bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enteral nutrition to improve nutritional status, treatment tolerance, and outcomes in patients with esophageal cancer undergoing concurrent chemoradiotherapy (CCRT): Results of a prospective, randomized, controlled, multicenter trial (NCT 02399306).
Authors: Li Tao , Lv Jiahua , Zhu Guangying , Li Jie , Zhu Shu chai , Wang Jianhua , Xing Ligang , Yang Daoke , Xie Conghua , Shen Liangfang , Zhao Ren , Shi Hanping , Lang Jinyi 
Published: September 2018

4033 Background: Patients with esophageal cancer undergoing CCRT are at high risk of malnutrition. The aim of this study was to investigate the influence of enteral nutrition on nutritional status, treatment tolerance and outcomes in esophageal cancer patients undergoing CCRT. Methods: Patients with inoperable esophageal cancer were randomly assigned (2:1 ratio) to the enteral nutrition group (EN group) or the control group. Patients in the EN group were supported with individual enteral nutrition intervention according to the nutritional status assessment results. The control group was treated with conventional diet guidance. The primary endpoint was the change in body weight from baseline after treatment. Secondary endpoints were nutrition related blood parameter changes, treatment tolerance and outcomes. Results: Between Mar. 2015 and Jan. 2017, 158 patients from ten hospitals were randomised into the EN group (n = 106) and the control group (n = 52). Following CCRT, patients in EN group lost only 0.72±3.27 kg of body weight compared with 2.10±2.89 kg in the control group (P < 0.001). Participants who received EN had less decline than controls in serum albumin (2.66±5.05 g/L and 4.75±4.94 g/L, P < 0.001) and hemoglobin (10.29±15.78 g/L and 18.48±14.66 g/L, P < 0.001). Grade 3/4 leukopenia in the control group was significantly more frequent than the EN group (33.3% vs. 20.0 %, P = 0.011). Patients supported on EN experienced greater chemoradiotherapy completion rates (92.5% vs. 67.3%, P = 0.001) and lower infection rates (18.8% vs 31.7%, P = 0.021). There was significant difference in tumor response between two groups (EN group: 81.1%, control group: 67.3%, P = 0.004). The 1- and 2-year OS rates in the EN group were significantly greater (89.6% and 75.4%, respectively) compared with the control group (78.5% and 57.9%, respectively). Conclusions: Enteral nutrition may be advantageous in patients with esophageal cancer undergoing CCRT by improving nutritional status, treatment tolerance and outcomes. Clinical trial information: NCT 02399306.
A phase II study of early FDG-PET evaluation after one-cycle chemotherapy in patients with locally advanced esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy: Final report.
Authors: Huang Ta-Chen , Lin Chia-Chi , Tzen Kai-Yuan , Wu Yun-Chun , Cheng Jason Chia-Hsien , Lee Jang-Ming , Wang Hsiu-Po , Huang Pei-Ming , Hsu Feng-Ming , Yeh Kun-Huei , Cheng Ann-Lii , Hsu Chih-Hung 
Published: September 2018

4042 Background: The optimal use of the metabolic tumor response measured by 18fluorodeoxyglucose positron emission tomography (FDG-PET) in the treatment of esophageal cancer is currently unknown. We launched a phase II clinical trial to evaluate the early metabolic response to one-cycle chemotherapy in locally advanced esophageal squamous cell carcinoma (ESCC) patients, who subsequently received neoadjuvant chemoradiation (neo-CRT) followed by surgery. Methods: ESCC patients with stage T3 or N1M0 or M1a (AJCC, 6th edition) were enrolled to receive one-cycle chemotherapy, day 1 and 8 doses of paclitaxel, cisplatin, and 24-hour infusional 5-fluorouracil and leucovorin, followed by paclitaxel/cisplatin- based 40Gy neo-CRT and surgery. FDG-PET was performed at baseline and day 14 of the one-cycle chemotherapy. The primary endpoint is pathological complete