sVEGFR1, sTIE-2/TEK, VEGF, VEGF-C, and VEGF-D) and inflammation (IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70 and IL-13) markers (Meso-Scale Discovery) and by ELISA for HGF and SDF-1α (R&D Systems). Results: ~90% of tissue samples showed DKK1+ expression in tumor cells (range 1 to 100%); intensity (weak 1+ to strong 3+); and localization (cytoplasmic and/or nuclear). Early data has not identified a correlation between DKK1 staining and response. One pt with an ongoing durable response had an activating mutation in β-catenin. Analysis of plasma biomarkers is ongoing. Conclusions: Analysis of DKK1 staining, tumor genetics, and prospective angiogenic/inflammatory biomarkers are ongoing to identify a predictive biomarker for DKN-01. The majority of EC/EGJ tumor biopsies were IHC DKK1+. Broader genomic screens are underway to further characterize DKN-01 sensitivity; mechanistically plausible activating mutations in β-catenin may be a biomarker for DKN-01. Clinical trial information: NCT02013154.
Positive radial resection margin after esophagectomy for esophageal cancer patients treated at a tertiary center and its impact on survival.
Authors: Shah Parth Kishore , Cameron Miles , Frakes Jessica M. , Fontaine Jacques , Coppola Domenico , Hoffe Sarah E. , Almhanna Khaldoun , Pimiento Jose Mario 
Published: March 2017

162 Background: Although residual tumor at the radial margin can be expected to have a significant impact on the recurrence or overall survival of patient with node negative esophageal cancer (EC), its impact on recurrence and overall survival of patients with node positive EC has not been well characterized. Methods: A retrospective review of patients who underwent esophagectomy for EC at a single institution over a 16 year period (1999-2015) was performed. Pre-operative clinical parameters, stage as well as oncologic management were reviewed as well as the impact of positive radial margin on overall survival of pre-treatment node positive tumors was analyzed using descriptive statistics. Results: The study group consisted of 437 patients (46%) with pre-treatment stage IIB or III out of 945 patients with EC undergoing esophagectomy. The mean age of patients was 63 years with male predominance (85%). Neoadjuvant therapy (NAT) was administered to 87% of patients. Trans-thoracic surgery was performed in 86% of patients and trans-hiatal in 14%. Positive radial margin on final pathology was identified in 14 patients (3.2%); none of these had squamous histology. Neither the surgical approach nor the use of NAT was associated with radial margin positivity (p = 0.6). The median overall survival was significantly lower in the patients with positive radial margin when compared to the rest of the cohort (13.6 months v/s 41.2 months, p = 0.004). Moreover, when focused only on patients with post treatment pathologic T3 and T4 disease, margin positive disease remained associated with worse survival (p = 0.04). However, when final N status is included in multivariate analysis margin positivity loses significance. Conclusions: Radial margin positive disease after surgical resection for EC is associated with worse overall survival. This finding was significant regardless of the pathologic T stage; however, pathologic nodal staging was the most important factor for prognostication in locally advanced EC. Adenocarcinoma is the predominant pathology identified in patients with positive radial margin and concurrent node positivity.
Incidence of brain metastasis from esophageal cancer.
Authors: Ashman Jonathan Ben , Welch Gabrielle , Patel Naresh P. , Jaroszewski Dawn E. , Fleischer David , Rule William G. , Paripati Harshita , Ramirez Francisco , Ross Helen J. 
Published: March 2017

