bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-reported distress and symptoms predict post-esophagectomy outcomes.
Authors: Salo Jonathan C. , Meadors Patrick Leland , Trufan Sally J , Gower Nicole Lee , Watson Michael David , Jeck Lauren A , Hill Joshua S. , Walsh Declan 
Published: May 2019

e15567 Background: Esophagectomy is accompanied by significant morbidity, mortality and altered quality of life. Understanding the factors responsible for adverse post-operative outcomes is essential for risk stratification in the selection of patients for surgery. Patient-reported measures are important not only as treatment outcome metrics, but also in predicting tolerance to therapy. Postoperative length of stay is a convenient measurement of patient tolerance of surgery. Our study aim was to determine whether preoperative patient-reported measures could add additional predictive power to clinical variables in predicting postoperative length of stay. Methods: A tablet-based symptom screening tool measured Distress, Anxiety (GAD-2), and cancer-related symptoms preoperatively. A generalized linear model predicting postoperative length of stay was constructed using age, gender, insurance status, income, T stage, and sarcopenia (hand-grip strength < 25kg). Patient-reported variables were then evaluated for their ability to predict length of stay in addition to these clinical factors. Factors found not significant (p > 0.05) are indicated N.S. Results: Esophagectomy (n = 58): Median age 62 (IQR 54-70) and 46 men (79%). Adenocarcinoma in 52 (90%). Neoadjuvant chemoradiation administered in 37 (64%). Major complications occurred in 13 (22%). Median postoperative length of stay was 8 days (IQR 6-10). Distress, Pain, Nausea/Vomiting, Trouble Swallowing, and Insurance or Financial Concerns independently predicted postoperative longer length of stay on multivariable analysis, while accounting for preoperative clinical factors. Conclusions: Preoperative cancer patient symptom reporting adds additional information to traditional clinical factors in predicting length of stay post-esophagectomy. Patient-reported measures may identify patients who benefit from interventions for preoperative optimization.[Table: see text]
Phase I study of irinotecan/5-fluorouracil/leucovorin (FOLFIRI) with sunitinib for advanced gastroesophageal cancers (EGC).
Authors: Mukherjee Sarbajit , Fountzilas Christos , Boland Patrick McKay , Attwood Kristopher , Tan Wei , Khushalani Nikhil I. , Iyer Renuka V. 
Published: May 2019

e15569 Background: Sunitinib (S) is a multi-targeted tyrosine kinase inhibitor with activity against VEGFR, PDGRF, KIT, FLT-3, and RET. S is synergistic with chemotherapy in preclinical models. We hypothesized that S+FOLFIRI combination will have increased efficacy in advanced EGC. Methods: This was a phase I study for patients with advanced chemo naïve EGC. Dose escalation used a standard 3+3 design. The primary objective was to determine the tolerability and safety of S+FOLFIRI. Secondary objectives were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Results: Twenty-three patients participated in the study (Male 78%, Female 22%). Median age was 60 (Range: 37-77) years. Median follow up time was 67.5 (95% CI: 58.9, 76) months. The most frequently reported adverse events were neutropenia (78%; G3/4: 43%), nausea (74%; G3/4:13%), diarrhea (65%; G3/4: 4%), vomiting (61%, G3/4: 9%) lymphopenia (52%; G3/4: 13%) and fatigue (52%; G3/4:17%).Two dose limiting toxicities (DLTs) were noted each at dose level (DL) 1 and 1A, one at DL 1B and 3 at DL 2 (Table 1). Maximum tolerated dose was determined at DL 1B. At the time of data reporting 21 patients had died. Two patients came off the study per investigator request. All patients were evaluated for efficacy. The median OS and PFS were 12.4 (95% CI: 8.9, 16.5) months and 6.2 (95% CI: 3.4, 13.5) months, respectively. Conclusions: S+FOLFIRI was reasonably tolerated, with a manageable safety profile and signs of clinical activity in patients with advanced EGC. This study was supported by a research grant from Pfizer, Inc. Clinical trial information: NCT00524186. [Table: see text]
Is it possible to effectively treat second-line gastric cancer, given the prognosis factors?
Authors: Manikhas Georgy M. , Orlova Rashida , Beliak Natalia P. , Kutukova Svetlana I. , Erdniev Sanal , Zhukova Natalia V. , Popova Natalia V. , Ivanova Anastasia , Antimonik Nina , Avramenko Inna , Zorina Ekaterina 
Published: May 2019

