ABSTRACT
BACKGROUND AND PURPOSE: Recurrent malignant gliomas have a very poor prognosis. This trial aimed to evaluate the benefits of reirradiation in case of recurrent glioblastoma multiforme (GBM) using hypofractionated stereotactic radiotherapy (hFSRT) after primary high-dose percutaneous irradiation. PATIENTS AND METHODS: Between 1998 and 2008, 53 patients with recurrent GBM were treated by hFSRT based on CT and MR imaging. At the time of recurrence, a median total dose of 30 Gy (20-60 Gy) was delivered in median fractions of 3 Gy/day (2-5Gy). RESULTS: The reirradiation was well tolerated (no acute or late toxicity > grade 2), despite the relatively large median tumor volume (35.01 ml). Karnofsky Performance Score was the strongest predictor for survival after reirradiation (p = 0.0159). Tumor volume (p = 0.4690), patient age (p = 0.4301), second operation (p = 0.6930), and chemotherapy (p = 0.1466) at the time of reirradiation did not affect survival. After hFSRT, the median survival was 9 months, and the 1-year progression-free survival (PFS) amounted to 22%.The median overall survival from initial diagnosis was 27 months. 1-year survival from first diagnosis was 83%, 2-year survival 45%. The median time to progression from the end of initial irradiation to recurrence was 12 months. 1-year PFS before reirradiation was 40%. CONCLUSION: hFSRT as a secondary treatment of recurrent GBM is a feasible and effective treatment option. Only minor side effects were observed with prolonged life expectancy of 9 months.
Subject(s)
Brain Neoplasms/mortality , Brain Neoplasms/surgery , Glioblastoma/mortality , Glioblastoma/surgery , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/surgery , Radiosurgery/mortality , Aged , Dose Fractionation, Radiation , Female , Humans , Incidence , Male , Middle Aged , Radiotherapy Dosage , Reoperation/mortality , Survival Analysis , Survival Rate , Treatment OutcomeABSTRACT
The effects of toxic and nontoxic compound treatments were investigated by high resolution custom developed 2-11 pH gradient NEPHGE (non equilibrium pH gradient electrophoresis) two-dimensional electrophoresis. Two models were compared: (i) in vivo rat and (ii) the human cell line HepG2, to test their suitability in a proteomics based approach to identify a toxicity marker. 163 and 321 proteins were identified from the rat liver and the HepG2 proteome. These represent various isoforms of 113 and 194 different NCBI annotated gene sequences, respectively. Nine compounds were selected to induce proteome variations associated with liver toxicity and metabolism. The rat liver proteome database consists of 78 gels, the HepG2 database of 52 gels. Variant proteins were assessed regarding their usefulness as a toxicity marker by evaluating their treatment specificity against multiple control treatments. Thirteen potential toxicity marker proteins were found in rat liver and eight in HepG2. Catalase and carbamoylphosphate synthetase-1 isoforms were found to be significantly changed after treatment by 4/4 and 3/4 toxic compounds in rat liver, respectively. Aldo-keto-reductase family 1, member C1 was implicated for 3/4 liver cell toxic compounds in HepG2. Our approach was able to differentiate the quality of potential toxicity markers and provided useful information for an ongoing characterization of more compounds in a wider number of toxicity classes.
