Molecular landscape and therapeutic alterations in Asian soft-tissue sarcoma patients.

BACKGROUND: Soft-tissue sarcoma (STS) is a rare solid malignant tumor with numerous histologic subtypes. Current studies on targeted therapy for STS are in preclinical and early-phase trials. Genomic differences largely influence the prognosis of patients even with the same subtype. To investigate the genomic alterations (GAs) and the potential of targeted therapy in STS, we analyzed the genomic landscape, the therapeutic GAs, and biomarkers of immunotherapy in Chinese STS patients. METHODS: Targeted sequencing covering 425 genes was performed, from which we obtained the results of tissue samples from 351 Chinese STS patients of all ages covering different histologic subtypes. Bioinformatics analysis of altered genes with nonsynonymous mutations, copy-number variations, and gene fusions were performed. OncoKB therapeutic GAs and relevant biomarkers including TMB, MSI, and HRD were further examined for potential targeted therapy. RESULTS: In total, 2743 GAs were identified in 330 genes with a median of 6 (1-38) per case. The top 11 frequently altered genes were: TP53, MCL1, MDM2, CDK4, MYC, CDKN2A, GNAS, RB1, ATRX, CDKN2B, and FGFR1. OncoKB defined therapeutic GAs were found in 23 genes in 43% of the patients. In general, 9.4% of the patients had high-TMB, 2.8% had MSI, and 13.7% had HRD. A significant difference in the percentage of patients with OncoKB therapeutic GAs were observed between the most frequent two subtypes, leiomyosarcoma and liposarcoma. Altogether, 54% of the patients had the potential to respond to a targeted therapy. CONCLUSION: This study indicated the potential efficacy of targeted therapy on many STS patients, and also provided insight for novel precision therapy. The clinical efficacy of combining targeted therapy and immunotherapy can be further investigated.

Predictive Value of Circulating Tumor Cells in Prognosis of Stage III/IV Colorectal Cancer After Oxaliplatin-based First-line Chemotherapy.

BACKGROUND/AIM: Insufficient data exist to support the concept of the circulating tumor cell (CTC) level as a prognostic factor for platinum-based first-line chemotherapy. This study investigated the impact of CTCs on the prognosis of patients with advanced colorectal cancer (CRC) after receiving platinum-based chemotherapy. Analyses were carried out of clinicopathological features and molecular phenotypes to clarify independent risk factors for a high CTC count. PATIENTS AND METHODS: Patients diagnosed with stage III/IV CRC (n=76) were included in the study. The blood samples of patients were evaluated for CTCs using the CellRich™ platform system. Immunohistochemistry (Ias used to analyze epithelial-mesenchymal transition-associated biomarkers E-cadherin and vimentin. Univariate and logistic regression analyses were then conducted to analyze the risk factors for CTC expression. Additionally, the influence of oxaliplatin on disease-free survival after first-line chemotherapy or during chemotherapy was analyzed through a 2-year follow-up. RESULTS: Patients in the CTC+ group experienced shorter DFS after receiving oxaliplatin first-line chemotherapy than patients in the CTC- group (p<0.01). In addition, univariate analysis revealed that the tumor M-stage, tumor location, RAS mutation, high expression of vimentin, and deletion of E-cadherin expression were correlated with a high CTC count. Multivariate analysis suggested that the presence of RAS gene mutations and high vimentin expression were independent risk factors for high CTC loads (p<0.01). CONCLUSION: CTC positivity can indicate the efficacy of first-line chemotherapy with oxaliplatin in stage III/IV colorectal cancer. This may be linked to tumor epithelial-mesenchymal transition in patients with CTCs. Moreover, RAS gene mutation and high expression of vimentin were identified as independent risk factors for a high CTC count.

Comparison of postoperative laparoscopic and open total mesorectal excision on lower urinary tract function in men with rectal cancer.

OBJECTIVES: This study investigated male voiding dysfunction (VD) or lower urinary tract function in rectal cancer (RC) patients after laparoscopic or open total mesorectal excision with pelvic autonomic nerve preservation (PANP). METHODS: One hundred and eighty-seven male RC patients admitted between January 2016 and May 2019 were enrolled in this study, 112 of whom underwent laparoscopic total mesorectal excision (LTME) and 75 underwent open total mesorectal excision (OTME). The International Prostatic Symptom Score (IPSS) was compared between the two groups. RESULTS: The postoperative IPSS in patients with RC was elevated on day 7 and gradually decreased during the first month after surgery. Compared with the OTME group, the IPSS scores decreased less in the LTME group at week 1, and months 1 and 3 postoperatively (6.82 ± 2.13 vs 10.15 ± 3.86, 5.70 ± 2.45 vs 7.21 ± 2.0, and 5.01 ± 2.09 vs 5.75 ± 2.55, respectively; P < 0.05). The VD rate was significantly lower in the LTME group than the OTME group at 1, 2, and 3 weeks postoperatively (21.4% vs 26.8%,13.4% vs 25.3%, and 9.8% vs18.6%, respectively; P < 0.05); however, there was no major difference in the incidence of VD 6 months postoperatively between the two groups (P > 0.05). VD was more frequent in the OTME group than the LTME group 6 months postoperatively, but the difference was not statistically significant (odds ratio = 1.857, 95% CI, 0.964-3.645, P = 0.064). CONCLUSIONS: LTME may be superior to OTME with respect to PANP of lower urinary tract function in males with RC.