Clinical efficacy of tumor organoid-guided cancer therapy for locally advanced unresectable or metastatic breast cancer.

Patient-derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid-guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC). The primary outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Forty-six PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 78.4% (95% CI 64.9%-91.9%) in predicting clinical responses. Thirty-six OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs. 5.0 months; hazard ratio 0.53 [95% CI 0.33-0.85]; p = .01) and improved disease control (88.9% vs. 63.8%; odd ratio 4.26 [1.44-18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis in hormone receptor-positive, human epidermal growth factor receptor 2-negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO-based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization.

How cynicism and exhaustion influence the turnover intention of medical social workers: moderation effect of social work educational background and organizational type.

Although exhaustion and cynicism are two dimensions of burnout, due to professionalism, they have different influence on the turnover intentions of medical social workers. Using a sample of 405 medical social workers in China, this study found that the influence mechanisms of exhaustion and cynicism on turnover intention are different. Social work educational background has a significant moderation effect on the relationships between exhaustion, cynicism, and turnover intention. A moderation effect of organizational type was also observed, although it was not significant.

Neoadjuvant Chemotherapy and Neoadjuvant Chemotherapy With Immunotherapy Result in Different Tumor Shrinkage Patterns in Triple-Negative Breast Cancer.

PURPOSE: This study aims to explore whether neoadjuvant chemotherapy with immunotherapy (NACI) leads to different tumor shrinkage patterns, based on magnetic resonance imaging (MRI), compared to neoadjuvant chemotherapy (NAC) alone in patients with triple-negative breast cancer (TNBC). Additionally, the study investigates the relationship between tumor shrinkage patterns and treatment efficacy was investigated. METHODS: This retrospective study included patients with TNBC patients receiving NAC or NACI from January 2019 until July 2021 at our center. Pre- and post-treatment MRI results were obtained for each patient, and tumor shrinkage patterns were classified into three categories as follows: 1) concentric shrinkage (CS); 2) diffuse decrease; and 3) no change. Tumor shrinkage patterns were compared between the NAC and NACI groups, and the relevance of the patterns to treatment efficacy was assessed. RESULTS: Of the 99 patients, 65 received NAC and 34 received NACI. The CS pattern was observed in 53% and 20% of patients in the NAC and NACI groups, respectively. Diffuse decrease pattern was observed in 36% and 68% of patients in the NAC and NACI groups. The association between the treatment regimens (NAC and NACI) and tumor shrinkage patterns was statistically significant (p = 0.004). The postoperative pathological complete response (pCR) rate was 45% and 82% in the NAC and NACI groups (p < 0.001), respectively. In the NACI group, 17% of patients with the CS pattern and 56% of those with the diffuse decrease pattern achieved pCR (p = 0.903). All tumor shrinkage patterns were associated with achieved a high pCR rate in the NACI group. CONCLUSION: Our study demonstrates that the diffuse decrease pattern of tumor shrinkage is more common following NACI than that following NAC. Furthermore, our findings suggest that all tumor shrinkage patterns are associated with a high pCR rate in patients with TNBC treated with NACI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04909554.

18F-FDG PET/CT-based deep learning radiomics predicts 5-years disease-free survival after failure to achieve pathologic complete response to neoadjuvant chemotherapy in breast cancer.

BACKGROUND: This study aimed to assess whether a combined model incorporating radiomic and depth features extracted from PET/CT can predict disease-free survival (DFS) in patients who failed to achieve pathologic complete response (pCR) after neoadjuvant chemotherapy. RESULTS: This study retrospectively included one hundred and five non-pCR patients. After a median follow-up of 71 months, 15 and 7 patients experienced recurrence and death, respectively. The primary tumor volume underwent feature extraction, yielding a total of 3644 radiomic features and 4096 depth features. The modeling procedure employed Cox regression for feature selection and utilized Cox proportional-hazards models to make predictions on DFS. Time-dependent receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were utilized to evaluate and compare the predictive performance of different models. 2 clinical features (RCB, cT), 4 radiomic features, and 7 depth features were significant predictors of DFS and were included to develop models. The integrated model incorporating RCB, cT, and radiomic and depth features extracted from PET/CT images exhibited the highest accuracy for predicting 5-year DFS in the training (AUC 0.943) and the validation cohort (AUC 0.938). CONCLUSION: The integrated model combining radiomic and depth features extracted from PET/CT images can accurately predict 5-year DFS in non-pCR patients. It can help identify patients with a high risk of recurrence and strengthen adjuvant therapy to improve survival.

