Table of Contents Purpose of This PDQ Summary General Information Cellular and Histopathologic Classification
Stage Information Treatment Option Overview Nonmetastatic Childhood Soft Tissue Sarcoma Metastatic Childhood Soft Tissue Sarcoma Recurrent/Progressive Childhood Soft Tissue Sarcoma Get More Information From NCI Changes to This Summary (12/05/2008) More Information
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood soft tissue sarcoma. This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board.
Information about the following is included in this summary:
- Incidence and risk factors.
- Cellular and histopathologic classification.
- Stage information.
- Treatment options.
This summary is intended as a resource to inform and assist clinicians and other health professionals who care for pediatric cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric and Adult Treatment Editorial Boards use a formal evidence ranking system in developing their level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is also available in a patient version, which is written in less-technical language, and in Spanish.
Back to Top General Information
The National Cancer Institute (NCI) provides the PDQ pediatric cancer treatment information summaries as a public service to increase the availability of evidence-based cancer information to health professionals, patients, and the public.
Cancer in children and adolescents is rare. Children and adolescents with
cancer should be referred to medical centers that have a multidisciplinary team
of cancer specialists with experience treating the cancers that occur during
childhood and adolescence. This multidisciplinary team approach incorporates the skills
of the primary care physician, pediatric surgical subspecialists, radiation
oncologist, pediatric hematologist/oncologist, rehabilitation specialist,
pediatric nurse specialists, social workers, and others to ensure that
children receive treatment, supportive care, and rehabilitation that will
achieve optimal survival and quality of life. Refer to the PDQ Supportive Care summaries for specific information about supportive care for children and adolescents with cancer.
Guidelines for pediatric cancer
centers and their role in the treatment of pediatric patients with cancer have
been outlined by the American Academy of Pediatrics.[1] At these pediatric
cancer centers, clinical trials are available for most types of cancer
that occur in children and adolescents, and the opportunity to participate in
these trials is offered to most patients/families. Clinical trials for
children and adolescents with cancer are generally designed to compare
potentially better therapy with therapy that is currently accepted as standard.
Most of the progress made in identifying curative therapies for
childhood cancers has been achieved through clinical trials. Information about
ongoing clinical trials is available from the NCI Web site.
In recent decades, dramatic improvements in survival have been achieved for children and adolescents with cancer. Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.
Pediatric soft tissue sarcomas are a group of malignant tumors that originate
from primitive mesenchymal tissue and account for 7% of all childhood
tumors.[2] Rhabdomyosarcomas, tumors of striated muscle, and undifferentiated
sarcomas account for more than half of all cases of soft tissue sarcomas in
children. (Refer to the PDQ summary on Childhood Rhabdomyosarcoma Treatment for more
information.) The remaining nonrhabdomyosarcomatous soft tissue sarcomas
(NRSTSs) account for approximately 3% of all childhood tumors.[3] This heterogeneous
group of tumors includes neoplasms of smooth muscle (leiomyosarcoma),
connective tissue (fibrous and adipose), vascular tissue (blood and lymphatic
vessels), and the peripheral nervous system.[4] Synovial sarcomas,
fibrosarcomas, and malignant peripheral nerve sheath tumors predominate in pediatric patients.[5-9]
NRSTSs are more common in adults [4] than
in children; therefore, much of the information regarding the treatment and
natural history of children with these lesions has been on the basis of
findings from adult studies. Pediatric NRSTSs, however, are often associated with a better outcome. This
difference is most pronounced for infants and children younger than 4 years
with fibrosarcoma that is locally aggressive but not metastatic. These patients have an excellent prognosis when chemosensitive and treated with surgery
only.[3,4,10,11] Soft tissue sarcomas in older children and adolescents often
behave similarly to those in adult patients.[3,4]
Although they can develop in any part of the body, NRSTSs arise most commonly in the trunk and extremities.[5,6,12] These
neoplasms can present initially as an asymptomatic solid mass, or they may be
symptomatic because of local invasion of adjacent anatomical structures.
Systemic symptoms (e.g., fever, weight loss, and night sweats) are rare.
Hypoglycemia and hypophosphatemic rickets have been reported in cases of
hemangiopericytoma, whereas hyperglycemia has been noted in patients with
fibrosarcoma of the lung.[4]
Genetic and environmental factors influence the development of
NRSTS. Heritable cancer-associated
changes of the p53 tumor suppressor gene can occur in families with Li-Fraumeni
syndrome.[13] Members of these families have an increased risk of developing
soft tissue tumors, bone sarcomas, breast cancer, brain tumors, and acute
leukemia.[3] Approximately 4% of patients with neurofibromatosis type 1
develop malignant peripheral nerve sheath tumors, which usually develop after a
long latency; some patients develop multiple lesions.[4,14,15] Some
NRSTSs (particularly malignant fibrous
histiocytoma) can develop within a previously irradiated site; others (e.g.,
leiomyosarcoma) have been linked to Epstein-Barr virus infection in patients
with AIDS.[3,4,16]
Synovial sarcomas are the most common NRSTS reported in children. The most common location is the lower extremity
followed by upper extremity, trunk, abdomen, and head and neck. Approximately
30% of patients with synovial sarcoma are younger than 20 years. The
most common site of metastasis is the lung.[17] Factors such as International Union Against Cancer/American Joint Committee on Cancer stage III/stage IVA, tumor
necrosis, truncal locations, elevated mitotic rate, age, and histologic grade have been associated with
a worse prognosis in adults.[18-20]
(Refer to the PDQ summary on Childhood Rhabdomyosarcoma Treatment for more information.
Refer to the PDQ summary on Ewings Family of Tumors Treatment for more
information on extraosseous Ewing, peripheral neuroepithelioma, and Askin
tumor.)
The prognosis and biology of NRSTS tumors vary greatly depending on the age of
the patient, the primary site, tumor size, tumor invasiveness, histologic
grade, depth of invasion, and extent of disease at diagnosis. Because
long-term related morbidity must be minimized while disease-free survival is maximized, the ideal therapy for each patient must be
carefully and individually determined utilizing these prognostic factors before
initiating therapy for these patients.[6,10,17,21-23]
References
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Guidelines for the pediatric cancer center and role of such centers in diagnosis and treatment. American Academy of Pediatrics Section Statement Section on Hematology/Oncology. Pediatrics 99 (1): 139-41, 1997.
[PUBMED Abstract]
-
Pappo AS, Pratt CB: Soft tissue sarcomas in children. Cancer Treat Res 91: 205-22, 1997.
[PUBMED Abstract]
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Miser JS, Triche TJ, Kinsella TJ, et al.: Other soft tissue sarcomas of childhood. In: Pizzo PA, Poplack DG, eds.: Principles and Practice of Pediatric Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven, 1997, pp 865-888.
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Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 4th ed. St. Louis, Mo: Mosby, 2001.
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Dillon P, Maurer H, Jenkins J, et al.: A prospective study of nonrhabdomyosarcoma soft tissue sarcomas in the pediatric age group. J Pediatr Surg 27 (2): 241-4; discussion 244-5, 1992.
[PUBMED Abstract]
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Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec.
[PUBMED Abstract]
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Fletcher CD, Dal Cin P, de Wever I, et al.: Correlation between clinicopathological features and karyotype in spindle cell sarcomas. A report of 130 cases from the CHAMP study group. Am J Pathol 154 (6): 1841-7, 1999.
[PUBMED Abstract]
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Skytting BT, Bauer HC, Perfekt R, et al.: Clinical course in synovial sarcoma: a Scandinavian sarcoma group study of 104 patients. Acta Orthop Scand 70 (6): 536-42, 1999.
[PUBMED Abstract]
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Herzog CE: Overview of sarcomas in the adolescent and young adult population. J Pediatr Hematol Oncol 27 (4): 215-8, 2005.
[PUBMED Abstract]
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Dillon PW, Whalen TV, Azizkhan RG, et al.: Neonatal soft tissue sarcomas: the influence of pathology on treatment and survival. Children's Cancer Group Surgical Committee. J Pediatr Surg 30 (7): 1038-41, 1995.
[PUBMED Abstract]
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Neville H, Corpron C, Blakely ML, et al.: Pediatric neurofibrosarcoma. J Pediatr Surg 38 (3): 343-6; discussion 343-6, 2003.
