bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anlotinib plus TQB2450 (PD-L1 blockade) combined with nab-paclitaxel and cisplatin as first-line treatment for advanced biliary tract cancer: A single-arm, open-label phase II clinical trial.
Authors: Jin Shui-Ling , Qiao Shishi , Li Ren-Feng , Zhang Weijie , He Wei , Su Chang , Li Lu-Hao , Pan Jie , Guo Wen-Zhi , Zong Hong 
Published: January 2024

498 Background: Efficacy and prognosis of chemotherapy in first-line setting for patients with advanced biliary tract cancer (BTC) was dismal currently. Recently, PD-1/PD-L1 blockades combined with dual chemotherapy in first-line setting exhibited superior efficacy for patients with BTC. Nevertheless, it's important to highlight that both the TOPAZ-1 and KEYNOTE-966 trials had reported a median OS of less than 13 months. This underscored the necessity for further advancements to meet the demands of clinical practice. Anlotinib, a novel multitarget TKI primarily targeting VEGFR1-3, demonstrated promising therapeutic activity as second-line therapy for patients with BTC. Therefore, this study was designed to explore the efficacy and safety of anlotinib plus TQB2450 (PD-L1 blockade) combined with nab-paclitaxel and cisplatin as first-line therapy in advanced BTC. Methods: Patients with previously untreated metastatic or locally advanced BTC (ICC, ECC, GBC) were recruited and treated with anlotinib (10mg, po, d1~14, q3w) and TQB2450 (1200mg, iv, d1, q3w) plus nab-paclitaxel (200mg/m2, iv, d1, q3w) and cisplatin (60mg/m2, iv, d1, q3w) until disease progression or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 using CT scans every two cycles. Adverse events were recorded by severity in accordance with the NCI CTC AE Version 5.0. The predefined sample size was 20. Primary endpoint was ORR and secondary endpoints included safety, DCR, PFS, OS and biomarker explore. Results: From April 2023 to Aug 2023, a total of 18 patients were enrolled, 14 patients who had received first tumor response were included in this analysis. The best overall response indicated that there were 6 PR (42.9%), 7 SD (50.0%) and 1 PD (7.1%). Therefore, the preliminary ORR was 42.8% (95%CI: 17.7%-71.1%), DCR was 92.9% (95%CI: 66.1%-99.8%). Median PFS of the 14 patients was not yet reached. Additionally, safety profile exhibited that the regimen was tolerable. The most common treatment-emergent adverse events among the 18 patients with the incidence >30% were leukopenia (67%), fever (39%), pain in extremity (33%) and malaise (28%). Common grade ≥3 treatment-emergent adverse events were leukopenia (28%), fever (6%), malaise (6%), stomachache (6%), oral mucositis (6%), thrombocytopenia (6%), vomit (6%), rash (6%) and hypotension (6%). Conclusions: Preliminary results suggested that anlotinib plus TQB2450 combined with nab-paclitaxel and cisplatin as first-line therapy in advanced BTC exhibited encouraging efficacy and manageable adverse events. The conclusion should be validated in more patients consecutively. Clinical trial information: NCT05812430 .
Fruquintinib combined with sintilimab plus transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma: A single-arm phase II study.
Authors: Shao Guoliang , Zeng Hui , Zhang Zhewei , Luo Jun , Zhang Dinghu 
Published: January 2024

499 Background: Tyrosine kinase inhibitor combined with immune checkpoint inhibitor has been reported a synergetic survival benefit in patients with unresectable hepatocellular carcinoma (uHCC). TACE induces tumor necrosis and tumor antigen release was believed to increase immune responses of anticancer immunotherapies. This study aimed to evaluate the safety and efficacy of fruquintinib combined with sintilimab plus TACE for uHCC. Methods: This study was a single-arm, open-label phase Ⅱ exploratory clinical study (NCT05971199). Eligible patients were China liver cancer stage (CNLC) Ⅱb-Ⅲa and not candidates for surgical resection or ablation, or liver transplantation, at least one target lesion evaluable, ECOG performance status of 0-1, and Child-Pugh score ≤7. Enrolled patients would receive treatment with TACE (TACE was repeated on demand, but < 5 times) followed by sintilimab 200 mg every 3 weeks and fruquintinib (5 mg QD, 2w on/1w off) until intolerable toxicity or disease progression. The primary endpoint was progression free survival (PFS). The secondary endpoints included adverse events (AEs), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) per mRECIST. Results: As of August 20, 2023, 15 enrolled patients with uHCC were treated. Mean follow-up time is 10.7 months. The median age was 58 years. At present, 10 patients were included for efficacy and safety analysis evaluation. Number of patients with CNLC stage Ⅱb and Ⅲa was 0 (0 %) and 15 (100 %), respectively. The median PFS and OS data are not yet mature. The ORR and DCR were 80% and 100% respectively based on mRECIST (1 CR, 10%; 7 PR, 70%; 2 SD, 20%). The most common (≥ 10%) TRAEs (≥ Grade 3) were elevated glutamic oxaloacetic transaminase, hypertension, proteinuria. No unexpected toxicity or treatment-related deaths occurred. Conclusions: Fruquintinib combined with sintilimab and TACE is a promising and tolerable therapeutic regimen for patients with CNLC Ⅱb-Ⅲa uHCC. This study is still ongoing and further follow-up is required to obtain final survival results. Clinical trial information: NCT05971199 .
Efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib and tislelizumab for unresectable hepatocellular carcinoma: A single-arm, phase II study.
Authors: Xu Yongkang , Fu Shumin , Mao Ye , Yi Fengming , Jiang Weiming , Feng Long , Wu Jianbing 
Published: January 2024

500 Background: Unresectable hepatocellular carcinoma (uHCC) patients (pts) had high unmet medical needs in practice. Retrospective studies suggested a potent antitumor effect and long-term survival benefit of hepatic arterial infusion chemotherapy (HAIC) plus programmed death-1 inhibitor and lenvatinib. This prospective phase II study aimed to evaluate the efficacy and safety of HAIC combined with lenvatinib and tislelizumab in uHCC pts. Methods: Eligible pts were aged ≥18 years and had histologically confirmed uHCC, ECOG PS ≤1, Child-Pugh (C-P) A/B, and ≥1 measurable lesion per RECIST 1.1. Pts received HAIC of modified FOLFOX (oxaliplatin, 85 mg/m2; leucovorin, 400 mg/m2; 5-fluorouracil bolus, 400 mg/m2 on day 1; 5-fluorouracil infusion, 2400 mg/m2 for 46 h), lenvatinib (8 or 12 mg once daily for body weight <60 or ≥60 kg), and tislelizumab (200 mg every 3 weeks). HAIC was allowed to repeat on demands. Primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints included ORR per mRECIST, disease control rate (DCR), surgical conversion rate, progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: Between June 2021 and January 2023, 46 pts were enrolled. The median age of pts was 51-year-old, most were male 42 (91.3%), ECOG PS 0 33 (71.7%), C-P A 44 (95.7%), tumor diameter ≥10 cm 31 (67.4%), multiple tumors 33 (71.7%), vascular invasion 38 (82.6%), extrahepatic metastasis 7 (15.2%). As of August 15, 2023, . All pts entered efficacy and safety analysis, ORR was 52.2% (0 complete response [CR], 24 partial response [PR]) per RECIST 1.1; ORR was 84.8% per mRECIST, with 5 CR and 34 PR. DCR was 95.6% per either RECIST 1.1 or mRECIST. Surgical conversion rate was 21.7% (10/46). Median PFS was 10.9 (95% CI, 8.0-13.8) months; 12-month OS rate was 41.3%. COX analysis revealed that ECOG PS 1 (HR, 3.17; 95% CI, 1.43-7.03; p=0.005), multiple tumors (HR, 3.68; 95% CI, 1.22-11.14; p=0.021), and extrahepatic metastasis (HR, 4.04; 95% CI, 1.57-10.40; p=0.004) were independently associated with poor PFS. Any-grade AEs occurred in 43 (93.5%) pts, the most common were proteinuria (43.4%), aspartate aminotransferase (AST) increased (35.8%), and alanine aminotransferase (ALT) increased (32.1%). Grades ≥3 AEs occurred in 10 (21.7%) pts and mainly included AST increased (7.5%), hypertension (3.8%), and hyperbilirubinemia (3.8%). Conclusions: HAIC combined with lenvatinib and tislelizumab showed meaningful clinical benefits and acceptable safety in uHCC pts. The study is ongoing, OS will be reported later. Clinical trial information: ChiCTR2200064384 .
