bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute and chronic deterioration in liver function after transarterial radioembolization (TARE) in US patients (pts) with hepatocellular carcinoma (HCC).
Authors: Miksad Rebecca A. , Piscaglia Fabio , Xia Fang , Fellous Marc Mardoche , Ogasawara Sadahisa 
Published: January 2019

439 Background: TARE is available in several countries for the treatment of hepatic malignancies, including unresectable HCC. Liver function deterioration in pts treated with TARE has been reported in real-world practice but less is known about incidence at a national US level. To better understand the prevalence of liver function deterioration after TARE, a retrospective analysis was performed using a database of US HCC pts. Methods: HCC pts treated with index TARE between Jan 1, 2010 and Dec 31, 2015 were identified in Optum’s integrated database using standard codes. Eligible pts had at least one laboratory (lab) value at baseline ( < 30 days before TARE), acute period ( < 30 days post TARE), and chronic period (90–180 days post TARE) and did not undergo additional/repeat HCC treatment before any further lab test in the chronic period. Due to lack of universally accepted criteria for liver function deterioration, clinically meaningful lab parameter changes were predefined by experts (Table). Changes in liver function from baseline were assessed in the acute and chronic periods. Results: Of 790 Optum TARE pts, 78 (10%) were eligible. Majority of pts were excluded due to lack of lab data and due to additional HCC treatments prior to lab tests in the chronic period. 50 (64%) were male and median age was 66 yrs. At baseline, 20 pts (26%) had extrahepatic spread (EHS). The incidence of liver function deterioration varied by parameter (Table). Albumin was the parameter most likely to be changed in both the acute and chronic periods. Conclusions: Although anti-tumor effects are thought to be optimized about 3 months after TARE, this retrospective, post-hoc, real-world analysis demonstrated decreased liver function 90–180 days after TARE. TARE, a liver-directed therapy, was used in some pts with EHS. Limitations include missing data, small sample size, and difficulty establishing causation. These results suggest that chronic liver function deterioration 90–180 days after TARE may be observed in some HCC pts. [Table: see text]
Genomic alterations (GA) predicted to confer lack of benefit from trastuzumab in advanced esophagogastric cancers (EGC): Analysis of 527 HER2-amplified (HER2amp) cases.
Authors: Klempner Samuel Jacob , Chao Joseph , Bailey Mark , Kim Seung Tae , He Jie , Lipson Doron , Ali Siraj Mahamed , Miller Vincent A. , Ross Jeffrey S. , Lee Jeeyun , Schrock Alexa Betzig 
Published: January 2019

44 Background: The addition of trastuzumab to chemotherapy improves survival in first line treatment of advanced HER2 overexpressing EGC. However, the response rate is under 50% in this molecularly heterogeneous group of cancers. Genomic alterations (GA) associated with lack of benefit from trastuzumab are understudied. Methods: We prospectively analyzed clinical samples from patients with EGC using hybrid-capture based comprehensive genomic profiling (CGP). Pre-specified literature review was used to determine GA associated with de-novo trastuzumab resistance. Results: From 2,245 gastroesophageal junction (GEJ) adenocarcinomas and 1,883 gastric adenocarcinomas (GC) we identified 395 HER 2-amplified GEJ (18%) and 132 HER 2-amplified (HER2amp) GC (7.0%) cases. Median HER 2 copy number was 19 in GEJ and 16 in GC samples. PIK3CA GA and METamp were observed in ~9% and ~5% of both HER 2amp and non- HER2amp EGC cases; however, co-amplification of cell-cycle mediators CDK6 and CCCNE1 were each significantly enriched in HER 2amp cases (Table). MYCamp and deleterious SMAD4 GA were also significantly enriched in cases with Her2amp. CDKN2A GA were common regardless of HER 2amp, particularly in GEJ . In cases with >100 estimated HER 2 copies, only PIK3CA GA were significantly less frequent than in those with 6-99 copies (2.3% vs. 9.8%, P =0.04). All HER 2amp cases were microsatellite stable. A clinically annotated HER 2amp cohort will be presented. Conclusions: GA predicted to decrease trastuzumab sensitivity exist in a significant portion of HER 2amp EGC, although not all are enriched relative to non- HER 2amp cases. CGP may provide additive information to traditional HER2 testing and identify patients less likely to benefit from therapy. Larger clinical datasets are needed to validate our observations. [Table: see text]
Changes in liver function following real-world transarterial chemoembolization (TACE) in US patients (pts) with hepatocellular carcinoma (HCC): The LiverT study.
