bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analytical and clinical validation of the TruCheck platform for diagnostic triaging of symptomatic cases suspected of colorectal cancer.
Authors: Akolkar Dadasaheb B , Patil Darshana , Fulmali Pradip , Fulmali Pooja , Patil Revati , Bendale Kiran , Adhav Archana , Patel Shoeb , Khan Shabista , Dhasarathan Raja , Rajan Vishal , Chougule Rohit , Shejwalkar Pradyumna , Ainwale Akshay , Garte Mohini , Sonawane Rahul , Purane Madhav , Chaudhari Yogeshwar , Sagar Prajakta , Nerkar Shubhangi 
Published: January 2021

24 Background: Trucheck is a non-invasive approach for diagnostic triaging of symptomatic individuals who are suspected of Colorectal Cancer (CRC) and have been advised an invasive biopsy. Trucheck evaluates blood samples for presence of Circulating Ensembles of Tumor Associated Cells (C-ETACs: EpCAM+, Pan-CK+, CD45±) originating from a primary Colorectal Adenocarcinoma (CR-AD: CDX-2, CK-20, Muc2); such C-ETACs are unexpected in asymptomatic individuals as well as in individuals with benign Colorectal conditions. Methods: For Analytical Validation, spike-recovery analysis was performed using control cells / cell lines for EpCAM (SKBR-3), Pan-CK (SKBR-3), CD45 (PBMCs), CDX2 (CaCO2), CK20 (HCT15) and MUC2 (SW620) to determine the Sensitivity, Specificity, Accuracy, Limit of Detection, Linearity and Precision. Clinical Validations were performed using 15 mL blood samples from 587 participants. An initial Retrospective Clinical Pre-validation was based on blood samples from 350 known cases of CR-AD and 20 cases of non-CRC. The Prospective Clinical Validation was performed on blood samples collected prior to any invasive procedures from 217 symptomatic cases suspected of CRC. Results: Analytical Validation indicated 100% Sensitivity, 100% Specificity, 100% Accuracy, 90% Precision and significant linearity (R2≥0.98) for all ICC markers. Clinical Pre-validation indicated 84.9 % Sensitivity and 100% Specificity for CR-AD v/s non-CRC. In the Prospective Clinical Validation cohort, histopathological evaluation (HPE) of biopsied tumor tissue indicated benign Colorectal conditions in 10 cases and CR-AD 207 of the 217 suspected cases. Based on HPE as the standard, the Trucheck approach had 90.3% Sensitivity, 100% Specificity and 95.2% Accuracy. Conclusions: Symptomatic individuals suspected of CRC may benefit from the sensitive and specific non-invasive Trucheck approach. Individuals positive for CR-AD-specific C-ETACs can be prioritized for further clinical procedures while C-ETAC negative individuals can be considered for alternate diagnoses. The Trucheck approach can eliminate the need for (and risks associated with) invasive colon biopsies in a significant proportion of suspected cases and is especially useful where
Investigating chemopotentiation by low-dose fractionated radiation therapy for disseminated intra-abdominal gastric cancer.
Authors: Carrier France , Parekh Palak , Solano-Gonzalez Eduardo , Ma Xinrong , Tighe Kayla , Casildo Andrea , Zodda Andrew , Johnstone Christopher , Poirier Yannick , Mahmood Javed , Bhalla Kavita , Li Sheri , Lapidus Rena G. 
