tbuckley/cabot-search huggingface dataset:
Impact of Race/Ethnicity on Clinical and Genomic Characteristics, Trial Participation, and Genotype-Matched Therapy among Patients with Metastatic Breast Cancer
Authors: Rupali Sood, Andrzej Niemierko, Lianne Ryan, Laura Spring, Beverly Moy, Aditya Bardia, Neelima Vidula
Journal: Clinical Cancer Research (2025)

Abstract Background: Race/ethnicity may affect outcomes in metastatic breast cancer (MBC) due to biological and social determinants. We evaluated the impact of race/ethnicity on clinical, socioeconomic, and genomic characteristics, clinical trial participation, and receipt of genotype-matched therapy among patients with MBC. Methods: A retrospective study of patients with MBC who underwent cell-free DNA testing (cfDNA, Guardant360â, 74 gene panel) between 11/2016 and 11/2020 was conducted. Receipt of genotype-matched therapy targeted at a cfDNA actionable mutation was determined. Pearson's chi-squared and Wilcoxon rank-sum tests were used to compare categorical and continuous variables between groups. Multivariable logistic regression was used to assess the association of race and receiving matched therapy. Results: 425 patients with MBC and cfDNA results were identified (White: 369, Black: 27, Hispanic 15, and Asian 14). White patients traveled further for cancer care than other groups (p&amp;lt;0.001). White patients had the highest rates of commercial insurance, Black patients had the highest rates of state-supported insurance, and Asian patients had the highest uninsured rates (p&amp;lt;0.001). Clinical trial enrollment did not differ by race/ethnicity (p=0.34). The proportion of patients with ≥1 actionable mutation in cfDNA did not vary by race/ethnicity (p=0.18). The highest rates of matched therapy were observed in White patients (p&amp;lt;0.001). After multivariable logistic regression adjusting for subtype, commercial vs. other insurance, Charlson comorbidity index, and distance to center, White patients remained more likely to receive matched therapy (p=0.024). Conclusions: Racial/ethnic minority patients were less likely to receive matched therapy. Further research is needed to identify barriers to precision medicine.
Emerging prodrug and nano-drug delivery strategies for the detection and elimination of senescent tumor cells
Authors: Tao Wang, Xianbao Shi, Xiaolan Xu, Jiaming Zhang, Zhengdi Ma, Chen Meng, Dian Jiao, Yubo Wang, Yanfei Chen, Zhonggui He, Ying Zhu, He-Nan Liu, Tianhong Zhang, Qikun Jiang
Journal: Biomaterials (2025)
An ultrasound-driven PLGA/Zn-KNN hybrid piezoelectric scaffold with direct and immunoregulatory antibacterial activity for bone infection
Authors: Yuhao Zheng, Shu Wang, Wenhe Jin, Zhuoxuan Li, Guoju Yang, Xiaoxu Li, Ning Li, Yue Wang, Fan Sheng, Zhiming Song
Journal: Bioactive Materials (2025)
Role of major cardiovascular surgery-induced metabolic reprogramming in acute kidney injury in critical care
Authors: Tiago R Velho, Francisco Pinto, Ricardo Ferreira, Rafael Maniés Pereira, António Duarte, Makoto Harada, Katharina Willmann, Dora Pedroso, Tiago Paixão, Nuno Carvalho Guerra, Ana Neves-Costa, Isa Santos, Ryan Gouveia E Melo, Dulce Brito, Ana G Almeida, Ângelo Nobre, Rui Wang-Sattler, Thomas Köcher, Luís Mendes Pedro, Fausto Pinto, Luís Ferreira Moita
Journal: Intensive Care Medicine (2025)
MELK prevents radiofrequency ablation-induced immunogenic cell death and antitumor immune response by stabilizing FABP5 in hepatocellular malignancies
Authors: Bu-Fu Tang, Wang-Ting Xu, Shi-Ji Fang, Jin-Yu Zhu, Rong-Fang Qiu, Lin Shen, Yang Yang, Qiao-You Weng, Ya-Jie Wang, Jia-Yi Ding, Xiao-Jie Zhang, Wei-Qian Chen, Li-Yun Zheng, Jing-Jing Song, Biao Chen, Zhong-Wei Zhao, Min-Jiang Chen, Jian-Song Ji
Journal: Military Medical Research (2025)

