bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treg cells and the response to neoadjuvant chemotherapy combined with immunotherapy in resectable esophageal squamous carcinoma.
Authors: Jiang Bo , Yang Xin , Yu Pengyi , Zhang Chu , Li Chunyang , Tang Wenhua , Zhang Junling , Huang Mengli 
Published: June 2023

e14626 Background: More and more studies focus on the neoadjuvant chemotherapy combined with immunotherapy (chemo-immunotherapy) in resectable esophageal squamous carcinoma (ESCC). Herein, we aimed to evaluate the efficacy and safety of neoadjuvant programmed cell death protein 1 inhibitors with chemotherapy and explore tumor microenvironment (TME) profiles. Methods: Patients with previously untreated, resectable, stage III ESCC in the third affiliated hospital of Soochow University were enrolled. Each patient received two-four cycles of neoadjuvant chemo-immunotherapy before surgical resection. The TME profiles of formalin-fixed paraffin-embedded tumor samples at baseline were evaluated by multiplex immunofluorescence to discover novel biomarkers of response to neoadjuvant chemo-immunotherapy. Results: Twenty patients were included, all of whom underwent R0 resection. 85% (17/20) of patients underwent 2 cycles of neoadjuvant therapy. TP53 (13/20,65%) was were high-frequency mutated gene, followed by CDKN2A (5/20,25.0%) and PIK3CA (3/20, 15.0%). PD-L1 positive (TPS≥1%) was found in only 3 patients. Postoperative pathological evaluation showed that 18 patients (90.0%) were major pathologic response (MPR), of which 5 patients (28.0%) achieved pathological complete response (pCR). Neoadjuvant therapy has acceptable side effects. TME profiles at baseline showed no significant correlation between PD-L1 and pathological response. The density of Treg cell in the tumor area was significantly lower in pCR patients than in MPR patients (P=0.0302). Conclusions: Neoadjuvant chemo-immunotherapy was well tolerated and was effective therapy for resectable ESCC. Treg cells may serve as potential predictive biomarkers.
Clinical and pathological description of patients with triple negative breast cancer undergoing neoadjuvant chemotherapy and pembrolizumab in a Brazilian cancer center.
Authors: Sousa Isadora Martins de , Marin Comini Ana Carolina Carolina , Borges Italo Barradas e Silva , Tavares Monique Celeste 
Published: June 2023

e14632 Background: High-risk early triple-negative breast cancer (TNBC) is frequently associated with early recurrence and high mortality. Studies suggest a sustained clinical benefit in patients with TNBC who have a pathological complete response (PCR) after neoadjuvant chemotherapy (NACT). In TNBC, the combination of cancer immunotherapy based on PD-1/PD-L1 immune checkpoint inhibitors with chemotherapy was effective both in advanced and early setting phase 3 clinical trials, in this last scenario the addition of pembrolizumab to platinum containing NACT resulted in a significant increase of pathological complete response. Methods: We performed a retrospective observational cohort study of patients with early TNBC, stage I-III who received neoadjuvant treatment with chemotherapy based on doxorubicin, cyclophosphamide, paclitaxel and carboplatin associated with pembrolizumab treaties from January 2022 to January 2023, in AC Camargo Cancer Center, São Paulo, Brazil, to evaluate their clinical-pathological characteristics. Results: All 52 patients were women, 60,4% premenopausal, with a median age of 42 years old when diagnosed, 59.6% had comorbidities, most commonly hypertension, and 1.9% had an autoimmune disease. About 16.7% germline mutation in the BRCA 1 and 8.3% in the BRCA 2 gene. Regarding pathological characteristics of the tumor, 98% were invasive ductal carcinoma, 78% with histological grade III, 89.8% had nuclear grade III, 51.1% with score 3 mitoses. There were 56,3% with weak, 35,4% with moderate, and 8,3% with intense Tumor Infiltrating Lymphocytes Stromal (TILS). In 47.1% of cases, the ki67 was greater than 80%. The expression of HER 2 was low in 23,8%. About the clinical stage of the tumor 65.4% were cT2 and 17.3% cT3, being cN0, cN1 and cN2a was 40.4%, 36.5% and 13.5%, respectively and grouped clinical stage 40.45 IIA, 25% IIB and 19.2% IIIA. Treatment-related toxicities 20% patients had immune related toxicities, being the main one 30% endocrinologic and 20% hepatic, being that 36.4% occurring after the second cycle. Due to the toxicities, 22.2% of the patients had their treatment delayed. In terms of treatment, 68.6% had begun with platinum and taxane, and 7.8% received dense dose AC (ACdd). Now, only 42.6% of the patients have completed all NACT and 53.2% are still on treatment. From these, 56.8% had complete clinical response, 2.3% stable disease and and those who have already finished and operated 66.7% complete pathological response. Conclusions: Our cohort is mostly pre-menopausal cT2, cN0, stage IIA. Twenty percent of them had IRT, the most common being endocrine and hepatic, which occurred early after the second cycle, leading to treatment delay in 22.2%. About 8% received ACdd, of the patients who completed the treatment and underwent surgery, 66.7% had a complete pathological response.
