bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning-based multimodal prediction of prognosis in patients with resected intrahepatic cholangiocarcinoma.
Authors: Schmauch Benoit , Brion Eliott , Ducret Valérie , Nasar Naaz , McIntyre Sarah , Sin-Chan Patrick , Maussion Charles , Jarnagin William R. , Chakraborty Jayasree 
Published: June 2023

4121 Background: Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy and the second most common primary liver cancer. About a third of patients may benefit from surgery but recurrence is common and the overall survival is low. Accurate prognosis modeling that can predict response to treatment and outcome remains an unmet clinical need. Deep learning methods provide a new opportunity to better predict prognosis by extracting distinguishing characteristics interrogating multiple data sources, which appears to be superior to unimodal modeling. This study aimed to construct a predictive model of patient outcome and identify predictive biomarkers based on a combination of clinical, genomic, histological and radiological data. Methods: We analyzed 83 patients with iCCA that underwent surgery and designed a multi-modal model to predict overall survival (OS) and progression-free survival (PFS). Among these patients, each had one to three hematoxylin/eosin histology slides. As a pre-processing step, each histology slide was decomposed into patches, each patch was fed into a ResNet feature extractor to extract a feature representation of the patch, and the features across patches were aggregated with maximum pooling to yield a 2048-dimensional vector representation for each slide. Among these 83 patients, 76 patients had their tumors profiled for somatic genomic alterations using MSK-IMPACT, a deep targeted-sequencing assay. A binary matrix across altered genes and samples was created as an input to the prediction model. Cox proportional hazard models specific to each modality (clinical data, histological slides, and altered genes) were then designed and their predictions were averaged to produce the final log-risk score. The models were validated using a 5-fold, 5-repeat cross-validation with patient-level splits. Results: A model using only clinical and routine histological data achieved a concordance index of 0.74 (95% confidence interval, 0.64-0.82) for OS and 0.73 (0.64-0.78) for PFS. Adding information about genetic alterations improved performance for OS (0.80, 0.70-0.88) and similar performance for PFS (0.72, 0.64-0.79). Both models outperform a staging-based patient stratification. Conclusions: This study demonstrates that machine learning models can improve survival prediction using multi-modal data after resection of intrahepatic cholangiocarcinoma. Such models have the potential to improve risk stratification and treatment recommendations. [Table: see text]
Efficacy and safety of HepaSphere drug-eluting bead transarterial chemoembolization combined with hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma.
Authors: Liu Baojiang , Gao Song , Guo Jianhai , Kou Fuxin , Liu Shaoxing , Zhang Xin , Feng Aiwei , Wang Xiaodong , Cao Guang , Chen Hui , Liu Peng , Xu Haifeng , Gao Qinzong , Yang Renjie , Zhu Xu 
Published: June 2023

4122 Background: Transarterial chemoembolization (TACE) is widely applied and shows good efficacy in advanced hepatocellular carcinoma (HCC). Recently, hepatic arterial infusion chemotherapy (HAIC) has also gained popularity in the treatment of HCC. Several studies have described the comparison between HAIC and TACE or TACE combined with HAIC. However, the evaluation between TACE plus HAIC and HAIC is rarely reported. Here, we observed the performance of HepaSphere DEB-TACE combined with HAIC (Hepa-HAIC) comparing to HAIC in patients with advanced HCC. Methods: 167 patients diagnosed as advanced HCC and treated in Peking University Cancer Hospital from May 2018 to May 2022 were enrolled in this retrospective study, composed of 74 patients received HepaSphere DEB-TACE combined with HAIC-FOLFOX (Hepa-HAIC) and 93 patients received HAIC-FOLFOX. More than 60% patients experienced other treatments before the enrollment. To avoid the selection bias, propensity score matching (PSM) was conducted and applied for the efficacy and safety analysis between these two cohorts. The primary endpoints are progression-free survival (PFS) and overall survival (OS); the secondary endpoint includes objective response rate (ORR), disease control rate (DCR) and safety. Results: Propensity-matching yielded 48 pairs and the baselines were almost equal in Hepa-HAIC and HAIC cohorts after matching. Median PFS and median OS were both higher in matched Hepa-HAIC cohort (median PFS:8.9 vs. 5.8 months, P=0.035; median OS:22.4 vs. 9.5 months, P=0.027), which were consistent with pre-matching analysis. The ORR in Hepa-HAIC and HAIC cohorts was 75.0% and 37.5%, respectively; DCR was 93.8% after Hepa-HAIC and 81.3% after HAIC. There was no treatment-related death. Serious adverse events were similar in these two groups, except alanine aminotransferase (ALT) and vomiting. There was more frequency of Grade 3–4 ALT elevation in Hepa-HAIC (33.3% vs. 8.3%, P=0.003) while more incidence of vomiting in HAIC group (29.2% vs. 12.5%, P=0.044). Conclusions: All of the observed PFS, OS, ORR and DCR in Hepa-HAIC group are superior to HAIC group, which indicates the combination of HepaSphere DEB-TACE and HAIC may lead to improved outcomes with comparable safety profile in advanced HCC. [Table: see text]
Preliminary results of sequential transarterial chemoembolization and stereotactic body radiotherapy followed by immunotherapy using single tremelimumab regular interval durvalumab in locally advanced, unresectable hepatocellular carcinoma (START-FIT using STRIDE): A single-arm, phase II study.