165 Background: Distant metastases are common in primary esophageal cancer, but data conflict regarding the rates of brain metastases (BM) ranging from 0% to 13%. We sought to investigate whether the incidence of BM from esophageal malignancies is increasing in the modern era. Methods: After IRB approval, a single institution retrospective review identified 583 patients (pts) treated between 1/1997 and 1/2016 for stage I-IV cancer of the esophagus/esophagogastric junction with at least 3 months follow-up. Data collected included demographic information, primary diagnosis date and staging, histologic subtype, treatment regimens for primary and BM, date of BM diagnosis, status of neurologic symptoms and extracranial disease at BM diagnosis, and date of death. Data were analyzed by Fischer’s exact test and Kaplan-Meier analysis. Results: The overall cohort was comprised of 495 pts (85%) with adenocarcinoma and 82 pts (14%) with squamous cell carcinoma. 492 pts (84%) were male; the median age was 68 years (range 26-90). BM were identified in 22 pts (3.8%) with a median latency of 11 months from the primary diagnosis. Of the pts with BM, the primary histology was adenocarcinoma in 21 pts and squamous cell carcinoma in 1 pt ( P = 0.3). BM developed in 12 pts who were initially treated for locally advanced disease and in 10 pts who presented with distant metastases. Diagnosis of BM was at the time of initial presentation in 4 of these 10 stage IV pts. A solitary BM was identified in 9 pts. Initial treatments of BM were surgical resection followed by stereotactic radiosurgery (SRS; n = 5); surgical resection followed by whole brain radiotherapy (WBRT; n = 1); WBRT alone (n = 13); SRS alone (n = 3). Overall survival (OS) following diagnosis of BM was 18% at 1 year with a median of 4 months. OS was superior for pts who had surgical resection as initial treatment of BM compared to pts treated with WBRT or SRS alone (1-year OS 67 vs. 0%; median OS 13.5 vs. 3 months; P = 0.003). Conclusions: The incidence of BM is low in esophageal cancer with no statistically significant increased rate of BM developing in patients with adenocarcinoma compared with squamous cell carcinoma. Outcomes were poor overall for pts who developed BM, but pts who were appropriate for neurosurgical resection had improved survival.
The efficacy and feasibility of weekly 5-FU and cisplatin based radical concurrent chemoradiation therapy(CRT) in patients with esophageal cancer.
Authors: Jeong Joon Won , Yang Ji Hyun , Ro Sang Mi , Kim In-Ho , Roh Sang Young 
Published: March 2017

169 Background: Concurrent chemoradiotherapy(CCRT) has become a promising treatment for esophageal cancer. Mostly, however, 3 week or 4 week interval of conventional FP(5-fluorouracil plus cisplatin) regimen is adopted, which is usually associated with moderate to severe treatment-related toxicities. Studies about weekly regimen of FP CCRT are little known, thus we studied the efficaty, tolerability and toxicities of weekly FP CCRT regimen. Methods: From February 2010 to august 2015, Patients staging from I to III esophageal cancer(according to AJCC 7th edition) were enrolled, who were received radiation therapy with dose of from 50.4Gy to 60Gy(5 days/week) and 5-FU 1000mg/BSA with cisplatin 30mg/BSA weekly. Results: From February 2010 to august 2015, 50 patients: male/female 47/3, median age 71.5 (47-78), all of 50 patients was squamous carcinoma, well/moderately differentiated carcinoma 1/18. 45 patients completed CRT without dose reduction, 9 patients received less than 6 cycles of chemotherapy, 4 patients received less than 50.4Gy of radiotherapy. Major toxicities of grade 3 or less were as follows: neutropenia 52%, thrombocytopenia 21%, nausea & vomiting 10%, fatigue 10%, anemia 5%. Toxicities over grade 4 was seen only in 1 patient. 15 patients showed complete response. The median overall survival was 10.67 months(4-48). The median disease-free survival was 16.9 months. Conclusions: Weekly regimen of concurrent CRT with 5-FU and cisplatin resulted in less toxicities over grade 3. Although, this regimen still showed non-inferiority to previous conventional 4 week-interval FP CCRT regimens in terms of PFS and OS. In this study, 82% of our patients had completed CCRT without any interruption. Hence, our results suggest that CRT with weekly 5-FU and cisplatin as definitive treatment for esophageal cancer could be a tolerable regimen.
One-dimensional and two-dimensional tumor size measurement for prediction of lymph node metastasis in differentiated early gastric cancer with minute submucosal invasion.
Authors: Kim Tae Jun , Lee Hyuk , Pyo Jeunghui , Min Yang Won , Min Byung-Hoon , Lee Jun Haeng , Kim Jae J. 
Published: March 2017

