Development and external validation of a prediction model for brain metastases in patients with metastatic breast cancer.

BACKGROUND: Breast cancer patients with brain metastasis (BM) have a poor prognosis. This study aims to identify the risk factors of BM in patients with metastatic breast cancer (MBC) and establish a competing risk model for predicting the risk of brain metastases at different time points along the course of disease. METHODS: Patients with MBC admitted to the breast disease center of Peking University First Hospital from 2008 to 2019 were selected and retrospectively analyzed to establish a risk prediction model for brain metastases. Patients with MBC admitted to eight breast disease centers from 2015 to 2017 were selected for external validation of the competing risk model. The competing risk approach was used to estimate cumulative incidence. Univariate Fine-Gray competing risk regression, optimal subset regression, and LASSO Cox regression were used to screen potential predictors of brain metastases. Based on the results, a competing risk model for predicting brain metastases was established. The discrimination of the model was evaluated using AUC, Brier score, and C-index. The calibration was evaluated by the calibration curves. The model was assessed for clinical utility by decision curve analysis (DCA), as well as by comparing the cumulative incidence of brain metastases between groups with different predicted risks. RESULTS: From 2008 to 2019, a total of 327 patients with MBC in the breast disease center of Peking University First Hospital were admitted into the training set for this study. Among them, 74 (22.6%) patients developed brain metastases. From 2015 to 2017, a total of 160 patients with MBC in eight breast disease centers were admitted into the validation set for this study. Among them, 26 (16.3%) patients developed brain metastases. BMI, age, histological type, breast cancer subtype, and extracranial metastasis pattern were included in the final competing risk model for BM. The C-index of the prediction model in the validation set was 0.695, and the AUCs for predicting the risk of brain metastases within 1, 3, and 5 years were 0.674, 0.670, and 0.729, respectively. Time-dependent DCA curves demonstrated a net benefit of the prediction model with thresholds of 9-26% and 13-40% when predicting the risk of brain metastases at 1 and 3 years, respectively. Significant differences were observed in the cumulative incidence of brain metastases between groups with different predicted risks (P < 0.05 by Gray's test). CONCLUSIONS: In this study, a competing risk model for BM was innovatively established, with the multicenter data being used as an independent external validation set to confirm the predictive efficiency and universality of the model. The C-index, calibration curves, and DCA of the prediction model indicated good discrimination, calibration, and clinical utility, respectively. Considering the high risk of death in patients with metastatic breast cancer, the competing risk model of this study is more accurate in predicting the risk of brain metastases compared with the traditional Logistic and Cox regression models.

Spine-Related Malpractice Claims in China: A 2-year National Analysis.

STUDY DESIGN: Retrospective cross-sectional study. OBJECTIVE: To investigate the prevalence, characteristics, and risk factors of spine-related malpractice claims in China in a 2-year period. METHODS: The arbitration files of the Chinese Medical Association (CMA) were reviewed for spine-related malpractice claims. Descriptive statistics and correlation analysis were conducted on claim characteristics, clinical data, plaintiff's main allegations, and arbitration outcomes. RESULTS: A total of 288 cases of spinal claims filed in the CMA between January 2016 and December 2017 were included. Most claims were found in lumbar degenerative disorders (59.4%), lumbar trauma (13.2%), and cervical degenerative disorders (11.8%). The most common adverse events (AEs) leading to claims were new neurologic deficit (NND) (47.6%), infection (11.5%), and insufficient symptom relief (10.4%). The most common patient allegation was surgical error (66.0%), although the main arbitrated cause of AEs was disease/treatment itself (49.0%), while providers were judged as mainly responsible in only 47.3% cases. In multivariate regression analysis, cervical spine, misdiagnosis/mistreatment, and unpredictable emergency correlated with more severe damage to patients; minimally invasive surgery was predictive of judgment in plaintiff's favor, while claims in the eastern region and unpredictable emergencies were predictive of defendant's favor; only NND was associated with being arbitrated as surgical error in surgical cases where surgeons accepted major liability. CONCLUSION: The current study provided a descriptive overview and risk factor analysis of spine-related malpractice claims in China. Gaining improved understanding of the facts and causes of malpractice claims may help providers reduce the risk of claims and subsequent litigation.

De novo metastatic lobular breast carcinoma: A population-based study from SEER database.

