INCREASED SURVIVAL IN GLIOBLASTOMAS AND ANAPLASTIC ASTROCYTOMAS TREATED WITH CONFORMAL RADIOTHERAPY AND HYPERTHERMIA

Introduction: Malignant gliomas and astrocytomas represent a class of aggressive neoplasms that are generally resistant to conventional therapies. The basic approach to treatment involves a combination of surgery, radiotherapy and chemotherapy. Among chemotherapeutic agents Nitrosoureas (CCNU) and Temozolomide (TMZ) have a certain activity against gliomas and astrocytomas. Recently, TMZ was demonstrated to be well tolerated and active as a single agent or in combination with radiotherapy. The median survival time for high grade gliomas is 10-12 months and the prognosis is dismal. New therapeutic approaches are justified. Several studies in vitro on glioblastomas have demonstrated that hyperthermia plus chemotherapy has a higher cytotoxicity than chemotherapy alone. Furthermore, heat has a cytotoxic effect by itself and an anti-vascular effect. This last effect is of outmost importance due to the high neoangiogenesis present in these tumors. Patients and Methods: Between January 2001 and April 2008, 29 patients with aggressive brain tumors [11 glioblastomas (GBM), 14 astrocytomas (6 AstroIV, 8 Astro II degree, 1 Oligoastrocytoma), 2 ependymomas and 1 medulloblastoma] have been treated with conformal radiotherapy (CRT), chemotherapy and hyperthermia (HT). Twenty five of these patients (11 GBM and 14 astrocytoma) (9F, 16M; median age 44.6 plus or minus 9.85) have been treated with the CFRT + TMZ + HT and were eligible to be compared with a group of 27 patients with 18 GBM and 9 astrocytomas (12F, 15 M median age 50.93 plus or minus 13.9y) treated with CFRT and TMZ alone. All the patients of the two groups have been resected and later treated with CRT + TMZ or HT. HT was administered using a Synchrotherm radiofrequency (RF) device developed by DUER registered , Vigevano, Italy. It consists of the following components: 1) a RF generator (13.56 MHz) 2) a pair of mobile plates or electrodes with independent superficial cooling system, 3) a heat exchanger, 4) a computerized control console. A thermal profiles to obtain a probable deposition of the energy were obtained by heating patterns produced in a static phantom under various conditions. The 25 patients were treated combining chemotherapy, radiotherapy and hyperthermia with the following sequence. HT was applied 2 h after CRT administration, and the patents used orally 120 mg of CCNU two hs prior HT or a median dose of 200 mg of temozolomide (TMZ). BCNU or TMZ was administered once per HT cycle, generally at t