bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastric microbiome signature to predict metachronous recurrence after endoscopic resection of gastric neoplasms.
Authors: Lee Hokyoung , Shin Cheol Min , Chang Young Hoon , Yoon Hyuk , Park Young Soo , Kim Nayoung , Lee Dong Ho 
Published: January 2024

399 Background: It is well-established that the gastric microbiota undergoes significant alterations during the process of gastric carcinogenesis. This study aimed to identify gastric mucosa-associated microbiome (MAM) for the prediction of metachronous recurrence after endoscopic resection of gastric neoplasms. Methods: Subgroup analyses were conducted for 81 patients (early gastric cancer: dysplasia = 55:26) from a prospective cohort (Clinical Trials No. NCT04830618). Demographic data, and history of Helicobacter pylori eradication therapy, endoscopic and histologic findings were incorporated. The profile of Gastric MAM obtained from non-cancerous corporal biopsy specimens and was analyzed by 16S rDNA sequencing. Results: Over a median follow-up duration of 53.8 months, 16 metachronous gastric neoplasms (10 adenomas and 6 adenocarcinomas) developed. Baseline gastric MAM varied with H. pylori infection status, but was unaffected by the presence of atrophic gastritis, intestinal metaplasia or synchronous lesions. The group with metachronous recurrence did not exhibit distinct phylogenetic diversity compared with the group devoid of recurrence. β-diversity analysis showed significant difference between the two groups (weighted UniFrac distance, PERMANOVA p = 0.006). In the LEfSe analysis, metachronous recurrence group had an increased abundance of Corynebaceriaceae, Comamonadaceae, Corynebacterium, Curvibacter, and a decreased abundance of Helicobacteraceae, and Helicobacter. The total study population were classified into two distinct gastrotypes by baseline Gastric MAM (gastrotype 1: Helicobacter-dominant, gastrotype 2: Akkermansia-abundant). MAM of gastrotype 1 had higher abundance of Helicobacter pylori, and lower abundance of Akkermansia¸ Comamodaceae, Muribaculacae , Streptococcus, Corynebacteriaceae , Cutibaterium. Patients in gastrotype 2 showed higher risk of metachronous recurrence than gastrotype 1 (hazard ratio = 4.621 by Cox proportional hazard model, p-value = 0.0185). Conclusions: Gastric cancer patients can be classified into two distinct gastrotypes by their MAM profiles, which were associated with different risk of metachronous recurrence. MAM profiling of gastric cancer patients is expected give insight into their risk of metachronous recurrence. Clinical trial information: NCT04830618 .
De-risking 1st line chemotherapy-free immune checkpoint inhibitor (ICI) use for patients with advanced gastroesophageal cancer (aGEJ) with tumor mutational burden (TMB).
