bluuebunny/crossref_metadata_2025 huggingface dataset:
An organ-preserving strategy in patients with esophageal squamous cell carcinoma treated with immunochemotherapy.
Authors: Zhang Bo , Guo Yijia , Kou Xiaoge , Zhuang Wu , Ye Huangyang , Yang Mudan , Liu Yunpeng , Yu Guohua , Qi Xiao , Wang Qingyu , Huang Jing
Published: January 2025

424

Background:
This study evaluated the strategy of dose-dense chemotherapy plus a PD-1 inhibitor with selective organ-preservation in patients with advanced esophageal squamous cell carcinoma (ESCC).
Methods:
Patients with locally advanced or metastatic (confined to the supraclavicular lymph nodes) ESCC were enrolled to receive treatment with a PD-1 inhibitor plus albumin bound-paclitaxel, cisplatin and 5-FU every two weeks. After six cycles of treatment, patients with clinical complete response (cCR) confirmed by computed tomography (CT), endoscopy and biopsy underwent an organ-preserving strategy with continuation of immunochemotherapy. The primary endpoint was cCR rate in the intention-to-treat population. A post hoc analysis was also conducted in patients with advanced ESCC who had a best response of CR after immunochemotherapy from three prospective studies we previously reported. Consecutive patients who had not received esophagectomy prior to immunochemotherapy, and had durable CR as confirmed by imaging, endoscopy with or without biopsy were identified to provide supporting evidence for the organ-preserving strategy.
Results:
A total of twenty patients were enrolled. At data cut-off (September 12, 2024), eight patients fulfilled the criteria of cCR (40%), while six patients actually adopted the organ-preserving strategy. 75% of the patients experienced ≥ grade 3 treatment-related adverse events (TRAEs), most commonly neutropenia and leukopenia. All TRAEs were managed with appropriate medical care. In the post hoc analysis, out of 71 patients who had a best response of CR to immunochemotherapy in three previous trials, sixteen consecutive patients who had not received esophagectomy before immunochemotherapy, and remained CR assessed with CT at data cut-off were identified. Although endoscopy was not mandatory during follow-up, twelve patients underwent endoscopic exams, and none of them had suspected tumor with endoscopic visualization. Biopsies were taken for eight patients, and were all negative for tumor. The median follow-up for these twelve patients reached 42.7 months, suggesting a long-term disease-free survival after immunochemotherapy.
Conclusions:
Dose-dense nab-paclitaxel, cisplatin and 5-FU combined with a PD-1 inhibitor showed encouraging cCR rate and manageable safety, making organ-preservation a possible subsequent approach in patients with advanced ESCC. Clinical trial information: ChiCTR2300072992.
Chemoimmunotherapy plus radiotherapy in advanced esophageal squamous-cell carcinoma.
Authors: Nie Keke , Han Xiang , Zhang Ling , Hou Qiuyu , Ji Youxin
Published: January 2025

437

Background:
Chemotherapy plus Immune checkpoint inhibitors (ICIs) have improved survival outcomes of patients with advanced or metastatic esophageal squamous-cell carcinoma in both first- and second-line settings. However, the benefit of additional radiotherapy for the residual esophageal lesion after chemo-immunotherapy remains unclear.
Methods:
We conducted a one-arm, three-center, open label study involving patients who were treatment naïve, radiological and histological confirmed advanced or metastatic squamous-cell esophageal carcinoma. Enrolled patients were expected the survival time was three months or longer; and ECOG performance status score was 0 or 1. In induction phase, patients received four cycles of TP regimen chemotherapy (docetaxel, 75/mg
2
, iv on day 1 and cisplatin, 75mg/m
2
, iv on day 1) combined with PD-1 inhibitor (sintilimab, 200mg intravenous infusion on day 1) every 21 days. Patients who finished four cycles of chemo-immunotherapy with stable disease (SD) or partial response (PR) were initiated 50Gy/25f irradiation for residual tumors. 3-4weeks after radiotherapy, maintenance sintilimab therapy was administered every 21 days for another 31 cycles or until disease progression or intolerable toxicity.
Results:
Total of 39 patients were enrolled in this study, 30 of them could be evaluated in efficiency and toxicities. All of them were male and were squamous-cell carcinoma in histology. 12/30 (40.0%) patients were in stage III, and 18/30 (60.0%) were in stage IV. 29/30 (96.7%) patients completed four cycles chemo-immunotherapy, the complete response (CR) rate was 6.7% (2/30), the partial response (PR) rate was 53.3% (16/30) and disease control rate (DCR) was 86.7% (26/30). The median depth of response (DpR) was 34.5% for chemoimmunotherapy and was 64.0% after radiotherapy. The progression-free survival (PFS) was 16.4 months and the overall survival (OS) was not reached. The most common grade 3 or worse adverse event was neutropenia and occurred in 3 (10.0%) patients.
Conclusions:
Four cycles sintilimab plus cisplatin and docetaxel followed by radiotherapy for residual tumors and maintained sintilimab had high response rate, prolonged PFS and tolerable toxicities as first line treatment in patients with advanced or metastatic esophageal squamous-cell carcinoma. Longer OS is promising and more patients enrolled in this study is needed in future.
Clinical trial information: NCT06138028
.

Clinicopathological features and patient factors.