[PUBMED Abstract]
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Zeytoonjian T, Mankin HJ, Gebhardt MC, et al.: Distal lower extremity sarcomas: frequency of occurrence and patient survival rate. Foot Ankle Int 25 (5): 325-30, 2004.
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Chang F, Syrjänen S, Syrjänen K: Implications of the p53 tumor-suppressor gene in clinical oncology. J Clin Oncol 13 (4): 1009-22, 1995.
[PUBMED Abstract]
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deCou JM, Rao BN, Parham DM, et al.: Malignant peripheral nerve sheath tumors: the St. Jude Children's Research Hospital experience. Ann Surg Oncol 2 (6): 524-9, 1995.
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Stark AM, Buhl R, Hugo HH, et al.: Malignant peripheral nerve sheath tumours--report of 8 cases and review of the literature. Acta Neurochir (Wien) 143 (4): 357-63; discussion 363-4, 2001.
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McClain KL, Leach CT, Jenson HB, et al.: Association of Epstein-Barr virus with leiomyosarcomas in children with AIDS. N Engl J Med 332 (1): 12-8, 1995.
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Pappo AS, Fontanesi J, Luo X, et al.: Synovial sarcoma in children and adolescents: the St Jude Children's Research Hospital experience. J Clin Oncol 12 (11): 2360-6, 1994.
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Trassard M, Le Doussal V, Hacène K, et al.: Prognostic factors in localized primary synovial sarcoma: a multicenter study of 128 adult patients. J Clin Oncol 19 (2): 525-34, 2001.
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Guillou L, Benhattar J, Bonichon F, et al.: Histologic grade, but not SYT-SSX fusion type, is an important prognostic factor in patients with synovial sarcoma: a multicenter, retrospective analysis. J Clin Oncol 22 (20): 4040-50, 2004.
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Ferrari A, Gronchi A, Casanova M, et al.: Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution. Cancer 101 (3): 627-34, 2004.
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Marcus KC, Grier HE, Shamberger RC, et al.: Childhood soft tissue sarcoma: a 20-year experience. J Pediatr 131 (4): 603-7, 1997.
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Pratt CB, Pappo AS, Gieser P, et al.: Role of adjuvant chemotherapy in the treatment of surgically resected pediatric nonrhabdomyosarcomatous soft tissue sarcomas: A Pediatric Oncology Group Study. J Clin Oncol 17 (4): 1219, 1999.
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Pratt CB, Maurer HM, Gieser P, et al.: Treatment of unresectable or metastatic pediatric soft tissue sarcomas with surgery, irradiation, and chemotherapy: a Pediatric Oncology Group study. Med Pediatr Oncol 30 (4): 201-9, 1998.
[PUBMED Abstract]
Back to Top Cellular and Histopathologic Classification
Nonrhabdomyosarcomatous soft tissue tumors are fairly readily distinguished
from rhabdomyosarcoma or Ewing family of tumors; however, classification of childhood nonrhabdomyosarcomatous soft tissue sarcoma (NRSTS) type is often difficult. Obtaining adequate tumor tissue is crucial to allow for conventional
histology, immunocytochemical analysis, and other studies such as light and electron microscopy, cytogenetics, fluorescence in situ hybridization,
and molecular pathology.[1,2] For this reason, open biopsy (or multiple core-needle biopsies) is strongly encouraged
so that adequate tumor tissue can be obtained to allow for all of these crucial
studies to be performed.
Chromosomal Abnormalities
Many NRSTSs are
characterized by chromosomal abnormalities. Some of these chromosomal
translocations lead to a fusion of two disparate genes. The resulting fusion
transcript can be readily detected by using polymerase chain reaction-based
techniques, thus facilitating the diagnosis of those neoplasms that have
translocations. Some of the most frequent aberrations seen in
nonrhabdomyosarcomatous soft tissue tumors are listed in Table 1.
Table 1. Frequent Aberrations Seen In Nonrhabdomyosarcomatous Soft Tissue
Tumorsa
Histology
|
Chromosomal Aberrations
|
Genes Involved
|
Alveolar soft part sarcoma |
t(x;17)(p11.2;q25) |
ASPL/TFE3 [4-6] |
Clear cell sarcoma (malignant melanoma of soft parts) |
t(12;22)(q13;q12) |
ATF1/EWS
|
Congenital fibrosarcoma/ mesoblastic nephroma |
t(12;15)(p13,q25) [4] |
ETV-NTRK3 [4] |
Dermatofibrosarcoma |
t(17;22)(q22;q13) |
COL1A1/PDGFB
|
Desmoplastic small round cell tumors |
t(11;22)(p13;q12) |
WT1/EWS [7] |
Extraskeletal myxoid chondrosarcoma |
t(9;22)(q22;q12) |
EWS-CHN
|
Hemangiopericytoma |
t(12;19)(q13;q13.3) and
t(13;22)(q22;q13.3) |
|
Infantile fibrosarcoma |
t(12;15);+11; also +8,+17,+20 |
ETVG(TEL)/NTRK3
|
Leiomyosarcoma |
t(12;14) |
|
Low-grade fibromyxoid sarcoma |
t(7;16)(q33;p11) |
FUS/BBF2H7 |
Malignant fibrous histiocytoma |
19p+, ring chromosome |
|
Myxoid liposarcoma |
t(12;16)(q13;p11) |
FUS/CHOP
|
Neurofibrosarcoma |
Deletion 17q11.2 |
|
Rhabdoid tumor |
t(1;22)(p36:q11.2) [4] |
SNFS/INI1 [4] |
Synovial sarcoma |
t(x;18)(p11.2;q11.2) |
SYT/SSX
|
aAdapted from Sandberg [3] and Slater et al.[4]
|
|
Histologic Classification
Pediatric soft tissue sarcomas are classified histologically according to the
soft tissue cell they resemble and include the following:[1]
Tumors of fibrous tissue
Fibrohistiocytic tumors
Tumors of adipose tissue
Tumors of smooth muscle
Tumors of blood and lymph vessels
- Angiosarcoma.
- Lymphangiosarcoma.
- Hemangiopericytoma.
- Hemangioendothelioma.
Tumors of peripheral nervous system
Tumors of bone and cartilage
- Extraosseous osteosarcoma.
- Extraosseous myxoid chondrosarcoma.
- Extraosseous mesenchymal chondrosarcoma.
Tumors of more than one tissue type
- Malignant mesenchymoma.
- Malignant Triton tumor.[8]
- Malignant ectomesenchymoma.[9]
Tumors of unknown histogenesis
Selected Soft Tissue Sarcomas in Children
Alveolar soft part sarcoma
This is a tumor of uncertain histogenesis. A consistent chromosomal translocation t(X;17)(p11.2;q25) juxtaposes the ASP gene with the TFE3 gene.[5] ASPS almost never has an objective response to chemotherapy.[10] In children, ASPS often presents with metastases,[11] and sometimes has a very indolent course. There are single case reports of objective responses to interferon-alpha and to bevacizumab.[12,13]
Angiosarcoma
A review of 20 years of experience in the Italian and German Soft Tissue Sarcoma Cooperative Group identified 12 children with angiosarcoma.[14] Only one objective response to chemotherapy was observed, and the overall behavior of this tumor was identical to angiosarcoma in adults.
Dermatofibrosarcoma
Dermatofibrosarcoma is a rare tumor, but many of the reported cases arise in children.[15] The tumor has a consistent chromosomal translocation t(17;22)(q22;q13) that juxtaposes the COL1A1 gene with the PDGF-beta gene. Most tumors are cured by surgical resection. When surgical resection cannot be accomplished or the tumor is recurrent, treatment with imatinib has been effective.[16]
Desmoid tumors
Desmoid tumors are low-grade malignancies with very low potential to metastasize. The tumors are locally infiltrating, and surgical control can be difficult because of the need to preserve normal structures. These tumors also have a high potential for local recurrence. Desmoid tumors have a highly variable natural history, including well documented examples of spontaneous regression.[17] Repeated surgical resection can sometimes bring recurrent lesions under control.[18]
Inflammatory myofibroblastic tumor
Inflammatory myofibroblastic tumor (IMT) is an incompletely characterized neoplasm of intermediate biologic potential. It recurs frequently but metastasizes rarely.[19] Roughly half of IMTs exhibit a clonal mutation that activates the anaplastic lymphoma kinase (ALK)-receptor tyrosine kinase gene at chromosome 2p23.[20]
There are no well-documented responses to chemotherapy. There are case reports of response to either steroids or non-steroidal anti-inflammatory drugs.
