Prognostic prediction of oxidative stress related hematological biomarkers in locally advanced cervical cancer patients undergoing chemoradiotherapy.

OBJECTIVE: This investigation aimed to develop and validate a novel oxidative stress score for prognostic prediction in locally advanced cervical cancer (LACC) patients receiving chemoradiotherapy. METHODS: A total of 301 LACC patients were enrolled and randomly divided into a training and a validation set. The association between oxidative stress parameters and prognosis was analyzed for oxidative stress score (OSS) establishment. A Cox regression model was conducted for overall survival (OS) and progression-free survival (PFS). A nomogram prediction model was developed using independent prognostic factors from the training set and validated in the validation set. RESULTS: A novel OSS was established with four oxidative stress parameters, including albumin, total bilirubin, blood urea nitrogen, and lactate dehydrogenase. Multivariate regression analysis identified OSS as an independent prognostic factor for OS (p = 0.001) and PFS (p < 0.001). A predictive nomogram based on the OSS was established and validated. The C-indexes of the nomogram in the training set were 0.772 for OS and 0.781 for PFS, while in the validation set the C-indexes were 0.642 for OS and 0.621 for PFS. CONCLUSION: This study confirmed that preoperative OSS could serve as a useful independent prognostic factor in LACC patients who received CCRT.

Ratiometric determination of etomidate based on an albumin-based indicator displacement assay (IDA).

The first fluorescent sensor based on the indicator displacement assay (IDA) for on-site determination of etomidate.

A novel dual-color fluorescent sensor with two pKas for on-site detection of pH in food.

Tracking pH fluctuations in food samples is important for ensuring food freshness. Fluorescent probes have been widely applied as promising tools for the on-site detection of pH changes; however, most of them can be applied only at either lower or higher pH ranges because their response structures commonly have a single acid dissociation constant (pKa). To address this problem, we designed a fluorescent sensor, called HMB, containing a methylpiperazine group with two pKa values, which exhibited a unique dual-color response to pH changes over a wide pH range. Furthermore, the HMB-based test strips are easily prepared and used as portable labels for the visual monitoring of food spoilage that results in microbial and anaerobic glycolytic pathways in real food (such as cheese and shrimp). To the best of our knowledge, this is the first fluorescent pH sensor with two pKa values, and we expect that this work will inspire more sensor designs for food quality control.

Effect of bolus materials on dose deposition in deep tissues during electron beam radiotherapy.

Several materials are utilized in the production of bolus, which is essential for superficial tumor radiotherapy. This research aimed to compare the variations in dose deposition in deep tissues during electron beam radiotherapy when employing different bolus materials. Specifically, the study developed general superficial tumor models (S-T models) and postoperative breast cancer models (P-B models). Each model comprised a bolus made of water, polylactic acid (PLA), polystyrene, silica-gel or glycerol. Geant4 was employed to simulate the transportation of electron beams within the studied models, enabling the acquisition of dose distributions along the central axis of the field. A comparison was conducted to assess the dose distributions in deep tissues. In regions where the percentage depth dose (PDD) decreases rapidly, the relative doses (RDs) in the S-T models with silica-gel bolus exhibited the highest values. Subsequently, RDs for PLA, glycerol and polystyrene boluses followed in descending order. Notably, the RDs for glycerol and polystyrene boluses were consistently below 1. Within the P-B models, RDs for all four bolus materials are consistently below 1. Among them, the smallest RDs are observed with the glycerol bolus, followed by silica-gel, PLA and polystyrene bolus in ascending order. As PDDs are ~1-3% or smaller, the differences in RDs diminish rapidly until are only around 10%. For the S-T and P-B models, polystyrene and glycerol are the most suitable bolus materials, respectively. The choice of appropriate bolus materials, tailored to the specific treatment scenario, holds significant importance in safeguarding deep tissues during radiotherapy.

Ferroptosis: a new mechanism of traditional Chinese medicine for cancer treatment.

