Development and Validation of Deep Learning Model for Intermediate-Stage Hepatocellular Carcinoma Survival with Transarterial Chemoembolization (MC-hccAI 002): a Retrospective, Multicenter, Cohort Study.

Background: There are few effective prediction models for intermediate-stage hepatocellular carcinoma (IM-HCC) patients treated with transarterial chemoembolization (TACE) to predict overall survival (OS) is available. The learning survival neural network (DeepSurv) was developed to showed a better performance than cox proportional hazards model in prediction of OS. This study aimed to develop a deep learning-based prediction model to predict individual OS. Methods: This multicenter, retrospective, cohort study examined data from the electronic medical record system of four hospitals in China between January 1, 2007, to December 31, 2016. Patients were divided into a training set(n=1075) and a test set(n=269) at a ratio of 8:2 to develop a deep learning-based algorithm (deepHAP IV). The deepHAP IV model was externally validated on an independent cohort(n=414) from the other three centers. The concordance index, the area under the receiver operator characteristic curves, and the calibration curve were used to assess the performance of the models. Results: The deepHAP IV model had a c-index of 0.74, whereas AUROC for predicting survival outcomes of 1-, 3-, and 5-year reached 0.80, 0.76, and 0.74 in the training set. Calibration graphs showed good consistency between the actual and predicted OS in the training set and the validation cohort. Compared to the other five Cox proportional-hazards models, the model this study conducted had a better performance. Patients were finally classified into three groups by X-tile plots with predicted 3-year OS rate (low: ≤ 0.11; middle: > 0.11 and ≤ 0.35; high: >0.35). Conclusion: The deepHAP IV model can effectively predict the OS of patients with IM-HCC, showing a better performance than previous Cox proportional hazards models.

Efficacy and safety of cadonilimab in previously treated recurrent or metastatic nasopharyngeal carcinoma(COMPASSION-06): A phase II multicenter study.

OBJECTIVE: This study was designed to assess the efficacy and safety of cadonilimab monotherapy, a first-in-class, bi-specific PD-1/CTLA-4 antibody, in patients with previously treated recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). PATIENTS AND METHODS: This multicenter, open-label, single-arm, phase II clinical trial enrolled patients with R/M-NPC who had failed first-line platinum-based chemotherapy and second-line single agent or combined chemotherapy, and immunotherapy-naive. Patients received cadonilimab for 6 mg/kg once every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) in full analysis set (FAS) assessed by investigators according to RECIST v.1.1. The secondary endpoint included progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to response (TTR) and safety. RESULTS: A total of 23 patients were assessed. The median time from first dose to data cutoff was 16.56 (range, 0.8-25.2) months. ORR was 26.1 % (95 %CI:10.2-48.4). The ORR were 44.4 % (95 %CI: 13.7-78.8) and 14.3 % (95 %CI:1.8-42.8) in patients with tumor PD-L1 expression ≥50 % and <50 %, respectively. ORR was achieved in 40.0 % (95 %CI:12.2-73.8) of patients with EBV-DNA level <4000 IU/ml (n = 10) and 15.4 % (95 %CI:1.9-45.4) of those with ≥4000 IU/ml. The median PFS was 3.71 months (95 %CI: 1.84-9.30). respectively. Median OS was not reached, and the 12-month OS rate was 79.7 % (95 % CI:54.5-91.9). Only two patients (8.3 %) experienced Grade ≥3 treatment-related adverse events (TRAEs) with hypothyroidism (30.4 %), rash (21.7 %) and pruritus (21.7 %) being the most prevalent TRAEs. CONCLUSION: Cadonilimab monotherapy demonstrated a promising efficacy and manageable toxicity in patients with previously treated R-M/NPC and provide an efficacious salvage treatment option.

Anoikis related genes may be novel markers associated with prognosis for ovarian cancer.

