bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world experience and outcomes of hepatocellular carcinoma (HCC) treated with transarterial radioembolization (TARE).
Authors: Das Parthib , Min Eric , Paul Samuel , Manne Ashish 
Published: January 2024

463 Background: TARE has been the preferred choice of locoregional therapy to advanced HCC in recent years. We attempted to identify factors contributing to the success of TARE in this retrospective review. Methods: HCC patients who received at least one TARE between 1/1/2015 and 8/30/22 at Ohio State University were included in this study. The patient's baseline characteristics at diagnosis (BLC) were extracted by chart review with post-procedural complications and survival outcomes. Descriptive statistics and log-rank test for survival outcomes were conducted using JMP Pro 16 (SAS Institute Inc., Cary, NC). Results: Our cohort had 144 patients with median age of diagnosis (dx) of 65 years, 81 % Caucasians, 81% males, 5% and 51% with hepatitis B and C, respectively; 24% and 21% ascites (As) and hepatic encephalopathy (HE) at dx, respectively; 72% (n=125) had just one procedure (24 had two planned procedures which were considered as 1), 12% (17) and 1% (2) had second and third procedures for recurrence, respectively. Immune checkpoint inhibitor (ICI) and other systemic therapy (tyrosine kinase inhibitor (TKI) or ramucirumab (Ram)) were given to 27% (5 before and 34 after TARE) and 24% (5 before and 30 after TARE), respectively. Other HCC-related BLC includes the number of lesions 1 vs 2-3 vs multiple = 45% vs 33% vs 22%; single lobe vs two lobes = 66 vs 33%; portal vein tumor thrombosis (PVTT) = in main portal vein vs. non-main veins (left or right or lower level) vs no PVTT = 14% vs 10% vs 76%. Median overall survival (OS) and time to recurrence after the first TARE (TTR) were 11 and 4 months (m), respectively. The only BLC that significantly influenced TTR was As (3 vs 4 m, p=0.008). Factors impacting OS were discussed in the table. Follow-up imaging (median = 3m) was available for response evaluation in 107/144 (indeterminate response (IR) reported in 25), and the response noted was reflective of OS (objective response vs. disease progression vs indeterminate, 22 vs 6 vs 8.5 m, p<0.001). Conclusions: Careful patient selection based on BLC and the use of ICI (before or after) could improve the outcomes in HCC patients treated with TRAE. Larger prospective studies are needed to validate the study. [Table: see text]
Defining ablative radiotherapy in patients with hepatocellular carcinoma: An expert consensus.
Authors: Yanagihara Ted K. , Tepper Joel E. , Moon Andrew M , Barry Aisling S , Molla Meritxell , Seong Jinsil , Torres Ferrán , Lawrence Theodore Steven , Reig Maria , Dawson Laura A. ,   mDelphi Committee Members
Published: January 2024

485 Background: External beam radiotherapy (EBRT) is a highly effective treatment in select patients with hepatocellular carcinoma (HCC). However, there are many types of EBRT described in the literature with no formal definition of what constitutes “ablative.” Thus, we convened a group of international experts to provide consensus on the parameters that define ablative EBRT in HCC. Methods: A Steering Committee was convened to generate a series of Key Criteria (KC) that could be used to define ablative EBRT for HCC. KC were based on factors related to dose, fractionation, radiobiology, target identification, and delivery technique. An international panel of experts participated in a modified Delphi (mDelphi) process to independently answer questions for each KC. Respondents were given 30 days to respond in round 1 of the mDelphi and 14 days to respond in round 2. A threshold of ≥ 70% was used to define consensus for answers to each KC. Results: Invitations were sent to 40 individuals and 35 (88%) returned responses. In the first round of the mDelphi, 3 of 7 KC reached consensus. In the second round, 100% of participants returned responses and consensus was reached in 3 of the remaining 4 KC. Based on this mDelphi analysis, there was expert agreement that ablative EBRT for HCC should be defined as 1) a BED10 ≥ 80 Gy, 2) daily imaging and multi-phasic contrast used for target delineation should be used, 3) treatment breaks (e.g., for adaptive EBRT) are allowed, but the total treatment time should be ≤ 6 weeks, 4) the equivalent dose when treating with protons should use a conversion factor of 1.1, and 5) there is no single conversion factor for carbon ions. In one KC, which questioned the expert’s opinion on the α/β ratio of HCC, consensus was not achieved. Conclusions: Using an mDelphi method assessing expert opinion, we provide the first consensus definition of ablative EBRT for HCC. Empiric data are required to define the α/β of HCC.
Efficacy and safety of surufatinib in biliary tract cancer: Preliminary results of a real-world study.
Authors: Zhang Zongli , Ma Changlin , Li Enshan , Gao Yanchao , Bao Guangjian , Lu Jun , Sun Kejian , Zhou Xu , He Qiang , Xu Yunfei , Li Kangshuai , Yang Faji 
Published: January 2024

486 Background: When applied in the second-line treatment for biliary tract cancer (BTC) pts, surufatinib (a small-molecule inhibitor of VEGFR1-3, FGFR1 and CSF-1R) monotherapy has demonstrated moderate clinical efficacy and has demonstrated favorable tolerability and safety profiles. This study was to evaluate the efficacy and safety of surufatinib as a therapy for BTC in a real-world setting. In particular, pts who received resection for BTC with positive margins would be eligible for this study. This population indicates a poor prognosis, for their tumor environment is complex, which is an obstacle to R0 resection. However, no proper treatment for this population has been recommended yet. Methods: This is an ongoing single-arm, multi-center, open-label real-world study conducted in China. The study would enroll 200 pts with unresectable or surgical resection with positive margins BTC. Pts would receive surufatinib with or without combination as adjuvant (namely pts with positive margin after resection), first- or further-line therapy, at a proper dose (200-300mg) judged by physicians once per day in 28-day cycles. The primary endpoint is relapse-free survival (RFS) for pts whose primary lesions were resected, and progression-free survival (PFS) for those had evaluable lesions. If available, tumor assessments were performed every 2 cycles ± 7 days according to RECIST version 1.1. Results: By Sep 10, 2023, 56 eligible pts had been enrolled, of whom 16 (28.6%) were female. The median age was 64 (range: 39-81). 28 (50.0%), 24 (42.9%), and 4 (7.1%) pts received surufatinib as adjuvant, first-line, and above treatment, respectively. As to location, 23 cases were intrahepatic cholangiocarcinoma (ICC), and 33 cases were extrahepatic cholangiocarcinoma (ECC) or gallbladder cancer (GBC). With a median follow-up time of 9.5 (range: 1.1-20.3) mo, the global mRFS/mPFS was 10.4 (95% CI: 9.0-13.9) mo. The mRFS of pts who received surufatinib as adjuvant treatment was 11.3 (95% CI: 10.4-NA) mo, and mPFS of those who received surufatinib as systematic treatment was 9.0 (95% CI: 7.8-10.8) mo. Pts with ICC demonstrated an mRFS/mPFS of 10.4 (5.8-NA) mo, and those with ECC or GBC demonstrated 10.4 (9.5-NA) mo. The global mOS was 15.8 (12.4-NA) mo. Among those with primary lesion unresected (n=28), 2 pts (7.1%) achieved CR, 5 (17.9%) pts PR, 16 (57.1%) pts SD, and 5 (17.9%) pts suffered PD. The ORR was 25.0%, and DCR was 82.1%. No new safety signal was observed. Conclusions: Surufatinib exhibited promising efficacy and manageable toxicity on pts with BTC in the real-world setting. Clinical trial information: NCT05064852 .
Recurrence in the pelvic side wall after lateral lymph node dissection for rectal cancer.
Authors: Takao Misato , Kawai Kazushige , Takagi Maki , Funatsu Nozomi , Natsume Soichiro , Nakano Daisuke , Yamaguchi Tatsuro 
Published: January 2024

49 Background: Locally advanced rectal cancer poses a persistent challenge due to the risk of local recurrence, which impacts patient outcomes and quality of life. To address this, lateral pelvic lymph node dissection (LPND) has emerged as a surgical approach to improve local control. However, comprehensive studies evaluating the outcomes and patterns of recurrence after LPND are limited. This retrospective study aimed to fill this gap and provide insights into the effectiveness of LPND. Methods: We conducted a retrospective analysis of 515 patients diagnosed with stage II-III lower rectal cancer who underwent TME and LPND between January 2005 and August 2022. Clinicopathological data were collected, and tumor staging followed the TNM classification system. Recurrence patterns, survival rates, and factors influencing lateral pelvic recurrence were assessed. Results: In our cohort, 18.8% of patients had pathologically positive lateral lymph nodes. Patients with lateral lymph node metastasis exhibited significantly lower 5-year relapse-free survival (31.6%) and overall survival (47.8%) rates compared to those without metastasis (69.5% and 84.7%, respectively). Local recurrence occurred in 20.1% of all patients, with 6.7% experiencing lateral pelvis recurrence (LPR) and 17.4% central pelvis recurrence. Multivariate analysis identified age over 75, lateral lymph node metastasis, and adjuvant chemotherapy as independent risk factors for LPR. Conclusions: Lateral pelvic lymph node dissection remains a valuable tool in managing locally advanced rectal cancer. Our findings underscore the importance of surgeon expertise in performing LPND and the potential benefits of combining treatments to further reduce lateral recurrence. LPND should continue to be explored and refined to enhance patient outcomes in this challenging clinical scenario.
Qualification of major pathological response as a surrogate endpoint for relapse-free survival following neoadjuvant immunotherapy for hepatocellular carcinoma.
Authors: D'Alessio Antonio , Stefanini Bernardo , Blanter Julia , Adegbite Benjamin , Fulgenzi Claudia A.M. , Celsa Ciro , Manfredi Giulia F , Pai Madhava , Goldin Robert D. , Shu Daniel , Su Yung-Yeh , Baretti Marina , Anders Robert A. , Yarchoan Mark , Hsu Chiun , Marron Thomas Urban , Pinato David James 
Published: January 2024

