tbuckley/cabot-search huggingface dataset:
Coronary Ectasia: Prevalence, Angiographic Characteristics and Clinical Outcome
Authors: Mohamed Ztati
Journal: Clinical Cardiology and Cardiovascular Interventions (2024)

Background/Aim: Coronary artery ectasia (CAE) is defined as diffuse dilation of the coronary arteries and differs from coronary aneurysms by being non-localized. The condition is rare, often associated with atherosclerosis, and poses significant management challenges due to its unclear pathophysiology and varied clinical presentations. The study aims to provide insights into the hospital's experience with CAE and evaluate its prognostic factors. Materiels and methods: This retrospective study evaluated 28 patients with CAE from 1692 individuals who underwent coronary angiography between January 2021 and January 2024. Patients with other heart conditions were excluded. CAE diagnosis was based on coronary artery dilation ≥1.5 times the adjacent normal segment. Data on clinical characteristics, myocardial perfusion, and stenosis were collected, and coronary lesions were classified using the Markis classification system. Results: CAE was observed in 1.65% of the study population, with most patients being male smokers, averaging 55 years of age. Of the CAE patients, 74% had significant lesions, 59% had multi-vessel involvement, and 25% presented with spontaneous thrombosis. Left ventricular dysfunction was noted in 60% of patients. Pharmacologic treatments included aspirin for all, while 9 patients also received anticoagulation therapy. Percutaneous coronary intervention (PCI) was conducted in select cases with thrombus formation or significant stenosis. Conclusion: CAE remains a poorly understood condition with a significant thrombotic risk. Atherosclerosis was the predominant cause, and management strategies, especially for thrombosis, remain individualized. Optimal treatment is still unclear, and large multicenter studies are needed to develop better treatment guidelines for CAE patients.
Efficacy and safety of anlotinib as a later-line treatment for advanced colorectal cancer.
Authors: Yang Song, Lili Liu, Jie Min, Xianghui You, Xue Yang, Feng Zhang, Xiaofeng Huang, Chenggong Liao, Hong Shi, Haichuan Su
Journal: Journal of Clinical Oncology (2025)

194 Background: Colorectal cancer (CRC) is increasingly prevalent in China, with rising incidence and mortality rates. Often, early-stage CRC presents with no symptoms, leading to most patients being diagnosed at an advanced stage, where prognosis is poor. First- and second-line treatments for advanced CRC typically include chemotherapy combined with cetuximab or bevacizumab. However, third-line therapies such as regorafenib, furosemide, and TAS102 have shown limited efficacy. Anlotinib, a multi-targeted tyrosine kinase inhibitor (TKI), has demonstrated improved progression-free survival (PFS) in refractory metastatic CRC (mCRC) in a phase III trial (NCT02332499), showing both efficacy and manageable toxicity. This report provides updated results from extended follow-up. Methods: This study enrolled 73 patients with advanced colorectal cancer who had undergone at least two prior standard treatments and were treated with oral anlotinib hydrochloride (8-12 mg daily, days 1-14 of a 21-day cycle) between November 2021 and March 2024 at Tangdu Hospital. Patients were treated until disease progression or intolerable adverse events. Efficacy was assessed using RECIST version 1.1, and adverse reactions were evaluated using CTCAE version 5.0. The primary endpoints were PFS, disease control rate (DCR), and adverse events (AEs), while secondary endpoints included overall survival (OS). Results: Of the 73 patients included, 38 had an ECOG performance status (PS) of 0-1, and 35 had a PS of 2. Clinical staging identified 18 patients with stage IIIB/IIIC and 55 with stage IV disease. Patients received anlotinib doses of 8 mg (n=11), 10 mg (n=44), or 12 mg (n=18), with 48 patients also receiving chemotherapy and 25 receiving anlotinib alone. The median PFS was 4.0 months (95% CI: 3.4-4.6), and the median OS was 7.0 months (95% CI: 5.7-8.3). Subgroup analysis indicated that patients under 60 years of age, those without liver metastases, and those with ECOG PS 0-1 derived greater benefit from anlotinib. The most common treatment-related adverse event was hypertension (19.2%). Other notable adverse events included elevated AST (11.0%), proteinuria (6.8%), and jaundice (6.8%). Most adverse reactions were grade 1-2, although 1 patient experienced grade ≥3 gastrointestinal bleeding. Conclusions: Anlotinib showed promising efficacy and a favorable safety profile as a later-line treatment for advanced colorectal cancer. These findings suggest that anlotinib may be a viable clinical option for advanced CRC, though larger-scale clinical trials are necessary to confirm these results and further define its role in treatment.