Ferroptosis, distinct from apoptosis, is a novel cellular death pathway characterized by the build-up of lipid peroxidation and reactive oxygen species (ROS) derived from lipids within cells. Recent studies demonstrated the efficacy of ferroptosis inducers in targeting malignant cells, thereby establishing a promising avenue for combating cancer. Traditional Chinese medicine (TCM) has a long history of use and is widely used in cancer treatment. TCM takes a holistic approach, viewing the patient as a system and utilizing herbal formulas to address complex diseases such as cancer. Recent TCM studies have elucidated the molecular mechanisms underlying ferroptosis induction during cancer treatment. These studies have identified numerous plant metabolites and derivatives that target multiple pathways and molecular targets. TCM can induce ferroptosis in tumor cells through various regulatory mechanisms, such as amino acid, iron, and lipid metabolism pathways, which may provide novel therapeutic strategies for apoptosis-resistant cancer treatment. TCM also influence anticancer immunotherapy via ferroptosis. This review comprehensively elucidates the molecular mechanisms underlying ferroptosis, highlights the pivotal regulatory genes involved in orchestrating this process, evaluates the advancements made in TCM research pertaining to ferroptosis, and provides theoretical insights into the induction of ferroptosis in tumors using botanical drugs.

Vitamin D Alleviates Cadmium-Induced Inhibition of Chicken Bone Marrow Stromal Cells' Osteogenic Differentiation In Vitro.

Vitamin D is a lipid soluble vitamin that is mostly used to treat bone metabolism-related diseases. In this study, the effect of Cd toxicity in vitro on osteogenic differentiation derived from BMSCs and the alleviating effect of lα, 25-(OH)2D3 were investigated. Cell index in real time was monitored using a Real-time cell analyzer (RTCA) system. The activity of alkaline phosphatase (ALP), and the calcified nodules and the distribution of Runx2 protein were detected using ALP staining, alizarin red staining, and immunofluorescence, respectively. Furthermore, the mitochondrial membrane potential and the apoptotic rate of BMSCs, the mRNA levels of RUNX2 and type Ⅰ collagen alpha2 (COL1A2) genes, and the protein expression of Col1 and Runx2 were detected using flow cytometry, qRT-PCR and western blot, respectively. The proliferation of BMSCs and osteogenic differentiation were enhanced after treatment with different concentrations of lα, 25-(OH)2D3 compared with the control group. However, 5 µmol/L Cd inhibited the proliferation of BMSCs. In addition, 10 nmol/L lα,25-(OH)2D3 attenuated the toxicity and the apoptosis of BMSCs treated by Cd, and also promoted the osteogenic differentiation including the activity of ALP, and the protein expression of Col1 and Runx2. lα, 25-(OH)2D3 can alleviate cadmium-induced osteogenic toxicity in White Leghorn chickens in vitro.

Intermolecular proton transfer from flavonol to human serum albumin triggers a red-shifted ratiometric fluorescence response.

Intermolecular proton transfer from a flavonol-based probe to the arginine (Arg222) in drug site 1 of human serum albumin triggers an unusual red-shifted ratiometric fluorescence response, which can be applied in the point-to-care diagnosis of hypoalbuminemia.

Neoadjuvant immunotherapy for colorectal cancer: Right regimens, right patients, right directions?

Neoadjuvant chemoradiotherapy (NACRT) or chemotherapy (NACT) followed by radical resection and then adjuvant therapy is considered the optimal treatment model for locally advanced colorectal cancer (LACRC). A recent total neoadjuvant therapy (TNT) strategy further improved the tumour regression rate preoperatively and reduced local-regional recurrence in locally advanced rectal cancer (LARC). However, distant metastasis was still high, and little overall survival benefit was obtained from these preoperative treatment models. According to mismatch repair protein expression, MSI-H/dMMR and non-MSI-H/pMMR statuses were defined in colorectal cancer (CRC) patients. Due to the special features of biologics in MSI-H/dMMR CRC patients, this subgroup of patients achieved little treatment efficacy from chemoradiotherapy but benefited from immune checkpoint inhibitors (ICIs). The KEYNOTE-177 trial observed favourable survival outcomes in metastatic CRC patients treated with one-line pembrolizumab with tolerable toxicity. Given the better systemic immune function, increased antigenic exposure, and improved long-term memory induction before surgery, neoadjuvant ICI (NAICI) treatment was proposed. The NICHE trial pioneered the use of NAICI treatment in LACRC, and recent reports from several phase II studies demonstrated satisfactory tumour downsizing in CRC. Preclinical rationales and preliminary early-phase human trials reveal the feasibility of NAICI therapy and the therapeutic efficacy provided by this treatment model. Better tumour regression before surgery also increases the possibility of organ preservation for low LARC. However, the optimal treatment strategy and effective biomarker identification for beneficiary selection remain unknown, and potential pitfalls exist, including tumour progression during neoadjuvant treatment due to drug resistance and surgery delay. Given these foundations and questions, further phase II or III trials with large samples need to be conducted to explore the right regimens for the right patients.

