bluuebunny/crossref_metadata_2025_split huggingface dataset:
A real-world application of liquid biopsy (LB) in metastatic colorectal cancer (mCRC).
Authors: Procaccio Letizia , Del Re Marzia , Crucitta Stefania , Gianfilippo Giulia , Daniel Francesca , Di Antonio Veronica , Gallimberti Sara , Munari Giada , Zanella Giulia , Alberti Giulia , Rizzato Mario Domenico , Rasola Cosimo , Maddalena Giulia , Prete Alessandra Anna , Bergamo Francesca , Zagonel Vittorina , Lonardi Sara , Danesi Romano , Fassan Matteo , Loupakis Fotios 
Published: February 2020

48 Background: First-line decision making is the key to the successful management of mCRC patients (pts). RAS/BRAF status is essential to choose the best targeted agent. In hub centers, a not negligible proportion of pts referred from elsewhere may not have standard tissue-based (STB) molecular results available at the time of first oncologic visit (T0). LB may help circumvent these hurdles. Methods: A monoinstitutional prospective head-to-head comparison of LB versus (vs) STB testing was conducted in a real-world setting. Selection criteria included: mCRC with unknown RAS/BRAF status at T0, tissue from primary or metastases archived in external centers, no previous anti- EGFR agents. At T0, pts underwent plasma sampling for LB testing and procedure for tissue recovery. RAS/BRAF genotyping was carried out by droplet digital PCR on circulating-free (cf) DNA. Primary endpoint was the comparison of time to LB (T1) vs STB (T2) results. Secondary endpoints were the overall percent agreement (OPA), specificity, sensitivity, positive and negative predictive value (PPV and NPV) of LB. Urinary (u) cfDNA testing was also explored. Results: A total of 33 pts were included. Mean T1 was 7 (2-12) days (d) as compared to 22 (7-65) d mean T2. T2 included a mean time for tissue recovery of 17 d. The OPA between LB and STB analysis was 83%. Compared to STB testing, LB specificity and sensitivity were 90% and 80%, respectively, with a PPV of 94% and NPV of 69%. In detail, at STB and LB testing, RAS mutation was found in 50% and 43% of pts; BRAF mutation in 17% and 13%, respectively. LB results included 1 false positive and 4 false negative (FN). FN showed a significantly lower tumor burden (i.e. total tumor volume) at basal CT scan. Concordance between STB and ucfDNA testing was 89%, with a sensitivity of 83% and specificity of 100% recorded for ucfDNA analysis. Conclusions: Faster turnaround time, high concordance and accuracy are 3 key-points supporting the adoption of LB in routinary mCRC care, in particular when decision on first-line is urgent and tissue recovery from external centers may require a long time. Results should be interpreted with caution in LB wild-type cases with low tumor burden.
Survival by line of therapy of older patients with advanced biliary tract cancer (BTC).
Authors: Bobiak Sarah , Danese Mark D. , Lubeck Deborah P. , Gleeson Michelle L. 
Published: February 2020

497 Background: Overall survival (OS) in advanced or metastatic BTC has not been adequately described outside the clinical trial setting. Further, real-world descriptions of OS by line of therapy, including in patients who do not receive systemic chemotherapy, are not widely available. In this study, we used data from a recent cohort of US patients available in the SEER-Medicare linked database to examine OS from diagnosis of advanced or metastatic BTC as well as from initiation of first- and second-line treatment. Methods: Patients with advanced or metastatic BTC diagnosed between 2010 and 2013 were identified in SEER-Medicare, with follow-up through 2014. Demographic and clinical characteristics were analyzed. The Kaplan-Meier estimator was used to describe OS from diagnosis among all patients, OS from diagnosis among patients who did not receive systemic treatment, and OS by line of treatment, from date of treatment initiation. The Cox proportional hazards model was used to identify demographic and clinical factors associated with survival. Results: Of the 1,461 eligible patients aged ≥66 years, 39% had gallbladder, 22% had intrahepatic, 22% had extrahepatic, and 9% had ampulla of Vater cancer. More than two-thirds of patients had stage IV disease, and 38% of patients (n = 558) received systemic chemotherapy. Systemic treatment patients were somewhat younger, more likely to be white, have stage IV cancer and less likely to have mobility limitations (24% vs. 38%) than patients who did not receive systemic treatment. Among all patients, unadjusted median OS from diagnosis was 5.6 months (95% CI 5.0-6.1). Among patients who were not treated, unadjusted median survival was 3.3 months (n = 903; 95% CI 2.8-4.0) from diagnosis. When OS was evaluated by line of treatment, median OS was 8.2 months (n = 558; 95% CI 7.6-9.0) from first-line initiation and 5.6 months (n = 220; 95% CI 4.6-6.5) from second-line initiation. Conclusions: Among newly diagnosed, older US patients, less than half receive systemic treatment for their advanced BTC, and outcomes among both treated and untreated patients remain poor. There is an immediate need for better therapies to treat patients with advanced BTC.
Association of socioeconomic disparities with underutilization of palliative care in patients with metastatic foregut cancer.
Authors: Ju Michelle , Porembka Matthew R. 
Published: February 2020

