bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between heart dosimetric parameters, cardiac events and overall survival for patients with stage III esophageal cancer treated with definitive radiotherapy.
Authors: Cai Guoxin , Yu Jinming , Meng Xue 
Published: May 2019

e15561 Background: Heart exposure to irradiation can cause cardiac events (CEs). The impact of radiation heart dosimetric parameters (RHDPs) on overall survival (OS) in esophageal cancer is not known. The aim of this study was to determine the association between heart dosimetric parameters and CEs and OS in patients with stage III esophageal cancer. Methods: 346 patients with esophageal cancer treated with definitive radiotherapy (RT) from 2011 to 2013 were enrolled retrospectively. We mainly observed three types of CEs: ischemic diseases (myocardial infarction and unstable angina), pericardial diseases (symptomatic effusion and pericarditis), and arrhythmia. We performed logistic regression or Cox proportional hazards models to evaluate the relationship between RHDPs, CEs and OS. Results: Median follow-up was 28 months and median prescribed doses was 60 Gy. Three and five-year OS was 43.9% and 16.8%, respectively. The number of patients who had ischemic diseases, pericardial diseases and arrhythmia in five years since they received treatment was 19, 12 and 26, respectively. Ischemic diseases was associated with pre-existing heart disease (P = .0016) and percentage of heart volume receiving ≥5 Gy (heart V5) (P = .0037), arrhythmia was associated with pre-existing heart disease (P = .0020), heart V5 (P = .0003) and mean heart dose (MHD) (P = .0021), but pericardial diseases was not correlated with RHDPs. In univariate analysis, smoking status, performance status, tumor location, lung V5, mean lung dose (MLD), heart V30, MHD and gross tumor volume (GTV) were significantly associated with three-year OS, and performance status, tumor location, concurrent or sequential chemotherapy, lung V5, heart V5, heart V30, MHD and GTV were correlated with five-year OS. In multivariate analysis, only poor performance status (hazard ratio (HR) 1.56; 95% confidence interval (CI), 1.16-2.10; P = .003 and HR 1.80; 95% CI, 1.15-2.82; P = .010) and larger GTV (HR 1.53; 95% CI, 1.14-2.05; P = .004 and HR 1.64; 95% CI, 1.07-2.49; P = 0.023) independently indicate worse three and five-year OS, and smoking status (HR 1.37; 95% CI, 1.03-1.82; P = 0.032) predict three-year OS only. Conclusions: Heart dose is associated with the occurrence of CEs, but it could not independently predict OS for patients with stage III esophageal cancer treated with definitive radiotherapy.
A novel EUS-guided liquid fiducial marker for image-guided radiotherapy in esophageal cancer: The safety and efficacy in vitro and vivo evaluations.
Authors: Sun Liangchao , Meng Xue 
Published: May 2019

e15573 Background: The true tumor extent of esophageal cancer is hard to visualize on current modalities during radiotherapy. In this study, we evaluated the safety and feasibility of the mixture of N-Butyl Cyanoacrylate and lipiodol to find the most optimal application as the fiducial marker to marking the true tumor extent in esophageal radiotherapy. Methods: Four types of injection matches (1:1-0.1ml, 1:1-0.15ml, 1:3-0.1ml, 1:30.15ml) were injected via syringes in subcutaneous tissue in rats model. Gross histopathological changes, weight, skin score, nodule volume, neutrophil counts and macrophage counts were observed to analyses the effect of different mixing ratios and injection volumes to find the best match. Evaluations following ISO standard criteria are further delivered to test the biocompatibility of the best applicable setting of this fiducial maker. Results: At 7th week, 42 markers (42/48, 87.5%) were still visualized on CT images. No serious adverse events or obvious artifacts were noted through the study. The overall review about the histopathological reaction of the NBCA/Lipiodol was considered to be a combination of acute inflammation, chronic inflammation, granulation tissue, foreign-body reaction and fibrous capsule formation in development. The quantitative analysis showed that when the density of NBCA was low (1:3), lower injection volume (0.1ml) brought the lower weights (p < 0.001). When the injection volume is high (0.15ml), the high NBCA (1:1) caused the lower weight (p < 0.001). At the most time points, the lower injection volume had the lower weights. High injection volume created a 0.079 cm3 increase in nodule size than low volume and high NBCA density also increased the nodule size. As for the inflammatory cells counts, the 3rd week was a key time point, before which the neutrophils decreased sharply and the macrophages keep almost steady, but after that the neutrophils stayed a low level and the macrophages started a rapid growth. On the comparisons of different index (Table), it is showed that the 1:3-0.15ml had an excellent performance as the fiducial marker and final biocompatibility test proved its safety. Conclusions: Overall, our results show that the mixture of NBCA/Lip as the fiducial marker is safe and feasible and the setting of 1:3-0.15ml was most optimal.[Table: see text]
Combining neoadjuvant chemoradiation with adjuvant chemotherapy in multimodality treatment for patients with potentially curable esophageal carcinoma.
Authors: Arays Ruta , Kibirova Albina , Auber Miklos L , Higa Gerald M. , Pahuja Shalu 
Published: May 2019

