tbuckley/cabot-search huggingface dataset:
Current status and treatment outcomes of intraductal papillary mucinous carcinoma in Korea: A multi-center cohort study.
Authors: Hee-Eon Lim, Jong-chan Lee, Woo Hyun Paik, Yoon Suk Lee, Jin Ho Choi, Joo Kyung Sophie Park, Young Hoon Choi, Kang Won Lee, Jae Min Lee, HyeonKi Kim, Wootaek Seo, Kwangrok Jung, Jaihwan Kim, Jin-Hyeok Hwang
Journal: Journal of Clinical Oncology (2025)

812 Background: The spectrum of intraductal papillary mucinous neoplasm (IPMN) varies from benign cysts to intraductal papillary mucinous carcinoma (IPMC). There is a lack of large-scaled data on IPMC and high-grade dysplasia. We aimed to study the real-world status and treatment outcomes of IPMC in South Korea. Methods: This is a retrospective, multicenter study conducted in South Korea. We reviewed the electronic medical records of patients who were histologically diagnosed with IPMC or high-grade (HG) dysplasia between 2011 and 2020, and analyzed the baseline characteristics, treatment patterns, and survival. Results: A total of 388 patients were eligible from six institutes (145 female [37%]; median age 67.8; 259 IPMC [67%] vs 129 HG dysplasia [33%]). The median overall survival for IPMC patients was 75 months, compared to 133 months for HG dysplasia. In IPMC group, 217 (84%) were underwent surgical resection and 42 (16%) did not underwent surgery due to general condition or advanced stage whose median overall survival was 83 months and 49 months respectively. In resected IPMC, 104 (48%) received adjuvant chemotherapy (gemcitabine single 48%, 5FU+leucovorin 33%, others 19%) and 66 (30%) experienced recurrence and median recurrence-free survival (RFS) was 20 months. Among IPMC group, 11 (4.2%) was in advanced stage and eight of those received palliative chemotherapy (FOLFIRINOX 62.5%; gemcitabine single 25%; gemcitabine with erlotinib 12.5%). In HG dysplasia, 108 (84%) patients underwent surgery, and 21 (16%) patients did not undergo surgery whose OS were 171 and 133 months, retrospectively. In patients with resected HG dysplasia, 29 (27%) experienced recurrence and median RFS was 21 months. Conclusions: IPMC generally showed longer survival and a lower recurrence rate than those of historical data in PDAC, with HG dysplasia demonstrating even better outcomes. In real world, similar chemotherapy regimens used for PDAC were applied to IPMN patients. Treatment status of intraductal papillary mucinous carcinoma and high-grade dysplasia. IPMC(259) IPMN-HG(129) Total(388) Median overall survival (month) 75 133 85 Treatment OP 217(84%) 108(84%) 325(84%) Adjuvant chemotherapy 104(48%) 19(18%) 123(38%) Recurrence rate 66(30%) 29(27%) 95(29%) Median recurrence-free survival (month) 20 19 21 Palliative chemotherapy 8(3%) NA Progression rate 5(63%) NA Progression-free survival (month) 13 NA
Association between immune-related adverse events and prognosis after immune checkpoint inhibitor in hepatocellular carcinoma: A meta-analysis and systematic review.