PURPOSE: Patients with metastatic lobular breast carcinoma constitute a heterogeneous group with distinguishing features. Our aim was to describe the features and survival of them, and further subdivide them into subcategories for prognostic stratification and treatment planning. PATIENTS AND METHODS: Patients with de novo metastatic breast cancer from 2010 to 2018 were identified using the SEER database. Multivariate logistic regression analysis was conducted to calculate odds ratios. The within-pair difference was minimized by propensity score matching. Multiple comparisons based on Cox proportional hazards model were performed to investigate the interactions of M1 subcategory and treatment modality on survival. RESULTS: A total of 1,675 patients with de novo metastatic lobular breast carcinoma were identified, they were more likely to have HR+/HER2- subtype, low histologic grade, low T/N stage, fewer metastatic sites, but worse prognosis compared with patients with metastatic ductular breast carcinoma. The M1 stage was subdivided into 3 subcategories with significantly different prognoses. The benefits of primary tumor surgery were more pronounced in M1a/b disease, whereas the benefits of chemotherapy increased with the progression of metastatic disease. CONCLUSION: Patients with metastatic lobular breast carcinoma have unique clinicopathological characteristics and metastatic patterns. M1 subcategory assists prognosis stratification and treatment planning for such patients.

Brain metastasis in de novo breast cancer: An updated population-level study from SEER database.

PURPOSE: Although there are current studies on breast cancer brain metastasis, population-level analysis is still lacking. As treatment for metastatic breast cancer has improved, an updated population-level analysis is necessary. Our aim was to use the SEER database to characterize the incidence and survival of patients with brain metastases at the initial diagnosis of breast cancer. PATIENTS AND METHODS: Patients with breast cancer from 2010 to 2018 were identified using the SEER database. The stratified incidence and median survival of patients with BM at diagnosis were described. Multivariate logistic and Cox regression were performed to determine the covariates associated with brain metastasis and survival outcomes, respectively. Multiple comparisons based on Cox proportional hazards model were performed for the analysis of interactive effects on overall survival. RESULTS: A total of 2,248 patients with brain metastases at the initial diagnosis of breast cancer were identified, accounting for 0.40% of all patients with breast cancer, and 7.26% of patients with metastatic disease. Incidence proportions were highest, and survival outcomes were worst among patients with hormone receptor (HR)-negative human epidermal growth factor receptor 2 (HER2)-positive and triple-negative subtypes. For patients with brain metastases, the prognostic differences among different molecular subtypes have been gradually narrowing, and the survival benefits from various treatment methods have been all increased over time. CONCLUSION: Our study provides an updated population-level estimate of the incidence and survival for patients with brain metastases at the diagnosis of breast cancer, thus may help early identification, prognostic stratification and treatment planning for such patients.

Survival Benefit of Surgical Treatment Added Into Systemic Treatment for Isolated Breast Cancer Liver Metastases: A Systematic Review and Meta-Analysis.

Background: Compared with systemic treatment alone, whether surgical treatment combined with systemic treatment can improve survival outcomes of patients with isolated breast cancer liver metastases (BCLM) is still controversial. This meta-analysis was designed to evaluate the efficacy of surgical treatment for patients with isolated BCLM. Methods: A systematic search of PubMed, Embase, and Cochrane Library up to May 13, 2021 was conducted for relevant studies. The primary outcome was overall survival. The meta-analysis was performed using R software. The quality of the pooled study was assessed using the Newcastle-Ottawa scale. The publication bias was evaluated by funnel plots and Begg's and Egger's tests. Fixed- and random-effects models were applied according to heterogeneity. Results: 9 retrospective studies involving 13 cohorts (7 unmatched cohorts and 6 matched cohorts) were included in this study. The surgical cohorts had better overall survival than the systemic cohorts in the pooled analysis of all the included studies, in the subgroup analysis of liver resection, and in the subset of the matched cohorts. Conclusions: Compared with systemic treatment alone, surgical treatment combined with systemic treatment was proven to be associated with superior survival outcomes, which should be considered in selected patients with isolated BCLM.

