bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of baseline hepatitis B viremia and management on outcomes in patients (Pts) with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP): Outcomes from REACH-2.
Authors: Galle Peter R. , Kudo Masatoshi , Llovet Josep M. , Finn Richard S. , Karwal Mark , Pezet Denis , Kim Tae-You , Yang Tsai-Sheng , Zagonel Vittorina , Tomasek Jiri , Phelip Jean Marc , Touchefeu Yann , Koh Su-Jin , Stirnimann Guido , Wang Chunxiao , Ogburn Kenyon , Abada Paolo , Widau Ryan C. , Zhu Andrew X. 
Published: February 2020

569 Background: REACH (NCT01140347) and REACH-2 (NCT02435433) were global, randomized, blinded, placebo (PL)-controlled phase 3 trials of ramucirumab (RAM) in pts with advanced HCC following sorafenib. REACH-2 limited enrollment to pts with AFP ≥400 ng/mL, and met its primary OS endpoint, consistent with the prespecified REACH subgroup with baseline AFP ≥400 ng/mL. Analysis of pooled individual pt data from REACH (AFP ≥400 ng/mL) and REACH-2 showed improved OS with RAM vs PL for pts with hepatitis B virus (HBV) etiology (7.7 vs 4.5 mos; HR 0.74, 95% CI 0.55, 0.99). Here we investigate survival and liver function in REACH-2 pts with HBV etiology tested for serum HBV DNA. Methods: Pts had advanced HCC, Child-Pugh A, ECOG PS 0/1, AFP ≥400 ng/mL, prior sorafenib treatment, and were randomized (2:1) to receive RAM 8 mg/kg or PL Q2W. Pretreatment serum HBV DNA was quantified by HBV-specific PCR (Roche) by a central lab. HBV DNA > 15 IU/mL were detectable (HBV DNA+), < 15 IU/mL were undetectable (HBV DNA-). OS in pooled treatment arms was evaluated using Kaplan-Meier method and Cox proportional hazards model. Liver function was assessed at baseline and before each cycle with the ALBI linear predictor. Outcomes were assessed by concomitant antiviral therapy. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Results: Of 107 REACH-2 pts with HBV etiology, 106 had available PCR samples and were included in a pooled analysis (70 RAM and 36 PL pts). 48 pts were HBV DNA+ and 58 pts were HBV DNA-. HBV DNA+ pts had poorer median OS vs HBV DNA- pts (5.3 vs 10.1 mos, unstratified HR 1.45 95% CI 0.93, 2.28). HBV DNA+ pts taking concomitant antiviral therapy (n = 36) had numerically improved OS compared with those without (n = 12) (5.8 vs 4.0 mos). No difference in OS was noted for HBV DNA- pts by antiviral therapy use (n = 39 antiviral; n = 19 no antiviral) (10.2 vs 9.7 mos for yes vs no antiviral). In pts taking antiviral therapy, regardless of HBV DNA serology, liver function was improved and liver injury/failure related AEs were less frequent. Conclusions: Our data reinforce the use of antiviral therapy to improve outcomes in pts with advanced HBV-associated HCC and elevated AFP. Clinical trial information: NCT02435433.
Oncology precision medicine for hepatobiliary and pancreatic cancer: Insights and updates upon an institutional review.
Authors: Bellini Geoffrey , Sich Nicholas , Godden Jennifer Jo , Weese James L. , Papenfuss Wesley Allan , Chevinsky Aaron , Ruggeri Antony , Thompson Michael A. 
Published: February 2020