506 Background: Neoadjuvant use of immune checkpoint inhibitors (ICI) is feasible and achieves pathological responses in a subset of patients with hepatocellular carcinoma (HCC). However, it is not clear whether pathological response to ICI translates into long-term survival benefit. Methods: We analysed patient-level data from 86 subjects recruited to 4 prospective phase I/II clinical trials of ICI prior to liver resection (LR) in 9 centres in the United States, Europe, and Asia and included a cohort of 23 patients (pts) receiving neoadjuvant ICI off trial. Radiological response was assessed with RECISTv1.1. Major (MPR) and complete pathological response (pCR) were considered as ≥70% and 100% non-viable tumour in the resected specimen, respectively. Pathological responses were correlated with radiologic overall response rates (ORR) and relapse-free survival (RFS). Results: Out of 109 pts treated between 10/2017 and 09/2023, 55 pts (50.5%) received a double ICI combination, 35 (32.1%) ICI monotherapy, and 19 (17.4%) an antiangiogenic/ICI combination. In 19 pts (17.4%) an adjuvant ICI course was administered for a median time of 5.5 months (m) (interquartile range [IQR] 3.7-6.0). Most of pts were male (77.6%) with underlying viral chronic liver disease (68.2%), performance status 0 (83.5%), BCLC 0-A (55%), a median tumour diameter of 6.0 cm (IQR 3.9-9.9) without portal vein thrombosis (75.7%). After a median follow-up of 27.3 m (95% CI 21.5-33.0), 35 (32.1%) relapses and 14 (12.8%) deaths occurred. Radiologic ORR was 28.5% (n=31), with 3.7% complete responses (CR, n=4) and 24.8% partial responses (PR, n=27). Out of 100 pts evaluable for a pathological response, 33% achieved MPR and 19% pCR. MPR was more likely in patients who had achieved a radiologic PR or CR (82%) as compared to those who did not (14% p<0.001), however linear correlation suggested an imperfect correlation between ORR and MPR (R2 0.43, p<0.0001). Median RFS was 43.5m (95%CI, 27.5-59.6), while median overall survival was not reached (NR). mRFS was significantly improved in pts with MPR (NR vs 28.3m [95%CI, 13.1-43.5], hazard ratio [HR] 0.27 [95%CI, 0.11-0.69], p = 0.003) and with pCR (NR vs 32.8m [95%CI, 15.2-50.4], HR 0.20 [95%CI, 0.05-0.82], p=0.013). Conclusions: This study is the first to qualify the role of MPR as a putative surrogate endpoint for recurrence-free survival in pts treated with neoadjuvant immunotherapy for HCC. Validation in larger phase III clinical trials is warranted.
Update results from ALTER-H004 study: Anlotinib combined with TACE as adjuvant therapy in patients with hepatocellular carcinoma (HCC) at high risk of recurrence after surgery: A single arm, multi-center, phase II clinical trial.
Authors: Wu Zheng , Wang Zheng , Zhang Lei , Song Xiaojing 
Published: January 2024