Authors: Miksad Rebecca A. , Ogasawara Sadahisa , Xia Fang , Fellous Marc Mardoche , Piscaglia Fabio 
Published: January 2019

441 Background: Acute elevations of serum transaminases and bilirubin after TACE are commonly observed in pts with HCC. However, real-world incidence of chronic liver damage after TACE is unclear. LiverT is a retrospective, observational study to assess potential chronic deterioration of liver function of HCC pts after a single TACE in US real-world practice. Methods: Eligible HCC pts underwent index TACE between Jan 1, 2010 and Mar 31, 2016 and did not undergo repeat/additional HCC treatment in the subsequent 90 days. Pts were identified from Optum’s integrated database using standard codes. At least one laboratory value was required within 30 days prior to index TACE (baseline = latest value within period) and 30–90 days after TACE (chronic period = latest value within period). Due to lack of universally accepted liver function deterioration criteria, clinically meaningful changes in laboratory parameters were predefined by experts (Table). Subgroup analyses explored the impact of HCC etiology, diabetes status, anticoagulation use, and presence of portal vein thrombosis. Results: Of 5142 Optum TACE pts, 572 (11%) were eligible; exclusions were primarily due to lack of HCC diagnostic code and laboratory availability; 411 (72%) were male and median age was 62 yrs. Although lower than acute liver deterioration (0–29 days post-TACE), 30–90 day chronic liver deterioration varied by parameter and ranged from 15% to 31% (Table). Overall, sub-groups showed similar patterns. Conclusions: We report real-world chronic deterioration of liver function 30–90 days after a single TACE in a cohort of HCC pts. Limitations include missing data, small sample size, and difficulty establishing causation. Subsequent HCC treatments may be limited by liver function; therefore, further characterization of post-TACE chronic deterioration of liver function for HCC is important. [Table: see text]
Stereotactic-body radiotherapy for portal vein tumor thrombosis in hepatocellular carcinoma patients.
Authors: Jeong Bae Kwon , Choi Hoon Sik , Kang Ki Mun , Jeong Hojin , Lee Yun Hee , Ha In Bong , Song Jin Ho 
Published: January 2019

442 Background: Portal vein tumor thrombosis (PVTT) is commonly accompanied by hepatocellular carcinoma (HCC) patients, and in these cases the treatment options became limited and treatment outcome was poor. Stereotactic body radiotherapy (SBRT) is one of the possible treatment options, which can deliver higher doses with highly conformal target have conducted for treatment of PVTT. However, only few studies about the SBRT have reported, even treatment schedules were not consistent. In this study, we report our institutional experience of treating PVTT in HCC patients using SBRT. Methods: 24 HCC patients with PVTT were treated with SBRT at our institution. All patients had unresectable HCC with PVTT, baseline liver function of Child-Pugh class A or B. SBRT was performed by Cyberknife based on 4D-simulation and 4D-planning. The prescription dose was 45 Gy in 3 fractions in 17 (70.8%) patients, and was modified to 39 to 42 Gy in 3 to 4 fractions in 7 (29.2%) patients whose target was large or adjacent to the bowel. After SBRT, transarterial chemoembolization (TACE) was performed in 16 (66.7%) patients within 3 months. Results: There were 2 (8.3%) patients of PVTT showed complete response, and 11 (45.8%) patients showed partial response. Stable disease was found in 7 (29.2%) patients, and progression in 4 (16.7%) patients. The response rate was lower in patients with tumor thrombus at main portal vein than those at branch of portal vein (main, 30% vs. branch, 71.4%, p = 0.052). The 1- and 2-year overall survival (OS) was 67.5%, 48.2%, respectively, with median survival of 20.8 months. The combination SBRT followed by TACE, and presence of grade 3 hepatic toxicities impacted on survival. The 1-year OS was 71.4% in patients whom TACE was combined after SBRT, which was higher than that of 14.6% who were treated with SBRT alone (p < 0.001). The 1-year OS was 81.1% in patients who did not occur grade 3 hepatic toxicity, while 0% in patients who had grade 3 hepatic toxicity (p = 0.002). Conclusions: SBRT is a relatively effective treatment option for HCC patients of PVTT. Especially combined with TACE. Finding an optimal dose schedule which can reduce hepatic toxicity, while keeping the response seems important to increase the survival.
