bluuebunny/crossref_metadata_2025 huggingface dataset:
Oncogenic aberrations in primary gastric cancer tumors to predict metachronous peritoneal metastasis.
Authors: Zhao Joseph J , Huang Kiekyong , Chia Daryl K A , Law Jia Hao , Tan Angie Lay Keng , So Jimmy Bok Yan , Tan Patrick , Sundar Raghav
Published: January 2024

392

Background: Peritoneal metastases (PM) in gastric cancer (GC) portend a poor prognosis. Yet, there are a paucity of data on underlying genomic alterations predictive of GCPM. Methods: Two-hundred and nine patients who underwent primary tumor (PT) surgical resection were included in the prospective cohort. Whole exome sequencing (WES) of these resected PT GC specimens (average coverage 129X for tumor samples, 70X coverage for matched normal/blood controls) were undertaken. Participants were followed-up longitudinally for peritoneal metastases. Results: Fifty-one (51/209, 24.4%) patients developed PM after a median follow-up duration of 87.0 months and had poorer survival outcomes compared to patients without metastasis (log-rank, p<0.001). Patients with bulkier and more advanced tumors were at increased hazard of PM (T-stage and N-stage stratified analysis, log-rank, p<0.0001). Consistent with known clinical outcomes, The Cancer Genome Atlas (TCGA) genomically stable (GS) subtype (log-rank, p=0.0059) and mesenchymal subtype GC were associated with a higher proclivity for peritoneal organotropism (log-rank, p=0.020). Among patients who developed PM, TP53 was the most commonly altered driver mutation (25/51, 49.0%), followed by ARID1A (9/51, 17.6%), CDH1 (8/51, 15.7%), PIK3CA (6/51, 11.8%). Comparing the PTs of patients with PM against those PTs without PM, ELF3, CDH1 and PIGR were significantly associated with PM (all adjusted p<0.05). Amongst TCGA GS tumors, ARID1A mutations (p=0.018) were significantly associated with PM compared to patients with GS tumors with no metastasis. CDH1 mutations were found to significantly co-occur with PIGR and RHOA mutations and was mutually exclusive to TP53. ARID1A mutations were also found to significantly co-occur with multiple other mutations such as PTEN, PIK3CA, ERBB2, and KRAS. Conclusions: CDH1, PIGR, ELF3 mutations in primary GC tumors were found to be significantly associated with metachronous PM.
Molecular profiling of hepatoid adenocarcinoma and adenocarcinoma with enteroblastic differentiation.
Authors: Matsumoto Yosuke , Hatakeyama Keiichi , Terashima Masanori , Soneda Wataru , Koseki Yusuke , Kenichiro Furukawa , Fujiya Keiichi , Tanizawa Yutaka , Tadakazu Shimoda , Sugino Takashi , Bando Etsuro
Published: January 2024

394

Background: Hepatoid adenocarcinoma (HAD) and adenocarcinoma with enteroblastic differentiation (ACED) are rare types of gastric cancer that produce alpha-fetoprotein (AFP) and morphologically resemble liver or fetal gut cells. The molecular characteristics of these tumors are poorly understood. We aimed to investigate the molecular profile of HAD and ACED in the comparison with common type of gastric cancer. Methods: We analyzed tissue and blood samples from 496 patients who underwent gastrectomy for gastric cancer and participated in the Project HOPE (High-tech Omics-based Patient Evaluation) in our hospital, from 2014 to 2019. We excluded patients with other special types of gastric cancer, remnant gastric cancer and preoperative chemotherapy. We analyzed gene mutation, copy number, and gene expression between 10 HAD/ACED and 486 common types of gastric cancers. Results: The mutated genes with high frequency (> 20%) in HAD/ACED were TP53 (100%) CSMD3 (30%), LRP1B, FAT3, TG, APOB, CREBBP, PASK, DROSHA and STK40 (20%). The tumor mutation burden (TMB) of all the cases were less than 10. TMB of HAD/ACED was equivalent to that of common type of gastric cancer with microsatellite stable type. The copy number of 20q13.2 encoding SALL4 was significantly gained in HAD/ACED ( p = 0.03). Furthermore, 17 genes were highly expressed in these tumors, and many of these genes were associated with hepatocytes and fetal organs, including LIN28B, IGF2BP1, and HMGA2, which are related to TP53 mutation. Conclusions: Our molecular profiling revealed similarities between HAD/ACED and hepatocytes/fetal organs and high expression of LIN28B, IGF2BP1 and HMGA2, which are associated with TP53 inactivation. These results suggest that these genes may define morphological features of HAD/ACED.
Comprehensive genomic profiling of advanced anal adenocarcinoma.
Authors: Ogura Nozomu , Hirano Hidekazu , Shiraishi Kouya , Fujii Hiroyuki , Hirose Toshiharu , Shoji Hirokazu , Okita Natsuko Tsuda , Takashima Atsuo , Koyama Takafumi , Kato Ken
Published: January 2024