Leiomyosarcoma
A 24-year retrospective analysis of the Italian cooperative group identified one child with leiomyosarcoma.[21] A retrospective analysis of the St. Jude Children’s Research Hospital experience from 1962 to 1996 identified 40 children with NRSTS; none had leiomyosarcoma.[22] Among 43 children with HIV/AIDS who developed tumors, eight developed Epstein-Barr virus–associated leiomyosarcoma.[23]
Liposarcoma
A 24-year retrospective analysis of the Italian cooperative group identified two children with liposarcoma.[21] The tumors did not respond to chemotherapy. Outcomes were the same as those observed in adults with liposarcoma.[24]
Malignant fibrous histiocytoma
At one time, MFH was the single most common histiotype among adults with soft tissue sarcomas. Since it was first recognized in the early 1960s, however, MFH has been plagued by controversy in terms of both its histogenesis and its validity as a clinicopathologic entity. The latest World Health Organization classification no longer includes MFH as a distinct diagnostic category but rather as a subtype of an undifferentiated pleomorphic sarcoma.[25]
Malignant peripheral nerve sheath tumor
MPNST arises in children with type 1 neurofibromatosis (NF1), and it arises sporadically.[26] Features with favorable prognosis have been reported to include absence of NF1, less invasiveness, lower stage, and an extremity as the primary site.[26,27] Chemotherapy has achieved objective responses in childhood MPNST. The role of adjuvant chemotherapy following resection of MPNST has not been prospectively evaluated. A retrospective survey of cancer centers in Japan identified 56 patients with MPNST, mostly adults, but including children and adolescents.[28] This survey identified large tumor size, metastasis at presentation, and high histologic grade as unfavorable prognostic features. In this report, documentation of NF1 did not confer an inferior prognosis.
Synovial sarcoma
Synovial sarcoma is considered to be more chemotherapy responsive than many other soft tissue sarcomas. There is ample documentation of objective responses of synovial sarcoma to systemic chemotherapy.[21,29-31] The value of adjuvant chemotherapy following resection of localized disease has not been conclusively supported in prospective trials, but most pediatric oncologists favor adjuvant chemotherapy for all but the smallest, completely resected tumors.[30,32-34]
Diagnosis of synovial sarcoma is made by immunohistochemical analysis,
ultrastructural findings, and demonstration of the specific chromosomal
translocation t(x;18)(p11.2;q11.2). This abnormality is specific for synovial
sarcoma and is found in all morphologic subtypes. Synovial sarcoma results in rearrangement
of the SYT gene on chromosome 18 with one of the subtypes (1, 2, or 4) of the
SSX gene on chromosome X.[35,36] Synovial sarcoma can be subclassified as
monophasic fibrous type, biphasic type with distinct epithelial and spindle
cell components, or poorly differentiated. Poorly differentiated synovial
sarcoma has features of monophasic or biphasic synovial sarcoma but also a
variable proportion of poorly differentiated areas characterized by high
cellularity, pleomorphism, and polygonal or small round-cell morphology,
numerous mitoses, and often necrosis.[37]
Undifferentiated soft tissue sarcoma
Patients with undifferentiated sarcoma have been eligible for participation in rhabdomyosarcoma trials coordinated by the Intergroup Rhabdomyosarcoma Study Group and the Children’s Oncology Group. The rationale for this inclusion was the observation that patients with undifferentiated sarcoma have similar sites of disease and outcome to those with alveolar rhabdomyosarcoma. In therapeutic trials for adults with soft tissue sarcoma, patients with undifferentiated sarcoma are included with all other histologies and treated in a similar manner. Contemporary treatment for adult soft tissue sarcoma utilizes ifosfamide and doxorubicin, sometimes with the addition of other chemotherapy agents, surgery, and radiation therapy. No data are available to compare these two approaches.
Biopsy Technique for Soft Tissue Sarcoma
When a suspicious lesion is identified it is crucial that a complete workup followed by adequate biopsy be performed. Generally, it is better to image the lesion prior to any interventions. A core-needle biopsy or limited open biopsy that obtains an adequate amount of tissue for histopathology, immunohistochemistry, and molecular genetics is mandatory, given the diagnostic importance of translocations. Image-guided needle biopsy techniques must also obtain an adequate tissue sample and usually require obtaining multiple cores of tissue. Incisional biopsies are acceptable but should not compromise subsequent wide local excision. Transverse extremity incisions should be avoided to reduce skin loss, as should extensive surgical procedures prior to definitive diagnosis.
Soft Tissue Sarcoma Tumor Grading System
In most cases, accurate histopathologic classification of soft
tissue sarcomas alone does not yield optimal information about their clinical
behavior. Therefore, several histologic parameters, including degree of
cellularity, cellular pleomorphism, mitotic activity, degree of necrosis, and
invasive growth, are evaluated in the grading process. This process
is used to improve the correlation between histologic findings and clinical
outcome.[38] In children, grading of soft tissue sarcomas is compromised by
the good prognosis of certain tumors such as infantile fibrosarcoma. In
addition, testing of a grading system within the pediatric population is
difficult because of the rarity of these neoplasms. In March 1986, the Pediatric
Oncology Group conducted a prospective study on pediatric soft tissue
sarcomas other than rhabdomyosarcoma and devised the grading system that is
shown below. Analysis of outcome for patients with localized soft tissue
sarcomas other than rhabdomyosarcoma demonstrated that patients with grade 3
tumors fared significantly worse than did those with grade 1 or grade 2
lesions. This finding suggests that this system can accurately predict the
clinical behavior of nonrhabdomyosarcomatous soft tissue tumors in
children.[2,38,39]
Grade 1 lesions
- Myxoid and well-differentiated liposarcoma.
- Deep-seated dermatofibrosarcoma protuberans.
- Well-differentiated or infantile (patient 4 years or younger) fibrosarcoma.
- Well-differentiated or infantile (patient 4 years or younger)
hemangiopericytoma.
- Well-differentiated malignant peripheral nerve sheath tumor.
- Extraosseus myxoid chondrosarcoma.
- Angiomatoid malignant fibrous histiocytoma.
Grade 2 lesions
In grade 2 lesions,
which are soft tissue sarcomas not included in grade 1 and grade 3 lesions, less than 15% of the surface area shows necrosis, and there are fewer than five
mitotic figures per ten high-power fields (40X objective). As secondary
criteria of grade 2 tumors, the incidence of nuclear atypia is not marked, and the tumor is
not markedly cellular.
Grade 3 lesions
- Pleomorphic or round cell liposarcoma.
- Mesenchymal chondrosarcoma.
- Extraosseous osteosarcoma.
- Triton tumor (MPNST with
rhabdomyosarcomatous elements).
- Alveolar soft part sarcoma.
- Synovial sarcoma.
- Epithelioid sarcoma.
- Clear cell sarcoma (MMSP).
Any other sarcoma not included in grade 1 in which more than 15% of the surface
area is necrotic or in which there are more than five mitotic figures
per ten high-power fields (40X objective) is considered a grade 3 lesion. Marked atypia and cellularity
are less predictive but may assist in placing tumors in this category.
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Ladanyi M, Lui MY, Antonescu CR, et al.: The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene 20 (1): 48-57, 2001.
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Carli M, Ferrari A, Mattke A, et al.: Pediatric malignant peripheral nerve sheath tumor: the Italian and German soft tissue sarcoma cooperative group. J Clin Oncol 23 (33): 8422-30, 2005.
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[PUBMED Abstract]
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Okada K, Hasegawa T, Tajino T, et al.: Clinical relevance of pathological grades of malignant peripheral nerve sheath tumor: a multi-institution TMTS study of 56 cases in Northern Japan. Ann Surg Oncol 14 (2): 597-604, 2007.
[PUBMED Abstract]
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Pappo AS, Devidas M, Jenkins J, et al.: Phase II trial of neoadjuvant vincristine, ifosfamide, and doxorubicin with granulocyte colony-stimulating factor support in children and adolescents with advanced-stage nonrhabdomyosarcomatous soft tissue sarcomas: a Pediatric Oncology Group Study. J Clin Oncol 23 (18): 4031-8, 2005.
