bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoting multidisciplinary care for patients with unresectable hepatocellular carcinoma (HCC): Findings from a quality improvement initiative across two community cancer centers.
Authors: Baron Ari David , Delcuze Bethany , Guzzone Francesca , Carter Jeffrey D. , Heggen Cherilyn 
Published: January 2023

528 Background: Evolving treatment paradigms in HCC are increasing the need for multidisciplinary coordination and a focus on patient-centered care. Identifying real-world challenges HCC care teams face in implementing these critical practices is necessary to inform educational interventions and optimize patient outcomes. Methods: In March–April 2021, 22 health care professionals (HCPs) who treat HCC at 2 US community oncology clinics completed surveys assessing practice patterns, challenges, and confidence related to multidisciplinary and patient-centered care in HCC and participated in interdisciplinary audit and feedback sessions. Patient charts evaluated pre- and post-intervention assessed changes in clinical practice. Inclusion criteria included confirmed HCC diagnosis, age ≥ 18 years, and ≥ 2 visits in the one-year chart abstraction period. Results: Participants represented the interprofessional HCC care team: medical oncologists (38%), gastroenterologists (8%), hepatologists (4%), internal medicine (17%), advanced practice professionals (4%), and nurses (29%). Baseline and follow-up patient charts included 50% and 47% Stage II-III HCC patients and 50% and 53% Stage IV HCC patients, respectively. Top reported barriers to multidisciplinary tumor board use were ineffective interdepartmental coordination/collaboration (43%) and low volume of referrals (38%). HCPs aimed to resolve these gaps through improved collaboration between multidisciplinary teams (33%) and earlier referrals to a medical oncologist (29%). Providing patient-centered supportive care was identified by 33% of HCPs as the top challenge in HCC patient care. Of HCPs surveyed, 77% estimated that ≤ 25% of patients are evaluated for/referred to distress/behavioral health services. Chart audits after educational intervention and action plan implementation showed improvements in supportive care utilization (see table). A critical component of patient-centered care, shared decision-making (SDM) was reported by 24% of HCPs. HCPs reported patient resistance to SDM (33%) and low patient health literacy (29%) as top barriers to SDM. Chart documentation of HCP participation in SDM increased post intervention (see table). Conclusions: In current real-world practice, HCC care teams report challenges in interdisciplinary collaboration and referrals, providing supportive care, and involving patients in SDM. These identified gaps represent key opportunities for future interventions to improve HCC care. [Table: see text]
A sequential therapy with sorafenib followed by regorafenib against single-line atezolizumab and bevacizumab in advanced hepatocellular carcinoma (HCC): Indirect treatment comparisons (ITC) using the RESORCE study.
Authors: Partridge Jamie , Aceituno David , Paracha Noman , Thom Howard 
Published: January 2023

537 Background: Our objective was to explore ITC of sequential therapy with sorafenib followed by regorafenib (sorego) against atezolizumab+bevacizumab (atezobev) in HCC. Naïvely comparing median Overall Survival (OS) from sorafenib initiation on sorego in the RESORCE trial with atezobev from IMbrave150 is biased by population imbalance and selection of patients who survived on sorafenib in RESORCE. We used unanchored Matching Adjusted Indirect Comparison (MAIC) and novel survivorship bias adjusted anchored ITC (SBITC) to overcome these limitations. Methods: Overall Survival (OS) from sorafenib initiation in RESORCE on sorego were compared with reconstructed Individual Patient Data (IPD) OS based on Kaplan-Meier curves from IMbrave150 on atezobev. In MAIC, the sorego arm of RESORCE was weighted on reported baseline characteristics to match the IMbrave150 atezobev arm. In SBITC, sorafenib IPD from IMbrave150 were sampled with replacement and added to the RESORCE BSC arm to correct for “survivorship bias”. Sample size was sufficient for follow-up prior to RESORCE randomisation to be within 5% of sorafenib follow-up in IMbrave150. Anchored Bucher ITC was used to compare to unadjusted IMbrave150 with bootstrapping to obtain standard errors. Hazard Ratios (HRs) were used to compare OS. Results: MAIC gave an OS HR of 0.75 (95% confidence interval 0.60, 0.93; p-value=0.007). Effective sample size (ESS) was reduced from 379 to 271.75. SBITC gave a HR of 0.63 (0.52, 0.76; p-value <0.001) requiring an average of 83 sorafenib patients to be added from IMbrave150. Conclusions: We proposed MAIC and SBITC to overcome biases in naïve comparisons of OS on sorego with atezobev in HCC. However, MAIC is limited to baseline characteristics in IMbrave150 and does not adjust for “survivorship bias”. SBITC depends on sample size from IMbrave150, and makes no adjustment for imbalance in baseline characteristics. Despite these limitations, our methods were consistent with naïve comparisons and suggested longer OS with sorego compared to atezobev in patients with HCC.
Malignant portal vein tumor thrombosis (PVTT) in patients with hepatocellular (HCC) carcinoma: Insights from a Western single-institutional cohort.
Authors: Vikash Sindhu , Bteich Fernand , Jiang Julie , Kanmaniraja Devaraju , Acuna-Villaorduna Ana , Saenger Yvonne M. , Goel Sanjay , Kaubisch Andreas 
Published: January 2023

