BACKGROUND
There is no standard therapy for recurrent glioblastoma (rGBM), which has a poor survival, from 3 to 10 months. Radiotherapy is an available option for patients with rGBM, and it could invoke DNA damage, thus leading to tumor cell death. Niraparib is a poly(ADP-ribose) polymerase inhibitor. Preclinical data showed that Niraparib enhances the radiosensitivity of glioblastoma cells. Thus we hypothesize that radiotherapy synergizes with Niraparib to improve the clinical efficacy of anti-tumor.Method:We conducted a phase 2 study combining Niraparib, radiotherapy, and maintenance Niraparib in 30 patients with rGBM. Niraparib(300mg QD) was started at cycle 1 of radiotherapy (55Gy total) and continued until progression or unacceptable toxicity The primary endpoint was 6 month PFS. Secondary endpoints included toxicity, QoL, and OS Result:As of 4/31/2022, 14 patients with a median age of 47 years old (range 26-69) were enrolled. 64.29% were female. Eight patients(57.1%)had experienced ≥ 2 previous therapy(range 1-4). The MGMT methylation status was available for 12 patients, and 9(64.3%)had unmethylated MGMT. The median follow-up was 167 days (95%CI 124-263). PFS 6 was 36% (95%CI 12.17%-60.92%), OS 6 was 82.61%(95%CI 46.51%-95.34%). The mPFS was 157 days (95%CI 93-188), the mOS was not reached (95%CI 188-NA), three patients had an OS of more than 10 months by the data submitted. The ORR was 35.7%, one patient achieved CR,four achieved PR. Niraparib combined radiotherapy showed efficacy in controlling local lesions. At 1 and 3 months, local control rate was 85.7% and 64.3% ,respectively. The most common serious adverse event was thrombocytopenia(28.57%)which could be controlled by adjusting the dosage of Niraparib.
CONCLUSION
Niraparib combined radiotherapy is well tolerated and shows efficacy in rGBM patients. Survival data will be updated.Clinical registration number: NCT04715620
The potential of long noncoding RNAs (lncRNAs) as symptomatic and prognostic biomarkers in oncotherapy for hepatic carcinoma has been revealed. However, the specific mechanisms of lncRNAregulated tumor progression and metastasis are not completely known. The RNA and miRNA sequencing data of liver cancer in The Cancer Genome Atlas database were analyzed. A competing endogenous RNA (ceRNA) was constructed, and its effects on the progression and metastasis of tumors and the survival rates of patients with tumor were evaluated. Differentially expressed mRNAs, miRNAs, and lncRNAs were identified. A liver cancer-associated ceRNA network, namely, FAM224A/hsa-mir-139/RAD54B, was then established. FAM224A/hsa-mir-139/RAD54B assumed a significant part in liver malignancy movement and metastasis. A series of cell experiments was conducted to prove the importance of ceRNAs, and the binding between RNAs was validated through a dual-luciferase reporter assay. The FAM224A/hsa-mir-139/RAD54B network in liver cancer was identified. FAM224A may be an important prognostic factor and treatment target for liver cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.