Published: January 2021

242 Background: Treatment options are rather limited for gastrointestinal cancer patients whose disease has disseminated into the intra-abdominal cavity. There is currently no modality that has been shown to prolong survival of this patient sub-population. Here, we designed pre-clinical studies to evaluate the potential application of chemopotentiation by Low Dose Fractionated Radiation Therapy (LDFRT) for disseminated gastric cancer and evaluate the role of a likely biomarker, the Dual Oxidase 2 (DUOX2) enzyme. Methods: Nude mice were injected orthotopically with human gastric cancer cells expressing endogenous or lower levels of DUOX2 and randomly assigned to four treatment groups: 1; vehicle alone, 2; chemotherapy consisting of a modified regimen of docetaxel, cisplatin and 5’-fluorouracil (mDCF) for three consecutive days, 3; Low Dose- Whole Abdomen Radiation Therapy (LD-WART) (5 fractions of 15 cGy in three days), 4; mDCF and LD-WART. Blood was harvested at day 14 and 45 and cancer progression was evaluated by fluorescence imaging (Xenogen). Results: The combined regimen was well tolerated in all animals and led to DUOX2 upregulation, increased serum protein oxidation and reduced cancer progression in the DUOX2 positive tumors. Tumors expressing lower DUOX2 levels were more sensitive to chemotherapy but no additional benefit was obtained with LD-WART. The potential clinical significance of these findings is exemplified by a tumor microarray demonstrating that only about 46% of human gastric tumors expressed DUOX2. The molecular mechanisms underlying DUOX2 effects in response to the combined regimen include NF-kB upregulation and VEGF down regulation. Moreover, the combined regimen of mDCF and LDFRT was also effective on a Cancer Stem Cell (CSC)-Like subpopulation of mouse gastric cancer cells. Conclusions: Taken together these data suggest that DUOX2 could be used as a potential biomarker for patient stratification for chemopotentiation by LD-WART for positive tumors while chemotherapy alone would be more effective for DUOX2 negative tumors. The absence of added toxicity suggests that these cycles could be repeated.
Colonosight: Multitarget RNA-FIT assay for noninvasive detection of advanced colorectal neoplasia.
Authors: Barnell Erica Kay , Kang Yiming , Barnell Andrew Ross , Kruse Kimberly Ray , Fiske Jared , Pittz Zachary R , Khan Adnan , Holmes Faith L. , Heubner Thomas A , Griffith Malachi , Griffith Obi , Chaudhuri Aadel A , Wurtzler Elizabeth Marie 
Published: January 2021

25 Background: Effective colorectal cancer (CRC) prevention and screening requires sensitive detection of all advanced neoplasias (colorectal cancer and advanced adenomas). Existing noninvasive screening approaches cannot accurately detect precancerous adenomas with high sensitivity. Here we describe a multi-factor assay (RNA-FIT test) that combines 8 stool-derived eukaryotic RNA (seRNA) biomarkers, patient demographic information (smoking status), and a fecal immunochemical test (FIT) to sensitively detect advanced colorectal neoplasias and other precancerous adenomas in a 1,305 average risk (45-75 age) prospective cohort. Methods: Average-risk patients undergoing colorectal cancer screening were prospectively evaluated with the RNA-FIT assay prior to an optical colonoscopy. RNA-FIT test results were generated using an ordinal regression model and results were compared to the colonoscopy findings. The model was initially assessed via 5-fold internal cross-validation of the training set and the ultimate model performance was assessed on a hold out testing set. Results: Of the 1,305 eligible patients recruited, 939 were included in the training set and 366 samples were reserved for the hold out testing set. When evaluating all 5 folds of the training set, internal cross validation attained a 61% sensitivity for advanced neoplasias (n = 69), 22% sensitivity for other adenomas (n = 279), 80% specificity for hyperplastic polyps (n = 155) and 86% specificity for no findings on a colonoscopy (n = 436). When employed on the testing set, the RNA-FIT test attained a 62% sensitivity for advanced neoplasias (n = 52), 27% sensitivity for other adenomas (n = 139), 78% specificity for hyperplastic polyps (n = 74) and 84% specificity for no findings on a colonoscopy (n = 101). Sensitivity for colorectal cancer and advanced adenomas with high-grade dysplasia / carcinoma in-situ was 100% in both the training set (n = 6) and hold out testing set (n = 5). Sensitivity for villous / tubulovillous adenomas was 65% in the training set (n = 23) and 60% in the hold out testing set (n = 15). Additional retrospective sample collection from patients with CRC is ongoing to further validate assay sensitivity for CRC. Conclusions: The RNA-FIT assay demonstrated clinically relevant detection of all advanced neoplasia, including early carcinomas, advanced adenomas, and other precancerous lesions. This assay could represent a noninvasive option to prevent colorectal cancer development through precancerous adenoma detection.