response (pCR) to neo-CRT. We hypothesized that early PET responders, defined as > 35% reduction of maximum standardized uptake value (SUVmax) from the baseline, would significantly improve pCR. Results: Between Feb 2008 and Mar 2012, 66 patients (M: F = 61: 5) were enrolled. Their clinical stages were: II or III, 56; IVA, 10. Forty seven received surgery. The pCR rate per surgical population was 34.0%. The median progression-free survival (PFS) and overall survival (OS) for the whole study group was 16 months (95% CI 9-27) and 22 months (95% CI 16-40), respectively. A total of53 patients were evaluable for PET response. The early PET response was not associated with high pCR rate or better survivals. However, in an exploratory analysis, the post-chemotherapy SUVmax was an independent prognostic factor for pCR, PFS and OS. A predictive model for pCR composed of weight loss and the post-chemotherapy SUVmaxwas established with an AUC of 0.84. Conclusions: Our study failed to validate the predictive value of predefined early PET response to one-cycle chemotherapy for pCR to neo-CRT in locally advanced ESCC patients. However, the FDG-PET SUVmax after one-cycle chemotherapy may have prognostic and predictive significance, and may be explored in further studies. Clinical trial information: NCT01034332.
A multicentre, phase II study with cabazitaxel in previously treated patients with advanced or metastatic adenocarcinoma of the oesophagogastric junction and stomach (CABAGAST).
Authors: Schmalenberg Harald , Pauligk Claudia , Zander Thomas , Reichart Alexander , Lindig Udo , Kleiss Mathias , Müller Lothar , Bolling Claus , Seufferlein Thomas , Reichardt Peter , Kullmann Frank , Eschenburg Henning , Schmittel Alexander , Egger Matthias , Block Andreas , Al-Batran Salah-Eddin , Goetze Thorsten Oliver 
Published: September 2018

4054 Background: This is a single-arm study to determine prolonged ( > = 4 months) disease control rate with cabazitaxel administered in second- (or later) setting for patients with advanced or metastatic adenocarcinoma of the esophagogastric junction (EGJ) and stomach. Methods: 65 patients with advanced EGJ and stomach cancer were treated with 20mg/m2 Cabazitaxel every 3 weeks for a maximum of 6 cycles. Main objective of the study was a prolonged Disease Control Rate (pDCR: CR, PR or SD lasting at least 4 months). Secondary Outcome Measures were overall survival (OS), progression-free survival (PFS), response rate by subgroup (with vs without previous treatment with a taxane) and toxicity. Patients were assessed for tumor response every 6 weeks during therapy and during follow-up (up to 12 months). Results: 65 patients (median age: 63, range 31-86 years) were assigned. Median no. of prior therapies was 2. 80% had received prior taxane therapy. Patients received a median of 2 cycles of cabazitaxel. Efficacy results are shown for the per protocol (PP) population. pDCR rate was 12.7%, (95%CI: 5,3%- 24.5%). pDCR was 20.0% in 2nd line patients (95%CI: 6.8%-40.7%) and 30.0% (95%CI: 6.7%-65.2%) in all lines in patients without prior taxane use. Response Rate was 5.5% (95%CI: 1.1%-15.1%) in total PP and 20.0% in the population without prior taxane use. Median OS was 4.6 months (7.4 months without prior taxane vs 3.8 months with prior taxane). Median PFS was 1.38 months (95%CI: 1.28- 1.87) with and 2.01 months (95%CI: 0.20- 4.67) without prior taxane use. Most common grade 3/4 toxicities were neutropenia in 13% of the patients, pain (12%), leucopenia (10%), anemia (10%), fatigue (10%) and nausea (10%). Conclusions: Cabazitaxel is active in heavily pretreated patients with metastatic and advanced esophagogastric junction and gastric adenocarcinoma. Toxicity is moderate. Patients without prior taxane use derived more benefit from Cabazitaxel. Clinical trial information: NCT01956149.
