bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of patients (pts) with disease relapse despite absence of molecular residual disease (MRD) after resection of colorectal oligometastases (CRM): Implications from PRECISION study.
Authors: Kobayashi Shin , Takamoto Takeshi , Shiomi Akio , Takahashi Amane , Shiozawa Manabu , Shimizu Yasuhiro , Kagawa Yoshinori , Nobuoka Daisuke , Yamauchi Junichiro , Kato Takeshi , Oki Eiji , Taketomi Akinobu , Takahahshi Yu , Natsume Soichiro , Niguma Takefumi , Kani Satoru , Nakamura Yoshiaki 
Published: August 2024

3602 Background: Detection of MRD after curative-intent resection of CRM is prognostic for disease relapse and may guide decisions regarding adjuvant chemotherapy (ACT). However, some pts without MRD detected immediately after resection may also experience disease relapse. We explored the features of pts enrolled in a prospective multicenter study with disease relapse who did and did not have post-resection MRD. Methods: Pts with previously untreated resectable CRM scheduled for surgery were prospectively enrolled between March 2021 and October 2022. Pretreatment genomic alterations were assessed in circulating tumor DNA (ctDNA) by Guardant360, while MRD was assessed 4 weeks after resection with a methylation-based ctDNA MRD assay (Guardant Reveal). Characteristics of pts who were MRD negative but relapsed later were analyzed. Results: Of 118 eligible pts enrolled, pretreatment ctDNA was detected in 99 (84%), 62 (53%) of whom had poor genomic profile, defined as a mutation in BRAF, RAS, PIK3CA, and/or SMAD4. Of 110 pts who underwent surgery, postoperative MRD was detected in 35 (32%). With a median follow-up time of 11.0 months (m), 37 pts recurred, of whom 14 were MRD negative and 23 MRD positive. MRD negative pts were more likely to develop lung metastases (64.3% vs. 30.4%, p=0.09) but less likely to have liver metastases (21.4% vs. 60.9%, p=0.03). Median recurrence-free survival (RFS) of MRD-negative relapsed pts was longer than that of MRD positive pts (8.6 m vs. 3.5 m; hazard ratio [HR], 0.28 [95% CI, 0.13-0.58]). Among MRD-negative pts with recurrence, risk factors most associated with recurrence were a history of lymph node metastases (LNM) (odds ratio [OR], 6.20 [95% CI, 1.28-30.1]) and poor pre-operative genomic profile (OR, 3.85 [95% CI, 1.08-13.70]). Among all resected pts, LNM (HR, 2.55 [95% CI, 1.10–5.89]), poor genomic profile (HR, 2.97 [95% CI, 1.29–6.85]), and MRD positivity (HR, 6.36 [95% CI, 2.96–13.64]) were significantly associated with shorter RFS in multivariate analyses. Conclusions: Pts with a history of LNM or poor pre-operative genomic profile were at risk of recurrence despite the absence of MRD after curative-intent resection of CRM. Clinical trial information: UMIN000042490.
Efficacy of EpCAM CAR-T IMC001 in advanced gastric cancers.
Authors: Luo Tianhang , Fang Weijia , Lu Zhengmao , Tong Chuchu , Zhang Hangyu , Ai Guoqiang , Wang Suqiong , Hao Ruidong , Sun Minmin 
Published: August 2024

4043 Background: EpCAM is highly expressed in various cancer types of the GI system and serves as a promising prognostic/predictive marker and therapeutic target. IMC001 is an autologous EpCAM-targeting CAR-T cell exhibited promising anti-tumor activity in preclinical studies. The specificity of the extracellular humanized scFv of IMC001 was confirmed by membrane proteome array. Patient derived organoids study and murine GLP study indicated a favorable safety profile of IMC001. Previous IIT data showed promising safety and efficacy. Here we present updated clinical data with longer follow up and more pts treated in the expansion recommended dose of 1 million (M) CAR-T cells/kg. Methods: This first-in-human, open-label trial followed a 3+3 design with IMC001 monotherapy dose escalation of 0.3 (n=3), 1 (n=3) or 3 (n=3) M/kg after lymphodepletion chemotherapy, 2 additional pts had been enrolled at dose-expansion (1M/kg). Eligible patients were those with EpCAM-positive (expression ≥1+ staining intensity in ≥10% tumor cells) advanced gastric cancers who had failed or not tolerated at least 2 lines of chemotherapy and were ECOG 0 or 1. The objective was to assess the safety, PK/PD profile and preliminary efficacy of IMC001. Results: As of Dec 30, 2023, 11 pts were infused with IMC001, 10 with evaluable efficacy are included in the efficacy