Short-course radiotherapy (SCRT) followed by fruquintinib plus adebrelimab and CAPOX in the total neoadjuvant therapy of locally advanced rectal cancer (LARC): A multicenter, single-arm, open-label, phase II study (UNION TNT).
Authors: Zhenyu Lin, Peng Zhang, Lei Zhao, Hong Ma, Hongli Liu, Junli Liu, Ximing Xu, Dandan Lin, Zhen Zhang, Fan Xia, Kaixiong Tao, Tao Zhang
Journal: Journal of Clinical Oncology (2025)

192 Background: We have demonstrated that neoadjuvant SCRT followed by PD-1 inhibitor plus CAPOX for LARC patients (pts) showed a higher pCR rate and a well-tolerated safety profile in phase III UNION study. Fruquintinib is a potent and highly selective VEGFR inhibitor, which had been approved for previously treated mCRC pts. This study aimed to investigate the efficacy and safety of SCRT followed by fruquintinib plus adebrelimab and CAPOX as a total neoadjuvant therapy for high-risk LARC pts. Methods: In this prospective, open-label, multi-centers, single-arm phase 2 study (NCT06234007), pts diagnosed with newly diagnosed and high risk LARC were recruited. Pts received SCRT (25Gy/5f) followed by six cycles of fruquintinib (4mg, qd, po, q3w,for the initial 6 pts in the safety run-in period, dosage would be adjusted based on dose-limited toxicities in the 1st cycle) combined with adebrelimab (1200mg, iv, d1, q3w) and CAPOX (q3w). Primary endpoint was CR rate (including clinical CR &amp; pathologic CR). Secondary endpoints included 3-year EFS rate, OS, R0 resection rate and safety. Results: As of 30 Aug 2024, 45 pts were enrolled (median age 59 years [range: 24-75], 26 males, 23 clinical T4 stage and 20 clinical N2 stage, 36 with EMVI positive, 31 with MRF positive, 22 tumor located ≤5cm from the anal verge). Up to 20 Sep 2024, all pts completed SCRT, 73.33% (33/45), 57.78% (26/45) and 31.11% (14/45) pts completed two, four and six cycles of combination therapy, respectively. At data cut-off, of 33 pts included in the efficacy analysis, 28 pts underwent MRI examination and mrTRG results were available, the remaining 5 pts had early surgery due to AEs/serious AEs. 35.7% (10/28) and 46.43% (13/28) pts were classified as mrTRG1 and mrTRG2, respectively. Of 19 pts who underwent surgery, R0 rate was achieved in all 19 pts (100%) and pCR was achieved in 12 pts (63.16%). Moreover, 1 pt achieved cCR during neoadjuvant therapy, thus the treatment strategy provided a CR rate of 65% (1 cCR plus 12 pCR divided by 20). Grade 3/4 adverse effects (AEs) occurred in 16 pts (47.06%), and most commonly were lymphocyte count decreased (n=6, 18.18%), diarrhea (n=5, 15.15%) and AST increased (n=2, 6.06%). 4 serious AEs reported with intestinal perforation and all achieved pCR after surgery therapy. No treatment related death was reported. Conclusions: SCRT followed by fruquintinib combined with adebrelimab and CAPOX as a total neoadjuvant therapy showed promising CR rate and favorable pCR for high-risk LARC pts, and the safety profile was generally manageable. This treatment strategy might be a potential option as neoadjuvant therapy for high-risk LARC pts. Updated data will be presented in the future. Clinical trial information: NCT06234007 .