The aim of this study was to determine the prognostic significance of anoikis related genes (ARGs) in ovarian cancer (OC) and to develop a prognostic signature based on ARG expression. We analyzed cohorts of OC patients and used nonnegative matrix factorization (NMF) for clustering. Single-sample gene-set enrichment analysis (ssGSEA) was employed to quantify immune infiltration. Survival analyses were performed using the Kaplan-Meier method, and differences in survival were determined using the log-rank test. The extent of anoikis modification was quantified using a risk score generated from ARG expression. The analysis of single-cell sequencing data was performed by the Tumor Immune Single Cell Hub (TISCH). Our analyses revealed two distinct patterns of anoikis modification. The risk score was used to evaluate the anoikis modification patterns in individual tumors. Three hub-genes were screened using the LASSO (Least Absolute Shrinkage and Selection Operator) method and patients were classified into different risk groups based on their individual score and the median score. The low-risk subtype was characterized by decreased expression of hub-genes and better overall survival. The risk score, along with patient age and gender, were considered to identify the prognostic signature, which was visualized using a nomogram. Our findings suggest that ARGs may play a novel role in the prognosis of OC. Based on ARG expression, we have developed a prognostic signature for OC that can aid in patient stratification and treatment decision-making. Further studies are needed to validate these results and to explore the underlying mechanisms.

Design, Preclinical Evaluation, and Clinical Translation of 68Ga-FAPI-LM3, a Heterobivalent Molecule for PET Imaging of Nasopharyngeal Carcinoma.

Extensive research has been conducted on radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) and p-Cl-Phe-cyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH2 (LM3) peptides for imaging of FAP and somatostatin receptor 2 (SSTR2)-positive tumors. In this study, we designed and synthesized a FAPI-LM3 heterobivalent molecule radiolabeled with 68Ga and evaluated its effectiveness in both tumor xenografts and patients with nasopharyngeal carcinoma (NPC). Methods: The synthesis of FAPI-LM3 was based on the structures of FAPI-46 and LM3. After radiolabeling with 68Ga, its dual-receptor-binding affinity was evaluated in vitro and in vivo. Preclinical studies, including small-animal PET and biodistribution evaluation, were conducted on HT-1080-FAP and HT-1080-SSTR2 tumor xenografts. The feasibility of 68Ga-FAPI-LM3 PET/CT in a clinical setting was evaluated in patients with NPC, and the results were compared with those of 18F-FDG. Results: 68Ga-FAPI-LM3 showed high affinity for both FAP and SSTR2. The tumor uptake of 68Ga-FAPI-LM3 was significantly higher than that of 68Ga-FAPI-46 and 68Ga-DOTA-LM3 in HT-1080-FAP-plus-HT-1080-SSTR2 tumor xenografts. In a clinical study involving 6 NPC patients, 68Ga-FAPI-LM3 PET/CT showed significantly higher uptake than did 18F-FDG in primary and metastatic lesions, leading to enhanced lesion detectability and tumor delineation. Conclusion: 68Ga-FAPI-LM3 exhibited FAPI and SSTR2 dual-receptor-targeting properties both in vitro and in vivo, resulting in improved tumor uptake and retention compared with that observed with monomeric 68Ga-FAPI and 68Ga-DOTA-LM3. This study highlights the clinical feasibility of 68Ga-FAPI-LM3 PET/CT for NPC imaging.

A Pilot Study of Anlotinib as a Combination Treatment in Advanced Nasopharyngeal Carcinoma.

AIMS: To investigate the short-term objective response and treatment toxicity of anlotinib as a combination treatment in patients with Recurrent or Metastatic Nasopharyngeal Carcinoma (RM-NPC). METHODS: Patients with RM-NPC who received anlotinib as a combination treatment between March 2021 and July 2022 were retrospectively analyzed.The efficacy and safety of anlotinib as a combination treatment were analyzed. RESULTS: A total of 17 patients with RM-NPC were included in this study. Of these patients, 2 (11.8%) had local recurrence, 4 (23.5%) had cervical lymph node recurrence, and 11 (64.9%) had distant failure. The most common metastatic site was the liver (47.1%), followed by the lung (23.5%) and bone (23.5%). Anlotinib was given as first-line treatment in 3 patients (17.6%), second lines treatment in 7 patients (41.2%), and third to six-lines treatment in 7 patients (41.2%). All patients received anlotinib combined with chemotherapy and/or immunotherapy. One patient achieved a complete response (5.9%), 7 patients had a partial response (41.2%), 5 patients had stable disease (29.4%), and 4 patients had progressive disease (23.5%). The overall disease control rate and the overall response rate were 76.5% and 47.1%, respectively. The median progression-free survival was 8.1 months, and the median overall survival was not reached. The incidence of grade 3 adverse events was 30%. No unexpected side effects or treatment-related death were observed. CONCLUSION: Anlotinib, as a combination treatment, has a promising antitumor activity and a manageable safety profile in patients with RM-NPC. Our results add to the growing evidence that supports the benefits of combining antiangiogenic drugs in RM-NPC. Randomized controlled clinical trials investigating the evaluation of anlotinib are warranted.

