bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment patterns of gemcitabine-based chemotherapy in patients with de novo and recurrent advanced biliary tract cancer.
Authors: Dayyani Farshid , Stirnadel-Farrant Heide A. , Hu Jenny , Lin Yian , Kebede Nehemiah , Valerio Stephen J. , Ahn Daniel H. 
Published: January 2024

454 Background: Biliary tract cancers (BTC) are often diagnosed at advanced stages (aBTC) when prognosis is poor. In the Phase 3 TOPAZ-1 study (NCT03875235), durvalumab plus gemcitabine and cisplatin (GemCis) significantly improved overall survival versus placebo plus GemCis. To better understand the context of the TOPAZ-1 trial results in the US, we looked at first-line (1L) treatment patterns in participants with aBTC treated with GemCis and other gemcitabine (Gem)-based chemotherapy (CT) regimens. Methods: This retrospective observational cohort study used linked electronic health records and medical and pharmacy claims data from the Optum Market Clarity Database. Adults diagnosed with de novo or recurrent aBTC, who initiated 1L Gem-based CT between January 2016 and March 2022, were identified and followed from the index date (defined as the first administration of Gem-based CT on or after initial BTC diagnosis date) until death, end of continuous enrollment, or end of study period, whichever occurred first. Variables including patient demographics, clinical characteristics, and treatment patterns were described. Results: A total of 580 patients were included in the analysis with either de novo aBTC (n=481, 82.9%) or recurrent aBTC (n=99, 17.1%) with median follow-up time of 10.4 (interquartile range: 6.4, 17.5) and 12.0 (interquartile range: 6.3, 21.9) months, respectively. Mean (SD) age was 64.6 (11.2) and 66.8 (10.4) years, with 45.7% and 54.5% male in the de novo and recurrent aBTC groups, respectively. Most patients were white (77.6%). The most frequent site of primary tumor diagnosis was single-site intrahepatic (overall 62.8%, de novo 66.7%, recurrent 43.4%). In the 12 months prior to index date, 38.5% of patients had biliary obstruction, 30.2% had biliary stents, 29.3% had jaundice, and 17.1% had nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Common comorbidities included cardiovascular disease (50.9%), obesity (46.8%), and diabetes (35.2%). The most common 1L CT was GemCis followed by Gem for both the de novo (n=355, 73.8% and n=36, 7.5%) and recurrent groups (n=58, 58.6% and n=26, 26.3%), respectively. Approximately half of participants (50.9%) switched to a new line of treatment, 33.3% discontinued 1L CT, and 15.9% remained on 1L CT at last follow-up. Most frequent 2L treatments included fluorouracil/oxaliplatin (36.9%) and capecitabine (14.2%). Further analysis will characterize outcomes and regimen duration. Conclusions: Findings from this retrospective study showed that the most common 1L therapies were GemCis and Gem among both de novo and recurrent patients with aBTC. These results provide insight into aBTC treatment practices and may help inform treatment decisions.
Real-world testing, treatment patterns, and outcomes following liquid biopsy in advanced cholangiocarcinoma.
Authors: Mahipal Amit , Clemens Keelia M. , Liao Jiemin , Weipert Caroline M. , Bucheit Leslie , Khushman Moh'd M. 
Published: January 2024

455 Background: Cholangiocarcinoma (CCA) is an aggressive cancer with a poor prognosis. Given failure rates of up to 27% of CCA tissue biopsies, liquid biopsy has become an important tool to identify actionable molecular alterations. It is estimated tissue-based testing identifies IDH1 mutations and FGFR2 fusions in 12% and 9% of patients with advanced CCA (aCCA), respectively. Here we examined the rate of molecular alteration detection using circulating tumor DNA (ctDNA) testing, treatment patterns in aCCA, and outcomes for patients receiving ivosidenib following ctDNA-detected IDH1 mutations. Methods: Real-world data was sourced from GuardantINFORM, which comprises aggregated commercial payer health claims and de-identified records from >330,000 patients with clinical ctDNA testing via Guardant360 (G360), from 2014 to 2023. Patients with aCCA and >1 treatment claim after G360 results were included (N=1726). Patient outcomes were assessed via real-world time to treatment discontinuation (rwTTD), real-world time to next treatment (rwTTNT), and real-world overall survival (rwOS), all assessed in months. Log rank test was used to compare Kaplan-Meier survival curves. Results: Of 1495 patients with >1 ctDNA alteration detected, a guideline-recommended biomarker was identified in 18% of patients. In patients with intrahepatic CCA (n=403), 11% had an IDH1 mutation, 9% an FGFR2 fusion, 1% MSI-H detected, 1% BRAF V600E mutation, <1% ERBB2 amplification and <1% RET fusion. Testing was performed prior to first-line therapy, after first-line therapy and after second-line therapy in 34%, 46% and 21% of patients respectively. Gemcitabine and cisplatin represented the most common first-line therapy (48%). FOLFOX (21%), gemcitabine and cisplatin (13%), and capecitabine (11%) were the most common second-line therapies. Among ivosidenib-naïve patients with an IDH1 mutation, 58 (20%) started therapy within 90 days of ctDNA test: 36% received ivosidenib, 57% received chemotherapy, 7% received other therapy. Patients with IDH1 mutations treated with ivosidenib (n=21) had numerically improved rwTTD and rwTTNT compared to those receiving chemotherapy (n=33) [rwTTD: 4.6 (95% CI:2.6-8.6) vs 2.8 (95% CI:2.0-6.3), p=0.1011; rwTTNT 11.0 (95% CI:5.7-NE) vs 5.2 (95% CI:3.3-NE); p=0.2559]. There was no difference in rwOS between patients receiving ivosidenib vs not. However, sample size was small. Conclusions: The rate of actionable molecular alterations detected via ctDNA is 18%, comparable to reports from tissue-based testing. Patients with aCCA are often tested before starting first or second LOT. Patients with ctDNA-detected IDH1 mutations treated with ivosidenib and had a trend toward improved rwTTD and rwTTNT, although it did not reach statistical significance. This data supports the clinical utility of liquid biopsy to identify aCCA patients who may benefit from targeted therapy.
Characterization of outcomes and genomic alterations (GA) in combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA).
Authors: Haro-Silerio Jaime , Fox Daniel Aaron , Bhamidipati Deepak , Hu Zishuo Ian , Koay Eugene Jon , Ludmir Ethan B. , Tran Cao Hop Sanderson , Vauthey Jean-Nicolas , Newhook Timothy E. , Tzeng Ching-Wei D. , Chun Yun Shin , Mahvash Armeen , Metwalli Zeyad , Habibollahi Peiman , Cox Veronica L. , Kang Hyunseon , Chatterjee Deyali , Kaseb Ahmed Omar , Javle Milind M. , Lee Sunyoung S. 
Published: January 2024

458 Background: Hepatobiliary cancers comprise a heterogeneous spectrum of invasive carcinomas involving the liver and bile ducts. Due to its rarity, the prognosis and clinical outcomes data are poorly understood. This study aims to provide insight into the response to therapeutic options and GA in patients (pts) with cHCC-CCA. Methods: We conducted a retrospective analysis of clinical outcomes data and GA at MD Anderson (MDA) from 2009 to 2023 in pts with cHCC-CCA. Pt characteristics were compared using Fisher’s exact test and Mann-Whitney U. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier and the log-rank test. Results: 40 pts with cHCC-CCA were analyzed. Hepatitis B and C were the most common etiologies (Table). 25.0% had portal vein tumor thrombus and 72.0% had advanced disease (M1/N1) at diagnosis. Radiographic washout was seen in 55.9%. Elevation of CA19-9, AFP, and both was in 42.5, 57.5, and 30.0%. Cirrhosis at diagnosis was 35.0%. Pts who underwent surgery (n=10) had significant OS benefit (55.6 vs. 14.1 m, p<0.001). Y90 (n=4)/radiation therapy (n=10) provided significant OS benefit in pts who did not undergo surgery (23.3 vs 10.9 m; p=0.012). 34 pts received 1st line systemic therapy: 10 pts received gemcitabine/cisplatin (GC) combined with immunotherapy (GCI): GC + nivolumab (n=5), durvalumab (n=3), or atezolizumab/bevacizumab (AB, n=2). GCI was compared to other regimens (OR, n=24) including chemotherapy alone (GC, FOLFIRI, FOLFOX), HCC-directed therapy alone (AB, lenvatinib, nivolumab), or chemotherapy plus lenvatinib or bevacizumab with mPFS of 7.0 vs. 2.9 m (p=0.014) showing significant PFS benefit. Pts who received GCI trended to better OS compared to OR (18.9 vs. 12.0 m, p=0.380). 2 pts treated with GC+AB had complete responses to date at 36.0 and 14.0 m. Of 31 pts who underwent GA testing, the 2 most frequent GAs were TP53 (38.7%) and TERT (35.5%) mutations. Neither impacted OS: TP53 15.8 vs. 17.6 m (p=0.746); TERT 9.8 vs. 23.3 m (p=0.355). Conclusions: GCI had survival benefit compared to OR in cHCC-CCA. Pts who present with early stage of disease should be evaluated early for surgical resection or maximize local therapy in the case of nonresectable disease to improve survival. [Table: see text]
Clinical characteristics and the course of hepatobiliary and pancreatic malignant tumors with high microsatellite instability after pembrolizumab administration: A multicenter observational study.