[PUBMED Abstract]
-
Okcu MF, Despa S, Choroszy M, et al.: Synovial sarcoma in children and adolescents: thirty three years of experience with multimodal therapy. Med Pediatr Oncol 37 (2): 90-6, 2001.
[PUBMED Abstract]
-
Pappo AS, Rao BN, Jenkins JJ, et al.: Metastatic nonrhabdomyosarcomatous soft-tissue sarcomas in children and adolescents: the St. Jude Children's Research Hospital experience. Med Pediatr Oncol 33 (2): 76-82, 1999.
[PUBMED Abstract]
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Brecht IB, Ferrari A, Int-Veen C, et al.: Grossly-resected synovial sarcoma treated by the German and Italian Pediatric Soft Tissue Sarcoma Cooperative Groups: discussion on the role of adjuvant therapies. Pediatr Blood Cancer 46 (1): 11-7, 2006.
[PUBMED Abstract]
-
Raney RB: Synovial sarcoma in young people: background, prognostic factors, and therapeutic questions. J Pediatr Hematol Oncol 27 (4): 207-11, 2005.
[PUBMED Abstract]
-
Okcu MF, Munsell M, Treuner J, et al.: Synovial sarcoma of childhood and adolescence: a multicenter, multivariate analysis of outcome. J Clin Oncol 21 (8): 1602-11, 2003.
[PUBMED Abstract]
-
van de Rijn M, Barr FG, Collins MH, et al.: Absence of SYT-SSX fusion products in soft tissue tumors other than synovial sarcoma. Am J Clin Pathol 112 (1): 43-9, 1999.
[PUBMED Abstract]
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Krsková L, Sumerauer D, Stejskalová E, et al.: A novel variant of SYT-SSX1 fusion gene in a case of spindle cell synovial sarcoma. Diagn Mol Pathol 16 (3): 179-83, 2007.
[PUBMED Abstract]
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van de Rijn M, Barr FG, Xiong QB, et al.: Poorly differentiated synovial sarcoma: an analysis of clinical, pathologic, and molecular genetic features. Am J Surg Pathol 23 (1): 106-12, 1999.
[PUBMED Abstract]
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Parham DM, Webber BL, Jenkins JJ 3rd, et al.: Nonrhabdomyosarcomatous soft tissue sarcomas of childhood: formulation of a simplified system for grading. Mod Pathol 8 (7): 705-10, 1995.
[PUBMED Abstract]
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Skytting B, Meis-Kindblom JM, Larsson O, et al.: Synovial sarcoma--identification of favorable and unfavorable histologic types: a Scandinavian sarcoma group study of 104 cases. Acta Orthop Scand 70 (6): 543-54, 1999.
[PUBMED Abstract]
Back to Top Stage Information
Clinical staging has an important role in predicting the clinical outcome and
determining the most effective therapy for pediatric soft tissue sarcomas. As
yet, there is no well-accepted staging system that is applicable to all
childhood sarcomas; the system from the American Joint Commission for Cancer
(AJCC) that is used for adults has not been validated in pediatric studies, however, the current Children's Oncology Group (COG) trial is using the AJCC staging system (see Table 2 below) to facilitate comparison of results with other pediatric and adult soft tissue sarcoma trials.[1] Two
systems are currently in use for staging pediatric nonrhabdomyosarcomatous soft
tissue tumors. The surgicopathologic staging system used by the Intergroup
Rhabdomyosarcoma Study (see below) is based on the amount of tumor that remains
after initial surgery and whether the disease has metastasized.[2]
Nonmetastatic Disease
-
Group I: Tumor completely resected with histologically negative margins.
-
Group II: Grossly resected tumor with microscopic residual tumor.
-
Group III: Incomplete resection or biopsy with gross residual tumor.
Metastatic Disease
-
Group IV: Any localized or regional tumor with distant metastases present
at the time of diagnosis.
Recurrent/Progressive Disease
- Any soft tissue sarcoma that recurs after initial treatment or progresses after radiation therapy,
chemotherapy, or initial surgery.
The other schema typically used to stage pediatric soft tissue tumors is the
TNM system of the International Union Against Cancer.[3] In
this staging system, T1 lesions are those that are confined to the organ of
origin, and T2 lesions invade adjacent organs. These categories can be
subclassified to reflect the maximum tumor diameter (a: ≤5 cm; b: >5 cm).
Nodal involvement is indicated by N1 (N0: no nodal involvement), and the
presence of distant metastases at the time of diagnosis is indicated by the M1
(vs. M0) designation. Several adult and pediatric series have shown that
patients with large or invasive tumors have a significantly worse prognosis
than do those with small, noninvasive tumors.
These two staging systems have proven to be of prognostic significance in
pediatric and adult nonrhabdomyosarcomatous soft tissue sarcomas (NRSTSs).[4-8] In a
review of a large adult series of nonrhabdomyosarcomas, superficial extremity
sarcomas have a better prognosis than deep tumors. Thus, in addition to grade
and size, the depth of invasion of the tumor should be considered.[9]
Although a standardized staging system for pediatric NRSTS does not exist, the current COG trial is using the sixth edition AJCC staging system for soft tissue sarcomas (with central pathology review) described in Table 2 below.[10]
Table 2. AJCC Staging System for Soft Tissue Sarcomasa
|
Primary Tumorb
|
Regional Lymph Nodes
|
Distant Metastasis
|
Histologic Gradec
|
Stage I
|
Any tumor size, superfical or deep |
N0 |
M0 |
G1 |
G2 |
Stage II
|
T1a (tumor ≤5 cm in maximal diameter, superficial) |
N0 |
M0 |
G3 |
T1b (tumor ≤5 cm in maximal diameter, deep) |
N0 |
M0 |
G3 |
T2a (tumor >5 cm in maximal diameter, superficial) |
N0 |
M0 |
G3 |
Stage III
|
T2b (tumor >5 cm in maximal diameter, deep) |
N0 |
M0 |
G3 |
Stage IV
|
Any tumor size, superfical or deep |
N1 |
M0 or M1 |
G1, G2, or G3 |
Any tumor size, superfical or deep |
N0 or N1 |
M1 |
G1, G2, or G3 |
G1 = well differentiated; G2 = moderately differentiated; G3 = poorly differentiated; M0 = no distant metastasis; M1 = distant metastasis; N0 = no regional lymph node metastasis; N1 = regional lymph node metastasis
|
aAdapted from AJCC Cancer Staging Manual.[10]
|
bSuperficial tumor is located above the superficial fascia without invasion of the fascia; deep tumor is located either exclusively beneath the superficial fascia or superficial to the fascia with invasion of or through the fascia. All intraperitoneal visceral lesions, retroperitoneal, pelvic, and intrathoracic tumors, and the majority of head and neck tumors are classified as deep tumors.
|
cThe histologic grade established by central pathology review is to be used for staging purposes.
|
References
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Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 4th ed. St. Louis, Mo: Mosby, 2001.
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Maurer HM, Beltangady M, Gehan EA, et al.: The Intergroup Rhabdomyosarcoma Study-I. A final report. Cancer 61 (2): 209-20, 1988.
[PUBMED Abstract]
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Harmer MH, ed.: TNM Classification of Pediatric Tumors. Geneva: UICC, 1982.
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Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec.
[PUBMED Abstract]
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Pisters PW, Leung DH, Woodruff J, et al.: Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 14 (5): 1679-89, 1996.
[PUBMED Abstract]
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Coindre JM, Terrier P, Bui NB, et al.: Prognostic factors in adult patients with locally controlled soft tissue sarcoma. A study of 546 patients from the French Federation of Cancer Centers Sarcoma Group. J Clin Oncol 14 (3): 869-77, 1996.
[PUBMED Abstract]
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Pappo AS, Fontanesi J, Luo X, et al.: Synovial sarcoma in children and adolescents: the St Jude Children's Research Hospital experience. J Clin Oncol 12 (11): 2360-6, 1994.
[PUBMED Abstract]
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Pratt CB, Maurer HM, Gieser P, et al.: Treatment of unresectable or metastatic pediatric soft tissue sarcomas with surgery, irradiation, and chemotherapy: a Pediatric Oncology Group study. Med Pediatr Oncol 30 (4): 201-9, 1998.