Role of adjuvant chemotherapy in patients with stage II-III ampullary cancer.
Authors: Semenov Nikolay , Zhukova Lyudmila , Grechukhina Katerina , Izrailov Roman , Dalgatov Kamil , Khatkov Igor 
Published: January 2024

508 Background: Survival benefits for patients (pts) with ampullary cancer (AC) on adjuvant chemotherapy (ACT) remain unknown. Some studies support post-operative treatment, while others state the opposite. Also, there are no clear evidence indicating that histopathological types (pancreaticobiliary (PB-type) and intestinal (IN-type)) can be used to guide the adjuvant setting. The aim of this study is to assess the ACT efficacy in different histopathological types of ampullary adenocarcinoma (pathological stages II-III). Methods: 81 pts were enrolled in the study in total, 45.7% were males, median age was 66.0 (range 43.9-83.8) years. 36.9% were IN-type, 50.8% – PB-type, and 12.3% – mixed. Almost all (97.5%) pts underwent Whipple procedure. 50 pts (61.7%) received ACT: 78.0% – 5-FU-based regimen and 22.0% – gemcitabine-based. Results: There was no clinical benefit in pts administered with ACT in terms of overall survival (OS): median OS was 55.5 months versus 43.6 month in observation arm; p=0.93. The ACT (FU-based or gemcitabine-based) did not correlate to improve OS in patients with IN-type: 38.0 months in patients who received ACT versus 30.5 months in those who did not; p=0.75. The ACT has shown better survival benefit in patients with PB-type compared to observation, however there was no statistical difference: 21.1 and 43.6 months, respectively; p=0.52. 5-FU-based ACT did not show any benefits compared to gemcitabine-based therapy in this subgroup. Conclusions: The use of adjuvant chemotherapy (FU-based or gemcitabine-based) in patients with II-III stage ampullary cancer was not associated with improved overall survival in our trial. There was no clinical benefit from addition of ACT either despite the heterogeneity of the tumor tissue origin (IN-type or PB-type).
Real-world effectiveness and safety of trifluridine-tipiracil (FTD/TPI) and bevacizumab (BEV) in refractory metastatic colorectal cancer (mCRC): The BeTAS trial.