Abstract Background Radiofrequency ablation (RFA) is an efficient treatment with unlimited potential for liver cancer that can effectively reduce patient mortality. Understanding the biological process related with RFA treatment is important for improving treatment strategy. This study aimed to identify the critical targets for regulating the efficacy of RFA. Methods The RFA treatment in hepatocellular carcinoma (HCC) tumor models in vivo, was analyzed by RNA sequencing technology. The heat treatment in vitro for HCC tumor cells was also constructed to explore the mechanism after RFA treatment in tumor cells. Nanoparticles with high affinity to tumor cells were applied as a new therapy to interfere with the expression of maternal embryonic leucine zipper kinase (MELK). Results It was found that RFA treatment upregulated MELK expression, and MELK inhibition promoted RFA efficacy by immunogenic cell death and the antitumor response, including anti-tumoral macrophage polarization and increased CD8 + T cell cytotoxicity in HCC. Mechanically, MELK binds to fatty acid-binding protein 5 (FABP5), and affects its ubiquitination through the K48R pathway to increase its stability, thereby activating protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling axis to weaken the RFA-mediated antitumor effect. In addition, the synthesis of arginylglycylaspartic acid (RGD)-lipid nanoparticles (LNPs) targeting tumor cell-intrinsic MELK enhanced RFA efficacy in HCC. Conclusion MELK is a therapeutic target by regulating RFA efficacy in HCC, and targeting MELK via RGD-LNPs provides new insight into improving RFA efficacy in HCC clinical treatment and combating the malignant progression of liver cancer.
The potential of lazertinib and amivantamab combination therapy as a treatment strategy for uncommon EGFR-mutated NSCLC
Authors: Seung Yeon Oh, Sewon Park, Seoyoung Lee, Eun Ji Lee, Tae Ho Kim, Su-Jin Choi, So Young Park, Jae Hwan Kim, Sun Min Lim, Jii Bum Lee, Byoung Chul Cho, Min Hee Hong, Mi Ran Yun
Journal: Cell Reports Medicine (2025)
Neoadjuvant SHR-1701 (a bifunctional anti-PD-L1/TGF-βRII agent) combined with chemoradiotherapy for resectable locally advanced esophageal squamous cell carcinoma (ESCC): A phase II trial.
Authors: Chengixn Liu, Wei Huang, Chengrui Fu, Hongfu Sun, Qian Zhao, Changhong Zhao, Xiaoyu Chen, Baosheng Li
Journal: Journal of Clinical Oncology (2025)

410 Background: Neoadjuvant chemotherapy or chemoradiotherapy followed by surgery is the standard of care for resectable locally advanced ESCC. SHR-1701, a new bifunctional fusion protein composed of a monoclonal antibody against PD-L1 fused with the extracellular domain of TGF-β receptor II, may enhance antitumor activity in combination with neoadjuvant standard therapies in ESCC patients (pts). The aim of this phase II trial is to determine the safety and efficacy of neoadjuvant chemoradiotherapy plus SHR-1701 followed by esophagectomy in pts with locally advanced resectable ESCC. Methods: Pts with resectable thoracic ESCC, diagnosed as clinical stage of cT1b-cT2N+M0 or cT3-cT4aNxM0 per AJCC 8th were eligible. Preoperative therapy included SHR-1701 (30 mg/kg every 3 weeks for 2 cycles), albumin paclitaxel (50 mg/m 2 , once a week for 5 weeks), carboplatin (AUC=2, once a week for 5 weeks) and radiotherapy (41.4Gy in 23 fractions). Following esophagectomy, pts received SHR-1701 up to 1 year. The primary endpoint was pathological complete response (pCR) rate in the per-protocol population. Secondary endpoints included R0 resection rate, major pathological response (MPR) rate, disease free survival (DFS) and safety. Results: Between Dec. 2021 and Feb. 2023, 43 pts were screened and 41 met the inclusion criteria, among whom the clinical stage I, II, III, and IVa at baseline were 1 (2.4%), 8 (19.5%), 31 (75.6%), and 1 (2.4%), respectively. All 41 pts received neoadjuvant SHR-1701 combined with chemoradiotherapy. As of Mar. 2024, 30 pts underwent surgery, and all achieved R0 resection. There was no in-hospital and postoperative 30-day mortality. 