[PUBMED Abstract]
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Brooks AD, Heslin MJ, Leung DH, et al.: Superficial extremity soft tissue sarcoma: an analysis of prognostic factors. Ann Surg Oncol 5 (1): 41-7, 1998 Jan-Feb.
[PUBMED Abstract]
-
American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002.
Back to Top Treatment Option Overview
Because of the rarity of pediatric nonrhabdomyosarcomatous soft tissue
sarcomas (NRSTSs), all children, adolescents, and young adults with these tumors should
have their treatment planned by a multidisciplinary team composed of pediatric
oncologists, surgeons, and radiotherapists. 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.
Every attempt should be made to resect the primary tumor with negative
margins before or after chemotherapy. The timing of surgery depends on an assessment of the feasibility and morbidity of surgery. Involvement of a surgeon with special expertise in the resection of soft tissue sarcomas in the decision is highly desirable. Sentinel lymph node mapping is employed at some centers to identify
the regional nodes that are the most likely to be involved, though its
contribution has not been clearly defined.[1,2] If the original operation
failed to achieve pathologically negative tissue margins, a second procedure
should be performed to obtain clear, but not necessarily wide margins.[3-7] When the initial operation was done without the knowledge that cancer was present, a re-excision of the affected region should always be considered, even in the absence of a mass on magnetic resonance imaging.[8] When
there is concern about the adequacy of the surgical margin, radiation therapy
is indicated.[9] This is particularly important in high-grade tumors with
tumor margins less than 1 cm.[10,11] Thus, by using these two treatment
modalities, local control of the primary tumor can be achieved in more than 80%
of patients.[12,13] Although combined surgery and radiation therapy have
dramatically improved outcome in adults and children with soft tissue sarcomas
over the past 20 years,[9] the morbidity of high-dose radiation therapy is of
concern in infants and young children with these tumors.[14] Brachytherapy and
intraoperative radiation may be applicable in select
situations.[13,15,16] Preoperative radiation therapy has been associated with
excellent local control rates [17-19] but has been associated with an increased rate of wound complications in adults.[20] Patients in the pediatric age group with unresected NRSTS have a poor outcome. Only about one-third of patients treated with multimodality therapy remain disease free.[20,21]
Therapeutic strategies for children and adolescents with soft tissue tumors are
similar to those for adult patients, though there are important differences.
For example, the biology of the pediatric form of the neoplasm may differ
dramatically from that of the adult lesion. Limb-sparing procedures are more
difficult to perform in pediatric patients. In addition, the morbidity of
radiation therapy in young children may be much greater than that observed in
adults. Lastly, the concern regarding potential long-term side effects of
combined modality therapy (radiation, surgery, and chemotherapy) is greater for
children, whose survival may be much longer than that of adults. Therefore, to
maximize tumor control and minimize long-term morbidity, treatment must be
individualized for children and adolescents with nonrhabdomyosarcomatous soft
tissue tumors. These patients should be enrolled in prospective studies that
accurately assess any potential complications.[22]
The role of adjuvant (postoperative) chemotherapy remains controversial. A meta-analysis of updated data from adult soft tissue sarcoma patients from all available randomized trials concluded that recurrence-free survival was better with adjuvant chemotherapy.[23] The
largest prospective pediatric trial failed to demonstrate any benefit with adjuvant
vincristine, dactinomycin, cyclophosphamide, and doxorubicin.[12] Synovial sarcoma appears to be more sensitive to chemotherapy than many other soft tissue sarcomas, and children with synovial sarcoma seem to have a better prognosis.[24-28] A German trial suggested a benefit for adjuvant chemotherapy in children with synovial sarcoma.[29] A meta-analysis also suggested that chemotherapy may provide benefit.[30] Many treatment centers advocate adjuvant chemotherapy following resection of synovial sarcoma in children and young adults; unequivocal proof of the value of this strategy from prospective, randomized clinical trials is lacking.
References
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Neville HL, Andrassy RJ, Lally KP, et al.: Lymphatic mapping with sentinel node biopsy in pediatric patients. J Pediatr Surg 35 (6): 961-4, 2000.
[PUBMED Abstract]
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Neville HL, Raney RB, Andrassy RJ, et al.: Multidisciplinary management of pediatric soft-tissue sarcoma. Oncology (Huntingt) 14 (10): 1471-81; discussion 1482-6, 1489-90, 2000.
[PUBMED Abstract]
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Okcu MF, Despa S, Choroszy M, et al.: Synovial sarcoma in children and adolescents: thirty three years of experience with multimodal therapy. Med Pediatr Oncol 37 (2): 90-6, 2001.
[PUBMED Abstract]
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Sugiura H, Takahashi M, Katagiri H, et al.: Additional wide resection of malignant soft tissue tumors. Clin Orthop (394): 201-10, 2002.
[PUBMED Abstract]
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Cecchetto G, Guglielmi M, Inserra A, et al.: Primary re-excision: the Italian experience in patients with localized soft-tissue sarcomas. Pediatr Surg Int 17 (7): 532-4, 2001.
[PUBMED Abstract]
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Chui CH, Spunt SL, Liu T, et al.: Is reexcision in pediatric nonrhabdomyosarcoma soft tissue sarcoma necessary after an initial unplanned resection? J Pediatr Surg 37 (10): 1424-9, 2002.
[PUBMED Abstract]
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Paulino AC, Ritchie J, Wen BC: The value of postoperative radiotherapy in childhood nonrhabdomyosarcoma soft tissue sarcoma. Pediatr Blood Cancer 43 (5): 587-93, 2004.
[PUBMED Abstract]
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Kaste SC, Hill A, Conley L, et al.: Magnetic resonance imaging after incomplete resection of soft tissue sarcoma. Clin Orthop (397): 204-11, 2002.
[PUBMED Abstract]
-
Marcus KC, Grier HE, Shamberger RC, et al.: Childhood soft tissue sarcoma: a 20-year experience. J Pediatr 131 (4): 603-7, 1997.
[PUBMED Abstract]
-
Blakely ML, Spurbeck WW, Pappo AS, et al.: The impact of margin of resection on outcome in pediatric nonrhabdomyosarcoma soft tissue sarcoma. J Pediatr Surg 34 (5): 672-5, 1999.
[PUBMED Abstract]
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Skytting B: Synovial sarcoma. A Scandinavian Sarcoma Group project. Acta Orthop Scand Suppl 291: 1-28, 2000.
[PUBMED Abstract]
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Pratt CB, Pappo AS, Gieser P, et al.: Role of adjuvant chemotherapy in the treatment of surgically resected pediatric nonrhabdomyosarcomatous soft tissue sarcomas: A Pediatric Oncology Group Study. J Clin Oncol 17 (4): 1219, 1999.
[PUBMED Abstract]
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Merchant TE, Parsh N, del Valle PL, et al.: Brachytherapy for pediatric soft-tissue sarcoma. Int J Radiat Oncol Biol Phys 46 (2): 427-32, 2000.
[PUBMED Abstract]
-
Suit H, Spiro I: Radiation as a therapeutic modality in sarcomas of the soft tissue. Hematol Oncol Clin North Am 9 (4): 733-46, 1995.
[PUBMED Abstract]
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Schomberg PJ, Gunderson LL, Moir CR, et al.: Intraoperative electron irradiation in the management of pediatric malignancies. Cancer 79 (11): 2251-6, 1997.
[PUBMED Abstract]
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Nag S, Shasha D, Janjan N, et al.: The American Brachytherapy Society recommendations for brachytherapy of soft tissue sarcomas. Int J Radiat Oncol Biol Phys 49 (4): 1033-43, 2001.
[PUBMED Abstract]
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Sadoski C, Suit HD, Rosenberg A, et al.: Preoperative radiation, surgical margins, and local control of extremity sarcomas of soft tissues. J Surg Oncol 52 (4): 223-30, 1993.
[PUBMED Abstract]
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Virkus WW, Mollabashy A, Reith JD, et al.: Preoperative radiotherapy in the treatment of soft tissue sarcomas. Clin Orthop (397): 177-89, 2002.
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Zagars GK, Ballo MT, Pisters PW, et al.: Preoperative vs. postoperative radiation therapy for soft tissue sarcoma: a retrospective comparative evaluation of disease outcome. Int J Radiat Oncol Biol Phys 56 (2): 482-8, 2003.