The Nationwide Cancer Genome Screening Project in Japan, SCRUM-Japan GI-screen: Efficient identification of cancer genome alterations in advanced esophageal cancer.
Authors: Nakashima Yuichiro , Kojima Takashi , Hara Hiroki , Kato Ken , Kajiwara Takeshi , Hironaka Shuichi , Nakatsumi Hiroshi , Kato Takeshi , Moriwaki Toshikazu , Naruge Daisuke , Esaki Taito , Izawa Naoki , Kadowaki Shigenori , Tamura Takao , Miki Izumi , Sudo Tomohisa , Nomura Shogo , Shitara Kohei , Ohtsu Atsushi , Yoshino Takayuki 
Published: September 2018

4062 Background: We have conducted the Nationwide Cancer Genome Screening Project in Japan since April 2015 using Next Generation Sequencing in advanced non-colorectal gastrointestinal (GI) cancer (aNon-CRC), called as the SCRUM-Japan GI-SCREEN. The objective is to evaluate the frequency of cancer genome alterations in aNon-CRC and to identify patients who are candidate for clinical trial for corresponding targeting agents. Methods: This study is ongoing with the participation of 20 major cancer centers. Patients with aNon-CRC, including advanced esophageal cancer (aEC), who plan to or receive chemotherapy were eligible. DNA and RNA were extracted from FFPE tumor samples and were analyzed by the Oncomine Cancer Research Panel (OCP) which allows to detect gene mutation, copy number variant (CNV) and fusions across 143 genes in a CLIA certified CAP accredited laboratory. The detected genomic variant data were classified according to genetic drivers of cancer including gain- and loss-of-function or single nucleotide variant based on the Oncomine Knowledgebase. In this presentation, we show the results of aEC cohort. Results: As of October 31st in 2016, a total of 180 aEC samples were analyzed. The sequence with the OCP was successfully performed in 121 (67.2%). Out of 157 patients except for the 23 patients in which precise data is not collected, the proportion of sample and histology type is followed; surgical specimen 58.0%, squamous cell carcinoma 92.4%. The frequently detected mutations in 114 samples of which results were available were TP53 (77.2%), NFE2L2 (23.7%), CDKN2A (9.6%), PIK3CA (7.0%), RB1 (6.1%), and CNVs were CCND1 (37.7%), EGFR (7.9%), MYC (7.9%), SOX2 (6.1%), ATP11B (5.3%), NKX2-1 (5.3%). ERBB2 amplification was identified in 3 cases (2.6%) and FGFR3-TACC3fusion was identified in one case (0.9%). Conclusions: This nationwide screening system is efficient to detect rare gene alterations in aEC. This novel knowledge provides an intriguing background to investigate new target approaches and represents a progress toward more precision medicine. Clinical trial information: UMIN000016344.
A phase 2 trial of regorafenib as a single agent in patients with chemotherapy refractory advanced and metastatic biliary adenocarcinoma/cholangiocarcinoma.