9 (30.0%) pts achieved pCR in both primary tumor and lymph nodes (ypT0N0), and 12 (40.0%) pts had complete pathological response of the primary tumor with residual disease in lymph nodes alone (ypT0N+). Treatment-related adverse events (TRAEs) occurred in all pts, and most of TRAEs were grade 1-2. Notable toxicity included pneumonitis (31.7%) and anastomotic leak (12.2%). Conclusions: The addition of SHR-1701 to neoadjuvant chemoradiotherapy in ESCC demonstrated promising efficacy with acceptable toxicity, and might be a promising approach for neoadjuvant treatment. Clinical trial information: ChiCTR2000041562.
Updated results of ALTER-H006: A phase II study of benmelstobart (PD-L1 inhibitor) plus anlotinib as adjuvant therapy in hepatocellular carcinoma (HCC) with high risk of recurrence after radical resection.
Authors: Xianhai Ma0, Xiaohui Duan, Dongde Wu, Cuncai Zhou, Yifeng Tian, Jian Shen, Guohui Xu, Yannan Bai
Journal: Journal of Clinical Oncology (2025)

601 Background: Although radical resection offers one of the most favorable prognosis for hepatocellular carcinoma (HCC), the rate of postoperative recurrence remains high, which is the primary cause of mortality in HCC patients. The optimal adjuvant treatment strategy for patients is still under active investigation. Herein we evaluated the efficacy and safety of the anti-angiogenic tyrosine kinase inhibitor, anlotinib, plus benmelstobart, a novel programmed death-ligand 1 (PD-L1) inhibitor as an adjuvant treatment for HCC with high risk of recurrence after radical resection. Methods: This study enrolled patients diagnosed with HCC confirmed through histological or cytological examination, whose age was 18-75, with ECOG 0-1, Child-Pugh class A, 4~8 weeks after R0 resection with any of the following high-risk factors for recurrence: a) tumor nodules ≥4; b) portal vein tumor thrombus (PVTT): vp1 or vp2; c) hepatic vein tumor thrombus (HVTT): vv1 or vv2. Enrolled patients received anlotinib (12 mg, p.o., qd, d1-14, q3w) plus benmelstobart (1200 mg, i.v., d1, q3w) until disease recurrence or unacceptable toxicity or up to 18 cycles (~1 year), whichever occurred first. Tumor assessment was performed at the end of the second cycle and every four cycles thereafter, according to RECIST v1.1. The predefined sample size was 37. The primary endpoint was 1-year recurrence-free survival (RFS) rate. Secondary endpoints included RFS, 1-year overall survival (OS) rate, and safety. Results: As the cutoff date of September 13,2024, a total of 38 patients (pts) were enrolled and 35 pts included in per-protocol set analysis. The majority of the 38 pts were male (94.7%, n = 36), and the median age was 56.5 years (range: 33-75). 18 pts (47.3%) had CNLC Stage IIb and 20 (52.6%) had CNLC Stage IIIa HCC. Among them, 35 pts received at least once tumor assessment. According to RECIST 1.1, of the 35 pts, 18 had no recurrence, 15 experienced relapse, 1 dropped out and 1 discontinued due to serious adverse events. The 1-year RFS rate was 59.97% (95%CI: 39.12-79.68) and the primary median RFS was 16.89m(95%CI: 6.82-26.96). The 1-year OS rate was 91.47% (95%CI: 69.23-97.86). 34 of 38 pts (89.5%) experienced treatment-related adverse events (TRAEs). The most common grade 3 TRAEs occurred in 17 pts (44.7%) including hypertension (32%) and neutropenia(5.3%). No grade 4 or 5 TRAEs were observed. Conclusions: The present study indicated that anlotinib plus benmelstobart as adjuvant treatment for HCC with high risk of recurrence after radical resection exhibited promising efficacy and tolerable safety profile. The conclusion should be validated in more participants included subsequently. Clinical trial information: NCT05111366 .
