Ultrafractionated Radiation Therapy (3 Daily Doses of 0.75 Gy) - A New and Promising Radiotherapy Schedule for Glioblastoma Patients

Malignant glioma is one of the most radio-resistant tumor types and accounts for approximately 60% of all primary brain tumors in adults (Behin et al., 2003; Black, 1991a, 1991b; DeAngelis, 2001). There are three distinct histological types: anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and glioblastoma multiforme (GBM). The prognosis of malignant glioma patients remains dismal (Behin et al., 2003; Black, 1991a, 1991b; De Angelis, 2001). The median survival for patients with newly diagnosed GBM is 8 to 15 months, prognosis is slightly better for newly diagnosed AA with a median survival of 24 to 36 months, and the prognosis for AO gives a median survival of 60 months (Behin et al., 2003; Black, 1991a, 1991b; De Angelis, 2001). For AA and GBM, the standard of care consists of surgical resection of as much of the tumor as is considered to be safe, followed by radiation and chemotherapy and has been so for many decades (Behin et al., 2003; Black, 1991a, 1991b; DeAngelis, 2001, Fine et al., 1993; Stewart, 2002; Walker et al., 1978, 1980). A new standard procedure for GBM has recently been defined by the EORTC phase III trial which randomized patients in two groups, receiving either temozolomide (TMZ) concomitant and adjuvant to radiation therapy or radiation therapy alone (Stupp et al., 2005). A significant increase in overall survival (OS) was seen in the radiation therapy plus TMZ group compared to the radiation therapy alone group. Survival rates were respectively 14.6 and 12.1 months. For AO, the standard treatment is surgical resection followed by radiation therapy (Stupp et al., 2005). Adjuvant chemotherapy does not provide significant benefits in OS (Van den Bent et al., 2006). Radiation therapy remains the backbone of care for glioblastomas, even in patients who have undergone a prior presumed complete resection. The infiltrative nature of these tumors makes a truly complete resection nearly impossible in most cases (Behin et al., 2003; Black, 1991a, 1991b; DeAngelis, 2001, Fine et al., 1993; Hall, 1978; Stewart, 2002; Walker et al., 1978, 1980). Standard fractionated radiation therapy delivers a total radiation dose of 60 Gy given in 30 fractions over 6 weeks. The target is usually the tumor bulk as visualized on CT or MRI, with a wide margin of 2-3 cm (Behin et al., 2003; Black, 1991a, 1991b; DeAngelis,