Decision-making experiences related to mastectomy: A descriptive qualitative study.

AIM: To obtain an in-depth understanding of women's decision-making experiences related to mastectomy. DESIGN: A descriptive qualitative interview study. METHODS: Individual semi-structured interviews were conducted face-to-face with 27 Chinese women with breast cancer who underwent mastectomy at two tertiary hospitals in mainland China between September 2020 and December 2021 after obtaining the appropriate ethical approvals. Interviews were conducted in Mandarin. Data were analysed using inductive content analysis. RESULTS: Mean age of participants was 48 years (range 31-70). Most participants had low education, low monthly family income, had a partner and health insurance, had been diagnosed with early breast cancer, and had not undergone reconstructive surgery. Six categories related to decision-making experiences emerged: (1) Emotions affecting decision-making, (2) Information seeking for decision-making, (3) Beliefs about mastectomy and the breast, (4) Participation in decision-making, (5) People who influence decision-making, and (6) Post-decision reflection. Participants did not mention the role of nurses in their decision-making process for mastectomy. CONCLUSIONS: This study adds valuable insights into the limited evidence on women's experience with decision-making about mastectomy from a Chinese perspective, which is important given the continuing high prevalence of mastectomy in many regions. Future studies from other countries and ethnic groups are recommended to gain diverse knowledge. IMPACT: The findings of this study are useful for nurses and other healthcare professionals in the multidisciplinary team to better support women with breast cancer in their decision-making process regarding mastectomy. The findings could inform future interventions to support treatment decision-making and may be relevant to women living in similar socio-medical contexts to those in mainland China. REPORTING METHOD: The study was reported following the Standards for Reporting Qualitative Research checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Kcnh2 deletion is associated with rat embryonic development defects via destruction of KCNH2­integrin ß1 complex.

The Kv11.1 potassium channel encoded by the Kcnh2 gene is crucial in conducting the rapid delayed rectifier K+ current in cardiomyocytes. Homozygous mutation in Kcnh2 is embryonically lethal in humans and mice. However, the molecular signaling pathway of intrauterine fetal loss is unclear. The present study generated a Kcnh2 knockout rat based on edited rat embryonic stem cells (rESCs). Kcnh2 knockout was embryonic lethal on day 11.5 of development due to a heart configuration defect. Experiments with human embryonic heart single cells (6.5­7 weeks post­conception) suggested that potassium voltage­gated channel subfamily H member 2 (KCNH2) plays a crucial role in the development of compact cardiomyocytes. By contrast, apoptosis was found to be triggered in the homozygous embryos, which could be attributed to the failure of KCNH2 to form a complex with integrin ß1 that was essential for preventing the process of apoptosis via inhibition of forkhead box O3A. Destruction of the KCNH2/integrin ß1 complex reduced the phosphorylation level of AKT and deactivated the glycogen synthase kinase 3 ß (GSK­3ß)/ß­catenin pathway, which caused early developmental abnormalities in rats. The present work reveals a basic mechanism by which KCNH2 maintains intact embryonic heart development.

Residual plasma Epstein-Barr virus DNA after intensity-modulated radiation therapy is associated with poor outcomes in nasopharyngeal carcinoma.

Aim: To investigate the effects of residual plasma Epstein-Barr virus (EBV) DNA levels after 3 months of intensity-modulated radiation therapy (IMRT) (postIMRT-EBV DNA) on prognosis in patients with nasopharyngeal carcinoma. Methods: Data from 300 patients were retrospectively collected for analysis. Results: Of these patients, 25 (8.3%) and 275 (91.7%) had positive and negative postIMRT-EBV DNA, respectively. Multivariate survival analysis showed that EBV DNA >688 IU/ml was independently associated with inferior distant metastasis-free survival (p = 0.003) and progression-free survival (p = 0.002). Moreover, postIMRT-EBV DNA was independently associated with inferior locoregional recurrence-free survival (hazard ratio: 4.325; p = 0.018), distant metastasis-free survival (hazard ratio: 10.226; p < 0.001) and progression-free survival (hazard ratio: 10.520; p < 0.001). Conclusion: Positive postIMRT-EBV DNA is a prognostic biomarker for nasopharyngeal carcinoma.