502 Background: Metastatic foregut cancers (MFC) are frequently associated with debilitating symptoms that have significant negative impact on patients’ quality of life. Palliative care (PC) is effective in mitigating disease-, psychosocial-, and treatment-related effects. However, PC remains heavily underutilized. The aim of our study was to characterize the rate of PC utilization in MFC and determine the impact of various clinicopathologic and socioeconomic factors associated with the receipt of PC. Methods: We conducted a retrospective review of 277,957 National Cancer Database patients diagnosed with MFC between 2004-2013. Chi-squared tests were used to analyze differences between groups. Logistic regression was performed to assess the impact of factors on the likelihood of receiving PC. Results: PC utilization increased among all groups over time (12.3% 2004-2006 vs. 14.7% 2007-2010 vs. 16.4% 2011-2013 for all cancers). Female sex, Medicaid, median income < $46,000/year, higher education level, higher Charlson/Deyo Score, and pancreatic or biliary cancers were associated with increased likelihood of PC interventions. Additionally, patients treated at an academic center or integrated network cancer program were more likely to receive PC than patients treated in the community setting. When receipt of PC was stratified by race, Hispanics were significantly less likely to have undergone palliative interventions compared to non-Hispanic Whites (OR 0.70, 95% CI 0.66-0.73). Patients with Medicare or private insurance were less likely to receive PC than uninsured patients (OR 0.92, 95% CI 0.87-0.97 and 0.81, 95% CI 0.77-0.89, respectively). Conclusions: Differences in palliative care receipt rates exist with regards to racial/ethnic and socioeconomic factors such as insurance status, median household income, and education level. Patients receiving care in the community setting were also less likely to receive palliative care than those treated at academic or integrated network cancer program centers. Further studies are needed to delineate why these disparities exist with regards to palliative care utilization.
Comparison of the frequency of adverse events requiring interventions determined by telephone follow up in hepatocellular carcinoma patients treated with sorafenib and lenvatinib.
Authors: Morishita Koki , Suzuki Hidetaka , Tauchi Junko , Takeno Misaki K , Hayashi Kohei , Ikeda Masafumi 
Published: February 2020

507 Background: The REFLECT trial demonstrated that lenvatinib is non-inferior to sorafenib for first-line treatment of unresectable hepatocellular carcinoma (uHCC). However, no comparison of the frequency of adverse events (AEs) requiring interventions has been reported yet between uHCC patients receiving sorafenib and those receiving lenvatinib. At the National Cancer Center Hospital East, Japan, pharmacists conduct telephone follow-up (TF) during the first month after the start of treatment with sorafenib or lenvatinib in uHCC patients, for the purpose of detecting and treating AEs early. The aim of this study was to reveal the frequency of AEs requiring interventions between patients receiving sorafenib and those receiving lenvatinib, based on TF. Methods: The characteristics, AEs and contents of intervention by TF of 56 uHCC patients who had been started on treatment with sorafenib and lenvatinib were reviewed retrospectively. The study subjects were 33 patients initiated on sorafenib treatment and monitored by TF from March 2017 to March 2018 (Group S) and 23 patients initiated on lenvatinib treatment and monitored by TF from March 2018 to March 2019 (Group L). Results: The total numbers of TFs in Group S and Group L were 91 and 48, respectively. The rate of AEs requiring interventions was significantly higher in Group S as compared to Group L (Group S, 17.6% (16/91); Group L, 4.2% (2/48); p = 0.032). The frequencies of the interventions, including use of supportive treatments (A), withdrawal of sorafenib or lenvatinib (B), and medical examination (C), differed between the two groups (A/B/C: Group S, 8/5/3 times vs. Group L, 2/0/0 times). The most frequently observed AE that necessitated intervention in Group S was the hand-foot syndrome (HFS) (75.0%, 12/16). Conclusions: The frequency of interventions for AEs appears to be higher in uHCC patients receiving sorafenib than in those receiving lenvatinib. Although a great number of patients taking sorafenib had symptomatic AEs, such as HFS, early detection of the symptoms through TF contributed to prevention of treatment withdrawal on account of AEs.
Early experiences with triple immunochemotherapy in young adults with high-risk fibrolamellar carcinoma.
Authors: O'Grady Claire , Gliksberg Ariel , Kent Paul 
Published: February 2020

