bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time to sustained improvement in bowel movement frequency with telotristat ethyl: Analysis of the phase III telecast study.
Authors: Dillon Joseph , Lapuerta Pablo , McKee Chad 
Published: January 2019

395 Background: Telotristat ethyl (TE) is approved to treat inadequately controlled carcinoid syndrome (CS) diarrhea in combination with somatostatin analog (SSA) therapy. Understanding the time to onset of sustained BM frequency improvement is important when considering the use of TE in patients with CS diarrhea. We present data on time to sustained improvement and worsening in BM frequency during the double-blind treatment (DBT) period of TELECAST, a phase 3, randomized, placebo-controlled, double-blind study in patients with CS that required additional treatment, primarily due to gastrointestinal symptoms. Methods: Stable dose SSA was not required. Patients were treated with TE 250 mg 3 times per day (tid), TE 500 mg tid, or placebo tid. Sustained response was defined as the time from the first double-blind dose date to the first day of 2 consecutive weeks with BM frequency change of at least 30% from baseline. The time to the first sustained response in the TELECAST study was examined among treatment groups and analyzed using Cox regression. Results: There were 26 patients on placebo and 25 patients on either 250 mg or 500 mg telotristat groups. Sustained improvement in BM frequency over the 12-week DBT period was achieved in 6, 16, and 16 patients on placebo, TE 250 mg, and TE 500 mg treatment groups. Median time to sustained ≥ 30% improvement was 4-5 weeks with TE at both dosing levels, with no median reached on placebo. First occurrence of sustained improvements in BM frequency occurred within 4-68 days. Time to sustained worsening was delayed on the 500-mg dose of TE (no percentile reached) and is statistically significant (p = 0.021, HR: 0.25) Conclusions: Treatment with telotristat ethyl may provide sustained BM frequency reduction within 4-5 weeks (median) of initiating therapy. No median was reached on placebo due to fewer patients with sustained improvement. Additionally, TE 500 mg tid may also offer additional clinical benefit by reducing sustained BM worsening. Clinical trial information: NCT02063659.
Precision oncology in pancreatobiliary cancers: A longitudinal study.
Authors: Sadaps Meena , Estfan Bassam N. , Sohal Davendra , Khorana Alok A. 
Published: January 2019

399 Background: Precision oncology – the use of next-generation sequencing (NGS) to identify therapeutic options for advanced cancer patients – is being used widely, but its utility in patients with pancreatobiliary (PB) cancers has not been studied systematically. We evaluated the prevalence of actionable alterations and their impact on therapeutic decision-making in patients with PB cancers. Methods: We conducted a retrospective cohort study of consecutive patients seen at the Cleveland Clinic between 2013 and 2016 with incurable solid tumor malignancies, in whom FoundationOne™ (Cambridge, MA) NGS was ordered. All results were reviewed at a multidisciplinary genomics tumor board (GTB), which determined actionability and made therapeutic recommendations. Treatment decisions (on label, off label, or clinical trials) based on said recommendations were reviewed. Results: The study population was 600 patients, of whom 53 had PB cancers. For these 53, median age was 59.6 years; 62.2% (33/53) were female; 86.8% (46/53) were Caucasian. Eight samples (15.1%) had inadequate tissue; of 45 resulted cases, 21 (46.7%) were recommended treatment, including clinical trials (n = 19) and off-label drugs (n = 2). The most common targets for therapy were FGFR (5/21) and CDKN2 (3/21). Of 21 patients with recommendations, only two (9.5%) received genomics-driven therapy, compared with 31.7% (86/271) of patients with other solid tumor malignancies (p = 0.03). One received an IDH1 inhibitor, and one received dabrafenib and trametinib for a BRAF alteration; both on clinical trials. At time of last follow-up, best responses were unknown and partial response, respectively. Unavailability of clinical trials in the vicinity (9.5%), and clinical trial ineligibility, mainly due to poor performance status (9.5%), were common reasons for lack of actionability. Conclusions: Benefit from precision oncology in the PB population is low, with only 4.4% (2/45) of patients with NGS results eventually receiving genomics-driven therapy. Benefit to patients will not improve until access to clinical trials is enhanced and patients are evaluated for these trials earlier in the course of their disease, when their performance status is likely to be higher.
Effect of region and hospital attribute on outcome of gastric patients treated with apatinib: Data from post-marketing phase IV study.
Authors: Zhong Haijun , Qin Shukui , Li Jin , Deng Wenying , Wen Lu , Wang Junsheng , Zhang Guifang , Jia Tongfu , Yang Jianwei , Ba Yi , Bai Yuxian , Wang Mei , Wang Lin , Liu Likun , He Yifu , Tao Min , Xie Congying , Ye Feng , Wu Xiang-yuan , Lin Xiaoyan 
Published: January 2019