Authors: Maruki Yuta , Ikezawa Kenji , Sasaki Mitsuhito , Kobayashi Satoshi , Todaka Akiko , Tsumura Hidetaka , Okano Naohiro , Terashima Takeshi , Yamashita Tatsuya , Kawamoto Yasuyuki , Kojima Yasushi , Imaoka Hiroshi , Hosoi Hiroko , Morizane Chigusa , Ueno Makoto , Ikeda Masafumi , Okusaka Takuji 
Published: January 2024

459 Background: The Keynote-158 trial have resulted in an expanded approval for pembrolizumab (Pem) in solid tumors with high microsatellite instability (MSI-H). In the trial, Pem was administered to patients with MSI-H solid tumors, excluding colorectal cancer, and the overall response rate (ORR) was 34%. However, the ORR for pancreatic (PANC) and biliary tract (BT) cancer were 19% (4/22 cases) and 41% (9/22 cases), respectively, suggesting the possibility of varying treatment efficacy by the primary tumor site. In this study, we aimed to clarify the clinical characteristics of patients with MSI-H and the efficacy of Pem administration in hepatobiliary and pancreatic (HBP) cancers. Methods: A multicenter observational study of patients with HBP cancer with MSI-H was conducted from March 2020 to March 2023. This study consists of prospective and retrospective cohorts. We evaluated the efficacy of PEM administration in patients with PANC and BT, respectively. Results: We enrolled 51 patients, including 32 in the prospective cohort; males comprised 51% of the patients. The BT, PANC, and liver were the primary sites in 26, 24, and 1 patients, respectively. MSI-H diagnostic methods were the MSI kit (FALCO) and comprehensive genome profile in 43 (84%) and 8 (16%) patients, respectively. Intrahepatic cholangiocarcinoma (ICC) was the most common cancer in BT tumor; ICC was observed 13 (50%) patients, followed by perihilar, gallbladder, and distal bile duct (including ampullary cancer) cancers in 6, 4, and 3 patients, respectively. Some rare histological types were observed, two patients had neuroendocrine carcinoma and one had hepatoid carcinoma in PANC. One had an undifferentiated carcinoma in BT. Five and six patients with PANC and BT tumors, respectively, had one or more first-degree relatives with lynch syndrome-related disease. Pem was administered to 96% and 88% of the patients with PANC and BT tumors, respectively. The ORR was 30% in PANC and 73% in BT tumors (p=0.003). In BT tumor, three patients demonstrated complete response as follows: two with ICC and one with perihilar cholangiocarcinoma. The median progression-free survival was 3.2 months (95% confidence interval [CI], 1.3–14.4) and 16.3 months (95% CI, 8.7 to not reached) in patients PANC and BT tumors (p=0.08), respectively. Grade 3/4 immune-related adverse events occurred in 13% and 29% of the patients with PANC and BT tumors, respectively. Conclusions: ICC was the most common BT cancer with MSI-H. Pem was significantly more effective in BT tumors than in PANC tumors, with higher ORR. Clinical trial information: UMIN000040591 .