Smartphone-based on-site detection of hydrogen peroxide in milk by using a portable ratiometric fluorescent probe.

The on-site detection of hydrogen peroxide (H2O2) is important for maintaining food safety as the ingestion of H2O2 can lead to serious pathological conditions. However, most reported fluorescent probes require a fluorometer to ensure readable signal output and reliable detection result. Consequently, the fluorescent detection of H2O2 can be realized only within a standard laboratory setting. Herein, we report a novel supramolecular strategy that can successfully convert the typical off-on response to H2O2 into a ratiometric response, which allows the on-site detection of H2O2 when used in conjunction with a smartphone-based 3D-printed miniaturized testing system. This method has acceptable sensitivity, good anti-interference ability, and desirable accuracy compared to a standard detection method. More importantly, this portable ratiometric method can be used to detect H2O2 residue in commercial milk samples with the simple testing apparatuses.

Hypofractionated versus conventional intensity-modulated radiation irradiation (HARVEST-adjuvant): study protocol for a randomised non-inferior multicentre phase III trial.

INTRODUCTION: Short course regimen has become the major trend in the field of adjuvant radiotherapy for patients with breast cancer. Hypofractionated radiotherapy (HF-RT) regimen of 40-42.5 Gy in 15-16 fractions has been established as a preferred option for whole breast irradiation. However, few evidences of hypofractionated regional nodal irradiation (RNI), especially involving internal mammary nodes (IMNs), could be available during the era of intensity-modulated radiation therapy (IMRT). Against this background, we design this trial to explore the hypothesis that HF-RT regimen involving RNI (including infraclavicular, supraclavicular nodes and IMNs) will be non-inferior to a standard schedule by using IMRT technique. METHODS AND ANALYSIS: This is an open-label randomised, non-inferior, multicentre phase III trial. Patients with breast cancer with an indication for RNI after breast conserving surgery or mastectomy are randomised at a ratio of 1:1 into the following two groups: hypofractionated regimen of 2.67 Gy for 16 fractions or conventional regimen of 2 Gy for 25 fractions. The dose was prescribed to ipsilateral chest wall or whole breast and RNI (including infraclavicular, supraclavicular nodes and IMNs, lower axilla if indicated). The trial plans to enrol a total of 801 patients and all patients will be treated using IMRT technique. The primary endpoint is 5-year locoregional recurrence. The secondary endpoints include 5-year distant metastasis free survival, invasive recurrence-free survival, overall survival, accumulative acute radiation-induced toxicity and accumulative late radiation-induced toxicity, cosmetic outcomes and quality of life. ETHICS AND DISSEMINATION: The study has been approved by the Ethical Committee of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine (version 2018-95-3) and approvals from ethical committee of each participating centre have also been obtained. Research findings will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03829553.

Correlation between Ferroptosis-Related Gene Signature and Immune Landscape, Prognosis in Breast Cancer.