Readjustment of nodal staging by integrating tumor deposits and positive lymph nodes in patients with stage III colon cancer: a population-based analysis.

Whether tumor deposits (TDs) should be classified as lymph node metastasis or distant metastasis remains controversial. To address this predicament, we conducted this study to identify the predictive value of TDs on the survival of patients diagnosed with stage III colon cancer (CC). 12,904 eligible patients diagnosed with stage III CC between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The best cutoff point of TD quantity was determined based on the difference in survival. Cox proportional hazards model was employed to perform univariate and multivariate analyses. The Kaplan-Meier method and log-rank test were performed to calculate the differences between overall survival (OS). Our results showed that the number of TDs was a significant prognostic factor in patients with stage III CC (P < 0.0001). We added the number of TDs to the pN stage and devised a new pN stage, there were no significant differences in the survival of npN, except npN2a (P > 0.05). Upon re-staging to the same npN stage, the difference in survival between TDs+ and TDs- disappeared (P > 0.05). The median survival times for N2aTDs > 4 and N2bTDs > 4 were 33 and 37 months, respectively, which were significantly shorter than that of N2TDs- (65 months) and represented the worst survival rates among all groups. In conclusion, the number of TDs indicated a poor prognosis for patients with stage III CC. Incorporating TDs into the pN is feasible to predict prognosis.

A machine learning-based PET/CT model for automatic diagnosis of early-stage lung cancer.

Objective: The aim of this study was to develop a machine learning-based automatic analysis method for the diagnosis of early-stage lung cancer based on positron emission tomography/computed tomography (PET/CT) data. Methods: A retrospective cohort study was conducted using PET/CT data from 187 cases of non-small cell lung cancer (NSCLC) and 190 benign pulmonary nodules. Twelve PET and CT features were used to train a diagnosis model. The performance of the machine learning-based PET/CT model was tested and validated in two separate cohorts comprising 462 and 229 cases, respectively. Results: The standardized uptake value (SUV) was identified as an important biochemical factor for the early stage of lung cancer in this model. The PET/CT diagnosis model had a sensitivity and area under the curve (AUC) of 86.5% and 0.89, respectively. The testing group comprising 462 cases showed a sensitivity and AUC of 85.7% and 0.87, respectively, while the validation group comprising 229 cases showed a sensitivity and AUC of 88.4% and 0.91, respectively. Additionally, the proposed model improved the clinical discrimination ability for solid pulmonary nodules (SPNs) in the early stage significantly. Conclusion: The feature data collected from PET/CT scans can be analyzed automatically using machine learning techniques. The results of this study demonstrated that the proposed model can significantly improve the accuracy and positive predictive value (PPV) of SPNs at the early stage. Furthermore, this algorithm can be optimized into a robotic and less biased PET/CT automatic diagnosis system.

Surgical management of broad-based sessile vocal cord polyps: Transnasal vocal fold polypectomy versus microlaryngoscopic surgery: Our experience in 159 cases.

OBJECTIVES: In this study, we retrospectively reviewed and compared the treatment outcomes and complications of office transnasal vocal fold polypectomy (TVFP) with those of microplarygoscopic surgery (MLS) for different clinical and histopathological features of broad-based sessile vocal fold polyps. METHODS: We retrospectively reviewed the records of 159 consecutive patients with broad-based sessile vocal fold polyps treated by TVFP or MLS. The differences in efficacy and complication between these two surgical techniques were compared according to the different types of vocal fold polyps. RESULTS: Satisfactory outcomes of both TVFP and MLS treatments were reported in patients with oedematous, gelatinous and vascular types of vocal fold polyps (p > .05). The efficacy of TVFP was slightly worse than MLS in fibrous polyps group (p < .05). The TVFP-treated patients did not exhibit obvious complications, whereas several MLS-treated patients had suffered different complications. CONCLUSION: The therapeutic effects of both TVFP and MLS on the treatment of broad-based sessile vocal cord polyps are related to their clinical characteristics and histological types. Satisfactory outcomes are achieved in oedematous, gelatinous, and vascular types of polyps after either surgical procedure. TVFP has fewer surgical complications than MLS which can be a preferred option for the treatment of broad-based sessile vocal cord polyps at outpatient setting. TVFP also can be an alternative surgery option for patients who could not tolerate general anaesthesia or laryngeal suspension. In contrast, MLS has proven to be a particularly advantageous treatment in patients who have fibrous type of polyps.