Case report: solitary splenic metastasis occurring 19 months after primary treatment for occult breast cancer.

Occult breast cancer, commonly presenting with axillary lymphadenopathy, is an extremely rare entity of breast cancer. Metastasis to the spleen as a single site is rarely seen and has been little reported in literature. Herein we described a case of a 60-year-old patient who presented with an asymptomatic solitary splenic mass 19 months after axillary lymph node dissection, regional radiotherapy, and systemic therapy. Laparoscopic splenectomy was performed, and histopathological examination confirmed metastasis from occult breast cancer. Then, the patient was administered with oral vinorelbine and dual-targeted treatment. With over 10 months of follow-up, there is no evidence of recurrence or metastasis of malignancy. To our knowledge, this study reports the first case of solitary splenic metastasis from occult breast cancer and highlights the importance of considering splenic metastasis as the only site of recurrence during follow-up of primary cancer, regardless of its rarity. If possible, splenectomy may be a therapeutic strategy.

Homologous recombination deficiency predicts the response to platinum-based neoadjuvant chemotherapy in early-stage triple-negative breast cancer patients: a systematic review and meta-analysis.

Background: Recent studies have shown that homologous recombination deficiency (HRD) may be correlated with the pathological complete response (pCR) rate. This meta-analysis aimed to determine the predictive value of HRD for the pCR rate in patients with triple-negative breast cancer (TNBC) receiving platinum-based neoadjuvant chemotherapy (NCT). Methods: Published articles were searched in the PubMed, Embase, Medline, Web of Science, and Cochrane databases up to 1 June 2021, and studies reporting the pCR rate for HRD carriers on platinum-based NCT were selected. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined for the pCR rate, clinical response rate, and Grade 3 or higher adverse events (AEs) using the random-effects model. Bias risk was evaluated using the Cochrane Collaboration tool (PROSPERO, registration number CRD42021249874). Results: Seven studies were eligible. The results showed that HRD carriers had higher pCR rates than non-HRD carriers across all treatment arms (OR = 3.84, 95% CI = [1.93, 7.64], p = 0.0001). Among HRD carriers, the pCR rate was higher in patients on platinum-based NCT than in those without platinum exposure (OR = 1.95, 95% CI = [1.17, 3.23], p = 0.01). We did not observe marked pCR improvements in non-HRD carriers. Among HRD carriers, the pCR rates in the mutant and wild-type breast cancer susceptibility gene (BRCA) groups did not differ significantly (OR = 2.00, 95% CI = [0.77, 5.23], p = 0.16), but HRD carriers with wild-type BRCA had a significant advantage over non-HRD carriers on platinum-based NCT (OR = 3.64, 95% CI = [1.83, 7.21], p = 0.0002). Conclusion: HRD is an effective predictor of increased pCR rates in platinum-based NCT, especially in wild-type BRCA patients. Adding platinum to NCT for non-HRD carriers can increase the incidence of AEs but may not improve the therapeutic effect.

Evaluation Model for Hospital Response Capability for Public Health Emergency.

OBJECTIVES: We aimed to explore and create an evaluation model to assess hospital response capability for a public health emergency (PHE). METHODS: Grounded theory was used to construct a comprehensive evaluation index system. Combining with the index system and previous studies and policy documents, we investigated surge capability of hospitals in a PHE. The factor analysis method was used to establish the model. RESULTS: The comprehensive evaluation system with 11 primary and 30 secondary indicators was constructed. A total of 89 secondary and tertiary hospitals were surveyed in China. The evaluation model (C = 0.587C1 + 0.151C2 + 0.140C3 + 0.122C4) was established. Four factors were identified, namely, preparation factor, treatment factor, emergency awareness factor, and prehospital first-aid factor. CONCLUSIONS: A public health emergency could bring huge losses and a capable hospital response was necessary. There was an urgent need to evaluate hospital capability for a PHE.