Immunotherapy for MSI-H colorectal cancer with isolated peritoneal metastases.
Authors: Daniel Aryeh Metzger, Olivia Watman, Ying Li, Alessio Pigazzi, Despina Siolas, Mehraneh D. Jafari
Journal: Journal of Clinical Oncology (2025)

187 Background: NCCN guidelines recommend immunotherapy for MSI-H colon cancer (CC) with isolated peritoneal metastases (iPM); however, limited data support its benefit. This study aimed to evaluate the impact of immunotherapy in this population. Methods: Patients diagnosed with MSI-H CC with iPM from 2016-2019 were selected from the NCDB. Patients who received immunotherapy were compared to those who did not. Overall survival was assessed using Kaplan-Meier analysis and multivariate Cox proportional hazard regression. The trend of immunotherapy utilization from 2016-2020 was analyzed using the Cochran-Armitage test. Results: We analyzed a cohort of 444 patients, with 161 (36%) receiving immunotherapy. Patients in the immunotherapy group were, on average, younger (63 vs. 71 years; P&lt;0.001), with balanced gender distribution between groups. Among those who received immunotherapy, 70% were treated as a first-line agent, and 30% after chemotherapy. Immunotherapy was more commonly administered in the adjuvant setting (66%) compared to neoadjuvant (7%) or without surgery (27%). Immunotherapy was associated with significantly longer median survival (33.6 vs. 14.9 months; P&lt;0.001). In multivariate analysis, immunotherapy was associated with improved overall survival, whether given as a first-line agent (HR 0.54, 95% CI 0.39-0.74; P&lt;0.001) or second-line after chemotherapy (HR 0.59, 95% CI 0.37-0.94; P=0.03). Additionally, primary tumor resection (HR 0.44, 95% CI 0.32-0.60; P&lt;0.001), but not metastatectomy (HR 0.96, 95% CI 0.71-1.29; P=0.8), was associated with prolonged survival. Patients who received both immunotherapy and primary tumor resection (n=118) had a median survival of 43.8 months. From 2016 to 2020, the utilization of immunotherapy in this cohort increased from 29% to 37% (χ^2=0.23, P=0.63). Conclusions: Utilization of immunotherapy remains low in MSI-H CRC with iPM and did not change significantly during the study period. Immunotherapy is associated with improved overall survival and should be considered for appropriate candidates. The combination of primary tumor resection and immunotherapy yielded the best overall survival.
Efficacy and safety of glecirasib (JAB-21822) monotherapy and in combination with cetuximab in patients with KRAS G12C-mutated advanced colorectal cancer.
Authors: Jian Li, Jing Huang, Yi Ba, Baoshan Cao, Suxia Luo, Wenhua Li, Zhengbo Song, Liangjun Zhu, Jianping Xiong, Guangyu An, Yanqiao Zhang, Zhihua Li, Yongsheng Li, Yanhong Gu, XingYa Li, Chenghui Huang, Qihan Fu, Changlu Hu, Lin Shen
Journal: Journal of Clinical Oncology (2025)

191 Background: Glecirasib (JAB-21822), a highly selective, covalent and oral KRAS G12C inhibitor, has demonstrated a favorable safety profile and promising efficacy result as a monotherapy in NSCLC. We previously reported preliminary data of glecirasib monotherapy (NCT05009329) and in combination with cetuximab (NCT05194995) in KRAS G12C-mutated advanced Colorectal Cancer (CRC); here, we present the updated efficacy results. Methods: Patients (pts) with advanced CRC harboring KRAS G12C mutation were enrolled and treated with either single agent glecirasib (800mg QD) or glecirasib (800mg QD) combined with cetuximab. The primary endpoint was overall response rate (ORR). The secondary endpoints included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Results: As of June 30, 2024, 44 pts received glecirasib (median follow up was 21.9 months). The median age was 55.5 years with female (38.6%) /male (61.4%), ECOG PS 0 (25.0%) /1 (75.0.