40 Background: The single-arm, open-label, multi-center, Phase IV trial of apatinib was conducting in patients (pts) with advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction with a target sample size of 2000+. We aimed to analyze the effect of region and hospital attributes on clinical outcomes. Methods: From April 2015 to July 2017, 1037 subjects were enrolled, among which 820 were evaluable in the survival analysis. Results: The incidences of adverse events (AEs) and severe AEs (SAEs) are listed in Table. Overall, both incidences were higher in Southern center compared to Northern Center (p=0.002 and <0.001). More SAEs occurred in developed cities (p=0.028) and in hospitals not specialized in oncology (p=0.028). For efficacy, the median overall survival (mOS) of subjects in Northern Center and Southern centers were 8.71 and 5.72 mos (p<0.001), and the median progression free survival (mPFS) was 5.36 and 3.25 mos (p=0.002), respectively. The mOS of subjects in developed and developing cities were 6.18 and 5.72 mos (p=0.105), and the mPFS was 3.02 and 4.73 mos (p=0.013), respectively. The mOS of subjects in hospital specialized and those not in oncology were 7.59 and 5.78 mos (p=0.014), and the mPFS was 4.73 and 3.84 mos (p=0.068), respectively. Conclusions: Region and attribute hospital can affect the safety and clinical outcome of apatinib in treating gastric cancer in the real world. Patients Northern, developing city or hospitals specialized in oncology experience less SAEs but have better clinical benefit. Clinical trial information: NCT02426034. [Table: see text]
Improvement of carcinoid syndrome (CS) symptoms and quality of life (QoL) in CS patients treated with somatostatin analogs (SSAs): Results from longitudinal patient surveys.
Authors: Halperin Daniel M. , Huynh Lynn , Beaumont Jennifer L , Cai Beilei , Bhak Rachel , Narkhede Sahil , Duh Mei Sheng , Neary Maureen , Cella David 
Published: January 2019

400 Background: Limited information is available on the longitudinal impact of CS symptoms and QoL in CS patients (pts) who received SSAs in real-world setting. This study aimed to examine change in CS symptoms and QoL in CS pts treated with SSAs using the validated FACT-G instrument. Methods: Pts with CS symptoms in the US were recruited through an advocacy group to complete a two-part, anonymous online survey. Time point 1 (T1) survey was fielded from July-October 2016 and time point 2 (T2) was administered 6 months later. Eligible pts were ≥ 18 years old with CS symptoms and treated with SSA or non-SSA. Analyses were performed to assess change in FACT-G QoL scores between T1 and T2. Severity ratings of CS symptoms in the past month were classified as mild, moderate, severe, or not applicable. Duration of SSA treatment was categorized as ≤ 2, > 2-5, and > 5 years. Results: Among 89 pts who completed T1 and T2 surveys, 98% were treated with SSA (T1 or T2; median duration of 5 years). Higher proportion of pts in T2 did not report diarrhea (16% vs. 7%, p < 0.05) or flushing (28% vs. 18%, p < 0.05) vs. T1. Among pts treated with SSAs for ≤ 2, > 2-5 and > 5 years, mean change in FACT-G total score was +3.7, 0.0, and -1.2, respectively. Pts treated with SSAs for ≤ 2 years showed a clinically relevant improvement in QoL on FACT-G by exceeding the minimal important difference (MID) of > 3.0. Additionally, in a subgroup of pts who experienced improvement in flushing (N=17) and diarrhea (N=31), a mean change of +3.0 in FACT-G total score was observed for flushing, indicating better QoL, whereas a nominal mean change was reported for diarrhea. Pts whose flushing and diarrhea symptoms worsened had a mean change of -2.2 and -1.2 in FACT-G total score, respectively, showing worsened QoL. Conclusions: This longitudinal survey study showed that improvement in flushing resulted in positive benefit in QoL, while worsening of flushing/diarrhea resulted in decline in QOL. Improvement in CS symptoms and QoL was most pronounced in the early years after SSA treatment initiation. Less impact on change in QoL may be observed in later years possibly due to disease progression and late-effects of cancer treatment.
Predictors of recurrence in patients with surgically resected pancreatic neuroendocrine tumors.
Authors: Harris Cynthia , Kim Michelle Kang , Baeg Kiwoon Joshua , Lee Mi Ri , Starr Julie , Brais Lauren K. , Ward Stephen , Stashek Kristen , Chan Jennifer A. , Labow Daniel M. , Sarpel Umut , Schwartz Myron E. , Sung Max W. , Wisnivesky Juan P. , Warner Richard R. P. , Metz David C. , Kulke Matthew H. 
Published: January 2019