Tissue cadherin 17 (CDH17): A favorable prognostic determinant of colorectal cancer using digital image analysis.
Authors: Ng Lui , Sun Stella , Shan Wing Yu , Leung Pauline , Luk John Moon , Foo Dominic Chi-Chung 
Published: June 2023

e14651 Background: Colorectal cancer (CRC) is the third most diagnosed malignancy and the second leading cause of cancer-death globally. The identification of robust prognostic markers for risk stratification of CRC would facilitate the accurate selection of high-risk patients for adjuvant therapies, hence improving patients’ survival and quality of living. Cadherin 17 (CDH17) is a validated biomarker for CRC characterized by its overexpression in tumor tissues (Zheng et al., 2021). CDH17 expression in tissue samples can be reliably detected by immunohistochemistry (IHC), which could potentially provide useful information for malignancy monitoring and prognosis. Nevertheless, the implementation of IHC in clinical settings is hindered by the lack of standardized guidelines. In this regard, the present study employed a standardized automated IHC platform and a digitalized sample scoring system to investigate CDH17 tissue expression and examine its clinical prognostic value in CRC. Methods: IHC was performed to assess CDH17 expression on paired tumor and adjacent non-tumor tissues from a cohort of 198 retrospective CRC cases, using the Lic3 antibody and an automated IHC system integrated with AI-digital imaging analysis. The M-score was generated for CDH17 membrane staining according to the formula (1 × % of weakly stained cells + 2 × % moderately stained cells + 3 × % of strongly stained cells)/6. Clinical correlation analysis with TNM, differentiation, and metastasis was determined. The prognostic value of tissue CDH17 was evaluated by Kaplan-Meier curves and Cox regression analyses on patients’ OS and RFS. Comparison of M-score and pathologist visual scoring was made to assess the validity of software-derived IHC scoring. Results: A significantly higher tissue CDH17 level was observed in CRC patients with advanced tumour staging (Early vs. Late stage, p = 0.0493; Mann-Whitney U test) and distant metastasis (p = 0.0188; Mann-Whitney U test). CRC patients with high M-score (M-ScoreHigh; cut-off = 30) were associated with poorer OS and shorter RFS (OS, p = 0.015; RFS, p = 0.018; Log-rank test). Subgroup analysis revealed that M-ScoreHigh in early-stage CRC predicts patients’ disease recurrence of less than 2 years after curative surgery (p = 0.025; Log rank test). Multivariate cox regression analysis showed that CDH17 was an independent prognostic factor for OS (HR = 1.918, 95% CI = 1.001-3.676, p = 0.05). A comparison of software-derived CDH17 M-score with pathologist scoring demonstrated good correlation of 0.7257 (p < 0.0001, n = 36; Pearson correlation). Conclusions: The present study suggests that CDH17 is a potential biomarker of poor prognosis for CRC. Quantification of tissue CDH17 level using a standardized automated IHC platform and digital image analysis could aid in patient stratification which allows efficient treatment strategies for better survival outcomes.
Efficacy of STC-1010, a new allogenic cancer vaccine in colorectal cancer models.
