Primary Spine Tumors

Abstract

1. Radiation therapy is an extremely important modality in the management of primary spine tumors. However, the relative radioresistance of many of these tumors requires high doses for durable local tumor control. In general, radiation doses in excess of 70 Gy are necessary to adequately control macroscopic disease. Likewise, doses greater than 60 Gy in 2 Gy fractions, and preferably over 66 Gy, are required to treat positive microscopic margins. Traditional concepts of spinal cord tolerance establish the TD5/5 (the dose at which there is a 5% probability of a complication within 5 years) at 45–54 Gy in 2 Gy fractions, beyond which there appears to be a significantly increased risk of developing radiation myelitis [1]. In addition to the spinal cord, toxicities to paraspinal structures, such as small and large bowel, kidneys, and esophagus, must also be considered during spinal irradiation. Unfortunately, the radiation tolerances of these organs range from 23 to 65 Gy. The requirement to adhere to these normal tissue constraints severely limits the dose that can be delivered to spine tumors using conventional radiotherapy techniques and hence curbs the probability for achieving durable local tumor control and, potentially, cure. The need to deliver dose-escalated radiation therapy while minimizing treatment-related morbidity has led to the development of novel radiotherapy techniques such as image-guided intensity-modulated radiation therapy. In addition, there has been a renewed focus on charged particle therapy, in particular, proton beam therapy, the subject of the current chapter. 2. The principal advantage of proton beam therapy in treating spine tumors lies in its dose distribution. In contrast to conventional photon-based radiotherapy where, after a short buildup region, energy deposition decreases exponentially with increasing depth in tissue, the physical characteristics of the proton beam result in increasing energy deposition with penetration distance with the majority of the energy being deposited at the end of a linear track, in what is termed the Bragg peak [2] (Fig. 21.1). Beyond the Bragg peak, the position of which is primarily determined by beam energy, there is virtually no exit dose. This region of maximum energy deposition can be positioned within the target for each beam direction, allowing the creation of a highly conformal high-dose region and a reduction in integral dose of approximately 50–60% [3, 4]. The steeper dose gradients and lower integral doses that characterize proton beam therapy make it a highly attractive modality in the management of malignancies arising in the spine. 3. In spite of their well-recognized advantages, proton beam therapy is not without problems and uncertainties. First and foremost, one must consider the biologic unknowns of proton beam therapy [5]. One of the most fundamental challenges of proton beam radiotherapy is RBE uncertainties [6]. In clinical practice, an invariant 1.1 RBE for protons is generally used, but this disregards the growing body of laboratory evidence demonstrating variability in RBE values for protons with depth. Clonogenic cell survival data approximate RBE values for protons (at 2 Gy per fraction) to be 1.1–1.15 from the entrance to the center of the spread-out Bragg peak (SOBP), increasing to 1.35 at the distal edge and 1.7 at the distal falloff [7]. Further, biologic parameters such as tissue type, cell cycle phase, oxygenation level, and alpha/beta ratio have also been shown to influence RBE values in addition to physical parameters such as dose and linear energy transfer (LET) [2, 8, 9]. For instance, RBE values have been found to increase by up to 20% with decreasing alpha/beta ratio [10]. Several strategies to mitigate RBE uncertainties have been proposed in the literature including tapering the SOBP distal edge (by reducing the physical dose within the terminal few millimeters of the proton SOBP), probabilistic and worst-case robust optimization, yielding plans that are less sensitive to range and RBE uncertainties, as well as prioritizing LET optimization within treatment planning attempting to shift LET hotspots into target volumes and away from treatment margins and organs at risk [11].