Breast cancer (BC) is the most commonly diagnosed cancer and second leading cause of cancer-related death in women worldwide. Ferroptosis, an iron-dependent newly discovered mode of cell death, can be induced by lenaltinib and plays an important role in the biological behaviors of BC. Therefore, the prognostic value of ferroptosis-related genes (FRGs) in BC warrants further investigation. FRG expression profiles and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO). Immune-related pathways were found in the functional analysis. Significant differences in enrichment scores for immune cells were observed. Some patients from TCGA-BRCA were included as the training cohort. A six-gene prediction signature was constructed with the least absolute shrinkage and selection operator Cox regression. This model was validated in the rest of the TCGA-BRCA and GEO cohort. The expressions of the six FRGs were verified with real-time quantitative polymerase chain reaction and immunohistochemistry in the Human Protein Atlas. Relapse or metastasis was more likely in the high-risk group. Risk score was an independent predictor of disease-free survival. Collectively, the ferroptosis-related risk model established in this study may serve as an effective tool to predict the prognosis in BC.

Ferroptosis-Related lncRNA Signature Correlates with the Prognosis, Tumor Microenvironment, and Therapeutic Sensitivity of Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the most prevalent form of esophageal cancer in China and is closely associated with malignant biological characteristics and poor survival. Ferroptosis is a newly discovered iron-dependent mode of cell death that plays an important role in the biological behavior of ESCC cells. The clinical significance of ferroptosis-related long noncoding RNAs (FRLs) in ESCC remains unknown and warrants further research. The current study obtained RNA sequencing profiles and corresponding clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and FRLs were obtained through coexpression analysis. Consensus clustering was employed to divide the subjects into clusters, and immune-associated pathways were identified by functional analysis. The current study observed significant differences in the enrichment scores of immune cells among different clusters. Patients from TCGA-ESCC database were designated as the training cohort. A ten-FRL prediction signature was established using the least absolute shrinkage and selection operator Cox regression model and validated using the GEO cohort and our own independent validation database. Real-time quantitative polymerase chain reaction was used to verify the expression of the ten FRLs, and the ssGSEA analysis was employed to evaluate their function. In addition, the IMvigor database was used to assess the predictive value of the signature in terms of immunotherapeutic responses. Multivariate Cox and stratification analyses revealed that the ten-FRL signature was an independent predictor of the overall survival (OS). Patients with ESCC in the high-risk group displayed worse survival, a characteristic tumor immune microenvironment, and low immunotherapeutic benefits compared to those in the low-risk group. Collectively, the risk model established in this study could serve as a promising predictor of prognosis and immunotherapeutic response in patients with ESCC.

Hypoxia-induced oxidative stress and apoptosis in gills of scaleless carp (Gymnocypris przewalskii).

Scaleless carp (Gymnocypris przewalskii) are well adapted to low oxygen environment, but their specific adaptation mechanism to hypoxic condition remains unclear. The gill is an important respiratory organ that plays a crucial role in regulating hypoxic stress. Here, we established fish hypoxic stress model, as well as investigated oxidative stress, apoptotic responses, and relative enzyme activities in the gills of scaleless carp after exposure to various levels of hypoxic stress. The results demonstrated that gill lamellar height and basal length increased significantly under severe hypoxic stress, and interval lengths between lamellae increased significantly under hypoxic stress. Furthermore, lamellar epithelial cells underwent apoptosis, cytoplasmic contraction, and mitochondrial expansion, and the number of apoptotic cells increased significantly after exposure to severe hypoxic stress for 24 h. Subsequently, Bcl-2 and Caspase 3 mRNA levels, as well as Bcl-2/Bax expression ratio were significantly increased after exposure to severe hypoxic stress for 24 h, indicating upregulation of anti-apoptotic processes. Moreover, malondialdehyde and hydrogen peroxide levels were significantly increased after exposure to hypoxic stress for 24 h. Superoxide dismutase activity increased significantly after exposure to severe hypoxia for 8 h and then decreased, while glutathione peroxidase activity and total antioxidant capacity increased significantly under hypoxic stress. Taken together, the results indicated that scaleless carp gills respond to acute hypoxic conditions by undergoing lamellar morphology remodeling, enhanced apoptosis, and increased antioxidant enzymatic activity. The study findings provided new insight into the adaptation mechanisms of scaleless carp in response to hypoxic challenge.

Using Weighted Gene Co-Expression Network Analysis to Identify Increased MND1 Expression as a Predictor of Poor Breast Cancer Survival.

