123IN - The Biological Rationale and Potential Role of Radiation Dose Escalation in Patients with Brain Metastases

Abstract

ABSTRACT The majority of patients with BM from solid tumors have a prognosis of only a few months based on extracranial tumor activity and performance status. The standard of care for these patients consists of palliative treatment with steroids, and, if appropriate, a short course of whole brain radiotherapy (WBRT). Several prognostic classification systems such as the RPA classification [Gaspar 1997] or the DS-GPA [Sperduto 2008] enable identifying a subset of patients that may have long-term survival, provided that the BM are treated aggressively. Although neurosurgery is the traditional treatment for single BM at an accessible location, radiosurgery (RS) has been established as a non-invasive alternative. RS involves high-precision delivery of a single fraction of approximately 20 Gy directed to the lesion, resulting in local control rates of 60-90%, dependent on the size and aspect (poorer control for necrotic lesions). The survival benefit of RS has only been confirmed for a single BM in a randomized study [Andrews 2004], but improved functional autonomy was observed in all groups with 1-3 BM. The question whether WBRT should be added to RS has been a long-standing unresolved issue with proponents highlighting the better intracranial control, and opponents pointing out the neurocognitive toxicity of WBRT and available salvage options. As the risk of developing new BM following RS alone is not only dependent on extracranial tumor activity (reseeding) but also on the number of initially treated BM (misdiagnosis of occult BM), a more differentiated approach may be better suited. A well selected patient group with multiple BM in good performance status and absent progressive extracranial disease may be candidates for recently developed advanced radiation planning and delivery. Techniques such as volumetric intensity-modulated arc therapy (VMAT, RapidArc) or Tomotherapy have enabled fast and accurate delivery of fractionated stereotactic integrated boosts to multiple BM in combination with WBRT. The integrated approach of this technique allows steep dose gradients outside the BM, thereby minimizing toxicity. Early experiences with this technique have reported relatively high intracranial control rates. Disclosure F.J. Lagerwaard: The Department of Radiation Oncology has research agreements with Varian medical systems and BrainLAB AG. The author has received honoraria for presentations from Varian medical systems and BrainLAB AG