4

Background: Anal adenocarcinoma (anal AD) is a rare and aggressive gastrointestinal malignancy. Because of its rarity, no standard therapy is established and treatment strategy for advanced rectal adenocarcinoma (rectal AD) is extrapolated. Little is known for genetic alterations (GAs) and their therapeutic implications in advanced anal AD. We aim to investigate to clarify genomic profiles of advanced anal AD in comparison of advanced rectal AD. Methods: We retrospectively extracted data on patients with advanced anal AD and advanced rectal AD who underwent comprehensive genomic profiling (CGP) tests and were registered for the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan. CGP tests were performed by NCC Oncopanel or FoundationOne CDx. We examined somatic GAs, microsatellite instability (MSI) status, and tumor mutation burden (TMB). TMB-high was defined as ≥10 mutations/Mb. Actionable GAs were counted if they were classified as “pathogenic/oncogenic” or “likely pathogenic/likely oncogenic” variants. Druggable GAs are actionable GAs with approved drugs for anal AD or other types of cancer or clinical trials showing efficacy for either anal AD or different types of cancer. Results: From June 2019 to April 2023, 45 patients with anal AD and 1915 patients with rectal AD were enrolled into the C-CAT database. In the anal AD group, most common actionable GAs were TP53 (89%), KRAS (51%), ERBB3 (22%), MYC (20%), SMAD4 (20%), and ERBB2 (11%). Compared with the rectal AD group, the anal AD group had a significantly higher frequency of actionable GAs in ERBB3 (22% vs. 2%, p < 0.01), MYC (20% vs. 8%, p < 0.01), and BRCA2 (7% vs. 1%, p < 0.01), and a significantly lower frequency of actionable GAs in APC (7% vs. 85%, p < 0.01). The proportion of MSI-high and TMB-high in the anal AD group and the rectal AD group were 0% vs. 0.2% (p = 0.79), and 7% vs. 5% (p = 0.54). Common druggable GAs in anal ADs included KRAS G12D mutation (22%), ERBB2 amplification (7%), BRCA2 mutation (7%), BRAF V600E mutation (2%). Compared with the rectal AD group, the anal AD group had a significantly higher frequency of druggable GAs in BRCA2 mutation (7% vs. 1%, p < 0.01). Conclusions: The present study showed that anal AD had a different profile of GAs compared with advanced rectal AD. CGP tests are useful tool for identifying druggable GAs in advanced anal AD for expanding therapeutic opportunities.
Evaluation of a real-world clinico-genomics database of patients with upper gastrointestinal (GI) malignancies in Japan.
Authors: Peter Senaka A. , Rogers James R. , Liu Xinyue , Chen Cai
Published: January 2024

400

Background: The genomic profile of gastrointestinal (GI) cancers provides essential information for precision medicine, however, there is limited availability of real-world data in Asian populations as they are not well-represented in most publicly accessible clinico-genomic databases. In this retrospective study, we evaluated the clinical and genomic characteristics of upper GI cancer patients in the database from an academia-industry collaborative nationwide cancer genome screening project in Japan. Methods: The Screening Projectfor Individualized Medicine in Japan (J-SCRUM) GI-SCREEN enrolled advanced GI cancer patients from 26 sites before planned or during systemic therapy from 2015 to 2019. Archived formalin-fixed paraffin-embedded tumor tissue was analyzed by next-generation sequencing (NGS) using Oncomine Cancer Research Panel and Oncomine Comprehensive Assay. Patients with gastric (GC), esophageal (EC) and pancreatic (PC) cancers were identified in the database. The frequency of key actionable genomic alterations in each cancer cohort was explored and compared to similar upper GI cohorts in The Cancer Genome Atlas (TCGA), a publicly available genomics database initiated in 2005 and concluded sample collection in 2013 with most samples from White cancer patients. Results: A total of 872 GC (mean age at registration [SD]: 64y [12]; percent males: 65%), 265 EC (64y [9]; 78%) and 495 PC (64y [10]; 60%) patients were identified. The majority (>70%) of samples were obtained from primary sites. Adenocarcinoma was the most common histological type for GC (85%) ad PC (76%), while squamous cell (76%) was the most common among EC patients. In the GC cohort, the prevalence of key actionable genomic alterations in J-SCRUM GI-SCREEN vs TCGA (N = 380) was, TP53 mutation (49% vs 49%), ERBB2 amplification (14% vs 13%), PIK3CA mutation (11% vs 14%), MYC amplification (9% vs 12%) and MET amplification (2% vs 3%). In the EC cohort, the prevalence in J-SCRUM vs TCGA (N = 182) was TP53 mutation (77% vs 87%), NFE2L2 mutation (21% vs 10%), PIK3CA mutation (9% vs 9%) and CDKN2A mutation (8% vs 8%). In the PC cohort, the prevalence in J-SCRUM vs TCGA (N = 150) was KRAS hotspot mutation (90% vs 93%), KRAS G12D (43% vs 41%), KRAS G12V (32% vs27%), TP53 mutation (58% vs 64%), BRCA1/2 deleterious mutation (5% vs 5%), ATM deleterious mutation (6% vs 5%) and MYC amplification (5% vs 5%). Conclusions: As part of a nationwide cancer genome screening project, J-SCRUM GI SCREEN database provides comprehensive genomic information for Asian population (Japan). The prevalence of key actionable gene alterations in each tumor type was highly comparable between J-SCRUM GI-SCREEN and TCGA data.
Real world prevalence of biomarkers for treatment of advanced gastric cancer or gastroesophageal junction cancer in a cohort of Colombian patients.
Authors: Ballen Diego Felipe , Ojeda Kelman , Gualdron Ana , Tellez Nicolas , Molina Pimienta Luisana
Published: January 2024

