The efficacies and biomarker investigations of antiangiogenic agents and PD-1 inhibitors for metastatic soft tissue sarcoma: A multicenter retrospective study.

Objective: To investigate the efficacy and safety of antiangiogenesis-immunotherapy in patients with advanced STS in China, and to explore the potential factors of prognosis. Patients and Methods: This retrospective study was conducted at three hospitals in China, and the patients with metastatic STS who were ineligible for or declined anthracycline-based chemotherapy received antiangiogenic agents (anlotinib or apatinib) plus programmed death-1 (PD-1) inhibitors (camrelizumab or sintilimab) between June 2019 and May 2022. The primary endpoint was progression-free survival rate at 6 months (6-month PFSR), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) and toxicity. Biomarkers that might affect the prognosis were explored. Results: Thirty-nine patients were included: five patients with alveolar soft tissue sarcoma (ASPS) and 34 with non-ASPS. With a median follow-up of 18.2 months, the 6-month PFSR was 51.3%, with the ORR of 20.5% and DCR of 76.9%. The median PFS and OS were 7.0 months and 17.2 months. The 6-month PFSR for patients with ASPS and non-ASPS was 80.0% and 47.1%, respectively. The most common adverse events were hypothyroidism (56.4%), followed by fatigue (46.2%), and hypertriglyceridemia (43.6%). No treatment-related deaths were observed. Patients with low baseline NLR (NLR < 4) had better 6-month PFSR than those with high NLR (NLR ≥ 4) (82.4% vs. 31.6%). Conclusion: Antiangiogenic agents plus PD-1 inhibitors showed acceptable toxicity and promising efficacy in patients with advanced STS, especially patients with ASPS, and a low NLR might serve as a reliable biomarker for 6-month PFSR, PFS, and OS. It provides a reference for randomized controlled trials.

Sentinel lymph node metastasis diagnosis using ultrasound plus magnetic resonance lymphangiography in breast cancer.

Background: Ultrasound diagnosis is a highly specific tool and widely applied, but is associated with low sensitivity in detection of sentinel lymph nodes (SLNs). The diagnostic value of routine ultrasound combining magnetic resonance lymphangiography (MRL) for the detection of SLNs in breast cancer metastasis is still unclear. This study used ultrasound combined with MRL to explore the diagnostic value of detecting SLN metastasis in breast cancer. Methods: This study included female breast cancer patients who received modified radical mastectomy at the Department of Breast Surgery, the First Affiliated Hospital of Zhengzhou University between January 2016 and January 2019. The gold standard of SLNs is pathological results. The patients were divided into three groups: (I) Group A: an ultrasound plus MRL (contrast agent injected outside the areola) group; (II) Group B: an ultrasound plus MRL (contrast agent injection around the areola) group; and (III) Group C: an ultrasound plus MRL group (this group comprised patients from the two aforementioned groups). Results: A total of 432 patients were included. The overall detection rate and overall diagnostic accuracy of SLNs in breast cancer differed significantly among the three groups (all P<0.05). Ultrasound plus MRL showed a best overall detection rate 56.02%, and a best diagnostic accuracy 95.83%. The detection rate and diagnostic accuracy of axillary SLNs varied markedly among the three groups (P<0.05). The detection rate and diagnostic accuracy when the internal mammary node was the SLN differed notably between the ultrasound plus MRL (contrast agent injected outside the areola) and ultrasound plus MRL (contrast agent injection around the areola) groups and between the ultrasound plus MRL (contrast agent injection around the areola) and ultrasound plus MRL groups (all P<0.05). Conclusions: Ultrasound plus MRL may be advantageous for the detection of SLN metastasis in breast cancer and predicting breast cancer prognosis.

Efficacy and Safety of Anlotinib Combined with Liposomal Doxorubicin Followed by Anlotinib Maintenance in Metastatic Soft Tissue Sarcomas.

PURPOSE: Anlotinib is a novel tyrosine kinase inhibitor with promising anti-tumor activity in patients with advanced soft tissue sarcomas (STS) in China. Liposomal doxorubicin monotherapy showed an encouraging effect on this disease. The aim of this study was to evaluate the efficacy and safety of anlotinib combined with liposomal doxorubicin followed by anlotinib maintenance in patients with metastatic STS. PATIENTS AND METHODS: This is a multicenter, retrospective, observational study. We reviewed 27 patients with metastatic STS from July 2018 to December 2019, who were treated with anlotinib combined with liposomal doxorubicin followed by anlotinib maintenance in the absence of the tumor progression or intolerable adverse events (AEs). RESULTS: Of the 27 patients included, 2 patients had complete response (CR), 9 patients obtained partial response (PR), 11 patients achieved stable disease (SD). The objective response rate was 40.7%, the disease control rate was 81.5%, and the median progression-free survival (PFS) was 7 months (95% CI, 5.3-8.1 months). The progression-free rate (PFR) at 3 and 6 months was 81.5% and 59.3%, respectively. Most AEs were mild and acceptable. The most frequent grade 3/4 AEs were leukopenia (33.3%), febrile neutropenia (7.4%), and anemia (7.4%). No deaths related to the treatment were reported. CONCLUSION: This study shows that anlotinib combined with liposomal doxorubicin followed by anlotinib maintenance is effective in patients with metastatic STS, and most AEs of this combined therapy are mild and acceptable. Further investigation on its efficacy is warranted.