SOX/FOLFOX+nivolumab followed by conversion surgery for HER2 negative primary gastric or gastroesophageal junction cancer with oligo-metastasis or borderline resectable tumors: Early results of a consecutive 41 cases.
Authors: Masashi Nishino, Takaki Yoshikawa, Hirokazu Shoji, Yurina Fujisaki, Rei Ogawa, Takeyuki Wada, Tsutomu Hayashi, Yukinori Yamagata, Yasuyuki Seto
Journal: Journal of Clinical Oncology (2025)

487 Background: Gastric or gastroesophageal junction cancer with oligo-metastasis or borderline resectable tumors could be cured by conversion surgery after primary chemotherapy. Because SOX/FOLFOX plus Nivolumab showed high clinical response regardless of CPS score, this nivolumab-based chemotherapy followed by surgery may be promising strategy for these tumors. Methods: The study examined the patients who had HER2 negative primary gastric or gastroesophageal junction cancer with synchronous oligo-metastasis or borderline resectable tumors. Oligo-metastasis was defined as peritoneal dissemination localized to the upper abdomen, para-aortic lymph node metastasis, liver metastasis limited up to 3 segments, mediastinal lymph node metastasis, ovarian metastasis, or esophageal intramural metastasis. Borderline resectable tumors were defined as regional lymph node metastasis forming bulky mass or primary tumors invading adjacent organs. The patients with these tumors were treated with primary chemotherapy with SOX/FOLFOX plus Nivolumab for 3 to 22 months, then were proceeded to conversion surgery in case the tumors are responded to chemotherapy and are considered to achieve R0 resection based on the MDT conference. Results: During November 2021 and February 2024, 41 consecutive patients were included in the study. Disease status was peritoneal dissemination in 1, para-aortic lymph node metastasis in 26, liver metastasis in 5, mediastinal lymph node metastasis in 1, ovarian metastasis in 1, esophageal intramural metastasis in 2, bulky nodal metastasis in 6, and primary tumors invading pancreas in 1 (distant oligo-metastasis in 34 patients and borderline resectable in 7). CPS score was &gt;5 in 13, 5&gt; and &gt;1 in 23, and &gt;1 in 5 patients. Chemotherapy regimen was SOX+Nivo in 38 and FOLFOX+Nivo in 3. Of 41 patients, 33 (80.5%) (SOX+Nivo: 30, FOLFOX+Nivo: 3) were proceeded to the conversion surgery, and 32 patients achieved R0 resection. 6 patients showed disease progression and 2 patients were judged as unresectable. Major pathological response (disappearance more than 80% of the primary tumor) rate was 54.5% (18/33) and pCR rate was 33.3% (11/33). Conclusions: SOX/FOLFOX plus Nivolumab for HER2 negative gastric or gastroesophageal junction cancer with oligo-metastasis or borderline resectable tumors achieved a high R0-conversion surgery rate and pathological response rate.
Evaluating the clinical benefits of anti-cancer drugs approved by Food and Drug Administration for gastrointestinal neoplasms for the past two decades.