402

Background: Gastric cancer (GC) is the leading cause of cancer-related deaths in Colombia, GLOBOCAN estimated 6.451 deaths in 2022. Development of immune checkpoint inhibitors and HER2 target therapy with chemotherapy had improved overall survival in advanced setting, but we do not have data about the prevalence of biomarkers used for selection of these patients in Colombia or Latin-America. Our aim is to describe the prevalence of biomarkers used currently for selection of treatment in a real-world multicenter cohort of advanced gastric and gastroesophageal junction (GEJ) cancer. Methods: We did a retrospective observational multicenter study of patients with advanced GC/GEJ cancer treated at three reference cancer centers in Bogota, Colombia between January 1, 2023 and July 31, 2023. We reviewed medical history and pathology reports looking for the prevalence of biomarkers used for selection of first line systemic therapy. Ventana 4B5 for HER2 IHQ evaluation and Dako 22C3 for PDL1 expression by CPS were used. MMR proteins were evaluated by IHQ nuclear expression. Results: 101 patients with advanced GC/GEJ were included. The median age was 61 years (range 18-83), 53,5% of patients were men, 92.1% were gastric cancer and 87,1% were de novo stage IV. Signet ring cells were found in 40%, peritoneal carcinomatosis was documented in 59% and 75,2% were distal tumors (no cardias or GEJ involvement). PDL1 positivity, defined as CPS ≥1 was found in 30.6%, using CPS ≥ 5 cutoff just 22.7% of them were positive. HER2 positivity and MMR deficiency were found in the same proportion of patients 5%. Among young patients (< 50 years) 80% had diffuse histology, 30% were CPS ≥5. HER2 status and PDL1 testing was unknown in 21% and 29% respectively. Conclusions: Among these real-world patients, both HER2 and PDL1 positivity was lower than reported in other regions. Higher incidence of distal tumors, signet ring cells and diffuse histology could explain this difference. Correlation of PDL1 positivity between 22C3 and 28.8 was unknown in our population. Our study remarks the high medical need for investigation of biomarkers and developing of prospective studies for correlation and other targets like Claudins and FGFR2b.[Table: see text]
Association of methylation silencing of ULK2 via epithelial-mesenchymal transition and differentiated gastric cancers.
Authors: Motoo Iori , Nanjo Sohachi , Ando Takayuki , Yasuda Ichiro
Published: January 2024

404

Background: Diffuse-type gastric cancers (DGC) typically have a poor prognosis related to their invasion and metastasis, in which the epithelial–mesenchymal transition (EMT) is the initiation step. ULK2 plays a role in the autophagy initiation, which might provide a survival advantage in cancer cells. Although knock-down of ULK2 reportedly induces autophagy and EMT in a lung cancer cell line, the mechanism of EMT via the downregulation of ULK2, as well as its clinical significance, remains yet unclear. The present study, therefore, aims at clarifying this mechanism and its clinical significance in gastric cancers. Methods: We examined ULK2 mRNA expression in gastric cancer tissues and normal gastric tissues of healthy people. The effects of knock-downed ULK2 were examined in two gastric cancer cells, which were investigated in terms of their gene expression changes by the mRNA microarray. Furthermore, to investigate the carcinogenic process from normal gastric epithelial cells, we used RGE cells, which were conditionally immortalized normal gastric epithelial cells developed from a transgenic rat. Results: ULK2 mRNA expression of gastric cancer tissues was significantly lower than H. pylori-negative normal tissues. ULK2 was strongly expressed in normal tissues and intestinal-type gastric cancers (IGC) but was scarcely expressed in DGC by immunohistochemical staining. Furthermore, we found that the ULK2 methylation level of gastric cancer tissues was higher than H. pylori-negative normal tissues and IGC. Then, we validated whether knock-down of ULK2 could induce autophagy, cell migration, and EMT in NUGC3 and MKN45 cells. Using mRNA microarray analysis, we confirmed that knock-down of ULK2 changed expressions of oncogenic genes associated with cell migration and EMT. Autophagy inhibitor suppressed cell migration and EMT induced by knock-down of ULK2 in NUGC3 and MKN45. Additionally, we found that knock-down of Ulk2 induced apoptosis in normal gastric epithelial cells. Conclusions: Methylation silencing of ULK2 in gastric cancer cells could induce cell migration and EMT by means of autophagy induction, causing transformation to poorly differentiated cancers.
Impact of DNA mismatch repair status on prognosis of patients with locally advanced gastric cancer in a Mexican population.
Authors: Diaz Romero Maria del Consuelo , Miyagui-Adame Sayako Mariana , Calderillo Ruiz German , Ruiz-Garcia Erika , Herrera Marytere , Leon-Takahashi Alberto , Lino-Silva Leonardo , Espinoza Ruelas Luis Adrián , García Elizabeth , Zilli Hernandez Stefan
Published: January 2024

408

Background: Gastric cancer (GC) is among the five most frequent and mortal cancers in the world. In Mexico, GC is the second cause of death from cancer in men between 30 and 59 years old. The role of deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) in locally advanced gastric cancer (LAGC) is still controversial. We aimed to evaluate the overall survival (OS) of patients with LAGC, according to MMR status and treatment. Methods: Retrospective study included patients from the National Cancer Institute of México, with locally advanced gastric adenocarcinoma diagnosis between 2008 and 2017. The Kaplan Meier, Log Rank, and Cox Regression methods were used to analyze the relation between MMR status and overall survival in LAGC. MMR status was assessed using immunohistochemistry. Results: A total of 103 patients with LACG were enrolled for analysis. The prevalence of dMMR in GC was 13.59% (n=14). The median OS was 101.9 months in the dMMR group vs. 86.2 months in the proficient MMR (pMMR) group (HR 0.54, 95% CI 0.19 - 1.52, p=0.23), with a 3-year OS of 71.4% vs 65.1% respectively. Survival was also analyzed according to MMR status and choosing treatment. OS was 106.8 months in the dMMR surgery alone group, 78.4 months in the dMMR group treated with both surgery and chemotherapy, 33.1 months for pMMR group with surgery alone, and 89.2 months in the pMMR group treated with surgery plus chemotherapy (p=0.014). Conclusions: In this analysis, OS tended to improve in dMMR group. pMMR surgery alone patients had a superior OS than other groups, while adding chemotherapy to surgery treatment seems to have a role only in pMMR patients. [Table: see text]
Real-world clinical characteristics and treatment patterns among people with hepatocellular carcinoma in the United States (US) treated with resection or ablation.
Authors: Parikh Neehar , Underwood Dex L. , Hu Jenny , Stirnadel-Farrant Heide A. , Kebede Nehemiah , Patel Ravi , Garcia-Reyes Kirema
Published: January 2024

