bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of radiomics of metastatic lesions in gastroesophageal adenocarcinoma (GEA) with tumoral DKK1 mRNA expression and other immune biomarkers in patients (pts) treated with DKN-01.
Authors: Sirard Cynthia A. , Klempner Samuel J. , Naik Girish S. , Kagey Michael , Nolte Zak , Hindosh Ziad , Burkett Andre , Korn Ronald Lee 
Published: February 2020

429 Background: Dickkopf-1 (DKK1) modulates Wnt and PI3K/AKT signaling pathways and contributes to an immune suppressive tumor microenvironment. Recently, anti-DKK1 antibody (DKN-01) [D] plus pembrolizumab (P) in GEA tumors has demonstrated clinical activity. Radiomic Quantitative Texture Analysis (QTA) is a non-invasive method for imaging biomarker discovery that can predict molecular drivers of cancer from CT scans obtained during clinical trials. QTA may be a useful tool for predicting DKK1 expression and other immune biomarkers in metastatic lesions from GEA pts treated with DKN-01. Methods: 13 pts with GEA (12 M; 1F; age 37-81) enrolled in D+P Phase I/II trial with high vs low DKK1 RNA Scope H-Scores (H Score > 35; n = 6 vs H-Score < 35; n = 7) were identified. Metastatic Target lesions (TLs) from baseline CTs with IV contrast underwent additional QTA analysis (TexRAD, CE mark, Essex, UK) after RECIST analysis. ROIs were placed on the TLs and histogram frequency curves (HFC) of the metastatic tumor pixels were generated. First order tumor HFC statistical results (i.e. mean, Standard Deviation-SD, Skewness, Kurtosis, MPP) were correlated with tumoral DKK1 mRNA expression, baseline plasma DKK1 levels and other biomarkers (PD-L1 CPS and MDSCs) along with tumor shrinkage using Pearson’s r correlation (significance p < 0.05). Results: Tumor derived QTA parameter (QTA SD) of the largest metastatic TL from each subject was positively correlated with DKK1 RNAscope H-score (r = 0.661, p value = .014) meaning larger SD texture scores had greater DKK1 expression. Also, tumor derived QTA parameter (QTA MPP) was correlated with baseline plasma DKK1 (r = -0.461, p = 0.005). Finally, QTA SD was correlated with PD-L1 expression (r = 0.630, p = 0.028) and TL shrinkage (r = -0.590, p = 0.034). Conclusions: Radiomics of GEA tumor metastasis using QTA showed significant correlations between tumor texture, tumor DKK1 mRNA expression and baseline plasma DKK1 suggesting that tumor textures may provide a non-invasive tool for assessing DKK1. Although promising as a imaging biomarker, further studies are required to validate these findings. Clinical trial information: NCT02013154.
Effect of proton pump inhibitors on the occurrence and development of gastric cancer and the polarization of macrophages in the microenvironment to M2-type.
Authors: Lu Xiao-Qing , Zhang Shengxiao , Zhang Huan-Hu 
Published: February 2020

437 Background: Long-term use of Proton pump inhibitors was associated with an increased gastric cancer(GC) risk in subjects even after HP eradication therapy. In contrast some basic research showed that PPI inhibited the growth of GC. In the tumor-microenvironment (TME), macrophages that are recruited around the tumor are activated to form the tumor-associated macrophages (TAMs), which are the most abundant mononuclear cells in the tumor infiltrating leukocytes. Many studies have shown that TAMs are associated with poor prognosis of tumors. Methods: Immunohistochemistry was used to detect the phenotype of macrophages in patients with gastric cancer treated with PPI or without PPI. Transcriptomics sequencing analyzed the signal pathways that were highly expressed in PPI-treated gastric cancer for further exploring the mechanism of PPI's main role in gastric cancer cells. In vitro, explore the effects of PPI on gastric cancer cells and the next step on macrophages. The effects of PPI on the growth of gastric cancer and the degree of infiltration and phenotype transformation of macrophages were verified by in vivo experiments. Results: In the gastric cancer tissues treated with PPI, the macrophage phenotype is mostly M2 type, thereby exerting a cancer promoting effects. Transcriptome results showed high expression of genes associated with endoplasmic reticulum stress in gastric cancer tissues after PPI treatment, compared with patients who were not treated with PPI. Among them, GRP78 is a classic marker of endoplasmic reticulum stress. It was not only highly expressed in gastric cancer treated by PPI, but also acted on macrophages through exosomes secreted by gastric cancer cells, and caused macrophage to polarize to M2. Conclusions: PPI caused GC cells to overexpress GRP78 which was secrete into the microenvironment through exosomes, thereby transforming macrophages into M2 type under the action of GRP78. Finally M2 type macrophages promoted the progression of gastric cancer.
Association of ascitic neutrophil to lymphocyte ratio with prognosis in patients with advanced gastric cancer
Authors: Kim Jae-Joon , Oh So Yeon , Park Kwonoh , Oh Sang-Bo 
Published: February 2020