Authors: Martinez Lago Nieves , Gonzalez Borja , Gallardo Martin Elena , Fernandez Montes Ana , Cousillas Castiñeira Antia , Grana Suarez Begona , Carral Maseda Alberto , Pellon Augusto Maria Luz , Gonzalez Villarroel Paula , De La Camara Gomez Juan , Fernández Mercedes Salgado , Reboredo Lopez Margarita ,   Galician Research Group on Digestive Tumors (GiTUD)
Published: January 2024

51 Background: In the Sunlight Trial, the combination of FTD/TPI + BEV demonstrated significantly extended Overall Survival (OS) and Progression-Free Survival (PFS), along with an improved Disease Control Rate (DCR), compared to FTD/TPI alone in patients with refractory mCRC. The BeTAS trial aimed to evaluate the real-world effectiveness and safety of the FTD/TPI + BEV combination in patients with refractory mCRC. Methods: We conducted a multicenter, retrospective, observational study involving patients with mCRC who were refractory or intolerant to standard therapies (including oxaliplatin, irinotecan, fluoropyrimidines, anti-VEGF, and anti-EGFR if RAS/BRAF wild-type) and were treated with FTD/TPI + BEV at six university hospitals affiliated with the Galician Research Group on Digestive Tumors (GiTUD) in Northwest Spain. Results: A total of 110 patients were enrolled in the BeTAS trial between July 2019 and August 2023. The median age was 66 years (range 33-88 years), with 62.7% being male. Notably, 18.2% of patients had an ECOG performance status of 2, 50.9% had RAS mutations, 27.3% had three or more metastatic locations, and 72.7% had liver metastases. Additionally, 26.4% had a time since the diagnosis of the first metastases of less than 18 months, and 46.4% were categorized as the poor prognostic Tabernero´s Subgroup. Most patients (77.3%) received FTD/TPI + BEV as a third-line treatment, with 88.9% having received previous anti-VEGF therapy. Notably, 13.6% received FTD/TPI at a dose of 30 mg/m2, and 6.4% received prophylactic GCSF. The median number of cycles received was 4 (range 1-21 cycles). Among 97 evaluable patients, the overall response rate (ORR) was 2.1%, and the disease control rate (DCR) was 46.4%. With a median follow-up of 15.5 months, the median PFS was 4.2 months (95% CI, 3.5-4.9 months), and the median OS was 9.9 months (95% CI, 7.3 - 12.5 months). The most common grade 3-4 toxicities included neutropenia (41.8%), asthenia (7.3%), and hepatic toxicity (5.5%). No treatment-related deaths were reported. Conclusions: The BeTAS trial findings affirm the real-world effectiveness and safety of FTD/TPI + BEV in the context of routine clinical practice, even in a population with a poor prognosis and extensive prior treatment history.
Comparing resection and stereotactic body radiation therapy for hepatocellular carcinoma with macrovascular invasion: A propensity score matched study.
Authors: Yan Michael , Li Zhihao , Muñoz-Schuffenegger Pablo , Santiago Anna , Claasen Marco , Bucur Roxana , McGilvray Ian M. , Moulton Carol-Anne , Reichman Trevor , Shwaartz Chaya , Cleary Sean P. , O'Kane Grainne M. , Grant Robert C , Kim Tae , Naidoo Catherine Soo Yee , Hosni Ali , Wong Rebecca KS , Mesci Aruz , Sapisochin Gonzalo , Dawson Laura A. 
Published: January 2024

521 Background: Macrovascular invasion (MVI) in hepatocellular carcinoma (HCC) patients is a poor prognostic factor. Current guidelines endorse systemic therapy for MVI. Local therapies present a potential for obliteration of MVI and improved survival. Surgery has been the standard local therapy at our institution, and stereotactic body radiotherapy (SBRT) has emerged as an alternative local therapy for this patient population. Methods: In this retrospective study, one-to-one optimal pair propensity score matching was used to compare outcomes of HCC patients with MVI who underwent surgery or received SBRT. Matching was done based on sex, age, ECOG, cirrhosis presence, Child-Pugh class, number of tumours, tumour volume, alpha-fetoprotein level, ALBI score, Japanese Classification of portal vein invasion, and hepatic vein invasion. Overall survival was estimated using the Kaplan-Meier method and between group differences determined using the log-rank test. The cumulative incidence of recurrence, accounting for the competing risk of death, was compared using Gray’s test. Results: Ninety of 193 patients were included after matching (45 patients in both the surgery and SBRT groups) (Table). The SBRT group had a median OS of 15 months (95% CI: 10-38), while in the surgery group it was 24 months (95% CI: 11-81). Comparing the 12-, 36-, and 60-month overall survival (OS) rates between the SBRT group (57%, 33%, 15%) and the surgery group (58%, 37%, 34%), there was no statistically significant differences (p=0.16); the 5-year OS was double in the surgical resection group. The 12-, 36-, and 60-month cumulative incidence of HCC recurrence in the SBRT group (47%, 73%, 75%) was comparable to the surgery group (69%, 69%, 69%) (p=0.89). Conclusions: Long term survival is possible in patients with HCC and MVI in a substantial minority of patients with HCC and MVI treated with local therapies. There was no statistical difference in outcomes; however, surgical resection resulted in numerically longer survival outcomes compared to SBRT after propensity score adjustment. There is rationale for investigating both local therapies with systemic therapies in future clinical trials. [Table: see text]
A decade of chemotherapy management in hepatocellular carcinoma: A single-center study in Latin America.
