Biomedical Engineering Reference
In-Depth Information
1.
Introduction
Gliomas are the most common primary brain tumors in adults, with a
worldwide incidence of approximately 7 out of 100,000 individuals per year.
Although brain tumors constitute only a small proportion of overall human
malignancies, they carry high rates of morbidity and mortality. Mortality
is still close to 100% and the average survival of patients with glioblastoma
multiforme (GBM) is less than 1 year when classical treatment is used.
Recent progress in multimodal treatment of this disease has led to only a
slight increase in average survival up to 15-18 months. The effectiveness of
the actual chemotherapeutic approach and multimodal targeted therapies
remains modest in gliomas.
Gliomas are brain tumors with histological, immunohistochemical and
ultra structural features of glial differentiation. Approximately 50% of pri-
mary brain tumors are gliomas, arising from astrocytes, oligodendrocytes,
or their precursors and ependymal cells. Gliomas are classified from I to
IV according to the World Health Association (WHO) malignancy scale.
Grade I gliomas are benign with a slow proliferation rate and include py-
locitic astrocytoma most common in pediatric age. Grade II gliomas are
characterized by a high degree of cellular differentiation and grow diffusely
into the normal brain parenchyma and are prone to malignant progression.
They include astrocytoma, oligodendroglioma and oligoastrocytoma. Grade
III lesions include anaplastic astrocytoma, anaplastic oligoastrocytoma and
anaplastic oligodendroglioma. These tumors show a higher cellular density
and a notable presence of atypia and mitotic cells. Grade IV tumors are the
most malignant and also the most frequent gliomas and include glioblas-
toma and gliosarcoma. These tumors presented microvascular proliferations
and pseudopalisading necrosis.
Conventional brain tumor treatments include surgery, radiation therapy
and chemotherapy. Surgical treatment is invasive but represents the first
approach for the vast majority of brain tumors due to difficulties arising
in early stage detection. However, after surgical resection, the residual pool
of invasive cells rises to recurrent tumor which, in 96% of cases arise ad-
jacent to the resection margins [1]. Aggressive treatment modalities have
extended the median survival from 4 months to 1 year, but the survival is
often associated with significant impairment in the quality of life. Radiation
therapy and chemotherapy are non-invasive options often used as adjuvant
therapy, but may also be effective for curing early-stage tumors. In patients
with recurrent GBM, the 6-months progression-free survival is only 21%
after treatment with temozolomide [2]. Adjuvant radiotherapy gives limited
benefits and causes debilitation side effects which reduce its efficacy [3]. The
effectiveness of systemic chemotherapy is limited by toxic effects on healthy
cells, generally resulting in morbidity or mortality of the patient. Moreover,
the presence of the BBB limits the passage of a wide variety of anticancer