analysis. The median time from diagnosis to enroll was 17.0 months (range 6.9-31.2). All pts were in stage IV, with more than 2 lines previous chemotherapy (1 pt failed 1st line and refused a 2nd line treatment), all had metastasis and 72.7% (8/11) had 2 or more metastasis organs. CAR T-cell expansion was observed in most pts; the median Cmax was 547, 500 and 9540 copies/μg gDNA in the 0.3, 1, and 3M/kg dose groups respectively, median Tmax was 7 days (7-28), with a persistence of IMC001 range from 4 to 12 weeks. Significant elevations of serum levels of cytokines were observed in most patients. Three out of 10 evaluable pts achieved PR response and 6 remained SD, with a DCR of 90%. For the recommended dose of 1M/kg, 2 out of 5 pts had PR (ORR 40%), including 1 pt underwent successful radical gastrectomy around W27 after IMC001 infusion and remained survival for more than 81 wks. The other PR pt had a tumor reduction of 48% at W16. The other 2 SD pts had an OS of 55 wks and 43 wks. Patients were well tolerated with no unexpected safety signals were observed at the recommended dose. Conclusions: This phase I study in advanced gastric cancer resulted in durable response with a favorable safety and efficacy profile especially for the recommended dose of 1M/kg, demonstrate a promising of EpCAM CAR-T therapy in advanced GC pts. Further expanding of this dose with larger patient population and longer follow-up shall bring the hope to this unmet medical need. Clinical trial information: ChiCTR2100047129.
Tislelizumab plus intensity modulated radiotherapy in resectable hepatocellular carcinoma with macrovascular invasion: A prospective, single-arm, phase II trial.
Authors: Pan Hongyu , Zhou Liuyu , Cheng Zhuo , Yang Cheng , Zhang Jin , Shen Ningjia , Ma Hongbin , Li Yao , Jin Riming , Zhou Weiping , Wu Dong , Sun Wen , Wang Ruoyu 
Published: August 2024

4118 Background: Hepatocellular carcinoma (HCC) patients (pts) with macrovascular invasion (MVI) have dismal prognosis, and limited evidence for perioperative therapies is available. This study aims to explore the safety and feasibility of perioperative tislelizumab (a PD-1 monoclonal antibody) plus intensity modulated radiotherapy (IMRT) for resectable HCC with MVI. Methods: This single-arm phase II trial enrolled resectable HCC pts with MVI, as assessed by the investigators before surgery. Pts were treatment-naïve, with ECOG of 0-1, and had adequate organ and bone marrow function. Eligible pts received 3 cycles of tislelizumab (200mg, d1, Q3W) and concurrent IMRT (45 Gray in 15 fractions). After surgical feasibility assessment, HCC resection is scheduled after IMRT, followed by adjuvant tislelizumab up to one year. The primary endpoints include overall response rate (ORR) and overall survival (OS). Secondary endpoints are significant pathological response (viable tumor cells <10%), recurrence-free survival (RFS) and safety. Results: From Oct 21, 2020 to Feb 15, 2023, 30 pts were enrolled, with most pts 26 (86.7%) were males and 29 pts (96.7%) had HBV infection. 28 pts (93.3%) had Child-Pugh grade A and 29 pts (96.7%) had ECOG PS 0. The types of vascular invasion were main portal vein (n=9), branched portal vein (n=15), major hepatic vein (n=2), or both portal and hepatic vein (n=4). In 30 pts, ORR was 30.0% (RECIST1.1), DCR was 36.6% and the median OS was 18.7 months. 15 (50%) underwent radical surgical resection followed by adjuvant tislelizumab, 10 (66.7%) achieved a significant pathological response. By Sep 30, 2023, median RFS was not reached with a median follow-up of 21.77 months (95% CI 12.50-31.03) post-surgery. Of the pts who underwent surgery, 7 (46.7%) pts experienced tumor relapse with 1-year RFS rate was 60%. The most common events of any grade were increased thyroid stimulating hormone (TSH) (83.3%), leukopenia (60.0%) and anemia (53.3%). 4 (13.3%) pts experienced grade 3 TRAEs (leukopenia, increased TSH and increased alkaline phosphatase).An exploratory analysis suggests that pts who underwent surgery have longer median OS (not reached versus 7.0 months, p=0.025). AFP reduction after perioperative therapy was found to be prognostic of RFS. Conclusions: The effectiveness and tolerability of tislelizumab plus radiotherapy as perioperative therapy for resectable HCC with MVI is worth further exploration. Clinical trial information: ChiCTR2000036385.