%), and 79.5% having received ≥ 2 prior lines of therapy. The confirmed ORR and DCR were 22.7% (10/44) and 86.4% (38/44), respectively. Median DoR was 4.4months (95%CI: 4.2, 9.7) , median PFS was 5.6 months (95%CI: 4.1, 7.0), and median OS was 16.0 months (95%CI: 8.8, 26.3). Any grade treatment-related adverse events (TRAEs) occurred in 41 (93.2%) pts, the most common ones (&gt;20%) being anemia, blood bilirubin increased, hypertriglyceridemia and white blood cell count decreased. Grade 3-4 TRAEs occurred in 9 (20.5%) pts. No grade 5 TRAEs occurred. No patient discontinued treatment due to TRAEs. Among the47 pts treated with combination regimen (median follow up was 18.7 months), the median age was 54.8 years with female (53.2%)/ male (46.8%), ECOG PS 0 (44.7%) /1 (55.3%), and 74.5% having received ≥ 2 prior lines of therapy. The confirmed ORR and DCR were 50% (23/46) and 87.0% (40/46), respectively. Median DoR was 5.1 months (95%CI: 4.1, 6.9), median PFS was 6.9 months (95%CI: 5.4-6.9), and median OS was 19.3 months (95%CI: 13.1, NE). Any grade TRAEs occurred in 46 (97.9%) pts, the most common ones (&gt;20%) being rash, skin fissures, blood bilirubin increased, ALT increased, AST increased, anemia and proteinuria. Grade 3-4 TRAEs occurred in 9 (19.1%) pts. No grade 5 TRAEs occurred. 2(4.3%) pts discontinued treatment due to TRAEs. Conclusions: Glecirasib in combination with cetuximab demonstrated better efficacy compared with glecirasib monotherapy in advanced KRAS G12C mutated advanced CRC, while maintaining a favorable safety profile. Clinical trial information: NCT05009329 , NCT05194995 .
A phase 1 dose-escalation study of GCC19CART: A novel CAR T-cell therapy for metastatic colorectal cancer in the United States.
Authors: Bridget P. Keenan, Christopher Hanyoung Lieu, Marwan Fakih, Alan P. Venook, Dongqi Chen, Eric Keith Rowinsky, Victor Lu, Lei Xiao, Benjamin L. Schlechter
Journal: Journal of Clinical Oncology (2025)

175 Background: GCC19CART, the first clinical candidate from the CoupledCAR solid tumor platform, pairs solid tumor CAR T-cells with CD19-targeting CAR T-cells to enhance proliferation, activation, and persistence against solid tumors. GCC19CART targets guanylate cyclase-C (GCC), a known mucosal marker. Building on the promising results from a clinical trial in China, a phase 1 study was initiated in the US for patients with metastatic colorectal cancer (mCRC) refractory to standard chemotherapy. As of August 14, 2024, a total of 9 subjects have been treated. Methods: Subjects were initially screened for GCC expression, however screening was discontinued after &gt;95% of subjects with mCRC demonstrated GCC expression by immunohistochemistry (95/98). Eligible subjects underwent leukapheresis, lymphodepleting chemotherapy (fludarabine 30mg/m 2 and cyclophosphamide 300mg/m 2 on day-3), and then infusion of a single dose GCC19CART. Objective response was assessed by RECIST v1.1. Results: Four subjects have been enrolled at dose level 1 (1x10 6 cells/kg) and 5 subjects at dose level 2 (2x10 6 cells/kg). The most common adverse events were cytokine release syndrome (CRS) in 9/9 subjects (Grade 1: 6/9 [66.7%] and Grade 2: 3/9 [33.3%]) and diarrhea in 8/9 subjects (Grade 1: 3/9 [33.3%], Grade 2: 3/9 [33.3%], Grade 3: 2/9 [22.2%]). Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 2/9 subjects (Grade 2: 1/9 [11.1%] or Grade 3: 1/9 [11.1%]) and resolved rapidly with corticosteroid and dasatinib treatment. Three out of 9 subjects had a mild tremor (Grade 1) that resolved with corticosteroids. One subject experienced a dose-limiting toxicity (DLT) at dose level 2, presenting with Grade 3 diarrhea, Grade 4 enterocolitis and Grade 5 sepsis, and died from fungal sepsis 48 days post-infusion. At dose level 1, the overall response rate (ORR) was 50.0% (2/4). Two subjects demonstrated a partial response (PR) with one confirmed PR, while 1 additional subject had partial metabolic response on PET/CT with stable disease (SD) and 1 patient had progressive disease. At dose level 2, the ORR was 80% (4/5), including 1 subject with a pathological complete response, and 3 with a confirmed partial response, of which 1 had a complete metabolic response on PETCT. Conclusions: Preliminary results indicate that GCC19CART exhibits significant clinical activity in patients with refractory mCRC. Adverse events were related to GCC19CART mechanism and in line with what has been observed with other CAR T-cell products. Strategies to further optimize the management of treatment-related diarrhea are currently being implemented. The trial is ongoing and updated data will be presented. Clinical trial information: NCT05319314 .