Authors: Chiang Chi Leung , Chang Stephen Lam , Chan Sik-Kwan , Lee Ann Shing , Chiu Keith Wan Hang , Yeung Vanessa Ting Yan , Wong Natalie Sean Man , Lee Venus Wan Yan , Lau Vince Wing Hang , Man Nancy Kwan , Kong Feng-Ming Spring , Chan Albert Chi Yan 
Published: June 2023

4124 Background: Sequential transarterial chemoembolization and stereotactic body radiotherapy followed by immunotherapy (IO) (START-FIT) using anti-PD-L1 has demonstrated promising efficacy in locally advanced HCC (laHCC). We aimed to evaluate START-FIT activity using anti-PD-L1 and anti-CTLA-4 IO backbone. Methods: Adult patients with laHCC not suitable for curative resections were recruited. Each with tumor at least 5cm, maximum three tumors, and child-Pugh A5-B7 liver function. Patients had single TACE, 5-SBRT 28 days after, then single Tremelimumab (300mg) and regular 4-week interval Durvalumab (1500mg) at 7 days upon SBRT completion. Primary endpoint was overall response rate (ORR) per modified Response Evaluation Criteria in Solid Tumors (mRECIST); secondary endpoints included progression-free survival (PFS), overall survival (OS), and treatment-related (TR) adverse event (AE) [NCT04988945]. Results: During 11 Dec, 20 and 3 Oct, 22, 16 patients were enrolled with median age 66 (range (r): 51–84 years), 14 (87.5%) were male, the lesion(s) diameter median sum was 11.2 cm (r: 5.8–15cm), and 11 (68.8%) had macrovascular invasion (n=6, hepatic vein, n=4, branched portal vein, n=1 both). With median 11.3 months (r: 3.7–24.5 months) follow-up time, the best ORR was 81.3% (95% CI: 54.4–96.0%) (Complete response CR: n=7, 43.8%; partial response PR: n=6, 37.5%; static disease SD + progressive disease PD: n=3, 18.7%). The 6 and 12-month PFS rates was 86.7% (95% CI: 69.3–100%) and 58.7% (95% CI: 33.6–84.4%), while 6 and 12-month OS rates was 100% (95% CI: 91.7–100%) and 83.3% (95% CI: 62.2–100%) respectively. The 12-month OS with CR vs. PR vs. SD+PD was 100%, 75%, and 50% respectively. Four (25%) and one patient (6.3%) experienced TRAEs and immune-related AE of grade 3 or worse respectively. Conclusions: START-FIT using STRIDE is safe and effective in unresectable laHCC resulted in 43.8% CR rate and promising survival. Clinical trial information: NCT04988945 . [Table: see text]
Primary analysis of a phase II study of atezolizumab plus bevacizumab for TACE-unsuitable patients with tumor burden beyond up-to-seven criteria in intermediate-stage hepatocellular carcinoma: REPLACEMENT study.
Authors: Ueshima Kazuomi , Kudo Masatoshi , Tsuchiya Kaoru , Kato Naoya , Yamashita Tatsuya , Shimose Shigeo , Numata Kazushi , Kodama Yuzo , Tanaka Yasuhito , Kuroda Hidekatsu , Itoh Shinji , Aikata Hiroshi , Hiraoka Atsushi , Moriguchi Michihisa , Wada Yoshiyuki , Nakao Kazuhiko , Tateishi Ryosuke , Ogasawara Sadahisa , Yamamoto Kouji , Ikeda Masafumi 
Published: June 2023

4125 Background: Intermediate-stage hepatocellular carcinoma (HCC) is a heterogeneous disease; therefore, the efficacy of transarterial chemoembolization (TACE) is affected by tumor burden, resulting in a wide range of survival outcomes. Multiple recent guidelines suggest that systemic therapy is preferable for patients with intermediate-stage HCC who are TACE unsuitable because of high tumor burden, such as beyond up-to-seven criteria. The Phase III IMbrave150 study established atezolizumab plus bevacizumab (atezo+bev) as the standard of care in patients with unresectable HCC. Here, we investigated whether atezo+bev is potentially superior to TACE in efficacy and safety in TACE-naïve patients with unresectable intermediate-stage HCC beyond up-to-seven criteria. Methods: In this multicenter, phase II study, atezo 1200 mg + bev 15 mg/kg q3w were administered to eligible patients (as defined above plus having Child-Pugh A liver function) enrolled from Dec 2020 to Sep 2021 until discontinuation due to disease progression, adverse events (AEs), or other reasons. Overall survival (OS) follow-up continued for 2.5 years after enrolment. The primary endpoint was progression-free survival (PFS) assessed by mRECIST by investigator; secondary endpoints were objective response rate (ORR), PFS by RECIST v1.1, OS, and safety. In an exploratory analysis, we conducted propensity score matching (PSM) analysis to compare the efficacy between atezo+bev and TACE, the data of which were retrospectively collected in patients treated with TACE in each participating center from Jan 2017 to Dec 2017. Results: In total, 74 patients were enrolled (male, 87.8%; mean age, 73.7 years; median [range］maximum tumor diameter by pre-treatment CT, 4.8［1.0,13.0］cm). Median (min, max) follow-up was 15.0 (1.6, 21.6) months. Median PFS was 9.1 (95%CI: 7.1, 10.2) months (by mRECIST; primary endpoint). ORR was 45.9 (95%CI: 34.3, 57.9) % by mRECIST. Median OS was not reached (NR) (95%CI: NR, NR). 12-month OS rate was 84.6 [95%CI: 74.0, 91.2]%. The most frequent AEs (any grade ≥10% of patients) were hypertension, proteinuria, malaise, anorexia, edema, pruritis, and diarrhea. Conclusions: Atezo+bev provides clinical benefits to TACE-unsuitable patients with intermediate-stage HCC beyond up-to-seven criteria. Results of the exploratory PSM analysis will be presented. Clinical trial information: jrcts071200051 .
The efficacy of radical hepatectomy versus stereotactic body radiotherapy for primary hepatocellular carcinoma: A propensity score matching analysis.
Authors: Hu Yulin , Kong Feng-Ming Spring , Ji Ren 
Published: June 2023

4130 Background: Recent international guidelines have included stereotactic body radiotherapy (SBRT) which outstanding tumor control as a treatment option for hepatocellular carcinoma (HCC) in several settings. However, data evaluating surgery and SBRT are limited, and results published were controversial. The retrospective study aims to compare the efficacy of hepatectomy and SBRT for HCC. Methods: The study population started with patients in databases of primary HCC, treated with curative hepatectomy or SBRT, regardless of tumor number, tumor size, cirrhosis and portal vein thrombosis. Patients with prior cancer treatment other than transarterial chemoembolization were excluded. In order to reduce the potential confounding effect of treatment and selection bias, 3-to-1 propensity score models were constructed based on each patient’s estimated propensity score. The variables significant for overall survival were considered for the match, including age, sex, Child-Pugh score, ECOG performance status score, maximum diameter, BCLC stage, prothrombin time, total bilirubin, albumin, and white blood cell. Overall survival and progression-free survival were compared. Results: A total of 174 patients, 154 in hepatectomy group and 20 in SBRT group, were analyzed. 125 men and 29 women, mean 56.2 years of age, in hepatectomy group. 12 men and 8 women, mean 70.5 years of age, in SBRT group. ECOG was a significant favorable factor for overall survival. Maximum diameter, portal vein embolization, aspartate transferase and albumin was significant favorable factors for disease-free survival of patients with primary hepatocellular carcinomas. Before PSM, patients in the hepatectomy group tended to be younger, had better performance status, less cirrhosis, less tumor number and had better hepatic function than those in the SBRT group ( P < .05). The 3-year overall survival rate and median progression-free survival time for the surgical resection and SBRT groups were 77.9% vs 35.4 (P = .003) and 30 vs 20 month (P = .486), respectively. After PSM, 80 patients, 60 in hepatectomy group and 20 in SBRT group, were analyzed. The 3-year overall survival rate and median progression-free survival time for the surgical resection and SBRT groups were 71.9% vs 56.6 (P = .92) and 17 vs 26 month (P = .656), respectively. The patients of hepatectomy group had less cirrhosis, better liver function and less tumor number than those in 20 with SBRT. Conclusions: For primary HCC, regardless of tumor size and tumor number, stereotactic body radiotherapy can provide similar result on overall survival and tumor control compared to hepatectomy. Stereotactic body radiotherapy can also be less invasive and provide less inpatient time. So stereotactic body radiotherapy can be a effective treatment for patients with primary HCC.
Racial disparities in the outcomes of liver transplantation in the treatment of hepatocellular carcinoma.
Authors: Kamal Syeda Ashna Fatima , Vikash Sindhu , Sohail Haris , Kilani Yassine , Vikash Fnu 
Published: June 2023

4131 Background: According to the National Comprehensive Cancer Network (NCCN), liver transplantation (LT) is currently the treatment of choice for patients with early hepatocellular carcinoma (HCC). A retrospective study in 2016 showed a difference in mortality among races in patients undergoing treatment for HCC. Our study is the first to compare the outcomes of mortality, morbidity and hospital utilization of HCC patients undergoing LT among races in the US. Methods: This is a retrospective longitudinal study of patients with a primary diagnosis of HCC. We retrieved data from the Nationwide Inpatient Sample (NIS) databases from the years 2016 to 2020 using ICD-10 codes. Multivariate regression analysis was applied to compare the outcomes in races, adjusted for patient and hospital confounders. A T-Test and Chi Square test were performed to compare baseline characteristics. We used STATA Version 17.0 Software for analysis. The p-value was set at p < 0.05 for statistical significance. Results: Among a total of 112,110 adults with HCC, 2.8% (n=3,150) underwent LT. Blacks had lower rates of LT. Blacks and Hispanics were found to have a lower income (p= 0.000). No difference in the Charlson Comorbidity index was noted among races (p=0.5519), however, Blacks had more smokers (p=0.0149). Hispanics had a significant increase in THC compared to Whites (coefficient: 102,058 US Dollars, p=0.033, CI95%: -109,404 - 119,787), with no difference in the length of stay among races. Blacks had higher rates of mortality (p=0.004), acute kidney injury (AKI) (p=0.001), and similar rates of transplant complications. Conclusions: Our study showed that while Blacks have lower rates of LT, they have a higher rate of mortality and morbidity following LT. Large scale studies are necessary to help determine factors associated with these findings.
ACTION-1 phase Ib/3 trial of RYZ101 in somatostatin receptor subtype 2–expressing (SSTR2+) gastroenteropancreatic neuroendocrine tumors (GEP-NET) progressing after 177Lu somatostatin analogue (SSA) therapy: Initial safety analysis.
Authors: Morris Michael , Ulaner Gary A. , Halperin Daniel M. , Strosberg Jonathan R. , Mehr Samuel H. , Li Daneng , Soares Heloisa P. , Anthony Lowell Brian , Kotiah Sandy Diana , Jacene Heather , Pavel Marianne E. , Kunz Pamela L. , Ferreira Denis Vasconcelos , Li Joanne , Ma Kimberly , Rearden Jessica , Moran Susan , Hope Thomas A. , Singh Simron 
Published: June 2023

4132 Background: RYZ101 (225Ac-DOTATATE) is a first-in-class, highly potent alpha-emitting radiopharmaceutical in development for treating SSTR2+ solid tumors. Alpha-particles (as emitted by 225Ac) have a shorter path length (40–100 μm) and higher linear energy transfer (80–100 keV/μm) than beta-particles, causing more frequent double-strand DNA breaks and potentially higher cancer cell kill rates and less damage to healthy tissues. ACTION-1 (NCT05477576) is a 2-part, global, randomized, controlled, open-label, phase 1b/3 trial of RYZ101 in patients (pts) with advanced well-differentiated SSTR+ GEP-NETs progressing after 177Lu-SSA therapy. Part 1 (phase 1b) aims to determine safety, pharmacokinetics, and recommended phase 3 dose (RP3D) of RYZ101. Methods: Part 1 is an uncontrolled dose de-escalation study with a Bayesian optimal interval design. Escalation (0.197) and de-escalation (0.298) boundaries based on a target dose-limiting toxicity (DLT) rate of 25% were applied. Pts received RYZ101 IV every 8w for up to 4 cycles. Planned dose levels (n=6/level): Level 0 (starting dose), 120 kBq/kg (3.2 µCi/kg); if necessary, Level –1, 90 kBq/kg (2.4 µCi/kg); Level –2, 60 kBq/kg (1.6 µCi/kg). No dose escalation above starting dose was permitted. DLT was assessed for 56d after the first RYZ101 treatment. Treatment-emergent adverse events (TEAEs) were graded by NCI-CTCAE v5.0. Dose de-escalation decisions and safety data review were overseen by a Data Review