Читать книгу Intracranial Gliomas Part II - Adjuvant Therapy - Группа авторов - Страница 56

The use of adjuvant irradiation for low-grade gliomas (LGG) is controversial. The EORTC 22845 study randomized patients with such neoplasms to receive surgery alone with delayed FRT at the time of tumor progression, or surgery immediately followed by early FRT to a dose of 54 Gy [26]. PFS was improved in patients receiving early postoperative FRT (5.3 vs. 3.4 years; p < 0.0001); however, there was no difference in overall survival. At one year, seizures were better controlled in the early FRT group [26].

At the same time EORTC opened protocol 22844 randomizing patients with cerebral LGG to receive postoperative FRT to a dose of either 45 Gy in 25 fractions or 59.4 Gy in 33 fractions [27]. With a median follow-up of 74 months, no difference in overall survival or PFS was noted. In a follow-up report, quality of life (QOL) data were analyzed showing a lower level of functioning and greater symptom burden in those receiving high-dose treatment [28]. An intergroup trial randomized patients with LGG to receive either 50.4 Gy in 28 fractions or 64.8 Gy in 36 fractions [29]. Once again, no difference in survival was noted. A doubling of grade 3–5 radiation necrosis was marked in the high-dose arm [29].

Several negative prognostic factors were identified in the EORTC trials including astrocytoma histology, age ≥40 years, lesion diameter ≥6 cm, tumor crossing midline, and the presence of neurologic deficit [30]. High-risk patients with more than 3 negative prognostic factors had a median survival of 3.7 vs. 7.8 years in low-risk patients [30]. In the RTOG 9802 study, patients with LGG were defined as having either favorable risk (age <40 years and gross total resection [GTR]) or unfavorable risk (either age ≥40 years or less than a GTR). The favorable risk group was observed. Patients in the unfavorable risk group were randomized to receive FRT alone to a dose of 54 Gy or FRT followed by 6 cycles of PCV chemotherapy [31]. With a median follow-up of 5.9 years, no difference in overall survival was noted for the entire cohort. However, a post hoc analysis on those patients surviving at least 2 years revealed an improvement in overall survival (hazard ratio [HR] 0.52; p = 0.02) and PFS (HR 0.44; p < 0.001) for patients treated with FRT followed by PCV chemotherapy [31]. Updated analysis of the study cohort with a median follow-up period of 11.9 years has confirmed statistically significant improvement of overall survival and PFS in patients treated with FRT followed by adjuvant PCV chemotherapy [32].

The EORTC has completed a study in high-risk patients with LGG randomized to receive either FRT alone or TMZ alone. These results are pending. An intergroup trial is currently open randomizing patients with LGG to receive FRT alone or FRT with concurrent and adjuvant TMZ.