Authors: Sun Weijing , Normolle Daniel Paul , Bahary Nathan , Ohr James , Lembersky Barry C. , Patel Krishna , Patel Anuj K. , Lee James J. , Chu Edward , Streeter Natalie , Drummond Summer , Morcos John P. , Sulecki Matthew Gerard , Geller David A. , Marsh J. Wallis , Tsung Allan , Zeh Herbert 
Published: September 2018

4081 Background: Biliary adenocarcinoma/cholangiocarcinoma is a rare but aggressive neoplasm. Most patients present with unresectable or metastatic disease with 5-year survival rate ~5%. No second-line regimen has demonstrated clinical benefit in this disease. Regorafenib is an oral multi-kinase inhibitor with potent antitumor activity. This single arm phase II study evaluates the efficacy and safety of regorafenib as a single agent in advanced or metastatic biliary carcinoma/cholangiocarcinoma pts who failed systemic chemotherapy. Methods: Patients with ECOG PS 0-1and adequate liver, kidney and bone marrow function were given regorafenib orally once daily, 21 days on and 7 days off in a 28-day cycle. The initial dose of 160 mg was given to the first 3 patients. After toxicity assessment, the dose was reduced to 120 mg for the subsequent pts. The primary endpoint is PFS with the null hypotheses of 2.0 months, and median PFS ≥3.5 months as evidence of the study drug activity (α = 0.10, 80% power). Secondary objectives include OS, RR, and DCR. Results: Thirty-seven patients received at least one dose of regorafenib, of whom 28 were evaluable for efficacy. All had previous gemcitabine/cisplatin treatment. The mean age was 62.5 (34.5-82.8) with 17 (46%) females. PR was achieved in 3 (10.7%), SD in 18 (64.3%, with DCR of 75%), and PD in 7 (25%). For all 37 patients, median PFS was 3.55 months (95% CI = 2.1- 5.72) and mOS was 5.55 months (95% CI = 4.04 -NA) with survival rate of 42 % at 12 months, and 38% at 18 months. Medan PFS and OS of 30 patients who had ≥1 cycle were 3.91 months (95% CI = 3.55-9.79) and 13.4 months (95% CI = 5.06 - NA), respectively. The overall toxicity profile was as expected, with G3/4 AE’s of 40.5%. The most common toxicities were HTN, hypophosphatemia, hand-foot skin reaction, and increased serum bilirubin. Dose modification was required in 11 (30.6%) patients. Tumor samples were collected in 80% of patients, with planned correlative studies underway. Conclusions: This study showed promising efficacy of regorafenib in chemotherapy refractory advanced/metastatic cholangiocarcinoma. Further studies to confirm the clinic efficacy are recommended. Clinical trial information: NCT02053376.
Effect of sorafenib (S) starting dose and dose intensity on survival in patients with hepatocellular carcinoma (HCC): Results from a Canadian multicenter HCC database.
Authors: Alghamdi Mohammed Abdullah , Lee-Ying Richard , Sim Hao-Wen , Samawi Haider , Knox Jennifer J. , Romagnino Adriana , Ko Yoo-Joung , Chan Kelvin K. , Swiha Mina , Batuyong Eugene , Cheung Winson Y. , Tam Vincent C. ,   On Behalf of the CHORD Consortium
Published: September 2018

4084 Background: The SHARP trial showed that S improves survival in advanced HCC. Full dose (FD) S at 400mg bid can be difficult to tolerate, so some clinicians begin with a reduced dose (RD) & escalate as tolerated to maximum dose. The purpose of this study was to determine whether starting dose or dose intensity of S affects survival. Methods: All patients treated with S for HCC from 01/2008 to 06/2016 in British Columbia, Alberta, Ontario (Princess Margaret Cancer Centre & Sunnybrook Odette Cancer Centre), were included. Patient demographics, clinical, tumor characteristics, S starting dose & mean dose intensity were collected & analyzed. Patients were dichotomized into starting FD or RD of S. Mean dose intensity was categorized into > 75%, 50-75% & < 50%. Survival outcomes were assessed with Kaplan-Meier curves & compared with the log-rank test. A Cox-proportional hazard model was constructed with starting dose, dose intensity & relevant clinical & pathologic factors to assess their impact on survival. Results: We included 681 patients. Median age 64 years, 80% men, 37% East Asian, & most frequent causes of liver disease were hepatitis B (33%) & C (29%). ECOG performance status prior to starting S was 0 in 30% & 1 in 60%. Most patients were Childs-Pugh A (86%) at start of S. Overall median survival was 9.1 months (m). S was started at FD in 42% of patients & 31% had a dose intensity > 75%. The median survival for starting FD & RD was 9.4 m & 8.9 m, respectively (p = 0.15). The median survival for a dose intensity > 75% was 9.5 m, 50-75% was 12.9 m & < 50% was 7.1 m (p = 0.005). In multivariate models that adjusted for demographic, stage, performance status, AFP, prior treatment, toxicity & liver function, starting dose (HR 1.1, 95%CI 0.86-1.3, p = 0.51) & dose intensity (50-75% HR 0.93, 95% CI 0.73-1.2; < 50% HR 0.89, 95% CI 0.69-1.1, p = 0.65) were not predictors of survival. Conclusions: Based on our multi-center database, starting HCC patients on a RD of S may be a reasonable since it does not appear to compromise survival. Patients receiving a dose intensity of S at 50-75% appear to have a superior median survival, though this is not significant after controlling for baseline characteristics.