Neoadjuvant PD-1 blockade in mismatch repair-deficient or microsatellite instability-high, locally advanced and resectable colorectal cancer: A retrospective real-world analysis.
Authors: Yugui Lian, Chang Su, Ruihua Zhao, Yanbang Lian, Quanbo Zhou, Shui-Ling Jin, Shihao Guo, Zhenqiang Sun, Zhiyong Zhang, Guixian Wang, Yang Fu, Yunlong Wang, Weitang Yuan, Xiang-Bo Wan
Journal: Journal of Clinical Oncology (2025)

185 Background: Neoadjuvant PD-1 blockade therapy has shown encouraging efficacy in patients with mismatch repair- deficient (dMMR)/microsatellite instability-high (MSI-H) locally advanced colorectal cancer. However, data from the real-world setting are scarce. Methods: We retrospectively collected clinical data of patients with dMMR/MSI-H locally advanced colorectal cancer diagnosed between 2022-2024 that received neoadjuvant anti-PD-1 monotherapy at the First Affiliated Hospital of Zhengzhou University. Pathological complete response, clinical complete response, R0 resection rate, and safety were analyzed. All statistical analyses were conducted using SPSS Statistics, version 22.0. Results: A total of 45 patients were enrolled. As of the data cutoff (Sep 15, 2024), the median follow-up was 14.0 months (range: 4.0-31.4). The median age was 53 years (range: 29.0–78.0) and 25 (55.6%) of 45 patients were male. 32 (71.1%) patients had clinical stage III disease and 39 (86.7%) patients had colon cancer. A higher proportion of patients (53.3%) had clinical T4 stage. 37 patients underwent the surgery of whom 29(78.9%) had a pathological complete response. The R0 resection was 100%. The median treatment duration was 4 cycles (range: 2-10). Among the 18 patients who received equal to or less than 4 cycles, the pCR rate was 77.8%, while for the remaining 17 patients who had more than 4 cycles of treatment, the pCR rate was 84.2%. Eight other patients had a clinical complete response and chose the watch and wait strategy. Treatment-related adverse events ≥3-4grade were observed in 3 patients. All patients survived without any disease recurrence. Conclusions: In this retrospective analysis, anti-PD-1 monotherapy is effective and tolerable for patients with dMMR/MSI-H locally advanced colorectal cancer. This study shows that pCR rate increases is associated with a longer treatment cycles probably. Further analysis of larger real-world datasets with longer follow-up will be essential to validate these results.
Liposomal irinotecan + 5-fluorouracil + leucovorin + bevacizumab as second-line therapy in metastatic colorectal cancer (IRIS): A multi-center, single-arm, prospective, phase II study.