Authors: Cruz Diaz Wagner Eduardo , Macetas Jackeline , Lazaro Miriam , Haro Varas Juan Carlos Carlos , Pacheco Cristian , Calderón Anticona Mónica , Anampa Vargas Jessica Diana , Serrano Cardoso Mariana , Paitan Amaro Victor Roman , Castro Oliden Victor , Montenegro Paola Catherine 
Published: January 2024

524 Background: Hepatocellular carcinoma (HC) is the most common primary tumor of the liver and is a significant health problem worldwide with check-point inhibitors and oral multikinase inhibitors (TKI) as the first-line therapy for advanced diseases. While chemotherapy treatment may not be standardized in current clinical management guidelines, it remains the only available treatment option in numerous Latin American countries. Methods: A retrospective review was carried out, in patients older than 18 years, between January 2011 and December 2020. 127 patients were analyzed and identified, they had received at least one course of chemotherapy at the Instituto Nacional de Enfermedades Neoplásicas in Lima, Perú. Results: The median age was 40 years, 40 female patients (31.5%) and 87 male patients (68.5%). Among the participants, 77 patients (60.62%) were diagnosed with hepatitis B, 2 patients (1.57%) had hepatitis C virus infections, and 48 patients didn´t have viral hepatitis. 72 patients (91.13%) underwent antiretroviral treatment. Non-cirrhotic patients were 118 (92.91%) and 111 (87.4%) had a Child A score. Chemotherapy was administered as first-line treatment to 118 patients (92.91%), with 47.61% receiving 5-FU-based chemotherapy, 11.11% Adriamycin, and 8.7% Gemcitabine-based chemotherapy. A smaller subset, consisting of 8 individuals (6.29%), received sorafenib as their first-line treatment. The overall survival (OS) rates at 12, 36, and 60 months were 74.14%, 20.69%, and 1.72%, respectively. Regarding disease-free survival (DFS) rates at 12, 24, and 48 months were 28.89%, 6.67%, and 2.22%, respectively. Conclusions: In this updated data for advanced hepatocellular carcinoma, we observed a subset of patients with advanced HC achieved favorable outcomes, with a median OS of 20.37 months and a median DFS of 6.6 months. Additional research is necessary to enhance our understanding of the molecular characteristics and resistance pathways of hepatocellular carcinoma in Peru and their correlation with the favorable survival rates observed in response to chemotherapy treatment.
Genomic characterization of cholangiocarcinoma with autoimmune etiologies.
Authors: Wang Xin , Hamza Oumaima , Chan-Seng-Yue Michelle , Zhang Amy , Jang Gun Ho , Borgida Ayelet , Kapur Manny , Dodd Anna , Bucur Roxana , Wilson Julie , Vogel Arndt , Gallinger Steven , Notta Faiyaz , O'Kane Grainne M. , Sapisochin Gonzalo , Knox Jennifer J. , Grant Robert C. 