408 Background: Current surveillance guidelines regarding follow up of patients with resected pancreatic neuroendocrine tumors (PNETs) are based on limited data, and there have been few studies evaluating recurrence risk in such patients. We assessed disease-free survival (DFS) in a large, multi-institutional cohort of patients with resected PNETs. Methods: Patients with surgically resected, non-metastatic PNETs between 1990-2017 were identified using institutional databases at three institutions: Mount Sinai Hospital, Dana-Farber Cancer Institute, and University of Pennsylvania. Recurrence date was defined as the imaging date documenting first recurrence (n = 56); if an imaging date was not available, then July 1 of that year was used in calculations (n = 9). Kaplan-Meier analysis was used to estimate DFS; multivariate Cox regression analysis was used to assess DFS adjusted for patient and disease-related characteristics, including tumor stage and grade. Results: We identified a total of 418 patients with surgically resected, non-metastatic PNETs between 1990-2017. Of these patients, 299 patients had complete stage and tumor grade information and were used for subsequent analysis. Patients were 48.6% male with a median age of 57.5 years at time of surgery. The distribution of AJCC stage and grade was as follows: 170 (56.9%) patients were stage I, 129 (43.1%) were stage II; 167 (55.9%) had grade 1, 121 (40.5%) had grade 2, and 11 (3.7%) had grade 3 tumors. Median follow-up was 2.6 years (interquartile range = 4.2); during this time, 65 (21.7%) patients developed disease recurrence. After adjusting for potential confounders, patients with more advanced stage and higher tumor grade were significantly more likely to develop disease recurrence (Hazard Ratio (HR): 6.9, 95% CI: 2.5-19.1 for stage II; HR 4.0 (1.7-9.5) for grade 2; HR 2.6 (0.4-17.8) for grade 3). Both higher stage and tumor grade were associated with decreased DFS (p < 0.0001 for both). Conclusions: In surgically resected PNETs, with a median follow-up time of 2.6 years, both higher stage and higher grade are associated with decreased DFS. Further follow up of this cohort is planned.
Predictive factors of submucosal fibrosis before endoscopic submucosal dissection for superficial squamous esophageal neoplasia.
Authors: Kim Byung Wook 
Published: January 2019

41 Background: Endoscopic submucosal dissection (ESD) is an effective treatment modality for superficial squamous esophageal neoplasia (SSEN). However, submucosal fibrosis is an important obstacle to successful ESD. The aim of this study was to determine the ESD outcome in relationship to the degree of submucosal fibrosis of SSEN and to identify factors for predicting submucosal fibrosis. Methods: We retrospectively analyzed endoscopic and pathologic factors related to submucosal fibrosis in 41 patients with SSEN who underwent ESD. Also, en bloc resection, complication rate, and procedure time according to the degree of submucosal fibrosis were evaluated. Masson’s trichrome staining was used to evaluate histologic submucosal fibrosis. Results: A depressed type tumor (vs. nondepressed type tumor, P= 0.002), longer diameter of tumor greater than 20 mm (vs. longer diameter of tumor ≤ 20mm, P= 0.036), and delayed ESD after initial diagnosis (vs. immediate ESD after initial diagnosis, P= 0.005) were independent factors predictive of submucosal fibrosis. The severity of submucosal fibrosis was significantly associated with a higher complication rate such as bleeding and perforation. Also, as the severity of the submucosal fibrosis increased, the amount of time required for the ESD procedure increased. Conclusions: Longer diameter of tumor greater than 20 mm and macroscopic depression are endoscopic predictive factors of submucosal fibrosis in SSEN. Moreover, to avoid submucosal fibrosis, ESD should be attempted immediately after biopsy for the diagnosis of SSEN.
Subgroup analysis by baseline (BL) weight-associated parameters: A phase III study of liposomal irinotecan (nal-IRI)±5-fluorouracil/leucovorin (5-FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based (gem) therapy.
Authors: Macarulla Teresa Mercade , Hubner Richard , Blanc Jean-Frédéric , Wang-Gillam Andrea , Li Chung-Pin , Bodoky Gyorgy , Dean Andrew Peter , Yanshen Shan , Jameson Gayle S. , Lee Kyung-Hun , Chiu Chang-Fang , Schwartsmann Gilberto , Braiteh Fadi S. , Cunningham David , Chen Li-Tzong , Von Hoff Daniel D. , Mamlouk Khalid Kevin , de Jong Floris A , Siveke Jens T. 
Published: January 2019

