Pseudoprogression in children, adolescents and young adults with non-brainstem high grade glioma and diffuse intrinsic pontine glioma

Abstract

Pseudoprogression (PsP) is a treatment-related phenomenon which hinders response interpretation. Its prevalence and clinical impact have not been evaluated in children/adolescents. We assessed the characteristics, risk factors and prognosis of PsP in children/adolescents and young-adults diagnosed with non-brainstem high grade gliomas (HGG) and diffuse intrinsic pontine gliomas (DIPG). Patients aged 1-21 years diagnosed with HGG or DIPG between 1995 and 2012 who had completed radiotherapy were eligible. PsP was assessed according to study-specific criteria and correlated with first-line treatment, molecular biomarkers and survival. Ninety-one patients (47 HGG, 44 DIPG) were evaluable. Median age: 10 years (range, 2-20). Eleven episodes of PsP were observed in 10 patients (4 HGG, 6 DIPG). Rates of PsP: 8.5 % (HGG); 13.6 % (DIPG). Two episodes of PsP were based on clinical findings alone; nine episodes had concurrent radiological changes: increased size of lesions (n = 5), new focal enhancement (n = 4). Temozolomide, MGMT methylation or H3F3A mutations were not found to be associated with increased occurrence of PsP. For HGG, 1-year progression-free survival (PFS) was 41.9 % no-PsP versus 100 % PsP (p = 0.041); differences in 1-year overall survival (OS) were not significant. For DIPG, differences in 1-year PFS and OS were not statistically significant. Hazard ratio (95 %CI) of PsP for OS was 0.551 (0.168-1.803; p = 0.325) in HGG; and 0.308 (0.107-0.882; p = 0.028) in DIPG. PsP occurred in both pediatric HGG and DIPG patients at a comparable rate to adult HGG. PsP was associated with improved 1-yr PFS in HGG patients. PsP had a protective effect upon OS in DIPG patients.

Pseudoprogression after radiation therapies for low grade glioma in children and adults: A systematic review and meta-analysis

“…Finally, there is limited evidence to suggest that 1p/19q co-deletion, typical of LGG, lowers the incidence of PsP after radiation [33,37]. Other genetic alterations such as methylation of the MGMT promoter region and mutation of IDH1 gene have also been associated with increased PsP as well [38,39], although we recognize that opposing evidence suggesting no effect also abounds [40,41]. More granular reporting for molecular data, will provide greater insights into possible stratification of LGG patients by radiation modality.…”

Advanced ADC Histogram, Perfusion, and Permeability Metrics Show an Association with Survival and Pseudoprogression in Newly Diagnosed Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium

“…Chassot et al 34 reported 4/22 (18%) cases of pseudoprogression in children with DIPG treated with RT + TMZ and found no difference in overall survival between pseudoprogression and true progression cases. Carceller et al 35 reported 6/44 (13.6%) cases of pseudoprogression in a DIPG cohort treated with various different treatment regimens and found no difference in overall survival between pseudoprogression and true progression groups. We also observed no evidence of a significant difference in overall survival among our patients with pseudoprogression versus those with true early progression (P ¼ .75).…”

Increased risk of pseudoprogression among pediatric low-grade glioma patients treated with proton versus photon radiotherapy

“…Among high-grade glioma patients (both children and adults), PsP predicts improved diseaserelated outcomes. 6,[46][47][48] Among LGG patients, this relationship is not as well defined, with reports conflicting regarding the interaction between PsP and outcome. 8,11,12 A B C…”