e15570 Background: Ramucirumab is the first anti-angiogenic targeted agent to demonstrate improved survival as monotherapy or in combination with CT among patients with disseminated stomach cancer. Methods: Under our supervision there were 24 patients: 12 men (50%) and 12 women (50%), from 29 to 72 years old, the median age was 52 years (95% CI 43.56-60.32). The median time to diagnosis of the 4th stage of the disease was 2 months (95% CI 0-11.44). All patients received 1 line of treatment; the median duration of 1-line therapy was 5 months (95% CI 4.00-6.83). Results: The duration of therapy with ramucirumab ranged from 2 to 16 months; median duration was 5.0 months (95% CI 3.00-7.44). The therapy with ramucirumab in 11 patients (45.83%) was followed by SD, in 3 patients (12.50%) - PR, in 4 patients (16.67%) - PD, and in 6 patients (25 , 00%) assessment of the effectiveness of therapy was not conducted due to the deterioration of the general condition during treatment. Thus, the ORR was 58.33%. The median overall survival was 18 months (95% CI 14–23). In order to identify adverse factors affecting overall survival, we constructed a Cox's regression model showing the dependence of overall survival on unfavourable prognosis factors. In general, the constructed model was reliable - p = 0.0013. The gender of the patients (p = 0.0642), the time before staging the 4th stage of the disease (p = 0.4312) and the duration of the 1st line therapy (p = 0.8675) did not have a significant effect on the survival of patients. Such factors as the patients' age (p = 0.0121), the localisation of the primary tumor (p = 0.0441), the differentiation of the tumor (p = 0.0095), the fact of removal of the primary tumor (p = 0.0133) had a significant impact, general status on the ECOG scale (p = 0.0250), the presence of anemia (p = 0.0192), damage to the peritoneum (p = 0.0022) and damage to metastases of more than 3 organs (p = 0.0062). Conclusions: An increase in OS in patients who received a combination of ramucirumab and paclitaxel can be considered clinically significant for this patient population and will allow considering this therapeutic regimen as a new standard of second line treatment of patients with poor prognosis of gastric cancer.
Preoperative CA 19-9 and CEA as predictors of operative outcomes in resectable gastric cancer (GC).
Authors: Gangi Alexandra , David John , Guan Michelle , Placencio-Hickok Veronica , Hendifar Andrew Eugene , Klempner Samuel Jacob , Burch Miguel , Chao Joseph , Kamrava Mitchell , Tuli Richard , Gong Jun 
Published: May 2019

e15581 Background: We sought to investigate whether preoperative serum CA 19-9 and CEA levels are predictive of resectability, postoperative outcomes, and survival in resectable GC. Methods: The National Cancer Database (NCDB) was interrogated to identify resectable GC patients between 2004-2015. Gastric adenocarcinoma cases without M1 disease and who did or did not undergo definitive surgery were included. Pretreatment CA 19-9 and CEA levels were classified as high (≥98 U/mL) or low ( < 98 U/mL). Proportions of categorical variables were compared using the Chi-squared test (two-tailed). Hazard ratios (HRs) for overall survival (OS) were compared using multivariate Cox regression, adjusting for baseline demographic and clinical variables. Results: From 183,204 GC cases screened, a final 5,447 patients were available. Resection rates for patients with low (n = 1920) and high (n = 294) CA 19-9 were 69.2% and 40.8% (χ² 90.6, p < 0.00001). 69.6% were resectable with low CEA (n = 5044) and 35.1% were resectable with high CEA (n = 97, χ² 53.0, p < 0.00001). Mortality within 30 days of definitive surgery was 7.5% and 0% in those with high (n = 120) and low CA 19-9 (n = 1286, χ² 85.6, p < 0.00001). There was no significant difference between 30-day mortality across high and low CEA and between 30-day readmission rates across high and low CA 19-9 and CEA levels. Age, median income, high school graduation rate, Charlson comorbidity index, and AJCC clinical N stage all significantly correlated with OS in this cohort. Compared to low preoperative CA 19-9, high CA 19-9 was significantly associated with worse OS (HR 1.24, 95% confidence interval (CI) 1.13-1.37, p < 0.0001). Similarly, a high CEA correlated with worse OS compared to low CEA (HR 1.44, 95% CI 1.32-1.57, p < 0.0001). Conclusions: High preoperative CA 19-9 and CEA are associated wither lower resection rates and worse OS in resectable GC. CA 19-9 but not CEA level predicts for 30-day mortality. Prospective validation is warranted.
Novel genomic prognostic factors for nonsurgical esophageal squamous cell carcinoma treated with concurrent chemoradiotherapy.
Authors: Dai Honghai , Shao Yang , Tong Xiaoling , Wu Xue , Pang Jiaohui , Feng Alei , Yang Zhe 
Published: May 2019