Published: January 2024

531 Background: Chronic inflammation from autoimmune conditions is a well-recognized risk factor for cholangiocarcinoma in the Western world. Cholangiocarcinomas in the setting of autoimmune disease have earlier age-of-onset and worse prognosis. Currently, their biology is inadequately understood, and the risks and benefits of immunotherapy approaches in this population are unknown. We describe the clinical and genomic characteristics of a cohort of cholangiocarcinoma patients with autoimmune etiologies. Methods: In a prospective cohort of 43 patients with mismatch repair proficient cholangiocarcinoma, we performed whole-genome sequencing (WGS, n=43) and total RNA sequencing (RNA-seq, n=28). Among this cohort, 15 patients had cholangiocarcinoma with autoimmune etiologies, including primary sclerosing cholangitis (PSC, n=10), ulcerative colitis (UC, n=6), ankylosing spondylitis (AS, n=1), and Crohn’s disease (CD, n=3). Results: Patients with autoimmune conditions had a 6.46-fold higher Tumour Mutational Burden (TMB) ( P = 0.0010), characterized by higher load of indels ( P = 0.0006). TMB was greater than 10 mutations per megabase in 4 of 15 patients with autoimmune conditions and 0 of 28 patients in those without ( P = 0.0111). Autoimmune patients exhibited an enrichment in mutational signatures 5 ( P = 0.0154), 17 ( P = 0.0004), 28 ( P = 0.028) and 30 ( P = 0.0164). Despite a higher TMB, autoimmune tumours have similar patterns of driver mutations. Differential gene expression of bulk RNA-seq analysis revealed comparable transcriptional markers of immunogenicity, but autoimmune cancers are enriched in pathways involved with cell proliferation and cell-cycle checkpoints. One patient with PSC/UC was treated with gemcitabine, cisplatin, and durvalumab with a partial response, while another with Crohn’s disease had durvalumab added to gemcitabine and cisplatin at progression and experienced stable disease with a decreased CA19-9. Neither experienced immune-related adverse events. Conclusions: Cholangiocarcinoma with autoimmune etiologies have unique genomic features characterized by elevated TMB. Chemo-immunotherapy may be a novel therapeutic option in this subgroup of patients and warrants further study.
Association of FGFR2 structural alterations in intrahepatic cholangiocarcinomas with female gender and younger age.
Authors: Hu Zishuo Ian , Ross Jeffrey S. , Pavlick Dean C. , Hsieh David 
Published: January 2024

537 Background: FGFR2 fusions and other rearrangements are targetable alterations due to the advent of FGFR2 kinase domain inhibitors, and are considerably more common in intrahepatic cholangiocarcinomas (iCCA) than other cancer types. Understanding clinical factors associated with FGFR2 fusions and other rearrangements may guide precision oncology efforts. Prior studies indicate that FGFR2 alterations are more common in younger patients, but it remains unknown whether other demographics are specifically associated with FGFR2 structural alterations. Here, we reviewed the frequency of FGFR2 structural alterations in 8,898 iCCA patients from the AACR Genie and the Foundation Medicine databases. Methods: We reviewed the Foundation Medicine (n= 7,934) and AACR GENIE database (n=964) for intrahepatic cholangiocarcinomas. We identified iCCAs with FGFR2 structural alterations and mutations in other common driver genes and analyzed their distribution by age and sex. Results: FGFR2 structural alterations were more frequent in female (10.4%) compared to male (6.4%) patients across both cohorts. FGFR2 structural alterations had an association with an odds ratio of 2.5 (95% CI 1.6-3.7) and 1.7 (95% CI-2.0) with the female gender in the AACR GENIE and Foundation Medicine databases, respectively. The frequency of FGFR2 fusions/rearrangement was highest during reproductive years (up to age 40) and subsequently declined with age. This decline was greater in females than males. Mutations in other genes associated with iCCA including non-fusion FGFR2 alterations, and mutations in ARID1A, KRAS, and TP53 were not associated with gender or age. Conclusions: Our results show that FGFR2 structural alterations are significantly enriched in younger female patients with iCCA. Clinical assessment of FGFR2 alterations should be prioritized in this patient population, and future clinical studies in this molecular subtype should ensure inclusive enrollment practices. Further research is warranted to determine if the pathogenesis of FGFR2 structural alterations are driven by female biology including the involvement of sex hormones and the potential impact on the development of acquired resistance to FGFR2 kinase inhibitors.