552 Background: Macrovascular tumor invasion in the portal vein system is associated with poor survival and response to therapy. The Japanese portal vein invasion (Vp) classification is based on anatomical location of the thrombus and has been reported to predict prognosis in Asian cohorts of patients. Systemic treatment (ST) options have been increasing over the last decade, coupled with a refinement of radiation (RT) delivery and surgical techniques. Modern literature about HCC and PVTT is scarce in the West. Aim of this study was to characterize outcomes of PVTT patients stratified by Vp categories and by treatment strategies in a Western cohort of HCC patients. Methods: A total of 837 patients with HCC, treated at our tertiary referral center between 2010 and 2022, were retrospectively reviewed. 136 (16.3%) patients with PVTT at the time of diagnosis were identified. PVTT was diagnosed by contrast-enhanced computed tomography or magnetic resonance imaging. The extent of portal tumor-in-vein burden was characterized according to the Liver Cancer Study Group of Japan classification. Treatment modalities were delineated. Median OS was calculated for each group. Cox proportional hazard was used to compare OS between groups. Results: Etiology of liver disease was chronic hepatitis B in 18 (13%) patients, chronic hepatitis C in 79 (57%), alcohol in 53 (39%) and NASH in 10 (7%). Our group comprised 8 Vp1, 16 Vp2, 53 Vp3 and 59 Vp4 patients. 42% were in class Child-Pugh A, 42% B and 16% C. 14 (10%) patients underwent surgical resection of their tumor, 31 (23%) received radiation therapy, 90 (68%) were treated with systemic therapy, while 27 (23%) only received best supportive care (BSC). Median OS was 7.2 months in all comers; 16.0, 3.6, and 1.9 months when stratified by Child-Pugh class A, B, C respectively. Patients lived longer when they had more limited PVTT extent (Table). There was a trend towards worse OS in patients with Vp4 tumors compared to more peripheral thrombi (median OS 4.7 vs 12.8 mo, p=0.055). Patients treated with both ST and RT had a better OS than those treated with either alone (median OS 17.7 vs 5.7 mo, p=0.022). Median OS by treatment type is shown in Table. Conclusions: This retrospective study confirms an association between the extent of PVTT and OS in a Western HCC cohort. Patients with adequate hepatic reserve may benefit from more aggressive multi-modality treatment approaches. OS by PVTT extent and treatment modality.[Table: see text]
Outcomes of patients with hepatocellular carcinoma (HCC) treated in the lenvatinib (LEN) and immunotherapy era (2018-2021) compared to the sorafenib (SOR) era (2008-2018).
Authors: Lim Chloe , Amaro Carla Pires , Ding Philip Q. , Cheung Winson Y. , Tam Vincent C. 
Published: January 2023