Efficacy and safety of anlotinib combined with sintilizumab in locally advanced or metastatic anaplastic thyroid carcinoma.
Authors: Zhu Haohua , Liu Shaoyan , Shi Yuankai , Gui Lin 
Published: August 2024

6103 Background: Anaplastic thyroid carcinoma (ATC) is rare aggressive and fatal malignancy with poor prognosis. Antiangiogenic and multikinase inhibitors and programmed cell death protein-1 (PD-1) antibodies have conferred benefits for ATC. We aimed to assess the efficacy and safety of anlotinib plus sintilizumab in patients with locally advanced or advanced ATC. Methods: In this prospective study, patients with histologically confirmed locally advanced or metastatic ATC, received a combination therapy of anlotinib and sintilizumab. Anlotinib was started at 12 mg once daily for 14 days and combined with sintilizumab at a fixed dose of 200 mg every three weeks. The primary end point was objective response rate (ORR), assessed in patients who received at least one dose of treatment. Tumor samples were characterized by next-generation sequencing in 12 patients and PD-L1 expression levels in 14 patients. Results: Between June 1st, 2022 and August 21st, 2023, 18 patients with locally advanced or metastatic ATC were enrolled and received combination treatment. Best overall response (BOR) within all patients was 5.6% (1/18) complete remission, 38.9% partial remission (7/18), 33.3% stable disease (6/18), and 22.2% progressive disease (4/18). ORR was 44.4% for all patients and 80.0% for 5 patients with BRAF V600E mutation. The only one patient with PD-L1 negative also reached PR. Median follow up time was 14.6 months for all patients and 16.1 months for patients with BRAF V600E mutation. The median progression-free survival was 7.5 months (0.5 to 56.3 months) for all patients and 5.7 months (1.0 to 13.1 months) for patients with BRAF V600E mutation. Duration of treatment was 5.9 months (0.5 to 38.2 months), and 8 of 18 ATC patients are still on therapy. Grade III/IV toxicities were observed in 4 of 18 patients, necessitating dose reduction/discontinuation of anlotinib. The 1-year overall survival (OS) rate was 61.1% and median OS was 12.9 months (0.6 to 56.3 months), with 8 ATC patients being still alive without progression. Conclusions: The combination of anlotinib and sintilizumab demonstrated promising activity and manageable toxicity in patients with locally advanced or metastatic ATC, suggesting its potential as a viable therapeutic option for this patient population. Clinical trial information: ChiCTR2200067045. [Table: see text]
Dalpiciclib and chidamide in patients with HR+/HER2- advanced breast cancer and resistance to CDK4/6 inhibitors: A phase Ib trial.
Authors: Wang Tao 
Published: August 2024

e13072 Background: The combination of CDK4/6 inhibitors and endocrine therapy (ET) as first or second-line therapy could improve PFS and OS for patients with HR-positive/HER2-negative breast cancer. However, the standard treatment for patients who have failed CDK4/6 inhibitors has not been established. Histone deacetylase inhibitors (HDACi) inhibit the proliferation of tumor cells through a variety of ways, such as improving the expression level of p21 and other genes. In China, dalpiciclib (a CDK4/6 inhibitor) in combination with ET has been approved for patients with metastatic HR-positive/HER2-negative breast cancer. Chidamide (an HDAC inhibitor) has been approved for the treatment of metastatic HR-positive/HER2-negative breast cancer. The investigator's previous retrospective study has shown that chidamide combined with ET may be an optional sequential strategy for patients who have progressed on CDK4/6 Inhibitor. The aim of this study was to explore the efficacy and safety of dalpiciclib in combination with chidamide in locally advanced or metastatic HR+/HER2- breast cancer patients who have failed CDK4/6 inhibitors (NCT 05586841). Methods: This study is a single-arm, open-label, prospective, phase Ib, dose escalation clinical trial. Before entering this trial, all patients with HR-positive/HER2-negative locally recurrent or metastatic breast cancer (MBC) must have received ≤1 previous line of chemotherapy for MBC, and have failed CDK4/6 inhibitor therapy. The primary endpoint is maximum tolerated dose (MTD) of dalpiciclib in combination with chidamide. Patients were assigned to four groups to receive dalpiciclib and chidamide (Group A: dalpiciclib 125mg/d and chidamide 25mg/BIW; Group B: dalpiciclib 125mg/d and chidamide 20mg/BIW; Group C: dalpiciclib 100 mg/d and chidamide 25mg/BIW; Group D: dalpiciclib 100 mg/d and chidamide 20mg/BIW). Results: Fourteen patients were enrolled between 19/1/2023 and 30/1/2024 (Group A, N=4; Group B, N=3; Group C, N=4; Group D, N=3). All the patients were received ≥ 1 line CDK4/6 inhibitors and 11 patients (78.6%) received chemotherapy in advanced breast cancer. Two patients experienced dose-limiting toxicities (DLT, Group A, n=1; Group B, n=1). The incidence of adverse events of any grade was 100%. The most frequent grade 3-4 adverse events were neutropenia (100%) and thrombocytopenia (35.7%). The median follow-up was 251 days (range, 188.486-313.514), and median PFS was 201 days (95%CI: 158.49-243.51). 2 of 14 patients achieved partial response (PR; Group C, n=2), 10 of 14 patients achieved stable disease (SD) and 2 of 14 had progressive disease (PD; Group A, n=2). In this study, dose group C was identified as recommended phase II dose (RP2D). Conclusions: The combination of dalpiciclib and tucidinostat is an alternative treatment strategy in patients who have failed CDK4/6 inhibitors. Clinical trial information: NCT05586841 .