Factors
No. of patients (n=30) (%)

Gender
　

Male
30 (100.0)

Female
0 (0)

Age (year)
　

< 65
27 (43.3)

≥ 65
17 (56.7)

PD-L1 (CPS)
　

< 5
9 (30.0)

≥ 5
21 (70.0)

Clinical Stage
　

III
12 (40.0)

IV
18 (60.0)

Metastatic Pattern
　

Regional lymph node
12 (40.0)

Cervical & Supraclavicular
4 (13.3)

Abdomen
5 (16.7)

Lung
6 (20.0)
Efficacy, safety and DNA methylation analysis of cadonilimab combined with taxane and cisplatin as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): Updated results from an open-label, multicenter phase II trial (AK104-IIT-014).
Authors: Qu Wang , Gao Jing , Zhang Bo , Liu Yun , Guo Yijia , Yang Mudan , Huang Jing
Published: January 2025

463

Background:
Immune checkpoint inhibitors combined with chemotherapy had become the first-line standard treatment for advanced ESCC and cadonilimab, as a bispecific antibody simultaneously targeting PD-1 and CTLA-4, may further boost anti-tumor activity with a satisfied safety profile. Here, we present the updated data for the safety and efficacy of cadonilimab combination therapy as the first-line treatment in advanced ESCC. The correlation between DNA methylation and clinical response was also investigated.
Methods:
Treatment-naïve patients (pts) with unresectable locally advanced or metastatic ESCC were enrolled. Cadonilimab (10mg/kg, iv, d1, q3w) combined with paclitaxel or nab-paclitaxel (175 mg/m
2
, iv, d1, q3w) and cisplatin (65 to 75 mg/m
2
, iv, d1, q3w) were administrated for up to 6 cycles, then Cadonilimab (10mg/kg, iv, d1, q3w) monotherapy continued as maintenance until progressive disease or unacceptable toxicity, with a maximum of 24 months. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Plasma cell-free DNA samples were collected before and after treatment and prepared for methylation level sequencing.
Results:
As of September 20, 2024, 43 pts were enrolled with a median age of 61 years (range 44-75), 81.4% were male, 39.5% had PD-L1 CPS≥10 and 95.3% had metastatic diseases. All pts were evaluable for safety and efficacy. The ORR was 81.4% (95%Cl: 66.1%-91.1%) and DCR was 97.7% (95%Cl: 86.2%-99.9%). The median PFS (mPFS) was 7.05 months (mo) (95%Cl: 5.86-8.24) and OS analysis was immature. In the PD-L1 CPS≥10 pts, the ORR was 100.0% (95%Cl: 77.1%-100.0%) and mPFS was 7.05 mo (95%Cl: 5.19-8.91). In the PD-L1 CPS＜10 pts, the ORR was 77.3% (95%Cl: 54.2%-91.3%) and mPFS was 7.05 mo (95%Cl: 5.87-8.24). Six hyper-methylated CpG sites, EPTIN9、PKNOX2、DLEU7、SOX7、CNRIP1 and LINC00554 might be the candidate biomarkers as the mean pretreatment methylation levels were signiﬁcantly higher in the PR pts than those in the non-PR pts (p=7.8×10
-7
). Grade 3-4 treatment-related adverse events (TRAEs) were reported in 44.2% (19/43) pts, mainly including neutropenia (25.6%), leukopenia (9.3%) and hyponatremia (7.0%). The infusion-related reactions (IRR) occurred in 14.0% (6/43) and grade ≥3 IRR occurred in 4.7% (2/43) pts. 7 pts discontinued cadonilimab administration due to TRAEs.
Conclusions:
The updated results suggested that bispecific antibody cadonilimab combined with taxane and cisplatin as first-line treatment continued to show encouraging anti-tumor activity and manageable safety in pts with advanced ESCC. DNA methylation level might be a potential biomarker for guiding patient outcomes.
Clinical trial information: NCT05522894
.
The role of artificial intelligence in colorectal cancer and polyp detection: A systematic review.
Authors: Bai Sakshi , Singh Bipneet , Ethakota Jahnavi , Ogedegbe Oboseh John , Ntukidem Olanipekun Lanny , Chitkara Akshit , Rani Sindhu , Kumar Danesh , Hirth JoAnn , Malik Devin Birsingh
Published: January 2025

47

Background:
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Early detection and accurate diagnosis are essential for improving survival rates and optimizing therapeutic strategies. Recently, artificial intelligence (AI) technologies, such as machine learning algorithms, convolutional neural networks (CNNs), and computer-assisted diagnostic (CAD) systems, have significantly enhanced traditional diagnostic tools like colonoscopy and histopathology. This systematic review evaluates the current role of AI in CRC management, focusing on diagnostic improvements, predictive modeling, and outcome prediction.
Methods:
A comprehensive literature review was conducted using PubMed, Google Scholar, and MEDLINE using MeSH term to identify studies utilizing AI in CRC diagnosis and management, with a focus on diagnostic imaging, histopathological analysis, and predictive modeling. Studies were evaluated for the accuracy of AI-driven diagnostic systems and the predictive performance of AI models in clinical outcomes.
Results:
Out of 147 studies identified, 37 met the eligibility criteria for this review. AI tools such as CNNs, CAD systems, and EndoBRAIN showed high accuracy in CRC detection and polyp classification. Kudo et al. (2020) reported 98% CRC detection accuracy using EndoBRAIN. Blanes-Vidal et al. (2019) achieved 96.4% accuracy in polyp detection via DCNN. Additionally, Wang et al. (2019, 2020) demonstrated improved Adenoma Detection Rates (ADR) of 34.1% and 29.1%, respectively, using AI over traditional methods. For outcome prediction, AI models, including CNNs, predicted patient prognosis with reasonable accuracy, as highlighted by Skrede et al. (2020) with 76% accuracy in prognosis prediction.
Conclusions:
The systematic review and analysis of AI-assisted diagnostic modalities in colorectal cancer and polyp detection reveal promising results, with most models demonstrating high sensitivity, specificity, and accuracy. CNN-based models and CAD systems, in particular, show strong potential for improving detection rates and clinical outcomes in CRC screening. The studies included in this review demonstrate that AI can enhance diagnostic precision, particularly in identifying polyps and predicting clinical outcomes, with high validation rates. However, more external validation and long-term clinical studies are needed to fully establish the robustness of these AI tools in routine clinical practice.
Unraveling the role of interferon-stimulated neutrophils: A promising biomarker for immunotherapy efficacy and prognosis in gastric adenocarcinoma.
Authors: Pan Hongda , Liu Fenglin
Published: January 2025