Authors: Soo Young Hwang, Mohammad Saeid Rezaee-Zavareh, Abdelrahman M Attia, Emily Kaymen, Nguyen H. Tran, Ghassan K. Abou-Alfa, Amit Singal, Ju Dong Yang
Journal: Journal of Clinical Oncology (2025)

566 Background: Immune checkpoint inhibitors (ICIs) have become the preferred treatment for unresectable hepatocellular carcinoma (HCC). Conflicting data exist regarding the prognostic value of immune-related adverse events (irAEs) in these patients. We aimed to explore potential the association between irAEs and prognosis in HCC patients treated with ICIs. Methods: We searched PubMed, Scopus, Web of Science, and CENTRAL databases for articles published from inception to June 2024 using keywords including ICI, HCC, and irAEs. Two reviewers independently screened studies for eligibility and relevant data. A random effects model was used for statistical analysis, and subgroup analysis was performed by the grade of irAEs. Results: Of 3,028 studies, 25 (n=4,116 patients) met criteria for inclusion. Atezolizumab plus bevacizumab was the most common treatment regimen (n=10 studies). About half (49.5%) of patients experienced irAEs. irAEs were associated with increased objective response rate (ORR) (pooled OR: 1.72; 95% CI: 1.36 – 2.19, I 2 =39%), higher complete response rate (pooled OR: 1.45; 95% CI: 1.21-1.74, I 2 =74%), and longer progression-free survival (PFS) (pooled HR: 0.66; 95% CI: 0.52-0.84, I 2 =71%). Although irAEs were associated with longer overall survival, this difference was not statistically significant (pooled HR: 0.83; 95% CI: 0.62 – 1.11, I 2 =73%). Subgroup analysis showed a survival benefit for patients with grade 1-2 irAEs (pooled HR: 0.50; 95% CI: 0.36-0.67, I 2 =0%) but not for those with grade 3-4 irAEs (pooled HR: 0.95; 95% CI: 0.24-3.72, I 2 =84%). Conclusions: The development of irAEs is associated with a favorable prognosis in HCC, including improved PFS and higher ORR. A survival benefit was noted in patients with mild irAEs, but not in those with severe irAEs. Future studies are needed to determine if a differential survival benefit relates to the continuation vs. discontinuation of ICI therapy.
Aflibercept (AFL) vs. ramucirumab (RAM) -based therapy in patients with advanced colorectal cancer: Efficacy comparison using real-world data evidence from TriNetX platform.
Authors: Jesus Rodriguez-Pascual, Gema Hernández, Lisardo Ugidos, Alejandro Parralejo, Juan Diego Rodriguez-Castaño, Juan Jose Serrano, Angel Ayuso
Journal: Journal of Clinical Oncology (2025)

71 Background: FOLFIRI in combination with Aflibercept (AFL) or Ramucirumab (RAM) prolongs overall survival compared with FOLFIRI alone in patients with advanced colorectal cancer (aCCR) as second-line therapy, however, there are no comparative studies between them. Methods: Utilizing the TriNetX Global Collaborative Network, a platform that operates globally based on anonymized and aggregated clinical data, a sample of aCCR patients from 128 healthcare organizations (HCOs) who met the initial criteria was selected. 5-year overall survival (OS) was analyzed between these cohorts using a Kaplan-Meier analysis. Hazard Ratio (HR) and its 95% confidence interval (95%CI) were calculated to evaluate the difference between cohorts. Propensity Score Matching (PSM) was used to balance the cohorts based on age, gender, and race mitigating possible cofounding variables. All statistical analyses were conducted utilizing the TriNetX Analytics function in the online research platform. Results: A total of 1046 patients met the study criteria and were included in our study. 523 received AFL and 523r received RAM-based therapy. Patients treated with AFL showed a significant better OS compared to patients treated with RAM, both previous to PSM and before PSM (post-PMS median OS 430 days vs 317 days, HR 0.797, 95%CI 0.683-0.930). Conclusions: In this study, based on Real World data, Aflibercept showed superior results to Ramucirumab in advanced colorectal cancer patients treatment. To date this is the largest study comparison between this two therapeutic options.
Real-world outcomes of targeted therapies and local interventions in BRAF V600E–mutated metastatic colorectal cancer: A single-center retrospective study.
