Background. IDH-mutant anaplastic astrocytomas (AA) are chemosensitive tumours for which the best choice of adjuvant chemotherapy between procarbazine, CCNU and vincristine (PCV) or temozolomide (TMZ) after radiotherapy (RT) remains unclear. Methods. In a large cohort of patients with histologically proven WHO 2016 AA with IDH1/2 mutations included in the French national POLA cohort (n=355), the primary objective was to compare progression-free survival (PFS) between the two treatment regimens (n=311). Secondary endpoints were overall survival (OS), progression type, pseudoprogression rate, and toxicity.Results. The 4-year PFS in the RT + PCV arm was 70.8% vs 53.5% in the RT + TMZ arm, with a hazard ratio (HR) of 0.58 CI95% [0.38; 0.87], P=0.0074 in univariable analysis and 0.63 CI95% [0.41; 0.97], P=0.0348 in multivariable analysis. The 4-year OS in the RT + PCV arm was 84.3% vs 76.6% in the RT + TMZ arm, with a HR of 0.57 CI95% [0.30; 1.05], P=0.0675 in univariable analysis. Toxicity was significantly higher in the RT + PCV arm with more grade ≥3 toxicity (46.7% versus 8.6%, P<0.0001). Conclusions. RT + PCV significantly improved PFS compared to RT + TMZ for IDH-mutant AA. However, RT + TMZ was better tolerated.

HighlightsThe GIRAFE trial will evaluate an adaptive radiotherapy method.48 patients will be included.They will undergo 4 intermediate re-planning CTs ( iCTs) and 35 daily MVCT.MVCT adaptive segmentation will be compared with manual recontouring.Deformable contour deformation on iCTs will be compared with manual recontouring.

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