472

Background:
Despite significant advancements in immunotherapy, the identification of effective predictive biomarkers for treatment response in gastric adenocarcinoma (GAC) remains a critical challenge. Discovering such biomarkers could enhance patient stratification and improve therapeutic outcomes.
Methods:
We conducted a comprehensive analysis of 18 specimens obtained from 10 GAC patients, both prior to and following immunotherapy. Utilizing single-cell RNA sequencing, we compared the cellular composition and functional phenotypes of these specimens, with particular emphasis on tumor-infiltrating immune cells and the identification of previously uncharacterized neutrophil subclusters.
Results:
Our analysis identified eight distinct neutrophil subclusters, including Neu01_S100A12, Neu02_VEGF, Neu03_CCL3_CCL4, Neu04_IL1β, Neu05_CXCR4, Neu06_IFN-Stimulated, Neu07_Proliferative, and Neu08_B-cell_related. Notably, the presence of IFN-Stimulated neutrophils was positively correlated with the efficacy of immunotherapy in GAC, a finding that was further validated through analyses of public datasets and in-house cohort studies employing multiplex immunohistochemistry. Additionally, IFN-Stimulated neutrophils served as prognostic indicators across multiple datasets. Investigations revealed that these cells engage in significant cellular communication with other immune components within the tumor microenvironment, including CD8+ T cells, macrophages, and B cells, thereby promoting a pro-inflammatory and anti-tumor phenotype. Importantly, pan-cancer analyses demonstrated the consistent prognostic and immunotherapy efficacy-predicting potential of IFN-Stimulated neutrophils across various cancer types.
Conclusions:
IFN-Stimulated neutrophils represent a promising biomarker for predicting immunotherapy response and patient prognosis in GAC. Our findings offer novel insights into the underlying mechanisms of immunotherapy and highlight potential avenues for personalized treatment strategies in the management of GAC.
A method for classifying colorectal cancer and gastric/esophageal cancer using blood-based testing.
Authors: Forouzmand Elmira , Gittelman Rachel , Selewa Alan , Singer Meromit , Hoang Theresa , He Yupeng , Chudova Darya , Talasaz AmirAli
Published: January 2025

52

Background:
Identifying the cancer signal of origin is of great value in the clinical use of blood-based cancer testing, especially in those tests that have potential to assess for more than one cancer type. Thus, an approach that can accurately identify cancer signal of origin in order to guide subsequent diagnostic workup is impactful to the adoption of this new technology. Here, we report feasibility data using the DNA methylation signature of plasma cell-free DNA to differentiate between colorectal cancer (CRC) and gastric/esophageal cancer (GEC) types.
Methods:
We developed an algorithm to distinguish between CRC and GEC based on the DNA methylation signature of plasma cell-free DNA molecules from more than 3,000 differentially methylated regions. First, a regression model (a multi-cancer classifier) was trained to identify the samples with sufficient tumor derived methylation signal using 6,822 cancer samples of 24 cancer types and the samples from 4,423 cancer-free individuals. A second regression model (a CRC/GEC classifier) was trained to distinguish CRC from GEC cases on the samples with positive calls from the multi-cancer classifier. The second model was trained on methylation signals from advanced stage CRC samples, advanced stage GEC samples (including esophageal, gastroesophageal, and gastric cancers), and samples from cancer-free individuals.
Results:
The multi-cancer classifier identified 92% (2,954/3,204) of CRC and GEC samples as positive at 90% target specificity, including 93% (2,086/2,253) of CRC samples and 91% (868/951) of gastric/esophageal cancer samples. The performance of the CRC/GEC classifier is evaluated through 10-fold cross validation on these 3,204 cancer samples, where in each fold, an additional 6,298 samples from cancer-free individuals were also used in training. Among the 2,954 CRC and GEC samples detected by the multi-cancer classifier, 2,698 (91%) were accurately classified by the CRC/GEC classifier. Among the detected CRC samples, 91% (1,907/2,086) were correctly classified as CRC. Similarly, 91% (791/868) of the detected GEC samples were correctly classified. The precision of the CRC/GE prediction was also assessed and 91% (2,698/2,954) of the detected cancer samples were correctly classified. Of the 1,984 detected cancer samples predicted as CRC, 96% (1,907/1,984) were true CRC samples. Of the 970 detected cancer samples classified as GEC, 82% (791/970) were correct.
Conclusions:
This assay with high sensitivity and accurate CRC/GEC classification can effectively guide subsequent diagnostic workups following a positive result, maximizing potential clinical utility. Ongoing work will continue further refinements.
Disparities in liver cancer risk and outcomes in the LGBTQ community: A literature review.
Authors: Anamika Fnu , Chitkara Akshit , Figueroa Marciano , Adib Arshia , Patel Rushin
Published: January 2025