172 Background: Differentiated minute submucosal cancers ≤ 3 cm that exhibit no lymphovascular invasion are considered eligible for endoscopic resection; however, the ≤ 3 cm criterion remains debatable. The aim of this study was to verify the optimal tumor size cutoff for endoscopic resection eligibility, and to determine whether two-dimensional tumor size measurement would be more accurate for this purpose. Methods: The clinicopathological data of 574 patients undergoing curative surgery for differentiated minute submucosal cancer were reviewed retrospectively. A receiver operating curve analysis and bootstrapped samples were used to identify the optimal cutoff values for predicting lymph node (LN) metastasis. Results: Four hundred fourteen patients were eligible for the study.LN metastasis accompanied 2.5% of differentiated minute submucosal cancers that were ≤ 3 cm in size and lacked lymphovascular invasion. There was no lymph node metastasis in the tumors with 1D sizes ≤ 1.0 cm and 2D sizes ≤ 1.0 cm2. Using 10,000 bootstrapped data, optimal cutoff values were 2.9 cm (LN metastasis: 2.1%) and 8.3 cm2 (LN metastasis: 2.5% incidence) for one- and two-dimensional tumor size, respectively. Although the area under the curve was 0.611 ( P = 0.046) for two-dimensional size, specificity and accuracy were greater for the dichotomized two-dimensional measure than for the dichotomized one-dimensional measure ( P< 0.001, McNemar’s test). In addition, two-dimensional tumor size was the only significant risk factor for LN metastasis (odds ratio 1.09, 95% confidence interval 1.01–1.20). Conclusions: One-and two-dimensional cutoff values of 2.9 cm and 8.3 cm2 might be suitable for patients at high risk of post-operative morbidity and mortality. Two-dimensional tumor size is an acceptable measurement method for estimating the risk of LN metastasis.
Short and long-term effects of two different surgery approaches for remnant gastric cancer.
Authors: Chen Lin , Ren Yingkun , Zheng Yajie 
Published: March 2017

180 Background: To evaluate the short- and long-term effects of two different surgery approaches for remnant gastric cancer after distal gastrectomy. Methods: Clinical data of 48 remnant gastric cancer patients were collected retrospectively from the period of January 1st 2010 to December 31st 2012 in this matched-pair study. Twenty four patients in the experimental group underwent radical surgery in antegrade approach (starting from the esophagus to the gastrointestinal anastomosis), another 24 matched patients in the control group underwent radical surgery in retrograde approach (starting from the gastrointestinal anastomosis to the esophagus). Constants in the study were patient age, the operating surgeon, Borrmann type, TNM stage and operation range. Pearsonχ2 testor t-test were used to compare the clinicopathological characteristics between the two groups. Survival rates of 1- and 3-years were analyzed with Kaplan-Meier survival curve and compared with Log-rank test. Results: The 48 patients were treated successfully without any mortality during their hospital stay. The mean operative time and bleeding volume in the experimental and control groups were (126.6±5.7) min and (154.1±23.9)ml , and (168.3±11.7) min and (180.8±15.0)ml respectively. The difference in the mean operative times (t = -3.089, P = 0.005) and the mean bleeding volumes (t = -3.269, P = 0.004) were statistically significant. The average hospital stay after surgery and the average number of lymph nodes resected were (9.5±0.9) days and 18.7±1.6 in the experimental group,(9.2±0.8) day and 17.4±1.4 in the control group. There was no statistical differences between the two groups in terms of the average hospital stay (t = 0.692, P = 0.496) and the average number of resected lymph nodes (t = 2.101, P = 0.247). The overall 1- year and 3-years survival rates were 75%, 49% in the experimental group and 67%, 35% in the control group. There was also no statistical difference in the 1-year (P = 0.745) and 3-years (P = 0.878) survival rates. Conclusions: Compared with retrograde approach, performing radical surgery in antegrade way for remnant gastric cancer patients can shorten the operation time, reduce blood loss and simplify the operation procedure.
Adjuvant chemotherapy and outcomes in esophageal carcinoma.
Authors: Saeed Nadia , Mellon Eric Albert , Meredith Kenneth L , Hoffe Sarah E. , Shridhar Ravi , Frakes Jessica M. , Fontaine Jacques-Pierre , Pimiento Jose Mario , Kothari Nishi , Almhanna Khaldoun 
Published: March 2017