Authors: Klempner Samuel J. , Quintanilha Julia , Aboosaiedi Ali , Morley Samantha , Mitchell Jerry W. , Ross Jeffrey S. , Graf Ryon 
Published: January 2024

407 Background: ICI + chemotherapy (chemo-ICI) is becoming an increasingly common 1st line regimen for patients with aGEJ. However, direct outcome comparison between biomarker-enriched groups receiving chemo-ICI vs. ICI monotherapy (mono-ICI) is limited in phase III trials. We sought to evaluate if TMB might identify patients for whom mono-ICI vs. chemo-ICI might be de-risked. We prospectively hypothesized that (1) patients with TMB <10 mut/mB would have more favorable outcomes receiving ICI-chemo vs. mono-ICI and (2) patients with TMB ≥10 mut/mB would have diminished additional benefit from chemo-ICI vs. mono-ICI. Methods: This study included patients with aGEJ who received 1st line chemo-ICI or mono-ICI and tumor tissue genomic profiling by Foundation Medicine. Patient data was obtained by the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine gastric real-world clinico-genomic database (FH-FMI CGDB), originating from approximately 280 US cancer clinics (January/2011–March/2023). Real-world progression-free survival (rwPFS) and overall survival (rwOS) were compared between patients receiving chemo-ICI vs. mono-ICI by Cox models, adjusted by propensity scores accounting for disease stage at diagnosis, ECOG PS, PD-L1 score and microsatellite instability (MSI) status. Comparisons of the explanatory power of TMB (<10 vs. ≥10 mut/mB) vs. MSI status (MSI-H vs MSS) were performed by likelihood ratio test (LRT). Results: A total of 263 patients (176 receiving chemo-ICI and 87 mono-ICI) were included in the study. Patients with TMB <10 mut/mB had more favorable outcomes receiving chemo-ICI vs. mono-ICI for rwPFS (median 5.8 vs. 1.9 months, hazard ratio [HR]: 0.44, 95% confidence interval [CI] 0.26-0.76), p=0.0029) and rwOS (median 11.1 vs. 7.9 months, HR: 0.68, 95% CI 0.40-1.15, p=0.1489). Patients with TMB ≥10 mut/mB did not have reduced benefit from mono-ICI; curiously less favorable outcomes were observed with chemo-ICI vs. mono-ICI for rwPFS (HR: 3.27, 95% CI 1.19-8.97, p=0.0212) and rwOS (HR: 3.56, 95% CI 1.14-11.08, p=0.0286). Evaluating only the mono-ICI group, the LRT indicated that when TMB was added to a model evaluating only MSI status, there was an improvement in ICI outcome prediction (p=0.006 for rwPFS and p=0.003 for rwOS), but not when MSI was added to TMB (p=0.91 for rwPFS and p=0.40 for rwOS). Conclusions: aGEJ patients with TMB <10 mut/mB had more favorable outcomes receiving chemo-ICI vs. mono-ICI. In the TMB ≥10 mut/mB we did not observe more favorable outcomes among patients receiving chemo-ICI vs. mono-ICI. Curiously, we observed more favorable outcomes among those receiving mono-ICI in the TMB ≥10 mut/mB group. Among patients receiving mono-ICI, TMB better predicted mono-ICI outcomes compared to MSI status alone.
Revisiting non-invasive diagnosis of hepatocellular carcinoma in clinical reality.
Authors: Teufel Andreas , Qian Yuquan , Lu Qiaoyuan , Rodriguez Isaac , Min Xiangde , Froelich Matthias , Ümütlü Muzaffer Reha , Castrillon German A , Alaffita Carlos Romero , Garay Mora Juan Alberto , Guo Zhiqiang , Weiss Christel , Schönberg Stefan O. , Ebert Matthias Philip , Sun Ying-Shi 
Published: January 2024

441 Background: Current guidelines emphasize the use of CT or MRI for hepatocellular carcinoma (HCC) diagnosis, with strict regulation of biopsies. However, Hepatocellular-Cholangiocarcinoma (cHCC-CC), a liver cancer variant displaying histological elements of both HCC and cholangiocellular carcinoma (CCC), typically exhibits radiological features of both HCC and CCC on imaging studies. Additionally, platinum drugs represent the most promising initial treatment option for patients with unresectable or advanced cHCC-CC, deviating significantly from the treatment approach for HCC. Consequently, our study aims to assess the efficacy of imaging techniques in distinguishing between HCC, CCC, and cHCC-CC, highlighting its clinical significance. Methods: We conducted a database search to identify patients diagnosed with HCC, CCC, and cHCC-CC from June 2010 to September 2020. After implementing quality control measures, our study comprised 68 MRI scans from patients, including 30 with HCC, 23 with CCC, and 15 with cHCC-CC. Histological evidence confirming the diagnoses was obtained within a maximum of four weeks before or after the MRI scans. Subsequently, seven radiologists from Asia, Europe, North America, and South America, including