bluuebunny/crossref_metadata_2025_split huggingface dataset:
Checkpoint expression pre and post chemoradiation in operable esophageal cancer.
Authors: Kelly Ronan Joseph , Zaidi Ali Hussainy , Smith Matthew , Omstead Ashten N. , Kosovec Juliann E. , Matsui Daisuke , Martin Samantha A , Finley Gene Grant , Silverman Jan F , Werts E. Day , Jobe Blair A. 
Published: March 2017

139 Background: PD-L1 expression has been reported in 40% of gastroesophageal cancers, but little data exists with regards to expression of other immune checkpoints. Here, we examined baseline expression levels for multiple immune modulators in 31 resected esophageal adenocarcinomas (EAC) and investigated the change in expression levels post-chemoradiation. Methods: Slides were stained on a Ventana BenchMark ULTRA automated stainer for CTLA-4 (Santa Cruz Clone F-8, dilutions 1:100) and PD-L1 (Dako clone 22C3 prediluted). Tonsil tissue was used as a control for lymphocytes, and a provided tumor control was used for PD-L1. Positivity was classified as > 1%, and the stained cell type was recorded (lymphocytes or tumor). Additionally, laser capture microdissection was performed, and RNA was isolated and pre-amplified to determine expression levels of TIM-3, GITR, IDO-1, LAG-3, CD-137, OX-40, and KIR-3 using RT-PCR. Gene expression was calculated using the ΔΔ -Ct method, and intergroup comparisons were performed and normalized against a cohort of 15 pathologically confirmed normal esophageal epithelium cases. Results: Post-chemoradiation cases demonstrated increased expression for PD-L1, when compared to matched pre-chemoradiation controls [p-value = 0.0098]. Similarly, all immune modulators profiled by gene expression were significantly upregulated in matched post vs. pre samples, except for CD-137. There was no significant difference in percentage of 4-fold or more upregulation based on PD-L1 status for IDO-1, OX-40, CD-137 and KIR-1, indicating that these markers may function independently of PD-L1 positivity. Conclusions: PD-1 inhibiton in both the neoadjuvant and adjuvant setting is currently being investigated in EAC, but future studies may look to select patients according to personalized checkpoint expression patterns. [Table: see text]
Surgically treated esophageal cancer developed in a radiated field: Impact on peri-operative and long-term outcomes.
Authors: Mariette Christophe , Markar Sheraz , Gronnier Caroline , Pasquer Arnaud , Duhamel Alain , Behal Helene , Thereaux Jeremie , Gagniere Johan , Lebreton Gil , Brigand Cecile , Meunier Bernard , Collet Denis 
Published: March 2017

150 Background: The objectives of this study were to compare peri-operative and long-term outcomes from esophageal cancer (EC) (i) that arose in a previously radiated field (ECRF) versus primary (PEC) and among ECRF patients (ii) radiotherapy-induced (RIEC) versus non radiotherapy-induced EC (NRIEC). Methods: Data was collected from 30 European centers from 2000–2010. 2489 EC patients surgically treated were included in the PEC group and 136 in the ECRF group, including 61 in the NRIEC group and 75 in the RIEC group. Propensity score matching analyses were used to compensate for differences in baseline characteristics. Results: Compared to the PEC group, the ECRF group was characterized by less use of neoadjuvant chemoradiotherapy (0% vs. 29.5%; P < 0.001), less pathological stage III/IV (31.6% vs 39.2%, P = 0.036), greater incidence of R1/2 margins (21.3% vs. 10.9%; P < 0.001), increased in-hospital mortality (14.0% vs. 7.1%; P = 0.003) and overall morbidity (68.4% vs. 56.4%, P = 0.006). After matching, 5-year overall (28.8% vs. 50.5%; HR = 1.53, 95% C.I. 1.15-2.04; P = 0.003) and event-free (32.2% vs. 42.5%; HR = 1.56, 95% C.I. 1.18-2.05; P = 0.002) survivals were significantly reduced in the ECRF group. There were no significant differences in incidence or pattern of tumor recurrence. Comparing RIEC and NRIEC groups, there were no significant differences in short- or long-term outcomes before and after matching. Conclusions: ECRF is associated with poorer long-term survival related to a reduced utilization of neoadjuvant chemoradiotherapy and an increased incidence of tumor margin involvement at surgery. Outcomes are dictated by the limitations related to previous radiotherapy administration more than the radiotherapy-induced carcinogenesis.
Geographic and site variability in the treatment of patients with metastatic gastric cancer.
Authors: Hess Lisa M. , Zhu Yajun , Liepa Astra M. , Li Xiaohong , Schelman William R. , Fuchs Charles S. , Abrams Thomas Adam 
Published: March 2017

