Nicola Montemurro1, Giuseppe Nicolò Fanelli2, Cristian Scatena2, Valerio Ortenzi3, Francesco Pasqualetti4, Chiara Maria Mazzanti5, Riccardo Morganti6, Fabiola Paiar4, Antonio Giuseppe Naccarato2, Paolo Perrini7. 1. Department of Neurosurgery, Azienda Ospedaliera Universitaria Pisana (AOUP), Pisa, Italy; Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy. Electronic address: nicola.montemurro@unipi.it. 2. Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy; Division of Surgical Pathology, Pisa University Hospital, Pisa, Italy. 3. Division of Surgical Pathology, Pisa University Hospital, Pisa, Italy. 4. Department of Radiation Oncology, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. 5. Fondazione Pisana per la Scienza, Pisa, Italy. 6. Clinical Trial Statistical Support, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. 7. Department of Neurosurgery, Azienda Ospedaliera Universitaria Pisana (AOUP), Pisa, Italy; Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy.
Abstract
OBJECTIVE: Despite recent advances in diagnosis and treatment of the disease, the prognosis of patients with glioblastoma multiforme (GBM) remains poor. While the value of molecular pattern profiles at first diagnosis has been demonstrated, only few studies have examined these biomarkers at the time of recurrence. The aim of this study was to explore the impact of extent of resection at repeated craniotomy on overall survival (OS) of patients with recurrent GBM. In addition, we investigated the molecular pattern profiles at first and second surgery to evaluate possible temporal evolution of these patterns and to assess the effect of these modifications on OS. METHODS: We conducted a retrospective cohort study of 63 patients (mean age 59.2 years) surgically treated at least two times for recurrent GBM between 2006 and 2020. RESULTS: Median OS and progression-free survival (PFS) were 22 months (range 2-168 months) and 10 months (range 1-96 months), respectively. The OS following gross-total resection (GTR) at recurrence for patients with initial GTR (GTR/GTR) was significantly increased (42.6 months) compared with sub-total resection (STR) at reoperation after initial GTR (GTR/STR) (19 months) and with GTR at reoperation after initial STR (STR/GTR) (17 months) (p = 0.0004). Overall surgical morbidity resulted 12.7% and 11.1% at first and at second surgery, respectively. Changes in genetic profiles between first and second surgery of 1p/19q co-deletion, MGMT promoter methylation and p53 mutations occurred in 5.6%, 1.9% and 9.3% of cases, respectively. MGMT promoter methylation appeared to affect OS in univariate analysis at first (p = 0.038) and second surgery (p = 0.107), whereas p53 mutation appeared to affect OS only at second surgery (p = 0.01). In a multivariate analysis female sex (HR = 0.322, 95% CI 0.147-0.705; p = 0.005), PFS (HR = 0.959, 95% CI 0.934-0.986; p = 0.003), GTR at first and second surgery (HR = 0.195, 95% CI 0.091-0.419; p < 0.0001) and adjuvant chemotherapy at recurrence (HR = 0.407, 95% CI 0.206-0.809; p = 0.01) were associated with longer OS. CONCLUSIONS: This study confirmed the role of extent of resection (EOR) at first and at recurrence as a significant predictor of outcome in patients with recurrent GBM. In addition, this study highlighted the concept of a dynamic evolution of GBM genome after initial surgical resection, supporting the need of further studies to investigate the clinical and therapeutic implications of the changes in genetic profiles after initial surgery.
OBJECTIVE: Despite recent advances in diagnosis and treatment of the disease, the prognosis of patients with glioblastoma multiforme (GBM) remains poor. While the value of molecular pattern profiles at first diagnosis has been demonstrated, only few studies have examined these biomarkers at the time of recurrence. The aim of this study was to explore the impact of extent of resection at repeated craniotomy on overall survival (OS) of patients with recurrent GBM. In addition, we investigated the molecular pattern profiles at first and second surgery to evaluate possible temporal evolution of these patterns and to assess the effect of these modifications on OS. METHODS: We conducted a retrospective cohort study of 63 patients (mean age 59.2 years) surgically treated at least two times for recurrent GBM between 2006 and 2020. RESULTS: Median OS and progression-free survival (PFS) were 22 months (range 2-168 months) and 10 months (range 1-96 months), respectively. The OS following gross-total resection (GTR) at recurrence for patients with initial GTR (GTR/GTR) was significantly increased (42.6 months) compared with sub-total resection (STR) at reoperation after initial GTR (GTR/STR) (19 months) and with GTR at reoperation after initial STR (STR/GTR) (17 months) (p = 0.0004). Overall surgical morbidity resulted 12.7% and 11.1% at first and at second surgery, respectively. Changes in genetic profiles between first and second surgery of 1p/19q co-deletion, MGMT promoter methylation and p53 mutations occurred in 5.6%, 1.9% and 9.3% of cases, respectively. MGMT promoter methylation appeared to affect OS in univariate analysis at first (p = 0.038) and second surgery (p = 0.107), whereas p53 mutation appeared to affect OS only at second surgery (p = 0.01). In a multivariate analysis female sex (HR = 0.322, 95% CI 0.147-0.705; p = 0.005), PFS (HR = 0.959, 95% CI 0.934-0.986; p = 0.003), GTR at first and second surgery (HR = 0.195, 95% CI 0.091-0.419; p < 0.0001) and adjuvant chemotherapy at recurrence (HR = 0.407, 95% CI 0.206-0.809; p = 0.01) were associated with longer OS. CONCLUSIONS: This study confirmed the role of extent of resection (EOR) at first and at recurrence as a significant predictor of outcome in patients with recurrent GBM. In addition, this study highlighted the concept of a dynamic evolution of GBM genome after initial surgical resection, supporting the need of further studies to investigate the clinical and therapeutic implications of the changes in genetic profiles after initial surgery.
Authors: Rakesh Mishra; M D Krishna Narayanan; Giuseppe E Umana; Nicola Montemurro; Bipin Chaurasia; Harsh Deora Journal: Int J Environ Res Public Health Date: 2022-02-02 Impact factor: 3.390
Authors: Lucian Mărginean; Paul Andrei Ștefan; Andrei Lebovici; Iulian Opincariu; Csaba Csutak; Roxana Adelina Lupean; Paul Alexandru Coroian; Bogdan Andrei Suciu Journal: Brain Sci Date: 2022-01-14