BCLC subclassification and tumour characteristics to provide prognostication of outcomes in an Asian population of locally advanced hepatocellular carcinoma treated using selective internal radiation therapy with Yttrium-90.
Authors: Mathew Eshani Nastassia , Nadkarni Nivedita , Choo Su-Pin , Toh Han Chong , Tai David Wai-Meng , Goh Brian , Chung Alexander , Chan Chung Yip , Ng David , Goh Anthony , Lo Richard , Venkatanarasimha Nanda , Gogna Apoorva , Too Chow Wei , Abdul Latiff Julianah Bee , Thng Choon Hua , Chow Pierce K. H. 
Published: January 2019

443 Background: Selective internal radiation therapy (SIRT) with Yttrium-90 (Y90) is preferentially used in locally advanced hepatocellular carcinoma (HCC) patients in the Barcelona clinic liver cancer (BCLC) B or C cohort. However, the BCLC B cohort has a wide heterogeneity. To address this, Bolondi et al. proposed a BCLC B subclassification system. Additionally, the BCLC C cohort is also diverse in their Child-Pugh (CP) stage and extent of portal vein thrombosis (PVT). The effect of these subclassifications on survival outcomes has not been studied in HCC patients treated using SIRT. Methods: 392 HCC patients treated using SIRT from 1st January 2008 to 17th March 2017 were analyzed. These patients were classified according to the proposed subclassification system for the BCLC B cohort, and CP stage for the BCLC C cohort, and their survival outcomes reviewed. Results: 293 patients met the study’s inclusion criteria. For B1/B2/B3/B4/ C CP-A and C CP-B, the median OS was 48.3/28.7/14.4/13.7/12.8 and 6.6 months respectively. Overall comparison between the subgroups for median OS reached statistical significance (p < 0.001). The Cox proportional-hazards regression analysis found that tumour location defined as unilobar or bilobar disease significantly influenced median OS. In the BCLC C cohort, the extent of portal vein invasion significantly influenced median OS (p < 0.001). For the BCLC C CP-A group, median OS for segmental/sectoral branch invasion, right and/or left portal vein invasion and main portal vein trunk invasion was 24.1, 12.8 and 6.5 months respectively. Conclusions: Bolondi et al.’s subclassification system optimizes prognostic prediction by reducing the clinical heterogeneity in BCLC B HCC patients treated using SIRT. However tumour location, unaccounted for in the proposed subclassification, is also an important prognosticator. For the BCLC C cohort CP stage, extent of PVT, and tumour location were important predictors of treatment outcomes.
Safety and efficacy of the selective FGFR inhibitor debio 1347 in phase I study patients with FGFR genomically activated advanced biliary tract cancer (BTC).