153 Background: Previous work has demonstrated substantial heterogeneity in the treatment of metastatic gastric cancer (mGC) in the U.S. across all lines of therapy. However, the distribution of variability by region and clinical practice site is not well understood. Methods: De-identified patient-level electronic medical record (EMR) and claims data from IMS Oncology EMR and from Truven Marketscan, respectively, were used for this study. Eligible patients were age ≥ 18 years with newly diagnosed GC between 2007 and 2014. Metastases were identified by ICD-9 codes in the EMR and claims data or with evidence of stage IV or M1 disease in EMR. Patients classified with locally advanced/advanced disease were those who received chemotherapy without surgical intervention following diagnosis, regardless of absence or presence of metastases. Variability of treatment by line of therapy was measured by the Herfindahl-Herschman Index (HHI), a commonly used measure of market concentration in the business sector. The HHI was reported overall, by geographic region and practice site over time. Results: Overall, 2,368 IMS and 6,444 Truven patients treated for GC were identified; of these, 728 and 2,457 patients were classified with mGC in the IMS and Truven cohorts, respectively; 5,044 were diagnosed with advanced disease in Truven. Geographically (HHI regional scores ranged from 7-17), by line of therapy (7-17 in first line; 4-15 in second line), and over time, treatment variability was high. Practices treating a high volume of patients did not demonstrate lower variability than sites treating few patients with mGC. In the first-line setting, 83 of 87 and 223 of 228 regimens were used less than 5% of the time in patients with mGC in the IMS and Truven cohorts, respectively. Conclusions: Treatment variability was consistently high for all practice sites, geographic regions and year of diagnosis; in the business world a HHI score > 2000 is reflective of a monopoly whereas in this study, HHI scores were generally < 20, demonstrating high variability and the lack of any consistent treatment strategy. There is a need to identify best treatment practices to ensure care for patients with receive care that is in accordance with treatment guidelines.
Superior prognosis prediction performance of deep learning for gastric cancer compared to Yonsei prognosis prediction model using Cox regression.
Authors: Hyung Woo Jin , Son Taeil , Park Minseok , Lee Hansang , Kim Youn Nam , Kim Hyoung-Il , Kim Jong Won , Cheong Jae-Ho , Choi Seung Ho , Noh Sung Hoon , Kim Junmo 
Published: March 2017

164 Background: Staging systems for cancer are critical to predict the prognosis of patients. Current staging systems for gastric cancer have limitations to predict individualized and precise prediction of patient’s survival after treatment. We aimed to develop prediction model based on deep learning by estimating the survival probability of patients who underwent gastrectomy. Methods: To predict the survival probability, we used a deep neural network model which consisted of 5 layers: input layer, 3 fully connected layer, and output layer with 8 characteristics (age, sex, histology, depth of tumor, number of metastatic and examined lymph node, presence of distant metastasis, and resection extent) of patients which was previously published Yonsei prediction model using Cox regression. Each layer functioned as the nonlinear weighted sum of lower layer. Five-year overall survival was predicted using the deep learning method and it was compared to Yonsei prediction model. The average area under the curve (AUC) was compared between the models. For internal validation, 5-fold cross validations were carried out. We also performed external validation with a dataset from another hospital (n = 1549). . Results: Deep learning predicted 5-year overall survival of patients with an average accuracy of 83.5% in the test set. The average AUC of deep learning by integrating 8 characteristics was significantly higher than that of Yonsei prediction model (AUC: 0.844 vs. 0.831, P < 0.001) with the same variables. In the external validation the average accuracy of survival prediction was 84.1%. The AUC was also greater in a dataset from other hospital in Korea (AUC: 0.852 vs. 0.847, P = 0.023) Conclusions: Prognosis prediction with deep learning showed superior survival predictive power compared to prediction model using Cox regression. It can provide individualized and precise stratification based on the risk using characteristics of gastric cancer patients.
Lymph node metastasis in gastric cancer: Location of positive station to predict survival after preoperative therapy.
Authors: Ikoma Naruhiko , Estrella Jeannelyn , Blum Murphy Mariela A. , Chen Hsiang-Chun , Wang Xuemei , Fournier Keith F. , Mansfield Paul F. , Ajani Jaffer A. , Badgwell Brian D. 
Published: March 2017