510 Background: Fibrolamellar Carcinoma (FLC) is a rare liver cancer affecting young adults without underlying liver disease. Surgery is the only proven therapy, and recurrence is common. There are no proven systemic treatments, especially for high-risk FLC (unresectable, relapse, progression, metastatic). Research suggests that immunotherapy may work. We share our experience using systemic “triple immunochemotherapy” (TT): 2 week cycles of 7 days continuous infusion 5FU or oral capecitabine, interferon alpha-2b on days 1,3,5,7 or PEG-Interferon and nivolumab on day 1. Methods: Data from all patients who received TT from 5/2018 to 9/2019 was reviewed to assess tolerability, survival and toxicity. Results: 14 patients were treated with TT of which 10 (8F,2M with a median age of 20) were evaluable. They received a median of 13 cycles (6-31). At time of analysis, the median progression free survival was 6 months, 22% longer than prior to TT, with 80% of patients (8) stable or improving, 1 progression, and 1 who died 2 months after initiating TT. For the 4 patients who achieved surgical remission, none have relapsed (PFS 9 months). Overall objective response (CR+PR) and tumor control rate (CR+PR+SD) were 60% and 80%, respectively. There were no withdrawals from treatment due to side effects, though 2 had dose adjustments. All experienced mild adverse effects, most commonly fever and headache, but only 2 patients had grade 3 toxicity. Conclusions: Our early results of TT for high-risk FLC are promising, with good tolerability and treatment response, particularly in patients who have achieved surgical CR. Further longitudinal data is needed to confirm outcomes, especially in patients still early in their treatment. [Table: see text]
Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Subgroup analyses from CheckMate 040.
Authors: He Aiwu Ruth , Yau Thomas , Hsu Chiun , Kang Yoon-Koo , Kim Tae-You , Santoro Armando , Sangro Bruno , Melero Ignacio , Kudo Masatoshi , Hou Ming-Mo , Matilla Ana , Tovoli Francesco , Knox Jennifer J. , El-Rayes Bassel F. , Acosta-Rivera Mirelis , Neely Jaclyn , Shen Yun , Tschaika Marina , El-Khoueiry Anthony B. 
Published: February 2020

512 Background: NIVO monotherapy is approved in the United States and other countries for pts with HCC treated with sorafenib (SOR) based on CheckMate 040 (NCT01658878) results, which reported 14% objective response rate (ORR) and 16-month median overall survival (mOS; El-Khoueiry et al. Lancet 2017). Primary efficacy and safety of NIVO + IPI in pts with aHCC previously treated with SOR were presented recently (Yau et al. J Clin Oncol 2019). Here, we will present subgroup analyses from this study. Methods: Pts were randomized to 3 arms: [A] NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) or [B] NIVO 3 mg/kg + IPI 1 mg/kg Q3W (4 doses), each followed by NIVO 240 mg Q2W, or [C] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W. Treatment continued until intolerable toxicity or disease progression. Primary endpoints included safety/tolerability, ORR, and duration of response (DOR; investigator assessment per RECIST v1.1). Key secondary endpoints included disease control rate (DCR), OS, and progression-free survival (blinded independent central review [BICR] per RECIST v1.1); key exploratory endpoints included ORR (BICR per RECIST v1.1). Data cutoff was January 2019. Results: A total of 148 pts were randomized. Minimum OS follow-up from last pt randomization date to data cutoff was 28 months. At baseline, 34% of all pts had vascular invasion; 82% had extrahepatic spread; and 91% had Barcelona Clinic Liver Cancer stage C; 84% discontinued SOR because of disease progression and 14% because of toxicity. For all treated pts, ORR was 31% (7 had complete response), with median DOR of 17 months; DCR was 49%; the 30-month OS rate was 37%. NIVO + IPI was well tolerated; 38% of pts had grade 3–4 treatment-related adverse events (TRAEs; most common any grade: pruritus and rash; most common grade 3–4: aspartate aminotransferase increase and lipase increase); 5% had grade 3–4 TRAEs leading to discontinuation. Subgroup analyses based on duration of prior SOR therapy and other pt characteristics will be presented. Conclusions: NIVO + IPI led to clinically meaningful benefits, with a manageable safety profile in pts previously treated with SOR. NIVO + IPI may provide a new treatment option for these pts. Clinical trial information: NCT01658878.
Sex difference in patients with biliary tract cancer receiving chemotherapy: Post hoc analysis of ABC-01, -02, -03, -04, BILCAP.
Authors: Suzuki Eiichiro , Bridgewater John A. , Valle Juan W. , Primrose John Neil , Wagner Anna Dorothea , Lopes Andre , Fox Richard 
Published: February 2020