181 Background: Neoadjuvant chemoradiation (NCRT) and surgery is standard treatment for esophageal cancer (EC) in the U.S. The role of adjuvant chemotherapy (ACT) is unclear. Providers assign ACT inconsistently, and both its rationales and benefits have yet to be clearly defined. We sought to evaluate rationales and benefits for ACT in EC. Methods: This single institution retrospective review included 382 patients (pts) with EC who were treated at our tertiary referral center. All pts received NCRT and 46 received ACT. We reviewed medical records to obtain demographic and clinical information. Survival outcomes were analyzed with Kaplan-Meier method from date of death or last follow up and log-rank analysis. Case-control analysis was performed using a 2:1 nearest neighbor propensity score matching algorithm, and included 113 pts, 41 of which received ACT. Results: 46 of the 382 pts in our study who received NCRT and surgery for EC also underwent ACT; two pts had single agent paclitaxel, 9 had 5-F/U and leucovorin, 7 had 5-F/U and cisplatin, 5 had carboplatin and paclitaxel, 2 had carboplatin alone, and the remainder had other combinations. Pts who received ACT were younger (med. age = 60.2 v 63.8 yr, p = 0.047), more likely to have adenocarcinoma (91.3% v 85.1%, p = 0.034), and less likely to have positive LNs on pre-treatment EUS (60.1% v 77.4%, p = 0.018). Pts with pCR were less likely to receive further treatment (6.5% v 45.8%, p < 0.001), and pts with R1 resection were more likely to do so (15.2% v 4.2%, p = 0.007). With case-control analysis, no variables were significantly different between the two groups. The median follow-up times for the entire cohort and case-control analysis were 7.98 years and 8.89 years, respectively. There were no significant differences in overall (p = 0.975) or recurrence-free (p = 0.824) survival associated with ACT in either analysis. Conclusions: The role of CT following NCRT and surgical resection in pts with locally advanced ECis unclear. In the largest series to date, our single institution retrospective review found no significant difference in survival in pts who received ACT and those who did not. Prospective studies are needed to further identify the rationales for delivery of ACT, and to investigate any potential survival benefits.
Gastric linitis plastica: Have we moved beyond surgical palliation?
Authors: Woo Katherine , Luu Carrie , Almhanna Khaldoun , Coppola Domenico , Pimiento Jose Mario , Hodul Pamela Joy 
Published: March 2017

184 Background: Diffuse type gastric cancer (DGC), especially linitis plastica (LP), is associated with poor survival. Despite curative-intent surgical resection and improvement in perioperative therapy, doubt remains whether long term survival is possible in this aggressive disease. Methods: A retrospective review of the GC database at a comprehensive cancer center was reviewed from 2000 to 2016. Patient demographics, tumor characteristics, and treatment were evaluated. Patients with DGC were assessed. LP was defined as patients with DGC who had circumferential infiltration of the gastric wall for at least a third of the stomach length. Descriptive statistics were used to compare DGC and LP groups; survival was assessed by the Kaplan-Meier method. Results: Of 209 resected GC patients, 114 had diffuse histology; the majority were of the signet ring cell subtype. 38 (33.3%) had LP and 76 (66.7%) had DGC without linitis. LP patients were more likely to present at a later stage, with 27/38 patients (71%) with stage III and 4/38 patients (10.5%) with stage IV compared to 16/76 (21.1%) and 2/76 (2.6%) in the DGC group, respectively, p < 0.001. All patients underwent gastric resection with some for palliative intent including 6 patients found to have metastatic disease on exploration. R0 resection was achieved in 26 patients (68.4%) with LP. Median OS was 31.5 months for the cohort and 13.6 months for LP patients (p < 0.001); survival in LP patients did not improve with R0 resection. When survival was stratified by stage, patients with stage II LP still had a lower median OS than DGC (18.4 vs. 51.2 months, respectively, p = 0.015), though there was no survival differences in stage III and IV. Only half of patients with LP received preoperative chemotherapy or chemoradiation, perhaps due to need for surgical palliation of symptoms; receipt of preoperative therapy was not associated with survival in this subgroup. Conclusions: Gastric LP is associated with a poor prognosis. Early diagnosis and adherence to multimodal therapy may improve survival after surgical resection. Development of novel agents and improvement in neoadjuvant therapy is needed to improve outcomes in this aggressive disease.
Severe toxicity risk factor analysis of salvage radiotherapy for oligo-recurrence in the lymph nodes (LN) of esophagus carcinoma: From multi-institutional retrospective study.
Authors: Matsumoto Toshihiko , Nishina Tomohiro , Niibe Yuzuru , Yamashita Hideomi , Katsui Kuniaki , Kataoka Masaaki , Terahara Atsuro , Shimada Hideaki , Jingu Keiichi 
Published: March 2017