436

Background: Treatment guidelines for early-stage hepatocellular carcinoma (eHCC) include therapies with curative intent comprising three primary strategies: liver transplantation, surgical resection, or ablation (for small lesions). However, many people experience HCC recurrence, with recurrence rates of up to approximately 80% within 5 years after resection. Furthermore, contemporary insights into the eHCC treatment landscape and post-recurrence treatment patterns in the real-world setting are lacking. This study was designed to assess demographic and clinical characteristics and treatment patterns for people with HCC who received resection or ablation as a proxy for defining early-stage disease. Methods: This was a retrospective observational cohort study of adults with HCC treated with resection or ablation in the US, conducted using linked electronic health records and healthcare claims from Optum’s de-identified Market Clarity Data. Index date was the date of the first observed resection or ablation between July 2016 and March 2021. Baseline characteristics were assessed in the 6-month period prior to index, and patients (pts) were followed until end of continuous enrolment in a medical and pharmacy plan, death, or data cut-off (September 2022), whichever occurred first. Demographic and clinical characteristics and treatment patterns, including subsequent treatments, were described. Results: A total of 649 pts met the study criteria and were included in the analyses. The median duration of follow-up was 23.0 months (range: 0.03–74.55 months). The mean age at index was 64.1 years (median 64.0 years), with a majority male gender (72.9%) and White race (65.5%). A total of 385 pts (59.3%) underwent ablation only, 242 pts (37.3%) underwent resection only, and 22 pts (3.4%) underwent both procedures at index. Transarterial embolization alone was received by 57 (8.8%) pts and was the most common embolization procedure received during follow-up, followed by transarterial chemoembolization alone in 46 (7.1%) pts and transarterial radioembolization in 46 (7.1%) pts. A total of 88 (13.6%) pts received systemic therapies for HCC (tyrosine kinase inhibitors, programmed cell death protein-1/programmed cell death-ligand 1/cytotoxic T-lymphocyte-associated antigen 4 inhibitors, or angiogenesis inhibitors) during follow-up. Conclusions: In this real-world cohort, ablation was the most received curative intent therapy for HCC. Among treatments received during follow-up, locoregional therapies were used most often, followed by systemic therapies. Although limited by its retrospective, observational nature, short duration of follow-up, and availability of data in the database, the results of this analysis provide a contemporary landscape of early-stage treatments for HCC in the real-world setting.
Incidence patterns of colorectal cancer in Norway 1993-2022 by age, site, and morphology.
Authors: Ystgaard Mari Fjørtoft , Myklebust Tor Åge , Smeby Jørgen , Larsen Inger Kristin , Guren Tormod Kyrre , Kure Elin H. , Tveit Kjell Magne , Glimelius Bengt , Guren Marianne G. , Hamfjord Julian
Published: January 2024

44

Background: The incidence of colorectal cancer (CRC) has decreased or stabilized in most high-income countries, but an alarming increase is observed in younger adults. Norway has high CRC incidence, which increased until the past two decades, then stabilized. A national screening program started in 2022; hence, this study is on a screening-naïve population. We aim to describe up-to-date incidence patterns of CRC, with emphasis on age-specific differences in tumor site and morphology. Methods: We extracted data on all CRC cases diagnosed 1993 to 2022 from the Cancer Registry of Norway, with completeness estimated to be >99%. Data was stratified by age groups (20-49, 50-74, and ≥75), sex, primary tumor location and morphology. Age-adjusted incidence rates were calculated using Stata 17 and analyzed using Joinpoint regression to provide annual percentage change (APC) and average annual percentage change (AAPC) of incidence rates. Results: There were 107 524 cases eligible for analysis. In the age group ≥75, overall incidence increased (AAPC 0.8), mainly caused by right-sided colon cancer (RCC), which increased until 2016 (APC 2.5), followed by a slight decrease (APC -0.9). The age group 50-74 had stable incidence (AAPC -0.2). Incidence in the age group 20-49 increased (AAPC 1.3), caused by left-sided colon cancer (LCC) and rectal cancer (RC). When stratifying on morphology, incidence of mucinous carcinomas was stable (AAPC -0.6), approx. 10% of all CRC cases. Neuroendocrine neoplasms (NEN) increased in all age groups (AAPC 4.2), accounting for only 1.4% of all CRC cases; but contributed somewhat to the overall incidence in age group 20-49, in particular RC where 8.8% of cases were NEN. In the age group 20-49, adenocarcinomas had an AAPC of 1.4, mucinous carcinomas -0.8, and NEN 4.1. Conclusions: We found an increasing incidence of CRC in the youngest (<50) and elderly (≥75). LCC and RC incidence increased in the youngest age group, still increasing up until 2022. In contrast, the increase in the elderly was mostly due to RCC. Different incidence patterns of primary tumor locations in younger and older age groups may imply differences in etiology and prognosis, different biological features and possibly therapeutic implications. [Table: see text]
Disparities in surgical outcomes and survival based on insurance status among patients with fibrolamellar hepatocellular carcinoma: A national perspective.
Authors: Czaplicki Alec , Bine Christopher Reese , Lee Aron , Nielsen Eric , Silberstein Peter T.
Published: January 2024