Authors: Cleary James M. , Voss Martin Henner , Meric-Bernstam Funda , Hierro Cinta , Heist Rebecca Suk , Ishii Nobuya , Kirpicheva Yulia , Nicolas-Metral Valerie , Pokorska-Bocci Anna , Vaslin Anne , Venetz Werner , Zanna Claudio , Flaherty Keith , Tabernero Josep , Baselga Jose 
Published: January 2019

447 Background: BTC are aggressive tumors with limited treatment options and poor overall survival. Aberrant FGFR signaling has been implicated in BTC carcinogenesis. Debio 1347 is an orally available selective FGFRi with potent antitumor effect in preclinical model bearing FGFR alterations. Debio 1347 showed encouraging preliminary clinical activity and manageable treatment-emergent adverse events (TEAE) in its first-in-human (FIH) ph1 study (NCT1948297) dose-escalating part. Here we report only results from the BTC pts of this study. Methods: This FIH study enrolled pts with advanced solid malignancies harboring defined activating alterations of FGFR 1, 2, or 3: amplifications (amp), mutations (mut) and translocations (trans). Pharmacokinetics (PK) and pharmacodynamics were serially evaluated in blood, skin and/or tumor tissue. A confirmatory post-hoc analysis was performed centrally for all available biopsies. Results: Eight pts, six with intrahepatic cholangiocarcinoma (iCCA) and two with gallbladder cancer (GBC), were treated with Debio 1347 at doses between 60 and 150 mg orally daily in 28-day cycles. Among the iCCA pts, one had an FGFR2mut, one had an FGFR2 activating deletion (del), and one had an FGFR3mut; the other three had FGFR2trans. One of the two GBC pts had an FGFR3trans, the other one an FGFR2mut. All pts had prior systemic therapy (mostly 2 or 3 lines). The most common TEAEs were hyperphosphatemia (8/8), nail changes (5/8), nausea (5/8), dry mouth (4/8) and stomatitis (3/8). No grade ≥ 3 related TEAE were reported except grade 3 hyperphosphatemia (4/8). PK was comparable to that in pts with other solid malignancies.A partial response lasting up to 48 weeks was observed in an iCCA pt (FGFR2 del exon 5); three additional iCCA pts (FGFR2trans: ROCK1; KIAA1217; DDX21) and one GBC pt (FGFR3-TACC3 trans) had target lesions regression < 30% and stayed on trial between 24 – 37 weeks. Overall disease control was 62.5%. Conclusions: These results suggest that BTC pts with genomic events leading to activation of FGFR2/3 may benefit from treatment with Debio 1347. Further study is ongoing in the expansion cohort of this trial. Clinical trial information: NCT1948297.
Second-line chemotherapy for gallbladder cancer.
Authors: Wongjarupong Nicha , Hassan Mohamed Abdelrahim Muddathir , Sanhueza Cristobal T. , Hartgers Mindy L. , Hassan Fatima , Roberts Lewis R. , Mahipal Amit 
Published: January 2019

450 Background: The standard treatment for patients with gallbladder cancer is a combination of gemcitabine and cisplatin based on ABC-02 trial. However, there are no guidelines regarding treatment after first-line therapy. We retrospectively analyzed the efficacy and overall survival of different second-line regimens. Methods: We identified 203 patients with advanced gallbladder cancer who received palliative treatment between January 2000 and December 2015 at Mayo Clinic, Rochester. RECIST criteria was used to assess response. Results: 68 patients received second-line chemotherapy. Median age was 63 years (range: 32-86) and majority were males (60.6%). The median time from the diagnosis to the start of the second line chemotherapy was 8 (1-120) months. The most common used second-line chemotherapy were FOLFOX (14), gemcitabine alone (10), single agent fluoropyrimidine (11), gemcitabine with capecitabine (5), and capecitabine with oxaliplatin (4). There were 30 patients that received 5-fluorouracil based regimens, 20 patients received gemcitabine-based regimen, 3 patients received taxane-based regimen, and 15 patients received other types of chemotherapy. Median progression free survival and overall survival was 2.1 (1.8-2.7) and 16.7 (13.2-21.3) months respectively. There were 10 (52%), 11 (37%), 2 (67%), 5 (33%) with partial response and stable disease in 5-fluorouracil-based, gemcitabine-based, taxane-based, and others, respectively. There were no difference in PFS, with median PFS of 2.5, 2.0, 2.8 and 2.3 months, respectively (p=0.43). The overall survival were 15.7 (8.9-40.2), 15.0 (10.7-21.3), 40.3 (22.0-47.0), and 20.4 (9.2-30.7) months, respectively (p=0.83). There were 27 patients that received single agent chemotherapy and 41 patients that received combined regimen. There were 17 (42%) patients and 13 (48%) patients with partial response or stable disease in single and combined regimen. There were no differences in progression free survival and overall survival between single and multi agent chemotherapy. Conclusions: In this largest single institution study, second-line chemotherapy regimens for gallbladder cancer provided benefit in select patients and there is an urgent need to develop more active therapeutic regimens.