e15589 Background: Definitive concurrent chemoradiation therapy (dCRT) is the standard treatment for patients with nonsurgical esophageal squamous cell carcinoma (ESCC), yet patients demonstrated great variations in responses and post-treatment progression inevitably. Methods: To identify prognostic factors that could assist in clinical judgment and make predictions ahead of disease relapse, we performed a targeted next generation sequencing of 416 cancer-related genes on primary tumor biopsies from 47 ESCC patients with locally advanced or metastatic nonsurgical diseases. Patients were subjected to dCRT treatment and local recurrence free survival (LRFS), progression free survival (PFS) and overall survival (OS) times were analyzed. Results: TP53 (78%), NOTCH1 (32%), ARID1A (13%), FAT1 (13%) and CDKN2A (13%) are the most commonly mutated genes in ESCC, while copy number gains are frequently occurred in MCL1 (36%), FGF19 (34%), MYC (32%), CCND1 (27%), ZNF217 (15%), CDKN2A (13%) and YAP1 (11%). Multivariate analysis including clinical variables (age, gender and disease stage) and individual genetic alterations suggested that gender is an independent prognostic factor and male tend to have longer LRFS, PFS and OS after dCRT treatment. In addition, YAP1 amplification likely increased the risk of disease progression and death. To remove the impact of gender on prognosis, gender stratified survival analysis was performed and found that male patients with YAP1 amplification had significantly shorter LRFS (p = 0.002) and OS (p = 0.03), and also demonstrated a certain trend toward a shorter PFS (p = 0.06) than male patients without YAP1 amplification. Conclusions: YAP1 amplification might be a potentially useful biomarker in predicting treatment outcomes and selecting patients with high relapse risk for closely monitoring.
Improved survival following transarterial radioembolization of infiltrative-appearance hepatocellular carcinoma.
Authors: Nisiewicz Michael J , Patel Reema Anil , Dugan Adam J , Owen Joseph W 
Published: May 2019

e15591 Background: Infiltrative-appearance hepatocellular carcinoma (IHCC), also known as diffuse HCC, presents a distinct challenge to clinicians as evidence-based treatment guidelines have yet to be established. While transarterial radioembolization (TARE) has shown efficacy in HCC, many studies exclude IHCC in their analysis. The purpose of this study was to evaluate whether TARE of IHCC improves survival. Methods: With IRB approval, patients with IHCC were identified. Patient were divided into two groups: TARE versus systemic therapy/palliative care. Demographics, date of diagnosis, date of expiry, albumin, international normalized ratio (INR), sodium, alpha-fetoprotein (AFP), creatinine, Child-Pugh class, model for end-stage liver disease (MELD) score, and bilirubin were collected. Patients with bilirubin >3 were excluded. Mann-Whitney U test and Fisher’s exact test assessed for differences between groups. Kaplan-Meier survival analysis and Cox proportional hazard analysis were performed. Results: Forty-one patients were identified, 10 underwent TARE while the remaining 31 served as a control. Mean age was 62, 30 patients were male. The mean overall survival of the TARE treatment group was 16.6 months (506 days) and the mean overall survival of the control group was 5.6 months (170 days) (Log-rank p < 0.004), with a combined overall survival of 8.5 months (259 days). Cox proportional regression analysis revealed statistically significant associations between survival and albumin (hazard ratio 0.12, 0.032-0.41, p < 0.001), Child-Pugh class B (hazard ratio 0.25, 0.064-0.941, p < 0.041), and sorafenib therapy (hazard ratio 0.246, 0.071 – 0.847, p < 0.026). Conclusions: Transarterial radioembolization for patients with IHCC improves life expectancy compared to treatment with comfort measures or systemic therapy.[Table: see text]
Use of DNA methylation to distinguish gallbladder carcinoma.
Authors: Jiang Xiaoqing , Li Bin , Qiu Zhiquan , Yu Yong , Li Zhishuai , Zheng Jingjing , Wang Chenyang , Qiu Fujun , Fang Shuai , Li Bingsi , Zhang Zhihong 
Published: May 2019

