Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor of the digestive system worldwide, especially in China. Due to the lack of effective early detection methods, ESCC patients often ...present at an advanced stage at the time of diagnosis, which seriously affects the prognosis of patients. At present, early detection of ESCC mainly depends on invasive and expensive endoscopy and histopathological biopsy. Therefore, there is an unmet need for a non-invasive method to detect ESCC in the early stages. With the emergence of a large class of non-invasive diagnostic tools, serum tumor markers have attracted much attention because of their potential for detection of early tumors. Therefore, the identification of serum tumor markers for early detection of ESCC is undoubtedly one of the most effective ways to achieve early diagnosis and treatment of ESCC. This article reviews the recent advances in the discovery of blood-based ESCC biomarkers, and discusses the origins, clinical applications, and technical challenges of clinical validation of various types of biomarkers.
Background
The BYLieve trial (NCT03056755) confirmed efficacy and safety of alpelisib with fulvestrant for hormone receptor–positive (HR+), human epidermal growth factor receptor‐2–negative (HER2−), ...PIK3CA‐mutated advanced breast cancer (ABC), after cyclin‐dependent kinase 4/6 inhibitor (CDK4/6i) with an aromatase inhibitor (AI) as immediate prior therapy. Further analyses were performed to compare efficacy from BYLieve with effectiveness of standard treatment in the real‐world setting.
Materials and Methods
Patients who progressed on a CDK4/6i plus AI and were treated with alpelisib with fulvestrant in BYLieve were matched with a real‐world patient cohort who received standard‐of‐care from a deidentified clinico‐genomics database (CGDB). Primary and secondary endpoints were to compare progression‐free survival (PFS), estimated by the Kaplan‐Meier method, and the proportion of patients remaining progression‐free at 6 months, respectively, between the two cohorts.
Results
A total of 855 patients with PIK3CA‐mutant disease who had prior CDK4/6i plus hormone therapy were selected from the CGDB; further matching to 120 patients from BYLieve selected 95 patients without exposure to HER2‐targeting agents, clinical study drug, or alpelisib. In unadjusted and postmatching results, primary and secondary endpoints favored treatment with alpelisib with fulvestrant in BYLieve more than standard treatments in the real‐world cohort. Postadjustment, median PFS for patients treated with alpelisib in BYLieve was 7.3 versus 3.7 months in the real‐world cohort, and 6‐month PFS was 54.6% versus 40.1%, respectively.
Conclusion
Matched/weighted analysis comparing BYLieve with the real‐world setting further supports the clinical benefit of alpelisib with fulvestrant for treatment of HR+, HER2−, PIK3CA‐mutant ABC after CDK4/6i treatment.
Implications for Practice
Approximately 40% of patients with hormone receptor–positive (HR+), human epidermal growth factor receptor‐2–negative (HER2−) advanced breast cancer (ABC) have PIK3CA‐mutated tumors, which have been associated with endocrine therapy resistance. Alpelisib, an α‐selective phosphatidylinositol‐3‐kinase inhibitor, demonstrated significantly improved progression‐free survival in SOLAR‐1 and demonstrated clinical efficacy in BYLieve when combined with fulvestrant. Data are limited in comparing the efficacy of alpelisib combined with fulvestrant with effectiveness of standard therapy after CDK4/6i treatment. Using real‐world data, this is the first analysis comparing alpelisib combined with fulvestrant with standard treatments for HR+, HER2−, PIK3CA‐mutant ABC in the post‐CDK4/6i setting.
This article reports the efficacy of treatment with alpelisib combined with fulvestrant in a cohort of patients with PIK3CA‐mutated breast cancer compared with the effectiveness of real‐world standard treatments in the post‐CDK4/6i setting using data from a deidentified clinico‐genomics database (CGDB).
Despite their successful use in many conscientious studies involving outdoor learning applications, mobile learning systems still have certain limitations. For instance, because students cannot ...obtain real-time, contextaware content in outdoor locations such as historical sites, endangered animal habitats, and geological landscapes, they are unable to search, collect, share, and edit information by using information technology. To address such concerns, this work proposes an environment of ubiquitous learning with educational resources (EULER) based on radio frequency identification (RFID), augmented reality (AR), the Internet, ubiquitous computing, embedded systems, and database technologies. EULER helps teachers deliver lessons on site and cultivate student competency in adopting information technology to improve learning. To evaluate its effectiveness, we used the proposed EULER for natural science learning at the Guandu Nature Park in Taiwan. The participants were elementary school teachers and students. The analytical results revealed that the proposed EULER improves student learning. Moreover, the largely positive feedback from a post-study survey confirms the effectiveness of EULER in supporting outdoor learning and its ability to attract the interest of students.
Background
The research landscape examining social cognition (SC) impairment in patients with major depressive disorders (MDD) and bipolar disorders (BD) is notably scarce. Presently, assessments ...predominantly rely on static stimuli and self‐reported measures, which may not capture the dynamic dimensions of social cognition.
Objectives
This study aimed to validate the Chinese version of Movie Assessment of Social Cognition (MASC‐CH) and to investigate whether MDD and BD exhibit distinct patterns of SC impairments, shedding light on potential differences between these two mood disorders.
Methods
The study encompassed 197 participants, aged 18–65, distributed as follows: 21 BD, 20 MDD, and 156 healthy controls (HC). We focused on examining “cognitive” and “emotional” SC scores and “undermentalizing” and “overmentalizing” error patterns, with nonsocial inference as a control. Additional assessments included the Reading Mind in the Eyes Test (RMET) and the Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT). We also explored the association between depression severity (measured by the Hamilton Depressive Rating Scale, HDRS) and distinct SC dimensions between MDD and BD.
Results
The MASC‐CH exhibited strong validity and reliability for SC assessment. In group comparisons, BD participants scored significantly lower on MASC‐CH, while the MDD group scores were not significantly different from HC. Specifically, BD individuals had notably lower cognitive SC scores and made more undermentalizing and absence of mentalizing errors than MDD and HC. Additionally, a negative correlation between HDRS score and overmentalizing was observed in BD, not in the MDD.
Conclusions
The findings indicate that depression severity scores in BD were inversely related to MASC‐CH scores. In contrast, this relationship was not observed in the MDD group. These results underscore the importance of SC impairments as distinguishing characteristics of both BD and MDD. It provides valuable insights into the distinct social‐cognitive profiles of both mood disorders.
1. Patients with bipolar disorders exhibit impairment of social cognition 2. Patients with bipolar disorders displayed more errors with undermentalizing compared to patients with major depressive disorders
Our previous study showed that levels of circulating insulin-like growth factor binding protein-1 (IGFBP-1) has potential diagnostic value for early-stage upper gastrointestinal cancers. This study ...aimed to assess whether serum IGFBP-1 is a potential diagnostic and prognostic biomarker for CRC patients. IGFBP-1 mRNA expression profile data of peripheral blood in colorectal cancer (CRC) patients were downloaded and analyzed from Gene Expression Omnibus database. We detected serum IGFBP-1 in 138 CRC patients and 190 normal controls using enzyme-linked immunosorbent assay. Blood IGFBP-1 mRNA levels were higher in CRC patients than those in normal controls (P = 0.027). In addition, serum IGFBP-1 protein levels in the CRC group were significantly higher than those in normal control group (P < 0.0001). Serum IGFBP-1 demonstrated better diagnostic accuracy for all CRC and early-stage CRC, respectively, when compared with carcinoembryonic antigen (CEA), carbohydrate antigen19-9 (CA 19-9) or the combination of CEA and CA19-9. Furthermore, Cox multivariate analysis revealed that serum IGFBP-1 was an independent prognostic factor for OS (HR = 2.043, P = 0.045). Our study demonstrated that serum IGFBP-1 might be a potential biomarker for the diagnosis and prognosis of CRC. In addition, the nomogram might be helpful to predict the prognosis of CRC.
Insulin-like growth factor binding protein-3 (IGFBP3) has been reported to be related to the risk of some cancers. Here we focussed on serum IGFBP3 as a possible biomarker of diagnosis and prognosis ...for oesophageal squamous carcinoma (ESCC).
Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum IGFBP3 level in the training cohort including 136 ESCC patients and 119 normal controls and the validation cohort with 55 ESCC patients and 42 normal controls. The receiver operating characteristics curve (ROC) was used to assess the diagnosis value. Cox proportional hazards model was applied to select factors for survival nomogram construction.
Serum IGFBP3 levels were significantly lower in early-stage ESCC or ESCC patients than those in normal controls (p < .05). The specificity and sensitivity of serum IGFBP3 for the diagnosis of ESCC were 95.80% and 50.00%, respectively, with the area under the ROC curve (AUC) of 0.788 in the training cohort. Similar results were observed in the validation cohort (88.10%, 38.18%, and 0.710). Importantly, serum IGFBP3 could also differentiate early-stage ESCC from controls (95.80%, 52.54%, 0.777 and 88.10%, 36.36%, 0.695 in training and validation cohorts, respectively). Furthermore, Cox multivariate analysis revealed that serum IGFBP3 was an independent prognostic risk factor (HR = 2.599, p = .002). Lower serum IGFBP3 level was correlated with reduced overall survival (p < .05). Nomogram based on serum IGFBP3, TNM stage, and tumour size improved the prognostic prediction of ESCC with a concordance index of 0.715.