Efficacy and safety of nab-paclitaxel plus gemcitabine-cisplatin (GemCis/nab-P) in Korean patients with advanced biliary tract cancers (aBTC): Multicenter retrospective analysis.
Authors: Cheon Jaekyung , Lee Choong-kun , Sang Yunbeom , Kim Chan , Kang Beodeul , Chon Hongjae 
Published: January 2021

274 Background: A recent phase II trial (NCT02392637) demonstrated prolonged survival by treatment with GemCis/nab-P in patients (pts) with aBTC. Further evaluation in real-world setting is necessary to measure the clinical outcomes of GemCis/nab-P in daily practice in Asian pts. Methods: This is a multicenter retrospective analysis of data from 3 institutes in Korea. Between September 2019 and August 2020, a total of 104 pts who received GemCis/nab-P for the management of aBTC were included in this analysis. Results: Median age was 64 years (range, 34-84), and 60 pts (57.7%) were male. GemCis/nab-P was used as the starting regimen in 60 pts (57.7%), 16 pts (15.4%) received GemCis/nab-P after failure of GemCis ± investigational drug (mainly immune checkpoint inhibitors), and 28 pts (26.9%) added nab-P to initial Gem/Cis without progressive disease. Baseline characteristics were as follows: Intrahepatic cholangiocarcinoma (CCC)/extrahepatic CCC/gallbladder cancer in 42 (40.4%)/33 (31.7%)/29 (27.9%); metastatic or recurred/locally advanced in 82 (78.8%)/22 (21.2%) pts. According to RECIST v 1.1, objective response rates (ORR) and disease control rate (DCR) were 30.8% and 81.8% of all pts, 33.4% and 88.4% in initial GemCis/nab-P, 28.6% and 73.8% in intrahepatic CCC, 36.3% and 96.9% in extrahepatic CCC, and 27.6% and 75.9% in gallbladder cancer groups, respectively. In nab-P addition group, while the ORR and DCR of pts without GemCis failure were 39.3% and 85.7%, those with GemCis failure were 6.3%, 50.0%, respectively. Median overall survival and progression-free survival were not reached, with a median follow-up duration of 3.3 months (95% confidence interval [CI], 2.9-6.7). The most common grade 3-4 toxicities were neutropenia (n=36, 34.6%), anemia (n=17, 16.4%), thrombocytopenia (n=10, 9.6%), and febrile neutropenia (n=9, 8.1%). In patients with locally advanced BTC (n=22), 5 patients (22.7%) were converted to resectable disease and underwent surgery. Conclusions: GemCis/nab-P showed consistent real-life efficacy and safety outcomes for Korean aBTC pts compared with those from the phase 2 trial. [Table: see text]
Contemporary real-world treatment patterns and outcomes of patients with advanced/metastatic hepatocellular carcinoma receiving second-line systemic therapy in the United States.