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O'Sullivan B, Davis AM, Turcotte R, et al.: Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet 359 (9325): 2235-41, 2002.
[PUBMED Abstract]
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Spunt SL, Hill DA, Motosue AM, et al.: Clinical features and outcome of initially unresected nonmetastatic pediatric nonrhabdomyosarcoma soft tissue sarcoma. J Clin Oncol 20 (15): 3225-35, 2002.
[PUBMED Abstract]
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Miser JS, Triche TJ, Kinsella TJ, et al.: Other soft tissue sarcomas of childhood. In: Pizzo PA, Poplack DG, eds.: Principles and Practice of Pediatric Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven, 1997, pp 865-888.
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Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Sarcoma Meta-analysis Collaboration. Lancet 350 (9092): 1647-54, 1997.
[PUBMED Abstract]
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McGrory JE, Pritchard DJ, Arndt CA, et al.: Nonrhabdomyosarcoma soft tissue sarcomas in children. The Mayo Clinic experience. Clin Orthop (374): 247-58, 2000.
[PUBMED Abstract]
-
Ferrari A, Gronchi A, Casanova M, et al.: Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution. Cancer 101 (3): 627-34, 2004.
[PUBMED Abstract]
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Van Glabbeke M, van Oosterom AT, Oosterhuis JW, et al.: Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2,185 patients treated with anthracycline-containing first-line regimens--a European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol 17 (1): 150-7, 1999.
[PUBMED Abstract]
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Koscielniak E, Harms D, Henze G, et al.: Results of treatment for soft tissue sarcoma in childhood and adolescence: a final report of the German Cooperative Soft Tissue Sarcoma Study CWS-86. J Clin Oncol 17 (12): 3706-19, 1999.
[PUBMED Abstract]
-
Pappo AS, Devidas M, Jenkins J, et al.: Phase II trial of neoadjuvant vincristine, ifosfamide, and doxorubicin with granulocyte colony-stimulating factor support in children and adolescents with advanced-stage nonrhabdomyosarcomatous soft tissue sarcomas: a Pediatric Oncology Group Study. J Clin Oncol 23 (18): 4031-8, 2005.
[PUBMED Abstract]
-
Ladenstein R, Treuner J, Koscielniak E, et al.: Synovial sarcoma of childhood and adolescence. Report of the German CWS-81 study. Cancer 71 (11): 3647-55, 1993.
[PUBMED Abstract]
-
Okcu MF, Munsell M, Treuner J, et al.: Synovial sarcoma of childhood and adolescence: a multicenter, multivariate analysis of outcome. J Clin Oncol 21 (8): 1602-11, 2003.
[PUBMED Abstract]
Back to Top Nonmetastatic Childhood Soft Tissue Sarcoma
Treatment Options by Soft Tissue Sarcoma Type
For nonmetastatic pediatric nonrhabdomyosarcomatous soft tissue sarcomas (NRSTSs),
treatment with surgery alone is often curative.[1-6] If the initial surgery was performed without suspicion of malignancy, re-excision by a surgeon experienced in the treatment of soft tissue sarcoma is essential, even if imaging studies do not suggest the presence of residual tumor. Postoperatively, tumor-free margins must be confirmed through pathologic evaluation, and
re-excision must be performed if the margins are positive. If further
resection is not feasible, postoperative radiation therapy, or if possible,
brachytherapy should be used.[7,8] For patients with local recurrence,
re-excision of the mass is indicated.
-
Tumors with low potential for metastasis:
Fibrosarcomas and hemangiopericytomas are tumors with low potential for metastasis in infants and young children; desmoid
tumors, aggressive fibromatosis, dermatofibrosarcoma, and angiomatoid malignant fibrous histiocytomas
typically are also clinically less aggressive, rarely metastasize, and can often be
treated successfully with surgery alone.[1,9-11] In children with infantile fibrosarcoma,
preoperative chemotherapy has made possible a more conservative surgical
approach; agents active in this setting include vincristine, dactinomycin,
cyclophosphamide, and ifosfamide.[1,12] Responses to presurgical chemotherapy
with similar agents have been reported in cases of infantile
hemangiopericytoma.[1]
Desmoid tumors are well-differentiated fibrous lesions that rarely metastasize,
but they have a significant potential for local invasiveness and recurrence.
The treatment of choice is resection to achieve clear margins. If
postoperative margins are positive, 70% of patients will have a recurrence of
disease. When complete surgical excision is not feasible and the tumor poses
significant potential for mortality or morbidity, preoperative strategies that
include external-beam radiation therapy, postoperative interstitial
iridium I 192, nonsteroidal anti-inflammatory agents, antiestrogens, vinblastine,
and methotrexate should be considered.[13,14] Evaluation of the benefit of chemotherapy for treatment of desmoid tumors has been extremely difficult because desmoid tumors have a highly variable natural history. Large adult series and a single pediatric series have reported long periods of disease stabilization and even regression without systemic therapy.[15,16] A small series of mainly adult patients (n = 19) with desmoid tumors were treated with imatinib mesylate and showed infrequent objective responses.[17] A series of mainly adult familial adenomatous polyposis patients with unresectable desmoid tumors that were unresponsive to hormone therapy, showed that doxorubicin plus dacarbazine followed by meloxicam (a nonsteroidal anti-inflammatory agent) can be safely administered and can induce responses.[18] There are reports of objective responses to systemic chemotherapy in children with desmoid tumors. Combination chemotherapy using vinblastine and methotrexate has been used for the treatment of progressive desmoid tumor in children.[13] These should be interpreted cautiously in light of the variable natural history of the disease. Partially excised or recurrent lesions
that do not pose a significant danger to vital organs may be monitored closely
if other treatment alternatives are not available.[16,19-22] Whenever
possible, however, the treatment of choice is complete resection.
Treatment option under clinical evaluation:
The following treatment option is currently under investigation in national and/or institutional clinical trials. For more information about clinical trials, please see the NCI Web site.
- Imatinib mesylate used as a treatment in recurrent soft tissue sarcomas, bone sarcomas, and primary desmoid tumors.
- The pediatric neoplasms listed below exhibit similar biologic behavior to those
lesions in adults, and a discussion of their treatment follows.
- Fibrosarcoma in older children and adolescents.
- Malignant peripheral nerve sheath tumor (MPNST).
- Liposarcoma.
- Synovial sarcoma.
- Hemangiopericytoma in older children and young adults.
- Extraosseous osteosarcoma.
- Extraosseous chondrosarcoma.
- Malignant fibrous histiocytoma.
- Leiomyosarcoma.
- Epithelioid sarcoma.