553 Background: SOR was the standard first-line treatment for HCC for about a decade until the approval of LEN. Subsequently, atezolizumab + bevacizumab (A+B) were shown to have superior efficacy outcomes. The aim of this study was to compare effectiveness outcomes of HCC patients treated in the SOR era compared to the post-SOR era, when most HCC patients received first-line LEN or A+B. Methods: All HCC patients who started first-line systemic therapy at cancer centres in the Canadian province of Alberta between January 1, 2008 and December 31, 2021 were included in this study. Overall survival (OS), progression-free survival (PFS), and clinician-assessed response rate (RR) were retrospectively analyzed. Since LEN was first available to patients in Canada in August 2018, patients who started first-line systemic therapy between January 2008 to July 2018 were classified as treated in the “SOR era”, while patients treated from August 2018 to December 2021 were classified as being treated in the “post-SOR era”. Results: Of 372 total patients included, 230 were treated in the SOR era and 142 in the post-SOR era. Demographic and clinical characteristics are as follows for the SOR era and post-SOR era groups, respectively: median age was 63 and 64 years, 80% and 81% were male, 24% and 11% were of East Asian ethnicity. Most patients were ECOG 0-1 (85% and 91%), Child-Pugh A (84% and 85%), and ALBI grade 1 or 2 (96% and 98%) prior starting first-line therapy. Most common causes of liver disease included excess alcohol use (24% and 30%), Hepatitis C (37% and 48%), and Hepatitis B (27% and 15%). Most patients had advanced (BCLC C) stage disease in both groups (91% and 87%). Prior to systemic treatment 40% and 33% received TACE, 7% and 9% received TARE, and 3% and 14% received SBRT respectively. See table for first-line treatments received and outcomes. Median treatment duration was 3.2 months and 4.8 months, and median follow-up time was 9.6 and 11.0 months for SOR era and post-SOR era, respectively. Conclusions: In this real-world multicenter retrospective study, patients treated in the post-SOR era, where LEN and A+B were the more common first-line treatments, had superior overall survival, first-line response rates and progression-free survival. This study confirms the real-world progress that has been made in improving outcomes of HCC patients through systemic treatment advancements over the last 15 years.[Table: see text]
Safety of drug-eluting beads transarterial chemoembolization under the combination therapy with immune checkpoint inhibitors in unresectable hepatocellular carcinoma.
Authors: Chiu Sung-Hua , Chang Wei-Chou , Hsieh Chung-Bao , Feng An-Chieh 
Published: January 2023

556 Background: To analyze the safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) under the combination treatment with immune checkpoint inhibitors (ICI) in unresectable hepatocellular carcinoma (HCC). Methods: In this retrospective single-institution study, 208 HCC patients (152 male and 56 female; mean age, 64.70±11.46 years) who received DEB-TACE between 2018.Nov and 2021.Dec were enrolled. There were 74.0% patients had Barcelona Clinic Liver Cancer stage B HCC, 90.4% were Child-pugh A patients, 63.0% patients had albumin-bilirubin (ALBI) grade 2, and 51.0% patients were up-to-seven out. Among them, 50 patients (24.0%) who received ICI with interval less than 30 days with DEB-TACE were categorized as DEB-ICI group; the remaining 158 patients (76.0%) were categorized as DEB group. ALBI grade before and 90 days after DEB-TACE were recorded to evaluate liver function change. Complications within 90 days after DEB-TACE were considered as TACE-related and were compared between two groups. Results: DEB-ICI group had significant higher incidence rate of liver abscess than DEB group (14.0% versus 5.1%, p=0.0337); other TACE-related complications showed no difference between two groups. There were 23.9% patients in DEB-ICI group had elevated ALBI grade after DEB-TACE, which revealed no difference in comparison with 22.4% in DEB group ( p=0.8460). Univariate analysis confirmed that combination with ICI was an independent risk factor of liver abscess formation after DEB-TACE (odds ratio = 3.0523, 95% confidence interval: 1.0474-8.8947, p=0.0409). Among DEB-ICI group, patients received ICI before DEB-TACE had a trend to have higher risk of liver abscess formation than those who received DEB-TACE before ICI (23.8% versus 6.9%, p-value=0.0922). Conclusions: Combination treatment of ICI with DEB-TACE with interval less than 30 days increased risk of liver abscess formation after DEB-TACE.
Efficacy of atezolizumab/bevacizumab combination therapy in BCLC-C cirrhotic patients with hepatocellular carcinoma (HCC) according to the type of disease progression.
Authors: Pantzios Spyridon , Syriha Antonia , Mandilara Dionysia , Stathopoulou Ioanna , Barla Georgia , Galanis Petros , Elelfsiniotis Ioannis 
Published: January 2023