e15574 Background: Optimal multimodality treatment followed by surgical resection results in cure for less than half of patients with operable adenocarcinoma of the lower esophagus or GEJ. The current standard of care is either neoadjuvant chemoradiation established by the CROSS trial or perioperative chemotherapy established by MAGIC trial. We aimed to investigate whether additional treatment beyond current standards of care might improve outcomes. Methods: We performed a phase II, single center, investigator initiated study assessing the combination of neoadjuvant chemoradiation followed by esophagectomy and adjuvant chemotherapy in patients with resected esophageal/GEJ cancer. All patients received neoadjuvant infusional 5-fluorouracil at 225mg/m2 for 5 days with concurrent radiation at a dose of 4500 cGy followed by esophagectomy and 6 cycles of adjuvant paclitaxel 200mg/m2 on day 1, carboplatin AUC 6 on day 1 and infusion 5-fluorouricil 225 mg/m2 on days 1-7 (PCF) on a 28-day cycle. Results: 27 patients with stage IIA-IIIB (AJCC7) esophageal/GEJ tumors were enrolled on the protocol between 1999 and 2007. There were 23 males and 4 females with a median age at diagnosis 58 years. Twenty-five patients had adenocarcinoma, 1 had squamous and 1 had adenosquamous histology with 14 tumors located in GEJ and 11 in lower 1/3 of esophagus. The time between the surgery to start of PCF was 2.4 months. Fifteen patients (55.6%) had an R0 resection margin at the time of surgery. Only 8 (30%) patients could complete all 6 cycles of planned adjuvant chemotherapy, median number of cycles of chemotherapy administered was 1. Patients were followed for 10 years. Median progression free and overall survival was estimated to be 11.9 and 18.8 months respectively. At present time only one patient is alive and free of disease. One patient passed from an unrelated malignancy. Conclusions: Inferior survival results in this small study may be attributed to difficulty delivering adjuvant chemotherapy after prior chemoradiation, extensive surgery and delayed recovery. Total neoadjuvant therapy may overcome these obstacles in management of esophageal/GEJ cancer patients and should be explored in future studies.
Derived neutrophil-to-lymphocyte ratio and platelet to lymphocyte ratio as a prognostic marker for patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy.
Authors: Cai Guoxin , Yu Jinming , Meng Xue 
Published: May 2019

e15575 Background: Increasing study indicates that inflammatory biomarkers play a important role in predicting prognosis and therapeutic effect in esophageal squamous cell carcinoma. This research is designed to evaluate prognostic value of inflammatory biomarkers at baseline including neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), prognostic nutritional index (PNI) and fibrinogen to Albumin ratio (FAR) and the association between inflammatory biomarkers at baseline and symptomatic radiation pneumonitis in patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy. Methods: Patients with ESCC treated with definitive chemoradiotherapy from 2011 to 2015 were enrolled retrospectively. The operating characteristic analysis was used to determine optimal cut-off values of NLR, dNLR, MLR and PLR. The Kaplan-Meier method with a log-rank test and Cox regression model were used to evaluate the prognostic role of these biomarkers and the logistic regression was performed to investigate the association berween NLR and radiation pneumonitis. Results: 311 patients were included with a median follow-up of 24 months. The three-year survival rate is 24.12%. The optimal cut-of values of NLR, dNLR, MLR, PLR were 2.77, 1.70, 0.5 and 168.35, respectively. Univariate analysis revealed that tumor length, smoking and drinking status, performance status, tumor stage, tumor location, albumin level, NLR, dNLR, MLR, PLR, PNI, and FAR were significantly associated with progression-free survival (PFS) and overall survival (OS) (p < 0.05), but only tumor length, smoking status, performance status, tumor stage, dNLR and PLR were independent predictors of PFS and OS in multivariate model. Compared with separate marker, the prognostic predictive value of combined dNLR and PLR (coPLR-dNLR) was increased, and it was also a prognostic indicator when patients were stratified into early and advanced TNM stage. None of inflammatory biomarkers was significantly associated with symptomatic radiation pneumonitis in univariate and multivariate analysis. Conclusions: dNLR and PLR were powerful biomarker to predict prognosis in patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy, however inflammatory biomarkers could not predict the occurrence of symptomatic radiation pneumonitis.
Prognostic stratification of locoregional esophageal cancer (EC) patients (pts) treated with definitive chemoradiotherapy (dCRT).
Authors: Jeong Hyehyun , Bang Yeonghak , Im Hyeon-Su , Kang Jihoon , Yoon Dok Hyun , Kim Jong Hoon , Kim Yong-hee , Kim Hyeong Ryul , Lee Hyun Joo , JUNG Hwoon-Yong , Lee Gin-Hyug , Song Ho June , Kim Do Hoon , Choi Kee Don , Lee Jeong Hoon , Ahn Ji Yong , Ryu Jin-Sook , Cho Kyung-Ja , Kim Sung-Bae , Park Sook Ryun 
Published: May 2019