513 Background: High recurrence rate after curative resection significantly compromised the long-term survival of patients with HCC patients (pts). TACE as adjuvant therapy was proved to improve clinical outcomes for pts with high recurrence risk factors after hepatectomy. However, the prognosis of TACE reminded unsatisfactory and controversial. Therefore, this study aimed to identify the efficacy and safety of anlotinib as maintenance adjuvant treatment following inductional TACE in pts with HCC. The update results were reported here with longer follow-up duration. Methods: HCC pts with one of the following high risk factors after hepatectomy: ≥5 cm and <10 cm of tumor diameter, tumor number ≥3, tumor microvascular invasion M1 or M2, portal vein tumor thrombus resection (Cheng's classification I/II) were recruited. Eligible pts received cTACE treatment within 1-2 months after hepatectomy, on the 3-5th day after cTACE, oral anlotinib (12mg, qd, d1-d14, q3w) was given until disease recurrence or unacceptable toxicity. The predefined sample size was 30. The primary endpoint was disease free survival (DFS). Secondary endpoints included 1-year DFS rate, time to recurrence and safety. Results: The data cut-off date was March 2023, 29 pts were enrolled and 27 pts received at least once tumor assessment. The median follow-up was 21.8 (IQR, 17.3-26.3) months. Of 27 with assessable efficacy, mDFS was 24.2 (95% CI, not applicable-not applicable) months, with 12-, and 24-month DFS rates of 72.2% (95% CI, 50.4%-85.7), and 61.8% (95% CI, 38.8%-78.3%), respectively. 18 of 27 pts (66.7%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 4 pts (14.8%) included hypertension (7.4%), leukocytopenia (7.4%) and ascites (3.7%). No grade 4 or 5 TRAEs occurred. Conclusions: Anlotinib combined with TACE as adjuvant therapy in HCC pts at high recurrence risk exhibited encouraging efficacy and tolerable safety profile. And the conclusions needed to be confirmed in large scale clinical trials subsequently. Clinical trial information: NCT04213118 .
Histopathologic and genomic profile characteristics of biliary cancers related to pancreaticobiliary maljunction.
Authors: Tohyama Shodai , Ohyama Hiroshi , Ohno Izumi , Amemiya Kenji , Hirotsu Yosuke , Sakai Miho , Watabe Kazuki , Yamada Nana , Sugihara Jihei , Ohuchi Mayu , Kan Motoyasu , Nagashima Hiroki , Takahashi Koji , Okitsu Kohichiro , Mishima Takashi , Takayashiki Tsukasa , Mochizuki Hitoshi , Ohtsuka Masayuki , Kato Naoya , Omata Masao 
Published: January 2024

527 Background: Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic duct and bile duct anatomically merge outside the duodenal wall, and is associated with a high rate of biliary cancer. It has been reported that TP53 and KRAS mutations are found not only in the cancerous area but also in the noncancerous area. However, there is no report of precise mapping of genetic mutations throughout the gallbladder and bile ducts. Methods: Ninety-seven patients (including 31 patients with biliary cancer) who underwent cholecystectomy and cholangiectomy for PBM between 1990 and 2023 at our hospital and affiliated hospitals were included in the study, and consent forms were obtained from 36 patients. The panel targeting 60 genes frequently identified in biliary tract cancer was created in-house and deep sequenced to compare with clinicopathological features. To date, we have analyzed 4 patients with biliary tract cancer and 5 patients without it (with prophylactic resection). The same analysis was also performed on cancerous and noncancerous parts of patients of gallbladder cancer and cholangiocarcinoma without confluence abnormalities for comparison. Results: A total of 33 Samples (7 cancerous parts and 26 noncancerous parts) were examined for biliary tract cancer. We found a variety of functional gene abnormalities, including driver mutations such as TP53, ARID2, and BRCA2, in 9 non-cancerous areas including hyperplasia and normal bile duct mucosa. Some of these mutations were not shared with cancerous areas. On the other hand, in 46 samples from 5 patients who did not develop gallbladder cancer (prophylactic resection), Driver mutations were found in only 3 sites. Pathological findings of dysplasia/hyperplasia in these prophylactic resections were observed in 28 of the 46 sections. In addition, Driver mutations were rarely observed in noncancerous areas in patients with normal gallbladder or cholangiocarcinoma. Conclusions: Unlike conventional biliary tract cancers, the patients with PBM showed a great variety of genetic abnormalities in both cancerous and noncancerous areas. On the other hand, in patients of prophylactic resection without cancer, driver mutations were almost completely absent despite the presence of mucosal changes. We believe that these findings can develop better strategy for biliary cancers with PBM.
The role of pre-operative ctDNA in resectable intrahepatic cholangiocarcinoma.
Authors: Choi Woo Jin , Li Zhihao , Magyar Christian , Tin Antony , Spickard Erik , Sethi Himanshu , Liu Minetta C. , Bucur Roxana , Grant Robert C , Vogel Arndt , Knox Jennifer J. , Liu Geoffrey , Gallinger Steven , Sapisochin Gonzalo , O'Kane Grainne M. 
Published: January 2024