Authors: Ziqin Lin, Xiaoyu Xie, Jianwei Zhang, Huabin Hu, Jiayu Ling, Yue Cai, Zehua Wu, Yanhong Deng
Journal: Journal of Clinical Oncology (2025)

203 Background: Metastatic colorectal cancer (mCRC) patients with BRAF V600E mutations, especially those with microsatellite stable (MSS) tumors, have poor prognoses. Chemotherapy has limited efficacy in this subgroup, especially for second-line or subsequent-line treatments. Current research is increasingly focusing on the integration of targeted therapies and local interventions, but real-world evidence remains scarce, particularly from Asian cohorts. This study leverages real-world data to evaluate the impact of novel therapeutic combinations, including triplet and doublet targeted therapies, alongside local treatments in this high-risk patient population. Methods: This retrospective study includes MSS-type mCRC patients with BRAF V600E mutations treated at the Sixth Affiliated Hospital of Sun Yat-sen University between April 2014 and May 2024. Patients receiving targeted therapies were stratified into three groups: Triplet group (BRAF, EGFR, and MEK inhibitors, including Dabrafenib, Cetuximab and Trametinib), Doublet group (BRAF and EGFR inhibitors, including Dabrafenib and Cetuximab or Encorafenib and Cetuximab), and Doublet target-chemotherapy group (BRAF and EGFR inhibitors combined with chemotherapy, including Vemurafenib, Irinotecan, and Cetuximab). Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and objective response rate (ORR). Results: Among 239 enrolled patients, 58 received targeted therapy and 68 underwent conventional chemotherapy as second-line treatment. 63.5% (80/126) of these patients underwent local interventions, including primary tumor resection, metastasectomy, CRS±HIPEC, and liver ablation. Targeted therapy demonstrated significantly improved mPFS compared to conventional chemotherapy (5.5 vs. 4.2 months, HR = 0.44; 95% CI: 0.29-0.68, p &lt; 0.001). OS did not differ significantly between the two treatment arms (12.7 vs. 12.1 months, HR = 0.80; 95% CI: 0.50-1.25, p = 0.330). In the triplet group, ORR, mPFS, and mOS were 21%, 5.8 months and 18.0 months, respectively, showing a trend towards enhanced efficacy compared to the other targeted therapy groups, albeit without statistical significance. Patients who received targeted therapy (n=35) or chemotherapy (n=45) in combination with local interventions demonstrated significantly prolonged OS compared to those without local therapy (mOS: 22.3 vs. 9.6 months; HR = 0.19; 95% CI: 0.09-0.42; p &lt; 0.001 and 14.3 vs. 10.9 months; HR = 0.53; 95% CI: 0.29-0.98; p = 0.042, respectively). Conclusions: Optimal treatment for BRAF V600E mCRC remains under investigation. This study suggests that combining targeted therapies with selective local interventions may significantly improve patient survival in this challenging subgroup, warranting further prospective evaluation.
Concurrent transarterial chemoembolization plus atezolizumab and bevacizumab in unresectable hepatocellular carcinoma: Interim analysis from a multicenter real-world study (CHANCE 023).
Authors: Rong Yan, Haidong Zhu, Jian Lu, Gao-Jun Teng
Journal: Journal of Clinical Oncology (2025)

542 Background: Combining transarterial chemoembolization (TACE) with systemic therapies such as atezolizumab and bevacizumab (T+A) has shown potential efficacy in patients with unresectable Hepatocellular carcinoma (HCC) This interim analysis aims to evaluate the efficacy and safety of this combination therapy when administered concurrently within a two-month period. Methods: This multicenter, real-world study included patients diagnosed with unresectable HCC who received TACE combined with T+A from January 2020 to June 2024, across 37 centers in mainland China. The primary endpoint was overall survival (OS). This trial is registered with ClinicalTrials.gov, NCT06024252. Results: Out of a cohort of 335 patients, 293 (259 males) met the inclusion criteria, and 37.5% (112/293) adopted this regimen as second-line therapy. The interim analysis showed a median OS of 29.97 months and a one-year survival rate of 76.50%. The median PFS was 19.23 months, and the objective response rate (ORR) was 41.6%, with 26 complete responses and 96 partial responses. The disease control rate (DCR) was 84.6%. Common adverse events included bone marrow suppression, decreased white blood cell or platelet counts, among others. Serious adverse events occurred in 9.2% of patients (27/293) and were manageable with standard interventions. Conclusions: This study is a real-world analysis to highlight the potential benefits of combining TACE with T+A in this patient population. However, longer follow-up is required to better assess both overall survival and the long-term safety profile of this treatment strategy. Clinical trial information: NCT06024252 .
Physical activity and sedentary behavior patterns after early-onset colorectal cancer diagnosis.
