High grade gliomas do poorly in the long term and frequently recur. Initial treatment is maximum safe resection followed by radiation therapy concurrent with temozolomide. Temozolomide doses are generally daily at 75 mg/m2 for 42 days concurrent with radiation therapy. Radiation doses are 50 Gy (50.4 Gy) to the T2 edema on MRI with a 2 cm margin followed by a boost to the T1 enhancing area with a 1.5 - 2 cm margin corrected for anatomical barriers to spread. The final boost dose is 60 Gy (59.4 Gy). Prognosis remains dismal with OS2 27% and median survival 14.6 months. The disease generally recurs within 2 cm of the resection margin in nearly all patients.
Salvage radiation for recurrent therapy is limited, as in the modern series, most patients have already received a full course of radiation during primary treatments. Re-irradiation carries the risk of significant radiation morbidity and has been limited. More recently improved imaging modalities have permitted better visualization of recurrent tumor and better irradiation techniques have also permitted more accurate target definition and radiation delivery, which allows greater safety in re-irradiation.
Advances in radiobiology have also identified repair to radiation damage, depending on the primary dose and fractionation scheme, along with the time from initial irradiation. As of now, radiobiologists have not been able to identify the repair mechanisms in play nor their time rates. Typical course of radiation delivered at 1.8 - 2 Gy /fraction to 59.4 - 60 Gy/fraction yield an approximate BED (α/β = 2 (est.) for late effects) of 112.8 Gy2 and an EQD2 Dose of 56 Gy - 60 Gy. At 2 Gy/fraction to 60 Gy the BED is 120.0 Gy2.
Serial MRI imaging, physical examination and assessment of performance status is important. Evaluation for re-resection is useful, but surgical management is generally not offered. Second line chemotherapeutic drugs including bevacizumab and chemotherapeutic agents (irinotecan, temozolomide, carboplatin, carmustine), combination PCV (procarbazine, lomustine, vincristine) have all been used. Various radiation techniques including brachytherapy using I-125 implant, external beam highly conformal techniques (IMRT/3DCRT, IGRT) have been used with modest success with overall survivals reported at 8 - 12 months.
Most irradiation techniques use fractionated stereotactic techniques. SRS (single fraction) has been used but with the advent of better positioning and reproducibility and multi-leaf collimation techniques, re-irradiation of involved tissue is now more conformal, limiting additional brain doses outside of the recurrence field. Many centers treat to a total dose of 35 Gy at 2.5 Gy/fraction in 14 fractions. If the relapse volume is large (> 100 cm3) smaller dose per fraction schemes were preferred.
Prognostic factors are:
Re-irradiation of the brain carries significant risks, once normal tissue tolerance ranges are reached. Radionecrosis, neurocognitive decline, decreasing performance status and steroid dependency are common. Lawrence estimates the risk of radionecrosis at around 105 GyBED3 and notes greater risk with larger fraction sizes. The decision to re-treat must be carefully weighed against the sequalae of progressive disease and patient preference.