440

Background: Fibrolamellar hepatocellular carcinoma (FL-HCC), encompassing 1%-5% of all liver cancers, is a rare, malignant cancer that typically affects patients less than 40 years old. FL-HCC usually affects individuals with healthy livers and initially presents asymptomatically. Prior studies describe the importance of surgery on survival, with a 5-year survival of about 44%-68% with surgery versus 2%-17% without surgery. Disparities in outcomes regarding surgical factors and survival between private insurance, Medicare, Medicaid, and no insurance remain unknown. This study aims to determine differential surgical factors and survival of patients with FL-HCC based on insurance status. Methods: The National Cancer Database was used to identify patients diagnosed with FL-HCC from 2004-2019 using the histology code 8171 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, Chi-Square, ANOVA, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 29 and statistical significance was set at α=0.05. Results: Of the 436 patients included, 241 (55%) had private insurance and 96 (22%) had Medicare. Patients with private insurance had a longer median survival (49 months) than patients with Medicare (18 months; p<.001) and Medicaid (26 months; p<.004);no significant survival difference existed between Medicare, Medicaid, and no insurance (39 months) ( p’s≥.063). After controlling for age, income, tumor size, adjuvant therapy, receiving surgery, and surgical margins of primary site, private insurance was associated with an independent decrease in hazard (HR=.899; p=.004).Patients with private insurance received more surgery (68%) than those with Medicaid (50%), no insurance (48%), and Medicare (32%) ( p’s<.001); grade did not differ amongst insurance types ( p=.069).Furthermore, patients with private insurance had more surgical margins of the primary tumor site without residual tumor (57%) compared to those with Medicaid (40%), no insurance (38%), and Medicare (23%) ( p’s<.001).While patients with Medicare presented with greater co-morbidities, age at diagnosis (67), tumor size (476 mm), positive regional lymph nodes (90), and days between diagnosis and treatment (45), patients with private insurance presented at a younger age (31) with fewer co-morbidities, smaller sized tumors (366 mm), and fewer days between diagnosis and treatment (26) ( p’s<.018). Conclusions: Since patients with private insurance received the most surgery, best surgical margins, and displayed the highest overall survival, while patients with Medicare were diagnosed at the highest age with the largest tumor size and most positive regional lymph nodes, future research should explore ways to alleviate the disparity in factors affecting surgical resections and early diagnoses among insurance statuses.
Real-world (RW) characteristics, treatment patterns, and outcomes of patients with cholangiocarcinoma (CCA) treated with pemigatinib.
Authors: Saverno Kim , Brown-Bickerstaff Cherrishe , Kotomale Angele , Rodriguez Michael A. , Feinberg Bruce A. , Gordon Sarah , Ren Haobo , Braunstein Evan Mark , Kim Richard D.
Published: January 2024

444

Background: Pemigatinib demonstrated efficacy in fibroblast growth factor receptor (FGFR)–altered CCA in the FIGHT-202 trial; however, limited RW evidence exists on treatment patterns and outcomes in patients (pts) with CCA treated with pemigatinib. This study assessed characteristics, FGFR2 testing patterns, treatment patterns, and outcomes of pts treated with pemigatinib for locally advanced or metastatic CCA in the United States as part of routine clinical care. Methods: This retrospective, multisite cohort study included pts with a diagnosis of unresectable locally advanced or metastatic CCA who were initially prescribed pemigatinib on or after 04/17/2020. Eligible pts were ≥18 years at pemigatinib prescription and had ≥4 months (mo) of follow-up (unless <4 mo due to death). Pts who received pemigatinib as part of a clinical trial or those who received systemic therapy for another primary malignancy (other than cancer of unknown primary or hepatic cancer) were ineligible. Participating physicians from Cardinal Health’s Oncology Provider Extended Network—approximately 72% from community oncology practices—abstracted data from the medical records of eligible patients into electronic case report forms. Results were summarized using descriptive statistics. Results: Data from 120 pts (49% male; 55% White; 19% Hispanic; median age at pemigatinib prescription, 65 years) were collected from 18 physicians/practices. Testing for FGFR2 alterations was completed in 93% (n=111) of pts; of those, all but one patient (result unknown) tested positive, and 95% were tested using next-generation sequencing. At time of pemi prescription, 90% of pts had metastatic disease. Across all pts, 94% and 6% were prescribed pemigatinib as 2nd and 3rd line of therapy, respectively. The most common starting dosage was 13.5 mg daily for 14 days of 21-day cycle (87.5% of pts). Among the 60 pts who discontinued pemi during the 6.5-month median study follow-up period, 68% discontinued due to disease progression. Median RW progression-free survival (rwPFS) from date of pemigatinib initiation was 7.4 (95% CI: 6.4–8.6) mo. Among the 116 patients with tumor response data available, RW overall response rate (rwORR) was 61% (95% CI: 52% - 71%). Conclusions: This study complements the FIGHT-202 clinical trial by assessing the use of pemigatinib among a diverse population of patients with CCA under RW conditions. Secondarily, the rwORR and rwPFS from this study support the clinical benefit of pemigatinib demonstrated in FIGHT-202.
Comparing first-line (1L) atezolizumab plus bevacizumab (A+B) to lenvatinib (L) or sorafenib (S) in patients with unresectable hepatocellular carcinoma (uHCC): Findings from the National Veteran Health Administration (VHA) database.
Authors: Kaplan David Edward , Tan Amie , Xiang Cheryl , Mu Fan , Ogale Sarika , Hernandez Sairy , Li Jiayang , Lin Yilu , Shi Lizheng , Singal Amit G.
Published: January 2024