186 Background: This multi-institutional retrospective study suggested that salvage radiotherapy (RT) or chemoradiation therapy (CRT) for oligo-recurrence in the lymph nodes (LN) of esophagus carcinoma was one of therapeutic options. However risk factors of severe toxicities of these therapies are unclear. Methods: Between January 2000 and April 2015, a total of 237 cases that met the study criteria of oligo-recurrence were treated by RT or CRT in five hospitals. We investigated risk factors of severe toxicities in these patients. We used the fisher’s exact test and Cox proportional hazard model. Toxicities were evaluated by CTCAE v4.0. Results: The median follow-up time for 93 living cases was 29.6 months (range; 1.9-154.0 months). Systemic chemotherapy was administrated to 210 cases (88.6%). Median biological effective dose(BED) was 72 Gy(range: 48-84Gy).The 3-year overall survival (OS) was 37%, local control was 45%, progression-free survival was 24%. Radiation induced Grade 3 or worse adverse events were observed in 11 patients (4.6%), which were fistula (4patients,1.7%), pneumonia (2patients,0.8%), pleural effusion (2patients,0.8%), esophageal bleeding (1 patient, 0.4%), esophageal stenosis (1patient,0.4%), cardiac tamponade (1patient,0.4%), and hyperglycemia (1patient,0.4%) ) Treatment related death occurred in 4 patients, these deaths were attributed to drug-induced or radiation-induced interstitial pneumoniae, pleural effusion, esophageal bleeding, and esophago-bronchial fistula. Severe toxicity was only observed in patients with oligo-recurrence in regional lymph nodes or BED ³a60 Gy. In univariate analysis by Fisher’s exact test, Karnofsky performance status (KPS) <80 (p=0.0006) and oligo-recurrence in regional lymph nodes (p=0.0078) were the risk factor of severe toxicity. In multivariate analysis, KPS<80 (HR:11.81,95% CI: 2.67-51.29, p=0.0017) was the risk factor of severe toxicity. Conclusions: This study suggested that KPS<80 and oligo-recurrence in regional lymph nodes is the risk factor for severe toxicity in patients who received RT or CRT for oligo-recurrence in the LNs of esophagus.
Risk factor analyses of severe cicatricial stricture after chemoradiotherapy for stage II/III (T3) esophageal carcinoma.
Authors: Tsushita Natsuko , Honma Yoshitaka , Nagashima Kengo , Miyamoto Takahiro , Nakamura Shoko , Umezawa Rei , Ito Yoshinori , Shoji Hirokazu , Takashima Atsuo , Iwasa Satoru , Kato Ken , Hamaguchi Tetsuya , Itami Jun , Boku Narikazu 
Published: March 2017

190 Background: Severe benign cicatricial stricture (SBCS) is a major complication after chemoradiotherapy (CRT) for esophageal carcinoma (EC), and causes oral intake impairment leading to deterioration of quality of life even after being cured. Aim of this study was to investigate risk factors of SBCS. Methods: The subjects of this study were patients with stage II/III (T3) EC who received CRT and achieved complete response (CR) between 2000 and 2011. SBCS was determined as disability of passage by diameter-9mm endoscope. Results: Among 197 patients with Stage II/III (T3) treated by CRT, CR was obtained in 91 patients, who were included in this analysis. The median age was 63 years. Fifteen patients (16.5%) were female. The median follow-up time was 5.1 years. The cumulative incidence of SBCS was 15.0% (95%CI 9.0-24.5). Significant risk factors of SBCS were female (hazard ratio (HR) 3.3 (95%CI 1.1-10.0), p = 0.04), requirement of diced/liquid meal (HR 5.7 (95%CI 1.8-18.2), p = 0.003), tumor occupying 3/4 or grater of esophageal perimeter (HR 7.4 (95%CI 1.3-42.9), p = 0.03) and disability of endoscope passage (HR 12.7 (95%CI 4.2-38.5), p < 0.001) in univariate analysis. Hypoalbuminemia increased the risk of SBCS (HR 2.4 (95%CI 0.8-7.1), p = 0.12) marginally. As for the factors during CRT, grade 2-4 esophagitis significantly increased the risk of SBCS (HR 6.2 (95%CI 1.5-25.7), p = 0.01). Multivariate analysis showed that hypoalbuminemia (HR 3.5 (95%CI 1.1-11.1), p = 0.03) and disability of endoscope passage (HR 14.8 (95%CI 4.3-51.3), p < 0.001) were the significant risk factors of SBCS. Female (HR 1.5 (95%CI 0.5-4.9), p = 0.51) was not a significant risk factor in multivariate analysis. Conclusions: Obstructions before CRT, hypoalbuminemia and severe esophagitis during CRT are considered as risk factors of SBCS. Because SBCS occurred after completion of CRT, prophylactic treatment should be established especially for esophageal carcinoma patients with risk factors of SBCS.