443 Background: Approximately 40% of metastatic gastric cancer patients develop peritoneal carcinomatosis, and this condition leads patients to grave prognosis. Blood neutrophil to lymphocyte ratio (NLR) is associated with prognosis in various solid tumors, such as non-small cell lung cancer, colorectal cancer, and gastric cancer. We performed this study to investigate the prognostic significance of NLR of ascitic fluid. Methods: This is retrospective study. Patients were consecutive included if they; 1) had histologically confirmed gastric adenocarcinoma, poorly cohesive carcinoma, or poorly differentiated carcinoma, 2) were relapsed after curative resection or initially metastatic, 3) had ascites due to peritoneal metastases of gastric cancer, 4) had received paracentesis at least once and the result of ascites exam is available. Patients with clinically active infection in the time of paracentesis is excluded. If multiple times of paracentesis was done, we used initial result. Results: From March 2012 to August 2018, total 157 patients who were visited in Pusan National University Yangsan Hospital met the inclusion criteria. Median age is 58 (29-86) years and male patients was 63% (n = 99). In 38.9% (n = 61) patients, gastric cancer was diagnosed in primary site and in ascites synchronously. At the time of first paracentesis, 47.1% (n = 74) of patients had already been received palliative chemotherapy due to metastatic gastric cancer. In the ascites, mean and median NLR is 2.2±6.8 and 0.3 (0-65). All except 3 patients were expired, and the median survival time form paracentesis was 47 (95% confidence interval 38.6-55.4) days. In the Kaplan-Meier survival analysis, patients with higher NLR (≥0.33) have shorter survival from paracentesis (39 days, 95% CI 32.5-45.4) in compared to lower NLR ( < 0.33) (61 days, 95% CI 29.4-92.6, log-rank p = 0.011). In the additional analyses, higher neutrophil count (41 vs 72 days, p = 0.045) and lower protein level (32 vs 61 days, p = 0.018) of ascites are also poor prognostic factor. Conclusions: High NLR of malignant ascites is poor prognostic factor in patients with gastric cancer. The role of neutrophil in the malignant ascites should be tested in a new perspective.
Predictive value of the modified systemic inflammation score in patients undergoing curative resection of squamous cell carcinoma of the esophagus.
Authors: Kanda Mitsuro , Koike Masahiko , Shimizu Dai , Tanaka Chie , Kobayashi Daisuke , Sonohara Fuminori , Takami Hideki , Inokawa Yoshikuni , Hattori Norifumi , Hayashi Masamichi , Yamada Suguru , Nakayama Goro , Fujiwara Michitaka , Kodera Yasuhiro 
Published: February 2020

447 Background: Inflammation plays a critical role in the development and progression of cancers. Here we aimed to evaluate the clinical significance of the preoperative modified systemic inflammation score (mSIS) to predict long-term outcomes of patients with esophageal squamous cell carcinoma (ESCC). Methods: We included 443 patients who underwent curative resection of ESCC. The mSIS was formulated according to the serum albumin level (ALB) and lymphocyte-to-monocyte ratio (LMR) as follows: mSIS 0 (ALB ≥4.0 g/dL and LMR ≥3.4), mSIS 1 (ALB < 4.0 g/dL or LMR < 3.4), and mSIS 2 ( ALB < 4.0 g/dL and LMR < 3.4). Results: Patients were categorized into preoperative mSIS 0 (n = 165), mSIS 1 (n = 183), and mSIS 2 (n = 95) groups. Preoperative mSIS was significantly associated with age, preoperative body mass index, and pathological disease stage. The disease-specific survival times of patients in preoperative mSIS 0, 1, and 2 sequentially shortened ( P = 0.009), and mSIS 2 was identified as an independent prognostic factor (hazard ratio 2.63, 95% confidence interval 1.33–5.27, P = 0.0053). In most patient subgroups, the mSIS was associated with greater risk of disease-specific death. A stepwise increase in the prevalence of hematogenous recurrences was directly proportion to the mSIS. When patients were subdivided by mSIS before neoadjuvant treatment, there were no significant differences in disease-specific survival. Conclusions: Our findings demonstrate that the preoperative mSIS may serve as a powerful prognosticator of ESCC that definitively stratifies clinical outcomes as well as a tool for selecting treatment strategies.
Tissue levels of steroid hormones and their receptors, prolactin, and SHBG in patients with gastric cancer.
Authors: Kit Oleg Ivanovich , Frantsiyants Elena M. , Gevorkyan Yuriy A. , Soldatkina Natalya V. , Samoylenko Nikolay S. 
Published: February 2020