570 Background: Hepatobiliary cancers - hepatocellular carcinoma (HCC), intra or extrahepatic cholangiocarcinoma (I/EC), and gallbladder carcinoma (GB) - and pancreatic adenocarcinoma (PC) do have actionable alterations (AA). The importance of testing early in a patient’s (pts) course to identify oncology precision medicine (OPM) options could be paramount for progression free survival (PFS). Methods: We identified pts with HCC, IC, EC, GB or PC in our OPM database since the centralization of our system. Pts who underwent molecular panel testing had AA’s identified and stratified by cancer type. Treatment course was analyzed using swimmers plots. Results: 456pts were diagnosed with HCC, IC, EC, GB or PC. 104/456pts (23%) were ordered for molecular testing and 88/456pts (19.3%) completed testing: 18/88pts (20.4%) I/EC, 2/88pts (2.3%) HCC, 5/88pts (5.7%) GB, and 63/88pts (71.6%) PC. Of the PC pts, 3/63 (4.8%) had a BRCA mutation. These pts did not receive targeted therapy. Overall, 5/88pts (5.7%) had a BRAF mutation (2 PC, 2 I/EC, 1GB). Thus, 8/88 (9.1%) of tested pts became eligible for some form of targeted therapy over their treatment course. Of those with a BRAF mutation, only 2/5 pts had OPM testing sent with initial diagnostic workup, and 2/5 eventually began targeted therapy. One had a progression free survival (PFS) of 2.5months while the other discontinued secondary to toxicity. Conclusions: Our data showed that we are testing a minority of pts with pancreas and hepatobiliary cancers. Of those tested, it may have occurred too late in the course of illness to improve outcomes. Given the potential utility of uncovering potential germline alterations like BRCA1/2 as well as pragmatic AAs including somatic BRCA and BRAF, we are moving to a more systematic evaluation of pts to capture and respond to these issues. [Table: see text]
Primary versus metastatic intrahepatic cholangiocarcinoma: A comparative comprehensive genomic profiling (CGP) study.
Authors: Ross Jeffrey S. , Sokol Ethan , Vergilio Jo-Anne , Killian Keith , Lin Douglas I. , Williams Erik , Danziger Natalie , Ramkissoon Shakti H. , Severson Eric Allan , Hemmerich Amanda , Edgerly Claire I. , Huang Richard , Ali Siraj Mahamed , Madison Russell , Alexander Brian M , Venstrom Jeffrey Michael , Reddy Venkataprasanth P. , McGregor Kimberly , Elvin Julia Andrea , Schrock Alexa Betzig 
Published: February 2020

578 Background: Genomic alterations (GA) characteristic of IHCC are well known. We queried whether the GA of IHCC from primary tumor biopsies (p-bx) would differ from IHCC metastasis biopsies (m-bx). Methods: CGP was performed on 1,268 cases of advanced stage IHCC using p-bx in 1,048 cases and m-bx from 220 cases. Tumor mutational burden (TMB) was determined on 0.8-1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression in tumor cells (Dako 22C3) was measured by IHC. Results: M-bx sites included: lymph nodes (63), soft tissues (47), peritoneum (34), lung/pleura (27), omentum (15), bone (10), GYN tract (5), brain (2), Upper GI (2), colon (2), bladder (1), abdomen (1) and adrenal (1). The GA per sample were similar as were biomarkers of immuno-oncology (IO) drug response. The KRAS mutation frequency was doubled in the m-bx compared to the p-bx (p < 0.001), and enrichment of the potentially targetable KRAS G12C was also observed. Frequencies of untargetable GA were similar overall. IDH1 (p < 0.001) and FGFR2 GA known to be enriched in IHCC were less frequent in the m-bx cohort. GA in STK11 were more frequently identified in m-bx. Conclusions: GA found in p-bx vs m-bx in IHCC are significantly different; the m-bx cohort featuring greater KRAS and lower IDH1 and FGFR2 GA. This suggests that the m-bx group may contain a significant number of non-IHCC cases whose metastatic lesions were actually derived from other primary sites incorrectly assigned the diagnosis of IHCC. [Table: see text]
Progression-free survival in patients with cholangiocarcinoma with FGFR2 fusions or rearrangements: An exploration of response to systemic therapy.
Authors: Bibeau Kristen , Féliz Luis , Barrett Scott , Na Ling , Lihou Christine Francis , Asatiani Ekatherine 
Published: February 2020

588 Background: Most cholangiocarcinoma (CCA) patients (pts) are diagnosed with advanced disease and are ineligible for surgery. FGFR2 fusions or rearrangements are present in 10–16% of pts with intrahepatic CCA (iCCA) and are reported to be oncogenic drivers. However, little data are available on the role of FGFR2 genetic alterations in the response to systemic cancer therapy. FIGHT-202 is a phase 2 study of pemigatinib (a selective, potent, oral FGFR1–3 inhibitor) in pts with previously treated advanced/metastatic CCA (NCT02924376); primary results were reported at ESMO 2019. FIGHT-202 enrolled pts who progressed on ≥1 prior therapy, allowing the examination of the role of FGFR2 alterations on the response to prior therapy. The objective of this post hoc analysis was to evaluate progression free survival (PFS) on standard systemic therapy received prior to study enrollment among pts with CCA harboring FGFR2 fusions or rearrangements ( FGFR2+). Methods: Case report forms were reviewed to determine disease history and exposure to prior lines of systemic cancer therapies (LOSCT) in the advanced setting before receiving pemigatinib. Only pts with sufficient data on prior LOSCT were included in this analysis. Median PFS was calculated using the Kaplan-Meier method. Results: 102 pts were included in this analysis (median age 54.5, 61.8% female). Median PFS on first-line therapy was 5.5 (95% CI: 4.0, 8.0) months. Among the 38 pts (37.3%) with ≥2 prior LOSCT, median PFS on second-line therapy was 4.4 (95% CI: 3.0, 5.3) months. Conclusions: This analysis provides data about PFS on standard systemic therapies for pts with FGFR2+ CCA. Median PFS on first-line therapy was lower than historical published data, and median PFS on second-line therapy was slightly longer than previously reported, in unselected CCA populations. Limitations of this analysis include retrospective examination of investigator reported data, and that clinical trial participants may not truly reflect a general CCA patient population. The short PFS on standard therapies in pts with FGFR2+ CCA highlights the need for development of other options including targeted therapies to improve outcomes.
Preventive effects of gender and metabolic syndrome in 40s on colorectal cancer by colonoscopy.
Authors: KIM Hyun-Soo , Kim Su Young , Lee Jung Kuk 
Published: February 2020