166 Background: We sought to determine the association between the identification of positive lymph nodes on D2 lymph node dissection (LND) with stage and outcomes, in the era of preoperative treatment for gastric cancer. Methods: We reviewed data from a prospectively maintained database of gastric cancer patients who underwent resection of gastric or gastroesophageal cancer at our institution from 2005-2016. Central lymph nodes (CnLN) were defined as common hepatic, celiac, and proximal splenic artery lymph nodes (stations #8, 9, and 11p). Risk factors for CnLN metastases, and overall survival (OS) were examined. Results: We identified 356 patients, median age was 64 years (IQR 54-71) and 59% were male. Preoperative therapy was given in 66% of patients. D2 LND was performed in 80% of patients, and the median number of LN examined was 25 (IQR 18-34). Most patients (N = 244, 68%) had separately-examined CnLN in pathology and the median number of examined LNs was higher in this group (27 vs 19; p < 0.001). The CnLN positivity rate was 9.1% (22/244; #8: 4.8%, #9: 6.1%, and #11p: 4.8%), which was higher in advanced pT stage patients (pT0 - 3%, pT1 - 0%, pT2 - 6%, pT3 - 18%, pT4 - 13%; p = 0.001). If we assume that D2 LND was not performed on these patients, a total of 7 (3%, 7/244) patients would have had pN stage down-migration (6 with N1 to N0, 1 with N2 to N1). Of the 22 CnLN-positive patients, 10 (45%) had pN1, 2 (9%) had pN2, and 10 (45%) had pN3 stages. On multivariate analysis, EUS N stage (positive) was associated with positive CnLNs (OR 2.86 [95%CI 1.08-7.58]). Among 342 patients who had R0 resection, the median follow-up was 3.6 years, and the median OS was 11.6 years. Among patients who received preoperative therapy, pT3/4 stage (HR 2.44 [1.27-4.69]; p = 0.01) and positive CnLN (HR 5.44 [2.36-12.52]; p < 0.001) were negatively associated with OS by multivariate analysis. Conclusions: CnLN metastases are uncommon in gastric cancer, and are associated with an adverse impact on OS. However, long-term survival is still possible in patients with positive CnLN whom underwent a D2 lymph node dissection. Larger multi-institutional studies are needed to determine if CnLN positivity requires a separate staging category.
Retrospective analysis of neoadjuvant chemoradiotherapy with carboplatin/ paclitaxel versus FOLFOX in newly diagnosed esophageal or junctional cancers: A single instituition experience.
Authors: Nair Ranjit , Shah Usman , Kincaid Hope , Macfarlan Jennifer , Friedman Eliot Lawrence 
Published: March 2017

168 Background: The retrospective study aimed to evaluate carboplatin / paclitaxel (CP) versus FOLFOX in the neoadjuvant combined modality setting for newly diagnosed esophageal or junctional cancers. Methods: Patients with esophageal or junctional cancers treated in combined modality setting were included. During the study period, there were seventy three patients who had T2-4N0-1M0 esophageal and junctional carcinomas. Results: 49 (67%) patients received CP and 24 (33%) patients received FOLFOX. Concurrent radiation was delivered 5400-cGy in CP arm and 5040-cGy in FOLFOX arm. 38 (78%) patients in CP arm and 19 ( 79 %) in FOLFOX arm underwent curative resection. In CP arm, 11(12%) did not undergo curative resection due to disease progression (5/11), death secondary to infection (2/11) and poor functional status post chemotherapy (4/11). In FOLFOX arm, 5(21%) patients did not have surgery due to progressive disease (3/ 5), sepsis ( 1/ 5) and Tracheo–esophageal fistula ( 1 / 5). In patients who underwent curative resection, overall response rate (RR) was 92% in the CP arm with *CR–10(26%), PR–25 (66%), NR–3 (8%); in FOLFOX arm, RR was 100 % with *CR–6(32 %), PR–13(68 %), NR- 0 (p = 0.06). Median follow-up in all patients was 22 months, with median overall survival (OS) for the CP group 20-months and the FOLFOX group 30.5-months.With curative resection the median OS was 23-months in CP arm and 41-months in FOLFOX arm. Median relapse free survival (RFS) was 9.5-months in CP arm and 11 months in FOLFOX arm. 45% relapsed in the CP arm and 42% relapsed in the FOLFOX arm after curative resection. Conclusions: With CROSS trial in esophageal and juntional cancers, there has been a paradigm shift away from infusional 5-FU based regimens (5FU/cisplatin and FOLFOX). With this study, we demonstrated the activity of FOLFOX in comparison to CP in the neoadjuvant setting with concurrent radiotherapy in the treatment of localized esophageal cancers. There was a trend in clinical efficacy and response rate towards FOLFOX when combined with curative resection. To definitively assess this and compare the efficacy, long term prospective studies are needed.
Young age, disparities, and survival in gastric adenocarcinoma: Implications for screening strategies.
Authors: Gaitonde Shrawan G , Fischer Trevan D , Jones Maris S , Bandera Bradley , Stern Stacey , Goldfarb Melanie 
Published: March 2017