448 Background: Hormones and their receptors are important effectors providing interconnection between the primary tumor and metastatic niches. The aim of the study was to determine levels of steroid hormones and their receptors, prolactin (PRL) and SSBG in tissues of gastric cancer (GC), omentum and peritoneum. Methods: Levels of steroid hormones and their receptors, PRL and SSBG were determined by ELISA in tissues of primary tumors, omentum and peritoneum in main groups: 1 (M0) – GC T3-4аN0-3M0 (n = 24) and 2 (M1) – GC T3-4аN0-3M1 (n = 21); in tissues of the stomach, omentum and peritoneum – in the control group (non-cancer patients, n = 17). Results: In GC (М1), estradiol was reduced in primary tumors, omentum and peritoneum by 4.2, 4.0 and 8.6 times, respectively; increased levels of free testosterone (by 18.9, 2.0 and 2.8 times) and PRL (by 8.0, 7.6 and 1.7 times) were observed (p < 0.05). GC (М0) was characterized by high levels of estrogen receptors (ER) α – by 1.2 times (p < 0.05), progesterone (PR) – by 3.5 times and SSBG – by 1.4 times (p < 0.05); tissues of the omentum and peritoneum showed increased levels of ERα – by 2.4 and 3.9 times, ERβ – by 1.5 (p < 0.05) and 2.5 times, РR – by 2.2 and 1.5 times (p < 0.05). GC (М1) had low ERα levels. Conclusions: Decreased levels of estradiol, together with elevated levels of free testosterone and prolactin, in tumor tissues can be considered marking for peritoneal metastases. Correlation between the content of these hormones in the omentum and peritoneum and the presence of metastasis in the organs confirms the “seed and soil” principle.
The comparisons of the outcomes between surgical resection and proton beam therapy for single primary hepatocellular carcinoma.
Authors: Tamura Shunsuke , Okamura Yukiyasu , Sugiura Teiichi , Ito Takaaki , Yamamoto Yusuke , Ashida Ryo , Ogi Katsuhisa , Murayama Shigeyuki , Uesaka Katsuhiko 
Published: February 2020

482 Background: There are many treatment choices for hepatocellular carcinoma (HCC). Proton beam therapy (PBT) is considered a treatment option for HCC. The purpose of this study was to compare surgical resection (SR) and PBT in order to clarify the prognostic factors for operable HCC based on a single institution’s database. Methods: Patients with single primary nodular HCC ≤ 100 mm without vessel invasion on pretreatment imaging were divided into the SR group and PBT group. In the PBT group, the patients with unresectable HCC due to their liver function and/or performance status (PS) were excluded. Results: There were 314 and 31 patients who underwent SR and PBT, respectively. The median survival time in the SR group was significantly better than in the PBT group (104.1 vs. 64.6 months, p = 0.008). Regarding the relapse-free survival (RFS), there was no significant difference between the SR and PBT groups (33.8 vs. 14.0 months, p = 0.099). Conclusions: In RFS, the PBT group and the SR group were comparable. However, the PBT group was significantly worse than SR group in overall survival. SR may therefore be favorable as an initial treatment for HCC compared to PBT. Clinical trial information: 1856.
Biliary tract cancer (BTC) in the elderly: A real-world tertiary cancer center experience.
Authors: Salati Massimiliano , Caputo Francesco , Cerma Krisida , Spallanzani Andrea , Gelsomino Fabio , Santini Chiara , Bocconi Alessandro , Riggi Maria Laura , Luppi Gabriele , Casadei Gardini Andrea , Dominici Massimo 
Published: February 2020

