bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of circulating tumor DNA (ctDNA) versus tumor tissue clinical sequencing for enrolling patients (Pts) with advanced gastrointestinal (GI) cancer to matched clinical trials: SCRUM-Japan GI-SCREEN and GOZILA Combined Analysis.
Authors: Nakamura Yoshiaki , Taniguchi Hiroya , Bando Hideaki , Kato Ken , Esaki Taito , Komatsu Yoshito , Takahashi Naoki , Ueno Makoto , Kagawa Yoshinori , Nishina Tomohiro , Kato Takeshi , Yamamoto Yoshiyuki , Furuse Junji , Denda Tadamichi , Kawakami Hisato , Oki Eiji , Sunakawa Yu , Satoh Taroh , Yoshino Takayuki , Ohtsu Atsushi 
Published: February 2020

5 Background: Blood-based genomic profiling by ctDNA analysis has a promise to potentially identify actionable genomic alterations. However, utility of clinical sequencing with ctDNA compared with that with tumor tissue for enrolling cancer pts to matched clinical trials remains unclear. Herein we investigated the utility of ctDNA clinical sequencing by the SCRUM-Japan GI-SCREEN and GOZILA Combined Analysis. Methods: In the GI-SCREEN, tumor tissue samples of pts with advanced GI cancer were analyzed by a next generation sequencing (NGS)-based assay, Oncomine Comprehensive Assay since Feb 2015. In the GOZILA, plasma samples of pts with advanced GI cancer were analyzed by an NGS-based ctDNA assay, Guardant360 since Feb 2018. Tests were performed centrally by CLIA-certified and CAP-accredited laboratories. Pts with actionable alterations were enrolled to matched company-sponsored or investigator-initiated clinical trials. Results: As of Apr 2019, test results were generated in 5,029 out of 5,743 pts (88%) in GI-SCREEN and 1,089 out of 1,103 pts (99%) in GOZILA ( P < 0.0001).Median turnaround time (TAT) was 35 days in GI-SCREEN and 12 days in GOZILA ( P < 0.0001). There were no differences in other baseline characteristics between GI-SCREEN and GOZILA. Proportion of enrolling matched clinical trials in GOZILA was significantly higher than that in GI-SCREEN (126 pts [2.2%] in GI-SCREEN vs. 60 pts [5.4%] in GOZILA, P < 0.0001). Median time from GI-SCREEN or GOZILA enrollment to clinical trial enrollment was 5.9 and 1.0 months (mo), respectively ( P < 0.0001). The objective response rate (ORR) and progression-free survival (PFS) were not significantly different (ORR: 17.5 vs. 16.7%, P = 1.00; median PFS: 2.8 vs. 2.0 mo, P = 0.24). Conclusions: Clinical sequencing with ctDNA having the advantage of the shorter TAT enrolled more pts with advanced GI cancer to matched clinical trials than those with tumor tissue, without compromising the efficacy. Clinical trial information: UMIN000029315.
Role of hepatologists in management of hepatocellular carcinoma in the new era of transplant oncology.
Authors: Ashat Divya , Karwal Mark , Sun Shiliang , Laroia Sandeep , Tanaka Tomohiro 
Published: February 2020