Authors: Gupta Arjun , Girvan Allicia C , Sheffield Kristin M , Chen Yongmei , Kirsch Kelly Rae , Gonzalez Gugel Elena , Peachey Jessica , Cui Zhanglin Lin , Yarchoan Mark 
Published: January 2021

279 Background: Several therapies have recently gained regulatory approval in the United States (US) as second-line (2L) treatment options for patients with advanced unresectable or metastatic hepatocellular carcinoma (HCC). Treatment patterns and associated outcomes in a real-world population, especially in the contemporary era, remain understudied. Methods: This retrospective study utilized electronic health record data collected during routine patient care in outpatient oncology practices in the US. Adult patients diagnosed with advanced/ metastatic HCC between April 2017 and January 2020 were identified from the Concerto HealthAI database. Patients who survived at least one month from the end of first-line (1L) systemic therapy but did not initiate 2L therapy were classified as having received supportive care alone (SCA). Demographics, patient and disease characteristics, treatment patterns, and outcomes were described descriptively. Median overall survival (OS) from initiation of 2L therapy or end of 1L therapy for patients receiving SCA until death was estimated by the Kaplan-Meier method. Results: A total of 586 patients with advanced/ metastatic HCC were identified in the database. 330 patients received 1L therapy, and of those patients 63% (N= 207) received systemic 2L therapy (n= 105) or SCA (n= 102). At first diagnosis of advanced/ metastatic HCC, the median age was 64 years, and 86% were male. Of patients with ECOG status available at diagnosis (67%), 45% had ECOG status 0-1. The most common 1L agents prescribed were sorafenib (n= 126, 61%), lenvatinib (n= 28,14%) and sorafenib + nivolumab (n= 13, 6%) The most frequent agents prescribed in 2L were nivolumab (n= 44, 42%), sorafenib (n=18,17%), and lenvatinib (n=9, 9%). The median OS of patients receiving any systemic 2L therapy was 7.7 months (95% confidence interval 5.7-11.1) from time of receiving 2L therapy, whereas the median OS of patients receiving SCA was 5.0 months (95% confidence interval 3.3-7.1) from time of end of 1L therapy. Conclusions: In this contemporary national real-world cohort of patients with advanced/ metastatic HCC, a third of patients who received 1L therapy subsequently received 2L therapy. Next steps include investigating factors associated with non-receipt of 2L therapy, sequencing of therapies when multiple lines of therapies are received, and evaluating outcomes by type of agent received in 2L and beyond.
Anti-PD-1 antibody SHR-1210 combined with apatinib as adjuvant treatment in patients with hepatocellular carcinoma at high risk of recurrence after radical resection: Preliminary results from a multicenter, randomized, controlled phase II trial.
Authors: Zhao Hong , Zhao Jianjun , Jiang Li , Bi Xinyu , Qian Honggang , Du Shunda , Cai Jianqiang , Zhou Jianguo , Li Zhiyu , Liu Dongbin , Zhang Yubao , Zhang Ping 
Published: January 2021

285 Background: There is no globally recognized standard adjuvant therapy for HCC after radical resection. Herein, we explored to evaluate the efficacy and safety of anti-PD-1 antibody SHR-1210 combined with apatinib as adjuvant treatment versus hepatic arterial infusion (HAI) in HCC patients with high risk of recurrence after radical resection. Methods: This was an ongoing multicencer, randomized, controlled phase 2 trial. All HCC patients were Child-Pugh Class A, and confirmed as high risk of recurrence such as portal vein tumor thrombus (PVTT) involved in second-order branch or above, microvascular invasion (MVI) and microsatellite leisions. Eligible patients were randomly assigned (1:1) to receive SHR-1210 (200mg, q2w) and apatinib (250mg, q.d.) for 12 cycles, or two times of standard HAI treatments (epirubicin 80-100mg or epirubicin 50mg+oxaliplatin 50mg). The primary endpoint was recurrence-free survival (RFS), and the secondary endpoints included safety and quality of life score (QoL). Results: From Jun 12, 2019 to Sep 15, 2020, 32 Chinese HCC patients (pts) (16pts in SHR-1210-apatinib group and HAI group, respectively) had been recruited. Full analysis (FAS) population contained 29 pts and intention to treat (ITT) population included 32 pts. The hadzard ratio for relapse or death with SHR-1210-apatinib as compared with HAI was 0.48 (95% CI 0.12-1.75; P = 0.2992) and 0.38 (95% CI 0.11-1.20; P = 0.0910) in FAS and ITT population, respectively, at date cutoff. Median RFS was not reached and 10.5 months in SHR-1210-apatinib group and HAI group, respectively. The average QoL score during treatment was 48.8 and 49.2 in SHR-1210-apatinib group and HAI group, respectively. The most common grade 3 or 4 adverse events occurred in SHR-1210-Apatinib were γ-glutamyltransferase (GGT) increase (18.75%), leukopenia (12.50%), neutrophil count decrease, alanine and aspartate aminotransferase increase (12.50%), while in HAI group were lymphocyte count decrease (7.69%), hemoglobin increase (7.69%) and GGT increase (7.69%). Conclusions: In HCC patients with high risk of recurrence after radical resection, SHR-1210 combined with apatinib was tolerable, and might offer a new promising choice superior to HAI for adjuvant therapy in HCC, further study is needed to reach the pre-defined primary endpoint. Clinical trial information: NCT03839550.