e15605 Background: Gallbladder cancer (GBC), an uncommon malignancy with a high mortality rate, is often diagnosed late due to lack of early symptoms and the relative hidden nature of the gallbladder. Despite the advancements in imaging technologies, there is no reliable screening test for GBC. The role of aberrant DNA methylation in the process of tumorigenesis both at individual genes and a genome-wide scale has been well elucidated. It occurs very early in cancer development, thus capable of serving as a screening marker. Methods: Panel Design: Methylation data of tumor samples (12 types, n = 4,772), adjacent normal (8 types, n = 411), and normal white blood cells (n = 656) from TCGA and GSE were compared. Differentially methylated sites were derived using a Bayesian hierarchical model-DSS with an adjusted p-value < 0.05. Our panel covers 80,672 CpG sites, spanning 1.05Mb of human genome. This panel contains 12,196 GBC relevant CpG sites. We performed targeted bisulfite sequencing on 23 GBC patients (6 stage II-III, 17 stage IV) and 13 patients with non-malignant gallbladder diseases (cholecystitis and gallstones). Of the 23 GBC patients, we obtained adjacent normal tissue from 7 of them. Basic clinical features such as age, gender, of patients with GBC and patients with non-malignant gallbladder diseases were comparable. Results: Among the 12,196 GBC relevant CpG sites, 10,216 sites were statistically significantly hypermethylated and 275 sites were statistically significantly hypomethylated comparing to patients with non-malignant gallbladder disease as well as adjacent normal gallbladder tissues. Subsequently, we used the derived differentially methylated CpG sites to construct a linear regression model, achieving an area under curve of 99%. Collectively, the methylation levels were comparable between tissues with non-malignant disease and adjacent normal. Interestingly, when considering the 275 hypomethylated markers alone, we observed that the methylation level of adjacent normal tissues is significantly higher than tissues with non-malignant disease. Conclusions: Collectively, our panel can effectively distinguish GBC samples from non-cancerous samples, demonstrating the potential of DNA methylation in GBC screening. Furthermore, hypomethylation markers can be used to distinguish non-malignant disease from the healthy.
Hybrid capture-based genomic profiling of circulating tumor DNA from patients with advanced hepatocellular carcinoma.
Authors: Li Mao , Wei Ailin , Xie Wenzhuan , Zhao Jing , Zhao Zhengyi , Zhang Yuzi , Wang Guoqiang , Cai Shangli , Li Ang , Cao Dan 
Published: May 2019

e15606 Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies with a particularly high prevalence in China. The genomic profiling in HCC had been widely explored with tissue biopsy, however, given the intrinsic risks of invasive approach, blood-based circulating tumor DNA (ctDNA) has been proposed as a promising alternative. In this study, we aim to investigate whether the ctDNA may serve as a reliable tool to provide a more accurate molecular snapshot of HCC in Chinese patients. Methods: Plasma samples from 385 Chinese patients with advanced HCC were assayed for somatic genomic alternations by hybrid capture-based next-generation sequencing (NGS) with 150 genes and a mean sequencing depth of more than 3000×. The results were compared with our internal tissue genomic database of Chinese HCC patients (N = 873) tested by NGS and TCGA database (N = 373) tested by whole exome sequencing. Genomic alterations including single nucleotide variation (SNV), insertions/deletions, copy number variations, gene rearrangement and fusions were assessed. Results: Among 385 patients with ctDNA testing, somatic genomic alternations were detected in 97% of the patients (median = 5 alterations/patient). The most prevalent SNV mutations from ctDNA sequencing were TP53 (45.7%), TERT (19.5%), CTNNB1 (12.5%), and LRP1B (8.3%) compared to our tissue database (TP53 (61.2%), CTNNB1 (15.6%), TERT (13.3%), and LRP1B (11.0%)). While in TCGA database, the most common SNV mutations were found in TP53 (30.1%), CTNNB1 (26.0%), LRP1B (8.8%), ARID1A (8.6%), and SPTA1 (7.5%). Moreover, the level of MSAF was associated with detectable variant types, evidenced by a significant higher MSAF level observed when amplifications (P < 0.0001) or fusions (P = 0.008) were detected in the samples. Conclusions: Molecular analysis of patients with advanced HCC through ctDNA can serve as a reliable alternative to tissue biopsy. Chinese HCC patients may have different mutational landscapes to Western population. The utility of ctDNA analysis can provide therapeutically exploitable genomic profiles to identify potentially actionable gene alterations for targeted therapies.
Outcomes and patterns of failures after hypofractionated radiation therapy for intrahepatic cholangiocarcinoma.
Authors: Abu-Gheida Ibrahim , Patel Aashini , Zaid Mohamed , Elganainy Dalia , Javle Milind M. , Raghav Kanwal Pratap Singh , Vauthey Jean-Nicolas , Aloia Thomas A. , Tzeng Ching-Wei David , Minsky Bruce D. , Smith Grace L. , Holliday Emma B , Taniguchi Cullen M. , Koong Albert , Krishnan Sunil , Herman Joseph M. , Das Prajnan , Crane Christopher H. , Koay Eugene Jon 
Published: May 2019

