Clinical Outcomes of Pediatric Soft-tissue Sarcoma in the Extremities patients with extremity RMS compared to other sites.31 If microscopic
residual disease is present, primary re-excision should be performed, especially in extremity sites as this is often technically possible and these tumors otherwise carry such a poor prognosis.31
If achieving
negative margins with either primary surgery or re-excision would result in major functional or cosmetic loss, however, it is advisable to consider pre-operative chemotherapy and radiation followed by surgery. Results using this treatment system have shown improved outcomes in patients who can be changed from group III to group I.31
Radiation should be used for all patients with extremity RMS and alveolar subtype, no matter which group they are in, except for group I patients with ERMS. Since the rate of lymph node involvement in extremity RMS is so high, lymph node sampling is necessary and newer techniques such as sentinel node biopsy may be applicable. Complete nodal dissection has not improved prognosis in extremity RMS and is not recommended.
Future directions for extremity RMS include new chemotherapeutic agents and methods to decrease radiation risks. As part of the COG trials for intermediate-risk NRSTS, irinotecan and earlier administration of radiation are currently being investigated. The utility of positron- emission tomography in assessing tumor response to aid in determination of prognosis is also part of that investigation. Targeted therapy, particularly for ARMS but also for RMS in general, is a focus of this research. Decreasing the radiation field is the subject of several recent studies,32,33
and the hope is that late effects can be diminished with these new techniques.
Non-rhabdomyosarcoma Soft-tissue Sarcoma Pediatric NRSTS are a heterogeneous group that accounts for about 4 % of cancer cases in children and adolescents <20 years of age.1
While there is no agreed-upon staging system for pediatric NRSTS, many—including the current COG study—have integrated a risk-based system that incorporates many of the prognostic factors known to be significant. In this system, low-risk patients are those with resectable tumors that are either low grade or high grade and <5cm. Five-year overall survival for this group is very good, at about 90 %. Intermediate- risk patients are those with unresectable tumors or with high-grade tumors ≥5cm. Survival is about 50 % at five years. Patients with metastatic disease make up the high-risk group, and survival is about 15 % at five years.44
Current recommendations for patients with non-metastatic RMS include surgery and radiation to achieve local control with negative margins. In most cases this can be achieved with limb salvage surgery. Amputation is rarely required. If negative margins can be obtained surgically, it is debatable whether radiation should also be used. Many teams recommend this for high-grade sarcomas, but it has not been studied in a prospective manner in children. This is one component of the open, prospective COG study for NRSTS. Typically, radiation is not recommended for low-grade tumors.
The most
common pediatric subtypes are synovial sarcoma, malignant fibrous hystiocytoma, dermatofibrosarcoma protuberans, malignant peripheral nerve sheath tumor, and fibrosarcoma.1
likely to change over time as the term ‘malignant fibrous histiocytoma’ is used less frequently.
Unlike RMS, the incidence of NRSTS is higher in adolescents than in younger children, and extremity location represents at least 50 %.34–37 Also unlike RMS, nodal metastases are rare except for certain tumor types, such as clear-cell sarcoma, epithelioid sarcoma, and, less frequently, synovial sarcoma. Patients present with distant metastases in 15 % of cases, primarily the lung.34–37
Another major difference between RMS and NRSTS is the small number of prospective trials.37–40
Most of the information regarding
pediatric NRSTS comes from the extrapolation of data from adult studies in subtypes that may also present in older age groups and from larger retrospective series.34–36
From these studies, prognostic
factors similar to RMS have been identified and confirmed in NRSTS. This includes the extent of disease, tumor size, and quality of resection. Similar to adult soft-tissue sarcoma, grade is highly important as a prognostic factor. Unlike in adults, however, lower versus upper extremity, superficial versus deep location, and histological subtype have not been shown to affect prognosis for NRSTS in children.41,42
Survival in children is often found to be better US ONCOLOGY & HEMATOLOGY Conclusion
In summary, pediatric soft-tissue sarcoma of the extremities is a rare disease with variable outcomes depending on type. RMS of the extremities has such a poor prognosis compared RMS overall that much greater effort is needed to effect improvement. Pediatric NRSTS of the extremities is an arena where few prospective data exist, so continued focused efforts with this particular age group are needed. n
121 The proportions of these are
Radiation can be a powerful tool to achieve long-term local control if margins are positive and to reduce the size of an unresectable tumor (often in concert with chemotherapy), potentially making it resectable. Radiation carries significant risks, however, which are even more pronounced in a young population than in adults. Radiation affects the growth of bones and soft tissues, can cause permanent joint contractures and stiffness, and, most seriously, can induce secondary sarcomas later in life. Thus, the risks associated with radiation in a child must be weighed against the potential functional loss if a purely surgical approach is used.
The use of chemotherapy in children and adolescents with NRSTS, much as in adults, is highly debatable. The agents with the most activity are doxorubicin and ifosfamide, but response rates only approach 35–40 %.38,39
than in adults in these studies, even controlling for other important tumor factors. This has led many to believe that there are different biological factors at play in children compared with adults.3,43
Chemotherapy is currently often considered in patients with high-grade tumors >5cm and unresectable tumors, and as palliation in metastatic disease. The current COG study will prospectively evaluate chemotherapy in intermediate-risk patients.
For children and adolescents with metastatic disease at presentation, metastectomy can offer a rare chance for cure. Most often, however, the prognosis is dismal. The hope is that further phase I and II trials will identify new agents with particular activity in pediatric NRSTS.
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