410 Background: We report prognostic evaluation of BL weight-associated parameters (body-mass index [BMI], body surface area [BSA] and weight) in pts with mPDAC after progression following gem-based therapy (NAPOLI-1 trial; NCT01494506). Pts received nal-IRI+5-FU/LV, nal-IRI monotherapy or 5-FU/LV in NAPOLI-1, an international, randomised, phase 3 trial; nal-IRI+5-FU/LV treatment resulted in a 45% increased median OS vs. 5-FU/LV (unstratified HR = 0.67; p = 0.012). Methods: This exploratory subgroup analysis compares outcomes by BL BMI, BSA and weight, using primary survival analysis data from the ITT population for all treatment arms combined (n = 417) and the nal-IRI+5-FU/LV arm on its own (n = 117). Results: OS and PFS were not significantly different between BL BMI, BSA and weight median subgroups in the entire NAPOLI-1 ITT population (HR range 1.06–1.15; log-rank p-value range 0.21–0.60; Table) and in the nal-IRI+5-FU/LV arm (HR range 0.94–1.19; log-rank p-value range 0.43–1.00). Conclusions: This post-hoc subgroup analysis did not detect any prognostic impact on treatment outcome by BL BMI, BSA and weight for mPDAC pts progressed following gem-based therapy. This observation rules out a treatment-independent effect. No evidence of a predictive effect on nal-IRI+5-FU/LV efficacy was found. Clinical trial information: NCT01494506. [Table: see text]
Folfirinox (FFX) versus gemcitabine with nab‐paclitaxel (GNP) in the first line treatment (1LTx) of metastatic pancreatic cancer (mPC): A tertiary center experience.
Authors: Barrera Ivan , Hamalova Sabina , Ranger Jill , Rho Henry , Mamo Aline , Batist Gerald , Kavan Petr 
Published: January 2019

414 Background: The efficacy of FFX and GNP as 1LTx of mPC were established in phase 3 trials against Gemcitabine alone. However, no head‐to‐head trial has been performed. This analysis was conducted to compare the use of the two regimens in the 1LTx of mPC patients (pts). Methods: Retrospective study collected data of pts diagnosed with mPC (ECOG 0‐1) that received FFX or GNP as 1LTx at the Jewish General Hospital between 2010‐2016. Pt selection for 1LTx was based in ASCO Guidelines 2016 Criteria (AGC2016). Progression free survival (PFS) and overall survival (OS) were estimated using a Kaplan Meier method. Rate of 1LTx discontinuation and start of 2LTx was compared using two‐sided Fisher's exact test. Results: Among 75 pts with mPC (median age 69), 44 (59%) received FFX and 31 (41%) received GNP. In the FFX group 57% were male and 24 pts (55%) had primary tumors localized in the pancreatic head (PTPH). The majority of patients [n = 36 (82%)] had ECOG 1 at the start of FFX. The most common grade 3‐4 adverse events (AEs) were gastrointestinal symptoms (GI) [n = 12 (27%)], neutropenia (N) [n = 9 (20%)], fatigue (F) [n = 5 (11%)], and peripheral sensory neuropathy (PSN) [n = 2 (4%)]. In the GNP group 61% were male and 20 pts (65%) had PTPH. The majority of pts [n = 23 (74%)] had ECOG 1 at the start of GNP. The most common grade 3‐4 AEs were F [n = 8 (26%)], N [n = 4 (13%)], GI [n = 3 (10%)], and PSN [n = 2 (7%)]. Similar rates of 1LTx discontinuation due to AEs were seen in both groups: 5 pts (11%) in the FFX group due to GI, 2 pts (6.5%) in the GNP group due to F (p = 0.69). In the FFX cohort, 68.2% (30/44) went on to 2LTx whereas in the GNP cohort, 32% (10/31) received 2LTx (p = 0.0001). Of the FFX cohort receiving 2LTx, 40% (12/30) received GNP. The median PFS for the FFX and GNP groups were 5.75 and 4.63 months, respectively, and were not statistically significant (p = 0.523). The OS with FFX and GNP was 9.23 vs. 6.6 months (p = 0.09). Conclusions: For pts selected as per ASC2016, FFX and GNP cohorts showed similar PFS, OS, AEs, and 1LTx discontinuation rate. Our data highlight the importance of optimal therapeutic sequencing to prolong OS. A randomized trial will be needed to confirm 1LTx in mPC.
Clinical implication of nutrition for neoadjuvant therapy and impact of nutritional support in pancreatic cancer.
Authors: Tashiro Mitsuru , Yamada Suguru , Fujii Tsutomu , Hattori Norifumi , Takami Hideki , Suenaga Masaya , Niwa Yukiko , Hayashi Masamichi , Iwata Naoki , Kanda Mitsuro , Tanaka Chie , Kobayashi Daisuke , Nakayama Goro , Sugimoto Hiroyuki , Koike Masahiko , Fujiwara Michitaka , Kodera Yasuhiro 
Published: January 2019