We demonstrated that serum IGFBP3 was a potential biomarker of diagnosis and prognosis for ESCC. Meanwhile, the nomogram might help predict the prognosis of ESCC.
Key Message
Serum IGFBP3 showed early diagnostic value in oesophageal squamous cell carcinoma with independent cohort validation. Moreover, serum IGFBP3 was identified as an independent prognostic risk factor, which was used to construct a nomogram with improved prognosis ability in oesophageal squamous cell carcinoma.
Oral tongue squamous cell carcinoma (OTSCC) is one of the most aggressive oral tumors. The aim of this study was to establish a nomogram to predict overall survival (OS) of TSCC patients after ...surgery. 169 TSCC patients who underwent surgical treatments in the Cancer Hospital of Shantou University Medical College were included. A nomogram based on Cox regression analysis results was established and internally validated using bootstrap resampling method. pTNM stage, age and total protein, immunoglobulin G, factor B and red blood cell count were identified as independent prognostic factors to create the nomogram. The Akaike Information Criterion and Bayesian Information Criterion of the nomogram were lower than those of pTNM stage, indicating a better goodness-of-fit of the nomogram for predicting OS. The bootstrap-corrected concordance index of nomogram was higher than that of pTNM stage (0.794 vs. 0.665, p = 0.0008). The nomogram also had a good calibration and improved overall net benefit. Based on the cutoff value obtained from the nomogram, the proposed high-risk group had poorer OS than low-risk group (p < 0.0001). The nomogram based on nutritional and immune-related indicators represents a promising tool for outcome prediction of surgical OTSCC.
To evaluate the risk of second cancer (SC) in long-term survivors of retinoblastoma (Rb) according to classification of germline mutation, based on family history of Rb and laterality.
We assembled a ...cohort of 1,852 1-year survivors of Rb (bilateral, n = 1,036; unilateral, n = 816). SCs were ascertained by medical records and self-reports and confirmed by pathology reports. Classification of RB1 germline mutation, inherited or de novo, was inferred by laterality of Rb and positive family history of Rb. Standardized incidence ratios and cumulative incidence for all SCs combined and for soft tissue sarcomas, bone cancers, and melanoma were calculated. The influence of host- and therapy-related risk factors for SC was assessed by Poisson regression for bilateral survivors.
We observed a relative risk (RR) of 1.37 (95% CI, 1.00 to 1.86) for SCs in bilateral survivors associated with a family history of Rb, adjusted for treatment, age, and length of follow-up. The risk for melanoma was significantly elevated for survivors with a family history of Rb (RR, 3.08; 95% CI, 1.23 to 7.16), but risks for bone or soft tissue sarcomas were not elevated. The cumulative incidence of SCs 50 years after diagnosis of bilateral Rb, with adjustment for competing risk of death, was significantly higher for survivors with a family history (47%; 95% CI, 35% to 59%) than survivors without a family history (38%; 95% CI, 32% to 44%; P = .004).
Rb survivors with bilateral disease and an inherited germline mutation are at slightly higher risk of an SC compared with those with a de novo germline mutation, in particular melanoma, perhaps because of shared genetic alterations.
Oral tongue squamous cell carcinoma (OTSCC) is a prevalent malignant disease that is characterized by high rates of metastasis and postoperative recurrence. The aim of this study was to establish a ...nomogram to predict the outcome of OTSCC patients after surgery.
We retrospectively analyzed 169 OTSCC patients who underwent treatments in the Cancer Hospital of Shantou University Medical College from 2008 to 2019. The Cox regression analysis was performed to determine the independent prognostic factors associated with patient's overall survival (OS). A nomogram based on these prognostic factors was established and internally validated using a bootstrap resampling method.
Multivariate Cox regression analysis revealed the independent prognostic factors for OS were TNM stage, age, lymphocyte-to-monocyte ratio and immunoglobulin G, all of which were identified to create the nomogram. The Akaike Information Criterion and Bayesian Information Criterion of the nomogram were lower than those of TNM stage (292.222 vs. 305.480; 298.444 vs. 307.036, respectively), indicating a better goodness-of-fit of the nomogram for predicting OS. The bootstrap-corrected of concordance index (C-index) of nomogram was 0.784 (95% CI 0.708-0.860), which was higher than that of TNM stage (0.685, 95% CI 0.603-0.767, P = 0.017). The results of time-dependent C-index for OS also showed that the nomogram had a better discriminative ability than that of TNM stage. The calibration curves of the nomogram showed good consistency between the probabilities and observed values. The decision curve analysis also revealed the potential clinical usefulness of the nomogram. Based on the cutoff value obtained from the nomogram, the proposed high-risk group had poorer OS than low-risk group (P < 0.0001).
The nomogram based on clinical characteristics and serological inflammation markers might be useful for outcome prediction of OTSCC patient.
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