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A Phase II Study of 3D-Conformal Radiation Therapy plus Concurrent and Adjuvant Temozolomide in Newly Diagnosis Pure and Mixed Anaplastic Astrocytoma

2011; Elsevier BV; Volume: 81; Issue: 2 Linguagem: Inglês

10.1016/j.ijrobp.2011.06.469

1879-355X

Silvia Chiesa, Giuditta Chiloiro, Riccardo Autorino, S. Manfrida, Giuseppe Roberto D’Agostino, B. Diletto, Francesco Miccichè, Vincenzo Valentini, Carmelo Anile, M. Balducci,

Brain Metastases and Treatment

Anaplastic gliomas include pure astrocytomas (AA), oligodendrogliomas (AO) and mixed tumors. The current standard of care for first-line treatment is radiotherapy or chemotherapy. The role of combined modality treatment based on 3D- conformal radiation therapy (3D-CRT) and concurrent Temozolomide (TMZ) has to be defined. The aim of this phase II study was to evaluate survival, local control and toxicity of 3D-CRT plus concomitant and adjuvant temozolomide in this setting of patients. Patients (>18 yrs) with histological diagnosis of AA or AO were enrolled. Written consensus was obtained. After surgical resection, all patients were treated with 3D-CRT with concurrent TMZ (75 mg/m2 daily) from Monday to Friday. A total dose of 59.4 Gy/1.8 Gy daily was delivered to the surgical cavity with residual tumor, defined by T1-weighed MRI, plus 15-mm margin (CTV1). After a 4-week break, patients received also adjuvant chemotherapy with TMZ (150-200 mg/m2x 5 days) for at least 6 cycles. Acute toxicity was evaluated using RTOG criteria. The sample size of patients was assessed by the single proportion powered analysis. From October 2000 to August 2010, 59 patients (55.9% AA and 44.1% AO) were enrolled; 41 (69.5%) were male and 18 (30.5%) female. Median age was 41 years (range 18- 71). Thirty-five patients (59.3%) had a complete surgical resection and 23 patients (40.7%) presented a MR- proven residual tumor. Thirty-seven cases (63.1%) were classified as 1-3 RPA class and twenty-two (36.9%) as 4 RPA class. RTOG neurological toxicity G1-2 and G3 were 10.2% and 6.8%, respectively. RTOG hematological toxicity G1-2 and G3 was 16.9% and 10.1%, respectively. At a median follow-up of 55 months (range 3-123 months) 36 patients (61%) were alive. The median local control (LC) was 32 months and the 1 and 5-year LC was 90.8% and 42.3%, respectively. The median overall survival (OS) was 45 months (29 months for AA and not reach for AO) and the 1 and 5-year OS was 66.3%, and 34.2%, respectively (for AA 86.8 and 28.1%, respectively; for AO 95.7% and 56.5%, respectively [HR 4.1; 95%CI: 1.59-8.4]). A statistically significant difference in OS was found in patients with RPA class 1-3 (1 and 5-year OS 96.9%, and 70%) compared to those with RPA class 4 (1 and 5-year OS 79.7% and 7%) (p<0.001; HR: 0.18 IC: 0.05- 0.35). 3D-CRT and concurrent TMZ appear to represent a treatment well tolerated for WHO grade III gliomas and seems to increase local control and survival; a randomized controlled study is necessary to confirm these data.