title: Predictors of survival and effect of short (40 Gy) or standard-course (60 Gy) irradiation plus concomitant temozolomide in elderly patients with glioblastoma: a multicenter retrospective study of AINO (Italian Association of Neuro-Oncology).
abstract: The efficacy of temozolomide (TMZ) plus radiation therapy (RT) in elderly patients with glioblastoma is unclear. We performed a large multicenter retrospective study to analyze prognostic factors and clinical outcome in these patients. Inclusion criteria were age ≥65 years, newly histologically confirmed glioblastoma, ECOG PS 0-2, adjuvant treatment with RT plus TMZ. We enrolled 237 patients; the average age was 71 and ECOG PS was 0-1 in 196 patients; gross total resection was performed in 174 cases. MGMT was analyzed in 151 persons and was methylated in 56 %. IDH1 was assessed in 100 patients and was mutated in 6 %. Seventy-one patients were treated with RT 40 Gy and 166 with RT 60 Gy. Progression-free survival and overall survival (OS) were 11.3 and 17.3 months, respectively. Overall survival was 19.4 vs 13.8 months for patients treated with RT 60 Gy and 40 Gy (p = 0.02); OS was 17.7 versus 16.1 months for patients treated with gross total resection vs partial surgery (p = 0.02); OS was 21.2 versus 13.6 months for methylated and unmethylated MGMT (p < 0.001). On multivariate analysis, gross total resection, RT 60 Gy, methylated MGMT and ECOG PS 0-1 were independent predictors of longer survival. Twenty-five patients (10 %) had grade 3-4 haematological toxicity during the concomitant treatment. We showed that, in elderly patients in good clinical condition treated with concomitant treatment, standard-course irradiation might be more effective than short-course irradiation. Methylated MGMT remains the most important prognostic factor.
authors.affiliation: Department of Clinical and Experimental Oncology, Medical Oncology 1, Veneto Institute of Oncology IOV - IRCCS, via Gattamelata, 64, 35128, Padua, Italy. giuseppe.lombardi@ioveneto.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lombardi
authors.affiliation: Neuro-Oncology Unit, "Regina Elena" National Cancer Institute, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pace
authors.affiliation: Department of Radiotherapy, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pasqualetti
authors.affiliation: Department of Oncology, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Rizzato
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Faedi
authors.affiliation: Unit of Molecular Neuro-Oncology, Fondazione I.R.C.C.S. Istituto Neurologico C. Besta, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Anghileri
authors.affiliation: Department of Neuro-Oncology, University of Turin and City of Health and Science, University Hospital, Turin, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Nicolotto
authors.affiliation: Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.|IRCCS, Centro S. Giovanni di Dio - Fatebenefratelli, Brescia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Bazzoli
authors.affiliation: Department of Clinical and Experimental Oncology, Medical Oncology 1, Veneto Institute of Oncology IOV - IRCCS, via Gattamelata, 64, 35128, Padua, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Bellu
authors.affiliation: Neuro-Oncology Unit, "Regina Elena" National Cancer Institute, Rome, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Villani
authors.affiliation: Division of Medical Oncology, "Regina Elena" National Cancer Institute, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabi
authors.affiliation: Department of Radiotherapy, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferrazza
authors.affiliation: Department of Oncology, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Gurrieri
authors.affiliation: Biostatistics and Clinical Trials Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Monia
authors.initials: M
authors.lastname: Dall'Agata
authors.affiliation: Unit of Molecular Neuro-Oncology, Fondazione I.R.C.C.S. Istituto Neurologico C. Besta, Milan, Italy.
authors.forename: Marica
authors.initials: M
authors.lastname: Eoli
authors.affiliation: Neurosurgery Department, Azienda Ospedaliera di Padova, Padua, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Della Puppa
authors.affiliation: Department of Clinical and Experimental Oncology, Medical Oncology 1, Veneto Institute of Oncology IOV - IRCCS, via Gattamelata, 64, 35128, Padua, Italy.
authors.forename: Ardi
authors.initials: A
authors.lastname: Pambuku
authors.affiliation: Neurosurgery Department, University of Padua, Padua, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: D'Avella
authors.affiliation: Radiation Therapy and Nuclear Medicine Unit, Veneto Institute of Oncology IOV IRCCS, Padua, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Berti
authors.affiliation: Department of Neuro-Oncology, University of Turin and City of Health and Science, University Hospital, Turin, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Rudà
authors.affiliation: Department of Clinical and Experimental Oncology, Medical Oncology 1, Veneto Institute of Oncology IOV - IRCCS, via Gattamelata, 64, 35128, Padua, Italy.
authors.forename: Vittorina
authors.initials: V
authors.lastname: Zagonel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy; D019175:DNA Methylation / Q000187:drug effects / Q000528:radiation effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D007558:Italy; D017567:Karnofsky Performance Status; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide
keywords: Chemotherapy; Elderly; Glioblastoma; Radiation therapy; Temozolomide