e15578 Background: Although dCRT is the standard treatment for pts who have locally advanced unresectable EC or refuse surgery, the prognosis of these pts remains dismal. There are urgent needs to develop the novel treatment strategy based on prognostic stratification after dCRT. Methods: A total of 382 pts with locoregional EC without distant metastasis except for supraclavicular lymph node who received dCRT at Asan Medical Center in South Korea from 2006 to 2015 were included. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier method. Risk factors were analyzed using Cox regression. Risk scores were calculated by multiplying coefficients in Cox proportional hazard model. Results: Baseline characteristics were as follows: median age = 66 yrs (range: 40-85); male = 359 pts (94.0%); squamous cell carcinoma = 375 (98.2%); cTNM stage (AJCC 8th) I = 40 (10.5%), II = 122 (31.9%), III = 128 (33.5%), IV = 92 (24.1%). During median follow-up of 52.9 mo, median PFS was 13.5 mo (95% CI, 10.9-16.1), and median OS was 26.7 mo (95% CI, 19.8-33.7). In the univariate analyses, sex (only for PFS), weight loss (≥ 5 kg) during dCRT, cT stage, cN stage, cTNM stage, clinical response after dCRT, reason for dCRT were significant prognostic factors for PFS and OS. In the multivariate analyses, clinical response after dCRT, cTNM stage, and weight loss were independent prognostic factors for PFS and OS (Table). Risk-scoring model using these factors stratified pts into four groups: for median PFS (p < 0.0001), group 1 = 58.2 mo (95% CI, 43.5-73.0), group 2 = 17.0 mo (95% CI, 11.9-22.1), group 3 = 9.0 mo (95% CI, 7.0-11.1), and group 4 = 3.9 mo (95% CI, 3.7-4.2); for median OS (p < 0.0001), group 1 = 106.2 mo (95% CI, 44.9-167.6), group 2 = 38.0 mo (95% CI, 24.4-51.5), group 3 = 13.0 mo (95% CI, 8.5-17.6), and group 4 = 8.0 mo (95% CI, 7.4-8.6). Conclusions: In dCRT-treated locoregional EC pts, survival outcome significantly varied according to baseline clinical stage, treatment response, and dynamic change in body weight. Different treatment and surveillance strategies based on the risk score might be needed in these pts.[Table: see text]
Clinical significance of peritoneal molecular markers in patients with locally advanced gastric cancer (LAGC) without macroscopic peritoneal implants treated with perioperative chemotherapy (ChT).
Authors: Del Carpio Huerta Luis Paul , Calvo Mariona , Serra Olbia , Varela Mar , Hormigo Gloria , Baixeras Nuria , Navarro-Perez Valentín , Aranda Humberto , Miró Mònica , Romero Natalia , Galan MaCarmen 
Published: May 2019