501 Background: There have been global efforts to manage hepatobiliary malignancies such as hepatocellular carcinoma (HCC) in a multidisciplinary setting under the concept of transplant oncology. We published preliminary data of hepatology-directed treatment of HCC (Ann Hepatol 2019). However, the actual role of hepatologists in this setting is not well defined. Methods: We evaluated 107 patients with newly diagnosed HCC, undergoing locoregional therapy (LRT) as a first therapy (microwave ablation, TACE, TARE or SBRT) in our institution between 1/2017 to 2/2019 and being followed until 8/2019. Patients were divided into three groups based on referral pathways: outside referral directly to oncologists (O-group, n=24), internal referral from hepatologists to oncologists (H/O-group, n=62) and hepatologist directed HCC treatment (H-group, n=21). The hepatologist performed all microwave ablations in H-group; rest of the LRTs were performed by either interventional radiology or radiation oncology. Results: The baseline gender, etiology of liver disease, MELD score, Child-Pugh score, BCLC stage, CLIP score, AFP and proportion of patients within Milan criteria were similar between 3 groups ( p=n.s.). However, O-group included older patients (median 70 vs 63/62 y.o., p<0.01), and had larger HCC size (median diameter 41 vs 26/28mm, p<0.01). In H-group, there were more cases discussed in multidisciplinary tumor boards (77% vs 46%, p=0.012) and referrals for liver transplantation (71% versus 50%, p=0.046). Time between the diagnosis and the first procedure was shorter in H-group than others (median 53 vs 69 days, p=0.048). The rate of complete response/partial response per mRECIST criteria was highest in H-group (91 vs 66%, p=0.024). The 2-year cumulative survival was comparable among three groups (70, 74 and 76% in O-group, H/O-group and H-group, respectively, p=0.4). Conclusions: Hepatologists are often the first point of contact and can play a key (and even more direct) role in subsequent management of HCC. To further accomplish the concept of multidisciplinary approach and transplant oncology, primary/secondary care institutions might be a potential target for intervention for outreach.
Determination of quality of care for patients with hepatocellular carcinoma in Nova Scotia.
Authors: Ouellet Cathie , Ramjeesingh Ravi 
Published: February 2020

506 Background: Hepatocellular carcinoma (HCC) is the most common primary malignancy found in the liver. Little is known about the outcomes of HCC patients in the province of Nova Scotia (NS). There is suggestion that closer proximity to tertiary cancer center provides better outcomes for HCC patients. We postulate that cancer care for HCC patients differs based on a patient’s accessibility to an academic cancer care center. Methods: A retrospective chart review of HCC patients diagnosed from 2015 to 2017, looking at referrals patterns, treatments and wait time was undertaken. Patients who live within the urban area of Halifax, NS (N = 97), where the academic cancer center is, was compared to patients who live outside Halifax (rural, N = 70). Results: 167 patients were identified with a diagnosis of HCC, which included 139 males and 28 females with median age of 68 years old at HCC diagnosis. During that period, only 35.3% of patients diagnosed with HCC had a tissue diagnosis and 67.7% had a baseline AFP (16% had an AFP > 400). Just over 76% were diagnosed based on clinical features. Surgical intervention occurred in 15.6% and local treatments including radiation and TACE occurred in 35.3% of patients .Referral rate to Medical Oncology (MO) was 37.7%, of which 34.1% of patients had seen a MO at the time of data cut off (09-15-2019). 22 patients were eligible for systemic therapy but only 14 patients received systemic treatment (sorafenib n = 14). Conclusions: Initial data suggests patients who live in Halifax appear to have better outcomes than those outside. Further analysis is required to identify what differs between the urban and rural centers accounting for the seen difference in survival. [Table: see text]
Clinical and genomic factors associated with outcome following ablative radiotherapy for oligometastatic and oligoprogressive liver tumors.
Authors: Bitterman Danielle Sara , Niemierko Andrzej , Van Seventer Emily E. , Kim Daniel W. , Qadan Motaz , Blaszkowsky Lawrence Scott , Clark Jeffrey William , Zhu Andrew X. , Goyal Lipika , Keane Florence , Eyler Christine Elissa , Parikh Aparna Raj , Corcoran Ryan Bruce , Wo Jennifer Yon-Li , Hong Theodore S. 
Published: February 2020