Pancreatic exocrine insufficiency (PI) secondary to chronic use of long-acting (LA) somatostatin analogues (SA) in patients (pts) with gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
Authors: Saif Wasif M. , Smith Melissa H , Romano Alicia , Patel Rachna , Relias Valerie 
Published: January 2019

454 Background: SA are used in GEP-NETs and acromegaly. Side effects of SAs include biliary disorders, gastrointestinal disorders, injection-site pain and hyperglycemia. PI is often misdiagnosed as disease progression or failure to SA or diagnosed after a delay in pts receiving SA. We present our experience with PI developing in pts following chronic use of SA. Methods: Retrospective chart and pharmacy review of GEP-NETs pts (6/2009 - 6/2017) was completed. Data including demographics, dose/duration of long and short-acting SA, antidiarrheal, pancreatic enzyme replacement (PER), proton pump inhibitors (PPI), chromogranin A (CgA), urine 5-HIAA and quantitative fecal fat test (QFFT) was collected. Results: 110 GEP-NETs pts (Med. age: 56 yr) were identified. 104 pts received LA Octreotide acetate and 6 Somatuline Depot Injection. Of these, 23 received SA octreotide for worsening diarrhea, 96 had intensification of antidiarrheal and 1 got telotristat ethyl. 79 pts were evaluated by nutritionist and/or gastroenterology. QFFT was performed in 47 pts with worsening diarrhea despite stable or improved CgA/urine 5-HIAA. 19 had evidence of steattorrhea and received PER at a dose of 72,000 lipase units per meal. 13 received PPI concomitantly while 6 started when symptoms did not improve with PER. In addition, low fat diet was recommended. 14 of 19 had improvement in diarrhea within 4-8 weeks. 2 pts were non-compliant and 3 were found to have motility disorders. Deficiency of vitamins and trace elements was found in 11 of 19 pts, who received supplementation. Conclusions: Our experience constitutes first study addressing PI as a rare but serious complication of chronic use of SA. Although SA are used to treat diarrhea, paradoxically they can worsen diarrhea secondary to PI. It is believed that SA may inhibit secretion and release of hormones (amylase, trypsin, lipase, secretin, CCK, motilin, bile acid) leading to PI. Early recognition and diagnosis of this under-diagnosed and under-reported side effect of SA can improve not only diarrhea and weight in these pts but also can reduce cost of using short-acting SA and antidiarrheal.
SM-88 therapy in patients with advanced or metastatic pancreatic cancer.