e15583 Background: Presence of malignant cells in the peritoneal lavage (Cyt+) of patients with LAGC in absence of macroscopic peritoneal implants reflects bad prognosis and is a surrogate of metastatic disease. The presence of molecular markers (Mol+), such as CEA and CK20 mRNA, had also been suggested to carry the same bad prognosis as Cyt+ after upfront curative gastrectomy. There is no recommendation about the management of Mol+ patients (pts) within the current perioperative ChT. Methods: We retrospectively analyzed all pts treated in our high volume multidisciplinary team between 2011 – 2015, with LAGC amenable to surgical resection, without macroscopic peritoneal implants in laparoscopy staging and treated with perioperative ChT. Pre-treatment peritoneal Cyt and Mol analysis (CEA and CK20 mRNA detected by RT-PCR), as well other clinical factors were analyzed. Results: From a total a 310 pts, 60 were included. Median follow up was 72.9 months (m). Mean age was 60y, 37% had PS0, 37% had diffuse histology, 85% wereT4(a-b), 93% N+ stage and 50% were located in gastric body. Accordig Cyt and Mol markers: 3% were Cyt+ and 18% were Mol+, 63% were Cyt-/Mol-, 15% Cyt-/Mol+, 3% Cyt+/Mol+, 0% Cyt+/Mol-, and 18% were Cyt or Mol unknown (uk). 83% underwent gastric surgery, of them, 93% achieved R0. Median PFS (mPFS) was 61.9m. mPFS for Mol+ was 11.0m (95%CI 2.6-19.4) vs the rest (Mol-/uk and Cyt +/-/uk) 69.9m (95%CI 45.0-94.8), p < 0.001. HR = 3.8. mOS was 68.3m. mOS for Mol+ vs the rest was 20.7m (95%CI 4.5-36.8) and not reached, respectively, p = 0.002. HR = 3.4. Mol+ pts who underwent surgery had longer mOS than Mol+ pts which did not (not-reached vs 7.8m (95CI% 3.4-12.9), p = 0.03). In the multivariate adjusted analysis PS (0 vs 1-2) and Mol (- vs +) were significant both for mPFS and mOS. Mol+: HR = 4.0 (95%CI 2.0-11.0),p < 0.001 for mPFS and HR = 5.4 (95%CI 1.9-14.9),p = 0.001 for mOS. Conclusions: Molecular peritoneal analysis may identify a subset of LAGC patients with bad prognosis despite negative cytology and absence of peritoneal macroscopic implants (Cyt-Mol+). Gastric surgery and perioperative chemotherapy may improve prognosis in some Mol+ patients
Impact of Clostridium difficile infection on gastrointestinal malignancies.
Authors: Perimbeti Stuthi , Shrivastav Rishi , Jatwani Karan , Ward Kristine Marie , Styler Michael , Jain Maneesh Rajiv , Nandi Neilanjan 
Published: May 2019

e15586 Background: According to the Centers for Disease Control and Prevention, there were half a million documented cases with 83,000 re-infections and 29,000 deaths due to Clostridium Difficile Infection(CDI) in the year 2011. The influence of CDI on outcomes in gastrointestinal(GI) malignancies is not well described, although the incidence is known to be higher in this subgroup of patients. Methods: National Inpatient Sample 1999-2014 was analyzed to identify adult admissions (>18 years of age) using ICD-9-CM codes with a primary diagnosis of esophageal(EC), Gastric(GC), Colorectal(CRC), Small intestinal(SIC), Hepatobiliary(HCC) and Pancreatic(PC) cancers. ICD-9 code 00845 was used to stratify these for the presence of CDI. We performed Chi-Square test to determine the in-hospital mortality percentage, and Cox Proportional Hazard model to control for confounders and determine the Hazard Ratio(HR) of death within 30 days of admission during hospitalization in patients with and without CDI. Results: See Table. Conclusions: Despite controlling for potential confounders, patients with GI cancers and CDI are at an increased risk of death compared to those without CDI. Taking the more detrimental effects of CDI in this subgroup of patients into consideration, healthcare professionals should strive to avoid the inordinate use of antibiotics and strictly maintain current guidelines designed to prevent spread. It may be prudent to treat these patients as severe CDI, even if current criteria are not met. More scientific research is warranted in analyzing the specific outcomes of CDI in GI cancer patients and if more aggressive therapy for CDI is warranted, considering the limitations of this study. [Table: see text]
Survival of gastric cancer (GC) patients is not determined by the predominant genomic ancestry (PGA): Results from an ethnically admixed Brazilian cohort of GC patients.
Authors: Freitas Helano C. , Araujo Luiza Ferreira , Nunes Diana Noronha , Begnami Maria D. , Bartelli Thais Fernanda , de Amorim Maria Galli , da Silva Israel Tojal , Valieris Renan , Defelicibus Alexandre , Xerfan Mariana Pinheiro , Costa Wilson L. , Jesus Victor Hugo Fonseca , Pizzi Melissa , Dias-Neto Emmanuel 
Published: May 2019