Objective: We used bioinformatics analysis to identify potential biomarker genes and their relationship with breast cancer (BC). Materials and Methods: We used a weighted gene co-expression network analysis (WGCNA) to create a co-expression network based on the top 25% genes in the GSE24124, GSE33926, and GSE86166 datasets obtained from the Gene Expression Omnibus. We used the DAVID online platform to perform GO and KEGG pathway enrichment analyses and the Cytoscape CytoHubba plug-in to screen the potential genes. Then, we related the genes to prognostic values in BC using the Oncomine, GEPIA, and Kaplan-Meier Plotter databases. Findings were validated by immunohistochemical (IHC) staining in the Human Protein Atlas and the TCGA-BRCA cohort. LinkedOmics identified the interactive expressions of hub genes. We used UALCAN to evaluate the methylation levels of these hub genes. MethSurv and SurvivalMeth were used to assess the multilevel prognostic value. Finally, we assessed hub gene association with immune cell infiltration using TIMER. Results: The mRNA levels of MKI67, UBE2C, GTSE1, CCNA2, and MND1 were significantly upregulated in BC, whereas ESR1, THSD4, TFF1, AGR2, and FOXA1 were significantly downregulated. The DNA methylation signature analysis showed a better prognosis in the low-risk group. Further subgroup analyses revealed that MND1 might serve as an independent risk factor for unfavorable BC prognosis. Additionally, MND1 expression levels positively correlate with the immune infiltration statuses of CD4+ T cells, CD8+ T cells, B cells, neutrophils, dendritic cells, and macrophages. Conclusion: Our results indicate that the ten hub genes may be involved in BC's carcinogenesis, development, or metastasis, and MND1 may be a potential biomarker and therapeutic target for BC.

Epidemiology, Treatment and Prognosis Analysis of Small Cell Breast Carcinoma: A Population-Based Study.

Background: Primary small cell breast carcinoma (SCBC) is an uncommon malignancy with highly invasive behavior. The aim of this study was to find out more about the incidence, clinicopathologic characteristics and identify potential prognostic factors of SCBC. Methods: Data of patients with primary diagnosis of SCBC between 1975 and 2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The incidence after adjustment for age and percentage change per year in incidence were calculated. Disease-specific survival (DSS) and overall survival (OS) were analyzed among these SCBC patients identified from the SEER database. The whole cohorts were randomized into training and validation cohorts as ratio of 7: 3. Cox regression analysis was performed to determine predictors of survival with the training cohorts. Predictive models were constructed with training cohorts, and nomogram validation was performed using receiver operating characteristic curves, concordance indices and calibration curves in both training and validation cohorts. Results: 323 SCBC patients were enrolled finally during the research period. The overall incidence after adjustment for age between 1990 and 2018 was 0.14 per million per year, and the prevalence of the incidence has plateaued. Most of these tumors were poorly differentiated or undifferentiated. The most prevalent presenting stage was Stage II. Patients identified in this study were randomly divided into training (n = 226) and testing (n = 97) cohorts. Multivariate Cox proportional hazards model showed that chemotherapy, surgery and stage were important predictors of DSS and OS. Conclusion: SCBC is considered an infrequent breast neoplasm with aggressive characteristics. Tumor stage is associated with poor prognosis. Combination of surgery and chemotherapy is the main treatment for SCBC.

Relative contributions of sex hormones, sex chromosomes, and gonads to sex differences in tissue gene regulation.

Sex differences in physiology and disease in mammals result from the effects of three classes of factors that are inherently unequal in males and females: reversible (activational) effects of gonadal hormones, permanent (organizational) effects of gonadal hormones, and cell-autonomous effects of sex chromosomes, as well as genes driven by these classes of factors. Often, these factors act together to cause sex differences in specific phenotypes, but the relative contribution of each and the interactions among them remain unclear. Here, we used the four core genotypes (FCG) mouse model with or without hormone replacement to distinguish the effects of each class of sex-biasing factors on transcriptome regulation in liver and adipose tissues. We found that the activational hormone levels have the strongest influence on gene expression, followed by the organizational gonadal sex effect, and last, sex chromosomal effect, along with interactions among the three factors. Tissue specificity was prominent, with a major impact of estradiol on adipose tissue gene regulation and of testosterone on the liver transcriptome. The networks affected by the three sex-biasing factors include development, immunity and metabolism, and tissue-specific regulators were identified for these networks. Furthermore, the genes affected by individual sex-biasing factors and interactions among factors are associated with human disease traits such as coronary artery disease, diabetes, and inflammatory bowel disease. Our study offers a tissue-specific account of the individual and interactive contributions of major sex-biasing factors to gene regulation that have broad impact on systemic metabolic, endocrine, and immune functions.

