ABSTRACT
BACKGROUND: Some studies reported stereotactic body radiotherapy (SBRT) has demonstrated superior therapeutic results than conventional radiotherapy. Nevertheless, this statement is controversial and the trial attempting to prove this is underway. We conducted this systemic review and meta-analysis aiming to combine the latest and most complete information about the survival outcomes and toxicities following SBRT for locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC). METHODS: Items involving SBRT and pancreatic cancer were searched in PubMed, EMBASE, Cochrane Library, SCOPUS and Web of Science. Median overall survival (OS), 1/2/3-year OS, median progression-free survival (PFS), 1/2/3-year PFS and incidence of grade 3-5 toxicities were the endpoints of interest in this meta-analysis. These endpoint proportions were pooled and analyzed using R. RESULTS: For the LAPC series, the median OS was 14.1 months; pooled 1/2/3-year OS rates were 57%, 19% and 10%, respectively; the median PFS was 10 months; pooled 1/2/3-year PFS rates were 36%, 12% and 4%; pooled incidence rates of acute gastrointestinal (GI), acute hematologic and late GI toxicity (grade≥3) were 2%, 4% and 8%. For the BRPC series, the median OS was 17.5 months; pooled 1/2-year OS rates were 75% and 29%; the median PFS was 12.2 months; pooled 1/2-year PFS rates were 48% and 18%; the incidence rates of toxicity (grade ≥ 3) were all 0%. CONCLUSIONS: Our meta-analysis based on published results of OS, PFS and incidence rates of toxicity demonstrated that SBRT does not show desirable therapeutic result than the standard therapies for LAPC and BRPC.
ABSTRACT
UNLABELLED: The anti-cancer effects of metformin, the most widely used drug for type 2 diabetes, alone or in combination with ionizing radiation were studied with MCF-7 human breast cancer cells and FSaII mouse fibrosarcoma cells. Clinically achievable concentrations of metformin caused significant clonogenic death in cancer cells. Importantly, metformin was preferentially cytotoxic to cancer stem cells relative to non-cancer stem cells. Metformin increased the radiosensitivity of cancer cells in vitro, and significantly enhanced the radiation-induced growth delay of FSaII tumors (s.c.) in the legs of C3H mice. Both metformin and ionizing radiation activated AMPK leading to inactivation of mTOR and suppression of its downstream effectors such as S6K1 and 4EBP1, a crucial signaling pathway for proliferation and survival of cancer cells, in vitro as well as in the in vivo tumors. CONCLUSION: Metformin kills and radiosensitizes cancer cells and eradicates radioresistant cancer stem cells by activating AMPK and suppressing mTOR.