Risk factors of early thyroid dysfunction after definitive radiotherapy in nasopharyngeal carcinoma patients.

BACKGROUND: To explore the patterns and risk factors of early thyroid dysfunction in nasopharyngeal carcinoma (NPC) patients within 1 year after intensity-modulated radiation therapy (IMRT). METHODS: Patients with NPC who received definitive IMRT between April 2016 and April 2020 were included. All patients had normal thyroid function before definitive IMRT. The chi-square test, Student's T-test, Mann-Whitney U test, Kaplan-Meier method, receiver operating characteristics curve, and Cox proportional hazard analysis were used for statistical analysis. RESULTS: A total of 132 NPC patients were identified. Of these patients, 56 (42.4%) had hypothyroidism and 17 (12.9%) had hyperthyroidism. The median time to hypothyroidism and hyperthyroidism was 9 months (range, 1-12 months) and 1 month (range, 1-6 months) after definitive IMRT, respectively. In patients with hypothyroidism, 41 (73.2%) had subclinical hypothyroidism and 15 (26.8%) had clinical hypothyroidism. In those with hyperthyroidism, 12 patients (70.6%) had subclinical hyperthyroidism, and five patients (29.4%) had clinical hyperthyroidism. Age, clinical stage, thyroid volume, and V45 were independent risk factors for early radiation-induced hypothyroidism within 1 year after IMRT. Patients aged <47 years, stage III/IV disease, or pre-irradiation thyroid volume < 14 cm3 had higher risks of developing hypothyroidism. CONCLUSION: Primary subclinical hypothyroidism was the most common subtype of early thyroid dysfunction in NPC patients within 1 year after IMRT. Age, clinical stage, thyroid volume, and V45 were independent risk factors for early radiation-induced hypothyroidism in NPC patients.

Spatio-temporal distribution of organochlorine pesticides in agricultural soils of southeast China during 2014-2019.

Organochlorine pesticides (OCPs) are organic pollutants that are persistent and undegradable in the environment. To investigate their residual concentrations, spatial and temporal distributions, and the relationship with the crops planted, 12 individual OCPs in 687 soil samples from Jiangsu, Zhejiang and Jiangxi provinces of southeast China were examined. The detection frequencies of OCPs in the studied areas were 1.89%-64.9%. The concentrations of dichloro-diphenyl-trichloroethanes (DDTs), hexachlorocyclohexanes (HCHs), and endosulfans ranged from 0.01 to 5659 µg/kg, 0.03-3.58 µg/kg, and 0.05-3235 µg/kg, respectively. Jiangsu was mainly contaminated by p,p'-DDT, p,p'-DDD and endosulfan sulfate, Zhejiang was more polluted by OCPs except δ-HCH, and Jiangxi was more vulnerable to the contamination of OCPs except o,p'-DDE. The partial least-squares discrimination analysis (PLS-DA) model with RX2 36.3-36.8% revealed that compounds with similar chemical properties tended to appear in the same year and month. All crop lands were polluted by DDTs and Endosulfans. The highest concentrations of DDTs and Endosulfans were found in citrus and vegetable fields, respectively. This study offers new insight into the layout and partitioning of OCPs in agricultural land and into insecticide management on public health and ecological safety.

Development of FAPI Tetramers to Improve Tumor Uptake and Efficacy of FAPI Radioligand Therapy.

Radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) have shown promise as cancer diagnostic agents; however, the relatively short tumor retention of FAPIs may limit their application in radioligand therapy. In this paper, we report the design, synthesis, and evaluation of a FAPI tetramer. The aim of the study was to evaluate the tumor-targeting characteristics of radiolabeled FAPI multimers in vitro and in vivo, thereby providing information for the design of FAP-targeted radiopharmaceuticals based on the polyvalency principle. Methods: FAPI tetramers were synthesized on the basis of FAPI-46 and radiolabeled with 68Ga, 64Cu, and 177Lu. In vitro FAP-binding characteristics were identified using a competitive cell-binding experiment. To evaluate their pharmacokinetics, small-animal PET, SPECT, and ex vivo biodistribution analyses were performed on HT-1080-FAP and U87MG tumor-bearing mice. In addition, the 2 tumor xenografts received radioligand therapy with 177Lu-DOTA-4P(FAPI)4, and the antitumor efficacy of the 177Lu-FAPI tetramer was evaluated and compared with that of the 177Lu-FAPI dimer and monomer. Results: 68Ga-DOTA-4P(FAPI)4 and 177Lu-DOTA-4P(FAPI)4 were highly stable in phosphate-buffered saline and fetal bovine serum. The FAPI tetramer exhibited high FAP-binding affinity and specificity both in vitro and in vivo. 68Ga-, 64Cu-, and 177Lu-labeled FAPI tetramers exhibited higher tumor uptake, longer tumor retention, and slower clearance than FAPI dimers and FAPI-46 in HT-1080-FAP tumors. The uptake (percentage injected dose per gram) of 177Lu-DOTA-4P(FAPI)4, 177Lu-DOTA-2P(FAPI)2, and 177Lu-FAPI-46 in HT-1080-FAP tumors at 24 h was 21.4 ± 1.7, 17.1 ± 3.9, and 3.4 ± 0.7, respectively. Moreover, 68Ga-DOTA-4P(FAPI)4 uptake in U87MG tumors was approximately 2-fold the uptake of 68Ga-DOTA-2P(FAPI)2 (SUVmean, 0.72 ± 0.02 vs. 0.42 ± 0.03, P < 0.001) and more than 4-fold the uptake of 68Ga-FAPI-46 (0.16 ± 0.01, P < 0.001). In the radioligand therapy study, remarkable tumor suppression was observed with the 177Lu-FAPI tetramer in both HT-1080-FAP and U87MG tumor-bearing mice. Conclusion: The satisfactory FAP-binding affinity and specificity, as well as the favorable in vivo pharmacokinetics of the FAPI tetramer, make it a promising radiopharmaceutical for theranostic applications. Improved tumor uptake and prolonged retention of the 177Lu-FAPI tetramer resulted in excellent characteristics for FAPI imaging and radioligand therapy.

The aMAP Score is an Independent Risk Factor for Intermediate-stage Hepatocellular Carcinoma: A Large Retrospective Cohort Study.

Background: A less effective nomogram for patients with intermediate-stage hepatocellular carcinoma (HCC) to predict overall survival (OS) is available. This study aimed to investigate the role of age-male-albumin-bilirubin-platelet (aMAP) scores in the prognosis of patients with intermediate-stage HCC and develop an aMAP score-based nomogram to predict OS. Methods: Data on newly diagnosed intermediate-stage patients with HCC at Sun Yat-sen University Cancer Center between January 2007 and May 2012 were retrospectively collected. Independent risk factors affecting prognosis were selected by multivariate analyses. The optimal cut-off value for the aMAP score was determined using X-tile. The survival prognostic models were presented by the nomogram. Results: For the 875 patients with intermediate-stage HCC included, the median OS was 22.2 months (95% CI 19.6-25.1). Patients were classified into three groups by X-tile plots (aMAP score < 49.42; 49.42 ≤ aMAP score < 56; aMAP score ≥ 56). Alpha-fetoprotein, lactate dehydrogenase, aMAP score, diameter of main tumor, number of intrahepatic lesions, and treatment regimen were independent risk factors for prognosis. A predicted model was constructed with a C-index of 0.70 (95% CI: 0.68-0.72) in the training goup, and its 1-, 3-, and 5-year area under the receiver operating curve were: 0.75, 0.73, and 0.72. The validation group of the C-index is 0.82. Calibration graphs showed good consistency between the actual and predicted survival rates. The decision curve analysis suggested the clinical utility of the model, which may help clinicians guide clinical decision-making. Conclusion: The aMAP score was an independent risk factor for intermediate-stage HCC. The aMAP score-based nomogram has good discrimination, calibration, and clinical utility.