abdominal imaging experts (AIEs) and non-abdominal imaging experts (NIEs) or trainees, independently and blindly assessed the MRI scans. They evaluated various MRI features and established a differential diagnosis encompassing HCC, CCC, and cHCC-CC. Results: The AIEs demonstrated high proficiency in utilizing MRI images exclusively for diagnosing HCC (70%-100%) and CCC (73.9%-91.3%). They significantly outperformed NIEs/trainees (all p values < 0.01), achieving accuracy rates of 26.7%-66.7% for HCC and 21.7%-60.9% for CCC. However, their ability to accurately distinguish cHCC-CC (6.7%-53.3%) was limited and comparable to NIEs/trainees (26.7%-46.7%). Additionally, there was greater consistency in MRI feature assessment among AIEs for HCC and CCC when compared to cHCC-CC. Notably, no significant differences were observed in the impact of a cirrhotic background on the diagnosis of HCC and cHCC-CC among AIEs. Furthermore, there was no significant intercontinental variability in overall liver cancer diagnosis and the diagnosis rates of the three types of liver cancer by AIEs. Conclusions: MRI imaging demonstrated effective differentiation between HCC and CCC, especially when interpreted by experts in abdominal imaging. Nevertheless, the ability to accurately detect cHCC-CC was notably constrained across all participating radiologists. Consequently, liver biopsy continues to play a pivotal role in ensuring diagnostic precision and facilitating the selection of appropriate medical treatment strategies.
Prognostic value of the timing of immune checkpoint inhibitors infusion in patients with advanced hepatocellular carcinoma.
Authors: Pascale Alina , Allard Marc Antoine , Benamar Amal , Levi Francis , Adam Rene , Rosmorduc Olivier 
Published: January 2024

457 Background: Experimental and clinical data in melanoma and lung cancer suggest that the response to immune checkpoint inhibitors (ICI) may be influenced by circadian rhythms. However, similar findings are lacking in hepatocellular carcinoma (HCC). The aim of this study was to assess the impact of infusion timing of atezolizumab, an ICI, associated or not with bevacizumab, as first line systemic treatment in advanced HCC. Methods: We retrospectively analyzed all consecutive patients, who received, as first line systemic treatment, at least two cycles of atezolizumab +/- bevacizumab for advanced HCC in Paul Brousse Hospital, Villejuif, France, between January 2020 and October 2022. We split them in two groups: 1) patients receiving the first two cycles after 1 pm (afternoon group); 2) patients receiving at least one of the two first cycles before 1 pm (morning or mixed group). Cox regression models were used to assess the prognostic value of ICI infusion timing for the overall survival (OS). Results: A total of 131 patients were analyzed. 119 patients (90.8%) were male, with a median age of 70 years [35; 88]; 40 patients (31%) had performance status (PS) ≥ 1. 103 patients (79%) had cirrhosis; 61 patients (46.6%) had portal hypertension. 49 patients (37.4%) had metastatic HCC and 52 patients (40.6%) had portal vein thrombosis at diagnosis. The mean initial level of alpha-fetoprotein was 5,212.8 ng/mL (SD: 18,681.8). 36 patients (27.5%) received only atezolizumab. 41 patients were included in the first group and were compared to 90 patients included in the second group. There were no significant clinical differences between the two groups. The median OS was significantly lower in the afternoon group compared to the morning or mixed group (11.5 months vs 18.7 months, p = 0.015). In univariate analysis, PS ≥ 1 (p = 0.025), initial level of alpha-fetoprotein (p = 0.030), monotherapy by atezolizumab (p = 0.004) and the first two cycles of ICI infusion after 1 pm (p = 0.018) were significantly correlated with OS. The first two cycles of ICI infusion after 1 pm remains an independent factor significantly associated with OS in the multivariate Cox model, with HR 2.29, 95% CI: 1.27-4.14, p = 0.005 (Table). Conclusions: Our results suggest that the afternoon infusion of the first two cycles of ICI is associated with lower outcomes in patients with advanced HCC, independently of other prognostic factors. There may be confounding factors due to the variability of administration of further perfusions. Larger data are needed to confirm such findings. [Table: see text]
Efficacy and safety of a combination of sintilimab, bevacizumab plus gemcitabine, and albumin-bound paclitaxel for initially unresectable gallbladder carcinoma: A prospective, single-arm phase II study.