59 Background: This study was aimed at measuring the preventive effect of colonoscopy for CRC development depending on age of index colonoscopy, gender and metabolic syndrome among persons aged 40 to 59 years. Methods: Between January 2005 and December 2006, data for the population aged from 40 to 59 who underwent colonoscopy (CSP cohort) claimed were collected from National Health Insurance Service (NHIS). Non-CSP (N-CSP) subjects were also collected by 1:5 propensity score matching with parameters of age, sex, and metabolic profiles, smoking, alcohol and past history of cancer. After one year of washout period, the risk of developing CRC was estimated by the occurrence of new case from January 2009 to December 2014 using the link of National CRC Registry to NHIS database. Compared with N-CSP cohort, hazard ratios (HRs) were obtained via conditional logistic regression analysis to estimate the risk of CRC in CSP cohort by age groups. Results: A total of 2,339,359 subjects were included (CSP cohort: 395,738 and matched N-CSP cohort: 1,943,621). The HRs for developing CRC by ages of 40-44, 45-49, 50-54, and 55-59 years in a CSP cohort were 0.864 ( P = NS), 0.591 ( P < 0.001), 0.599 ( P < 0.001), and 0.524 ( P < 0.001) in men, and 0.774 ( P = NS), 0.841 ( P = NS), 0.598 ( P < 0.001), and 0.605 ( P < 0.001) in women, respectively. Interestingly, when confined to patients with metabolic syndrome in their 40s, HRs for CRC in the colonoscopy cohort were statistically significantly lowered to 0.372 in early 40’s and 0.386 in men of late 40s, respectively, but not in women of 40s. Conclusions: The CRC prevention effect of colonoscopy is expected from late 40s in men and early 50s in women. Furthermore, in cases with metabolic syndrome, the preventive effect of colonoscopy is expected in men of early forties.
Colorectal cancer prevalence and risk factors among the uninsured of Tampa Bay: A free clinic study.
Authors: Song Ethan , Patel Artish , Swanson Justin , Aponte Alexandra , MacDonald Madeline , Segarra Daniel , Shah Nirav , Ayoubi Noura , Mirza Abu-Sayeef 
Published: February 2020

61 Background: Uninsured patients with low socioeconomic status are at higher risk for developing colorectal cancer. There is limited quantifiable data regarding risk factors and prevalence of colorectal cancer in this vulnerable population. The purpose of this study is to assess the risk factors for colorectal cancer in the low income and uninsured patient population across nine free clinics around Tampa Bay, Florida. Methods: An IRB-approved manually extracted retrospective query of several medical record systems from nine free clinics in the Tampa Bay area in 2017 revealed 1,836 (36.1%) of 5,076 total patients who are over 50 years old. Patient demographics, weight, smoking status, alcohol use, type 2 diabetes status, inflammatory bowel disease and colorectal cancer prevalence were also extracted and analyzed. Results: Among patients over 50, the majority of patients were female (n = 1073, 58.4%) and of Hispanic ethnicity (n = 752, 41.0%). Of the 1,349 patients who reported their smoking status, 213 (15.8%) were active smokers and 218 (16.2%) were past smokers, with a mean 16.3 (SD = 15.5) pack year history. Of the 1,124 patients who reported their history of alcohol consumption, 217 (19.3%) were current consumers and 40 (3.6%) were past consumers. The average BMI of patients over 50 years was 30.2 (SD = 6.9), with 558 (30.4%) cases of diabetes. Eleven patients (0.6%) had a history of inflammatory bowel disease. The prevalence of documented colorectal cancer in this sample was 0.6% (n = 11) in our sample population. Conclusions: There is a high prevalence of risk factors for colorectal cancer in this sample of uninsured patients but a lower reported prevalence of colorectal cancer compared to the general population. Additionally, many known risk factors for colorectal cancer, such as diet, physical activity, or family history, are not routinely documented by free clinics. As these clinics provide opportune points of primary care, this baseline data should prompt more attention to colorectal screening and risk factor modification in this vulnerable population.
The antidiarrheal efficacy of a proprietary amino acid mixture (enterade) in neuroendocrine tumor (NET) patients: Updated data.
Authors: Chauhan Aman , Miller Rachel C. , Luque Laura , Weiss Heidi , Anthony Lowell Brian 
Published: February 2020