Extracorporeal Shockwave Therapy for Treating Chronic Low Back Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To assess the effectiveness and safety of extracorporeal shockwave therapy (ESWT) for the treatment of chronic low back pain (CLBP). METHODS: This was a systematic review and meta-analysis of randomized controlled trials (RCTs) designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement standard. We identified relevant studies by searching multiple electronic databases, trial registries, and websites up to April 30, 2021, and examining reference lists. We selected RCTs that compared ESWT, in unimodal or multimodal therapeutic approaches, with sham ESWT or other active therapies. Two investigators independently extracted data and assessed the risk of bias and quality of the evidence. The main outcomes were pain intensity and disability status, examined as standardized mean differences (SMD) with 95% confidence intervals (CI). The risk of bias was assessed by using Cochrane Back and Neck (CBN) Group risk of bias tool and Jadad score, and GRADE was applied to determine the confidence in effect estimates. Heterogeneity was explored using sensitivity analysis and meta-regression. RESULTS: Ten RCTs, including a total of 455 young to middle-aged individuals (29.2-55.8 years), were identified. Compared with control, the ESWT group showed lower pain intensity at month 1 (SMD = -0.81, 95% CI -1.21 to -0.42), as well as lower disability score at month 1 (SMD = -1.45, 95% CI -2.68 to -0.22) and at month 3 (SMD = -0.69, 95% CI -1.08 to -0.31). No serious shockwave-related adverse events were reported. CONCLUSION: The use of ESWT in CLBP patients results in significant and quantifiable reductions in pain and disability in the short term. However, further well-conducted RCTs are necessary for building high-quality evidence and promoting the application of ESWT in clinical practice.

A nomogram for predicting brain metastasis in patients with de novo stage IV breast cancer.

BACKGROUND: Brain metastasis (BM) is a very serious event in patients with breast cancer. The aim of this study was to establish a nomogram to predict the risk of BM in patients with de novo stage IV breast cancer. METHODS: We gathered female patients diagnosed with de novo stage IV breast cancer between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. After randomly allocating the patients to the training set and verification set, we used univariate and multivariate logistic regression to analyze the relationship between BM and clinicopathological features. Finally, we developed a nomogram which was validated by the analysis of calibration curve and receiver operating characteristic curve. RESULTS: Of 7,154 patients with de novo stage IV breast cancer, 422 developed BM. Age, tumor size, subtype, and the degree of lung involvement were significantly correlated with BM. The nomogram had discriminatory ability with an area under curve (AUC) of 0.640 [95% confidence interval (CI): 0.607 to 0.673] in the training set, and 0.644 (95% CI: 0.595 to 0.693) in the validation set. CONCLUSIONS: Our study developed a nomogram to predict BM for de novo stage IV breast cancer, thus helping clinicians to identify patients at high-risk of BM and implement early preventive interventions to improve their prognoses.

The detection rate of methylene blue combined with another tracer in sentinel lymph node biopsy of early-stage breast cancer: a systematic review and network meta-analysis.

BACKGROUND: Methylene blue (MB) alone or combined with 99mtechnetium-labeled sulphur colloid (Tc99m) or indocyanine green (ICG) is widely used for sentinel lymph node biopsy (SLNB) of early-stage breast cancer in developing countries and regions. However, studies investigating the effectiveness of MB combined with another tracer have produced heterogeneous results. The purpose of this network meta-analysis (NMA) was to evaluate the detection rate of MB alone, MB + Tc99m, and MB + ICG, and to examine the differences between the 3 methods. METHODS: We conducted a comprehensive electronic literature search on the PubMed, Embase, Web of Science, CNKI, and Wanfang Data databases from inception to October 2021. The meta-analysis included 7,498 patients in 49 studies. The risk of bias for each study was independently assessed as low, moderate, or high using criteria adapted from the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Fixed- and random-effects models were used to calculate pooled estimates. Mixed-comparison analysis using random-effects models. We assessed statistical heterogeneity by I2 statistics and evaluated publication bias using Begg's test. RESULTS: The identification rate (IR), false-negative rate (FNR), sensitivity (SEN), and accuracy rate (AR) using MB + Tc99m were 96%, 7%, 93%, and 96%, respectively; the IR, FNR, SEN, and AR using MB + ICG were 97%, 7%, 93%, and 97%, respectively. The NMA found that IR and AR between MB + ICG and MB + Tc99m was OR =1.37 (95% CI: 0.41-4.20) and OR =1.33 (95% CI: 0.56-3.32), respectively. DISCUSSION: Our results are similar to those of most previous studies, and meta-analysis showed that the MB + Tc99m or MB + ICG mapping methods can be used to obtain higher IR and lower FNR than MB alone. Our NMA showed no statistical significance between MB + Tc99m and MB + ICG with IR and AR. Both MB + Tc99m and MB + ICG can be used as effective mapping methods in SLNB of early-stage breast cancer to improve the detection rate.

Intraoperative radiotherapy versus whole-breast external beam radiotherapy, and other factors associated with the prognosis of early breast cancer treated with breast-conserving surgery and radiotherapy: a retrospective study from SEER database.