492 Background: Although BTC is mostly a disease of the elderly, only limited data ara available on the optimal management of this patient (pt) population. In fact, older pts are underepresented in clinical trials and results are seldom reported by age group. In this study, we aimed at evaluating pattern of care and treatment outcome in BTC aged ≥ 70 years and comparing them with their younger counterparts. Methods: Medical records of BTC followed at the Modena Cancer Centre from 2007 and 2019 were retrospectively reviewed.. Overall survival (OS) was estimated with the Kaplan-Meier curves and compared by log-rank test. Differences between categorical variables were assessed using the chi square test. Univariate and multivariate analyses were performed to assess the impact of covariates on survival. Results: A total of 120 BTC patients (49%) ≥ 70 were included in the analysis. 54% (64) were female, 47% (56) had iCCA, 41% (49) GBC, and 12% (15) eCCA. 68% (81) had unresectable locally advanced or metastatic disease. 32% (39) underwent surgical resection, 60% (72) were treated with first-line chemotherapy (1L), while 29% (21) of them went on to receive second-line (2L). No differences in terms of both chance to receive surgery (p=0.59) and survival (p=0.25) were recorded compared to youngers. In the advanced-disease setting, median OS was 8 months and was significantly worse than that of the younger counterparts (p<0.001). Older patients were less likely to receive 1L (p<0.001) and 2L (p<0.001) chemotherapy and doublet regimens (p<0.001). Female gender (p=0.031), ECOG PS 0 (p<0.001), stage III (p<0.001) and NLR>3 (p<0.001) were independently associated with a better prognosis in older BTC receiving 1L, with 1-year OS of 82% (95%CI 68-91, p=0.031). Conclusions: In this real-world study, no survival difference was found between older and non-older surgically-treated patients. Contrariwise, elderly BTC were less frequently treated with chemotherapy for advanced disease and their outcome is poorer than youngers. However, clinical and biochemical prognostic have been identified that may assist in selecting older pts more likely to benefit from systemic treatment, both in clinical trials and daily practice.
The adherence to The American Association for The Study of Liver Disease (AASLD) guidelines in treating patients with hepatocellular carcinoma: Institutional experience.
Authors: Manne Ashish , Escobar Daisy E. , Prodduturvar Pranitha , Henderson Phillip , Abdul-Rahim Osama , Hussain Zeiad , Liles Spencer , Fonseca Annabelle , Howard John Harrison , Mneimneh Wadad , Gilbert Robert , Pai Sachin Gopalkrishna , Khushman Moh'd M. 
Published: February 2020

496 Background: The American Association for the Study of Liver Disease (AASLD) guidelines outline an algorithm regarding the treatment modality of choice for patients with hepatocellular carcinoma (HCC) based on Barcelona Clinic Liver Cancer (BCLC) stage. The AASLD guidelines have several limitations and the adherence rate has been reported to be low. The adherence to AASLD guidelines in treating patients with HCC was explored in this study. Methods: Between 2017 and 2019, 106 patients with HCC were identified. In our cohort, 70 patients (66%) were discussed in the multidisciplinary tumor board (MDTB) and their first-line treatment modality was selected based on consensus recommendations from the MDTB team members. The adherence rate of MDTB recommendations to AASLD guidelines was calculated. Results: Median age was 65 (range 42-90). Males represented 84% while females represented 16%. Caucasians, African Americans and Asians represented 69%, 30% and 1% respectively. BCLC stage 0, A, B, C and D represented 7%, 32%, 23%, 27% and 11% respectively. First-line treatment modality of choice recommended by MDTB is summarized in Table. The overall adherence rate of MDTB recommendations to AASLD guidelines is 60%. For BCLC stage 0, A, B, C and D, the adherence rate was 60%, 86%, 44%,58% and 25% respectively. Conclusions: Our MDTB recommendations adherence rate to AASLD guidelines was 60%. The reported low adherence rate to the guidelines suggest that AASLD guidelines would benefit from further refinement and periodic update. [Table: see text]
Real-world experience of regorafenib in patients with hepatocellular carcinoma: A multicenter United Kingdom study.
Authors: Ross Paul J. , Ma Yuk Ting , Palmer Daniel H. , Lythgoe Mark Peter , Merrick Sophie , Samson Adel , Rao Ankit Rohit , Basu Bristi , Prasad Debi , Dhillon Tony , Lau David , Darby Suzanne , Orr James , Margetts Jane , Hubner Richard , Baijal Shobhit , Sharma Rohini , Faluyi Olusola Olusesan , Lee Lennard , Thillai Kiruthikah 
Published: February 2020