557 Background: HCC recurs in 70-80% of cases following potentially curative liver resection (LR) or radiofrequency ablation (RFA) and the immune component of the liver microenvironment plays a key role in early recurrence. The aim of our study was to retrospectively evaluate, under real life conditions, the overall survival (OS) of patients with advanced HCC (BCLC-C stage), either initially presented in the advanced stage or migrating from BCLC-A to BCLC-C stage within 2 years after curative LR or RFA, treated either with atezolizumab-bevacizumab (ATZ/BEV) combination or with TKIs sequentially (sorafenib as first line and cabozantinib as second line treatment). Methods: Sixty cirrhotic patients with advanced HCC (53 males, mean age 67y, 35% with diabetes, CPT-A=68.3%/CPT-B=28.3%, mean MELD/Na=11, ALBI grade I=28.3%/ALBI grade II=61.7%, 45% with varices) who either initially presented on the BCLC-C stage and were treated with ATZ/BEV (group A, N=19) or TKIs (group B, N=15) or who migrated from BCLC-A to BCLC-C stage within 2 years after LR or RFA and were treated with ATZ/BEV (group C, N=12) or TKIs (group D, N=14) were evaluated. Results: The four groups were comparable for all the baseline parameters evaluated (age p=0.9, gender p=0.1, platelets p=0.4, chronic liver disease etiology p=0.6, coexistence of diabetes p=0.3, presence of varices p=0.1, CPT stage p=0.1, ALBI grade p=0.3). Median OS was significantly higher for group C patients (mean survival 33.7m, median OS was not reached at the time of evaluation) compared to group D (mOS=27m), group A (mOS=13m) and group B (mOS=8m) patients, as presented in figure 1. It is important to note that the survival after HCC recurrence for group C patients (mean survival=18.2m, median OS was not reached at the time of evaluation) was significantly higher compared to those of group D patients (mOS=9m). Conclusions: Median survival of TKI-treated patients after HCC recurrence is less than 12m and is comparable to survivals observed in patients who initially classified in BCLC-C stage, irrespective of treatment schedule. ATZ/BEV combination therapy significantly prolongs survival in patients after early HCC recurrence, a finding that strongly supports the rationale for adjuvant ATZ/BEV therapy in high risk of recurrence patients.
Liver-directed combined radiotherapy for downstaging of over the Milan advanced hepatocellular carcinoma converting to liver transplantation.
Authors: Kim Yong Tae , Lee Jae Geun , Seong Jinsil 
Published: January 2023

561 Background: Recent success of combined immunotherapy sheds a light to the future of advanced hepatocellular carcinoma patients but still remains as a palliative setting. The best oncologic outcome for HCC can be obtained by curative surgery either by resection or liver transplantation (LT). Efficacy of liver-directed combined radiotherapy (LD-CRT) for downstaging and subsequent surgical resection in locally advanced HCC had been reported earlier by our team. In this study, we investigated the role of LD-CRT as a downstaging strategy for converting advanced hepatocellular carcinoma to LT. Methods: We reviewed 55 hepatocellular carcinoma patients who had undergone downstaging LD-CRT and subsequent liver transplantation from January 2009 to February 2022. Patients within Milan criteria at the time of receiving radiotherapy were excluded and clinical characteristics and histopathology of explant liver were evaluated. The overall survival and disease-free survival were assessed using the Kaplan-Meier method. Results: The median follow-up period was 48.6 months (range 6.9 – 151.7 months). Of 55 patients, 24 (43.6%) were treatment naïve. At the time of RT, 36 patients presented large tumor (tumor diameter >5 cm) or multiple lesions (>3 lesions), 37 with major vessel involvement or portal vein tumor thrombosis, and 7 with extrahepatic lesion. LD-CRT was given as localized concurrent chemoradiation (CCRT) for 41 patients (74.5%) and transarterial chemoembolization (TACE) plus RT for 10 patents (18.2%). Substantial downstaging has been achieved in 38 (69%) patients with initially over the Milan to within Milan. Specifically, 29 of 37 patients initially with major vessel invasion or with tumor thrombosis were successfully converted to microscopic vessel invasion or tumor thrombus-free status in explant liver. 5-year overall survival was 68.1% and 2-year disease-free survival was 51%, respectively. Recurrence after transplantation was observed in 18 patients(4 intrahepatic recurrence and 14 extrahepatic metastasis) and the majority (14/18) occurred within 2 years. Conclusions: Liver-directed combined radiotherapy as a downstaging strategy for liver transplantation achieved favorable oncologic outcomes in advanced hepatocellular carcinoma patients. This study suggests that active adoption of radiotherapy needs full consideration for locally advanced HCC patients, opening a chance for curative LT.
Combined transarterial chemoembolization and external beam radiotherapy for identifying surgical candidates for hepatocellular carcinoma with macroscopic vascular invasion: A propensity score-weighted analysis.
Authors: Yoon Sang Min , Lee Sumin , Jung Jinhong , Choi Jonggi , Shim Ju Hyun , Song Gi-Won , Park Jin-hong 
Published: January 2023

