title: 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.
authors.affiliation: Children & Young People's Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK. fernando.carceller@icr.ac.uk.|Division of Clinical Studies and Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK. fernando.carceller@icr.ac.uk.
authors.forename: Fernando
authors.initials: F
authors.lastname: Carceller
authors.affiliation: Department of Radiology, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, SM2 5PT, UK.
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Fowkes
authors.affiliation: Research Data Management and Statistics Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, SM2 5PT, UK.
authors.forename: Komel
authors.initials: K
authors.lastname: Khabra
authors.affiliation: Children & Young People's Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.|Division of Clinical Studies and Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK.|Clinical Research Unit - Pediatric Phase I-II Clinical Trials, Pediatric Oncology-Hematology Service, Hospital Niño Jesús, Av. de Menéndez Pelayo, num 65, 28009, Madrid, Spain.
authors.forename: Lucas
authors.initials: L
authors.lastname: Moreno
authors.affiliation: Department of Neuro Oncology, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, SM2 5PT, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Saran
authors.affiliation: Division of Clinical Studies and Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK.|Division of Molecular Pathology, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Burford
authors.affiliation: Division of Clinical Studies and Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK.|Division of Molecular Pathology, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Mackay
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69121, Heidelberg, Germany.
authors.forename: David T W
authors.initials: DT
authors.lastname: Jones
authors.affiliation: Division of Molecular Genetics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69121, Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Hovestadt
authors.affiliation: Children & Young People's Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.|Division of Clinical Studies and Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK.|Division of Molecular Pathology, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK.
authors.forename: Lynley V
authors.initials: LV
authors.lastname: Marshall
authors.affiliation: Children & Young People's Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.|Division of Clinical Studies and Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK.
authors.forename: Sucheta
authors.initials: S
authors.lastname: Vaidya
authors.affiliation: Department of Radiotherapy, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, SM2 5PT, UK.
authors.forename: Henry
authors.initials: H
authors.lastname: Mandeville
authors.affiliation: CRUK Cancer Imaging Centre, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Jerome
authors.affiliation: Department of Cellular Pathology, St George's Hospital, Blackshaw Road, London, SW17 0QT, UK.
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Bridges
authors.affiliation: Department of Clinical Neuropathology, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
authors.forename: Ross
authors.initials: R
authors.lastname: Laxton
authors.affiliation: Department of Clinical Neuropathology, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
authors.forename: Safa
authors.initials: S
authors.lastname: Al-Sarraj
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69121, Heidelberg, Germany.|Department of Pediatric Oncology and Hematology, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 672, 69120, Heidelberg, Germany.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pfister
authors.affiliation: CRUK Cancer Imaging Centre, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK.
authors.forename: Martin O
authors.initials: MO
authors.lastname: Leach
authors.affiliation: Children & Young People's Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.|Division of Clinical Studies and Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK.
authors.forename: Andrew D J
authors.initials: AD
authors.lastname: Pearson
authors.affiliation: Division of Clinical Studies and Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK.|Division of Molecular Pathology, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Jones
authors.affiliation: Department of Radiology, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, SM2 5PT, UK.
authors.forename: Dow-Mu
authors.initials: DM
authors.lastname: Koh
authors.affiliation: Children & Young People's Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.|Division of Clinical Studies and Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK.
authors.forename: Stergios
authors.initials: S
authors.lastname: Zacharoulis
mesh_terms: D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D020295:Brain Stem Neoplasms / Q000235:genetics* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy / Q000009:adverse effects; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D006657:Histones / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors; D000077204:Temozolomide; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; C000609950:H3-3A protein, human; D006657:Histones; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide
keywords: Brain tumors; Childhood; Children; Diffuse intrinsic pontine glioma; High grade glioma; Pseudoprogression