515 Background: There is increasing use of ablative radiotherapy (RT) for oligometastatic and/or oligoprogressive cancer, but the population who may benefit from this more aggressive treatment remains poorly defined. We aimed to identify factors associated with improved outcomes following ablative RT for oligometastatic/oligoprogressive liver tumors. Methods: We retrospectively analyzed 106 patients who had tumor genomic profiling and received a 5, 6, or 15-fraction course of ablative RT for liver metastases from 2008-2019. The interval off systemic therapy post-RT was calculated for patients who did not continue treatment through RT. Overall survival (OS) was estimated using the Kaplan-Meier method. The association between clinical and genomic variables and OS were assessed using uni- and multivariable Cox regression. Results: Median follow-up was 12.6 months. Median age was 61.3 years and 57% were male. The most common primary site was colorectum (42%), followed by pancreas (25%) and non-small cell lung cancer (10%). 42% had colorectal adenocarcinoma, 46% had other adenocarcinoma, and 12% had other histology. A BRAF/RAS family mutation (KRAS, NRAS, and/or BRAF) was present in 41%, 69% had > 1 metastasis, and 38% had extra-hepatic disease. Median biological effective dose (α/β = 10) (BED) was 92 Gy. The RT field encompassed all liver metastases in 91%, and 11% received radiosensitizing chemotherapy. Median time off systemic agents was 5 months. Patients with 1 vs > 1 metastasis had a longer interval off systemic therapy (9 vs 4 months, p = 0.026). Median OS was 12.6 months. The table shows the multivariable Cox model for OS. Conclusions: Presence of a BRAF/RAS family mutation, extra-hepatic metastases, exclusion of liver metastases from RT fields, lower BED, and concurrent radiosensitizing chemotherapy were associated with worse OS. This may inform patient selection and RT delivery for aggressive local therapy for liver metastases. [Table: see text]
Real-world treatment patterns and survival in patients (pts) with hepatocellular carcinoma in the United States.
Authors: Morse Michael , Meyer Anne-Marie , Lawrance Marcus , Pereira Marta , Mhatre Shivani K. , Gaillard Vincent , Dayyani Farshid 
Published: February 2020

519 Background: Outcomes in pts with hepatocellular carcinoma (HCC) vary by epidemiology, degree of hepatic dysfunction and tx. We analyzed the relationship between tx patterns and outcomes to help characterize emerging clinical data in the context of contemporary disease management. Methods: Retrospective observational study of the Flatiron Health de-identified electronic health record–derived database to analyze the relationship between first recorded tx (1tx) and overall survival (OS) in pts diagnosed with HCC (any stage) Jan 2011 to Nov 2018. Tx categories included transplant, resection/SBRT/RFA, TACE/TARE/TAE, tyrosine kinase inhibitor (TKI), cancer immunotherapy (CIT), and others. Descriptive statistics were used to summarize tx distribution and pt characteristics; Kaplan-Meier method was used to estimate OS by tx category. Results: A total of 2134 pts with HCC were categorized by 1tx: transplant (n = 35), resection/SBRT/RFA (n = 408), TACE/TARE/TAE (n = 830), TKI (n = 751), and CIT (n = 20). Pt demographics were generally similar across txs (Table). Overall, pts with HCC had a median OS of 16.6 mo; varying from 71.5 mo in pts receiving transplant to 5.0 mo in pts treated with TKI. Conclusions: Pts receiving systemic tx for HCC have poor prognoses in clinical practice. Despite the limitations of data availability, this study showed a substantial unmet need for more effective HCC tx options. [Table: see text]
RECIST v1.1 and irRECIST outcomes in advanced HCC treated with pembrolizumab (pembro).
Authors: Edeline Julien , Karwal Mark , Zhu Andrew X. , Finn Richard S. , Cattan Stéphane , Ogasawara Sadahisa , Verslype Chris , Dadduzio Vincenzo , Fartoux Laetitia , Vogel Arndt , Rosmorduc Olivier , Verset Gontran , Chan Stephen Lam , Knox Jennifer J. , Daniele Bruno , Cheng Ann-Lii , Goldmacher Gregory V. , Jensen Erin , Siegel Abby B. , Kudo Masatoshi 
Published: February 2020

