Effect assessment of methotrexate in combination with other chemotherapeutic agents for osteosarcoma in children: A protocol for systematic review and meta-analysis.

BACKGROUND: Osteosarcoma is a primary form of malignant bone tumor. It is commonly prevalent among children. Treating osteosarcoma with chemotherapy has had limited clinical outcomes due to side effects and the formation of drug resistance. Presently, a mixture of doxorubicin, cisplatin, ifosfamide, epirubicin methrotrexate, and other supplementary medications are used in osteosarcoma chemotherapy. Therefore, this study aims to investigate the clinical therapeutic effects of combining methotrexate with other chemotherapeutic agents to treat osteosarcoma in children. METHODS: The search of several electronic databases will lead to source related published studies. The electronic databases include both English (PubMed, EMBASE, Web of Science, and the Cochrane Library) and Chinese (China National Knowledge Infrastructure, WanFang, and China Biomedical Database) databases. All studies published from inception to November 19, 2020 are searched. Study selection, extraction of data, and evaluation of the bias risk in included studies are carried out by two authors independently. The software, RevMan 5.3, is used to analyze the data. RESULTS: This study provides evidence of substantial quality for the clinical therapeutic effects of methotrexate combined with other chemotherapeutic agents for treating osteosarcoma in children. CONCLUSION: The results of this study provide conclusive evidence with regards to the clinical application of methotrexate combined with other chemotherapeutic agents for treating osteosarcoma in children. ETHICS AND DISSEMINATION: Since this study will use published data, ethical approval is not required. SYSTEMATIC REVIEW REGISTRATION NUMBER: This protocol has been registered on INPLASY202110024.

The Heterogeneity Between Lynch-Associated and Sporadic MMR Deficiency in Colorectal Cancers.

Background: Previous studies demonstrated that prognosis of germline deficiency in mismatch repair protein (dMMR) was different from that of sporadic dMMR. The underlying mechanism has not been studied. Methods: From a prospectively maintained database, we collected dMMR colorectal cancer (CRC) patients identified by postoperative immunohistochemistry screening. According to genetic test, patients were grouped as Lynch-associated or sporadic dMMR. We compared the clinical-pathological features, prognosis, and immunoreactive differences between the two groups. By whole-exome sequencing and neoantigen detection pipeline, mutational frequencies and neoantigen burdens were also compared. All statistical tests were two-sided. Results: Sixty-seven sporadic dMMR and 85 Lynch-associated CRC patients were included in the study. Sporadic dMMR patients were older (P < .001) and their tumors were poorly differentiated (P = .03). The survival was better in the Lynch-associated group (P = .001). After adjustment, the difference still remained statistically significant (hazard ratio = 0.29, 95% confidence interval = 0.09 to 0.95, P = .04). The scores of Crohn's-like reaction (CRO; P < .001), immunoreactions in the invasive margin (IM; P = .01), tumor stroma (TS; P = .009), and cancer nest (CN; P = .02) of the Lynch-associated group were statistically significantly higher. The numbers of CD3+, CD8+, Foxp3+ tumor-infiltrating lymphocytes (TILs) in IM; CD3+, CD4+ TILs in TS; and CD3+, CD4+, CD8+ TILs in CN were statistically significantly higher in Lynch-associated dMMR patients. Based on the 16 patients who under went whole-exome sequencing, there were also more somatic mutations and neoantigen burdens in the Lynch-associated group compared with the sporadic dMMR group (439/pt vs 68/pt, P = .006; 628/pt vs 97/pt, P = .009). Conclusions: There are heterogeneities in dMMR CRCs. Lynch-associated dMMR patients present with more somatic mutations and neoantigens compared with sporadic dMMR, which probably results in stronger immunoreactions and survival improvement.

Effect of Neoadjuvant Chemoradiotherapy with Capecitabine versus Fluorouracil for Locally Advanced Rectal Cancer: A Meta-Analysis.

A meta-analysis was carried out to compare the efficacy and safety of capecitabine plus radiation with 5-fluorouracil (5-FU) plus radiotherapy (RT) as neoadjuvant treatment in locally advanced rectal cancer (LARC). We searched the Cochrane database, Ovid, Medline, Embase, ISI databases, and Chinese Biomedical Literature Database between January 1998 and October 2014. Trials of capecitabine compared with 5-FU plus RT as neoadjuvant treatment for LARC were considered for inclusion. RevMan software was used to analyze these data. Nine trials were included in this meta-analysis, which covered a total of 3141 patients. The meta-analysis showed that capecitabine group had statistically significant better pCR rates (OR, 1.34; 95% CI, 1.10-1.64; P = 0.003), T downstaging rates (OR, 1.58; 95% CI, 1.22-2.06; P = 0.0007), N downstaging rates (OR, 2.06; 95% CI, 1.34-3.16; P = 0.001), less distant metastasis (OR, 0.63; 95% CI, 0.44-0.88; P = 0.007), and lowered leucocytes (OR, 0.25; 95% CI, 0.11-0.54; P = 0.0005), but with higher incidence of hand-foot syndrome (HFS) (OR, 4.43; 95% CI, 1.59-12.33; P = 0.004). Capecitabine was more efficient than 5-FU in terms of tumor response in neoadjuvant treatment for patients with LARC and favourably low toxicity with the exception of HFS.