Real-world (RW) testing patterns of serum lactate dehydrogenase (LDH) and its prognostic value among patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Lenz Heinz-Josef , Lunacsek Orsolya , Ostojic Helene , Pan Xiaoyun , Dochy Emmanuelle , Vassilev Zdravko , Khan Nasreen 
Published: January 2024

46 Background: LDH is a potential prognostic biomarker of outcomes for pts with mCRC. This retrospective, observational cohort study describes RW LDH testing patterns and assesses LDH as a prognostic factor for overall survival (OS) in pts receiving chemotherapy (CT) for mCRC in the USA. Methods: Pts with mCRC, ≥18 years (yrs) of age, who initiated first line (1L) CT (index date) between January 1, 2016, and November 30, 2022, were identified in the nationwide de-identified Flatiron Electronic Health Record-derived database. Practice patterns for LDH testing are described. Pts were categorized into normal vs abnormal LDH baseline (≤3 months prior to/at index date) value based on the lab reference range. Prognostic relationship between normal vs abnormal LDH baseline value and OS was assessed using Kaplan-Meier and multivariate Cox proportional-hazards model. Results: Of 15,329 eligible pts, 57% were male, 49% were ≥65 yrs of age and 66% had ECOG performance status 0–1; 59% had stage IV disease at initial diagnosis; 29% had a KRAS mutation (at any time ≤30 days post-index; 35% not tested). Median time from mCRC diagnosis to index was 35 days. Most common 1L regimens were FOLFOX ± bevacizumab (48%), FOLFIRI ± bevacizumab (15%), and capecitabine (13%). Median follow up from index date was 15.6 months (mos); 60% died. LDH testing was performed in 2,547 pts (17%) during baseline and 3,379 pts (22%) post-index. Among those with ≥1 LDH test during each line of therapy (LOT), median number of LDH tests per pt was 4–6 and median time from line initiation to first LDH test was 7–10 days across the first five LOTs (Table). Among LDH tested pts during follow-up (n=3,379), 21% and 40% had abnormal and normal LDH values at baseline, respectively (39% missing). Demographic characteristics of abnormal vs normal LDH pts were similar; abnormal LDH pts were more likely to be ≥65 years (52% vs 49%), African American or Black (12% vs 7%), and reside in the Northeast (30% vs 21%). Median OS (95% CI) in pts with normal vs abnormal baseline LDH was 29.9 (28.3, 31.7) mos vs 16.8 (14.8, 18.2) mos. In multivariate Cox proportional-hazards model, pts with abnormal baseline LDH values had higher risk of death (HR 1.91, p<0.0001) after adjustment for pt demographic and clinical characteristics. Conclusions: In RW clinical practice in the USA, only one-fifth of mCRC pts receiving CT undergo LDH testing even though LDH value has been found to be a prognostic factor of OS. Efforts to increase LDH testing may help guide treatment decisions in this setting. [Table: see text]
Outcomes and prognostic factors of advanced biliary tract cancers in Saudi Arabia.
Authors: Alshammari Kanan , Alduaiji Reema , Alotaibi Lena , Alqadiri Reema , Alqahtani Laila , Alotaibi Faizah , Al-Fayea Turki , Sabatin Fouad , Alolayan Ashwaq , Alkaiyat Mohammad , Shehata Husam , Al Qahtani Joud , Algarni Mohammed Ahmed 
Published: January 2024

460 Background: Biliary tract cancers which include gallbladder adenocarcinoma, intrahepatic and extrahepatic cholangiocarcinoma are rare, and carry a poor prognosis. There is limited data on biliary tract cancers in the Saudi population. Methods: This single center retrospective study was conducted with data of eligible cases from the last 4 years. Survival, chemotherapy regimens, and variables such as neutrophil to lymphocyte ratio (NLR), and other potential prognostic variables were collected. Results: The study included 155 patients of which 75 had intrahepatic cholangiocarcinoma and 74 had gallbladder adenocarcinoma. The majority were females at 63% of patients. Overweight to obese patients represented 59% of the study cohort. The majority of patients (62%) had an ECOG performance status of 2 and below. Comprehensive genomic profiling was done to 20% of cholangiocarcinoma cases. Elevated CA19-9 tumor marker (> 37 micromol/L) was found in 57% of patients. De novo metastatic disease affected 82% of patients. One third of patients (33%) were not fit for first line chemotherapy, and were given best supportive care. First line chemotherapy of platinum + gemcitabine was given to 53% of fit patients, followed by gemcitabine alone given to 38%, followed by 5-Fluorouracil chemotherapy given to 9% of patients. Very few patients lived for 12 months or more at 16%. There was a significant association between NLR and progression free survival (PFS) with median PFS being 3.5 months in the NLR > 3 group (95% CI 1.2-6 months) versus median PFS of 9.8 months in the NLR < 3 group (95% CI 7.5-12 months, p=0.019). Conclusions: Biliary tract cancers still carry a poor prognosis. NLR ratio of more than 3 was found to predict a low PFS.
Single-institutional analysis of radiotherapy and orthotopic liver transplant for patients with unresectable cholangiocarcinoma.