528 Background: IO can cause pseudoprogression (PP): apparent tumor growth followed by stability or favorable response. We assess PP in aHCC treated with pembro (KEYNOTE-224 [ph 2], NCT02702414; KEYNOTE-240 [ph 3], NCT02702401). Methods: aHCC pts with PD on/intolerance to sorafenib received pembro 200 mg IV Q3W until unacceptable toxicity, study withdrawal, 2 y of therapy, or RECIST v1.1 PD; if pt clinically stable at PD, physician could continue therapy and repeat scans to confirm PD per irRECIST. PP=RECIST v1.1 PD then irRECIST response other than PD. Data cutoff: Jan 02, 2019 (KEYNOTE-240); Feb 13, 2018 (KEYNOTE-224). Results: 245/382 pembro-treated pts had RECIST v1.1 PD: 138 irRECIST repeat scan; 105 PD; 33 (8.6%; 33/382) outcomes other than PD. Of 33 PP, 29 had SD, 3 PR, 1 CR (irRECIST; 29 had this at first irRECIST scan; 4 [2 SD, 2 PR] at subsequent scan). For initial RECIST v1.1 PD, 16/33 PP had PD at first postbaseline scan (pembro cycles 2-4); 17/33 PP had PD at pembro cycles 4-18. Median (range) time to RECIST v1.1 PD in the 33 PP was 80 (37-378) days. OS shown in Table. KEYNOTE-240 had 135 PBO-treated pts: 8 (5.9%) PP; small samples bar meaningful interpretation. Conclusions: PP in aHCC, per irRECIST, has a similar incidence to other cancers (eg, melanoma) and does not seem to correlate with OS. Data may help physicians assess when to continue pembro after PD. Clinical trial information: NCT02702414, NCT02702401. [Table: see text]
Patient-reported outcomes (PRO) before and after colorectal cancer (CRC) by race in a national survey.
Authors: Barzi Afsaneh , Jiao Xiayu , Farias Albert John 
Published: February 2020

53 Background: There is significant disparities in the incidence, stage at diagnosis, and survival of CRC by race, however there is little evidence for disparities in patient reported health—an important quality of care metric. The SEER-CAHPS database (A linkage of Surveillance Epidemiology and End Results registry with Consumer Assessment of Healthcare Providers and Systems surveys) was used to explore the impact of CRC diagnosis on PRO. Methods: PRO was assessed by general health (GH) and mental health (MH). Responses of fair & poor to survey questions were classified as “modest”; and responses of excellent, very good, & good as “decent”. The responses were compared for surveys within 4 year window before or after CRC diagnosis. Logistic regression was used to identify variables associated with decline from decent to modest in the GH and MH. Results: The distribution of available surveys and outcome categories are presented in Table. CRC diagnosis was associated with a decline in MH (OR 1.42 95% CI 1.09 – 1.86 p-value < 0.05) and GH (OR 1.40 95% CI 1.17 – 1.67 p-value < 0.01). There was no association between race and decline in GH. However, compared to Whites, Blacks experienced lower odds of decline in MH (OR 0.396, 95% CI 0.185 - 0.848 p-value < 0.05). Hispanics had a trend for more pronounced decline in MH (OR 1.772, p value= 0.098). Tumor stage at diagnosis was a predictor of poorer GH (OR 1.75 95% CI 1.40 - 2.19 p-value < 0.01) and MH (OR 1.37 95% CI 1.00 - 1.87 p value = 0.048). Survey characteristics. Conclusions: Diagnosis of CRC is associated with decline in GH and MH across all racial groups, with worse MH and GH in patients with later stages of disease. Minorities experience gereater declines in MH. [Table: see text]
Respiratory-gated magnetic resonance image guided radiation therapy for hepatocellular carcinoma: A pilot study.
Authors: Kang Hyun-Cheol , Kim Jin Ho , Chie Eui Kyu 
Published: February 2020

