Chapter 8 - Principles of radiation therapy

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Abstract

Although resection remains the mainstay in the treatment of gliomas, microscopically complete resection of most central nervous system tumors remains challenging, and is, in fact, rarely accomplished. Considering their invasive nature, gross total resections to clearly negative margins often do or would require removal or transection of functional brain, with likely serious neurologic deficits. Consequently, radiotherapy has emerged as an indispensable component of therapy. It is delivered primarily by external-beam radiotherapy or brachytherapy techniques. Herein, we present the biologic principles, techniques, and applications of radiotherapy in glioma treatment today.

Section snippets

Biologic principles of radiotherapy

Discovered by Wilhelm Conrad Roentgen in 1895, and complemented by the Curies’ characterization of radioactivity 3 years later, X-ray radiation was quickly recognized for its potential medical applications (Daniel, 2006). On a cellular level, radiation imparts energy to a cell either through direct disruption of the deoxyribonucleic acid (DNA) genetic chain or through the production of free radicals within the cell cytosol (Kolesnick and Fuks, 2003). Although radiation likely has ramifications

Glioblastoma

Glioblastoma multiforme (GBM) is the most prevalent malignant primary brain tumor, and carries a particularly poor prognosis. Despite improvements in surgical management, the advent of modern systemic therapies such as temozolomide and bevacizumab, significant innovations in the delivery of radiotherapy, generally negative testing of targeted agents, and the development of an alternating electric-field device, this disease remains resistant, with rapid relapses being the norm. The current

Anaplastic glioma

Anaplastic gliomas, which may be subdivided into oligodendrocytic, astrocytic, and mixed subtypes, represent approximately one-quarter of high-grade gliomas. Despite some similarities, these tumors tend not to exhibit the necrosis and neovascularization characteristics of grade IV tumors. Patients with anaplastic disease have superior survival compared to GBM, with historic median survival rates of approximately 3 years and greater than 5 years for astrocytic and oligodendroglial tumors,

Low-grade gliomas

With approximately 2000 cases diagnosed per year, low-grade gliomas represent a heterogeneous population of tumors, in terms of both natural history and prognosis (Okazaki, 1983, Levin et al., 1993). The WHO classification divides these tumors into grades I and II (Louis et al., 2007). Pathologically, they are also divided into three primary groups: oligodendroglioma, oligoastrocytoma, and astrocytoma. The astrocytic tumors are further subdivided to include the pilocytic, diffuse, subependymal

Pilocytic astrocytoma

Pilocytic astrocytoma is a grade I entity with excellent prognosis. Resection remains the primary therapy for this disease. Radiation therapy may be considered for subtotally resected tumors but remains controversial (Wallner et al., 1988, Freeman et al., 1998). Several institutional experiences have shown improved disease control with the addition of adjuvant radiation, especially for recurrent disease; Wallner et al. reported 74 and 41% PFS rates at 10 and 20 years (Wallner et al., 1988,

Pediatric gliomas

The timing of radiotherapy and its role as an upfront therapy in particularly young patients remains a controversial and evolving field of investigation. As previously discussed, the early addition of adjuvant radiotherapy improves PFS (van den Bent et al., 2005), but this must be weighed against the toxicity of utilizing radiotherapy in children. Due to concerns regarding neurocognitive deficits and neurologic developmental issues, radiotherapy is often delayed until progression or

Other gliomas

Ganglioglioma, optic-pathway glioma, and brainstem glioma represent three rarer, but separate, entities. They are each briefly addressed below, focusing on the role of radiation therapy in their management.

Radiation technique

While surgery remains the mainstay of primary therapy in the treatment of gliomas, radiation therapy remains an integral modality. The invasive nature of most gliomas makes complete resection nearly impossible in many cases without devastating neurologic effects. Therefore, radiotherapy using either brachytherapy or external-beam techniques including proton/particle therapy, stereotactic radiosurgery, or fractionated stereotactic radiotherapy is employed frequently. Each modality has inherent

Brachytherapy

Most recurrences of high-grade gliomas continue to be local, and intuitively, dose escalation in the surgical bed may eventually offer better control (Hochberg and Pruitt, 1980, Wallner et al., 1989). With dose escalation beyond 60 Gy with external-beam techniques demonstrating no improvement in disease control of glioblastoma, there has been increased interest in employing more focal techniques such as brachytherapy (Walker et al., 1980, Marks and Wong, 1985, Bleehen and Stenning, 1991).

The use

External-beam radiotherapy and proton/particle beam radiotherapy

The majority of the discussion regarding individual disease entities above focuses on external-beam radiotherapy techniques. Historically, “teletherapy” was delivered with two-dimensional techniques, utilizing plain radiographs for target delineation. With such a complicated set of disease entities within an organ, the brain, that is not well visualized on plain radiographs, prevention of errors in targeting of the postoperative cavities and residual disease required generous planning margins.

Conclusions

Radiotherapy may be delivered by a number of techniques safely and effectively for the management of gliomas. Newer modalities, such as proton/particle therapies, offer the promise of dose escalation with significant sparing of normal brain tissue and structures, but these need to be tested further in prospective clinical trials. Radiation will remain a mainstay, especially of adjuvant therapy, in treatment of gliomas and may have an expanding role with the advent of newer technologies.

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