17 Background: Recent foreign publications have demonstrated increasing frequencies of gastric cancer in younger patients with differing biology and outcomes. This study will be the largest of gastric adenocarcinoma (GA) in young adults and aims to examine disparities and the impact of age on overall survival (OS). Methods: All patients diagnosed with primary GA from 2004-2013 in the National Cancer Data Base (NCDB) were reviewed for patient demographics, tumor characteristics, and treatment. Patients were grouped by age (AYA < 40, adult ≥ 40) and appropriate statistical analyses performed. Results: Of 49,278 patients, 1517 (3%) were < 40 years old. Compared to older adults, AYAs were more commonly female, represented an ethnic minority, and had more markers of socioeconomic disadvantage (SES) (all p < 0.001). They presented with higher grade tumors, higher tumor and nodal staging, and more metastatic disease at diagnosis (all p < 0.001). AYAs also more commonly received adjuvant radiation and/or chemotherapy (all p < 0.001). Five-year OS in AYAs was 32.9% vs 29.4% for older adults (p < 0.001). After controlling for competing factors, higher tumor grade (HR 1.61, CI 1.32-1.97), distant metastases (HR 2.22, CI 1.84-2.68), and increasing tumor (HR 2.69-5.44) and nodal stage (HR 1.84-2.35) independently decreased OS in AYAs whereas Hispanic (HR 0.78, CI 0.65-0.93) or Asian ethnicity (HR 0.72, CI 0.56-0.93) and receipt of adjuvant chemotherapy improved OS (HR 0.62, CI 0.52-0.75). Similar results were seen in older adults except that all markers of low SES decreased OS also. Age < 40 had an independent effect on OS only for early stage (stage I/II) disease, resulting in a 19% survival advantage compared to older adults (HR 0.81, CI 0.71-0.93). Conclusions: Young patients with GA are more ethnically diverse and SES disadvantaged compared to older adults, with disparities effecting OS more in older patients. When diagnosed at an early stage, young age independently improves OS, emphasizing the importance of early diagnosis especially in this age group. Further research is needed to address whether national screening strategies could improve survival for selected young patients.
Risk factors of lymph node metastasis in undifferentiated early gastric cancers.
Authors: Kim Il , Cheung DaeYoung , Kim Jin Il , Kim Jae J. 
Published: March 2017

171 Background: The aims of this retrospective study were to analyze risk factors of lymph node metastasis undifferentiated-type early gastric cancer (UD-type EGC) and to select the suitable patient for endoscopic resection. Methods: We analyzed 368 patients who had undergone gastrectomy with lymphadenectomy for UD-type EGC between November 2001 and July 2016 at the Yeouido St. Mary’s Hospital. Using clinicopathological factors of patient age, size, an endoscopic macroscopic tumor form, ulceration, depth, histology, lymphatic involvement (LI) and venous involvement (VI), LNM risk was examined and stratified by univariate analysis and multivariate analysis. Results: Of the 368 patients, the lymph node metastases rate in patients with EGC was 48 patients (13%). 204 (55 %) had mucosal cancers and 164 (45 %) had submucosal cancers. Univariate analysis revealed > 60 age, > 2 cm, submucosal(sm), poorly cohesive carcinoma as significant prognostic factors. On multivariate analysis, > 60 age (odd ratio , 2.20; 95% confidence interval, 1.19~4.06), submucosal(odd ratio , 9.38; 95% confidence interval, 4.08~21.56), poorly cohesive carcinoma (odd ratio, 0.33; 95% confidence interval, 0.12~0.86) were independent risk factors for lymph node involvement. Conclusions: LNM-related factors in undiff-EGC were age, depth and pathology. We proposed that risk factors for metastases should be considered when choosing surgery for EGC.
Dosimetric effects of deep inspiration breath hold for radiation treatment of esophageal cancer based on tumor location.
Authors: Doke Kaleigh , Badkul Rajeev , Aguilera Nathan , Mitchell Melissa Pulfer , Shen Xinglei , Lominska Chris 
Published: March 2017