Standard treatment options: Every attempt should be made to resect the primary tumor locally with negative
margins.[23,24] If the original operation failed to achieve pathologically negative
tissue margins, a second surgery may be indicated.[2] Although combined
surgery and radiation therapy have dramatically improved outcome in adults and
children with soft tissue sarcomas over the past 20 years,[7] the morbidity of
high-dose radiation therapy should be considered in infants and
young children with these tumors.[25] The use of brachytherapy and
intraoperative radiation therapy is under study.[8,26] Preoperative
radiation therapy has been associated with excellent local control rates in
adults;[27,28] this approach has not been used extensively in pediatric patients. The role of adjuvant (postoperative) chemotherapy remains controversial. Virtually all trials of adjuvant chemotherapy in adults with soft tissue sarcoma report the results of treatment for all patients in aggregate. This may obscure important differences in chemosensitivity among histologic subtypes of soft tissue sarcoma. A retrospective analysis of neoadjuvant chemotherapy in adults with soft tissue sarcoma suggested a benefit for patients with larger tumors.[29] The
largest prospective pediatric trial failed to document any benefit of adjuvant
chemotherapy with vincristine, dactinomycin, cyclophosphamide, and doxorubicin
in children with grossly resected tumors.[30] This trial also reported results in aggregate for a variety of soft tissue sarcomas. In patients with unresectable or metastatic disease treated with
vincristine, dactinomycin, and cyclophosphamide, the overall survival (OS) and disease-free
survival rates were 31% and 10%, respectively.[31] Achieving complete responses after aggressive chemotherapy, radiation therapy, and surgery is possible in most patients with more advanced NRSTS.[32] Chemotherapy for extraosseous osteosarcoma has not been well studied. Treatment has previously been recommended to follow soft tissue sarcoma guidelines rather than guidelines for osteosarcoma of bone.[33] Extraosseous osteosarcoma may be more chemosensitive in young patients than in adults.[33] A retrospective analysis of the German Cooperative Osteosarcoma Study identified a favorable outcome for extraskeletal osteosarcoma treated with surgery and conventional osteosarcoma chemotherapy.[34] (Refer to the PDQ summary on Osteosarcoma/Malignant Fibrous Histiocytoma of Bone for more information.) Synovial sarcoma appears to be more sensitive to chemotherapy than many other NRSTSs. Children with synovial sarcoma have a higher probability for both event-free survival (EFS) and OS than children with other types of NRSTS.[35,36] A German randomized trial suggested a benefit for adjuvant chemotherapy in children with synovial sarcoma.[37] A meta-analysis also suggested that chemotherapy may improve EFS but could not confirm improvement in OS.[24] Many treatment centers advocate adjuvant chemotherapy following resection of synovial sarcoma in children and young adults; unequivocal proof of the value of this strategy from prospective, randomized clinical trials is lacking. A study of 21 patients with small (<1 cm), localized synovial sarcomas showed an excellent survival rate with no metastatic events; only one patient received chemotherapy.[38] A retrospective analysis of synovial sarcoma in children treated in Germany and Italy identified tumor size (>5 cm or <5 cm in greatest dimension) as an important predictor of EFS.[39] In this analysis, local invasiveness conferred an inferior probability of EFS, but surgical margins did not predict outcome. A large retrospective analysis of the German and Italian experience with MPNST identified incomplete resection, large tumor size, tumor invasiveness, nonextremity primary site, and clinical diagnosis of neurofibromatosis as unfavorable prognostic findings.[23] There was a trend toward improved outcome with adjuvant radiation therapy. While 65% of measurable tumors had objective responses to ifosfamide-containing chemotherapy regimens, the analysis did not conclusively demonstrate improved survival for chemotherapy.[23] A series of 37 young patients with MPNST and neurofibromatosis type-1 (NF-1) showed that most patients had large invasive tumors, poorly responsive to chemotherapy; progression-free survival was 19% and overall 5 year survival was 28%.[40] Another series of older patients with MPNST found that those with NF-1 had a worse prognosis than those without NF-1.[41]
-
Alveolar soft part sarcoma (ASPS) is a tumor of uncertain histogenesis characterized by an x;17 translocation.[42] Pediatric ASPS seems to have a better outcome than its adult counterpart.[43] In a series of 19 treated patients, one group reported a 5-year OS rate of 80%, a 91% OS rate for patients with localized disease, a 100% OS rate for patients with tumors 5 cm or smaller, and a 31% OS rate for patients with tumors larger than 5 cm.[6] A subset of renal tumors found in young people
was previously considered to be renal cell carcinoma, but the subset now appears to be genetically
related to ASPS.[44]
Standard treatment options:
The standard approach is complete resection of the primary lesion.[6]
If complete excision is not feasible, radiation therapy should be
administered. The value of adjuvant chemotherapy in completely resected
ASPS remains unproven, particularly because patients
with unresected or metastatic tumors failed to respond to chemotherapeutic
agents frequently used to treat soft tissue sarcomas.[45] Patients with ASPS may relapse several years after a prolonged period of
apparent remission.[46]
Treatment options under clinical evaluation:
-
COG ARST0332 is a prospective study for children and young adults with soft tissue sarcomas other than rhabdomyosarcoma. Patients are stratified by tumor grade and extent. Patients with lower grade tumors and patients with small, completely resected high-grade tumors are observed after surgical resection alone. Patients with positive microscopic margins receive adjuvant radiation. Patients with high-grade tumors larger than 5 cm undergo resection and receive adjuvant chemotherapy and radiation. Patients with unresectable or metastatic disease receive neoadjuvant chemotherapy. Chemotherapy for all eligible patients is ifosfamide and doxorubicin.[47]
- The role of adjuvant chemotherapy in children with this malignancy has not
been tested. Because these tumors are rare, all children with ASPS should be enrolled in prospective clinical trials.
-
Desmoplastic small round cell tumor is a primitive sarcoma that most
frequently involves the abdomen, pelvis, or tissues around the testes.[48-50]
The tumor occurs mainly in males and invades locally but may spread to the lungs and elsewhere.
Cytogenetic studies of these tumors have demonstrated the recurrent
translocation t(11;22)(p13;q12), which has been characterized as a fusion of the
WT1 and EWS genes.[51]
Standard treatment options:
Complete resection of this tumor is rarely possible, thus effective treatment
must rely on chemotherapy and radiation therapy. Treatment for individuals
with desmoplastic small round cell tumor following surgery requires aggressive
chemotherapy with the agents that are used for the treatment of sarcoma
combined with appropriate radiation treatment. Prognosis is dependent on the
extent and aggressiveness of the tumor and its treatment.[48,49,52]
Whole abdominopelvic radiation therapy is feasible but has not significantly improved the outcome for this diagnosis.[53,54]
Treatment options under clinical evaluation:
-
Clear cell sarcoma (malignant melanoma) of soft parts (also called clear cell sarcoma of tendons and aponeuroses) is somewhat similar
to cutaneous malignant melanoma but is cytogenetically distinct; most cases
have a t(12;22)(q13;q12) translocation that has not been reported in
melanoma.[55] Patients who have small, localized tumors with low mitotic rate and intermediate histologic grade fare best.[56] Treatment is
primarily surgical with radiation therapy for uncertain or involved margins.
Antisarcoma chemotherapy is rarely effective.[57]
-
Hemangioendotheliomas are tumors found in infants that arise within the liver or
elsewhere and usually remain benign.[58] The tumors are sometimes associated with
consumptive coagulopathy, also known as the Kasabach-Merritt syndrome (or
phenomenon).[59-61] In older children and adults, hemangioendotheliomas may
occur elsewhere in the body and can metastasize to lungs, lymph nodes, bones,
and within the pleural or peritoneal cavities. The preferred pathologic
designation for these lesions in older persons is epithelioid
hemangioendothelioma, which connotes the possibility of distant spread.
These latter lesions are considered of intermediate malignant potential,
between benign hemangioma and angiosarcoma.[62,63] Treatment of the
asymptomatic liver hemangioendothelioma of a child younger than 1 year may
consist of close observation, because some tumors will regress. Symptomatic
lesions require urgent medical or surgical management, especially if
coagulopathy is present.[58-61] Epithelioid hemangioendothelioma of the liver
should be managed surgically; some patients may need orthotopic liver
transplantation because this disease does not respond to radiation therapy or
chemotherapy.[62]
-
Vascular tumors vary from hemangiomas, which are considered always benign, to
angiosarcomas, which are highly malignant.[64] Complete surgical excision
appears to be crucial for angiosarcomas and lymphangiosarcomas despite evidence
of tumor shrinkage in some patients in response to local therapy.[65-67]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with nonmetastatic childhood soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
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Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec.
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deCou JM, Rao BN, Parham DM, et al.: Malignant peripheral nerve sheath tumors: the St. Jude Children's Research Hospital experience. Ann Surg Oncol 2 (6): 524-9, 1995.
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Pappo AS, Fontanesi J, Luo X, et al.: Synovial sarcoma in children and adolescents: the St Jude Children's Research Hospital experience. J Clin Oncol 12 (11): 2360-6, 1994.
[PUBMED Abstract]
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Casanova M, Ferrari A, Bisogno G, et al.: Alveolar soft part sarcoma in children and adolescents: A report from the Soft-Tissue Sarcoma Italian Cooperative Group. Ann Oncol 11 (11): 1445-9, 2000.
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Merchant TE, Parsh N, del Valle PL, et al.: Brachytherapy for pediatric soft-tissue sarcoma. Int J Radiat Oncol Biol Phys 46 (2): 427-32, 2000.
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Loh ML, Ahn P, Perez-Atayde AR, et al.: Treatment of infantile fibrosarcoma with chemotherapy and surgery: results from the Dana-Farber Cancer Institute and Children's Hospital, Boston. J Pediatr Hematol Oncol 24 (9): 722-6, 2002.
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Skapek SX, Ferguson WS, Granowetter L, et al.: Vinblastine and methotrexate for desmoid fibromatosis in children: results of a Pediatric Oncology Group Phase II Trial. J Clin Oncol 25 (5): 501-6, 2007.