528

Background:
Liver cancer continues to be a significant public health concern, particularly among high-risk groups such as individuals with hepatitis infections, alcohol use disorders, and metabolic diseases. While liver cancer disparities have been well-documented among racial and ethnic minority groups, emerging research highlights significant health inequities within the LGBTQ community, including higher rates of risk factors and limited access to screening and care. This literature review aims to assess the extent of liver cancer disparities within the LGBTQ community and identify gaps in prevention, screening, and treatment.
Methods:
We performed a systematic search across PubMed, Scopus, and Google Scholar for peer-reviewed studies published between 2000 and 2024. The inclusion criteria focused on studies addressing liver cancer risk, prevalence, or outcomes in LGBTQ populations. Data on key liver cancer risk factors such as hepatitis B and C prevalence, alcohol use, obesity, and access to healthcare services were extracted and synthesized. Additionally, we reviewed public health reports and clinical guidelines relevant to LGBTQ health disparities.
Results:
The review identified significant disparities in liver cancer incidence and mortality among LGBTQ individuals. Hepatitis B infection rates were about 1.5 times higher, and hepatitis C rates up to 1.7 times higher among LGBTQ populations, particularly among gay and bisexual men. Alcohol use disorder was about 30-40% more prevalent in LGBTQ individuals, which further increases the risk of liver cancer. Screening for liver cancer in LGBTQ populations is underutilized, with rates approximately 20% lower than the general population. There were reported delays in diagnosis in LGBTQ community due to stigma, discrimination, and lack of culturally competent healthcare services. While some interventions targeting LGBTQ health have shown promise, the overall lack of targeted liver cancer prevention and treatment strategies remains a significant barrier.
Conclusions:
LGBTQ individuals face increased liver cancer risk due to a higher prevalence of key risk factors and inadequate healthcare access. Current screening and preventive strategies are insufficient for addressing these disparities. Targeted interventions, including enhanced screening efforts, hepatitis vaccination and treatment programs, and the development of LGBTQ-specific healthcare protocols, are needed to reduce the liver cancer burden in this underserved population. Policymakers and healthcare providers must address the unique needs of LGBTQ individuals to achieve equitable cancer outcomes.

Prevalence of liver cancer risk factors in LGBTQ vs. general population.

Risk Factor
LGBTQ Population (%)
General Population (%)

Hepatitis B Infection
15
10

Hepatitis C Infection
18
12

Alcohol Use Disorder
25
16

Metabolic Syndrome
22
18

Screening Rate
40
60
MRI imaging and machine learning based radiomics for detection of mixed HCC and CCA tumors: Still a need for liver biopsy?
Authors: Qian Yuquan , Lu Qiaoyuan , Rodriguez Isaac , Vácha Michael , Min Xiangde , Ümütlü Muzaffer Reha , Castrillon German A , Schreyer Andreas , Haimerl Michael , Schoenberg Stefan O. , Ebert Matthias Philip , Vellala Abhinay , Alaffita Carlos Romero , Mora Juan Alberto Garay , Guo Zhiqiang , Hesser Jürgen , Weiss Christel , Froelich Matthias , Sun Yingshi , Teufel Andreas
Published: January 2025

531

Background:
Primary liver cancer (PLC), comprising hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), is a leading cause of cancer mortality globally. The combined hepatocellular cholangiocarcinoma (cHCC-CC) subtype may be less common but is relevant to treatment efficacy. We therefore evaluated the diagnostic accuracy of various approaches in distinguishing these liver cancers.
Methods:
Patients diagnosed with HCC, CCA, and cHCC-CC at Beijing University Cancer Hospital and Institute, China were included. Radiologists of varying expertise independently assessed MRI scans, and we measured their diagnostic consistency. Radiomic features were extracted from MRI scans, and machine learning was applied to differentiate the cancer types.
Results:
Standard imaging was insufficient to reliably characterize cHCC-CC. Abdominal imaging experts (AIEs) had a higher mean sensitivity for HCC and CCA, 88% and 84% respectively, while non-experts (NIEs) had a lower sensitivity of 50% for HCC and 38% for CCA (HCC: p=0.03, CCA: p=0.008). Radiomic analysis found ‘Sphericity’ and ‘ClusterShade’ as the most relevant features. However, radiomics algorithms were also not sufficient to distinguish cHCC-CC from either HCC or CCA. Regarding sensitivity, the radiomic-based model was not better than radiologists for any of the three classes (p=0.065 for HCC, p=0.426 for CCA, and p=1.0 for cHCC-CC). The random forest algorithm yielded an accuracy of 76% in the test set, since it correctly classified most HCC and CCA, while only one quarter of cHCC-CC tumors.
Conclusions:
Until improved diagnostic tools are available, biopsy of liver cancer remains critical to the detection, diagnosis, and effective treatment of these cancers.
Prevalence and clinical characteristics of patients with brain metastases at diagnosis with advanced hepatocellular carcinoma in a retrospective registry.
Authors: Harris Quincy , Chen Jocelin , McGuire Joseph , Gordan John , Lim Huat Chye , Li Michael , Venook Alan P. , Griffin Ann C , Kelley Robin Kate
Published: January 2025

540

Background:
Hepatocellular carcinoma (HCC) is a cancer with poor prognosis and rising incidence. The combination of atezolizumab plus bevacizumab (A+B) prolongs survival as 1
st
line therapy in advanced HCC (aHCC) but confers a rare risk of serious bleeding. HCC brain metastases (BM) have high hemorrhage rates and contraindicate the A+B regimen. Alternative immunotherapies also prolong survival without increased bleeding risk. We conducted a retrospective review of a large, diverse, cancer center registry to estimate the prevalence of and identify clinical characteristics associated with BM in aHCC.
Methods:
The University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center (HDFCCC) registry was queried for new cases of HCC between 2004 and 2022. AJCC stage III or IV were defined as aHCC. Cases with central nervous system (CNS) metastases (including brain as well as skull, face, or orbit as adjacent high-risk sites) at diagnosis were identified. Key clinical covariates including demographics, liver disease etiology, and symptomatology were described.
Results:
Among 4002 new HCC cases, 832 were classified as aHCC. 12/832 (1.4%, 95% CI: 0.8, 2.5) had synchronous BM. Key demographics are displayed in Table. 10/12 (83%) patients with BM were symptomatic, including headache (25%), neurologic deficits (67%), and/or syncope (8%). Bleeding complications and/or hemorrhagic features were reported in 17%.
Conclusions:
BM are rare at diagnosis with aHCC, present in only 1.4% of this registry dataset. The majority (83%) were symptomatic, suggesting that routine CNS imaging may not have clinical utility in asymptomatic patients. A high proportion with BM at diagnosis had viral etiology. Limitations of this retrospective registry analysis include potential for underdiagnosis in asymptomatic patients and incomplete data for clinical covariates.