517 Background: The relationship between toxicity from chemotherapy and clinical outcome in biliary tract cancer (BTC) is uncertain. Aim: This post hoc analysis evaluated differences by sex in the frequency of adverse events (AEs) and overall survival (OS) and its impact on progression-free survival (PFS)/recurrence-free survival (RFS) for BTC patients. Methods: Individual patient data were retrieved from ABC -01, -02, -03, -04, and BILCAP study. AEs were graded according to National Cancer Institute's Common Toxicity Criteria v 4.02 and odds ratios along with 95%CI and p-values derived from logistic regression were used to assess the effect of sex on the risk of AEs. Time to event outcomes were evaluated using Cox regression and plotted using Kaplan-Meier plots. All statistical tests were two-sided. Results: Overall 994 patients-data were examined: 86 in ABC-01, 324 in-02, 124 in -03, 13 in -04 and 447 in BILCAP. A total of 484 (49%) were males (M) and 510 (51%) were females (F). 770 patients were evaluable for AEs because a total of 224 patients in BILCAP study belonged to the observation group. Urinary tract infection (M, 1.6%; F, 5.5%), nausea (M, 50.7%; F, 69.9%), vomiting (M, 29.1%; F, 46.1%), alopecia (M, 11.3%; F, 27.3%), are dominant in F, hyperbilirubinaemia (M, 36.7%; F, 29.1%) and thrombocytopenia (M, 43.1%; F, 34.3%) and hiccups (M, 2.4%; F, 0.5%) are dominant in M at any grade. Vomiting (M, 3.5%; F, 7.0%) and fatigue (M, 4.0%; F, 8.5%) are higher in F than in M for grade 3-5. The median OS (M, 16.2 months (Mo); F, 17.5 Mo), PFS (M, 6.4 Mo; F, 6.5 Mo) and RFS (M, 20.8 Mo; F 19.4 Mo) were similar. Amongst the subgroup of patients with gallbladder, F achieved longer OS (M, 11.5 Mo; F 13.3 Mo, 0.73 (95%CI:0.54,0.99), p = 0.041) and RFS than M (M, 20.8 Mo; median PFS for F not reached, HR:0.52 (95%CI:0.27,1.02), p = 0.057). Conclusions: Females with BTC have tended to have more AEs, especially grade 3+. Although no difference was observed in OS, PFS, and RFS between males and females for the overall cohort of patients, females with gallbladder cancer had an improved OS and RFS compared with males. These findings suggest, in BTC, sex may play a role when designing clinical trials as well as in making treatment decisions.
Initial lenvatinib therapy with no prior TACE in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria and Child-Pugh A liver function: A proof-of-concept study.
Authors: Kudo Masatoshi , Ueshima Kazuomi , Chan Stephen Lam , Aoki Tomoko , Hagiwara Satoru , Minami Yasunori , Ida Hiroshi , Takenaka Mamoru , Watanabe Tomohiro , Morita Masahiro , Ogawa Chikara , Wada Yoshiyuki , Ikeda Masafumi , Ishii Hiroshi , Izumi Namiki , Hiraoka Atsushi , Aikata Hiroshi , Nishida Naoshi 
Published: February 2020

