Despite the attendant risks associated with treatment, some patients with resectable pediatric and young adult NRSTS benefit from the administration of radiation. As the desired goal of radiation therapy is to optimize local control with a minimal effect on quality of life, several different strategies may be considered. Patients with subclinical disease may not require the same radiation dose as those who clearly have microscopic residual disease. Modifying the radiation dose according to extent of disease is a concept well known to radiation oncologists since Fletcher proposed a graduated dose scheme for adults with head and neck carcinoma to sterilize subclinical lymph nodes versus a higher dose to treat a primary site with microscopic or gross disease. Doses of 50
Gy were recommended for subclinical disease, 60
Gy for microscopic disease, and 70
Gy for gross disease [23
]. Using a similar paradigm, it may be feasible to use a lower dose in the setting of a clearly negative margin, such as 45–50
Gy, and a slightly higher dose of 50–55
Gy for a true microscopically involved margin.
In addition, the POG 8653 trial, which adjusted the radiation dose according to age, is supported by data suggesting younger children far better than older adolescents, even within the same histologic subtype, such as seen in synovial sarcoma.
Better understanding of which sarcomas are more likely to be radiosensitive, through analysis of the pathologic treatment effect in patients who have received preoperative radiation therapy, may allow dose adjustment. For example, Roberge et al. reported on the imaging and pathologic response of radiation therapy for extremity and truncal soft tissue sarcomas in 50 patients. This report showed an association between reduction in tumor volume by imaging predictive of a pathologic treatment response in the surgical specimen. Some histologic subtypes were shown to be very radiation therapy sensitive, such as myxoid liposarcoma, where a substantial decrease in tumor volume (82.1%) on imaging was associated with a high percent of tumor necrosis in the pathologic specimen. High-grade sarcoma which showed very minimal reduction (<1%) in the tumor volume by imaging was associated with minimal treatment-related effect seen in the pathologic specimen.
Other strategies to minimize late effects of treatment might be to consider the use of preoperative radiation therapy in those patients presenting with a large, invasive, and high-grade tumor that would likely require radiation therapy based on the pretreatment evaluation [24
]. Preoperative radiation has the potential advantage of treating a smaller volume with lower doses potentially resulting in fewer complications. A Canadian sarcoma randomized trial reported fewer long-term complications in patients who received preoperative radiation therapy as compared with postoperative therapy [25
One of the most effective ways to minimize the late effects of radiation therapy is to design the radiation field to protect the adjacent normal tissues. The best way to accomplish this is to use smaller treatment margins around the tumor volume. Historically, wide margins up to 5
cm or greater were used to treat potential subclinical disease far beyond the operative bed or radiographic findings. In turn, such a large volume would invariably include critical organs and normal tissues vital for form and function.
Krasin et al. prospectively tested whether a smaller margin on the target volume could be used and not compromise local control. Of 32 pediatric and young adults with a high-grade NRSTS, 27 received adjuvant radiation therapy. Using a 2
cm margin around the tumor volume at diagnosis and delivering a median cumulative postoperative radiation dose of 60
Gy (range 41.4–70.4
Gy) or a preoperative dose of 45
Gy (range 45–50.4
Gy), the 3-year cumulative local recurrence rate for patients who underwent a marginal or complete resection was <4%. There were no failures in the patients with clear surgical margins. Those who failed locally did so within the high-dose radiation volume, suggesting limited margin radiation therapy is an effective strategy to employ in pediatric patients with NRSTS. Techniques such as these would be expected to confer less normal tissue injury including a possible reduction in secondary cancer induction [26
A current COG trial for pediatric and young adults with NRSTS uses a risk-based stratification algorithm tailoring radiation therapy dose and volume based on tumor grade, size, and margin status. The results of this trial will hopefully provide critical answers to whom benefits from adjuvant radiation therapy.
In order to optimize the delivery of radiation therapy, immobilization and careful delineation of the target volume to treat are critical to the successful outcome. The standard of care today is to include 3 dimensional (3D) volumetric planning using cross-sectional imaging by either computed tomographic (CT) or magnetic resonance imaging (MRI). Effective immobilization techniques provide the ability to deliver extremely conformal treatment. Additionally, sarcomas located in the chest or abdomen may shift with diaphragmatic motion during radiation therapy. Accounting for respiratory movement is now possible to allow for further refinements in the concise delivery of radiation to the target volume.
Choosing the appropriate preoperative radiographic imaging study to fuse with a treatment planning CT/MRI scan is critical, particularly in the postoperative setting where anatomy of normal structures has returned to normal position. Furthermore treatment planning systems can format preoperative images to conform to the patient's new treatment position allowing better recreation of the precise location of the original tumor in relation to normal tissues and organs.
Delivery techniques, such as intensity modulated radiation therapy (IMRT) allow sculpting the radiation dose around vital structures. Although IMRT may deliver a higher integral dose than observed using a conformal 3-D plan, the shaping and deposition of radiation therapy is more precise [27
]. Particle therapy, such a proton beam therapy, has been used in pediatric patients at several centers around the world with reported results showing excellent dosimetric delineation of target with minimal scatter to normal tissues and little exit dose. The expectation is that there will be fewer late effects [28
]. Brachytherapy is another excellent tool to deliver conformal high dose to target volume. Although wound complications are reported to be higher in the implanted site using brachytherapy for sarcoma therapy, this treatment is a potentially daily precision radiation therapy delivery, and conebeam computed tomography (CBCT) helps ensure that normal tissues are within millimeters of the original simulated position. All these contemporary technologies contribute to keeping the radiation therapy dose as low as possible and hence minimizing normal tissue exposure.