Clinical characteristics of aHCC cases with BM at diagnosis between 2004-2022 in UCSF HDFCCC Registry.

Overall aHCC Cases (N=832)
Cases with BM (n=12)

Median age (range) (yrs.)
61 (8-92)
60 (48-65)

Race/ethnicity (%)AsianBlackCaucasianHispanic (any race)
29105715
2586717

Gender (%)MaleFemale
7921
7525

Etiology (%)Viral hepatitisUnknown/negative
2971
7525

Symptomatic BM (%)HeadacheNeurologic deficitsSyncope
NA
8325678

Hemorrhagic BM (%)
NA
17
Effectiveness of anti-epidermal growth factor receptor agents in elderly patients (age ≥ 70 years) with
RAS
wild-type metastatic colorectal cancer: Nationwide real-world data.
Authors: Wang Chao-Yuan
Published: January 2025

57

Background:
This study investigated the efficacy and safety of anti-epidermal growth factor receptor (EGFR) agents plus chemotherapy for elderly patients (aged > or = 70 years) with
RAS
wild-type metastatic colorectal cancer (mCRC) from nationwide data in Taiwan.
Methods:
Total 756 patients with
RAS
wild-type mCRC who received first-line therapy with anti-EGFR agents (Cetuximab) plus chemotherapy at nationwide multiple institutions from November 2016 to January 2021. The study explored the prognostic impact between two age groups (≥70 vs <70). Progression-free survival (PFS) and cancer-specific survival (CSS) were compared. Additionally, severe adverse events (SAEs) were also compared between two age groups.
Results:
The median PFS and CSS were comparable between the two age groups (14.0 vs 14.0 months,
p
= 0.098; 32.0 vs 35.0 months,
p
= 0.226, respectively). Moreover, subgroup analysis revealed similar PFS and CSS between two age groups in patients with synchronous or metachronous mCRC and left-sided or right-sided tumors (all
p
> 0.05). Regarding hematologic SAEs, a significant higher incidence of grade ≥ 3 anemia was found in elderly patient group (13.3% vs 5.0%,
p
= 0.003). However, no significant difference was observed in the incidence of non-hematologic SAEs (all
p
> 0.05).
Conclusions:
According to this nationwide real-world data, for patients carrying
RAS
wild-type mCRC treated with cetuximab plus chemotherapy, elderly patients could have comparable benefit as younger ones. Except for grade ≥ 3 anemia, other hematologic SAEs and non-hematologic SAEs revealed no significant difference between two age groups.
Clinical outcomes of camrelizumab + rivoceranib vs sorafenib (CARES-310) as first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC) of non-viral and viral etiology.
Authors: Shroff Rachna T. , Shi Wei , Wu Xiuzhi , Meng Xianzhang , Maj Melissa , Ryan Kristin , Galloway Chris , Alexander Laura
Published: January 2025

578

Background:
CARES-310 (NCT03764293) evaluated the combination of PD-1 inhibitor, camrelizumab (cam), and VEGFR-1-3 inhibitor, rivoceranib (rivo), compared to sorafenib (sor) for the treatment of uHCC. Cam + rivo significantly improved median overall survival (mOS) and median progression-free survival (mPFS) compared to sor (mOS, 23.8 months [mo] [95% CI 20.6, 27.2] vs 15.2 mo [95% CI 13.2, 18.5] hazard ratio [HR] 0.64 [95% CI 0.52, 0.79]; one-sided p<0.0001; mPFS, 5.6 mo [95% CI 5.5, 7.4] vs 3.7 mo [95% CI 3.1, 3.7]; HR 0.54 [95% CI 0.44, 0.67]; one-sided p<0.0001). The most common (≥10%) grade ≥3 treatment-related adverse events in the cam + rivo arm were hypertension (38.6%) and AST increased (20.2%).
Methods:
A post-hoc analysis of CARES-310 was performed, where mOS and mPFS were estimated using the Kaplan-Meier method and compared between the 3 etiology groups of non-viral, hepatitis C virus (HCV), and hepatitis B virus (HBV) using the log-rank test.
Results:
mOS was longer with camrelizumab plus rivoceranib compared with sorafenib in patients with non-viral (HR 0.68 [95% CI 0.39, 1.19]), HCV (HR 0.37 [95% CI 0.162, 0.84]), and HBV etiologies (HR 0.70 [95% CI 0.55, 0.89]) (Table). Similarly, mPFS was longer with camrelizumab plus rivoceranib compared with sorafenib in patients with non-viral (HR 0.55 [95% CI 0.34, 0.91]), HCV (HR 0.50 [95% CI 0.23, 1.06]), and HBV etiologies (HR 0.57 [95% CI 0.45, 0.72]) (Table).
Conclusions:
Cam + rivo in CARES-310 suggested clinically meaningful mOS benefit in non-viral and viral HCC vs sor and provides assurance of clinical benefit for first line treatment to patients with uHCC independent of etiology.
Clinical trial information: NCT03764293
.

Etiology Group
Camrelizumab + Rivoceranib (n=272)
Sorafenib(n=271)

Non-viral, n (%)
42 (15.4%)
45 (16.6)

mOS, mo (95% CI)
26.8 (10.3, NR)
15.2 (9.6, 23.2)

mPFS, mo (95% CI)
6.1 (4.1, 13.8)
3.7 (2.4, 5.5)

HCV, n (%)
22 (8.1)
29 (10.7)

mOS, mo (95% CI)
31.7 (10.8, NR)
13.3 (8.0, 21.5)

mPFS, mo (95% CI)
12.7 (3.7, NR)
3.7 (1.8, 9.1)

HBV, n (%)
208 (76.5)
197 (72.7)

mOS, mo (95% CI)
23.0 (18.9, 26.0)
15.6 (13.3, 19.2)

mPFS, mo (95% CI)
5.6 (5.5, 7.3)
3.7 (2.7, 3.7)

HCC, hepatocellular carcinoma; mOS, median overall survival; mPFS, median progression-free survival; mo, months; HR, hazard ratio; HCV, hepatitis C virus; HBV, hepatitis B virus, NR, not reached.