Mafosfamide Boosts GMI-HBVac against HBV via Treg Depletion in HBV-Infected Mice.

Chronic hepatitis B infection remains a significant worldwide health burden, placing persons at risk for hepatocellular cancer and hepatic fibrosis. Chronic hepatitis B virus (CHB) infection is characterized by elevated levels of immunosuppressive regulatory T cells (Tregs), which can inhibit the function of effector T cells and lead to an insufficient immune clearance response against HBV. Theoretically, suppression of Treg cell functionality and percentage could increase anti-HBV reactivity in CHB-infected patients, although this has not yet been explored. We attempted to enhance our previously established anti-CHB protocol utilizing the GM-CSF+IFN-α+rHBVvac regimen (GMI-HBVac) by incorporating mafosfamide (MAF), which has been utilized in anticancer therapy in the past. Intravenous administration of MAF to rAAV8-1.3HBV-infected mice resulted in a dose-dependent reduction of Tregs in the blood, rebounding to pretreatment levels 10 days later. To assess the potential benefit of adding MAF to the anti-CHB protocol, 2 µg/mL MAF was combined with the GMI-HBVac as an anti-Treg treatment in an HBV-infected animal model. When rAAV8-1.3HBV-infected mice were immunized with MAF+GMI-HBVac, peripheral blood Tregs decreased significantly, leading to dendritic cell activation, HBV-specific T cell proliferation, and the upregulation of IFN-gamma-producing CD8+T cells. In addition, MAF+GMI-HBVac vaccination stimulated T cell infiltration in HBV-infected livers. These effects may contribute to an enhanced immune response and the clearance of HBV-associated antigens, including serum HBsAg, serum HBcAg, and HBcAg+ hepatocytes. Overall, this is the first indication that MAF can act as an adjuvant with GMI-HBVac to deplete Tregs in mice with an established CHB infection. This unique therapeutic vaccine regimen produced a functional cure, as revealed by the remarkable clearance of HBsAg.

Decisional Conflict, Patient Involvement, and the Associated Psychological Factors Relating to Mastectomy Decisions Among Women With Breast Cancer: A Cross-sectional Study.

BACKGROUND: Most women with breast cancer in China have received a mastectomy despite emerging breast-conserving alternatives. Their decision-making relating to mastectomy is unclear. OBJECTIVE: To investigate decisional conflict, women's involvement, and psychological factors relating to mastectomy decisions. METHODS: Women with breast cancer 18 years and older who had a mastectomy were recruited from 2 hospitals in China. A conceptual framework adapted from the Ottawa Decisional Support Framework was used to guide this study. Data were collected using the 16-item Decisional Conflict Scale, the 9-item Shared Decision-Making Questionnaire, and a 19-item psychological factor list. RESULTS: A total of 304 women participated. Overall, they reported a low-level conflict and high-level involvement. "Cancer not return" was rated as the most important psychological factor influencing mastectomy decisions. Lower decisional conflict was predicted by higher involvement. Higher involvement was predicted by younger age and increased family income. CONCLUSIONS: This study is the first to demonstrate decisional conflict, involvement, and the associated factors specifically in Chinese women undergoing mastectomy. Results determined the importance of several psychological factors influencing mastectomy decisions. Future qualitative studies are required to deepen understanding of women's decision-making experiences regarding this surgery. IMPLICATIONS FOR PRACTICE: Nurses need to provide support to Chinese women in making treatment decisions, especially for older women, and those who are economically disadvantaged. Measures are needed to promote their involvement and improve their understanding of breast cancer and its treatments, which may help reduce decisional conflict, and potentially improve their satisfaction with treatment and quality of life.

A deep learning MRI-based signature may provide risk-stratification strategies for nasopharyngeal carcinoma.

