Pseudoprogression Is Frequent After Front-Line Radiation Therapy in Pediatric Low-Grade Glioma: Results From the German Low-Grade Glioma Cohort

Bison B.; Pietsch T.; Pham M.; Schmidt R.; Warmuth-Metz M.; Gnekow A.K.; Stock A.; Hancken C.V.; Kandels D.; Kortmann R.D.; Dietzsch S.; Timmermann B.

Research article (journal) | Peer reviewed

Abstract

Purpose: Expansion of magnetic resonance imaging T2- or T1-tumor lesion volume after radiation therapy (RT) may indicate pseudoprogression (PsPD). The differentiation between true progression and PsPD is a clinical challenge and underinvestigated in pediatric low-grade glioma (LGG). We evaluated radiologic criteria for PsPD after front-line RT and investigated the frequency and duration of PsPD after 3 RT-modalities within the framework of the German pediatric multicenter LGG-studies. Methods and Materials: Baseline and follow-up magnetic resonance imaging scans of 136 patients (72 male [52.9%], median age at start of RT of 11.3 years [range, 0.8-25.9]) of the Society for Pediatric Oncology-LGG 2004 study and LGG-registry cohorts (125iodine-interstitial [IS] RT [n = 51], photon-beam [XRT; n = 60], or proton-beam RT [PBT; n = 25]) were centrally evaluated for increasing: (1) total tumor-associated T2 lesion, (2) focal tumor-associated T2 lesion, and (3) contrast-enhancing tumor during a period of 24 months after RT. The pattern of these criteria initiated “suspicion” of PsPD; their evolution determined “definite” PsPD. Results: Definite PsPD was radiologically determined in 54 of 136 (39.7%) without differences in frequency between RT-modalities: IS 22 of 48 versus XRT 24 of 54 versus PBT 11 of 20; P = .780. Definite PsPD occurred at median 6.3 months (IS 7.2 months; XRT 4.4 months; PBT 6.5 months) after RT-initiation and persisted for median 7.2 months (IS 8.5 months; XRT 7 months; PBT 7.4 months). Appearance of necrosis within the focal tumor-associated T2 lesion proved to be a relevant associated predictor of definite PsPD (P < .001). Conclusions: PsPD is frequent after irradiation of pediatric LGG and independent of the RT modality (IS vs XRT vs PBT). Adequate identification of PsPD versus true progression is imperative to prevent unneeded salvage treatment.