A prospective analysis of germline alterations (GA) in biliary tract cancer (BTC).
Authors: Lowery Maeve Aine , Jordan Emmet , Kemel Yelena , Mukherjee Semanti , Cercek Andrea , Kemeny Nancy E. , Varghese Anna M. , Rusek Matthew , Boucher Taryn Mary , Mandelker Diana , Berger Michael F. , Ptashkin Ryan , Hyman David Michael , Klimstra David , Saltz Leonard , O'Reilly Eileen Mary , Robson Mark E. , Stadler Zsofia Kinga , Offit Kenneth , Abou-Alfa Ghassan K. 
Published: September 2018

4085 Background: The incidence of hereditary cancer predisposition syndromes in patients (pts) with BTC is unknown. Cholangiocarcinoma has been reported in pts with germline mutations in BAP1, BRCA1/2, and mismatch repair genes. These associations are poorly characterized to date and the majority of pts do not undergo clinical germline analysis (CGA). Methods: Pts with BTC were offered consent to CGA between 01/2016 and 01/2017 under an IRB approved protocol (NCT01775072). Using the MSK-IMPACT platform, 76 genes associated with hereditary cancer predisposition were analyzed for germline variants and matched tumor samples were analysed for somatic alterations in > 340 genes. Demographic and clinical data were collected. Results: 78 patients were accrued: Intrahepatic = 52, extrahepatic = 13, gallbladder = 13. Median age at diagnosis was 57 years (range 21-80), 45 (58%) had a positive family history of cancer in at least one 1st degree or two 2nd degree relatives. 7 patients had a personal history of cancer. A pathogenic or likely pathogenic GA was identified in 16 pts (20%). (See table). Conclusions: Prospective analysis of GAs in pts with BTC, unselected by family history or age, revealed potentially actionable findings in 20% of pts. CGA in pts with BTC may benefit patients and their families in view of screening and therapeutic implications. [Table: see text]
Blood measurements of neuroendocrine tumor (NET) transcripts and gene cluster analysis to predict efficacy of peptide radioreceptor therapy.