Authors: Hsieh Meng-Lun , Hannan Sumehra , Hanish Steven I. , Vagefi Parsia A. , Singal Amit G. , Wang Andrew Zhuang , Shah Jigesh A. , Mufti Arjmand R. , Sanford Nina Niu , Patel Madhukar S. , Rich Nicole E. , Aguilera Todd Anthony 
Published: January 2024

466 Background: There is increasing interest in effective strategies for locoregional therapy for cholangiocarcinoma, particularly given the evolving role of orthotopic liver transplant (OLT) for select patients. This single-institution retrospective study compares the clinical efficacy and toxicity of stereotactic body radiotherapy (SBRT), conventional fractionation chemoradiation (CRT), or SBRT as a bridge to OLT in patients with unresectable early stage and locally advanced cholangiocarcinoma. Methods: We reviewed a total of 31 patients from 2010 to 2023 with intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and perihilar cholangiocarcinoma who were treated with SBRT (n=22) or CRT (n=9). SBRT was delivered in 1-5 fractions, median dose of 40 Gy, and dose ranging from 16 Gy to 60 Gy. CRT was delivered in 13-28 fractions, median dose of 50.2 Gy, and dose ranging from 45 Gy to 52.5 Gy. Kaplan-Meier was used to analyze overall survival (OS), progression-free survival (PFS), and local control (LC). Acute and late G3+ toxicity was scored using CTCAE, version 5.0. Results: We identified 13 patients with ICC, 5 with ECC, and 13 with perihilar disease where SBRT or CRT was part of upfront definitive treatment. With a median follow-up time of 11 months, there was no statistical difference between SBRT vs. CRT for OS (median 21 vs. 22 months; p=0.36), PFS (median 14.2 vs. 11 months; p=0.09), and 1-year LC (73.2% vs. 66.7%; p=0.10). However, SBRT appeared to have lower proportions of acute grade 3+ (9.1% vs. 33.3%) and chronic grade 3+ toxicities (22.7% vs. 33.3%). Four patients with early stage perihilar or ICC underwent SBRT as successful bridge to transplant, with no evidence of disease progression at 5.4 months. An additional 2 out of 8 patients were removed from protocol due to disease progression and 2 others remain on protocol, awaiting OLT. Conclusions: In our series of unresectable cholangiocarcinoma, we found no difference in OS, PFS, and LC for patients treated with SBRT vs. CRT, although the former appeared to have lower toxicity and a trend towards improved PFS. Further research is needed to compare SBRT and CRT as definitive treatment or bridge to OLT for patients with unresectable cholangiocarcinoma.
Promising first-line immuno-combination therapies for unresectable hepatocellular carcinoma: A cost-effectiveness analysis.
Authors: Wen Feng , Huang Peng , Wu Qiuji , Yang Yang , Li Qiu 
Published: January 2024

469 Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related death all over the world, bringing a heavy social economic burden especially in China. Several immuno-combination therapies have shown promising efficacy in the first-line treatment of unresectable HCC and are widely used in clinical practice. However, which combination is the most affordable is unknown. The current study assessed the cost-effectiveness of the immuno-combinations as first-line treatment for patients with unresectable HCC from the Chinese payers' perspective. Methods: A Markov model was built based on five global, multicenter, open-label, phase III randomized trials (Himalaya, IMbrave150, ORIENT-32, CARES-310, LEAP-002) to investigate the cost-effectiveness of tremelimumab plus durvalumab (STRIDE), atezolizumab plus bevacizumab (A+B), sintilimab plus bevacizumab biosimilar (IBI305) (S+B), camrelizumab plus rivoceranib (C+R) and pembrolizumab plus lenvatinib (P+L). Three disease states were included: progression free survival (PFS), progressive disease (PD), and death. Medical costs were searched from the Red Book, published literatures, and West China Hospital. Cost-effectiveness ratios (CERs) and incremental cost-effectiveness ratios (ICERs) were evaluated to compare costs among different combinations. Sensitivity analyses were performed to assess the robust of the model. Results: The total cost and quality-adjusted life years (QALYs) of C+R, S+B, P+L, A+B and STRIDE were $12,109.27 and 0.91, $26,961.60 and 1.12, $55,382.53 and 0.83, $70,985.06 and 0.90, $84,589.01 and 0.73 respectively, resulting in the most cost-effective strategy of C+R with CER of $13,306.89 per QALY followed by S+B with CER of $24,072.86 per QALY. The S+B strategy would become the most cost-effective when the willing-to-pay threshold exceeded $73,500/QALY. In the subgroup analysis, with the application of Asia results in Leap-002 trial, the model results were the same as global data. In the sensitivity analysis, with the variation of parameters, the results were robust. Conclusions: As one of the promising immuno-combination therapies in the first-line systemic treatment for unresectable HCC, camrelizumab plus rivoceranib demonstrated the potential to be the most cost-effective strategy, which warranted further studies to best inform the real-world clinical practices.