Authors: Fares Jamal, Oudai Sahvan, Tanios S. Bekaii-Saab, Mohamad Bassam Sonbol
Journal: Journal of Clinical Oncology (2025)

820 Background: The number of FDA-approved anticancer drugs have increased in recent years with a more use of surrogate endpoints. However, it is unclear whether the same trend applies to GI cancers. Therefore, we aimed to evaluate the trend in FDA-approved GI cancer drugs over the past two decades and the associated clinical benefit. Methods: The FDA’s online database was searched for drugs approved for GI cancers from 2006 until 2024. Primary and secondary endpoints along with trial characteristics were extracted. ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) was assessed by two blinded investigators with a third resolving disagreements. We divided the study into period A (01/2006-12/2014) and period B (01/2015-08/2024). Results: Since 2006, FDA approved 62 regimens for GI cancer based on 70 trials, mostly (n= 45;72.6%) in period B. Most trials (n=44) were phase III with only 26 phase II: 22 single arm, and 4 randomized. All the 22 single-arm phase II trials were approved in period B with two randomized phase II trials approved in each period. Approvals based on phase III trials dropped by 33.5% (from n=15 to n=29) between the two periods. Half (n=34) of the approvals were based on overall survival (OS) benefit, while the use of objective response rate (ORR) as an endpoint has increased from 11.8% (n=2) in period A to 45.3% (n=24) in period B. Quality of life (QoL) was assessed only in 27% of the studies and found benefit only in 22.7%. The mean gain in OS was similar across both periods; 2.3 months [1.2-4.7]. Out of the 19 accelerated approvals, 17 were in period B, of which 23% (4/17) were based on secondary endpoint, 18% (3/17) were withdrawn, and 59% (10/17) received full approval. Substantial clinical benefit (ESMO score 4-5) was seen in 11.8% of the trials in period A and 19.6% in period B, with 17.4% overall from 2006-2024. Conclusions: Despite rising FDA approvals for GI cancer drugs since 2006, only 17.4% demonstrated substantial clinical benefit based on ESMO-MCBS. Recent approvals rely more on single-arm phase II studies and ORR, often without OS or QoL benefit. These trends underscore the need for more rigorous clinical trials that prioritize meaningful endpoint to ensure that new therapies provide real clinical value to the patient.
Phase 1/2 study of the trophoblast cell surface antigen 2 (TROP2) antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT) as monotherapy or combination therapy in gastrointestinal cancers: LIGHTBEAM-02A.
Authors: Michael J. Pishvaian, Takayuki Yoshino, Colin D. Weekes, Makoto Ueno, Richard S. Finn, Naimin Jing, Ken Hatogai, David E. Adelberg, Do-Youn Oh
Journal: Journal of Clinical Oncology (2025)

TPS846 Background: There is a significant need for new tolerable and effective therapeutic options for colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and biliary tract cancer (BTC) that can provide survival benefit. TROP2 is expressed broadly in several cancers, including CRC, PDAC, and BTC. Sac-TMT (formerly MK-2870/SKB264) is an ADC consisting of a humanized antihuman TROP2 monoclonal antibody, a linker, and a cytotoxic belotecan–derivative topoisomerase I inhibitor. The nonrandomized, open-label, phase 1/2 LIGHTBEAM-02A study (NCT06428409) is being conducted to examine the safety and efficacy of sac-TMT in gastrointestinal cancers. Methods: Approximately 130 patients will be assigned to 1 of 3 cohorts based on their disease. Patients in cohort 1 (CRC; n ≤ 50) must have previously treated locally advanced or metastatic colorectal adenocarcinoma; patients in cohort 2 (PDAC; n ≅ 40) must have previously treated locally advanced or metastatic PDAC; patients in cohort 3 (BTC; n ≅ 40) must have previously treated locally advanced or metastatic BTC. Cohort 1 is included in a dose-escalation phase to determine the recommended phase 2 dose of sac-TMT when used in combination with fluorouracil and leucovorin and an efficacy phase. In the dose-escalation phase, patients will receive sac-TMT 3 mg/kg or 4 mg/kg intravenously (IV) every 2 weeks (Q2W) on days 1 and 15 of each 4-week cycle plus 2400 mg/m 2 fluorouracil IV infused over 46-48 hours Q2W and 400 mg/m 2 leucovorin IV Q2W; in the efficacy phase, patients will receive the recommended phase 2 dose of sac-TMT with the same chemotherapy regimen as the dose-escalation phase. Patients in cohorts 2 and 3 will receive sac-TMT 4 mg/kg IV monotherapy Q2W on days 1 and 15 of each 4-week cycle. The primary objectives are to evaluate safety and tolerability and objective response rate per RECIST v1.1 by blinded independent central review (BICR). Secondary objectives are to evaluate duration of response and progression-free survival per RECIST v1.1 by BICR and overall survival. Enrollment is ongoing. Clinical trial information: NCT06428409 .