416 Background: Several studies have shown that nutritional support is important to reduce chemotherapy-related toxicities and improve tolerance to chemotherapy, but little is known about the nutritional influence of neoadjuvant therapy (NAT) for pancreatic cancer. The aim of this study was to assess the influence of NAT on nutritional status and the effectiveness of postoperative nutritional support in patients with NAT for pancreatic cancer. Methods: Between 2010 and 2017, 169 consecutive patients who underwent pancreatoduodenectomy of pancreatic cancer were enrolled, and divided into the neoadjuvant group (NAG, n = 70) and the control group (CG, n = 99). We assessed the change of nutritional index (body weight, albumin and rapid turnover proteins; retinol binding protein, prealbumin and transferrin), inflammatory index, and inflammation-based prognostic scores during NAT. Perioperative change of rapid turnover proteins at the point of pre-operation, postoperative day (POD) 5, POD12 and POD21, and perioperative and oncological outcomes between NAG and CG were evaluated. Finally, we divided NAG into nutrition group (n = 27) who received postoperative enteral immunonutrition from POD 1 to POD 21 and without nutrition group (n = 41), and compared perioperative change of rapid turnover proteins between two groups. Results: After NAT, the retinol binding protein, prealbumin, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and prognostic nutrition index significantly got worse in NAG (P < 0.05). The recovery of rapid turnover proteins after POD5 was significantly worse in NAG compared to CG (P < 0.05). There was no significant difference in the incidence of postoperative complications and time to adjuvant therapy between two groups. The recovery of retinol binding protein and prealbumin after POD12 was significantly better in nutrition group compared to without nutrition group (P < 0.05). Conclusions: NAT for pancreatic cancer could decrease nutritional status and its postoperative recovery. Postoperative enteral nutrition could be effective in patients with NAT for pancreatic cancer. Based on these results, we plan to perform the nutritional support at earlier stage of therapy.
Effect of cytoreductive surgery and HIPEC on survival in comparison to palliative chemotherapy for biliary carcinoma with peritoneal metastasis: A multi-institutional cohort from PSOGI and BIG RENAPE groups.
Authors: Mercier Frederic , Amblard Iris , Bartlett David L. , Levine Edward Allen , Baratti Dario , Piso Pompiliu , Morris David L. , Rau Beate , Tentes Antonios Apostolos K , Tuech Jean-Jacques , Quenet Francois , Akaishi Eduardo Hiroshi , Pocard Marc , Yonemura Yutaka , Lorimier Gerard , Delroeux Delphine , Villeneuve Laurent , Glehen Olivier , Passot Guillaume 
Published: January 2019

418 Background: Peritoneal metastasis from biliary carcinoma (PMC) is associated with poor prognosis when treated with chemotherapy. The objective was to evaluate the impact on survival of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and compare with conventional palliative chemotherapy for patients with PMC. Methods: A prospective multicenter international database was retrospectively searched to identify all patients with PMC treated with a potentially curative CRS/HIPEC (CRS/HIPEC group). The overall survival (OS) was compared to patients with PMC treated with palliative chemotherapy (systemic chemotherapy group). Survival was analyzed using Kaplan-Meier method and compared with Log-Rank test. Results: Between 1995 and 2015, 34 patients were included in the surgical group, and compared to 21 in the medical group. In the surgical group, median peritoneal cancer index was 9 (range 3-26), macroscopically complete resection was obtained for 25 patients (73%). There was more gallbladder localization in the surgical group compared to the medical group (35% vs. 18%, p= 0.001). Median OS was 21.4 and 9.3 months for surgical and medical group, respectively (p =0.007). Three-year overall survival was 30% and 10% for surgical and medical group, respectively. Conclusions: Treatment with CRS and HIPEC for cholangiocarcinoma with peritoneal metastasis is feasible and may provide survival benefit when compared to palliative chemotherapy.