Authors: You Benoit , Tortorelli Corinne , Wang Yan , Peyronnier Arnaud , Bessede Alban , Gongora Céline , Pinteur Benoit , Chalus Lionel , Alzeeb George , Bravetti Paul , Ghiringhelli François 
Published: June 2023

e14661 Background: Colorectal cancer (CRC) is the second cause of cancer-related death worldwide. Recent tremendous progresses have installed immunotherapy as a treatment option and opened multiple ways to address therapeutic challenges for MSI or MSS CRC patients. Accordingly, Brenus-Pharma developed a therapeutic cancer vaccine, the STC-1010, basing on the technology by stimulating tumor cells (STC) with physical (irradiation and heat shock) and chemical (via standard-of-care (SoC) chemotherapy) stress, coupled with the haptenization for overexpressing tumor-related antigens. Methods: The mouse version of STC-1010 (mSTC-1010) vaccine prepared using two CRC mouse cell lines (CT26 and CMT93) and one pancreatic cancer mouse cell line (LTPA), previously showed encouraging results in pre-clinical studies on MSS CT26 ‘cold-tumor’ and anti-PD1 resistant MSI MC38 ‘hot-tumor’ murine models. mSTC-1010 associated with immunostimulant (cyclophosphamide and GM-CSF at low doses), combined or not with chemotherapy (FOLFOX or FOLFIRI) led to a significant decrease of tumor volume, a M1-oriented macrophage response (immunohistochemical, iNOS/CD163 > 1), and an increase of T lymphocyte infiltration. Results: We confirmed these proof-of-concept efficacy with the human STC-1010 using three CRC human cell lines (HCT116, HT29 and Lovo). STC-1010 favored ex vivo an immune stimulation on human dendritic cells (DCs) which further primed CD8+ T cells to induce massive apoptosis of CRC cells (versus control). In HT29 in-ovo chicken embryo Chorio-Allantoid Membrane (CAM) assay, STC-1010 significatively increased IL-12, IL-2 and IFN-gamma expression (versus control) (p < 0.02). Results from this immune reactive model showed significant increase of tumor necrosis (p = 0,0267), metastasis regression (-49%), and increase infiltration of CD4+, CD8+ compared to control group. Conclusions: The good tolerability of the STC-1010 vaccine in different models allows to plan a first-in-human phase I/II clinical trial with MSS and MSI-H metastatic CRC (mCRC) patients. A dose-escalation phase Ia (STC-1010 plus immunostimulant, associated to mFOLFOX6 w/o bevacizumab) will be performed with MSS mCRC patients to evaluate the safety and the recommended phase 2 trial dose (RP2D). A subsequent expansion phase IIa part will assess STC-1010 efficiency, associated with SoC in first-line setting for MSS patients, and in second-line setting after immunotherapy for MSI-H, dMMR or Lynch syndrome mCRC patients.
SI-B003 (PD-1/CTLA-4) in patients with advanced solid tumors: A phase I study.
Authors: Wang Yakun , Li Yongsheng , Liu Jiyan , Luo Su-xia , Li Qi , Zou Wen , Wang Zhaoxiang , Peng Yujia , Xiao Sa , Wang Hongwei , Zhu Hai , Olivo Martin Sebastian , Zhu Yi , Shen Lin 
Published: June 2023

e14668 Background: Although marketed antibodies against PD-1/L1 or CTLA-4 have been shown to be efficacious in a variety of tumors, the overall response rate (ORR) remains low. SI-B003 is a PD-1/CTLA-4 bispecific antibody. We hypothesized that co-targeting PD-1 and CTLA-4 simultaneously could achieve a better anti-tumor activity due to cooperative binding to exhausted T-cell subsets. Methods: Patients with recurrent or metastatic solid tumors who had failed standard therapy were eligible to participate. SI-B003 was administered intravenously every other week (Q2W) in a four-week cycle. The phase Ia dose escalation consisted of an accelerated titration phase (the first 2 dose levels) and a mTPI-2 with a total of five dose levels: 0.1, 0.3→1.0, 3, 5 and 10 mg/kg. The phase Ib consisted of a dose expansion and indication expansion cohorts with 5, 10 mg/kg Q2W and 7.5mg/kg Q3W. The primary objectives of phase Ia were to assess dose-limiting toxicity (DLT), maximum tolerated dose (MTD) or maximum administration dose (MAD), and treatment emergent adverse events (TEAEs). The primary objectives of phase Ib included safety, tolerability, and identification of the recommended phase 2 dose (RP2D). Results: As of December 31, 2022, 60 patients with solid tumors received SI-B003 at six different dose levels (14 in Ia, 46 in Ib). Median age was 55.5 years. The median PFS (95%CI) was 3.7 (1.6~5.7) months. Among 56 evaluable patients, the objective response rate (ORR) (n/N, 95%CI) was 16.1% (9/56, 7.6~28.3%) and disease control rate (DCR) was 50.0% (28/56). Confirmed ORR, DCR, median duration of response (DoR) and median progression free survival (PFS) were 9.5% (2/21, 1.2~30.4%), 42.9% (9/21), NR and 2.1 (95%CI, 1.4~NA) months in the 5mg/kg Q2W group and 8.3% (2/24, 1.0~27.0%), 62.5% (15/24), 7.1 (95%CI, 1.9~NA) and 5.7 (95%CI, 1.9~8.7) months in 10mg/kg Q2W group respectively. One patient received 7.5mg/kg Q3W had a confirmed response and was still under treatment. Among 21 evaluable patients who had received prior PD-1/L1 treatment, the ORR and DCR were 14.3% (3/21, 3.1~36.3%) and 52.4% (11/21). The mDoR (95%CI) and mPFS (95%CI) were 4.2 (NA) months and 4.1 (1.4, 5.7) months. The most common TRAEs were rash (35%), AST increased (28%), ALT increased (28%). The most common grade ≥3 TRAEs were AST increased (3%). One patient died from an immune-mediated pneumonia. Conclusions: SI-B003 demonstrated a tolerable safety profile and preliminary anti-tumor activity in patients with recurrent or metastatic solid tumors. Anti-tumor effects of SI-B003 were observed in patients who had progressed on prior PD-1/L1 immunotherapy suggesting that SI-B003 may be beneficial for patients who have developed resistance to PD-1/L1 drugs. Clinical trial information: NCT04606472 .