Results used Cox proportional hazard model.

Confidence Intervals (CI) used the Brookmeyer and Crowley method.
IMMULAB: A phase II trial of immunotherapy with pembrolizumab in combination with local ablation for patients with early stage hepatocellular carcinoma (HCC)—The IKF-IMMULAB trial.
Authors: Vogel Arndt , Waidmann Oliver , Wirth Thomas Christian , Tobias Mueller , Mohr Raphael , Siegler Gabriele Margareta , Goetze Thorsten O. , De Toni Enrico N. , Philipp Alexander B , Gonzalez-Carmona Maria A , Hausner Guido , Geissler Michael , Fischer von Weikersthal Ludwig , Kestler Angelika , Finkelmeier Fabian , Klagges Jorge , Eickhoff Regina , Al-Batran Salah-Eddin , Saborowski Anna Lena
Published: January 2025

582

Background:
Ablation of neoplastic tissue through radiofrequency ablation (RFA), microwave ablation (MWA), or brachytherapy is a potentially curative option for patients with early stage hepatocellular carcinoma (HCC); however, recurrence rates are high. While updated results from IMbrave050 do not support the use of adjuvant therapy following resection or local therapy, the potential of peri-interventional systemic treatment as a potentially more effective approach to increase recurrence free and long-term survival remains to be determined. We propose that peri-interventional treatment with pembrolizumab may improve outcomes following local ablative therapies.
Methods:
This single arm phase II trial investigates peri-interventional treatment with pembrolizumab combined with RFA/MWA or brachytherapy, or - as recommended for tumors ≥ 3 cm - by combination with TACE in early stage HCC with maintained liver function. 200 mg of pembrolizumab (q3w) was administered intravenously for 2 cycles followed by radiologic imaging and local therapy. Pembrolizumab was continued for up to 12 months. Primary endpoint was radiological response rate according to RECIST 1.1 prior to local therapy.
Results:
30 pts (ECOG 0 or 1) were enrolled in 9 centers in Germany with a median age of 70 years (73.3% males, median tumor size 25 mm with minimum of 10 mm and maximum of 72 mm, 60% solitary lesions). All pts received at least 1 dose of study treatment and the median number of cycles was 13. ORR was 13.3% with 6.7% CR and 6.7% PR after two cycles. After a median follow-up of 34.5 months, median time to recurrence (TTR) was 16.43 months, with 8 pts remaining free of recurrence. mOS was not reached, with a 2y OS rate of 76% and a 3y OS rate of 66%. No new safety signs were observed. Subsequent local ablation was performed in 13 pts, and 10 pts started on systemic therapies (5 TKI, 3 ICI and 2 pts received TKI and ICI).
Conclusions:
In the IKF-IMMULAB trial the expected objective response rate of 30%, according to RECIST1.1., prior to local therapy was not reached. However, with recent evidence that radiologic response underestimates pathological response in ICI-treated HCC patients and supported by a 2y OS rate of 76% and a 3y OS rate of 66%, there is evidence for the efficacy of peri-interventional treatment with pembrolizumab without new safety signals.
Clinical trial information: NCT03753659
.
Understanding the unmet needs in colorectal cancer: Insights from patient and survivor experiences.
Authors: Newcomer Kimberley Lynn , Fenstermacher David A.
Published: January 2025

59

Background:
Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide among men and women combined. Despite improved survival rates, there remains a gap in understanding the specific unmet needs of CRC patients and survivors. These needs include emotional support, information on treatment options, coping strategies, quality of life (QoL), and overall healthcare experience. The stress of a diagnosis is often compounded by the emotional and physical demands of treatment, which extend into survivorship when the disease is not active.
Methods:
The Colorectal Cancer Alliance launched a survey for colorectal cancer patients, survivors, and caregivers. This IRB-approved cross-sectional study, comprising more than 153 questions, aimed to inform on patient profiles, diagnosis experience, resources, QoL, access to care, and treatment experience. Participation in the survey was solicited from the Alliance network of social media, email, and web-based communities, underscoring the collective effort to understand and address the needs of CRC patients and survivors.
Results:
The survey included 283 participants, primarily aged 46-55. Key findings showed that 74% of participants had difficulty finding someone who understood their experience, and 41% reported reduced support from others after treatment ended. Additionally, 54% struggled with fatigue, and 51% coped with ongoing stress. CRC significantly impacted careers (64%), dating lives (51%), desire to have children (43%), relationships with spouses or partners (58%), sex lives (80%), and participation in social activities (65%). Although many felt informed before treatment, 46% reported unmet needs for information on complementary or alternative therapies.
Conclusions:
These results highlight the profound psychosocial and physical challenges faced by CRC patients and survivors, emphasizing the need for healthcare providers to develop tailored treatment and survivorship plans and comprehensive support services. Insights from this survey will guide the Colorectal Cancer Alliance (Alliance) in creating targeted actions, care programs, and support initiatives to address these needs. The Alliance aims to enhance patient care and improve CRC patients' and survivors' QoL, potentially reshaping the future of CRC management and survivorship care.
Surufatinib combined with locoregional therapies and immune checkpoint inhibitor (ICI) for treating unresectable or metastatic intrahepatic cholangiocarcinoma.
Authors: Zhang Wan Guang , Zhang Zhan Guo , Zhao Jian Ping , Ding Ze Yang
Published: January 2025