Retrospective study of total neoadjuvant therapy for locally advanced rectal cancer.

Aim: To compare treatment outcomes of total neoadjuvant therapy (TNT) and the standard treatment for locally advanced rectal cancer (LARC). Materials & methods: Patients with LARC (cT2-4 and/or cN1-2) who were treated with preoperative chemoradiotherapy plus induction and consolidation chemotherapy followed by surgery or the standard treatment were recruited. Pathologic complete response (pCR) rate, overall survival, disease-free survival and the sphincter preservation rate as well as safety were evaluated. Results: 49 cases were treated with TNT and 71 cases received the standard treatment. Multivariate analysis demonstrated that TNT and tumor size were independent risk factors for pCR. Grade 3 chemoradiotherapy toxicity and postoperative complications were similar between the two groups. Conclusion: TNT improved the pCR rate for patients with LARC, with tolerable toxicities.

Plain language summary Outcomes of two treatment schemes were compared for locally advanced rectal cancer (LARC), including the new preoperative treatment strategy and conventional standard preoperative chemoradiotherapy. The new preoperative treatment strategy includes the addition of four cycles of preoperative chemotherapy to the standard treatment. A total of 49 cases were treated with the new preoperative treatment strategy and 71 cases received the standard treatment. Patients treated with the new preoperative treatment demonstrated higher rates of tumor regression and organ preservation. Additionally, chemoradiotherapy-related toxicity and postoperative complications were similar between the two treatment schemes. However, neither treatment strategy prolonged the survival of patients with LARC. This new preoperative treatment strategy should be recommended first for LARC.

The Role of Galectin-3 in 1α,25(OH)2D3-Regulated Osteoclast Formation from White Leghorn Chickens In Vitro.

Bones play an important role in maintaining the level of calcium in blood. They provide support for soft tissues and hematopoiesis and undergo continuous renewal throughout life. In addition, vitamin D is involved in regulating bone and calcium homeostasis. Galectin-3 (Gal-3) is a ß-galactoside-binding protein that can regulate bone cell differentiation and function. Here, we aimed to study the regulatory effects of Gal-3 on vitamin-D-regulated osteoclastogenesis and bone resorption in chicken. Gal-3 expression in bone marrow stromal cells (BMSCs) from 18-day-old chicken embryos was inhibited or overexpressed. BMSCs were then co-cultured with bone marrow monocytes/macrophages (BMMs) with or without addition of 1α,25(OH)2D3. The results showed that 1α,25(OH)2D3 upregulated the expression of Gal-3 mRNA and receptor activator of nuclear-factor κB ligand (RANKL) expression in BMSCs and promoted osteoclastogenesis, as shown by the upregulated expression of osteoclast (OC) markers (CtsK, CAII, MMP-9, and TRAP) and increased bone resorption, a method for measuring the bone resorption area in vitro. Knockdown of Gal-3 by small-interfering RNA (siRNA) in BMSCs downregulated the expression of RANKL mRNA and attenuated the effects of 1α,25(OH)2D3 on osteoclastogenesis and bone resorption. Conversely, overexpression of Gal-3 in BMSCs enhanced the effects of osteoclastogenesis and bone resorption by increasing the expression of RANKL mRNA. These results demonstrated that Gal-3 mediates the differentiation and bone resorption of osteoclasts regulated by 1α,25(OH)2D3.

Pyrotinib in the Treatment of Women With HER2-Positive Advanced Breast Cancer: A Multicenter, Prospective, Real-World Study.