Authors: Wang Miao , Zhou Jiamin , Xu Weiqi , Pan Qi , Mao Anrong , Zhang Ning , Feng Yun , He Xigan , Lin Zhenhai , Wang Longrong , Zhang Yongfa , Zhu Hongxu , Ding Zhiwe , Wang Yixiu , Yu Bingran , Zhang Ti , Wang Lu 
Published: January 2024

489 Background: Immune checkpoint inhibitors plus chemotherapy had demonstrated important therapeutic advantages in biliary tract cancers (TOP-AZ and Keynote-966). At present the data of gallbladder carcinoma (GBC) is in blank condition almost, and the effectiveness remains to be improved. Further, the addition of bevacizumab to PD-1 inhibitors has improved the clinical results in carcinomas, such as hepatocellular carcinoma, for which therapeutic options have been limited. This study intended to explore the safety and efficacy of sintilimab combined bevacizumab with chemotherapy in the first-line treatment of initially unresectable GBC. Methods: The study was an ongoing open-label, single-arm, phase II trial (Clinical Trial ID: NCT05757336), which consisted of 2 parts: safety-run-in part, where pts received sintilimab (200mg/kg, iv, d1, Q3W) + bevacizumab (7.5mg/kg, iv, d1, Q3W) + gemcitabine (1000mg/m2, iv, d1, Q3W) and albumin-bound paclitaxel (125mg/m2, iv, d1, Q3W), followed by experimental part to evaluate the efficacy and safety of this strategy. The primary endpoint was safety and objective response rate (ORR) assessed by RECIST v1.1. Secondary objectives included disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Results: No DLT was reported at safety-run-in part. Up to the end of Sept 2023, 15 patients were enrolled with a median age of 60.4 years (range 46-75), 26.7% were male. Median follow-up time was 3.68 months. All patients completed at least one tumor response evaluation, confirmed ORR was 60.0% and DCR was 93.3%. Median PFS and OS was not reached yet. Grade 3 TRAEs occurred in 40.0% of patients (n=6), and the most common TRAEs (incidence≥5%) among them were rash (20.0%), AST elevation (6.7%), fever (6.7%), platelet count decreased (6.7%), fatigue (6.7%), pneumonitis (6.7%). Conclusions: The combination of sintilimab, bevacizumab and AG chemotherapy was tolerable and showed a promising ORR in initially unresectable GBC patients. This regimen could be a feasible and safe option for initially unresectable GBC, but this needs further validation. Clinical trial information: NCT05757336 .
Preliminary results of ALTER-H006: A phase II study of TQB2450 plus anlotinib as adjuvant therapy in hepatocellular carcinoma (HCC) with high risk of recurrence after radical resection.