Impact of NAFLD on clinical outcomes in hepatocellular carcinoma treated with sorafenib: An international cohort study.
Authors: Howell Jessica , Samani Amit , Mannan Binish , Hajiev Saur , Aval Leila Motedayan , Abdelmalak Rebecca , Tam Vincent C. , Bettinger Dominik , Thimme Robert , Taddei Tamar Hamosh , Kaplan David Edward , Seidensticker Max , Sharma Rohini 
Published: January 2021

289 Background:The incidence of non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is increasing. The impact of NAFLD on overall survival (OS), treatment response and toxicity in patients with HCC treated with sorafenib is unknown. We examined the impact of NAFLD on OS and toxicity in an international cohort of patients receiving sorafenib. Methods:Clinical and demographic data were collected from patients consecutively treated at specialist centres in Europe and North America. The impact of NAFLD on OS, sorafenib-specific survival and sorafenib-related toxicity compared to other aetiologies of liver disease using multivariable Cox-proportional hazards and logistic regression modelling was assessed. Results:5201 patients were treated with sorafenib; 183 (3.6%) had NAFLD-associated HCC. NAFLD-associated HCC patients were more likely to be older women(median age 65.8 vs 63.0 years, p < 0.01 and 10.4% vs 2.3%, < 0.01), with a median BMI of 29.4. After controlling for known prognostic factors, no difference in OS in patients with or without NAFLD was observed(adjusted HR 0.94 (95% CI 0.76 -1.16), p = 0.57). NAFLD-associated patients had more advanced stage HCC when they commenced sorafenib (BCLC C/D 70.9% vs 58.9%, p < 0.01) and were more likely to be commenced on a lower starting dose of sorafenib (51.4 vs. 36.4%, p < 0.01). However, there was no difference in sorafenib-specific survival between NAFLD and other aetiologies(HR 0.99, 95% CI (0.85 – 1.16, p=0.92). Adverse events were similar between NAFLD and non-NAFLD HCC groups, including rates of ≥ grade 2 hypertension(6.3 vs. 5.8%, p = 1.00). A lower rate of severe hand foot syndrome was observed in the NAFLD population(3.8 vs. 12.4%, p = 0.03). Conclusions: OS in HCC does not appear to be influenced by the presence of NAFLD. NAFLD-associated HCC derive similar clinical benefit from sorafenib compared to other aetiologies.
Atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma: A cost-effectiveness analysis.
Authors: Wang Wenjun , Wang Jingjing , Zhang Xin , Wang Yikai , Shi Juanjuan , Jia Xiaoli , Dang Shuangsuo 
Published: January 2021

295 Background: In May 2020, atezolizumab plus bevacizumab was approved by US Food and Drug Administration for patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy due to improvement in overall and progression-free survival compared with standard sorafenib treatment. However, because of the high cost of atezolizumab plus bevacizumab, there is a need to assess its value by considering both efficacy and cost. The aim of this study is to evaluate the cost-effectiveness of atezolizumab plus bevacizumab vs sorafenib for patients with unresectable or metastatic HCC from the US payer perspective. Methods: A partitioned-survival model was developed to compare health care costs and clinical outcomes of atezolizumab plus bevacizumab vs sorafenib in first-line treatment of unresectable or metastatic HCC over 6-year horizon. Treatment effects were extracted from the IMbrave150 trial. Health care cost and health utility data were obtained from published studies and databases. Incremental cost-effectiveness ratio (ICER) was calculated as the ratio of the incremental cost to the incremental quality-adjusted life years (QALYs). One-way deterministic and probabilistic sensitivity analyses were used to examine model uncertainty. Additional subgroup analyses were performed. Results: Atezolizumab plus bevacizumab resulted in increase of 0.623 life-years, 0.484 QALYs and $158,781 per patient at the base case analysis. The ICER was $322,500 per QALY (95% confidence interval, $136,275 to $801,509 per QALY), with 0.5% and 4.1% chance of being cost-effective at a willingness-to-pay threshold of $100,000 and $150,000 per QALY, respectively. The ICER never went below $150,000 per QALY in the one-way sensitivity analyses and among patients of clinically relevant subgroups in the subgroup analyses. Conclusions: Atezolizumab plus bevacizumab is unlikely to be cost-effective compared with sorafenib in first-line treatment of patients with unresectable or metastatic HCC from the US payer perspective.