IMM27M, a humanized Fc-engineered anti CTLA-4 antibody, in patients with advanced solid tumors: A phase I dose-escalation study.
Authors: Wang Shusen , Zhang Qingyuan , Gao Quanli , Wu Shikai , Li Enxiao , Li Zhi-hua , Liu Ziquan , Zhao Xiwen , Gao Siman , Lu Qiying , Tian Wenzhi 
Published: June 2023

e14670 Background: IMM27M is a humanized Fc-engineered IgG1 CTLA-4 monoclonal antibody with enhanced ADCC. In pre-clinical models, IMM27M could enhance immune responses and promote Treg depletion. The pre-clinical results showed IMM27M induced a significantly stronger anti-tumor activity than ipilimumab and resulted in complete tumor remission even at a low dose. Methods: This study is an open-label, multi-center, phase I dose-escalation study conducted to evaluate the safety, tolerability, maximum tolerated dose/recommended dose for expansion, PK and anti-tumor activity in patients with advanced solid tumors. The study was designed with an accelerated titration followed by a standard 3+3 design. IMM27M (0.1,0.3,1,2,3 mg/kg) was administered as monotherapy on Day 1 of every 3 weeks. Results: As of 30 Dec 2022, the dose has been escalated to 2mg/kg. 11 pts (8 female, 3 male) were enrolled and treated (1 at 0.1 mg/kg, 3 at 0.3 mg/kg, 3 at 1.0 mg/kg, 4 at 2.0 mg/kg), including 3 pts with melanoma, 3 pts with breast carcinoma, 2 pts with RCC, 1 pt with HCC, 1pt with NSCLC and 1 pt with ovarian carcinoma. Median age was 52 years (range 36-72). 9 pts (81.8%) received ≥ 2 lines of previous systemic therapies and 7 pts (63.6%) received previous anti PD-1/PD-L1 treatment. Treatment-related adverse events (TRAEs) occurred in 10 pts (90.9%) to date. Most TRAEs were grade 1 or 2. The most common TRAEs (≥ 10%) of all grades were anaemia (n = 3 [27.3%]), white blood cell count decreased (n = 2 [18.2%]), lymphocyte count decreased (n = 2 [18.2%]), constipation (n = 2 [18.2%]) and rash (n = 2 [18.2%]). Grade ≥3 TRAEs occurred in 2 pts (18.2%): lymphocyte count decreased (G3, n = 1 [9.1%]) and immune-related lung disease (G3, n = 1 [9.1%]). Treatment related SAE patients only occurred in 1 pt (immune-related lung disease, possibly related to treatment), and this patient recovered after clinical treatment. No DLT was observed. No TRAE leading to treatment discontinuation was reported. In 10 response evaluable pts, 3 pts had SD as best response. One pt in 2.0 mg/kg dose cohort had tumor shrinkage of 17% at Week 6, who had metastatic melanoma and received 2 lines of previous treatments including anti PD-1. The treatment of this patient is ongoing. Preliminary PK analysis of IMM27 showed an approximate proportional dose curve and the mean t1/2 was around 11 days. Conclusions: IMM27M monotherapy in general was well-tolerated at the dose level evaluated and preliminarily anti-tumor activity in patients with advanced solid tumors. The dose escalation study of IMM27M in advanced solid tumors is ongoing. Clinical trial information: NCT05235438 .
Safety, tolerability, and pharmacokinetics of HLX26 (an anti-LAG3 antibody) in patients with advanced or metastatic solid tumors or lymphomas.
