title: Genetic and metabolic predictors of chemosensitivity in oligodendroglial neoplasms.
abstract: The -1p/-19q genotype predicts chemosensitivity in oligodendroglial neoplasms, but some with intact 1p/19q also respond and not all with 1p/19q loss derive durable benefit from chemotherapy. We have evaluated the predictive and prognostic significance of pretherapy (201)Tl and (18)F-FDG SPECT and genotype in 38 primary and 10 recurrent oligodendroglial neoplasms following PCV chemotherapy. 1p/19q loss was seen in 8/15 OII, 6/15 OAII, 7/7 OIII, 3/11 OAIII and was associated with response (Fisher-Exact: P=0.000) and prolonged progression-free (log-rank: P=0.002) and overall survival (OS) (log-rank: P=0.0048). Response was unrelated to metabolism, with tumours with high or low metabolism showing response. Increased (18)F-FDG or (201)Tl uptake predicted shorter progression-free survival (PFS) in the series (log-rank: (201)Tl P=0.0097, (18)F-FDG P=0.0170) and in cases with or without the -1p/-19q genotype. Elevated metabolism was associated with shorter OS in cases with intact 1p/19q (log-rank: (18)F-FDG P=0.0077; (201)Tl P=0.0004) and shorter PFS in responders (log-rank: (18)F-FDG P=0.005; (201)Tl P=0.0132). (201)Tl uptake and 1p/19q loss were independent predictors of survival in multivariate analysis. In this initial study, (201)Tl and (18)F-FDG uptake did not predict response to PCV, but may be associated with poor survival following therapy irrespective of genotype. This may be clinically useful warranting further study.
authors.affiliation: JK Douglas Laboratories, Clatterbridge Hospital, Bebington, Wirral, UK. carol.walker@ccrt.nhs.uk
authors.forename: C
authors.initials: C
authors.lastname: Walker
authors.forename: B
authors.initials: B
authors.lastname: Haylock
authors.forename: D
authors.initials: D
authors.lastname: Husband
authors.forename: K A
authors.initials: KA
authors.lastname: Joyce
authors.forename: D
authors.initials: D
authors.lastname: Fildes
authors.forename: M D
authors.initials: MD
authors.lastname: Jenkinson
authors.forename: T
authors.initials: T
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Broome
authors.forename: K
authors.initials: K
authors.lastname: Kopitzki
authors.forename: D G
authors.initials: DG
authors.lastname: du Plessis
authors.forename: J
authors.initials: J
authors.lastname: Prosser
authors.forename: S
authors.initials: S
authors.lastname: Vinjamuri
authors.forename: P C
authors.initials: PC
authors.lastname: Warnke
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008130:Lomustine / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009837:Oligodendroglioma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011344:Procarbazine / Q000627:therapeutic use; D011446:Prospective Studies; D015996:Survival Rate; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D019788:Fluorodeoxyglucose F18; D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine