bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world (RW) study in patients (pts) with metastatic colorectal cancer (mCRC) with long-term responses to regorafenib in the USA.
Authors: Kim Richard D. , Pan Xiaoyun , Ostojic Helene , Zhang Yiqiao , Lunacsek Orsolya , Pisa Federica , Peeters Marc 
Published: January 2024

48 Background: Anecdotal evidence suggests that some pts with mCRC experience significantly longer responses to REG in clinical care settings, including a case exceeding 9 years. However, comprehensive studies on long-term responders to REG are lacking. We evaluated demographic/clinical characteristics of pts with long-term response (LTR) to REG using duration of treatment (DOT) as a surrogate for treatment response. Methods: This was a retrospective cohort study using the US nationwide de-identified Flatiron Health Electronic Health Record-derived database. The study period was January 1, 2013 to May 31, 2023, and adult pts with mCRC who initiated REG monotherapy (index date) from July 1, 2013 to December 31, 2022 were included. DOT for pts with LTR of ≥5 months (LTR5 [primary objective]; mos) or ≥4 mos (LTR4 [secondary objective]) were determined. Results: A total of2,326 eligible pts (median age 64 yrs; 56% male) had initiated REG during the study period. Overall, 346 pts (15%; median age 65 yrs) had LTR5 and 503 pts (22%; median age 65 yrs) had LTR4. Among pts with LTR5, 46% had stage IV disease at initial diagnosis, 68% had ECOG performance status (ECOG PS) 0‒1 at index, 64% received prior bevacizumab (BEV), and of pts tested at index with results, the median carcinoembryonic antigen (CEA) level was 35 ng/mL, and 51% and 5% had a KRAS and BRAF mutation at index, respectively; pts with LTR4 had similar characteristics (Table). Median time from initial CRC diagnosis to index date was 39.2 mos for pts with LTR5 and 38.6 mos for pts with LTR4. Of pts who initiated REG before 2019 (n = 1,070), 14% had LTR5 and 21% had LTR4; of pts who initiated REG from 2019 onwards (n = 1,256), 16% had LTR5 and 22% had LTR4. Among pts with LTR5, 33% and 23% had received REG as third-line (3L) or fourth-line (4L) treatment, respectively; among pts with LTR4, 34% and 23% had received REG as 3L or 4L treatment, respectively. Median time to discontinuation of REG was 7.3 (95% CI 6.9, 7.8) mos in pts with LTR5 and 6.0 (95% CI 5.7, 6.2) mos in pts with LTR4. Median follow-up time (from index date) was 13.3 mos and 11.1 mos in pts with LTR5 and LTR4, respectively. Conclusions: This is the first large-scale RW evidence study to describe demographic/clinical characteristics of pts with LTR to REG. Pts demonstrating LTR typically had favorable ECOG PS at REG initiation, less advanced disease at initial diagnosis, and the majority had received prior BEV. [Table: see text]
Evaluating the safety and efficacy of the addition of liver radiation (RT) to atezolizumab and bevacizumab (A/B) in advanced hepatocellular carcinoma (HCC): A retrospective cohort analysis.
Authors: Brown Timothy J. , Amit Uri , Ben-Josef Edgar , Karasic Thomas Benjamin 
Published: January 2024

481 Background: Recently, the addition of stereotactic body RT to sorafenib in patients (pts) with advanced HCC demonstrated improved overall survival. However, A/B is the current standard of care for pts with advanced HCC based on IMBrave150. For these pts, RT may potentiate the antitumor immune response of A/B but carries the risk of bowel toxicity and impaired liver function. To date, there are limited data regarding safety and outcomes with the addition of liver RT to A/B in pts with advanced HCC. Here, we describe our single-center experience of adding RT to A/B for pts with advanced HCC. Methods: This single-center retrospective cohort study was conducted at the University of Pennsylvania. We identified all pts with HCC naïve to systemic therapy who received infusions of A/B and those who received RT to the liver within 30 days of starting A/B until discontinuation from 1/1/2020 until 2/2/2023. We assessed the real-world response rate (rwRR) determined from clinician impression after initiating A/B, safety outcomes, overall survival (OS), and time-to-progression (TTP) from initiation of A/B. Time-to-event outcomes were analyzed by the Kaplan-Meier method with log-rank test and Cox proportional hazards modeling. Results: We identified 49 pts (n=34 control, n=15 RT) with advanced HCC receiving first-line A/B. Those who received RT were more likely to have alcoholic liver disease (p=0.013) and were less likely to have ascites (p=0.04) but were otherwise balanced regarding demographics, prior locoregional therapies, presence of macrovascular invasion and extrahepatic spread, and baseline laboratories. The median RT dose was 63 Gy. The rwRR in the RT group was 73.3% (11/15) compared to 17.6% (6/34) in the control group (Risk Ratio (RR) 3.9, 95% CI 1.7-8.6, p<0.001). Two pts in the control group (5.8%) and one patient in the RT group (6.7%) experienced clinically significant bleeding (RR=1.1 95% CI 0.1-11.6). In the RT group, three pts (20%) developed worsening liver dysfunction after completing RT, concerning for possible radiation-induced liver disease. Six pts in the control group and one patient in the RT group developed immune-related adverse events leading to discontinuation of A/B. The median OS in the RT group was 14.4 mos and 10.8 mos in the control group (Hazard Ratio (HR) death 0.49 (95% CI 0.20-1.22, p=0.12)). Median TTP was 6.4 months (mos) with RT compared to 5.8 mos in the control group (HR progression 0.72 (95%CI 0.35-1.46, p=0.36. Conclusions: In our retrospective cohort, the addition of liver RT to standard A/B resulted in increased responses and a non-significant improvement in outcomes without an increased risk of bleeding. An assessment of changes in liver dysfunction by Child-Pugh and ALBI score is ongoing. Overall, these data support prospective trials to evaluate the addition of RT to A/B.
Therapeutic effectiveness of high-intensity focused ultrasound (HIFU) ablation in patients with unresectable hepatocellular carcinoma.
Authors: Kim Jin Il 
Published: January 2024

490 Background: High-intensity focused ultrasound (HIFU) ablation is a new therapeutic method for treatment of solid tumor. To determine the efficacy and safety of HIFU, we report our experience for local therapy of primary or metastatic hepatocellular carcinoma (HCC). Methods: From January 2015 to December 2022, forty- eight patients with unresectable HCC underwent single or two therapeutic sessions of HIFU under general anesthesia. Ten patients with liver metastasis from colon cancer and three patients with liver metastasis from stomach cancer were included. We used HIFU, ultrasound-guided extracorporeal system (HIFU Technology Company, Chongqing, China). Thirty-three patients received transarterial embolization before HIFU. Thirteen patients were treated with chemotherapy before HIFU. Technical effectiveness per patient and per masses was assessed according to clinical findings and MR imaging at follow-up. Complications were also recorded. Results: We treated total 78 tumors in 48 patients. The tumor size ranged from 1.3 cm to 12 cm in diameter. Small (< 3 cm), intermediate (3-5 cm) and large tumors (>5 cm) are 44, 24 and 10 patients, respectively. Average procedure time was 4 hours 10 minutes with 68 minutes treatment time. We made the artificial pleural effusion to get treatment field in 25 patients. Mean follow-up period was 52 weeks. For the technical effectiveness per patient as follows: complete ablation with no evidence of recurrence on follow up in 18%, apparent complete ablation of target mass with progression of new lesions on follow up in 29%, recurrence after apparent complete ablation in 26%, and incomplete ablation at 2 week follow up in 27%. Average post-procedure hospital day was 5.4 days. No severe complication except mild right upper quadrant pain was observed after treatment. Conclusions: HIFU is an effective and safe treatment option for local image-guided tumor ablation in patients with unresectable HCC. Although further study is necessary, these results show that HIFU may be helpful in treating unresectable HCC.
Adjuvant TACE plus lenvatinib as compared with TACE alone in patients with hepatocellular carcinoma at high risk of recurrence after surgery: A prospective controlled study.
Authors: Zhang Bin , Jin Renan , Xu Junjie , Chen Ming yu , Chen Jiang , Zhu Hepan , Cao Jiasheng , Song Chao , Yang Zaibo , Zhang Yewei , Liang Xiao 
Published: January 2024

505 Background: Hepatocellular carcinoma (HCC) remains the fourth leading cause of cancer related deaths globally. Radical resection is still the main curative approach for patients with resectable HCC in China. However, the high 5-year postoperative recurrence rate of about 40% to 70% had become the main negative factor affecting the long-term survival benefit. Although transarterial chemoembolisation (TACE) can effectively reduce the recurrence rate and improve disease-free survival (DFS) and overall survival (OS), the outcomes of patients at high risk of recurrence are still not satisfactory. Thus, there is an urgent need for new adjuvant treatment regimen to further improve the survival outcomes. In this study, we compared the efficacy and safety of the lenvatinib plus TACE with TACE alone for postoperative patients with HCC who were at high risk of recurrence. Methods: The factors associated with high risk of recurrence were defined as pathological suggested vascular invasion (including vascular embolus, cholangiocarcinoma embolus and microvascular invasion), suspicious positive surgical margin or surgical margin < 1cm, satellite lesion with cancer, positive lymph nodes, low differentiation and incomplete envelope. Eligible patients were those who had received radical resection for HCC and had risk factors above. Patients were assigned in a 1:1 ratio to receive the combination of lenvatinib and TACE or TACE alone. Results: From September 2019 to May 2023, 119 patients were enrolled in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. Sixty received TACE + lenvatinib and 59 received TACE only. The baseline characteristics were similar between two groups. The median duration of follow-up was 22.5 months (rang: 3 to 47) in TACE + lenvatinib group and 23 months (rang: 5 to 48) in TACE group. The 1-year DFS rate was 81.2% (95% CI: 70.8%-93.1%) in lenvatinib + TACE group, which was significantly higher than that of TACE group (58.3% [95% CI: 46.8%-72.7%], p = 0.0087; HR = 0.44 [95% CI: 0.23-0.83]). The median DFS was not reached (95% CI: 28-NR) in lenvatinib + TACE group, and was 20.0 months (95% CI: 12.0-NR) in TACE group. Patients' liver function after treatment with TACE + lenvatinib was comparable to that in the baseline. Conclusions: The preliminary results of this study suggested that adjuvant lenvatinib in combination with TACE can significantly improve DFS compared with TACE alone in patients with HCC at high risk of recurrence after surgery. The toxicity of combined treatment was tolerable and manageable. The follow up is still ongoing to observe the long-term benefit of this treatment regimen.
Liver toxicity following reirradiation and multiple-target SBRT for primary hepatocellular carcinoma.
Authors: Hall Jacob , Moon Andrew M , Young Michael , Tan Xianming , Darawsheh Rami , Danquah Flora , Tepper Joel E. , Yanagihara Ted K. 
Published: January 2024

514 Background: Stereotactic body radiation therapy (SBRT) is increasingly used to treat hepatocellular carcinoma (HCC), but its safety in the treatment of multiple synchronous or recurrent lesions is underreported. We aim to better characterize SBRT-related hepatic toxicity in this population. Methods: We conducted a retrospective analysis of patients with primary HCC who underwent SBRT for 2 or more synchronous or recurrent liver lesions. We collected patient characteristics and dosimetric data (mean liver dose, cumulative effective volume [Veff], cumulative volume of liver receiving 15Gy [V15Gy], and cumulative planning target volume [PTV]) along with liver-related toxicity (measured by albumin-bilirubin [ALBI] and Child-Pugh [CP] scores). We employed a linear mixed-effects model to assess the effect of multi-target SBRT on changes in ALBI. Results: There were 25 patients and 56 lesions with median follow-up of 29 months. Eleven patients had synchronous lesions and 14 had recurrent lesions treated with separate SBRT courses. Eight local failures occurred at a median of 8 months (range: 4 – 25 months) after SBRT. Among those receiving multiple SBRT courses, there were 7 lesions with overlap of V15Gy (median V15Gy overlap: 35mL, range: 0.5 – 388mL). There was no association between cumulative Veff, V15Gy, or PTV and change in ALBI. Four of 25 patients an increase of Child-Pugh (CP) score by ≥ 2 points, within 3 to 6 months after SBRT. Neither increase in CP nor ALBI were associated with cumulative Veff, V15Gy, and PTV. Comparing the groups that received SBRT in a single course versus multiple courses revealed no statistically significant differences in liver toxicity. Conclusions: LiverSBRT for multiple lesions in a single or in separate courses results in worsening of CP scores or ALBI in a small percentage of patients, suggesting a low risk of RILD. Prospective studies with a larger cohort are needed to better characterize safety in this population.
Des-gamma-carboxy prothrombin (DCP) as a biomarker for treatment response in hepatocellular carcinoma.
Authors: Conner Elizabeth , Chang Jeremy , Burgoyne Adam 
Published: January 2024

547 Background: Causes of variable disease response to first-line treatment with atezolizumab/bevacizumab (atezo/bev) in hepatocellular carcinoma (HCC) patients remain unclear. Identifying tumor markers that predict treatment efficacy may help raise clinical suspicion for early disease progression. The role of des-gamma-carboxy prothrombin (DCP) is not well established in Hepatitis B Virus (HBV) non-endemic areas. This study aimed to investigate DCP as a predictive biomarker of atezo/bev treatment response in HCC patients. Methods: This single-center retrospective analysis evaluated DCP and radiographic response in HCC patients who received atezo/bev in the first-line setting. DCP was measured at the time of best response evaluation and compared to day one of atezo/bev initiation. Elevated DCP was defined by >=7.5 ng/mL. DCP response was defined as a decrease of >=50% at response assessment compared with baseline. Treatment response was evaluated based on imaging modalities including computed tomography and/or magnetic resonance imaging. Objective response rate (ORR) was defined as the percentage of patients with complete response (CR) and partial response (PR). Disease control rate (DCR) was defined as the percentage of patients with CR, PR, and stable disease (SD). No Response (NR) was defined as the percentage of patients with SD and PD. Comparisons of treatment effects were performed using two-tailed Fisher Exact Probability Test. Results: A total of 53 HCC patients treated with atezo/bev as first-line therapy were included. The best treatment responses according to radiographic evaluation were as follows: CR 3.8%, PR 22.6%, SD 52.8%, and PD 20.8%, respectively. Patients with DCP response had ORR of 69% (odds ratio, 15.75; 95% CI, 3.50-70.9; P=.0002) and DCR of 100% ( P=.047). Patients with >=50% increase in DCP at response evaluation compared to day one of treatment had ORR of 4.5% and NR of 95% ( P=.0035). On day one of treatment, 70% of patients had an elevated DCP. There was no difference between elevated DCP vs non-elevated DCP on day one of treatment and ORR. Conclusions: This study found that DCP has utility in predicting response to atezo/bev for HCC patients in HBV non-endemic areas. Further studies are needed to confirm findings and evaluate the prognostic implications of DCP in HBV non-endemic areas.
Inflammation gene signature to predict survival outcomes in hepatocellular carcinoma (HCC): A machine-learning approach.
Authors: Al-Bzour Nour , Sahin Ibrahim Halil , Cavalcante Ludimila , Singh Meghana , Al-Bzour Ayah N. , Saeed Azhar , Saeed Anwaar 
Published: January 2024

551 Background: Inflammation is closely associated with HCC tumorigenesis. Understanding transcriptomic features of inflammatory response will elucidate potential therapeutic targets that could improve survival outcomes. Herein, we study the association between inflammation-based genes and survival outcomes in early-stage HCC. Methods: Transcriptomic and clinical data of 249 patients with resectable stage I and II HCC were obtained from The Cancer Genome Atlas. 132 genes associated with acute and chronic inflammatory response were identified from the molecular signature database. Those were then used in a principal component analysis (PCA) to cluster patients into high and low inflammation groups using the median of the first PCA. Inflammation related differentially expressed genes (DEGs) between the two groups were then identified & were fit in Least Absolute Shrinkage and Selection Operator model to reduce the multicollinearity. Uni- and multi-variate Cox proportional hazard model was used to find the independent predictors of survival. PCA was applied to significant genes to calculate the inflammation score (IS) and the optimal cut-off point was chosen based on survival. Log-rank test and Kaplan Meier curves were used to correlate the IS with overall survival (OS) & disease-free survival (DFS). Pearson’s Chi-squared, Wilcoxon rank sum, and Fisher’s exact tests were used to correlate the inflammation groups with clinical variables. Gene set variation analysis was performed to investigate enriched pathways between groups using the cancer hallmark gene sets. Results: We identified 6 inflammation-related DEGs associated with survival including: ADAM8, CCR7, FFAR3, S100A9, TNF, and TREM1. Two of those were independent predictors of survival: TREM1 & FFAR3. Based on IS cut off of 0.29 we have grouped patients into inflammation high (n=91) and inflammation low (n=158) groups. The low-inflammation group had significantly better OS & DFS (P=0.00039, P=0.039) respectively. No significant association was found between the inflammation groups and multiple variables including hepatitis B and C, alcohol and non-alcohol fatty liver disease. Stage I HCC patients had low-inflammation scores and better survival outcomes compared to stage II, indicative of an association between inflammation and HCC evolution. Pathway enrichment analysis notably showed significant enrichment in signal transduction pathways in the high inflammation group including Wnt/β-catenin, Notch, PI3K-AKT-mTOR, Hedgehog, TGFβ and upregulated KRAS signaling. Conclusions: Findings from this analysis highlight the close association between inflammation and survival outcomes in early-stage HCC and support the utility of an inflammation-based gene signature to predict survival in this disease setting. Our work also sheds light on potentially targetable pathways linked to IS that deserve further exploration.
Serologic, radiographic, and tissue-based markers associated with major pathologic response after treatment with neoadjuvant immunotherapy in patients with resectable hepatocellular carcinoma.
Authors: LaPelusa Michael Brian , Chamseddine Shadi , Xiao Lianchun , Hasanov Elshad , Bhosale Priya , Abugabal Yehia I. , Gok Yavuz Betul , Yadav Shalini S. , Tran Cao Hop Sanderson , Xu Li , Hu Zishuo Ian , Lee Sunyoung S. , Sakamuri Divya , Curran Michael A. , Jindal Sonali , Duda Gabriel Dan , Sharma Padmanee , Qayyum Aliya , Kaseb Ahmed Omar 
Published: January 2024