614 Background: Diarrhea is a common quality of life limiting symptom seen in neuroendocrine tumor patient. Diarrhea in these patients could be due to excessive serotonin production, secondary to post-operative short gut syndrome, steatorrhea from somatostatin analogs, bile acid colitis or intestinal bacterial overgrowth. In this study we summarize our single center experience with enterade. Methods: Medical records of all the NET patients treated with enterade for symptomatic diarrhea were retrospectively reviewed after appropriate IRB approval. Patients were treated at Markey cancer center between May 2017-June 2019. Results: Total 98 patients were offered enterade. enterade was instructed to be taken as one 8 Oz bottle BID for 1 week. Antidiarrheal efficacy data was available on 49 patients at the time of abstract submission. 37 (75%) patients had GEPNETs, 8 had bronchial NETs, 1 gynecological NET and 3 patients had unknown primary. 28 (57%) patients had history of prior bowel resection either for primary neuroendocrine tumor resection or debulking. 28 (57%) patients were on somatostatin analog at the time of initiation of enterade. 42 (85%) out of 49 patients reported subjective improvement in diarrheal symptoms. 27 (64%) out of these 42 responders reported at least 50 percent reduction in diarrhea frequency. Conclusions: 85% (42/49) neuroendocrine tumor patients reported improvement in diarrhea with enterade. 64% (27/42) reported more than 50% reduction in diarrhea frequency. A prospective Phase II study of enterade in neuroendocrine tumor patients with quality of life limiting diarrhea is currently being conducted (NCT03722511).
Phase I dose-escalation trial of trifluridine/tipiracil (TAS-102) and temozolomide in the treatment of advanced neuroendocrine tumors.
Authors: Uboha Nataliya Volodymyrivna , Lubner Sam Joseph , LoConte Noelle K. , Mulkerin Daniel , Eickhoff Jens C. , Deming Dustin A. 
Published: February 2020

615 Background: Systemic chemotherapy plays a role in treating neuroendocrine tumors. Trifluridine/tipiracil (FTD/TPI), known as TAS-102, is an antineoplastic agent that is non-cross resistant with 5-fluorouracil and capecitabine and that has a different toxicity profile. We are presenting results from a phase 1 portion of the study evaluating safety of FTD/TPI in combination with TMZ in patients in neuroendocrine tumors. Methods: Phase 1 portion to the study utilized “3+3” design to determine maximum tolerated doses (MTD) of FTD/TPI and TMZ when administered in combination. Patients with advanced NETs of any grade were eligible for participation. FTD/TPI was taken twice a day on days 1-5 and 8-12 and TMZ was taken daily on days 8-12 of a 28 day cycle. 3 dose levels (Lv) were evaluated. FTD/TPI was started at a goal dose of 35 mg/m2 twice daily. Three doses of TMZ were studied: 100, 150 and 200 mg/m2. Growth factor support was required during DLT evaluation period for all patients starting with the fourth subject on study. Results: Sixteen evaluable subjects (6 females, median age 64) enrolled in the phase 1 portion of the study (4 on Lv1, 6 on Lv2, 6 on Lv3). 3/16 had high-grade tumors, 8/16 had non-GI or unknown primary. No DLTs were observed on Lv1. One DLT was observed on Lv2 (grade 3 fatigue and inability to resume treatment) and 1 DLT on Lv3 (grade 4 thrombocytopenia). Overall the treatment was well tolerated. 7 subjects had grade ≥3 AEs at least possibly related to treatment, with neutropenia and lymphopenia being the most common. 4 subjects required dose reductions. 7 subjects remain on active treatment. 4 subjects discontinued treatment due to AEs and 1 due to clinical disease progression. Efficacy data is being collected and will be presented at the meeting. Conclusions: This study established MTD of FTD/TPI (35mg/m2 twice daily) and TMZ (200 mg/m2). This regimen is well tolerated. Enrollment into expansion cohort for patients with advanced Grade 1-2 pancreatic NETs is ongoing (NCT02943733). Clinical trial information: NCT02943733.
Single institution experience with peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET).
Authors: Duan Heying , Ninatti Gaia , Girod Bradley , Ferri Valentina , Kunz Pamela L. , Fisher George A. , Moradi Farshad , Davidzon Guido Alejandro , Franc Benjamin Lewis , Iagaru Andrei , Mari Carina 
Published: February 2020

