Therapeutic approach in glioblastoma multiforme with primitive neuroectodermal tumor components: Case report and review of the literature

Abstract

Abstract. Glioblastoma multiforme (GBM) is the most common and aggressive malignant glioma that is treated with first-line therapy, using surgical resection followed by local radiotherapy and concomitant/adjuvant temozolomide (TMZ) treatment. GBM is characterised by a high local recurrence rate and a low response to therapy. Primitive neuroectodermal tumour (PNET) of the brain revealed a low local recurrence rate; however, it also exhibited a high risk of cerebrospinal fluid (CSF) dissemination. PNET is treated with surgery followed by craniospinal irradiation (CSI) and platinum-based chemotherapy in order to prevent CSF dissemination. GBM with PNET-like components (GBM/PNET) is an emerging variant of GBM, characterised by a PNET-like clinical behaviour with an increased risk of CSF dissemination; it also may benefit from platinum-based chemotherapy upfront or following failure of GBM therapy. The results presented regarding the management of GBM/PNET are based on case reports or case series, so a standard therapeutic approach for GBM/PNET is not defined, constituing a challenging diagnostic and therapeutic dilemma. In this report, a case of a recurrent GBM/PNET treated with surgical resection and radiochemotherapy as Stupp protocol, and successive platinum-based chemotherapy due to the development of leptomeningeal dissemintation and an extracranial metastasis, is discussed. A review of the main papers regarding this rare GBM variant and its therapeutic approach are also reported. In conclusion, GBM/PNET should be treated with a multimodal approach including surgery, chemoradiotherapy, and/or the early introduction of CSI and platinum-based chemotherapy upfront or at recurrence.

ACT001, a novel PAI-1 inhibitor, exerts synergistic effects in combination with cisplatin by inhibiting PI3K/AKT pathway in glioma

“…However, GBM patients still have a poor median survival rate due to resistance to chemoradiotherapy. Platinum-based drugs, including cisplatin, are commonly used in tumour therapy 3,4 . Cisplatin has been used as a neoadjuvant therapy with temozolomide and as an adjuvant therapy with carmustine in malignant glioma therapy 5,6 .…”

Leptomeningeal Spread in Glioblastoma: Diagnostic and Therapeutic Challenges

“…Patients with LMS can suffer from cranial nerve palsies, increased intracranial pressure syndrome, hydrocephalus, meningism, and/or focal neurological deficits [1, 7, 15, 20, 33, 71–76]. Seizure frequency does not seem to increase during LMS development [77].…”

“…Astrocytic phenotype, high Ki67/Mib1 expression index [1, 29, 60, 85, 101, 102], and GFAP loss of expression either at initial diagnosis [10] or at recurrence [28, 29] were correlated with higher risk of LMS. Epithelioid GBM [26, 103, 104] and GBM with a neuronal component or primitive neuroectodermal tumor–like GBM [56, 74] disseminate more frequently to CSF.…”

“…Multiple chemotherapeutic regimens have been investigated: (a) temozolomide alone or combined with carmustine [7] or lomustine [55], (b) thiotepa alone [57, 58] or combined with procarbazine [20, 58, 64], (c) methotrexate [6, 15, 20, 57, 137], (d) cytarabine [19, 57, 128, 138, 139], (e) topotecan or irinotecan [15, 140, 141], and (f) platinum‐based agents with or without etoposide [56, 74]. Drug administration was either oral [7], intravenous [1, 6, 11, 15, 64, 142] intrathecal via Ommaya reservoir or lumbar puncture [6, 11, 19, 21, 57, 58, 138, 140, 141] or subcutaneous port [137], or combined [1, 6, 7, 11, 20, 110].…”

Treatment with Gold Nanoparticles Using Cudrania tricuspidata Root Extract Induced Downregulation of MMP-2/-9 and PLD1 and Inhibited the Invasiveness of Human U87 Glioblastoma Cells

“…There has been a substantial increase in the prevalence of glioblastoma, which has led to increased health concerns. In addition, the survival rate of glioblastoma patients is still poor, mainly due to the resistance, reoccurrence, metastasis, and severe treatment side effects [2,3]. Multiple extraneural metastasis of glioblastoma is responsible for the high patient mortality and poses a major challenge in the treatment of glioblastoma due to its complexity and multistep process.…”