528 Background: Genomic profiling of circulating tumor DNA (ctDNA) is increasingly used in intrahepatic cholangiocarcinoma (iCCA) to inform precision oncology approaches and determine resistance mechanisms to targeted therapies. The application of pre-operative ctDNA testing in the management of iCCA for prognostication remains unclear. Methods: In this retrospective study, we analyzed pre-operative plasma samples from 14 patients who underwent curative resection for iCCA without neoadjuvant therapy. A personalized and tumor-informed assay (Signatera; Natera, Inc.) was used for the detection and quantification of ctDNA. We correlated ctDNA profiles with baseline tumour characteristics and clinical outcomes. Results: The mean interval between pre-operative blood collection and surgery was 43 days (range: 1 to 90 days). ctDNA was detected in all patients except for one with stage Ia (AJCC 8th) disease (Table). The mean pre-operative ctDNA concentration was lowest in the stage Ia group [4.2 mean tumor molecules (MTM)/mL] and highest in the stage II group (134.0 MTM/mL). The mean pre-operative ctDNA concentration did not exhibit a linear correlation with disease recurrence or mortality rates, however, it showed a moderate-to-good linear correlation with the largest pathologic tumor size (R2 = 0.55). Among the three patients who had IDH1/2 mutations tracked in the plasma by Signatera, two patients had positive IDH1/2 detection in ctDNA with mean ctDNA concentrations of 83.7 MTM/mL (range: 33.8 to 133.5 MTM/mL). The patient with the second-highest ctDNA concentration (133.5 MTM/mL and 1818 days follow-up) had stage Ib disease with an IDH1 mutation but has shown no evidence of recurrence. Conclusions: In the pre-operative setting for iCCA resections, ctDNA can be reliably detected across all disease stages using a tumor-informed approach, even when blood is collected up to 90 days before surgery. While single time-point pre-operative ctDNA concentration levels do not appear to correlate with outcomes, similar to previous reports in colon adenocarcinoma, they may correlate with tumor volume. Further studies are needed to evaluate the utility of tumor-informed ctDNA testing in the post-operative setting to detect molecular residual disease for improved prognostication. [Table: see text]
Cost-utility analysis of sequential therapy with sorafenib followed by regorafenib versus single-line therapies in advanced hepatocellular carcinoma.
Authors: Grossman Jamie , Fawsitt Chistopher , Aceituno David , Paracha Noman , Özgürdal Kirhan , Thom Howard 
Published: January 2024

529 Background: Regorafenib is the only licensed second-line therapy available for patients with advanced hepatocellular carcinoma (HCC) that progress on first-line sorafenib in the UK. We evaluated the lifetime cost-effectiveness of a sequence of treatment with sorafenib followed by regorafenib (SOR-REG) compared with licensed single-line therapies for which there is no clear sequencing options available, including atezolizumab plus bevacizumab (ATEZO+BEV), which has become the standard of care in first-line treatment, as well as lenvatinib (LEN), followed by best supportive care (BSC). Methods: Assuming a UK National Health Service and Social Services perspective, we developed a probabilistic individual-level semi-Markov model with states reflecting progression-free survival, progression following first-line treatment, further progression following second-line treatment, and death. First-line overall survival (OS) and progression free survival (PFS) were informed by fractional polynomials network meta-analysis of published trials. Individual patient data from a phase 3 trial (RESORCE) on regorafenib and BSC informed OS and PFS in the second-line setting. Costs and utilities were sourced from published studies. Cost-effectiveness was summarized using incremental net monetary benefit (INMB), which could be positive or negative depending on direction of expected benefit associated with SOR-REG, and cost-effectiveness acceptability curves at willingness-to-pay (WTP) thresholds. Results: We found 1000 probabilistic samples and 1000 patients were sufficient for convergence. Lifetime costs were highest with ATEZO-BEV ([£80,963 [95% CI: £11,022, £97,369]), followed by SOR-REG (£38,373 [£31,064, £43,420]) and LEN (£37,351 [£5,020, £55,800]). Quality-adjusted life years (QALYs) were highest with ATEZO+BEV (1.021 [0.152, 1.239), followed by SOR-REG (0.942 [0.802, 1.057]) and LEN (0.755, [0.094, 1.092]). At a WTP threshold of £30,000 / QALY gained, SOR-REG had an INMB of £40,211 (95% CI -£2,099, £52,731) and £4,589 (-£8,044, £14,481) versus ATEZO+BEV and LEN, respectively. Conclusions: A sequence of SOR-REG for patients with advanced HCC is cost-effective at WTP thresholds of £30,000 / QALY gained due to lower lifetime costs and broadly comparable QALY gains with single-line ATEZO-BEV and LEN in the UK. Broader second-line treatment options are needed for patients receiving ATEZO+BEV and LEN as first-line therapies.