Expression of activating transcription factor 7 is correlated with prognosis of colorectal cancer.

BACKGROUND: It is important to identify some tumor-related factors for early detection, treatment, and evaluation of prognosis in colorectal cancer (CRC). In our study, we investigated the clinical and prognostic role of activating transcription factor 7 (ATF7) in CRC. MATERIALS AND METHODS: Expression of ATF7 was detected with immunohistochemistry in 72 cases with complete follow-up data and post-operation tissue specimens. Correlation between ATF7 and other clinicopathological factors was calculated with Chi-square test and the impact of ATF7 on survival were analyzed with Log-rank test and Cox regression models. RESULTS: Among 72 cases, ATF7 expression was detected in 43 cases (59.7%) and 29 cases (40.3%) without ATF7 expression. The correlation between ATF7 expression and pathological stage was investigated (P = 0.041). The 5-year overall survival (OS) of with or without ATF7 expression was 79% versus 51% respectively (P < 0.001) and the 5-year progression free survival (PFS) was 74% versus 41% (P < 0.001). The media OS was 69 months versus 52 months (P = 0.002) and the media PFS was 65 months versus 42 months (P = 0.002). ATF7 expression and numbers of lymph nodes involvement were prognostic factors for OS according to univariated and multivariated analysis and for PFS it was ATF7 expression and lymph nodes involvement. CONCLUSION: It is negatively related between ATF7 expression and pathological stage and positive correlation with OS and PFS in CRC. ATF7 expression is a favorable factor for survival of patients with CRC.

p63 Expression is a prognostic factor in colorectal cancer.

p63 is highly expressed in some malignant tumors and is associated with tumorigenesis, invasion and metastasis. The aim of our study was to evaluate the clinical significance of p63 in colorectal cancer (CRC). p63 expression was detected by immunohistochemistry in 66 CRC patients. Correlations between p63 expression and clinicopathological factors, progression-free survival (PFS) and overall survival (OS) were analyzed. Among the 66 CRC cases, 31 cases (47%) exhibited a high score of p63 expression, while 35 cases (53%) were marked with a low score. The p63 level correlated with peritumoral deposits (p=0.021). The 5-year OS rates in the low p63 score and high p63 score groups were, respectively, 49% and 74% (p<0.001). The 5-year PFS rates in the low p63 score and high p63 score groups were, respectively, 44% and 71% (p<0.001). Univariate analysis revealed that p63 expression was correlated with OS and PFS. Multivariate analysis suggested that p63 expression was an independent prognostic factor for OS (p=0.035). In conclusion, p63 was negatively correlated with peritumoral deposits and positively associated with OS and PFS in CRC. The data suggest that p63 is a potential prognostic factor for CRC.

Activating transcription factor 1 is a prognostic marker of colorectal cancer.

OBJECTIVE: Identifying cancer-related genes or proteins is critical in preventing and controlling colorectal cancer (CRC). This study was to investigate the clinicopathological and prognostic value of activating transcription factor 1 (ATF1) in CRC. METHODS: Protein expression of ATF1 was detected using immunohistochemistry in 66 CRC tissues. Clinicopathological association of ATF1 in CRC was analyzed with chi-square test or Fisher's exact test. The prognostic value of ATF1 in CRC is estimated using the Kaplan-Meier analysis and Cox regression models. RESULTS: The ATF1 protein expression was significantly lower in tumor tissues than corresponding normal tissues (51.5% and 71.1%, respectively, P = 0.038). No correlation was found between ATF1 expression and the investigated clinicopathological parameters, including gender, age, depth of invasion, lymph node status, metastasis, pathological stage, vascular tumoral emboli, peritumoral deposits, chemotherapy and original tumor site (all with P > 0.05). Patients with higher ATF1 expression levels have a significantly higher survival rate than that with lower expression (P = 0.026 for overall survival, P = 0.008 for progress free survival). Multivariate Cox regression model revealed that ATF1 expression and depth of invasion were the predictors of the overall survival (P = 0.008 and P = 0.028) and progress free survival (P = 0.002 and P = 0.005) in CRC. CONCLUSIONS: Higher ATF1 expression is a predictor of a favorable outcome for the overall survival and progress free survival in CRC.