Authors: Hoffman Steve , Stega Jeanetta , Zawisny Patricia , Gostout Zachary , Del Priore Giuseppe , Loushin Maria , Taylor Ben R 
Published: January 2019

457 Background: SM-88 (tyrosine derivative, mTOR inhibitor, CYP3a4 inducer and oxidative stress catalyst) is a relatively non-toxic, targeted therapy that utilizes the Warburg Effect in combination with oxidative stress to cause tumor cell death. Previously reported results (Phase I and preliminary Phase II) showed safety and efficacy for SM-88 in metastatic and recurrent cancers. Pancreatic cancer continues to have a poor prognosis with toxic standard of care (SOC) therapies, associated serious adverse events (SAEs), and QOL degradation. SM-88 is being evaluated as a minimally toxic alternative treatment. Methods: Retrospective chart review between 2012-17 of 12 patients with advanced or metastatic pancreatic cancer treated with SM-88 through a Phase 1 study (3/12) or compassionate use (9/12) with 10/12 evaluable. Although treatment regimens specifics varied, all were provided SM-88 therapy five days a week, administered by clinicians, orally or through subcutaneous injection; 7/10 patients received SM-88 mono therapy; and 3/10 received combination therapy (5FU-based). Results: 40% (4/10) of patients achieved survival benefit of greater than one year (mean 12.2 mo) (see table). Monotherapy patients maintained or improved ECOG PS and did not experience drug-related SAEs during treatment. 2/10 patients achieved partial responses. One patient maintained rPFS for 13 months despite positive margins post-surgery and elevated CA19.9 levels. Conclusions: SM-88 appears well tolerated and demonstrated notable survival times in comparison to expected SOC therapies. In addition, several of the patients demonstrating benefit had baseline ECOG PSs of 2, for which current SOC is palliative care only. For further evaluation, a North American Phase II trial in recurrent pancreatic cancer has been initiated. [Table: see text]
Second-line treatment of modified FOLFIRINOX or nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma.
Authors: Ozaka Masato , Sasaki Takashi , Yamada Ikuhiro , Kanata Ryo , Akiyama Dai , Katagiri Tomoko , Takano Koichi , Matsuyama Masato , Sasahira Naoki 
Published: January 2019

458 Background: Both FOLFIRINOX (FFX) and Nab-paclitaxel plus Gemcitabine(GnP) standard treatment in first-line treatment of metastatic pancreatic adenocarcinoma (MPA). It could be of interest to use them consecutively, knowing that there is currently no standard for second-line treatments for MPA. The aim of this study was to compare second-line modified FFX (mFFX) after GnP failure with second-line GnP after mFFX failure. Methods: From January 2015 to Jul 2017, medical records were retrospectively reviewed for consecutive patients receiving mFFX or GnP for a histologically proven MPA after failure of GnP or mFFX respectively. Patients were treated with mFFX (intravenous oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, 5-FU infusion 2,400 mg/m2 over 46 h, no bolus 5-FU) or GnP (Gemcitabine 1000 mg/m2/, nab-paclitaxel 125mg/m2 d1,8 15) until disease progression, patient refusal or unacceptable toxicity. Results: Second-line mFFX was administered to 50 patients and GnP was 25 patients. At baseline of second-line treatment, there was no difference in patient’s characteristics between mFFX group and GnP group. No significant difference in the response rate (mFFX, 16.6% vs. GnP, 10.5%, P = 0.63) or the disease control rate (mFFX, 50% vs. GnP, 64%, P = 0.82) was seen between the two groups. Median Progression free survival of GnP/mFFx were 4.3 months/4.6 months (p=0.89) and median survival (OS) from the 2nd line treatment of GnP/mFFx were 10.4 months/10.8 months (p=0.65) and OS from the first-line treatment of GnP/mFFx were 20.6 months/16.5 months (p=0.34). No toxic death occurred in both groups. There was no difference in the incident of adverse event between mFFX group and GnP group. Conclusions: Second-line mFFX and GnP achieved similar disease control and survival in unresectable pancreatic cancer. The use of the FFX and GnP in sequence is an attractive option to maximize disease control and survival. We need the clinical trial to compare with mFFX and GnP in sequence to guide the selection of initial chemotherapy.