593

Background:
Advanced metastatic ICC, characterized by poor survival and limited therapeutic options, may benefit from the combined use of surufatinib—a selective tyrosine kinase inhibitor targeting VEGFR 1, 2, and 3, FGFR1, and CSF-1R—and ICIs, alongside locoregional treatments like TACE, DEB-TACE, and HAIC.
Methods:
Eligible pts who were 18 -75 years old with histologically confirmed unresectable or metastatic intrahepatic cholangiocarcinoma were enrolled. Pts received surufatinib (250mg, orally daily), ICI, and locoregional therapies until surgery, disease progression, death, intolerable toxicity, or withdrawal of consent. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), conversion to surgical resection rate and safety.
Results:
By July 31, 2024, 20 pts were enrolled and 10 pts were evaluated. Median age was 56.4 years (range: 36-69), with a majority being male (70%). 9 pts were pathologically confirmed as adenocarcinoma, 1patient was small bile tract type. Treatment included DEB-TACE (20%), TACE (30%), and HAIC (50%). 50% (5/10) pts achieved partial response (PR), 20% (2/10) pts accepted conversion surgery, 30% (3/10) pts achieved stable disease (SD), and the confirmed ORR was 50%, DCR was 80%. The median PFS (95%Cl: 6.9-NA months) had not yet matured, with no significant differences in survival benefits based on age or gender, though TACE showed potential benefits. The most common AEs of all grades were nausea (30%), dizziness (30%), and headache (10%), No grade ≥ 3 TEAEs or new safety signals occurred.
Conclusions:
Surufatinib plus immune checkpoint inhibitor, along with locoregional therapies showed preliminary anti-tumor activity and manageable toxicity for the 1L treatment of ICC, providing an additional treatment option for pts with ICC.
Clinical trial information: NCT05236699
.
Mediation of the liver protective effect of the anti-cancer drug candidate namodenoson via adiponectin.
Authors: Fishman Pnina , Bareket-Samish Avital
Published: January 2025

604

Background:
Namodenoson (CF102) is a small, orally available, anti-cancer drug candidate, currently in pivotal phase 3 clinical study for the treatment of hepatocellular carcinoma. Adiponectin is a positive cytokine released by adipocytes and endothelial cells, known to induce liver-, cardio-, and neuro-protective effects. We evaluated the potential role of adiponectin as the mediator of the observed namodenoson-induced protective effects.
Methods:
Proteins extracted fromN1S1 tumor-bearing mice and from murine adipocyte culture treated with namodenoson or vehicle were analyzed using Western blot. Apoptosis was determined in the N1S1 tumor-bearing mice using the TUNEL assay. The effect of namodenoson on hepatic ischemia/reperfusion (IR) was evaluated in Wistar rats by temporarily clamping the hepatic vasculature; the effect on hepatic inflammation was evaluated in Con. A-induced hepatitis in mice. The STAM murine in-vivo model was used to study the effect of namodenoson on metabolic dysfunction-associated steatohepatitis (MASH). Adiponectin levels were determined in the serum of patients in the phase 2 trial evaluating namodenoson vs placebo in patients with metabolic dysfunction-associated steatotic liver disease (MASLD)/MASH.
Results:
The anti-cancer effect of namodenoson was attributed to its capability to bind to the A3 adenosine receptor, inducing inhibition of PI3K and subsequent de-regulation of the Wnt/β-catenin and NF-kB signal transduction pathways, resulting in apoptosis of liver tumor cells. At the same time, namodenoson demonstrated a liver protective effect manifested by prevention of hepatic IR injury, suppression of liver inflammation, and induction of anti-fibrotic and anti-steatotic effects. In adipocyte cell culture, namodenoson stimulated adiponectin production. An increase in adiponectin levels was also shown in the murine MASH model (STAM). These in-vitro and in-vivo results were consistent with translational data from the phase 2 study of namodenoson in MASLD/MASH where upregulation of adiponectin was observed with namodenoson (mean change from baseline of 539 ng/mL for namodenoson 12.5 mg BID vs -78 ng/mL for placebo,
P
= 0.032).
Conclusions:
The anti-cancer effect of namodenoson combined with its protective effects, position it as a unique drug inducing a dual effect in patients with advanced liver cancer.
Real-world data of durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer: A Thailand multicenter observational study.
Authors: Tanasanvimon Suebpong , Maneenil Kunlatida , Wirasorn Kosin , Thanasombunsukh Kijjakom , Korphaisarn Krittiya , Sathitruangsak Chirawadee , Wanchaijiraboon Passakorn , Siripoon Teerada , Teeyapan Nattaya , Charonpongsuntorn Chanchai , Suksombooncharoen Thatthan , Thambamroong Tawasapon , Laosuangkoon Wannisa , Ngokngarm Chavapon , Simseekeaw Pronwasun , Akewanlop Charuwan , Sirachainan Ekaphop ,   TSCO GI Group
Published: January 2025

607

Background:
Currently, durvalumab plus gemcitabine and cisplatin is a standard of care for patients with advanced biliary tract cancer (BTC). We aimed to evaluate efficacy and tolerability of durvalumab plus gemcitabine and cisplatin in real world experience in Thailand where there is high incidence of liver-fluke related cholangiocarcinoma (CCA).
Methods:
This is an observation study of patients with advanced BTC participating in the early access program of durvalumab since August 2023. Data were collected and analyzed for efficacy and toxicity.
Results:
Fifty patients participated the early access program in 14 centers across Thailand. Median follow-up time was 8.5 months. Median number of treatment cycles was 8.8 (1-16) cycles. Thirty six (72%) patients were alive and 8 (16%) patients were still on treatment. The mean age was 63 years, 60% were male and 92% were ECOG 0-1. There were 68% intrahepatic cholangiocarcinoma (CCA), 28% extrahepatic CCA and 8% gallbladder cancer. There were 29.5% objective response rate and 79.5% disease control rate. Median progression free survival (PFS) was 6.0 (95%CI 4.49-7.50) months. Eight (16%) patients were still on treatment with PFS more than 10 months. Grade 3 or 4 adverse events (AEs) were reported in 50% of patients. Most AEs were related to chemotherapy, there were 10% immune related AEs.
Conclusions:
In this real-world experience, durvalumab plus gemcitabine and cisplatin was efficacious and tolerable in Thai patients with advanced BTC.
Social determinants of health and financial burden among patients with pancreatic cancer at a tertiary cancer center.
Authors: Jazieh Khalid , Lee Minji K , Steinert Kimberly O. , Lin Miranda , McWilliams Robert R.
Published: January 2025