Authors: Andreana Natalie Holowatyj, Samantha R Keller, Allison Rosen, Rebecca Babyak, Katherine J Hunzinger
Journal: Journal of Clinical Oncology (2025)

74 Background: Sedentary lifestyle and physical inactivity are established risk factors for colorectal cancer diagnosed among adults younger than age 50 years (early-onset CRC). However, patterns of physical activity (PA) and sedentary behavior (SB) in patients after an early-onset CRC diagnosis are less understood. Methods: The Reproductive Health After Cancer Diagnosis and Treatment (REACT) Study is a patient-partnered, cross-sectional study in cooperation with 23 community partners and patient advocates that recruited adults with a first primary cancer (diagnosis age: 18-49 years) over an 8-week period (October to December 2021). Patient-reported sociodemographic, cancer and cancer impact, PA and SB questions were prospectively collected via questionnaire. Frequency, duration and intensity of leisure-time, work-related and transportation-related PA were summed as minutes per week (min/wk). Time spent on SB was calculated by hours spent sitting on a typical day. Diagnosis age- and year-adjusted Spearman correlation coefficients were calculated between PA and SB by cancer treatment status. Results: A total of 131 patients were diagnosed with a first primary early-onset CRC between 2016 and 2021 (median [IQR] age, 40.0 [35-45] years; 82.4% female) in REACT. One hundred thirteen patients (86.3%) were concerned about their physical fitness or getting enough exercise after cancer diagnosis—of whom 62.8% (n=71 of 113) were somewhat or very concerned about their physical fitness/exercise. Among 80 patients with early-onset CRC and complete PA/SB data (86.3% female), 28.8% were not adherent to PA guidelines for aerobic activity (≥150 min/wk) and 56.3% reported long sedentary time (&gt;6 hr/day). The proportion of patients across PA/SB groups also statistically significantly differed by treatment status among those diagnosed between 2019 and 2021 (p=0.049), but not between 2016 and 2018 (p=0.25). While PA was not significantly correlated with SB for early-onset CRC patients who were not actively undergoing treatment (r=-0.16, p =0.32), there was a statistically significant moderate inverse correlation between PA with SB among early-onset CRC patients under active cancer treatment (r=-0.58, p =0.004). Conclusions: One in every 2 early-onset CRC patients reported long sedentary time and one in every 4 early-onset CRC patients in this study did not meet the Physical Activity Guidelines for Americans. With over 80% of patients expressing concern about their physical activity and exercise after an early-onset CRC diagnosis, and differences in PA/SB patterns observed by treatment status, these findings warrant prospective, longitudinal studies of objectively-measured PA and SB among young patients in order to support tailored strategies (e.g., exercise prescriptions) that improve patient health and outcomes across the CRC continuum.
Prevalence and clinical characteristics of patients with brain metastases at diagnosis with advanced hepatocellular carcinoma in a retrospective registry.
Authors: Quincy Harris, Jocelin Chen, Joseph McGuire, John Gordan, Huat Chye Lim, Michael Li, Alan P. Venook, Ann C Griffin, Robin Kate Kelley
Journal: Journal of Clinical Oncology (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
Biomarkers associated with recurrence after salvage surgery for localized anal cancer (AC).