BACKGROUND: This study was aimed to investigate the prognostic factors of early breast cancer treated with breast-conserving surgery (BCS) and radiotherapy. Besides, we focused our attention exclusively on the comparison of the impact on prognosis between intraoperative radiotherapy (IORT) and whole-breast external beam radiotherapy (EBRT). METHODS: An observational cohort study was performed on patients with Tis-2 N0-1 M0 breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database who treated with BCS and radiotherapy. Cox regression analysis, Kaplan-Meier analysis, and propensity score matching (PSM) were used to estimate risk factors for overall survival (OS) and breast cancer-specific survival (BCSS). RESULTS: Of the 98,614 early breast cancer patients treated with BCS and radiotherapy, 97,164 (98.5%) patients underwent EBRT and 1,450 (1.5%) underwent IORT. Multivariable Cox regression analysis showed that early breast cancer patients with age ≥65, poor marital status, lack of medical insurance, histological grade III/IV (SEER 4 grades), high T stage, high N stage, and TNBC were associated with a decreased OS/BCSS, whereas ER-positive and PR-positive were associated with an improved OS/BCSS. No significant difference was observed in survival between IORT and EBRT groups (P=0.213 for OS, P=0.180 for BCSS), or between intraoperative beam radiation and intraoperative radioactive implants groups (P=0.319 for OS, P=0.972 for BCSS). CONCLUSIONS: Our study can help clinicians identify patients with poor prognosis after breast-conserving therapy. IORT may be an alternative to EBRT for early breast cancer patients who are unable to complete the long-term postoperative radiation treatment. Beam radiation and radioactive implants are both ideal alternatives for patients who choose IORT.

[Dominant species of cephalopods and their niche characteristics in offshore of northern South China Sea]. / å—æµ·åŒ—éƒ¨è¿‘æµ·å¤´è¶³ç±»ä¼˜åŠ¿ç§åŠå ¶ç”Ÿæ€ä½ç‰¹å¾.

To understand the relationships among dominant species of cephalopods in offshore nor-thern South China Sea, we examined the niche characteristics of these dominant species from both spatial and temporal dimensions using the index of relative importance (IRI), the niche breadth and overlap indices based on fishery resources data from the bottom-trawl survey for four seasons during 2014-2015. The results showed that five dominant species of cephalopods were recorded for four seasons, including Loligo edulis, L. chinensis, L. beka, Sepia esculenta, and L. duvaucelii. The first two species were shared by all seasons. Compared with historical data, the composition of dominant cephalopods species had changed. The cephalopods resource exhibited obvious temporal and spatial variations. Stock density was higher in the sea area extending from the southern Hainan Island to eastern Guangdong Province than that in Beibu Gulf. The seasonal variation was characte-rized by the largest in summer but the smallest in winter. The temporal and spatial niche analysis showed that there was inconsistent in the order between temporal and spatial niche breadths for domi-nant species. L. edulis (1.32) and L. chinensis (3.90) occupied the largest temporal and spatial niche breadths, respectively. The smallest of temporal and spatial niche breadths were shown for S. esculenta (0.98) and L. duvaucelii (2.04), respectively. Though the temporal niche overlap was numerically larger than the spatial niche overlap, both of them had higher values in interspecies among L. edulis, L. chinensis, L. beka, and the lower overlap for the species pairs between L. duvaucelii and other species. The result of correlation analysis suggested that niche breadth exhibited a significant negative correlation with variation in abundance on both temporal and spatial scales. The ecological niche could reflect the tempo-spatial changes of species resource, which enriched the traditional methods of fishery communities.

[Probability distribution characteristics of stock density in offshore of northern South China Sea.] / 南海北部近海渔业资源密度概率分布特征.

Based on catch data from the bottom trawl survey by eight cruises in offshore of northern South China Sea during 2014-2017, we analyzed the stock density distribution and explored its probability distribution with statistical method, which was further used to estimate the mean stock density in this region. The results showed that the coefficient of variation (CV) for stock density ranged from 0.67 to 1.03 for all the periods, indicating a highly uneven spatial distribution of stock density. The frequency distribution of fishery resource density was characterized by obvious right-skewed, which was dominated by stock density of 0-1000 kg·km-2. The results of one sample Kolmogorov-Smirnov test indicated that three probability distribution patterns were suitable for stock density in this region, including Lognormal, Gamma and Weibull distributions. In terms of the mean stock density estimation, the values from Lognormal showed no statistically significant difference from those from others, but the opposite result was obtained between Gamma and Weibull distributions. Compared with 1960s-1970s, the appropriate probability distribution pattern of stock density has changed from single to multiple types. Variation of the proportion of low catch resulted from the changes in the structure of fishery resources, fishing effort and climate change might cause the alte-ration of probability distribution.