Authors: Liu Rujiao , Zhang Jian , Chen Yang , Gao Shuiping , Hu Chen , Zhou Liang , Li Hua , Kang Wenying , Zhu Jun 
Published: June 2023

e14671 Background: HLX26 is a novel humanized anti-LAG3 monoclonal antibody. This study aimed to evaluate the safety, tolerability, and pharmacokinetics of HLX26 in patients with advanced or metastatic solid tumors or lymphomas. Methods: This was a first-in-class, multicenter, open-label, dose-escalation phase 1 study. Patients with histologically or cytologically confirmed advanced solid tumors or lymphomas who had failed or were not suitable for standard therapies were enrolled and received HLX26 at five dose levels (60, 150, 300, 500, or 800 mg, Q3W) intravenously. This study followed accelerated titration combined with a “3+3” design. HLX26 was given until disease progression with no clinical benefit, 2 years of treatment, experiencing intolerable toxicity, withdrawal of consent, or death, whichever occurred first. The primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) within DLT observation period, which was 3 weeks after the first dose of HLX26. Secondary endpoints included safety, pharmacokinetic and pharmacodynamic characteristics, preliminary efficacy, immunogenicity, and potential biomarker explorations of HLX26. Results: As of December 22, 2022, 12 patients with stage IV breast (n = 10, 83.3%) or rectum (n = 2, 16.7%) solid tumors were enrolled and received HLX26 at 60 mg (n = 1), 150 mg (n = 1), 300 mg (n = 3), 500 mg (n = 3), or 800 mg (n = 4). The mean age was 57.5 (range 31–73) years. No DLT was reported and the MTD was not determined as of yet. Eleven (91.7%) patients experienced treatment-emergent adverse events (TEAEs), most commonly hypercholesterolemia (41.7%), hypertriglyceridemia (25.0%), and hyperuricemia (25.0%). Most TEAEs were grade 1 (n = 8, 66.7%) and 2 (n = 2, 16.7%). Conclusions: In summary, no new safety signals were observed from 60 mg to 800 mg of HLX26. HLX26 was safe and well tolerated in patients with advanced or metastatic solid tumors. Clinical trial information: NCT05078593 .
The timing of statin initiation on survival outcomes of cancer patients treated with immune checkpoint inhibitors: A retrospective cohort study.
Authors: See Xin Ya , Chiang Cho Hsien , Chiang Cho Han , Chen Yuan-Jen , Chang Yu-Cheng , Wang Shih-Syuan , Peng Chun-Yu , Horng Chuan-Sheng , Hsia Yuanping , Chiang Cho Hung , Peng Cheng-Ming , Shiah Her-Shyong 
Published: June 2023

e14672 Background: Concomitant use of statins has been associated with improved survival outcomes in patients treated with immune checkpoint inhibitors (ICIs), but it is unclear if the timing of statin initiation plays a role in patient outcomes. We aimed to investigate the outcomes of patients who were started on a statin before and after initiation of ICI therapy. Methods: We performed a retrospective cohort study at two tertiary referral centers in Taiwan. We collected data on statin use including the timing of statin initiation, basic demographics, underlying comorbidities, and cancer information. We compared the overall survival (OS) and progression-free survival (PFS) between statin and non-statin users using Cox proportional hazard model analysis and Kaplan-Meier Survival analysis. Results: Among 734 patients who received ICIs, 76 patients received statins after ICI initiation, 52 patients received statins before ICI initiation, and 606 were non-statin users. Patients who received statins after ICI had a longer OS (median 37.6 vs. 11.3 vs. 10.3 months, p = 0.01) and PFS (median 10.5 vs. 5.6 vs. 6.3 months, p = 0.02) than patients who received statins before ICI and non-statin users. In Cox proportional hazard analyses, the use of statins after ICI was associated with a lower risk of mortality (HR, 0.65 [95% CI: 0.45-0.94], p = 0.02) or disease progression (HR, 0.71 [95% CI: 0.53-0.95], p = 0.02) compared with non-statin users. On the other hand, the use of statins before ICI was not associated with a lower risk of mortality (HR, 1.46 [95% CI: 0.96-2.22], p = 0.08) or disease progression (HR, 1.22 [95% CI: 0.86-1.73], p = 0.26) compared with non-statin users. These trends were observed in multivariate Cox proportional analyses adjusting for underlying comorbidities, cancer stage, type, and therapy. Conclusions: The use of statins after the initiation of immunotherapy is associated with improved survival outcomes. [Table: see text]