Alessandro D'Elia

Insights into pharmacotherapy of malignant glioma in adults

Malignant gliomas are the most common primary brain tumors in adults. In the past 10 years significant advances in the treatment of this entity have been made, mainly owing to a better understanding of molecular pathways and biological behavior of the oncogenetic process. This review treats the proven effective and promising approaches with chemotherapy. The standard care for glioblastoma is surgery and concomitant radio- and chemotherapy with temozolomide (TMZ), followed by adjuvant treatment with TMZ. It has been demonstrated to be the most effective treatment protocol. This standardized care allows the application and study of new types of treatment mainly in recurrences and nonresponding patients. Many different approaches have been investigated: the combination of cytotoxic and cytostatic agents as well as molecular targeted therapies have given some encouraging results. Further intensified regimens with TMZ and the local postsurgical application of slow-release polymers loaded with carmustine remain to be defined. The characterization of molecular markers thus becomes particularly important for the stratification of patients raising the possibility to individualize treatment.

Radio-induced low-grade glioma: report of two cases and review of the literature

With the increasing number of cancer survivors, we can observe a population that will present a higher risk of developing secondary long-term toxicities related to adjuvant chemo and radiotherapy regimens. Among these, children surviving from acute lymphoblastic leukemia (ALL) that were treated with prophylactic cranial irradiation represent a group of patients at a high risk of developing secondary brain tumors. Radiation-induced intracranial tumors have been documented since 1950, and today, more than one-hundred cases have been described. We report our experience with two young patients who were hospitalized for low grade gliomas and had a positive anamnesis for ALL and consequent radiotherapy.

Vincenzo Quercioli (1876-1939), researcher and pioneer of the atlas fracture.

A review of early 20th century literature regarding fractures of the atlas led the authors to discover a paper written in Italian by Professor Vincenzo Quercioli in 1908, at that time an assistant surgeon at the University of Siena. The work was published in the journal Il Policlinico, which at that time was directed by Professor Francesco Durante. The paper described the first case of a quadripartite fracture of the atlas, and it accurately reported the mechanism of injury, symptoms, neurological examination, treatment, complications, and cause of death of the patient. Quercioli performed an autopsy on the patient and gave a detailed description of anatomopathological features. In particular, he identified the 4 symmetrical fracture lines related to the arches of the atlas and the substantial integrity of the atlantoaxial ligaments, particularly the transverse ligament. Based on those findings, Quercioli concluded that the mechanism of trauma was an axial force. This force passed through the center of the vertebral ring and caused symmetrical displacement and compression of the articular masses. These concepts of dynamic physics led Quercioli to conclude that, because the atlas is wedge shaped, the masses of the atlas reacted to stress by moving away from the center. This reaction resulted in stretching the front and rear arches, which then fractured at their 4 points of weakness. The integrity of the spinal cord was intact, based on a negative neurological examination for CNS lesions. Thus, he concluded that these injuries were not fatal and could be cured by appropriate treatment with a Minerva cast and, in the presence of swallowing disorders, with a nasogastric tube. The case described by Quercioli was later mentioned in two classic works on atlas fractures by Sir Geoffrey Jefferson, published in 1920 and 1927. In those works, Jefferson proposed his classification of 5 different anatomopathological classes; this work is widely cited in the literature and should be considered a classic. The patterns and deductions that Jefferson reported on these fractures appeared to draw upon the scientific experience of Quercioli and his description of the quadripartite atlas fracture, which appeared to be unique, even in Jeffersons review. Therefore, the authors believe that they have identified another scientist and pioneer of the atlas fracture in Professor Vincenzo Quercioli. With his brilliant insights, which remain useful and valid, Quercioli led the way to further research on the subject.

Granular cell tumor of the neurohypophysis: a single-institution experience

Granular cell tumor (GCT) is a rare neoplasm occurring in the sellar and suprasellar spaces. It is a primary tumor of the neurohypophysis, presumably arising from the pituicytes, a distinctive glial cell of the neurohypophysis. GCTs in most reported cases show biologically benign behavior with slow growth. Only 70 cases of hypophyseal GCTs have been reported in the literature. We report a case of GCT in the neurohypophysis of a 46-year-old woman and discuss the histological and clinical features of this neoplasm together with the treatment modalities, reviewing the pertinent literature.

Transdural spread of glioblastoma multiforme with endonasal growth in a long-term survivor patient: case report and literature review

Glioblastoma (GBM) is the most aggressive primary tumor of the central nervous system (CNS) in adults. Its growth has been always described as locally invasive. This tumor rarely penetrates dura mater and invades extracranial structures. We present a case of GBM, which occurred in a 39-year-old man, with final involvement of the nasal cavity. The patient was operated four times in three years, and a personalized adjuvant chemotherapy regimen was administered in a neo-adjuvant fashion. Histopathological features of the tumor are described. To our knowledge, there are only 9 cases reported in the literature showing this growth pattern and the last case was reported in 1998.

Non‑conventional fotemustine schedule as second‑line treatment in recurrent malignant gliomas: Survival across disease and treatment subgroup analysis and review of the literature

Fotemustine (FTM) is a treatment option in recurrent malignant gliomas (MGs) after first-line Stupp treatment. The efficacy and the safety of fractionated FTM schedule proposed by Addeo et al was analysed in the present study in recurrent MGs patients. A retrospective analysis on 40 recurrent MGs patients and second-line fractionated FTM chemotherapy was performed. Response evaluation was assessed using RANO criteria and safety was assessed using CTCAE v.4.03. Subgroup analyses based on MGMT methylation, resurgery and reirradiation were performed. A review of the literature was also performed. The results revealed 5 partial responses (13%) and 19 stable diseases (47%) with a disease-control rate of 60%. Median progression-free survival (PFS) was 4 months, with a PFS of 33% at 6 months and 13% at 1 year. The median overall survival (OS) was 9 months and OS at 6 months was of 55% and at 1 year of 30%. Methylated patients experienced longer mPFS (6 vs. 3 months; p=0.004) and mOS (10 vs. 4 months; p<0.0001) compared with unmethylated patients. Patients treated with reirradiation experienced longer mPFS (5 vs. 3.5 months; p=0.48) and mOS (10 vs. 5 months; p=0.11). No survival benefit with resurgery was observed. Furthermore, the fractioned schedule was well tolerated, only 15% of patients developed severe myelotoxicities. Considering the present findings, fractionated FTM schedule is an efficient second-line option for MGs associated with an acceptable myelotoxicity profile. Additionally, MGMT methylation is associated with improved survival outcomes. However, this study highlights the requirement for further prospective randomized studies on resurgery and reirradiation.