446

Background: The approval of A+B has reshaped the treatment paradigm for patients with uHCC, establishing a new standard of care for 1L uHCC treatment. The VHA is the largest independent healthcare delivery network and the largest provider of liver-related care in the US. We aimed to compare patient characteristics and clinical outcomes between veterans who received 1L A+B and those who received L or S for unresectable HCC. Methods: Using data from the VHA National Corporate Data Warehouse (1/1/2017 - 12/31/2022), we conducted a retrospective cohort study in patients diagnosed with uHCC who initiated A+B after 2020 or initiated L or S after 2018. Child-Pugh (CP) scores were calculated using a previously validated algorithm. Kaplan-Meier and multivariable Cox regression methods were applied to compare overall survival (OS) between the groups. Results: We identified 405 eligible patients who received A+B, 453 received L, and 1,016 received S. Compared with patients receiving L or S, those treated with A+B had a higher proportion of CP A5 (47% and 35% vs. 54%, respectively; both p<0.05), a similar proportion of A6 (30% and 32% vs. 31%, p=0.683 and 0.681, respectively), a lower proportion of B7 (15% and 20% vs. 9%, respectively; both p<0.05), and a greater comorbidity burden as measured by the mean Charlson Comorbidity Index (CCI) (5.8 [L or S] vs 6.6 [A+B], both p<0.05). Median OS (mOS) was 12.8 months (95% CI: 10.6, 17.1) in the A+B cohort, compared to 9.5 months [95% CI: 7.8, 11.4] in the L cohort, and 8.0 months [95% CI: 7.1, 8.6] in the S cohort. In subgroup analyses, longer mOS was observed with A+B than with L or S in CP A patients and those with ALBI grades 1-2A; similar mOS was observed among those with more severe liver dysfunction (Table). In multivariable analysis, A + B was associated with a 26% lower risk of death relative to L (HR=0.74, 95% CI: 0.62-0.88) and 30% lower risk of death compared to S (HR = 0.70, 95%CI 0.60-0.82), both p<0.001. Conclusions: In a real-world VHA experience with A+B among diverse patient groups, a clinically notable survival benefit was observed with A+B compared to L or S. Future evaluations of the safety of using A+B in patients with greater liver dysfunction, including CP B and cirrhosis, are needed to evaluate the expanded use of A+B. [Table: see text]
Zanidatamab (zani) in previously treated HER2+ biliary tract cancer (BTC): Impact on patient-reported pain outcomes in the phase 2b HERIZON-BTC-01 study.
Authors: Pant Shubham , Fan Jia , Oh Do-Youn , Choi Hye Jin , Kim Jin Won , Chang Heung-Moon , Bao Lequn , Sun Hui-Chuan , Macarulla Teresa , Xie Feng , Metges Jean-Philippe , Ying Jie-Er , Bridgewater John A , Tejani Mohamedtaki Abdulaziz , Chen Emerson Yu-sheng , Wasan Harpreet Singh , Ducreux Michel Pierre , Ma Jiafang , Garfin Phillip M. , Harding James J.
Published: January 2024

450

Background: The HER2 bispecific antibody zani showed rapid, durable responses and a manageable safety profile in patients with HER2+ BTC in the pivotal HERIZON-BTC-01 study. Here we report pain outcomes and opioid use for patients in this trial. Methods: HERIZON-BTC-01 (NCT04466891), an ongoing, open-label, Phase 2b study, is assessing zani (20 mg/kg IV Q2W) in patients with HER2+ (gene amplification and immunohistochemistry 2+ or 3+ [Cohort 1] and 0 or 1+ [Cohort 2]), locally advanced, unresectable or metastatic BTC (gallbladder cancer, intra-/extra-hepatic cholangiocarcinoma) who received prior gemcitabine-containing treatment (tx). Exploratory endpoints assessed at baseline (BL) and every 8 weeks included the Brief Pain Inventory short form, the visual analog scale (VAS), and analgesic opioid use. Results: Of the 80 patients with HER2+ BTC in Cohort 1 who were assessed for primary efficacy (median age 64 yrs; 56% female), 1 (1%) had complete response (CR), 32 (40%) partial response (PR), 22 (28%) stable disease (SD), and 24 (30%) progressive disease (PD); 1 patient was not evaluable. Responders (CR or PR) generally reported improved pain scores and less pain interference with activities of daily living. Patients with PD generally had worsening pain scores and pain interference by time of best on tx score (BONT) (Table). Overall, patients who responded to zani reported improved quality of life (VAS scores) vs BL. Fewer patients with CR (0.0%; n=1) and PR (3.1%; n=32) increased opioid use overall post-BL vs patients with SD (9.1%; n=22) or PD (34.8%; n=23). Conclusions: Patients with HER2+ BTC who responded to zani reported less pain and pain interference compared with BL, further supporting the development of zani as a tx option for these patients, with the goal of improving patient outcomes. Clinical trial information: NCT04466891 . [Table: see text]
Real-world correlation of RFS and OS in early-stage hepatocellular carcinoma treated with curative intent: A retrospective analysis of SEER-Medicare data.
Authors: Mehta Neil , Desai Kaushal , Kamble Shital , Song Yan , Gao Emily , Malhotra Usha , Lax Angela , Sundaresan Sanjana , Downes Nathaniel , Zhang Adina , Siegel Abby B.
Published: January 2024

451

Background: Curative intent therapy with resection or ablation for early-stage HCC is associated with high incidence of recurrence. Effective adjuvant therapy is needed to improve outcomes. While OS is the preferred endpoint for demonstrating efficacy of new adjuvant therapies, recurrence-free survival (RFS) may better reflect the benefits associated with adjuvant therapy due to being independent of subsequent therapies upon recurrence. Additionally, RFS may provide insights into patient (pt) outcomes while OS data are immature. We assessed the correlation between OS and RFS in pts with early-stage HCC after treatment with curative intent. Methods: This study used the SEER-Medicare database (2007–2017). RFS was defined as time from curative intent therapy, by local ablation or surgical resection, until death or disease recurrence (first of: new HCC treatment, liver transplant, metastatic disease). OS was defined as time from curative intent therapy until death. Kaplan-Meier analyses were used, censoring on end of Medicare Parts A/B/D continuous eligibility or end of data availability. RFS/OS were summarized overall and by type of prior local therapy and risk of recurrence. Pts with a solitary tumor with histologic grade 3 or 4, solitary tumor >3cm, or multiple tumors were classified as high to very high risk. Pts with a solitary tumor not histologic grade 3 or 4 or a solitary tumor ≤3 cm were classified as low to intermediate risk. Correlation between RFS and OS was assessed using the Kendall’s τ rank correlation. Results: 611 HCC pts met the inclusion criteria (mean follow-up 3.3 years; mean age 73.3 years). Average (median) primary tumor size at diagnosis was 4.8 (4) cm. 91.6% of pts had a solitary tumor at diagnosis. 66.1% of pts experienced death or recurrence (Table). Median [IQR] OS and RFS post-curative intent therapy were 4.6 [1.8, NR] and 1.8 [0.8, 6.3] years, respectively. OS and RFS were poorer for those in the ablation (median OS 3.2 years; RFS 1.2 years) and high to very high risk of recurrence group (median OS 4.3 years; RFS 1.4 years). Kendall’s τ rank correlation model in the overall group demonstrated a statistically significant positive correlation between RFS and OS (τ = 0.66; 95% CI: 0.60–0.70; P < 0.001). Conclusions: Based on real-world data, a significant positive correlation between RFS and OS supports RFS as an efficacy marker and appropriate endpoint for pts in adjuvant HCC setting when OS data are immature. [Table: see text]
First-line therapies in a Latino-rich cohort of US patients (pts) with hepatocellular carcinoma (HCC) and Child Pugh B (CPB) cirrhosis.
Authors: Alfaro Moses Andrew , Arora Sukeshi Patel
Published: January 2024