Authors: Bodei Lisa , Kidd Mark S. , van der Zwan Wouter A , Drozdov Ignat , Baum Richard P. , Kwekkeboom Dik J. , Krenning Eric , Modlin Irvin Mark 
Published: September 2018

4091 Background: Peptide receptor radionuclide therapy (PRRT) capitalizes on somatostatin receptor (SSR) overexpression on NETs to deliver targeted isotope therapy. Objective prediction of efficacy remains to be established. Functional imaging of SSR expression (SRE) is used as a predictor of efficacy. Biomarkers e.g. circulating CgA, are ineffective. Circulating NET transcript analysis (NETest) integrated with tumor grade provides a Predictive Quotient Index (PQI) of PRRT. We validated the utility of this PRRT complementary diagnostic in a prospective, blinded study. Methods: 177Lu-PRRT (29.1±2.2 GBq). NETs ( n= 35); with progressive disease (66%). Baseline evaluations: Clinical status, Grade (Ki67), SRE, CgA (NeoLisa, ULN > 108ng/ml), and NETest (qRT-PCR - multianalyte algorithmic analyses, ULN > 14%). PQI: “omic” NETest gene expression (regulating metabolism and growth factor signaling) mathematically combined with Ki67 index. PQI has two prediction outputs: “responder” (R) vs “non-responder” (NR). Disease control was by RECIST criteria (R vs NR). All samples were blinded. Statistics: Cox proportional multiple regression, Kaplan-Meier survival, & McNemar-test. Results: At restaging, the overall response (disease control rate) was 77%; median PFS not reached (follow-up 4-13 months). Histology: GI: 5; GII: 21; GIII 1; and lung: TC: 2; AC: 5. SRE was Grade 3 (80%). Baseline CgA was 1556±1454ng/ml (89% elevated) and NETest was 60±21% (100% elevated) respectively. Predictive accuracies of SRE, clinical status, CgA levels ( > 2ULN) and NETest ranged from 25-54% (not-significant). PQI was the only predictive marker by multivariate analysis ( p= 0.002). The PQI diagnostic was 92% concordant with outcome and significantly more accurate than all other markers (McNemar: p< 0.002). Cox-proportional modeling confirmed PQI utility (OR: 9.1, p< 0.004). K-MS analysis identified significantly different mPFS between R (not reached) and NR (9.3 months; HR: 8.3, p< 0.0005). Conclusions: A pre-PRRT analysis of circulating NET genes, the predictive quotient index comprising “omic” analysis and grading, is validated to predict the efficacy of PRRT therapy in GEP and lung NETs.
Pre-existing symptoms, resource utilization, and healthcare costs prior to diagnosis of neuroendocrine tumors: A SEER-Medicare database study.
Authors: Shen Chan , Chu Yiyi , Dasari A. , Zhou Shouhao , Halperin Daniel M. , Xu Ying , Shih Ya-Chen T. , Yao James C. 
Published: September 2018

4092 Background: The incidence and prevalence of neuroendocrine tumors (NETs) are continually increasing. While it is known that NET symptoms often predate diagnosis, the prevalence of these symptoms and the impacts on resource utilization and costs are largely unknown. Methods: We identified 12,052 elderly patients diagnosed with NET between 1/2003 and 12/2011 by ICD-O-3 codes from the Surveillance, Epidemiology and End Results (SEER)-Medicare database with continuous Medicare Parts A and B enrollment during the one year before NET diagnosis. We used propensity score matching to identify a group of comparable elderly patients from a non-cancer Medicare cohort. We captured patients’ potentially relevant conditions (defined as > 1 indicative claim), resource utilization and costs from patients’ medical claims during the year before diagnosis. We examined a) resource utilization in terms of number of outpatient visits, percentage of patients having any emergency room (ER) visits and hospitalizations, and b) health care costs including inpatient, outpatient and total costs. We used chi-square test for categorical variables and Mann-Whitney U test for continuous variables. Results: NET patients were more likely to have diagnoses of diarrhea (8% vs. 2%), abdominal pain (37% vs. 8%), irritable bowel syndrome (1.5% vs. 0.6%), hypertension (72% vs. 55%), heart failure (16% vs. 8%), and peripheral edema (7% vs. 4%) compared to the non-cancer control group. They also had much higher resource utilization including number of outpatient visits (mean: 27.25 vs. 18.45); and percentage with ER visits (64% vs. 36%), and hospitalizations (66% vs. 34%). Similarly, NET patients incurred significantly higher total (mean: $32924 vs. $10048), outpatient (mean: $8869 vs. 4580), and inpatient costs (mean: $24055 vs. $10048). All p < 0.001. Conclusions: To the best of our knowledge, this is the first population-based study to examine potentially relevant pre-existing symptoms, resource utilization and healthcare costs before NET diagnosis. NET patients were more likely to have certain conditions and incurred higher resource utilizations and costs in the year preceding diagnosis of NET.