Is age an additional factor in the treatment of elderly patients with glioblastoma? A new stratification model: an Italian Multicenter Study

Author:

Ius Tamara1,Somma Teresa2,Altieri Roberto3,Angileri Filippo Flavio4,Barbagallo Giuseppe Maria35,Cappabianca Paolo2,Certo Francesco35,Cofano Fabio6,D’Elia Alessandro7,Della Pepa Giuseppe Maria8,Esposito Vincenzo79,Fontanella Marco Maria10,Germanò Antonino4,Garbossa Diego6,Isola Miriam11,La Rocca Giuseppe812,Maiuri Francesco2,Olivi Alessandro8,Panciani Pier Paolo10,Pignotti Fabrizio12,Skrap Miran1,Spena Giannantonio13,Sabatino Giovanni812

Affiliation:

1. Neurosurgery Unit, Department of Neurosciences, Santa Maria della Misericordia University Hospital, Udine;

2. Division of Neurosurgery, Department of Neurosciences, Reproductive and Odontostomatological Sciences, Università degli Studi di Napoli Federico II, Naples;

3. Department of Medical and Surgical Sciences and Advanced Technologies (G.F. Ingrassia); Neurological Surgery, Policlinico “G. Rodolico - San Marco” University Hospital, University of Catania;

4. Division of Neurosurgery, BIOMORF Department, University of Messina;

5. Interdisciplinary Research Center on Brain Tumors Diagnosis and Treatment, University of Catania;

6. Department of Neuroscience “Rita Levi Montalcini,” Neurosurgery Unit, University of Turin;

7. Department of Neurosurgery “Giampaolo Cantore”–IRCSS Neuromed, Pozzilli;

8. Institute of Neurosurgery, Fondazione Policlinico Gemelli, Catholic University, Rome;

9. Department of Human Neurosciences–“Sapienza” University of Rome;

10. Division of Neurosurgery, Department of Surgical Specialties, Radiological Sciences and Public Health, University of Brescia;

11. Department of Medicine, University of Udine;

12. Department of Neurosurgery, Mater Olbia Hospital, Olbia, Italy

13. Department of Neurosurgery, Alessandro Manzoni Hospital, Lecco; and

Abstract

OBJECTIVEApproximately half of glioblastoma (GBM) cases develop in geriatric patients, and this trend is destined to increase with the aging of the population. The optimal strategy for management of GBM in elderly patients remains controversial. The aim of this study was to assess the role of surgery in the elderly (≥ 65 years old) based on clinical, molecular, and imaging data routinely available in neurosurgical departments and to assess a prognostic survival score that could be helpful in stratifying the prognosis for elderly GBM patients.METHODSClinical, radiological, surgical, and molecular data were retrospectively analyzed in 322 patients with GBM from 9 neurosurgical centers. Univariate and multivariate analyses were performed to identify predictors of survival. A random forest approach (classification and regression tree [CART] analysis) was utilized to create the prognostic survival score.RESULTSSurvival analysis showed that overall survival (OS) was influenced by age as a continuous variable (p = 0.018), MGMT (p = 0.012), extent of resection (EOR; p = 0.002), and preoperative tumor growth pattern (evaluated with the preoperative T1/T2 MRI index; p = 0.002). CART analysis was used to create the prognostic survival score, forming six different survival groups on the basis of tumor volumetric, surgical, and molecular features. Terminal nodes with similar hazard ratios were grouped together to form a final diagram composed of five classes with different OSs (p < 0.0001). EOR was the most robust influencing factor in the algorithm hierarchy, while age appeared at the third node of the CART algorithm. The ability of the prognostic survival score to predict death was determined by a Harrell’s c-index of 0.75 (95% CI 0.76–0.81).CONCLUSIONSThe CART algorithm provided a promising, thorough, and new clinical prognostic survival score for elderly surgical patients with GBM. The prognostic survival score can be useful to stratify survival risk in elderly GBM patients with different surgical, radiological, and molecular profiles, thus assisting physicians in daily clinical management. The preliminary model, however, requires validation with future prospective investigations. Practical recommendations for clinicians/surgeons would strengthen the quality of the study; e.g., surgery can be considered as a first therapeutic option in the workflow of elderly patients with GBM, especially when the preoperative estimated EOR is greater than 80%.

Publisher

Journal of Neurosurgery Publishing Group (JNSPG)

Subject

Neurology (clinical),General Medicine,Surgery

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