453

Background: There are limited prospective clinical trials in patients with both HCC and CPB cirrhosis. As the prevalence of HCC and cirrhosis has been rising among Latinos in South Texas, it is crucial to examine the liver dysfunction within this demographic to understand the contributing factors to treatment patterns. Therefore, we conducted a retrospective analysis of 36 patients with both HCC and Child Pugh B (CPB) cirrhosis. Methods: A dataset of 65 patients with HCC and cirrhosis from 2009 – 2019 was used to identify 36 patients with CPB treated at a Latino-Rich NCI-designated Cancer Center. We further segmented patients of Child Pugh Class B by ALBI grades (1-3) to explore variations in demographics, liver dysfunction, and first-line therapies. Results: Median age overall of the cohort is 59 (50-71). Ethnicity: Latino White (83%), Non-Latino White (14%), Black (3%). Etiology: HCV (78 %) EtOH (50%), NASH (19%), and HBV (3%). ALBI Grade: I (6%), II (50%), III (44%). First line treatment in CPB: Sorafenib (86%), Nivolumab (8%), Lenvatinib (6%). Sorafenib was used across all ALBI grades, while Lenvatinib and Nivolumab were given only in ALBI II (Table). Conclusions: Sorafenib was more often given to patients with CPB cirrhosis, in the first line setting; however, more patients were treated with nivolumab or lenvatinib with ALBI II. Further investigation of survival based on ALBI levels and the trajectory of liver function over time in response to different treatment approaches is underway in a larger cohort who has received newer immunotherapy-based regimens. With more agents approved for HCC, prospective clinical trials are needed in CPB and HCC. [Table: see text]
Real-world use of pemigatinib (pemi) for cholangiocarcinoma (CCA) among racial and ethnic minorities in the United States.
Authors: Kim Richard D. , Brown-Bickerstaff Cherrishe , Kotomale Angele , Rodriguez Michael A. , Feinberg Bruce A. , Gordon Sarah , Savill Kristin M. Zimmerman , Ren Haobo , Blecker Michael , Saverno Kim
Published: January 2024

461

Background: Pemi received accelerated approval by the FDA in 2020 for treatment of patients (pts) with unresectable locally advanced or metastatic CCA with a fibroblast growth factor receptor 2 ( FGFR2) fusion or other FGFR2 rearrangement. A recent real-world study (RWS; submitted to ASCO-GI 2024) assessing characteristics, FGFR2 testing patterns, treatment patterns, and outcomes of pts treated with pemi for locally advanced or metastatic CCA in the US as part of routine clinical care found substantial racial and ethnic diversity in pts treated with pemi. The purpose of this analysis is to describe the findings of the pemi RWS for CCA by race and ethnicity. Methods: This was a retrospective cohort study in which US-based participating physicians from Cardinal Health’s Oncology Provider Extended Network abstracted data from eligible pts’ medical records into electronic case report forms. Eligible pts were ≥18 years of age, initially prescribed pemi for unresectable locally advanced or metastatic CCA on or after 4/17/2020, and had ≥4 mo of follow-up (unless <4 mo due to death). Pts who did not receive pemi or had received pemi in a clinical trial or systemic therapy for another primary malignancy (except for cancer of unknown primary or hepatic cancer) were excluded. Results were summarized by race (White, Black/African American, “Other” [pts with mixed race or a race other than White, Black/African American, or Unknown]) and ethnicity (Non-Hispanic, Hispanic) using descriptive statistics. Results: 18 physicians abstracted data for 120 eligible pts. Median follow-up from initial pemi prescription was 6.5 mo, at which time 71 pts (59%) were alive and 60 (50%) were still receiving pemi. The racial makeup of the study population was 55% White, 21% Black, 18% Other, and 7% Unknown. Ethnic composition was 78% Non-Hispanic, 19% Hispanic, and 3% Unknown. Key results are presented in the Table. Conclusions: The diverse population in this RWS is reflective of the heterogeneous CCA pt population in the US. These real-world overall response rates support the clinical benefit of pemi across racial and ethnic groups and complement the results of the clinical trial. [Table: see text]
The impact of CARE Frailty Index on overall survival in older adults with hepatocellular carcinoma.
Authors: Ozluk Ahmet Anil , Williams Grant Richard , Dai Chen , Malla Midhun , Siwakoti Krishmita , Outlaw Darryl Alan , Pywell Cameron , Gupta Garima , El-Rayes Bassel F. , Giri Smith , Akce Mehmet
Published: January 2024