532 Background: Hypofractionated RT has shown encouraging results in hepatocellular carcinoma (HCC) patients. However, HCC adjacent to the gastrointestnal (GI) tract should be carefully treated using the high-precision irradiation technique due to risk of radiation damage. We evaluated the feasibility of a respiratory-gated magnetic resonance image guided radiation therapy (RgMRg-RT) for hepatocellular carcinoma (HCC). Methods: Thirty-three patients with HCC underwent RgMRg-RT in our hospital from 2015 to February 2019, including patients with Child-Pugh A/B7 cirrhosis and unresectable tumors near the gastrointestinal tract. The median radiation dose was 50 Gy (range, 25–60) and median fraction number was 5 (range, 4–15). Gating was performed based on real-time magnetic resonance image without an external surrogate. Results: The median follow-up period was 11.7 months (range, 3.6–37.9 months). The rates of local control of the target tumor at 6 months and 1 year were 90.2 and 86.9%, respectively. The overall survival rates at 6 months, 1, and 2 years were 84.3, 76.3, and 61%, respectively. The median distances from gross tumor to the esophagus, stomach, duodenum and colon were 6.1 (range, 1.9-14.3), 6.4 (0-13.4), 3.8 (0-13.5) and 4cm (0.3-13), respectively. A total of 15 tumors (45.5%) were located within 2 cm of the gastrointestinal tract and 9 tumors (27.3%) within 1cm. Grades 3 treatment‐related bleeding was observed in one patient and one patient had radiation‐induced liver disease. Conclusions: Hypofractionated RgMRg-RT was a safe and potentially ablative therapy for HCC. RgMRg-RT is a good alternative treatment for patients with HCCs that are unsuitable for surgical resection or local ablative therapy.
Role of para-aortic lymph node sampling for patients with potentially resectable biliary cancer.
Authors: Ito Hiromichi , Ono Yoshihiro , Sato Takafumi , Inoue Yosuke , Takahashi Yu 
Published: February 2020

540 Background: While paraaortic lymph node (PALN) metastasis has been known as poor prognostic indicator for patients with biliary cancer and is regarded as distant metastasis in AJCC staging system. However, preoperative diagnosis of PALN metastasis by current imaging studies is not accurate and the incidence of PALN metastasis among patients with potentially resectable biliary cancer and its impact on their long-term outcomes remain unclear. Methods: The patients who underwent exploratory laparotomy with PALN sampling for potentially resectable biliary cancer at our institution from 2006 through 2018 were included. All patients were appropriately staged preoperatively with CT/MRI and patients with suspected PALN metastasis preoperatively were not considered resectable disease, and thus, such patients were not included. The incidence of PALN metastasis and long-term outcomes (recurrence-free and overall survivals [RFS, OS]) for patients with/without PALN metastasis were compared. Results: Total 383 patients with three types of biliary cancers (164 perihilar cholangiocarcinoma [PHCC], 115 distal cholangiocarcinoma [DCC] and 104 gallbladder cancer [GBCA]) were included. The median age was 71 years and 65% were man. Majority of them (362 patients [95%]) completed planned resection and 9 patients (2%) died of post-operative complications. PALN metastasis was confirmed on 33 patients (9%) among the entire cohort; the yield of positive PALN sampling was the highest in the patients with GBCA (14%), followed by 9% in those with PHCC and 4% in those with DCC. Among 33 patients with positive PALN, 20 underwent tumor resection. Median RFS and OS following resection for the patients with PALN metastasis were 11 months and 22 months, respectively, compared to 46 months and 56 months for those without, respectively ( p< 0.001 for both RFS and OS). There were no survivors beyond 5-years among those with PALN metastasis. Conclusions: The yield of routine intraoperative PALN sampling is not small even among patients with potentially resectable biliary cancer and positive PALN indicates poor long-term outcomes. This procedure can provide the opportunity to avoid morbid operation for patients who unlikely benefits.
Irreversible electroporation of the bile duct in swine: A pilot study.
Authors: Kim Sang Hyun , Lee Jae Min , Lee Kang Won , Kim Sang Hoon , Jang Se Hyun , Jeon Han Jo , Choi Seong Ji , Choi Hyuk Soon , Kim Eun Sun , Keum Bora , Jeen Yoon Tae , Chun Hoon Jai , Lee Hong Sik , Kim Chang Duck ,   Department of Gastroenterology, Korea University Anam Hospital
Published: February 2020