Authors: Mao Xianhai , Duan Xiaohui , Wu Dongde , Zhou Cuncai , Tian Yifeng , Shen Jian , Xu Guohui , Lai Jianlin 
Published: January 2024

494 Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. Surgical resection remains as the mainstay of curative treatment option, However, the recurrence rate after surgical resection could be high especially in patients with CNLC stage IIb (tumor number ≥ 4) and IIIa (vascular invasion). Herein we evaluated the efficacy and safety of the anti-angiogenic tyrosine kinase inhibitor, anlotinib, plus TQB2450, a novel programmed death-ligand 1 (PD-L1) inhibitor as an adjuvant treatment for HCC with high risk of recurrence after radical resection. Methods: This prospective, multiple-center, single-arm phase II study (NCT05111366) enrolled histologically confirmed resectable HCC pts for CNLC Stage IIb/IIIa with any of the following high-risk factors for recurrence: a) tumor nodules ≥4; b) portal vein tumor thrombus (PVTT): vp1 or vp2; c) hepatic vein tumor thrombus (HVTT): vv1 or vv2. At 4-8 weeks after R0 resection, adjuvant therapy was started with anlotinib (12 mg, p.o., qd, d1-14, q3w) plus TQB2450 (1200 mg, i.v., d1, q3w) until disease recurrence or unacceptable toxicity or up to 18 cycles (~1 year). Primary endpoint was 1-year recurrence-free survival (RFS) rate; secondary endpoints were RFS, 1-year overall survival (OS) rate, and safety. Results: Between January 2022 and August 2023, a total of 22 pts from 4 centers were enrolled, 21 pts included in per-protocol set analysis. The 21 pts were predominantly male (95 %, n = 20), and the median age was 50 years (range: 33–75). Eight pts (38%) had CNLC Stage IIb and 13(62%) had CNLC Stage IIIa HCC. Among them, 19 pts received at least once tumor assessment. According to RECIST 1.1, out of 21 pts, 16 showed no recurrence, 3 relapsed, 1 dropped out and 1 discontinued due to serious adverse events. The 1-year RFS rate was 62.31%（95%CI: 17.15-88.08）, while the median RFS was not mature. Additionally, safety profile exhibited that the regimen was tolerable. 16 of 22 pts (73%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 6 pts (27 %) including hypertension (13.5 %), neutropenia (9 %), and bleeding (4.5 %). Conclusions: The present study indicated that anlotinib plus TQB2450 as adjuvant treatment for HCC with high risk of recurrence after radical resection exhibited potential efficacy and tolerable safety profile. The conclusion should be validated in more participants included subsequently. Clinical trial information: NCT05111366 .
Comparison of neoadjuvant treatment modalities for locally advanced intrahepatic cholangiocarcinoma.
Authors: Garita Esteban , Tahir Muhammad Mohid , Sucre Santiago , Juarez Juan Jose , Peters Mary Linton Bounetheau , Sarwar Ammar , Bullock Andrea J. 
Published: January 2024

510 Background: The only curative therapy available for intrahepatic cholangiocarcinoma (IHCC) is resection. Nonetheless, most patients (pts) are diagnosed at a more advanced stage. In this population, using neoadjuvant treatment—locoregional therapies, systemic chemotherapy, or a combination—may improve survival outcomes and downstage them to resectable. We present data comparing survival outcomes (median overall survival [mOS], median progression-free survival [mPFS]) and resection rate (RR) among pts with locally advanced IHCC who received chemotherapy (CT-only), Y90-TARE with chemotherapy (Y90+CT) or Y90-TARE alone (Y90-only) as neoadjuvant treatment. Methods: A retrospective chart review of all pts from October 2015 to December 2022 with biopsy-proven IHCC was completed. Exclusion criteria included ECOG ≥ 2, stage IV extrahepatic disease, and having received previous treatment for IHCC. We defined the Y90+CT arm as pts who received ≤ 4 cycles before Y90 or chemotherapy < 8 weeks after Y90. Statistical analysis was performed with Chi-square, Fisher’s Exact, and Kruskal-Wallis tests. Kaplan-Meier analysis was used for survival calculations and a Log-rank test to compare the arms. Survival is reported as median and 95% confidence interval [CI]. Results: A total of 56 pts were included: 23 pts in the CT-only arm, 15 in the Y90+CT arm, and 18 in the Y90-only arm. The median age at diagnosis was 69 years (IQR 59-74), and 54% were male. There was no statistically significant difference in age at diagnosis or sex between the three arms. RR was 1/23 (4%), 5/10 (50%), and 7/11 (64%) in the CT-only, Y90+CT, and Y90-only arms, respectively (CT-only vs. Y90+CT, p<0.03; CT-only vs. Y90-only, p=0.01). mOS and mPFS for the cohort were 16.3 months [15.3–17.3] and 7.4 months [5.1–9.6]. Per arm, the mOS were 12.4 months [10.1—14.6], 24.3 months [23.3—25.3], and 24.3 months [23.0—25.6] for CT-only, Y90+CT, and Y90-only arms, respectively (CT-only vs. Y90+CT, p<0.03; CT-only vs. Y90-only, p<0.01). The mPFS were 3.5 months [1.1—5.9], 6.2 months [3.8—8.6], and 10.5 months [8.3—12.6], respectively (CT-only vs. Y90-only, p<0.01; Y90+CT vs. Y90-only, p<0.02). Conclusions: In the neoadjuvant setting, including Y90 as a treatment modality may improve survival outcomes and resection rates compared to using chemotherapy alone. Further analysis will include running the Cox multivariate regression model to control for factors that may affect treatment selection in this population.