561 Background: Neoadjuvant immunotherapy can induce a major pathologic response (MPR) in patients with resectable hepatocellular carcinoma (HCC), which may be associated with prolonged recurrence-free survival. This study aimed to understand which variables correlate with achieving an MPR. Methods: Patients with resectable HCC who received either neoadjuvant nivolumab plus ipilimumab or nivolumab alone and underwent surgery were included. 18 patients had baseline and post-treatment computed tomography, alpha-fetoprotein (AFP), and elastography. 17 of these patients had baseline and post-treatment tissue available for immunohistochemistry. Patients were classified into two groups: MPR, defined as necrosis of >70%, and no MPR. Data was summarized using descriptive statistics and compared using Wilcoxon rank sum test. P value <0.05 was considered statistically significant. Results: Statistically significant differences in objective response (OR) and changes in CD8, Granzyme B, and PD-1 expression were identified upon comparison of patients with an MPR to those without an MPR (Table 1). Additionally, numerical differences in baseline tumor size, change in AFP, and both non-tumor and tumor liver fibrosis (at baseline, after treatment, and interim change) were identified upon comparison of patients with an MPR to those without an MPR. Conclusions: Our data show that large baseline tumor size, greater OR, reduction in AFP, increase in liver and tumor fibrosis, and increase in CD8, Granzyme B, and PD-1 expression after receipt of neoadjuvant immunotherapy are associated with achieving an MPR in patients with resectable HCC. [Table: see text]
Epidemiological characteristics of patients with cholangiocarcinoma with and without ulcerative colitis: A retrospective cohort study.
Authors: Nieto Dominguez Alejandro , Eichinger Sarah Elizabeth , Olafimihan Ayobami Gbenga , Guifarro Rivera Daniel 
Published: January 2024

564 Background: Ulcerative colitis (UC) is correlated with gastrointestinal cancer. While the exact mechanism is unknown, it is thought that a chronic inflammatory state may result in the development of malignancies including cholangiocarcinoma. Patients with UC that develop cholangiocarcinoma usually have a poor prognosis and early detection is key to improve survival. Methods: We used the 2016-2019 National Inpatient Sample (NIS) database, the largest all-payer inpatient care database in the United States, to stratify all patients admitted with a diagnosis of cholangiocarcinoma with and without ulcerative colitis, to further characterize their epidemiological characteristics. Results: There were at total of 46,001 patients with a diagnosis of cholangiocarcinoma studied. Of these patients with cholangiocarcinoma, 401 had concomitant UC (0.87%). Individuals with UC in the database had an increased association with cholangiocarcinoma (OR=7.67, 95% CI 6.96-8.46) compared to those without UC. Patients with cholangiocarcinoma and UC tended to be younger (57.8 vs. 67.9 years old without UC), male (69.51% vs. 53.23% without UC), with private insurance (57.5%) vs. patients without UC who predominately had Medicare (59.46%). Patients with cholangiocarcinoma and UC had on average fewer Charleston Comorbidities (64.63% with 3 comorbidities) vs. patients without UC (74.52% with 3 comorbidities). Of patients with cholangiocarcinoma and UC, 65.85% were Caucasian (vs. 64.85% without UC), 6.1% were Black (vs. 10.09% without UC), 3.66% were Hispanic (vs. 12.37% without), and 24.39% were Asian or Pacific Islander (vs 12.79% without). Conclusions: In the population studied, there was a significant correlation between UC and cholangiocarcinoma. Patients with cholangiocarcinoma and UC tended to be younger with fewer comorbidities than their counterparts without. There were nearly double the percentage of Asian patients with cholangiocarcinoma and UC as compared to Asian patients without UC. Understanding the characteristics of patients with UC who develop cholangiocarcinoma is important as it could inform future best practices in potential screening and early detection of carcinomas in patients with UC. [Table: see text]