Zanidatamab (ZW25) in HER2-positive biliary tract cancers (BTCs): Results from a phase I study.
Authors: Meric-Bernstam Funda , Hanna Diana L. , El-Khoueiry Anthony B. , Kang Yoon-Koo , Oh Do-Youn , Chaves Jorge M , Rha Sun Young , Hamilton Erika P. , Pant Shubham , Javle Milind M. , Raghav Kanwal Pratap Singh , Fortenberry Allison , Gray Todd , Woolery Joseph , Lee Keun Wook 
Published: January 2021

299 Background: Treatment options are limited for patients with unresectable, locally advanced or metastatic BTCs progressing after first line treatment. Standard second line chemotherapy yields objective response rates (ORR) of < 10% and median overall survival of these patients is < 6 months. Human epidermal growth factor receptor 2 (HER2) overexpression/ amplification is observed in 5–19% of BTCs. Zanidatamab is a bispecific HER2-targeted antibody that has demonstrated durable single agent activity with good tolerability in a range of HER2-overexpressing cancers. Methods: In the expansion cohort of this phase I study (NCT02892123), the primary objective is to characterize safety and tolerability of zanidatamab and secondary objectives include evaluation of anti-tumor activity. This cohort includes BTC patients with centrally confirmed HER2 overexpression (immunohistochemistry [IHC] 3+ or IHC 2+/ fluorescence in situ hybridization [FISH]+), disease progression after standard of care therapy, and measurable disease per RECIST 1.1. Zanidatamab is administered at the previously identified recommended dose of 20 mg/kg every 2 weeks (Q2W). Tumors are assessed every 8 weeks (response confirmed at ≥ 4 weeks). Results: As of the data cutoff date (Jul 28, 2020), 20 patients (median age: 63 years [range, 42–78]) with BTC (11 gallbladder cancers, 5 intra- and 4 extra-hepatic cholangiocarcinomas) have been treated with zanidatamab. The median number of prior systemic therapies was 2.5 (range, 1–8), including five patients who had received prior HER2-targeted therapy (trastuzumab). Fourteen (70%) patients experienced zanidatamab-related adverse events (AEs), all of which were grade 1 or 2 in severity. The most common (occurring in ≥ 20%) zanidatamab-related AEs were diarrhea (n = 9) and infusion-related reactions (n = 6). A single treatment-related serious AE of grade 2 fatigue was reported in one patient. Among patients evaluable for response (n = 17), the confirmed ORR was 47% (n = 8; 95% confidence interval [CI]: 23, 72), the disease control rate was 65% (n = 11; 95% CI: 38, 86) and the median duration of response was 6.6 months (95% CI: 3.2, not estimable). Conclusions: Zanidatamab is well tolerated with promising and durable anti-tumor activity in patients with HER2 overexpressing BTC. Based on these data, zanidatamab is now being evaluated in an ongoing global Phase 2b study in patients with advanced HER2+ BTC that have progressed after treatment with a gemcitabine-containing regimen (NCT04466891). Clinical trial information: NCT02892123.