BACKGROUND: HER2-positive breast cancer was aggressive, resulting in a poorer prognosis. This multicenter study analyzed the real-world data of women treated with pyrotinib-based therapy, aiming to describe their characteristics, treatment regimens, and to investigate the clinical outcomes. METHODS: A total of 141 patients with HER2-positive breast cancer were enrolled from February 2019 to April 2020. Last follow-up time was February 2021. All patients were treated with pyrotinib-based therapy in 21-day cycles. The primary endpoint was progression-free survival (PFS). RESULTS: The median PFS (mPFS) for pyrotinib-based therapy was 12.0 months (95%CI 8.1-17.8) in all patients. Among the patients with liver metastases, mPFS was 8.7 months (95%CI, 6.3-15.4) compared to 12.3 months (95%CI, 8.8-23.3) for patients without liver metastases (P=0.172). In addition, patients receiving pyrotinib-based therapy as their >2 lines treatment had a numerically lower mPFS than those receiving pyrotinib-based therapy as their ≤2 lines treatment [8.4 (95%CI, 5.9-15.4) vs. 15.1 (95%CI, 9.3-22.9) months, P=0.107]. The mPFS was 12.2 months (95%CI, 7.9-18.8) in patients with previous exposure to trastuzumab and 11.8 months (95%CI, 6.8-22.9) in patients without previous exposure to trastuzumab (P=0.732). Moreover, mPFS in patients receiving regimens with and without capecitabine were 15.1 months (95%CI, 10.0-18.8) and 8.4 months (95%CI, 6.7-22.9), respectively (P=0.070). Furthermore, in patients with brain metastases, estimated 6-month PFS rate was 70.0%, and rate at 12 months was 60.0%. Seventy patients with measurable lesions were evaluable for response. The objective response rate was 38.6% and disease control rate was 85.7%. The most common adverse event was diarrhea (85.0%). CONCLUSION: Pyrotinib-based therapy showed promising efficacy in patients with HER2-positive breast cancer and was well tolerated, especially in patients treated with pyrotinib as ≤2 lines treatment and receiving regimens with capecitabine. The results of this real-world study further confirmed the intriguing efficacy of pyrotinib.

Predictors for Fear of Cancer Recurrence in Breast Cancer Patients Referred to Radiation Therapy During the COVID-19 Pandemic: A Multi-Center Cross-Section Survey.

OBJECTIVE: The outbreak of COVID-19 pandemic has greatly impacted on radiotherapy (RT) strategy for breast cancer patients, which might lead to increased distressing psychological symptoms. We performed a multi-center cross-section survey to investigate prevalence of fear of cancer recurrence (FCR) and predictors for FCR in patients referred to RT during pandemic. METHODS: 542 patients were consecutively enrolled from three regions in China including Yangtze Delta River Region, Guangdong and Shanxi province. Patients' characteristics were collected using an information sheet, Fear of progression questionnaire-short form, Hospital Anxiety/Depression Scale and EORTC QLQ-C30. The hierarchical multiple regression models were performed. RESULTS: 488 patients with complete data were eligible. The RT strategy was affected in 265 (54.3%) patients, including 143 with delayed RT initiation, 66 believing to have delayed RT initiation but actually not, 24 with RT interruptions, 19 shifting to local hospitals for RT and the remaining 13 influenced on both RT schedule and hospital level. The model explained 59.7% of observed variances in FCR (p<0.001) and showed that influence of RT strategy had significantly impacted on FCR (△R2 = 0.01, △F=2.966, p=0.019). Hospitals in Shanxi province (ß=-0.117, p=0.001), emotional function (ß=-0.19, p<0.001), social function (ß=-0.111, p=0.006), anxiety (ß=0.434, p<0.001) and RT interruption (ß=0.071, p=0.035) were independent predictors. CONCLUSIONS: RT strategy for breast cancer patients was greatly influenced during pandemic. RT interruption is an independent predictor for high FCR. Our findings emphasize the necessity to ensure continuum of RT, and efforts should be taken to alleviate FCR through psychological interventions.