Elderly patients with glioblastoma: the treatment challenge

Abstract

The treatment for elderly patients affected by glioblastoma represents a challenge in neuro-oncology. The recent randomized trials (the NOA-8 and the NCBTSG trials) showed an advantage of temozolomide for patients with O6-methylguanine methyltransferase methylated tumors. To date, no randomized trials compared the standard treatment (radiochemotherapy) with other therapeutic approaches, due to the idea that elderly patients do not tolerate aggressive therapy. Nonetheless, with the increased lifespan and the better quality of life, the nihilism in the treatment of elderly with cancer is obsolete. Molecular (including O6-methylguanine methyltransferase) and clinical tools (including the geriatric evaluation) are needed for choosing the proper therapy for patients over 70.

Keywords::

• elderly patients
• glioblastoma
• radiochemotherapy
• surgery
• temozolomide

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Glioblastoma (GBM) is increasing among elderly patients.

• • The standard treatment approach is still unclear in this setting of patients because the effectiveness of adjuvant radiochemotherapy followed by temozolomide (TMZ) was assessed only for patients under 70 years of age.

• • Surgery has a fundamental role both for cytoreduction and for obtaining samples for molecular analyses. Several authors have reported that surgery is the only factor independently associated with longer survival.

• • A randomized trial and a prospective single arm trial showed the survival advantage of radiotherapy (RT) compared with the best supportive care (7.3 vs 4.2 months, and 6 vs 1 months, respectively) without reducing quality of life in terms of severe adverse events, Karnofsky Performance Status (KPS) deterioration or cognitive functions.

• • The Neuro-oncology Working Group of the German Cancer Society (NOA-08 trial) failed to demonstrate the superiority of TMZ; in fact, the median overall survival (OS) was 8.6 versus 9.6 months in the TMZ and RT group, respectively, without statistical significance.

• • The Nordic Brain Tumor Study Group (NCBTSG trials) concluded that standard RT was associated with poor outcomes, while TMZ and hypofractionated RT did not differ in terms of survival, even if in the TMZ arm, hematological toxicity was higher compared with those reported in the RT arms.

• • At the moment, no randomized trial is conducted to determine which regime to prefer (standard vs less intensive vs palliative approach). Several retrospective and Phase II studies in patients over 65 showed the tolerability and effectiveness of standard approach reporting a mild toxicity and a median survival of 12–15 months.

• • It is important to differentiate the heterogeneous elderly population; only age is insufficient to discriminate the elderly who could undergo radical treatment and who could not, so ad hoc trials comparing standard and alternative approaches with the use of a standard nomogram for the treatment decision-making process, are necessary.