Stereotactic Body Radiation Therapy

The article by Song, Kavanagh, Benedict, and Schefter is an insightful and interesting summary of this new technologic approach to the treatment of extracranial tumors. The work summarizes the salient aspects of the emerging stereotactic body radiation therapy (SBRT) paradigm, and characterizes the rationale, methodologies, and perceived potential for this promising new approach to treatment. The authors present interesting perspectives on the challenges facing early adopters of the approach and, as early adopters, we find that our own experience supports many of the conclusions drawn by the authors. Several interesting aspects of the article are worthy of further discussion, in light of the fact that this new treatment paradigm is rapidly gaining increased acceptance, and a growing number of centers are implementing such SBRT programs as documented by recent publications.[1-3] Target Accuracy
As described by the authors, patient immobilization and reliable knowledge of the target's location is critical to the precise and effective delivery of very high doses of radiation in a single or limited number of sessions. The authors have summarized existing published data and have pointed out the potential for diminished biologic efficacy of SBRT if patient and target setup accuracy are compromised. With respect to intrafraction patient motion and uncertainties related to increasing treatment delivery time, we found that the immobilization system used in our facility (BodyFIX, Medical Intelligence, Schwabmuenchen, Germany) provides effective, yet comfortable patient restraint. Through the application of a doublevacuum system, the device was seen to be capable of not only accurately repositioning the patient into the correct location and orientation but also comfortably restraining the patient during treatment delivery. Although the term "comfortably restrained" may sound contradictory, it describes the perception reported by our patients of being incapable of conducting even intentional movements, yet not feeling uncomfortable due to this restraint. The repositioning accuracy of this system for SBRT has been rigorously tested and compares favorably with data available for other dedicated immobilization systems.[4] We believe such comfortable restraint to be valuable in the setting of the longer treatment times often inherent to very conformal delivery approaches. Dose and Fractionation
The authors accurately point out that while current dose/fractionation schemes are well tolerated, the optimal SBRT dose delivery schedule remains to be determined. Conceptually, in a single-dose delivery schedule, the prescribed dose should be sufficient to overcome malignant cell radiation resistance, as needed to eradicate viable tumor cells. It is interesting that the current SBRT practice of fractionating in three sessions of up to 20 Gy per fraction (with each fraction equivalent to the delivery of single doses that are sufficient for high tumor control probabilities in brain radiosurgery[5]) may accomplish this requirement in each of the three fractions delivered. An ongoing German prospective phase III multicenter trial comparing SBRT delivered in a single dose with a three-fraction regimen for liver metastases (single dose of 28 Gy vs 3 * 12.5 Gy) may help to answer this open question. It remains to be seen if this trial will confirm an anecdotal finding observed by several SBRT groups, including ours, of dramatic kinetics of early tumor response with the use of hypofractionated approaches-responses that have not been observed following single-dose delivery. Such observations may suggest that the actual biologic effective dose of current dose fractionation schedules may be even higher than estimated using the linear quadratic model. One possible explanation might be tumor reoxygenation and cell-cycle reassortment that renders the remaining tumor clones more susceptible to kill in a fractionated approach. Future studies using prospective quantitative and qualitative tumor response assessments in trials comparing single vs multiple fraction deliveries may elucidate this interesting phenomenon. Treatment Planning
The authors also discuss the use of computed tomography (CT) as the primary basis for SBRT treatment planning and, based on reported radiofrequency ablation experience, refer to the possible future use of positronemission tomography (PET) in the assessment of SBRT tumor response. Although published data on the value of incorporating PET metabolic tumor properties into the SBRT treatment planning target delineation process are unavailable, our experience in a series of more than 35 patients with planned CT and PET imaging for SBRT treatment simulation of pulmonary targets supports the perceived potential of this approach. Besides establishing a metabolic baseline for comparison with followup PET imaging to assess tumor response on a tumor-specific functional level, the implementation of PET for treatment planning has allowed for reduction of target volume by targeting a metabolically active subset of CT-appreciated tissue density. We have thus been able to offer SBRT to patients with CT abnormalities exceeding our institutional cutoff of 6 cm in maximum diameter. The preliminary experience in a small population (five patients) treated under this paradigm is encouraging, with tumor control observed for up to 14 months. Additionally, PET images offer objective tumor-property information when post-SBRT CT imaging reveals tissue densities ambiguous for residual tumor or scar tissue. Similarly, magnetic resonance imaging and magnetic resonance spectroscopy may have future utility in both treatment planning and assessment of tumor response. Assessment of Delivered Dose
The accurate assessment of the dose actually delivered in the low- electron-density, heterogeneous environment of lung lesions is currently a challenge to the effective delivery of SBRT for the lung. As discussed by the authors, the additional challenge of target motion subsequent to respiration, and interfraction target position variation serve to further complicate such an assessment, but exciting new technologies are currently being developed. The timely advent of so-called image- guided radiation therapy approaches and technologies may well serve to facilitate the development of the SBRT paradigm by making feasible the accurate relocalization required for safe and effective SBRT. Our own current standard approach entails the acquisition of a three-dimensional (3D) positional assessment via control CT acquired in the CT simulation suite immediately prior to treatment. Nevertheless, we eagerly anticipate the ability to acquire such 3D assessment data in the actual treatment room through the use of such developing technologies as in-room CT and/or cone-beam CT. The current development of sophisticated respiratory motion assessment software tools and so-called gated delivery approaches hold promise of addressing the respiratory motion problems previously mentioned, and sophisticated Monte Carlo dose calculation algorithms, which are currently evolving into clinically feasible forms, hold promise for allowing accurate assessments of delivered dose distributions, which will be necessary to define optimal dose and fractionation schemes for SBRT. Conclusions
Although challenges clearly exist and, as yet, questions related to the optimization of this emerging new treatment approach remain unanswered, we agree with the authors that the paradigm has already shown itself to possess exciting new potential for the effective treatment of extracranial lesions. Given the infancy of the modality, it is not surprising that such questions remain to be answered, but the evolution of the SBRT paradigm is quite fortuitously occurring in conjunction with the development of several exciting techniques such as image-guided radiation therapy, functional imaging, and Monte Carlo-based dose calculation. Beyond current documented successes, the SBRT delivery paradigm summarized by Song and colleagues appears poised to play an important future role in the treatment of a variety of extracranial tumor sites.