Committee. Data cut-off: 26 Oct 2022. Results: At data cut-off, 9 pts had received RYZ101 at 120 kBq/kg (median dose 8.9 MBq); 7 pts were DLT-evaluable. No DLTs occurred and no dose de-escalation steps were implemented. Baseline characteristics: median age 70y; male (n=6)/female (n=3); ECOG PS 0 (n=4)/1 (n=5); median disease duration 6.9y; primary tumor site GI (n=6)/pancreas (n=3). A safety summary is shown. No treatment-related serious AEs were observed. TEAE requiring dose reductions occurred in 2 pts (Grade 2 platelet count decreased, n=1; Grade 2 thrombocytopenia, n=1). Grade 3 or 4 TEAEs occurred in 3 pts (lymphocyte count decreased, n=2; skin infection, n=1; weight decreased, n=1). One serious adverse event (skin infection) was unrelated to treatment. Conclusions: RYZ101 was well tolerated at 120 kBq/kg, which was declared the RP3D. Part 2 (Phase 3) will commence after Part 1 and will compare RYZ101 at the RP3D with standard of care in pts with advanced SSTR2+ GEP-NETs with disease progression following prior 177Lu-labeled SSAs. Clinical trial information: NCT05477576 . [Table: see text]
Novel use of alternate (Alt) response (Rp) criteria (Cr) for early prediction of outcomes in pancreatic (P) neuroendocrine tumors (NETs): Utilizing banked imaging data from the ECOG-ACRIN E2211 study.
Authors: Vijayvergia Namrata , Handorf Elizabeth A. , Kunz Pamela L. , Alkim Emel , Burke Lauren M.B. , Catalano Paul J. , Graham Noah , Levin Laura , Li Weier , Meeker Caitlin R. , Rubin Daniel L , Narasimhan Sridharan Anush , O'Dwyer Peter J. , Wong Terence Z. , Anaokar Jordan 
Published: June 2023

4133 Background: The evaluation of treatment (Tx) Rp in NETs using CT/MRI scans can be difficult. Previous studies, including the E2211, have shown improved progression-free survival (PFS) but no significant difference in Rp as measured by RECIST 1.1 (R1.1) Cr. Thus, making it difficult to determine Tx effectiveness with short-term imaging, further complicated by differences in imaging protocols and inter-reader variability. Incorporating tumor density, using smaller threshold changes in tumor size, and novel quantitative features may be more sensitive and precise than R1.1 (e.g. CHOI in GIST) but they have not been studied for NETs. Methods: Banked CT images from the E2211 trial were repurposed to study novel Cr. Three radiologists provided a R1.1 assessment. Density and radiomic features were calculated from a 2D region of interest in the portal venous phase (as per CHOI Cr). Patients were classified as responders (PR), stable disease (SD), or progressive disease (PD) based on R1.1 and CHOI and compared with PFS to determine the best predictor. Radiomic features were analyzed using pyradiomics. Wilcoxon tests were used to compare scan quality by center type, agreement was measured using Cohen’s Kappa, and predictive value was quantified using the c-statistic and AUC for time-varying outcomes. Results: 67 patients had their scans repurposed for the study. Inter-reader agreement for overall imaging studies was fair, with only 5 of 9 PD cases noted by reviewer 1 being agreed upon by reviewer 2 (proportional agreement for PD = 0.56) and a Kappa of 0.6 (95% CI 0.41 – 0.79). The CHOI Cr showed improved prediction of PFS compared to R1.1 (12-month AUC 0.75 for CHOI vs 0.69 for R1.1, c-statistic 0.66 vs 0.64, p=0.22), and was able to predict improved PFS for PR versus SD at the first interval scan. This was not seen with R1.1 (table). Radiomics and texture analysis as a potential adjunct to CHOI is being studied and results will be presented. Conclusions: This study using repurposed banked imaging from an NCTN trial, found that there was significant variability in the interpretation of images, and that the R1.1 Cr had a poor correlation with Rp in PNETs. The CHOI Cr emerged as a better alternative as it may have a better correlation with PFS and the ability to predict outcomes at the point of first disease assessment. Importantly, CHOI Cr can be easily applied in clinical practice to inform treatment decisions. Further research is needed to confirm these findings and define the therapeutic importance. [Table: see text]