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.
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Acknowledgments
Ms Helen Underwood, Royal Marsden Registry department. Mr Karl Spolander, PACS manager. Ms Julie Mycroft, Royal Marsden Pharmacy. We acknowledge NHS funding to the NIHR Biomedical Research Centre (BRC) and the NIHR Clinical Research Facility at The Royal Marsden and the Institute of Cancer Research, as well as Experimental Cancer Medicines Centre (ECMC) funding. Additionally, F.C. holds a senior fellowship funded by the BRC and the Sohn Foundation. L.F., L.M. and L.V.M. are funded by the Oak Foundation (Grant OCay-04-169). A.D.J.P. is supported by Cancer Research UK (CRUK): programme grant C1178/A10294 - Chair in Paediatric Oncology. M.O.L. is an NIHR Senior Investigator. CRUK and Engineering and Physical Sciences Research Council (EPSRC) funding to the pediatric programme in functional imaging (C7809/A10342).
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CRUK and EPSRC funding to the CRUK Centre for Cancer Imaging (C1060/A16464, C1060/A10334).
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Carceller, F., Fowkes, L.A., Khabra, K. et al. Pseudoprogression in children, adolescents and young adults with non-brainstem high grade glioma and diffuse intrinsic pontine glioma. J Neurooncol 129, 109–121 (2016). https://doi.org/10.1007/s11060-016-2151-8
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DOI: https://doi.org/10.1007/s11060-016-2151-8