**4.7 Response to treatment**

406 Advances in the Biology, Imaging and Therapies for Glioblastoma

neurological examination and included Mini-Mental-Status score (MMS) and a quality-oflife questionnaire (EORTC – QLQ-C30, Brain Cancer Module BN-20) (Beauchesne et al., 2010). Baseline examination was performed at the end of radiation therapy regimen (within the first 10 days after completion of ultrafractionated irradiation) and then every 2 months until death. The first MRI (at the end of radiation therapy) constituted the baseline imaging to evaluate tumor response keeping in mind that radiation therapy artifacts if present should be taken into account when interpreting the images (Beauchesne et al., 2010). Tumor progression was defined according to the modified WHO criteria (Macdonald criteria) as an increase in tumor size by 25 percent (size of the product of the largest perpendicular diameters of contrast-enhancing tumor), the appearance of new lesions, or an increased need for corticosteroids (MacDonald et al., 1990). When there was tumor progression, patients were treated at the investigator's discretion, and the type of subsequent therapy

From September 2003 until June 2006, 31 patients were enrolled in this phase II study (16 males and 15 females). Median patient was 58 years (range 37 to 76). Median Karnofsky Performance Status (KPS) was 80, ranging from 60 to 100 (Beauchesne et al., 2010). The median time from diagnosis to the beginning of ultrafractionated radiation therapy was 6 weeks (ranging from 2 to 10 weeks) (Beauchesne et al., 2010). Four patients died before the beginning of irradiation and two decided to revert to the standard radiation therapy regimen after starting (Beauchesne et al., 2010). The radiation course was completed in 22 patients. Multi-focal glioblastoma was diagnosed in seven patients, four of whom received and completed the ultrafractionated regimen (Beauchesne et al., 2010). Neuropathology was review reviewed by a central laboratory and all but one case was diagnosed as glioblastoma as WHO classification, and one case was secondary and classified as anaplastic

No toxic death occurred during the ultrafactionated irradiation and no radiation therapy regimen was discontinued. All but three patients (25 patients) received the ultrafractionated irradiation, and 22 completed the course of the treatment (Beauchesne et al., 2010). Two patients with a very large tumor progressed during the radiation therapy, and radiation therapy leading to premature discontinuation after 48 and 56 Gy. The most common adverse event was fatigue, as is frequently observed in standard cranial radiation therapy (Beauchesne et al., 2010). Although the ultrafractionation regimen was a constraint to patients, it was well accepted; only one out of 25 changed his mind during the course of the treatment, and was withdrawn. Overall, the ultrafractionated regimen was well tolerated.

After a median follow-up of 4 years, two of the 31 initial patients were alive (6.5 %). The median survival was 9.53 months (Beauchesne et al., 2010). The OS at 6, 12, 18 and 24 months was respectively 74.19 %, 29.03 %, 19.35 % and 15.48 %. The median PFS was 5.09 months. The PFS at 6, 12, 18, and 24 months was respectively 45.16 %, 12.90 %, 6.45 % and 6.45 % (Beauchesne et al., 2010). No difference was found in the median survival for age and sex: 8.4 months for males vs. 8.9 months for females, 8.4 months for < 55 years vs. 9.5

(usually chemotherapy) was recorded (Beauchesne et al., 2010).

**4.4 Patient characteristics** 

oligodendroglioma.

**4.6 Survival** 

**4.5 Safety and tolerability** 

Tumor response was analyzed (at the end of the ultrafractionated regimen and then 2 months later) using the WHO criteria. Eight stabilizations (corresponding to a decrease of less than 25 % of perpendicular transversal diameters – no cerebral edema and mass effect) were observed among the patients who had received the ultrafractionated radiation therapy (Fig. 5) (Beauchesne et al., 2010). In addition, the doses of corticosteroids were stable or decreased for these patients. Stabilization of tumor responses was observed either at the end of radiation therapy or in the following months. In the remaining cases, the tumor was nonprogressive (Beauchesne et al., 2010). In most cases, corticosteroids were decreased and stopped for several weeks. Half of the long term survivors did not receive a chemotherapy line.

A MRI scan B MRI scan.

Fig. 5. A stabilisation response was seen on a cranial MRI. A- At the beginning of treatment. B- At the end of radiotherapy.