Uses of VEGF inhibitor bevacizumab in appendiceal adenocarcinoma.
Authors: Jacquelyn McCullough, Mahmoud M.G. Yousef, Abdelrahman M.G. Yousef, John Paul Y.C. Shen
Journal: Journal of Clinical Oncology (2025)

831 Background: Systemic treatment of metastatic appendiceal adenocarcinoma (AA) has been challenging due to a lack of well-established AA chemotherapy regimens and historical reliance on colorectal cancer (CRC) protocols. In the United States, but less commonly in Europe, bevacizumab is frequently incorporated in treatment of AA given its approved use for CRC. However, previously there have been no studies evaluating if there is a survival benefit attributable to bevacizumab in patients with AA. Methods: The Palantir Foundry system was used to extract data from the MD Anderson Cancer Center (MDA) electronic medical record for patients with biopsy-proven AA who received chemotherapy at MDA from 2015 to 2024. Only patients with complete staging and histopathology data were included in the analysis. Results: We identified 203 patients with AA who received chemotherapy at MDA and had complete tumor data. Of these, 43% (n=87) received bevacizumab at some point in their treatment. Patients who received bevacizumab were demographically similar to patients who received non-bevacizumab chemotherapy in terms of age at diagnosis, race, and sex; mucinous histology was more frequent in the bevacizumab cohort (52%, n=45 vs. 39%, n=45 in non-bevacizumab cohort). The 87 patients who received bevacizumab were treated with 1-6 lines of therapy per patient (mean = 1.57). The most frequently used bevacizumab-containing regimens were FOLFOX + bevacizumab (34%, n=46), FOLRIRI + bevacizumab (29%, n=40), 5-FU + bevacizumab (15%, n=21), and atezolizumab + bevacizumab (11%, n=15), with less common irinotecan + bevacizumab, TAS-102 + bevacizumab, and FOLFOXIRI + bevacizumab. Three regimens containing bevacizumab were discontinued due to complications: one instance of hand-foot syndrome attributed to xeloda, one instance of cardiomyopathy attributed to immunotherapy, and one bowel perforation with abdominal wall abscess attributed to bevacizumab. To determine if bevacizumab was associated with overall survival (OS) benefit we performed Kaplan-Meier analysis, with OS calculated from start of first line chemotherapy to death, in patients with metastatic AA who received either 5-FU doublet therapy alone or 5-FU doublet therapy with bevacizumab. Patients who received bevacizumab trended toward better OS (median 52 vs 25 months for doublet therapy alone, HR: 0.53, p= 0.059). The effect of bevacizumab was particularly notable in patients with signet ring cell histology; where bevacizumab use was associated with significantly longer OS (median OS 50 vs 14 months for doublet therapy alone, HR: 0.24, p= 0.034). Conclusions: Bevacizumab is frequently added to cytotoxic chemotherapy in the treatment of AA. These retrospective data suggest an OS benefit to adding bevacizumab to doublet chemotherapy, particularly in the case of signet ring cell histology.