Authors: Xuhua Hu, Bo Jiang, Lu Hongxia, Bin Yu, Bo Yi, Yudong Wang, Lingjun Zhu, Shengmian Li, Baokun Li, Dalu Kong, Zhiwu Wang, Wenbo Niu, Hongqing Ma, Shanchuan Wang, Yanglin Chen, Chao Lin, Rong Yang, Weiyou Zhu, Jia Liu, Guiying Wang
Journal: Journal of Clinical Oncology (2025)

195 Background: In patients with advanced colorectal cancer (CRC), the recommended second-line treatment following first-line therapy with oxaliplatin-based regimens is irinotecan-based therapy. Liposomal irinotecan, a novel formulation of traditional irinotecan, has demonstrated potential to enhance efficacy while minimizing toxicity. This study aims to investigate the efficacy and safety of liposomal irinotecan in combination with 5-FU/LV and bevacizumab as a second-line treatment option for metastatic CRC. Methods: This is a multi-center, single-arm, prospective, phase II study. Patients with metastatic CRC who received oxaliplatin-based chemotherapy as first-line treatment were enrolled to receive liposomal irinotecan + 5-fluorouracil + leucovorin + bevacizumab regimen until disease progression and/or unacceptable toxicity. The primary endpoint is objective response rate (ORR), secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 50 patients were enrolled from Jan 2024 to Jul 2024 across 6 sites in China. The median age was 56.5 years (range: 30.0-76.0), with 58.0% male and 36.0% ECOG 0. Among the patients, 38.0% had left-sided colon cancer, 24.0% had right-sided colon cancer, and 38.0% had rectal cancer. As of Sept 14, 2024, 39 patients had at least one tumor assessment and 19 patients were still on treatment. ORR and DCR were 20.5% (8/39, 95% CI: 9.3%-36.5%) and 84.6% (33/39, 95% CI: 69.5%-94.1%), respectively. Eleven patients had disease progression and 5 patients died, and the median PFS and OS were not reached. The relative dose intensity of liposomal irinotecan and 5-fluorouracil were 92.8% (range: 23.6%-109.6%) and 89.5% (range: 13.3%-116.8%), respectively. During treatment, 43 (86.0%) patients had at least one adverse event (AE) and 24 (48.0%) had grade 3-4 AE. Most common (≥ 10%) grade 3-4 AEs were neutropenia (20.0%), leukocytopenia (16.0%) and diarrhea (10.0%). No unexpected toxicities observed in this study. Conclusions: These preliminary results reveled that liposomal irinotecan + 5-fluorouracil + leucovorin + bevacizumab after oxaliplatin-based treatment for metastatic CRC was well tolerated with encouraging clinical activity, which warrants further follow up. Clinical trial information: NCT06184698 .
Use of Streptokinase for intravenous thrombolysis in pulmonary embolism: Practice and results (Data from the pulmonary embolism registry of Bogodogo University Hospital Center in Burkina Faso (PER/UHC Bogodogo-BF)
Authors: Taryetba Andre Arthur Seghda
Journal: Clinical Cardiology and Cardiovascular Interventions (2024)

Objective : The objective of this part of the registry was to evaluate the practices and results in terms of Streptokinase thrombolysis in pulmonary embolism. Methods : patients included in the pulmonary embolism registry were subdivided into those who had received streptokinase and those who had not. Chi-square and Fisher Exact tests were used in univariate analysis to determine the categorical variables associated with thrombolysis. To assess the clinical efficacy of streptokinase, vital constants at admission (t0) and 1h post-thrombolysis (t1) of thrombolyzed patients were matched and compared using the wilcoxon signed-rank test. Mean echocardiographic parameters were compared at t0 (admission) and t1 (24 hours). A p&lt;0.05 value defined the significance threshold for judging a difference not related to chance. Results: The proportion of thrombolysed patients was 13.7%. Streptokinase was used in patients at high risk of early death. Vital clinical parameters (blood pressure, oxygen saturation, respiratory rate) were significantly improved at the end of perfusion. Right ventricular dysfunction parameters were significantly improved after Streptokinase treatment. The proportion of minor bleeding was significantly higher in the Streptokinase group (11.6% vs 6% OR=2.9). Conclusion : Streptokinase is used to treat pulmonary embolism in patients who satisfy certain severity criteria. The result is a significant improvement in clinical and echocardiographic parameters, at the cost of an increased risk of minor bleeding.