173 Background: Deep inspiration breath hold (DIBH) has been shown to reduce heart and lung doses in radiation treatment of breast cancer and lymphoma. We investigated its application for treatment of esophageal cancer. Methods: Five patients who had DIBH simulation for diagnoses with chest scans were studied. Patients were simulated supine with 2 CT scans each: free breathing (FB) and DIBH using surface infrared markers. The patients were contoured using standard volumes as per RTOG 1010, including a 45 Gy planning target volume (PTV). Both a mid-esophagus and distal PTV were created for each of the model patients, by contouring 5 cm tumor volumes at the level of the carina and gastroesophageal junction. Normal structures were contoured as well. For distal tumors, the celiac nodes were covered electively as per RTOG 1010. Uniform three dimensional conformal radiotherapy plans were generated and normalized to provide 100% dose coverage to 95% of the PTV. Dose volume histograms were generated and evaluated. A 2-tailed paired student’s T-test was used to evaluate statistical significance. Results: When comparing the changes in dose to the normal structures with breath hold, a contrasting trend was seen between proximal and distal tumors. The mean heart dose and V40 decreased with breath hold for proximal tumor plans, however the heart dose metrics increased with breath hold for distal tumors. For the proximal tumor plans, the lung mean, V20, V10 and V5 decreased with breath hold in all patients. For distal tumors, mean lung doses trended towards an increase. Conclusions: Dosimetric parameters uniformly improved for proximal tumors with DIBH. By contrast, distal tumors often showed worsening of heart and lung dosimetry with DIBH. This appeared to be related to entry of the lung volume into the celiac nodal field, among other factors. [Table: see text]
Interim FDG-PET imaging during neoadjuvant chemoradiotherapy for esophageal cancer: Correlation with pathologic response.
Authors: Tandberg Daniel , Hong Julian C. , Cui Yunfeng , Ackerson Brad , Czito Brian G. , Willett Christopher , Palta Manisha 
Published: March 2017

175 Background: In this prospective study we evaluated whether changes in metabolic tumor parameters on interim flurodeoxyglucose positron emission tomography (FDG-PET) performed during neoadjuvant chemoradiotherapy (CRT) for esophageal cancer correlates with histopathologic tumor response. Methods: From February 2012 to February 2016, 60 patients with esophageal cancer underwent PET scans before therapy and after 30-36 Gy. Patients who underwent surgery after carboplatin/paclitaxel CRT were eligible for the current analysis. PET metrics of the primary site including maximum standardized uptake value (SUVmax), SUV mean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were extracted from the pre-treatment and interim PET based on a manual contour and SUV 2.5 threshold. Patients were called histopathologic responders if they had a complete or near complete tumor response based on the modified Ryan scheme. Relative changes in PET metrics between pre-treatment and interim PET were compared between histopathologic responders and non-responders using the Mann-Whitney test and binary logistic regression. Results: Twenty-six patients were included in the analysis. Adenocarcinoma was the most common histology (n = 23). Eleven patients (42%) had a complete or near complete pathologic response to CRT (histopathologic responders). Changes in PET metrics from pre-treatment to interim PET based on the manual contour were not significantly different between responding and nonresponding tumors. The relative reduction of SUVmax (Mean ± SD) was 38.2% ± 28.4% for histopathologic responders and 27.9% ± 31.4% for non-responders. The relative reduction in MTV, SUV mean and TLG was 36.1% ± 26.2%, 23.5% ± 21.3%, and 49.3% ± 28.3% for histopathologic responders and 28.6% ± 32.0%, 11.8% ± 19.1%, and 33.1% ± 38.5% for histopathologic non-responders, respectively. When analyzed based on the SUV 2.5 threshold there continued to be no significant difference in PET metrics. Conclusions: In this pilot study we observed changes in metabolic tumor parameters on PET performed during CRT for esophageal cancer. However, these changes did not predict for histopathologic responders.