e15588 Background: Clinical characteristics, treatment response and overall survival of GC patients differ between Asian and non-Asian countries. Here we evaluated the possible associations between PGA, clinical characteristics and survival in an admixed GC Brazilian cohort. Methods: We included 112 GC pts diagnosed and treated at AC Camargo Cancer Center (São Paulo, Brazil) before 2013. The study was approved by local IRB. Genomic DNA was used for capture-based enrichment of a customized gene panel including 99 genes. Libraries were sequenced in the NextSeq 500 platform (Illumina), using paired-end reads (2x75bp). Ancestries were determined through a set of ancestry informative markers (AIMs), covered by target and off-target reads, described by Elhaik et al. (2014). Results: An average of 406 AIMs were recovered from the available samples, revealing average ancestries was as follows: 55.4% European, 27.7% Asian, 8.9% African; 8% of subjects were highly admixed (HA; < 50% of any ancestry). We found no association between PGA and age at diagnosis (p = 0.58), tumor location (p = 0.34), Lauren (p = 0.24) and staging (p = 0.68). There was an association between PGA and gender (p = 0.04) and a marginal association between PGA and EBV (p = 0.056). BRCA2 was the only gene enriched in the Asian subgroup, compared to the other groups combined (p = 0.009). The median follow-up time was 95 months. We found no differences in median overall survival (OS) (p = 0.4) or disease-free survival (DFS) (p = 0.6) according to PGA. The HA subgroup presented worst survival outcomes compared to the other groups aggregated (mOS 34m; 95%CI 5-80 x mOS 71m; 95% CI 44-85, respectively), but the difference was not statistically significant (HR 1,73; 95% CI 0.74-4.05; p = 0.2). Even for patients with > 75% AIMs for any given ancestry, we found no differences in OS between Europeans (n = 25; mOS 86m; 95%CI 80-NA), Asians (n = 22; mOS 83m; 95%CI 51-NA) and Africans (n = 5; mOS 67m; 95%CI 22-NA), p = 0.4. Conclusions: The most prevalent ancestries in this Brazilian GC cohort were European, followed by Asian and African. Although we found associations between ancestry and a few clinical aspects, PGA was not associated with survival.
Dose-survival relationship in patients with hepatocellular carcinoma undergoing stereotactic body radiation therapy.
Authors: Su Ting-Shi , Liang Shi-Xiong , Li Lequn 
Published: May 2019

e15592 Background: Stereotactic body radiation therapy (SBRT) has become a treatment for hepatocellular carcinoma (HCC) from palliative to radical treatment. But there is no clear evidence of a dose-survival relationship among commonly-utilized radiation therapy schedules. We aimed to determine the comparative effectiveness of different SBRT dosing regimens for HCC. Methods: The dataset collected from Guangxi Zhuang Autonomous Region in China was used. In this large single-centered retrospective study, 604 patients treated with SBRT were included from 2011 to 2017. Biologically effective dose (BED10) and equivalent dose in 2 Gy fractions (EQD2) were assumed at an α/β ratio of 10. Overall survival (OS) was the primary endpoint. OS rates were estimated using Kaplan–Meier curves with a log-rank test. Results: The median tumor size was 5.2 cm (interquartile range [IQR], 1.1–21.0 cm). Median follow-up was 21 months in surviving patients (IQR, 3–82 months). The 1-, 3-, and 5-year OSs were 87.1%, 64.7%, and 60.9% in Barcelona Clinic Liver Cancer (BCLC)-A group; 72.9%, 37.2%, and 30.7% in BCLC-B group; and 44.3%, 18.6%, and 12.8% in BCLC-C group; respectively. Increasing the RT dose was associated with improved overall survival. Stereotactic ablative radiotherapy (SART) with BED10≥100 Gy, SBRT with EQD2≥74 Gy and BED10 < 100 Gy, and stereotactic conservative radiotherapy (SCRT) with EQD2< 74 Gy have 3 separate curves for long-term survival post-SBRT. On multivariate analysis, Clinical factors associated with improved OS were BED, alanine aminotransferase (ALT) , and BCLC stage. On the subgroup analysis, BED10 ≥100 Gy was still beneficial against HCCs of BCLC stage A, B, and C. Conclusions: Individualized dose for SBRT are recommended for the treatment of HCC due to different degrees of cirrhosis and liver volume. The RT dose was classified into three levels. If tolerated by normal tissue, SART with BED10 ≥100 Gy as a first-line ablative dose or SBRT with EQD2 ≥74 Gy as a second-line radical dose is recommended. Otherwise, SCRT with EQD2< 74 Gy is recommended as palliative irradiation.