Authors: Mir Lim, Van K. Morris, Sharia D. Hernandez, Kangyu Lin, Y. Nancy You, Ryan W Huey, Wei Lu, Larisa Kostousov, Leticia Campos Clemente, Edwin Roger Parra Cuentas, Luisa Maren Solis
Journal: Journal of Clinical Oncology (2025)

9 Background: While most patients with localized AC are cured by chemoradiation (cRT), some recur and require salvage surgery (SS). No adjuvant therapies are effective after SS. We profiled cRT-refractory AC tumors from SS to identify biomarkers linked to recurrence. Methods: Using an IRB-approved protocol, patients with localized, cRT-refractory AC were classified as recurrent (R; N=19) or non-recurrent (NR; N=10) according to outcome after SS. Digital spatial profiling whole transcriptome analysis (GeoMx) on FFPE AC evaluated expression of 18000+ genes on 40 regions of interest (ROI) for R vs 25 ROIs for NR AC cores, separated into “tumor” (panCK+) and “tumor microenvironment” (TME; panCK-). log2 transformed RNA counts were compared for expression between ROIs of R and NR AC (limma). For GSEA hallmark pathway analysis, normalized enrichment scores (NES) were calculated using genes with differential gene expression. Expression of immune biomarkers using multiplex immunofluorescence (mIF) were quantified (N/mm2) and compared with a student’s t-test. Results: With a median follow up of 26.6 months, median OS (29.1 months vs NR; p&lt; .001) was shorter for R AC. For NR AC, higher expression of genes associated with immune activation (p-adj&lt; .0001 for all) - B2M (fold change (FC) 33.0), HLA-DPA1 (FC 30.1), and HLA-DPB1 (FC 15.0) – and higher NES for “interferon alpha response” (NES 3.2) and “interferon gamma response” (NES 3.1) (FDR &lt; .05 for both) were observed. R AC had higher expression of genes (p-adj &lt; .0001 for all) regulating TGF-beta signaling – LY6K (FC 10.3) and BCAR3 (FC 3.6), and higher “EMT” (NES 2.1) and “TGF-beta” (NES 1.6) GSEA signatures (FDR&lt; .05 for both). On mIF, greater CD3+CD8+ T cells were observed in tumor (148 vs 42 N/mm2; p=.02) and TME (8.2 vs 2.8 N/mm2; p=.008) for NR AC. Increased Thy1+ cancer-associated fibroblasts were noted in tumor (4.2 vs 1.2 N/mm2; p=.04) and in TME (149 vs 69 N/mm2; p=.04) for R AC. Conclusions: Signatures of immune activation were observed with gene expression and mIF in AC patients cured by SS. R AC had higher immune suppressing profiles. These data support developing novel therapeutics that promote immune activation in trials of patients with cRT-refractory AC at high risk for recurrence after SS.
Outcomes in management of locally advanced rectal cancer with total neoadjuvant therapy in an underserved population.
Authors: Arup Ganguly, Ruchir Paladiya, Sushrut Ingawale, Suprabhat Giri, Vaidarshi Abbagoni, Jaykumar Ranchodbhai Thumar
Journal: Journal of Clinical Oncology (2025)

208 Background: The use of total neoadjuvant therapy is now standard of care and is favored when treating locally advanced rectal cancer but its treatment is seldom studied in an underserved population. Methods: A retrospective study was conducted on patients with Stage II and III locally advanced colorectal cancer treated with either total neoadjuvant therapy (TNT) followed by resection or conventional therapy (CT) with chemoradiation followed by surgery, with or without adjuvant treatment afterwards. Patients completed treatment between 2015 and 2023 at the Hartford Hospital Helen and Harry Gray Cancer Center at Hartford, Connecticut. Data collected included demographics, type of treatment, tumor location (high vs mid vs low) and pathological response to treatment spread out among the two groups. Propensity score matching was used to minimize baseline differences between the two groups, adjusted for age, gender, ethnicity and tumor location and Fisher’s exact test was performed to then check for significance. Results: Out of the 133 patients analyzed, 90 underwent TNT, and 43 received CT. The average age at diagnosis was 57.5 years (SD: 11.15). In the TNT group, 79 patients (87.7%) achieved either a partial or complete response (PCR), while 11 patients (12.3%) had No response (NR). Tumor locations in the TNT group were distributed as follows: 13.4% (n=12) had high tumors, 34.4% (n=31) had mid tumors, and 52.2% (n=47) had low tumors. In the CT group, 31 patients (72.9%) achieved PCR, while 12 patients (27.9%) had NR. Tumor locations in the CT group were distributed as follows: 9.3% (n=4) had high tumors, 51.2% (n=22) had mid tumors, and 39.5% (n=17) had low tumors. After propensity score matching and adjusting for demographic covariates, the TNT group demonstrated a higher proportion of responders compared to the CT group (p=0.048). Furthermore, 40% (n=36) of patients in the TNT group achieved a complete response, compared to 32% (n=14) in the CT group. Partial response rates were 39.5% (n=17) in the TNT group and 47.8% (n=43) in the CT group. Conclusions: TNT demonstrated superior pathological response rates compared to CT, which supports its growing role in the management of locally advanced rectal cancer even in this underserved population.