462

Background: Pre-treatment frailty is associated with unfavorable short and long-term outcomes among patients with hepatocellular cancer (HCC) post liver resection.However, there is a knowledge gap in identifying the subset of older adults with HCC at high risk for inferior survival outcomes. Methods: We evaluated the association between patient-reported geriatric assessment (GA)-based frailty index and overall survival (OS) among older adults (≥60y) diagnosed with HCC enrolled in a single institutional prospective registry (Cancer and Aging Resilience Assessment (CARE) registry). All patients underwent a patient-reported GA at enrollment that encompassed multiple health domains related to aging. To determine frailty, we utilized a 44-item CARE Frailty Index (CARE-FI) based on the principles of deficit accumulation (Giri S et al JAGS 2021). We categorized frailty into robust, pre-frail and frail. The primary outcome was OS from the time of GA. Comparison of survival between groups was made using log-rank statistic. A multivariable Cox regression model measured the independent association between frailty and OS adjusted for age, etiology, Child-Pugh score and cancer stage. Results: A total of 116 older adults with HCC were identified with a median follow-up 2.1 year, median age was 67y (63-72) with 82% males, 27% blacks, 64% with Child-Pugh-A and 78% with stage III/IV disease. Overall, 50.1% (n=58) were frail, 33.6% (n=39) pre-frail and 16.3% (n=19) robust. No significant clinico-demographic differences across the 3 frailty groups were observed. In univariable analysis, there was a marginally significant difference between the three frailty groups (p value 0.06). However, in multivariable analysis, being frail vs robust was associated with an increased risk of mortality (HR 2.6 [95% CI 1.03 – 6.56]; p=0.04) after adjustment for aforementioned confounders. Conclusions: Frailty status assessed by patient-reported GA using CARE-FI is associated with an increased risk of mortality in older adults with HCC. Frailty assessment should be encouraged and considered in prospective clinical trials to estimate the impact of treatment on the most vulnerable adults. [Table: see text]
Care delivery and patient self-management for people with primary liver cancer receiving 4R care sequence plans.
Authors: Therapondos George , Weldon Christine B. , Du Lingling , Mizrahi Jonathan , Palmer Carol , Medina Amanda , Sandow Tyler Allan , Gimenez Juan , Cohen Ari , O'Brien Michelle , Tan Amie , Trosman Julia R.
Published: January 2024

465

Background: The 4R Oncology Model (4R=Right information/care/patient/time) supports patient self-management1 and quality improvement.2 Here we report the impact of using 4R Care Sequence plans for patients with primary liver cancer cared for by a multi-disciplinary liver cancer team. Methods: We tested the impact of 4R care sequence plans on patient self-management and care delivery referrals at a liver cancer program via patient surveys. 4R Plans were provided to patients with primary liver cancer from Jan – Aug ’23 (4R cohort). Patient-reported data were analyzed to compare the control cohort of patients who received care pre-4R, Jan - Dec ’22 (N=42) to the 4R cohort (N=17). Statistical analysis used Fisher’s exact test. Results: Patient survey response rates: Control cohort 54% (42/78), 4R cohort 55% (17/31). Comparing the control cohort to the 4R cohort respectively, patients were male (52%, 65%), White (64%, 64%), Black (26%, 18%), average age (63.2, 64.7), and reported income less than $30,000 (45%, 53%). The 4R cohort significantly improved care delivery in three metrics, and directionally improved in the other care delivery metrics as compared to the control cohort (table). All four patient self-management metrics significantly improved in the 4R cohort vs. the control cohort (Table). Conclusions: The use of 4R Care Sequence plans for patients with primary liver cancer facilitated improvements in care delivery and patient self-management metrics. While there were directional improvements in all metrics, there is opportunity and room for additional improvements. The team will continue to work on efforts to improve these metrics and optimize the use of 4R Care Sequence plans for patients with primary liver cancer. 1. Trosman, JCOOP 2021. 2. Liu, JCOOP 2022. [Table: see text]
Preoperative endoscopic biliary drainage procedures may affect intrahepatic recurrence of cholangiocarcinoma after surgical resection.
Authors: Kim Jin-Oh
Published: January 2024

468

Background: To determine the impact of preoperative endoscopic nasal biliary drainage (ENBD) and/or endoscopic retrograde biliary drainage (ERBD) procedures on intrahepatic recurrence rate in patients with cholangiocarcinoma after surgical resection. Methods: Between January 2005 and January 2023, 143 patients diagnosed cholangiocarcinoma and received surgical resection. Among 143 patients, 99 patients were treated with preoperative ENBD and/or ERBD. We retrospectively analysed prognostic factors (age, gender, preoperative ENBD and/or ERBD, tumor differentiation, pT factor, lymph node metastasis, surgical margin, lymphovascular invasion, preoperative maximal total bilirubin, postoperative chemoradiation/chemotherapy/radiation therapy, CA19-9) for recurrence after surgical resection. Results: Intrahepatic recurrence after surgical resection was detected in 22 /99(22.2%) patients with preoperative ENBD and/or ERBD, and 5/44(11.4%) patients without preoperative ENBD and/or ERBD for median period of 12 months (range 0-48). On univariate analysis, intrahepatic recurrence rate of patients who underwent ENBD and/or ERBD (n=99) was higher than that of patients who did not (n=44) ( P=0.090) and and that of patients who had T3/T4 factor (n=74) was higher than that of who had T1/T2 factor (n=69) (P=0.168). Intrahepatic recurrence rateof patients who had elevated CA19-9 (> 200) (n=49) was higher than that of patients who had not (n=94) ( P=0.002). In multivariate analyses, preoperative ENBD and/or ERBD and elevated serum CA19-9 level (>200 ng/mL) were prognostic factors for intrahepatic recurrence, with hazard ratios (HR) of 2.154 (95% confidence interval (CI) 0.893-7.626, P = 0.080) and 3.647, (95% confidence interval (CI) 1.660-8.011, P = 0.001). Conclusions: Preoperative preoperative endoscopic nasal biliary drainage (ENBD) and/or endoscopic retrograde biliary drainage (ERBD) procedures may affect the intrahepatic recurrence of tumor in patient with cholangiocarcinoma after surgical resection. And serum elevated CA 19-9 level affected intrahepatic recurrence of tumor in patients with cholangiocarcinoma after surgical resection.