678

Background:
Financial toxicity (FT) represents a challenge for cancer patients that impacts treatment decisions, patient satisfaction, and quality of life. Social determinants of health (SDoH) screening may predict who is at risk of FT and could potentially benefit from financial interventions.
Methods:
This is a retrospective study of all cancer patients presenting to Mayo Clinic sites between Sept 2023 – Jun 2024. Patients completed SDoH questionnaires and were given risk scores of Low Risk, Medium Risk, and High Risk for SDoH categories: Financial Strain Risk, Transportation Risk, and Food Insecurity Risk. Patient financial data including active debt amounts, insurance coverage, and financial aid were collected. Patients with pancreatic ductal adenocarcinoma (PDAC) were compared to those with pancreatic neuroendocrine tumors (PNET) and patients with other cancers (Others). Categorical variables were compared with Pearson's Chi-squared test, continuous variables with Kruskal-Wallis rank sum test. P values < 0.05 were considered significant.
Results:
Data was obtained from 88,039 patients, 2,607 of whom had PDAC and 449 had PNET. Compared to PDAC patients, PNET patients and Others were more likely to have Medium/High risk scores for Financial Strain Risk (6% vs 6.5% and 8.5%, respectively) and Food Insecurity (1.7% vs 3.8% and 3.2%) (Table). There was no statistically significant difference in median medical debt and need of financial assistance between the groups. Among PDAC patients, there were differences in distributions among race, primary language spoken, and patient electronic record access depending on Financial Risk categories. African American patients had the greatest proportion of Medium/High risk (12.9%) compared to Asian (4.4%) and White (5.8%) patients (P<0.001). Among patients with English as their primary language, 64.9% had Low Risk scores compared to 27.7% with other primary languages (P<0.001). Patients with electronic record access were more likely to report High Risk scores (6.9%) compared to those without access (1.6%).
Conclusions:
Per patient responses collected, PDAC patients presenting to our center have lower risk of financial strain and similar medical debt levels compared to the remainder of cancer patients. Among PDAC patients, higher financial strain was experienced by non-whites (7.9% vs 5.8%).

Diagnosis
PDAC (N=2607)
PNET (N=449)
Other (N=84983)
p value

Current Financial Risk (Grouped)

< 0.001

- Low Risk
1662 (63.8%)
304 (67.7%)
59298 (69.8%)

- Medium/High Risk
157 (6.0%)
29 (6.5%)
7209 (8.5%)

- Unknown/Missing
788 (30.2%)
116 (25.8%)
18476 (21.7%)

Food Insecurity Risk

< 0.001

- Low Risk
1764 (67.7%)
308 (68.6%)
63235 (74.4%)

- Medium Risk
45 (1.7%)
17 (3.8%)
2703 (3.2%)

- Unknown/Missing
798 (30.6%)
124 (27.6%)
19045 (22.4%)

Median Active Debt in USD
1102.230
1020.010
1141.135

0.593
Investigating communication barriers impacting postoperative decision regret in patients with pancreatic ductal adenocarcinoma.
Authors: Li Judy , Li Thomas M , Geffner Adam , Neugarten Sophie , Correa Camilo , Sarpel Umut , Labow Daniel M , Gunasekaran Ganesh , Schwartz Myron E. , Tabrizian Parissa , Hiotis Spiros P , Park James O , Cohen Noah A
Published: January 2025

698

Background:
Patient communication barriers are associated with worse quality of care and clinical outcomes. However there are limited data exploring their impact on shared decision-making (SDM) in the preoperative setting, especially for pancreatic ductal adenocarcinoma (PDAC). This study investigates the impact of patient communication barriers on patient-physician communication surrounding the decision to pursue pancreatectomy.
Methods:
This cross-sectional study investigates the impact of communication barriers on the degree of decisional regret (DR) in patients with PDAC who have undergone curative-intent resection at least 6 months prior to study recruitment. Patients completed validated surveys assessing communication preferences, SDM participation, and DR. Health literacy was assessed by the BRIEF Health Literacy survey. Groups were stratified by presence or absence of DR, assessed by the Decisional Regret Scale (DRS). Characteristics and survey scores were compared by chi-square and independent t-test. Given significant findings, results of this interim analysis are reported below.
Results:
45 patients met inclusion criteria and completed all questionnaires. 19 (42.2%) patients expressed regret about their decision to pursue surgery with 5 patients expressing moderate to severe regret (DRS ≥25). Baseline characteristics were similar between groups. There were no significant differences in neoadjuvant or adjuvant treatments, or operative characteristics. Both groups reported high participation in preoperative SDM (average score 34.47 ± 9.67 in DR group vs 36.08 ± 8.88, P=0.567). Despite similar levels of education between groups, those expressing regret had a lower level of health literacy (14.68 ± 4.10 vs 17.35 ± 2.07, P=0.016). Fewer patients also identified English as their primary language in the DR group (78.9% vs 100%, P=0.026). While most patients preferred an active role in the final decision making process, fewer patients in the DR group reported this happening in actuality (ƙ= 0.635 vs ƙ=0.934).
Conclusions:
Almost half of patients expressed some regret pursuing surgery for PDAC. Despite similar educational backgrounds, a higher proportion of those expressing regret did not identify English as their primary language and had lower health literacy. While there was high participation in SDM, there was greater discordance between preferred and actual roles in the final decision making process. This identifies an important disparity to address in future preoperative discussions.