e15609 Background: Locally advanced unresectable intrahepatic cholangiocarcinoma (IHCC) remains incurable. Prior data has shown the effectiveness of hypofractionated radiation therapy (HRT) with biological equivalent doses (BED) greater than 80.5 Gy in improving local control and survival for this patient population. This is an updated report of our IHCC experience with HRT in 15 or 25 fractions using a simultaneous integrated boost technique. Methods: A retrospective analysis of 63 patients (median age 64, range 29-87) diagnosed between 2007-2016 who received HRT was performed. RT dose ranged from 58-90 Gy in 15 fractions and 62.5-100 Gy in 25 fractions, translating to a median BED of 97.5 (range 78.1-144 Gy). Median primary tumor size at diagnosis was 7.8 cm (2.4-17cm). Forty-eight (76%) patients received gemcitabine-based therapy prior to HRT. Results: Median follow up was 31 months (4-110). The 2 year overall-survival (OS), local-progression-free-survival (LPFS), intrahepatic-distant-metastasis-free-survival (IH-DMFS) and extraheptic-distant-metastasis-free-survival (EH-DMFS) were 71% (95% CI 58-82), 67% (95% CI 50-80), 40% (95% CI 28-54) and 40% (95% CI 27-54) respectively. Pattern of failure analysis revealed 16 patients with local failure after HRT, of which only 5 (8% of total) progressed within the high iso-dose field line (BED > 80.5). After HRT, 41 (65%) patients had intrahepatic metastasis that occurred outside the radiation field, and 34 (54%) patients developed extrahepatic metastasis. On multi-variate analysis, T-stage was an independent predictor of OS, LPFS, IH-DMFS, and EH-DMFS. Larger normal liver volume and 15 fraction treatments were independently associated with better LPFS and IH-MFS respectively. There were no significant HRT-related toxicities. Conclusions: HRT demonstrates safety and efficacy for durable local control and prolonged overall survival in patients with unresectable IHCC. Dominant modes of failure are outside the HRT field. Improvements in systemic therapies could further improve outcomes for this patient population.
Lenvatinib for the treatment of HCC: A single institute experience.
Authors: Chen San-Chi , Chao Yee , Chen Ming Huang 
Published: May 2019

e15611 Background: Lenvatinib, a multiple kinase inhibitor, is an emerging for the treatment of advanced HCC. In REFLECT study, lenvatinib demonstrated higher ORR and longer PFS than sorafenib as the first line treatment for patients with Child-Pugh score A and tumor less than 50% of liver occupation. However, the efficacy for patients failed with sorafenib, with Child-Pugh score B and C, tumor more than 50% of liver occupation is not clear. Methods: A retrospective clinicopathological analysis was performed on 70 patients with HCC who received lenvatinib in our institute between 2017 and 2018. Lenvatinib was given orally 10 mg once daily. Treatment response, progression-free survival, overall survival and prognostic factors were explored. Results: Among 70 patients in this cohort, the mean age was 59.7 year-old and 78.6% were male, 58.6% were HBV(+) and 18.6% HCV(+). Among these patients, 65.7% had experienced sorafenib and 57.1% anti-PD-1. Patients who were not eligible for REFLECT study including having tumor more that 50% of liver occupation (40%), main portal vein invasion (34.3%) and Child-Pugh Score B and C (30.0% and 21.4%) were also enrolled. Treatment response was evaluable in 51 patients. Best responses were CR in 1 patients (2%), PR in 21 (41%), SD in 23 (45%) and PD in 6 (12%) by mRECIST criteria. Tumor with > 50% of liver occupation has higher ORR. However, no significant difference of response was observed regarding etiologies, AFP levels, tumor types, Child-Pugh Score, main portal vein thrombosis, sorafenib and anti-PD-1 experienced. The median PFS was 5.3 months and OS 8.5 months. Regression analysis showed AFP > 20 and Child-Pugh score B and C were poor prognostic factors for survival. Conclusions: Lenvatinib is potent drug for both treatment naïve and sorafenib-resistance HCC. Lenvatinib is also effective for patients with Child-Pugh Score B and C, tumor > 50% of liver occupation who were ineligible to REFLECT study.