Neoadjuvant sintilimab, albumin-bound paclitaxel, and carboplatin for locally advanced resectable esophageal squamous cell carcinoma: A prospective phase 2 study.
Authors: Jiang Haiping , Ye Peng , Li Ning , Wu Hui , Ding Yongfeng , Xu Xin , Ma Ying , Teng Xiao-Dong , Ji Songxiao , Li Jingjie 
Published: August 2024

e16097 Background: Whether combined immunotherapy on the basis of neoadjuvant chemotherapy is beneficial for locally advanced esophageal squamous cell carcinoma (ESCC) remain to be inconclusive. This phase 2 study (ChineseClinical Trial Registry: ChiCTR2000041081) evaluate the efficacy and safety of neoadjuvant sintilimab, albumin-bound paclitaxel, and carboplatin in locally advanced ESCC. Methods: Patients with locally advanced ESCC (T2N+M0, T3N0-2M0, T4aN0-2M0, or no distant metastases, or viable or potentially viable) were enrolled and received 3 cycles of neoadjuvant sintilimab, albumin-bound paclitaxel, and carboplatin. Surgery was scheduled within four to six weeks of completing the neoadjuvant treatment. Three additional cycles of adjuvant sintilimab monotherapy or sintilimab plus chemotherapy were scheduled after a multidisciplinary discussion. The primary endpoint was the MPR rate. Results: From November 2020 to November 2021, twenty-four patients (median age: 64.5 years, men: 21/24,lower segment tumor location12/24,stage IV disease 15/24) were included in this study. All patients completed three cycles of neoadjuvant treatment and surgery. The median dose intensities for sintilimab, carboplatin and albumin-bound paclitaxel were 100% (range, 66.7–105.0%), 98.4% (range, 64.1–104.0%), and 100% (range, 38.1–105.8%), respectively. The R0 resection rate was 100%. The pCR rate and MPR rate was 33.3% and 41.7%. Among the 10 patients with PD-L1 CPS of ≥1, the pCR and MPR rates were 40% and 50%. 20 (83.1%) had TNM downstaging. The median DFS and median OS had not been reached yet, 500 days DFS and OS rate was 85.3% (95%CI 85.4%-97.2%) and 94.1% (95%CI 94.8%-100.0%). PD-L1 protein expression showed a higher life expectancy trend in the post-neoadjuvant therapy esophageal tissue samples than in the pre-therapy samples. The most common grade 3-4 treatment-related adverse events were anemia (29.2%), increased gamma-glutamyl transferase level (4.2%) and hyponatremia (4.2%). Emergency reoperation and intensive care were not required, and there were no postoperative mortalities. Conclusions: Neoadjuvant sintilimab, albumin-bound paclitaxel, and carboplatin preliminarily demonstrate encouraging clinical benefits and acceptable safety. Preoperative immunotherapy combined with chemotherapy alters the immune microenvironment of locally advanced resectable ESCC. Clinical trial information: ChiCTR2000041081.
Effect of perioperative medical therapy on prognosis in recurrent nasopharyngeal carcinoma: A comparative effectiveness research.