OBJECTIVE: As the prognosis of nasopharyngeal carcinoma (NPC) is influenced by various factors, making it difficult for clinical physicians to predict the outcome, the objective of this study was to develop a deep learning-based signature for risk stratification in NPC patients. METHODS: A total of 293 patients were enrolled in the study and divided into training, validation, and testing groups with a ratio of 7:1:2. MRI scans and corresponding clinical information were collected, and the 3-year disease-free survival (DFS) was chosen as the endpoint. The Res-Net18 algorithm was used to develop two deep learning (DL) models and another solely based on clinical characteristics developed by multivariate cox analysis. The performance of both models was evaluated using the area under the curve (AUC) and the concordance index (C-index). Discriminative performance was assessed using Kaplan-Meier survival analysis. RESULTS: The deep learning approach identified DL prognostic models. The MRI-based DL model showed significantly better performance compared to the traditional model solely based on clinical characteristics (AUC: 0.8861 vs 0.745, p = 0.04 and C-index: 0.865 vs 0.727, p = 0.03). The survival analysis showed significant survival differences between the risk groups identified by the MRI-based model. CONCLUSION: Our study highlights the potential of MRI in predicting the prognosis of NPC through DL algorithm. This approach has the potential to become a novel tool for prognosis prediction and can help physicians to develop more valid treatment strategies in the future.

Clinical Evaluation of 68Ga-FAPI-RGD for Imaging of Fibroblast Activation Protein and Integrin αvß3 in Various Cancer Types.

Radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) and Arg-Gly-Asp (RGD) peptides have been extensively investigated for imaging of FAP- and integrin αvß3-positive tumors. In this study, a FAPI-RGD heterodimer was radiolabeled with 68Ga and evaluated in patients with cancer. We hypothesized that the heterodimer, recognizing both FAP and integrin αvß3, would be advantageous because of its dual-receptor-targeting property. Methods: The effective dose of 68Ga-FAPI-RGD was evaluated in 3 healthy volunteers. The clinical feasibility of 68Ga-FAPI-RGD PET/CT was evaluated in 22 patients with various types of cancer, and the results were compared with those of 18F-FDG and 68Ga-FAPI-46. Results: 68Ga-FAPI-RGD was tolerated well, with no adverse events in any of the healthy volunteers or patients. The effective dose from 68Ga-FAPI-RGD PET/CT was 1.01 × 10-2 mSv/MBq. In clinical investigations with different types of cancer, the radiotracer uptake and tumor-to-background ratio (TBR) of primary and metastatic lesions in 68Ga-FAPI-RGD PET/CT were significantly higher than those in 18F-FDG PET/CT (primary tumors: SUVmax, 18.0 vs. 9.1 [P < 0.001], and TBR, 15.2 vs. 5.5 [P < 0.001]; lymph node metastases: SUVmax, 12.1 vs. 6.1 [P < 0.001], and TBR, 13.3 vs. 4.1 [P < 0.001]), resulting in an improved lesion detection rate and tumor delineation, particularly for the diagnosis of lymph node (99% vs. 91%) and bone (100% vs. 80%) metastases. 68Ga-FAPI-RGD PET/CT also yielded a higher radiotracer uptake and TBR than 68Ga-FAPI-46 PET/CT did. Conclusion: 68Ga-FAPI-RGD exhibited improved tumor uptake and TBR compared with 18F-FDG and 68Ga-FAPI PET/CT. This study demonstrated the safety and clinical feasibility of 68Ga-FAPI-RGD PET/CT for imaging of various types of cancer.

The emerging nanomedicine-based technology for non-small cell lung cancer immunotherapy: how far are we from an effective treatment.

Non-small cell lung cancer (NSCLC) is a prominent etiology of cancer-related mortality. The heterogeneous nature of this disease impedes its accurate diagnosis and efficacious treatment. Consequently, constant advancements in research are imperative in order to comprehend its intricate nature. In addition to currently available therapies, the utilization of nanotechnology presents an opportunity to enhance the clinical outcomes of NSCLC patients. Notably, the burgeoning knowledge of the interaction between the immune system and cancer itself paves the way for developing novel, emerging immunotherapies for treating NSCLC in the early stages of the disease. It is believed that with the novel engineering avenues of nanomedicine, there is a possibility to overcome the inherent limitations derived from conventional and emerging treatments, such as off-site drug cytotoxicity, drug resistance, and administration methods. Combining nanotechnology with the convergence points of current therapies could open up new avenues for meeting the unmet needs of NSCLC treatment.