522 Background: Intermediate-stage HCC is a heterogenous population with subgroups of patients that do not benefit from TACE. Hence, we conducted a matched cohort study to compare the efficacy of lenvatinib to TACE in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-7 criteria. Methods: This study first identified 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria [unresectable, beyond the up-to-7 criteria, without prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child-Pugh A liver function] were selected. Propensity score matching was used to adjust for patients’ demographics. Results: After propensity-score matching, outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials [1 Phase II and 13 Phase III REFLECT trial], 1 in early access program and 15 in real world setting) and 60 patients treated with cTACE as the initial treatment was compared. The lenvatinib group showed a higher objective response rate (73.3% vs. 33.3%; p < 0.001) and longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p < 0.001). Median overall survival was also significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p < 0.01). The change of ALBI score from baseline to the end of treatment were -2.61 to -2.61 for 30 patients in lenvatinib group (p = 0.254) and -2.66 to -2.09 in cTACE group (p < 0.01), respectively. Conclusions: In patients with large or multinodular intermediate-stage HCC exceeding the up-to-7 criteria with Child-Pugh A liver function, who usually do not benefit from TACE, lenvatinib is associated with better outcome than TACE. In particular, leventinib is associated with preservation of hepatic function during treatment while TACE is associated with deterioration of hepatic function.
First-in-human phase I trial of small activating RNA (saRNA) oligonucleotide MTL-CEBPA in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC).
Authors: Sarker Debashis , Sodergren Mikael , Plummer Elizabeth Ruth , Basu Bristi , Meyer Tim , Huang Kai-Wen , Evans T.R. Jeffry , Spalding Duncan , Ma Yuk Ting , Palmer Daniel H. , Chee Cheng Ean , Pinato David James , Reebye Vikash , McVeigh Daniel , Raulf Nina , Vasara Jenni , Andrikakou Pinelopi , Habib Robert , Blakey David , Habib Nagy A. 
Published: February 2020

554 Background: MTL-CEBPA is the first saRNA to enter clinical trials and targets the transcription factor C/EBPα, a master regulator of myeloid cell differentiation. We have previously reported a favourable safety profile of MTL-CEBPA given as a single agent QWx3 every 28 days, in patients with HCC (Sarker D et al, ASCO 2018). After discontinuation of MTL-CEBPA, three out of five patients treated with sorafenib off study have had maintained complete radiological response (CR) of 7-18 months duration; 2 patients demonstrated resolution of lung metastases > 1 year. Here we provide updated data on phase 1 patients treated with sorafenib off study as well as subsequent combination cohorts. Methods: MTL-CEBPA 130mg/m2 QWx3 or BIW and sorafenib 400mg bd were administered to patients with HCC using combination or sequential dosing regimens, in cohorts either tyrosine kinase inhibitor naive or resistant. On treatment liver biopsies evaluated changes in M2 macrophages (CD163). Flow cytometry of peripheral blood determined changes in myeloid cell populations. Results: 12 patients have been treated with MTL-CEBPA co-administered with sorafenib and 14 patients treated with MTL-CEBPA followed by sorafenib (23M/3F, median age 65.5years, range 44-83, ECOG PS 0/1: 18/8). The most common treatment-related AEs (all grades/grade 3) in this group include facial flushing (4/0), raised AST (3/1) raised ALT (2/1), fatigue (5/0), raised ALP (2/0), and anaemia (2/2), diarrhoea (3/0), rash (2/0) and anorexia (1/0). 1 TKI naïve patient in the co-administration cohort has maintained CR at 7 months and two patients have SD (ongoing at 3 & 4 months both in sequential cohort). IHC in the patient with CR has demonstrated 95% reduction in M2 macrophages with significant decrease in frequency of immature CD10- neutrophils (-85.7%; p = 0.0078), PMN-MDSCs (-49.3%; p = 0.00145) and M-MDSCs (-18.4%; P = 0.0072). All responding patients have underlying HBV or HCV. Conclusions: MTL-CEBPA is a novel saRNA targeting myeloid cells which may result in a significantly enhanced oncological response in HCC of viral aetiology. Updated safety and efficacy data will be presented. Clinical trial information: NCT02716012.