623 Background: Neuroendocrine tumors (NETs) are rare but increasing in incidence. The only curative treatment is surgery, which in many cases is not an option due to metastatic disease at diagnosis. The NETTER-1 study showed high efficacy and low toxicity of peptide receptor radionuclide therapy (PRRT) for midgut NETs. Here, we present our initial experience with PRRT in the treatment of patients with NET. Methods: Fifty-two patients (27 males and 25 females; 37 - 81 yo, mean ± SD: 61.8 ± 10.6 years) with documented progressive NET (25 pancreas, 17 small intestine, 1 coecum, 4 unknown primary, 3 paragangliomas, and 2 pheochromocytomas) were referred to undergo PRRT at our institution from July 2018 to September 2019. Laboratory tests were obtained at baseline, 1 week before each cycle and every 3 months following treatment. Progression-free survival (PFS), objective response rate (ORR) and toxicity were assessed. An interim overall survival (OS) analysis was performed. Results, when possible, were compared with the NETTER-1 trial. Lines of therapy were documented. Results: 22/52 (42%) patients completed all 4 cycles of PRRT. 18/52 (34%) patients are currently being treated. 12/52 (23%) patients had to discontinue treatment. Hematotoxicity was the only side effect which can be related to PRRT. The 6-month and 9-month PFS rate was 82.4% and 66.8% respectively vs. 89% and 84% in the NETTER-1 trial. The ORR was 36% vs. 18% in the NETTER-1 trial. In the interim OS analysis, 6 deaths occurred. In contrast to the NETTER-1 study, PRRT in our patient cohort was performed later in the course of treatment (median lines of therapy before PRRT = 4 ±1.3 (range 1-6)). Conclusions: Our preliminary data show overall good results of PRRT in patients with NETs. However, compared to the NETTER-1 trial, PFS is shorter which is most likely due to the extensive pretreatment, but ORR was higher. [Table: see text]
Validating enhancer signature classifications (ESCs) in pancreatic neuroendocrine tumors (PNETs).
Authors: Trinh Vincent Quoc-Huy , Shi Chanjuan , Berlin Jordan , Das Satya 
Published: February 2020

627 Background: Predicting recurrence risk (RR) for resected (res) PNET patients (pts) is challenging using existing pathologic criteria. Better predictive models to tailor surveillance for individual pts are needed. A recent study suggests expression patterns of the transcriptomic/epigenomic enhancers ARX and PDX1 may predict RR. In this study, distant metastases occurred almost exclusively in ARX+/PDX1- tumors. Our primary objective was to validate ESCs within our institutional cohort. Methods: We used a tissue microarray generated from res localized PNETs at Vanderbilt University Medical Center (VUMC) between 2002-2012. Clinical, pathological, and outcomes data were extracted from records. Immunohistochemistry was performed with PDX1 by Novus and ARX by Sigma. Patients were grouped as double-positives (DP), ARX+/PDX1-, ARX-/PDX1+ and double-negatives (DN). Time-dependent ROC analysis was performed in R (v3.6.1; survivalROC v1.0.3) to determine ARX and PDX1 positivity. Comparative analyses were performed in SPSS v23.0 (Kruskal-Wallis, Freeman-Halton exact test, Log-rank). Primary outcomes were progression-free survival (PFS) and cancer-specific survival (CSS). Results: 61 PNET specimens had adequate tissue for analysis. Table shows PFS plus CSS data by ESC distribution. Pts with ARX+ (DP & ARX+/PDX1-) tumors were younger (P=0.015) and possessed larger tumors (P=0.065). Pts with ARX+ tumors demonstrated shorter PFS (log-rank P=0.006) and a trend toward lower CSS (log-rank P=0.09). Notably, pts with ARX-/PDX1+ and DN tumors had no deaths and only 1 progression event over a median follow-up period of 91 months (m). Conclusions: Building upon earlier data that ARX+ res PNETs are more likely to relapse, we demonstrate that pts with such tumors have diminished PFS and a trend toward diminished CSS. ESCs need prospective validation but carry the potential to guide surveillance for res PNET patients. [Table: see text]