PROOF 301: Results of an early discontinued randomized phase 3 trial of the oral FGFR inhibitor infigratinib vs. gemcitabine plus cisplatin in patients with advanced cholangiocarcinoma (CCA) with an FGFR2 gene fusion/rearrangement.
Authors: Abou-Alfa Ghassan K. , Borbath Ivan , Roychowdhury Sameek , Goyal Lipika , Lamarca Angela , Macarulla Teresa , Shroff Rachna T. , Oh Do-Youn , Javle Milind M. , Tamas Catalin , Savastano David M , Van Veenhuyzen David Friedrich , Xu Cindy , Solanas Jacki , Freas Elizabeth 
Published: January 2024

516 Background: Infigratinib (BGJ398), an oral inhibitor of fibroblast growth factor receptor (FGFR)1-3 with demonstrated clinical activity and a manageable adverse event profile in a phase 2 study in patients with previously treated, unresectable or metastatic CCA with an FGFR2 fusion or other rearrangement, represented one of the few targeted treatment options after progression on first-line therapy, as per FDA conditional approval. The confirmatory phase III trial PROOF 301 of infigratinib versus gem/cis as frontline treatment of FGFR2 Gene Fusions/Translocations CCA was early discontinued. Here we report the efficacy and safety in the patients accrued prior to termination. Methods: Eligible patients were randomized 2:1 to infigratinib 125 mg on days 1-21 of a 28-day cycle vs intravenous gemcitabine (1000 mg/m2) + cisplatin (25 mg/m2) on days 1 and 8 of a 21-day cycle. The primary endpoint was progression-free survival (PFS), confirmed by blinded independent central review (BICR). Secondary endpoints included overall survival (OS), investigator determined PFS, overall response rate (ORR), best overall response (BOR), disease control rate (DCR), duration of response (DOR), and safety and tolerability. Crossover to the investigational arm was permitted at progression. Results: Over 40 months, a total of 1127 patients were pre-screened at 120 sites and 48 enrolled. In a 2:1 randomization, 29 patients received infigratinib and 19 received gem/cis. Upon progression, 2 patients crossed over from gem/cis to infigratinib. Median PFS (95% CI) by BICR was 7.4 (5.4, not evaluable [NE]) and 8.0 (3.4, NE) months with infigratinib and chemotherapy, respectively. The ORRs by BICR were 37.9 % with infigratinib and 15.8 % with gem/cis. Grade 3–4 adverse events occurred in 79.3% and 58.8% patients treated with infigratinib and chemotherapy. Conclusions: Infigratinib showed a preliminary signal of efficacy in the first-line treatment of FGFR2-rearranged CCA, but due to early termination of the study, the power is insufficient to draw conclusions regarding its efficacy in comparison to gem/cis. This study highlights the challenge of performing confirmatory studies in biomarker-selected subpopulations of rare tumors and the importance of exploring alternative approaches to delivering confirmatory data for regulatory purposes. Clinical trial information: NCT03773302 .