Arm 1: Radiation Therapy: 59.4 Gy (1.8 Gy x 33 fractions, 5 days a week x 6 weeks) plus Temozolomide 200 mg/m2 daily on days 1-5 of the first week of radiotherapy. Repeat Temozolomide every 28 days for a total of 12 cycles.

Arm 2: Radiation Therapy: 59.4 Gy (1.8 Gy x 33 fractions, 5 days a week x 6 weeks) plus BCNU (80 mg/m2) on days 1, 2, and 3 of the first week of radiotherapy and on days 56, 57, and 58, then every eight weeks for four cycles for a total of six cycles (maximum BCNU dose 1440 mg/m2)

Arm 3: Radiation Therapy: 59.4 Gy (1.8 Gy x 33 fractions, 5 days a week x 6 weeks) plus BCNU 150 mg/m2 on day 5 of radiotherapy and Temozolomide 150 mg/m2 on days 1-5 of the first week of radiotherapy. Repeat every eight weeks for a total of six cycles; BCNU will be given on day 5 of Temozolomide in these cycles. (maximum BCNU dose 900 mg/m2).

6.1 Dose Definition and Schedule

Limited volume irradiation will be used for treatment in this protocol. Treatment will be given in 1.8 Gy fractions (to isocenter), 1 fraction per day, 5 days per week to a dose of 59.4 Gy in 33 fractions. The initial 50.4 Gy in 28 fractions will include the initial target volume (T2-MR plus 2 cm margin) or contrast-enhancing lesion +2.5 cm when no edema is present. The final 9 Gy in 5 fractions will include the boost volume (T1 enhanced MR plus 1 cm margin).

6.2 Physical Factors

Treatment will be delivered with megavoltage machines of energies ranging from 4 to 8 MV photons. Source skin distance for SSD techniques or source axis distance for SAD techniques must be > 80 cm. There must be at least two shaped treatment fields with each field treated daily. Treatment with a single beam is not acceptable. Port films of each field will be taken weekly, except for opposed fields with identical blocking where one film from each of the opposed fields should be taken weekly.

6.3 Simulation, Immobilization, Localization

6.3.1 The patient may be treated in the supine or other appropriate position. Adequate immobilization and reproducibility of position will be ensured. The treatment volume for both the initial volume and the cone down volume will be based on MRI scan.

6.3.1.1 The post-operative MRI scan will determine the treatment volume for patients without complete tumor resection.

6.3.1.2 The pre-operative MRI scan will determine the treatment volume for patients without a post-operative MRI scan (per Section 3.1.6.1).

6.3.2 The initial treatment volume will include the T2 abnormality plus a 2 cm margin. If there is no surrounding edema, the initial treatment volume should include the contrast and noncontrast-enhancing lesion plus a 2.5 cm margin. The boost volume will include the contrast and noncontrast-enhancing lesion plus a 1 cm margin. If the tumor has been completely resected and the MR scan for RT planning is normal, the initial volume will be the surgical defect plus a 2 cm margin. The boost volume will be the surgical defect plus a 1 cm margin. The target volumes are to receive 95-105% of the prescribed dose.

6.4 Dosimetry

Two sets of composite isodose distributions drawn in a plane containing the central axis, one showing the initial target volume and one showing the boost target volume, should be submitted with the following isodose lines in Gy: 25.2 Gy, 45.4 Gy, 47.9 Gy, 50.4 Gy, 52.9 Gy, 53.5 Gy, 55.4 Gy, 56.4 Gy, 59.4 Gy, 62.4 Gy, and 65.3 Gy. The following quality assurance guidelines will apply:

6.4.1 If the initial target volume receives < 45.4 Gy or > 55.4 Gy, (i.e., < 90% or > 110% of the prescribed total dose), a major deviation will be scored. If the boost volume receives < 53.5 Gy or > 65.3 Gy (i.e., < 90% or > 110% of the prescribed total dose), a major deviation will be assigned.

6.4.2 If the initial target volume receives 45.4-47.8 Gy or 53.0-55.4 Gy (i.e., 90-94% or 106-110 of the prescribed total dose) a minor variation will be scored. If the boost volume receives 53.5-55.8 Gy or 63.0-65.3 Gy (i.e., 90-94% or 106-110% of the prescribed total dose), a minor variation will be assigned.

6.4.3 If the initial target volume receives 47.9-52.9 Gy (i.e., 95-105% of the prescribed total dose), no deviation will be scored. If the boost volume receives 56.4-62.4 Gy (i.e., 95-105% of the prescribed total dose), no deviation will be assigned.

6.5 Dose Specification

Doses are specified as the target dose that shall be prescribed to the isocenter of the target volume. For the following portal arrangements, the target dose shall be specified as follows:

6.5.1 For two opposed coaxial equally weighted beams: on the central ray at mid-separation of beams.

6.5.2 For an arrangement of two or more intersecting beams: at the intersection of the central ray of the beams.

6.5.3 For complete rotation or arc therapy: in the plane of rotation at the center of rotation.

6.5.4 Treatment with a single beam is not acceptable due to unacceptable tumor dose inhomogeneity.

6.5.5 The technique of using two opposing co-axial unequally weighted fields is not recommended due to unacceptable hot spots due to unacceptable dose inhomogeneity. However, if this technique is utilized the dose shall be specified at the center of the target area.

6.5.6 Other or complex treatment arrangements: at the center of the target area.

6.6 Dose Limitation to Critical Structure

The lens and cervical spine must be shielded from the direct beam at all times. When possible to do without shielding gross tumor, attempts should be made to limit the dose to the optic chiasm to 60 Gy, the retina of at least one eye (but preferably both) to 50 Gy, and the brain stem to 60 Gy.

6.7 Treatment Delays

RT will be delayed or interrupted if the absolute granulocyte count is < 500 or the platelet count is < 20,000. RT will not begin or resume until the absolute granulocyte count is > 500 and the platelet count is > 20,000. Hematological toxicities should be rated on a scale of 0-5 as defined in the revised NCI Common Toxicity Criteria.