Authors: Song Xiaole , Yu Hongmeng , Yan Li , Wang Xiaoshen , Zhang Huankang 
Published: August 2024

e18051 Background: Transnasal endoscopic (TEN) surgery has evolved to be an important treatment for rNPC.The role of perioperative chemotherapy or immunotherapy has not been determined yet. Methods: Three single arm, prospective researches were pooled to analyze the comparative effectivenessof neoadjuvant, adjuvant therapy and surgery only in rNPC patients undergoing TEN surgery through 2019 to 2023. Data was collected including sex, age, TNM staging, treatment modality and internal carotid artery (ICA) management in three investigator initial trials (NCT05011227, ChiCTR1900026341, NCT05350891). The primary and secondary outcomes were overall survival (OS) and local recurrence free survival (LRFS). Statistical analysis was performed using SPSS 29.0 (IBM).Variables with two-sided P-values <0.05 in log-rank tests were identified as significant. Multivariable Cox regression analysis was conducted to reveal the prognostic value of treatment modality. Results: Overall, 233 eligible participants were divided into three treatment groups (neoadjuvant, adjuvant, and surgery only group). The clinicopathological characteristics were balanced (Table). In a mean follow-up period of 605 days, the 1-year, 2-year OS rate were 91.9%, 83.3% respectively. According to Kaplan Merier survival analysis, immunotherapy± chemotherapy after surgery significantly improved OS compared with surgery only (P<0.001). Although no significance (P=0.176) was noted in neoadjuvant compared with surgery only group, partially because of the small sample size, the 1-,3-year OS rate was much higher. When blended together, neoadjuvant+adjuvant group also won over surgery only group regarding OS (P<0.001) and LRFS (P=0.002). Subgroup analysis also indicated that age≥52 (P=0.002), higher T staging (P<0.001), and embolization of ICA (P<0.001) were associated with worse prognosis. Sex showed no significant effect on survival (P=0.533). The above four factors were adopted for multivariate COX analysis, elucidating that age (P=0.005), T staging (P=0.024) and treatment modality (P=0.007) were independent predictor for OS, however, embolization of ICA (P=0.097) was not. Conclusions: Adjuvant therapy, as an independent predictor of OS, improved the overall survival in rNPC patients underwent TEN surgery. The efficacy of neoadjuvant therapy demanded solid evidence from larger sample size cohort. Clinical trial information: NCT05011227 , NCT05350891 , ChiCTR1900026341. [Table: see text]
Efficacy and safety of chidamide in combination with serplulimab and standard third-line treatments in advanced colorectal cancer: A single arm, exploratory phase 2 trial.
Authors: Li Wei , Xu Mengdan , Xu Caihua , Wu Mengyao , Chen Kai 
Published: August 2024

TPS3637 Background: The efficacy of third line and subsequent treatments for advanced colorectal cancer (mCRC) is suboptimal, and the available drug options are limited. Approximately 95% of mCRC patients belong to the type of satellite stability (MSS), which often shows poor response to single immunotherapy. Previous clinical trials have preliminarily demonstrated that the potential application of combining anti-angiogenesis drugs with immune checkpoint inhibitors (ICIs) in mCRC. Chidamide is an isoform selective inhibitor of histone deacetylase (HDAC). Studies have shown its synergistic effect with PD-1 monoclonal antibody in anti-tumor activity. Therefore, we aim to conduct further investigations centered on the combination of Chidamide+Serplulimab+standard third-line treatments in mCRC. Methods: This prospective, open-label, single-arm, exploratory multi-center clinical trial has been planned to enroll 30 patients with advanced CRC who have progressed after two lines of standard therapies. The key inclusion criteria are: pathologically confirmed colorectal malignancy; age ≥18 years, regardless of gender; estimated survival ≥3 months; ECOG score 0-1; at least one measurable lesion according to iRECIST criteria; requiring third-line or beyond treatment and no prior treatment with PD1 monoclonal antibody, regorafenib/fruquintinib or TAS-102±bevacizumab; adequate major organ function; and signed informed consent and good compliance, agreeing to cooperate with survival follow-up. Enrolled patients receive Chidamide (20mg twice a week), Serplulimab (3mg/kg on day 1 every two weeks), and standard third-line treatments (TAS-102 35mg/m² twice daily on days 1-5 and 8-12 of a 28-day cycle ± bevacizumab 5mg/kg on day 1 every two weeks or regorafenib 120mg daily or fruquintinib 5mg daily for three weeks followed by one week off ).The primary endpoints are safety and objective response rate (ORR) determined by investigators. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate(DCR), PFS rate at 6 months and 12 months, OS rate at 6 months and 12 months, DCR, quality of life score(QoL), and nutritional score PG-SGA. As of February 2024, eight patients have been enrolled in the study. Trial registration number: ChiCTR2300077213. Clinical trial information: ChiCTR2300077213.