title: MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients.
abstract: OBJECTIVE
  Standard therapy for glioblastoma (GBM) is temozolomide (TMZ) administration, initially concurrent with radiotherapy (RT), and subsequently as maintenance therapy. The radiologic images obtained in this setting can be difficult to interpret since they may show radiation-induced pseudoprogression (psPD) rather than disease progression.
  
  
  METHODS
  Patients with histologically confirmed GBM underwent radiotherapy plus continuous daily temozolomide (75 mg/m(2)/d), followed by 12 maintenance temozolomide cycles (150 to 200 mg/m(2) for 5 days every 28 days) if magnetic resonance imaging (MRI) showed no enhancement suggesting a tumor; otherwise, chemotherapy was delivered until complete response or unequivocal progression. The first MRI scan was performed 1 month after completing combined chemoradiotherapy.
  
  
  RESULTS
  In 103 patients (mean age, 52 years [range 20 to 73 years]), total resection, subtotal resection, and biopsy were obtained in 51, 51, and 1 cases, respectively. MGMT promoter was methylated in 36 patients (35%) and unmethylated in 67 patients (65%). Lesion enlargement, evidenced at the first MRI scan in 50 of 103 patients, was subsequently classified as psPD in 32 patients and early disease progression in 18 patients. PsPD was recorded in 21 (91%) of 23 methylated MGMT promoter and 11 (41%) of 27 unmethylated MGMT promoter (P = .0002) patients. MGMT status (P = .001) and psPD detection (P = .045) significantly influenced survival.
  
  
  CONCLUSIONS
  PsPD has a clinical impact on chemotherapy-treated GBM, as it may express the glioma killing effects of treatment and is significantly correlated with MGMT status. Improvement in the early recognition of psPD patterns and knowledge of mechanisms underlying this phenomenon are crucial to eliminating biases in evaluating the results of clinical trials and guaranteeing effective treatment.
authors.affiliation: Department of Medical Oncology, Bellaria-Maggiore Hospital, Azienda Unità Sanitaria Locale of Bologna, Bologna, Italy. alba.brandes@yahoo.it
authors.forename: Alba A
authors.initials: AA
authors.lastname: Brandes
authors.forename: Enrico
authors.initials: E
authors.lastname: Franceschi
authors.forename: Alicia
authors.initials: A
authors.lastname: Tosoni
authors.forename: Valeria
authors.initials: V
authors.lastname: Blatt
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pession
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tallini
authors.forename: Roberta
authors.initials: R
authors.lastname: Bertorelle
authors.forename: Stefania
authors.initials: S
authors.lastname: Bartolini
authors.forename: Fabio
authors.initials: F
authors.lastname: Calbucci
authors.forename: Alvaro
authors.initials: A
authors.lastname: Andreoli
authors.forename: Giampiero
authors.initials: G
authors.lastname: Frezza
authors.forename: Marco
authors.initials: M
authors.lastname: Leonardi
authors.forename: Federica
authors.initials: F
authors.lastname: Spagnolli
authors.forename: Mario
authors.initials: M
authors.lastname: Ermani
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D001927:Brain Diseases / Q000201:enzymology / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics* / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D018579:Patient Selection; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D011832:Radiation Injuries / Q000201:enzymology / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012189:Retrospective Studies; D000077204:Temozolomide; D013997:Time Factors; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide