Treatment Option Overview
Because of the rarity of pediatric nonrhabdomyosarcomatous soft tissue sarcomas (STSs), all children, adolescents, and young adults with these tumors should have their treatment coordinated by a multidisciplinary team comprising pediatric oncologists, pathologists, surgeons, and radiation oncologists. To better define the tumors' natural history and response to therapy, children with rare neoplasms should be considered for entry into national or institutional treatment protocols. Information about ongoing clinical trials is available from the NCI Web site.Surgery
Every attempt should be made to resect the primary tumor with negative margins before or after chemotherapy. Involvement of a surgeon with special expertise in the resection of STSs in the decision is highly desirable.
The timing of surgery depends on an assessment of the feasibility and morbidity of surgery. If the initial operation fails to achieve pathologically negative tissue margins or if the initial surgery was done without the knowledge that cancer was present, a re-excision of the affected area should be performed to obtain clear, but not necessarily wide, margins.[1-5] This surgical tenet is true even if no mass is detected by magnetic resonance imaging after initial surgery.; [Level of evidence: 3iiA]
Regional lymph node metastases at diagnosis are unusual and appear most likely with epithelioid and clear cell sarcomas. Sentinel lymph node mapping is employed at some centers to identify the regional nodes that are the most likely to be involved, although its widespread contribution to the staging and management of these tumors has yet to be clearly defined.[9-11]Radiation Therapy
Considerations for radiation therapy are based on the potential for surgery, with or without chemotherapy, to obtain local control without loss of critical organs, or significant functional, cosmetic or psychological impairment. This will vary according to patient variables, including age and gender, and tumor variables, including histopathology, site, size, and grade. Radiation therapy considerations include the same patient and tumor variables, surgical margin status, and expectations for radiation-induced morbidities such as impaired bone or muscle development, organ damage, or second malignancy. Radiation therapy can be given preoperatively or postoperatively, and the radiation field size and dose will again be based on patient and tumor variables and the operability of the tumor.
In general, radiation is indicated for patients with inadequate surgical margins and for larger, high-grade tumors.[12,13] This is particularly important in high-grade tumors with tumor margins smaller than 1 cm.[14,15]; [Level of evidence: 3iiDiv] With combined surgery and radiation therapy, local control of the primary tumor can be achieved in more than 80% of patients.[17,18] Preoperative radiation therapy has been associated with excellent local control rates.[19-21] This approach has the advantage of treating smaller tissue volumes because it does not necessitate treating a postsurgical bed; it also has the advantage of somewhat lower radiation doses because relative hypoxia from surgical disruption of vasculature and scarring is not present. Preoperative radiation therapy has been associated with an increased rate of wound complications in adults, primarily in lower extremity tumors, but the degree of this is questionable. Conversely, preoperative radiation therapy may lead to less fibrosis than with postoperative approaches, perhaps due to the smaller treatment volume and dose. Brachytherapy and intraoperative radiation may be applicable in select situations.[18,24,25]; [Level of evidence: 3iiiDii] In the recently closed COG-ARST0332 trial, preoperative radiation therapy was recommended for patients who presented with unresected tumor. The use of postoperative radiation therapy for patients who presented following primary resection was dependent on the tumor size, grade, and margin status.
Retroperitoneal sarcomas are a special issue since radiosensitivity of the bowel to injury makes postoperative radiation therapy less desirable. Reasons for this include the postoperative adhesions and bowel immobility that increase the risk of damage from any given radiation dose. This is in contrast to the preoperative approach in which the tumor often displaces bowel outside of the radiation field, and any exposed bowel is more mobile, which decreases exposure to specific bowel segments.
Radiation volume and dose depend on all patient, tumor, and surgical variables as noted above. Considerations include patient age and growth potential, the ability to avoid critical organs, epiphyseal plates, and lymphatics (but not the neurovascular bundles that are relatively radiation tolerant), and the functional/cosmetic outcome. Radiation margins are typically 2 cm to 4 cm longitudinally, and encompassing fascial planes axially. Radiation doses are typically 45 Gy to 50 Gy preoperatively, with consideration for postoperative boost of 10 Gy to 20 Gy if resection margins are microscopically or grossly positive, or planned brachytherapy if the resection is predicted to be subtotal. However, data documenting the efficacy of a postoperative boost are lacking. The postoperative radiation dose is 55 Gy to 60 Gy, or rarely, higher in the situation where unresectable gross residual disease exists.Chemotherapy
The role of adjuvant (postoperative) chemotherapy remains controversial. A meta-analysis of updated data from adult STS patients from all available randomized trials concluded that recurrence-free survival was better with adjuvant chemotherapy for patients with high-grade tumors larger than 5 cm. The largest prospective pediatric trial failed to demonstrate any benefit with adjuvant vincristine, dactinomycin, cyclophosphamide, and doxorubicin.Special Treatment Considerations for Children With STS
Many therapeutic strategies for children and adolescents with soft tissue tumors are similar to those for adult patients, although there are important differences. For example, the biology of the neoplasm in pediatric patients may differ dramatically from that of the adult lesion. Additionally, limb-sparing procedures are more difficult to perform in pediatric patients. The morbidity associated with radiation therapy, particularly in infants and young children, may be much greater than that observed in adults.
Improved outcomes with multimodality therapy in adults and children with STSs over the past 20 years has caused increasing concern about the potential long-term side effects of this therapy in children, especially when considering the expected longer life span of children versus adults. Therefore, to maximize tumor control and minimize long-term morbidity, treatment must be individualized for children and adolescents with nonrhabdomyosarcomatous STS. These patients should be enrolled in prospective studies that accurately assess any potential complications.References
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