541 Background: Irreversible electroporation (IRE) is a relatively new ablative method. However, the application of IRE ablation has not been attempted for the treatment of biliary disease. Minimally invasive approach using endoscopic retrograde cholangio-pancreatography (ERCP) can be a novel therapeutic modality for IRE ablation. In this study, we investigated the feasibility and effect of endoscopic IRE for biliary tract in animal model. Methods: A new catheter electrode was developed for endoscopic IRE ablation of biliary tract. The electrode for IRE ablation has two band-shaped electrodes on catheter tip. We performed ERCP and endoscopic IRE ablations on normal common bile duct in 6 Yorkshire pigs. Experimental parameters of IRE were 500V/cm, 1000V/cm and 2000V/cm (under 50 pulses, 100 µs length). Animals were sacrificed after 24 hours and ablated bile duct were collected. H & E stain, immunohistochemistry and western blot were performed. Results: Well-demarcated focal color changes were observed on the mucosa of the common bile duct under all experimental parameters. After IRE ablation, bile duct epithelium was disappeared around ablated area and it showed fibrotic change in H&E stain. Depth of change after IRE was different between each experimental parameters. Apoptotic change of bile duct was localized around mucosa in 500V. Diffuse transmural fibrosis of bile duct was shown after IRE ablation with 2000V. TUNEL immunohistochemistry showed the cell death of bile duct mucosa and submucosa along the electrode. Within 24 hours, no complication was observed in pigs after endoscopic IRE ablation. Conclusions: Endoscopic IRE ablation using ERCP was successfully performed on common bile duct by using catheter-shaped electrode. It can be a potential therapeutic option as minimally invasive ablation for treatment of biliary tumors.
Comparative efficacy of second-line treatments for advanced hepatocellular carcinoma: A network meta-analysis.
Authors: Parikh Neehar , Marshall Alexander , Huff Keith D. , Savidge Rachel , Betts Keith A. , Song Jinlin , Zhao Jing , Yuan Muhan , Kim Richard D. 
Published: February 2020

545 Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, and is often advanced at the time of diagnosis. This study conducted a network meta-analysis (NMA) to assess the comparative efficacy of second-line (2L) immunotherapy and tyrosine kinase inhibitors (TKIs) without biomarker selection for advanced HCC (aHCC), including nivolumab (NIVO) + ipilimumab (IPI), cabozantinib (CABO), regorafenib (REG), and placebo (PBO). Methods: Randomized trials for CABO and REG (CELESTIAL and RESORCE) were identified through a literature review and included in the NMA. NIVO (1mg/kg) + IPI (3mg/kg) (from CHECKMATE-040) was linked into the evidence network through a matching-adjusted indirect comparison (MAIC) vs. the PBO arm of the CELESTIAL trial. The CELESTIAL trial was chosen due to the similar study design and patient population as the CHECKMATE-040 trial. Clinically relevant characteristics were matched, which included age, sex, Barcelona clinic liver cancer stage, Eastern Cooperative Oncology Group status, α-fetoprotein level, and prior treatments. The NMA included CELESTIAL, RESORCE, and the MAIC results. Investigator-assessed ORR and hazard ratio (HR) of overall survival (OS) were compared in the NMA. Results: After matching the baseline characteristics in the MAIC, the ORR of NIVO+IPI was 30.4% and the HR vs. PBO was 0.35. In the NMA, NIVO+IPI had significantly higher ORR (31.2%) compared to TKIs and PBO (REG: 4.8%; CABO: 4.2%; PBO: 1.0%, differences are presented in Table). In addition, NIVO+IPI was associated with significantly prolonged OS vs. TKIs and PBO (HR: NIVO+IPI vs. REG: 0.56; NIVO+IPI vs. CABO: 0.46; NIVO+IPI vs. PBO: 0.35). Conclusions: The NMA showed that NIVO+IPI was associated with significantly higher ORR and prolonged OS compared to TKIs as 2L treatments for aHCC. [Table: see text]