499 Background: Regorafenib was the first treatment to demonstrate a survival benefit in patients with HCC after progression on sorafenib. The RESORCE trial found that regorafenib improved overall survival with acceptable toxicity, in patients with disease progression on sorafenib who tolerated ≥400mg sorafenib daily and had Child-Pugh A liver function. Methods: We performed a multicentre, retrospective, observational study of patients with HCC receiving regorafenib in the UK, following its availability in April 2018. Results: Data on a total of 104 patients were included from April 2018–August 2019, and 80.8% were male. Age was collected in 85 patients, with a median of 68 years (range 22–86). 23.5% had NAFLD, 21.2% had ALD, 12.9% had HBV, and 3.5% had HCV. Prior management included sorafenib (100%), TACE (30.8%), resection (12.9%). Duration of sorafenib treatment was evaluable in 99/104 patients, and reported a median of 8.7 months (range 1.8–76.6). Duration of regorafenib treatment was evaluable in 92/104 patients, and reported a median of 3.9 months (range 0.0–15.7). Following treatment with regorafenib, 6 patients (5.8%) achieved partial response, 37 (35.6%) achieved stable disease and 45 (43.3%) had progressive disease as the best response. 15 (14.4%) were not assessed and 1 (1.1%) had mixed response. Survival data is immature with 62/101 (61.4%) patients alive at the time of census with median survival currently 6.5 months. Fatigue was the most frequent AE, with 69/88 patients (85.2%) for all grades. 12/88 patients (14.8%) had Grade 3 fatigue. Other significant AEs include hand-foot syndrome (6/85 patients [7.3%] had Grade 3) and diarrhoea (4/83 patients [4.9%] had Grade 3). Conclusions: The population in our real-world experience of regorafenib for HCC had a similar duration of prior sorafenib to those in the RESORCE trial. However, there was different balance of aetiologies with a lower proportion of patients with HBV and HCV. The rate of partial response is similar to the RESORCE trial with fewer patients achieving stable disease. The incidence of fatigue was higher, but the incidence of hand-foot syndrome and diarrhoea were lower. Further expansion and follow-up of this population is warranted.
Eligibility of real-world patients with stage II/III colorectal cancer (CRC) in adjuvant chemotherapy (AC) trials.
Authors: Batra Atul , Kong Shiying , Cheung Winson Y. 
Published: February 2020

50 Background: The results of AC trials in stage II/III CRC are often generalized to real-world patients. However, clinical trials have stringent inclusion and exclusion criteria, which can potentially lead to poor generalizability of results and slow accrual. This study was conducted to determine the proportion of real-world patients with stage II/ III CRC who would be eligible for AC trials based on common eligibility criteria and to compare the outcomes in eligible and ineligible patients. Methods: We identified all patients diagnosed with stage II/III CRC in 2004-2015 from the Alberta Cancer Registry. Patients meeting any one of the following criteria were considered ineligible: age >75 years, anemia, comorbid conditions (heart disease, uncontrolled diabetes, kidney disease, liver disease) and history of a prior malignancy or immunosuppression. Logistic regression was used to describe the likelihood of receiving AC and Cox regression models were constructed to determine overall survival (OS). Results: A total of 7841 patients with stage II/III CRC were identified, of whom 52% were men and median age at diagnosis was 71 years (IQR: 61-79 years). Approximately 59% patients were deemed trial-ineligible and the most common reasons for ineligibility were advanced age (36%), renal dysfunction (27%), and cardiac disease (17%), respectively. In the real-world, 54% of eligible patients received AC as compared to 23% of ineligible patients [odds ratio 3.89, 95% confidence interval (CI) 3.53-4.28, P< 0.0001]. The 5-year OS of trial-ineligible patients who received AC was significantly better than those treated with surgery alone (table). Conclusions: Majority of real-world patients with stage II/ III CRC are unable to participate in AC trials due to strict exclusion criteria, but a fair proportion of these patients still derive some benefit from AC. The eligibility criteria of AC trials in CRC should be broadened to be more representative of real-world patients. [Table: see text]