562 Background: To evaluate the role of hepatic resection in patients with objective responses after combined transarterial chemoembolization (TACE) and radiotherapy (RT) for hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI). Methods: We retrospectively reviewed the patients treated with combined TACE and RT as a first-line treatment for HCC with MVI between 2010 and 2015. Some patients with objective responses underwent hepatic resection or liver transplantation. Surgical resectability was determined by the hepatobiliary and transplant surgeons of the multidisciplinary team for liver cancer. To investigate the role of surgery, patients with objective responses who did not undergo surgery were selected as a control group. The survival outcomes between the patients who received surgery and those who did not were compared using a propensity score-based stabilized inverse probability of treatment weighting method to minimize selection bias. Time-dependent survival analysis by surgery was performed. Results: Of the 170 patients with objective responses after combined TACE and RT, surgery was performed for 41 patients, including 8 liver transplantations. The unweighted surgery group was younger and had a higher proportion of solitary tumor and unilateral vascular involvement. After adjustment, the overall survival rates at 3 years were 61.0% and 28.6% in surgery and non-surgery groups, respectively. The most important prognostic factor for overall survival was surgery (adjusted Cox hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.17–0.46; p-value < 0.001). Complete response after TACE and RT was also a significant prognostic indicator for overall survival (adjusted HR, 0.41; 95% CI, 0.27–0.61; p-value < 0.001). There was no surgical mortality. Four patients (9.8%) required additional surgery for postoperative bleeding or graft failure. Conclusions: Hepatic resection was significantly associated with improved overall survival in patients with objective responses after combined TACE and RT for HCC with MVI.
Comparison of liver-directed combined radiotherapy versus sorafenib in patients with locally advanced hepatocellular carcinoma with portal vein tumor thrombosis: An Asian Liver Radiotherapy Group Study.
Authors: Seong Jinsil , Kim Jina , Cheng Jason Chia-Hsien , Nam Taek-Keun , Kim Jin Hee , Huang Wen-Yen , Aikata Hiroshi , Kim Myungsoo , Yue Jinbo , Lee Victor Ho-Fun , Zeng Zhaochong 
Published: January 2023

565 Background: While systemic treatment is the mainstay for advanced hepatocellular carcinoma (HCC), numerous studies have highlighted the added value of local treatment. This study aimed to investigate the clinical efficacy of liver-directed combined radiotherapy (LD-CRT) compared to sorafenib, a recommended treatment until recently in locally advanced HCC presenting portal vein tumor thrombosis (PVTT) using a multinational patient cohort. Methods: We identified HCC patients presenting PVTT treated with either sorafenib or LD-CRT in 10 tertiary hospitals over Asia during 2005-2014. Propensity score matching (PSM) was performed to minimize the imbalance in patient and tumor characteristics of the two groups. The primary endpoint was overall survival (OS), and secondary endpoints were distant metastasis free survival (DMFS), local failure free survival (LFFS), and treatment related toxicity. Results: Total 1,035 patients including 360 patients in the sorafenib group and 675 patients in the LD-CRT group were enrolled. The majority of patients in the sorafenib group received 400 mg of sorafenib twice a day initially, and the dose was reduced to 50% or 25% if adverse reactions were noted. LD-CRT was given in liver-directed concurrent chemoradiotherapy in 502 (74.4%) patients, followed by transarterial chemoembolization plus radiotherapy in 149 (22.1%) patients. After PSM, 336 patients from each group were matched, and all features were well balanced between the two groups. At a median follow up of 28.8 months (interquartile range, 16.5-63.6), the median OS was 11.0 and 17.1 months for the sorafenib and LD-CRT groups, respectively ( p=0.001). In addition, LD-CRT group showed significantly improved DMFS and LFFS compared to the sorafenib group (median DMFS 14.9 vs 9.6 months, p=0.004, and median LFFS 15.7 vs 9.6 months, p=0.002). Conversion rate to curative surgery was significantly higher in the LD-CRT group (8.6% vs 0.9%, p=0.002). Those who underwent surgery had younger median age (54 vs 59, p=0.024), smaller median tumor size (6.5 cm vs 8.9 cm, p=0.012), and more unilateral disease (75.0% vs 43.8%, p<0.001). OS and LFFS were significantly prolonged in patients who underwent surgical treatment. Grade 3 or higher toxicity was more frequently noted in the sorafenib group compared to the LD-CRT group (7.7% vs 0.7%, p<0.001). Conclusions: Analysis of a propensity score matched multinational patient cohort revealed that liver-directed combined RT improved survival outcomes of locally advanced HCC patients presenting PVTT. While further prospective studies are warranted, we carefully suggest active multimodal local treatment for locally advanced HCC presenting PVTT.