Use of radiation therapy for patients with soft-tissue and bone sarcomas

TREATMENT PLANNING

Treatment simulation

Following initial consultation with a radiation oncologist, the eligible patient undergoes a simulation, or a treatment planning session in which he or she is positioned so as to allow treatment to be carefully designed and subsequently delivered with precision. This typically requires fabrication of a customized immobilization device to allow for consistent positioning over the treatment course. Sarcomas require that special care be taken to properly immobilize both the proximal and distal joints. Additionally, radiopaque wires are used to delineate the anatomic boundaries of the tumor or scar. Computed tomographic (CT) scans are then obtained to enable image-based three-dimensional treatment planning. The patient setup is photographed, and setup indicators are recorded and marked on the patient’s skin, some with freckle-size tattoos and some with indelible marker.

The treatment fields are then designed on the CT-simulation data set with the aid of virtual reality–type techniques. In addition to delineation of tumor volumes, three-dimensional treatment planning is used to contour all nearby normal structures on each slice. The resulting structures can then be used to specify dose constraints and help determine the optimal beam geometries to ensure proper tumor coverage and minimize the potential for side effects by reducing the dose to organs at risk. In the case of sarcomas, several strategies for reducing the risk of side effects are especially relevant: (1) carefully sparing a portion of the circumference of uninvolved bone to minimize the risk of fractures; (2) carefully sparing a strip of normal tissue to minimize edema by permitting undisrupted lymphatic drainage from the extremity; and (3) keeping dosing to joint spaces and other adjacent organs below tissue tolerances as defined by Emami et al.¹²

Determining target volume

The target volume for RT is determined on the basis of physical examination, radiologic studies, anatomical considerations, and the natural history of the sarcoma.

In the preoperative setting, longitudinal margins of 5 cm beyond the tumor and tumor-associated edema and radial margins of 2 cm are treated to 50 Gy in 25 fractions. Surgery is undertaken approximately 4 weeks after completion of RT to allow for repair in normal tissues and minimize operative and postoperative complications. Following surgery, an RT boost may be added for positive margins (16 Gy) or gross residual disease (25 Gy).

In the postoperative setting, details on the extent of dissection or observations from the surgeons themselves must be considered. Information regarding the surgical approach must be noted and can influence the effectiveness of postoperative RT as well as the incidence of late side effects. When experienced surgeons are involved, scars and drain sites, which are at risk for subclinical disease, can be planned so that their inclusion in the RT portal allows for sparing a strip of skin to minimize complications. Surgical clip placement at the boundaries of the tumor bed also facilitates RT planning.¹³ Finally, prophylactic bone stabilization may reduce the risk of subsequent fracture in cases where circumferential bone radiation in high-risk sites is anticipated.

Recommendations on the volume that must be treated vary among different authorities. Some advocate treating the entire compartment because of the risk for microscopic seeding.¹⁴ Others recommend margins around the tumor or tumor bed ranging from less than 5 cm up to 15 cm.¹⁵ Most often the postoperative approach is to include the resection bed with a 2-cm radial margin, the incision, and any drain sites in the initial treatment volume and to base the longitudinal margin on the grade and size of the primary tumor (5–15 cm). This volume is treated to 50 Gy in 25 fractions followed by two sequential reductions in field size, with the total dose determined by the extent of resection: 60 Gy for negative margins, 66 Gy for microscopically positive margins, and 75 Gy for gross residual disease.

TREATMENT DELIVERY

Once treatment planning is completed, treatments begin and are given daily Monday through Friday. Each day, the patient is positioned in the immobilization device, the field measurements are set, and positioning is checked with measurement tools and external marking of the field borders on the skin. Daily image guidance techniques may be used to increase setup reproducibility. Typical treatment times, including set­up and actual delivery, are roughly 20 to 30 minutes daily.

While external beam RT is most commonly delivered as described above, brachytherapy, or intraoperative electron beam techniques, as well as proton or other charged-particle therapies, are also applied in selected cases.^16–18

SIDE EFFECTS

Side effects of RT in the setting of sarcomas can be divided according to their onset—ie, acute versus delayed.

Acute effects. Skin changes ranging from erythema to moist desquamation in the skin overlying the high-dose volume are common. Major wound complications (delayed wound healing or need for surgical intervention) occur in approximately 17% of patients after surgical resection with postoperative RT, and perhaps more commonly (35%) with preoperative RT,⁸ though these rates vary widely in the literature. Another frequently reported acute side effect is fatigue.

Delayed sequelae after conservative resection and RT of extremity lesions include a reduction in range of motion secondary to joint contracture, edema, and fibrosis, as well as pain and bone fractures, all of which can significantly limit function of the preserved limb. In centers treating high volumes of patients with soft-tissue sarcoma, the incidence of moderate to severe late effects is less than 10%.¹⁹ In contrast to acute wound complications, a higher rate of late complications, including fibrosis and edema, have been observed with postoperative RT relative to preoperative RT.⁹ When necessary, high-dose RT does not appear to compromise the viability of skin grafts used to repair defects after sarcoma surgery if adequate time is allowed for healing.²⁰

Regardless of the management approach, intensive rehabilitation led by physical therapy specialists is imperative in minimizing disabilities after treatment of soft-tissue sarcomas.

CONCLUSION

Outcomes of patients with musculoskeletal sarcomas are optimized at specialized sarcoma centers. For patients with soft-tissue sarcomas, effectively implementing an approach that combines conservative surgery and RT—and, in select cases, chemotherapy—achieves excellent local control rates while minimizing morbidity and maximizing long-term extremity function relative to aggressive surgery alone.