[PUBMED Abstract]
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Gandhi MM, Nathan PC, Weitzman S, et al.: Successful treatment of life-threatening generalized infantile myofibromatosis using low-dose chemotherapy. J Pediatr Hematol Oncol 25 (9): 750-4, 2003.
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Merchant NB, Lewis JJ, Woodruff JM, et al.: Extremity and trunk desmoid tumors: a multifactorial analysis of outcome. Cancer 86 (10): 2045-52, 1999.
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Faulkner LB, Hajdu SI, Kher U, et al.: Pediatric desmoid tumor: retrospective analysis of 63 cases. J Clin Oncol 13 (11): 2813-8, 1995.
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Heinrich MC, McArthur GA, Demetri GD, et al.: Clinical and molecular studies of the effect of imatinib on advanced aggressive fibromatosis (desmoid tumor). J Clin Oncol 24 (7): 1195-203, 2006.
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Gega M, Yanagi H, Yoshikawa R, et al.: Successful chemotherapeutic modality of doxorubicin plus dacarbazine for the treatment of desmoid tumors in association with familial adenomatous polyposis. J Clin Oncol 24 (1): 102-5, 2006.
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Merchant TE, Nguyen D, Walter AW, et al.: Long-term results with radiation therapy for pediatric desmoid tumors. Int J Radiat Oncol Biol Phys 47 (5): 1267-71, 2000.
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Zelefsky MJ, Harrison LB, Shiu MH, et al.: Combined surgical resection and iridium 192 implantation for locally advanced and recurrent desmoid tumors. Cancer 67 (2): 380-4, 1991.
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Weiss AJ, Lackman RD: Low-dose chemotherapy of desmoid tumors. Cancer 64 (6): 1192-4, 1989.
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Klein WA, Miller HH, Anderson M, et al.: The use of indomethacin, sulindac, and tamoxifen for the treatment of desmoid tumors associated with familial polyposis. Cancer 60 (12): 2863-8, 1987.
[PUBMED Abstract]
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Carli M, Ferrari A, Mattke A, et al.: Pediatric malignant peripheral nerve sheath tumor: the Italian and German soft tissue sarcoma cooperative group. J Clin Oncol 23 (33): 8422-30, 2005.
[PUBMED Abstract]
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Okcu MF, Munsell M, Treuner J, et al.: Synovial sarcoma of childhood and adolescence: a multicenter, multivariate analysis of outcome. J Clin Oncol 21 (8): 1602-11, 2003.
[PUBMED Abstract]
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Suit H, Spiro I: Radiation as a therapeutic modality in sarcomas of the soft tissue. Hematol Oncol Clin North Am 9 (4): 733-46, 1995.
[PUBMED Abstract]
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Schomberg PJ, Gunderson LL, Moir CR, et al.: Intraoperative electron irradiation in the management of pediatric malignancies. Cancer 79 (11): 2251-6, 1997.
[PUBMED Abstract]
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Sadoski C, Suit HD, Rosenberg A, et al.: Preoperative radiation, surgical margins, and local control of extremity sarcomas of soft tissues. J Surg Oncol 52 (4): 223-30, 1993.
[PUBMED Abstract]
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Cannon CP, Ballo MT, Zagars GK, et al.: Complications of combined modality treatment of primary lower extremity soft-tissue sarcomas. Cancer 107 (10): 2455-61, 2006.
[PUBMED Abstract]
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Grobmyer SR, Maki RG, Demetri GD, et al.: Neo-adjuvant chemotherapy for primary high-grade extremity soft tissue sarcoma. Ann Oncol 15 (11): 1667-72, 2004.
[PUBMED Abstract]
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Pratt CB, Pappo AS, Gieser P, et al.: Role of adjuvant chemotherapy in the treatment of surgically resected pediatric nonrhabdomyosarcomatous soft tissue sarcomas: A Pediatric Oncology Group Study. J Clin Oncol 17 (4): 1219, 1999.
[PUBMED Abstract]
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Pratt CB, Maurer HM, Gieser P, et al.: Treatment of unresectable or metastatic pediatric soft tissue sarcomas with surgery, irradiation, and chemotherapy: a Pediatric Oncology Group study. Med Pediatr Oncol 30 (4): 201-9, 1998.
[PUBMED Abstract]
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Nathan PC, Tsokos M, Long L, et al.: Adjuvant chemotherapy for the treatment of advanced pediatric nonrhabdomyosarcoma soft tissue sarcoma: the National Cancer Institute experience. Pediatr Blood Cancer 44 (5): 449-54, 2005.
[PUBMED Abstract]
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Wodowski K, Hill DA, Pappo AS, et al.: A chemosensitive pediatric extraosseous osteosarcoma: case report and review of the literature. J Pediatr Hematol Oncol 25 (1): 73-7, 2003.
[PUBMED Abstract]
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Goldstein-Jackson SY, Gosheger G, Delling G, et al.: Extraskeletal osteosarcoma has a favourable prognosis when treated like conventional osteosarcoma. J Cancer Res Clin Oncol 131 (8): 520-6, 2005.
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McGrory JE, Pritchard DJ, Arndt CA, et al.: Nonrhabdomyosarcoma soft tissue sarcomas in children. The Mayo Clinic experience. Clin Orthop (374): 247-58, 2000.
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Ferrari A, Gronchi A, Casanova M, et al.: Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution. Cancer 101 (3): 627-34, 2004.
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Ladenstein R, Treuner J, Koscielniak E, et al.: Synovial sarcoma of childhood and adolescence. Report of the German CWS-81 study. Cancer 71 (11): 3647-55, 1993.
[PUBMED Abstract]
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Michal M, Fanburg-Smith JC, Lasota J, et al.: Minute synovial sarcomas of the hands and feet: a clinicopathologic study of 21 tumors less than 1 cm. Am J Surg Pathol 30 (6): 721-6, 2006.
[PUBMED Abstract]
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Brecht IB, Ferrari A, Int-Veen C, et al.: Grossly-resected synovial sarcoma treated by the German and Italian Pediatric Soft Tissue Sarcoma Cooperative Groups: discussion on the role of adjuvant therapies. Pediatr Blood Cancer 46 (1): 11-7, 2006.
[PUBMED Abstract]
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Ferrari A, Bisogno G, Macaluso A, et al.: Soft-tissue sarcomas in children and adolescents with neurofibromatosis type 1. Cancer 109 (7): 1406-12, 2007.
[PUBMED Abstract]
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Hagel C, Zils U, Peiper M, et al.: Histopathology and clinical outcome of NF1-associated vs. sporadic malignant peripheral nerve sheath tumors. J Neurooncol 82 (2): 187-92, 2007.
[PUBMED Abstract]
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Ladanyi M, Lui MY, Antonescu CR, et al.: The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene 20 (1): 48-57, 2001.
[PUBMED Abstract]
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Fanburg-Smith JC, Miettinen M, Folpe AL, et al.: Lingual alveolar soft part sarcoma; 14 cases: novel clinical and morphological observations. Histopathology 45 (5): 526-37, 2004.
[PUBMED Abstract]
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Argani P, Antonescu CR, Illei PB, et al.: Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. Am J Pathol 159 (1): 179-92, 2001.
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Ogose A, Yazawa Y, Ueda T, et al.: Alveolar soft part sarcoma in Japan: multi-institutional study of 57 patients from the Japanese Musculoskeletal Oncology Group. Oncology 65 (1): 7-13, 2003.
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Lieberman PH, Brennan MF, Kimmel M, et al.: Alveolar soft-part sarcoma. A clinico-pathologic study of half a century. Cancer 63 (1): 1-13, 1989.
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Pappo AS, Devidas M, Jenkins J, et al.: Phase II trial of neoadjuvant vincristine, ifosfamide, and doxorubicin with granulocyte colony-stimulating factor support in children and adolescents with advanced-stage nonrhabdomyosarcomatous soft tissue sarcomas: a Pediatric Oncology Group Study. J Clin Oncol 23 (18): 4031-8, 2005.
[PUBMED Abstract]
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Leuschner I, Radig K, Harms D: Desmoplastic small round cell tumor. Semin Diagn Pathol 13 (3): 204-12, 1996.
[PUBMED Abstract]
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Kushner BH, LaQuaglia MP, Wollner N, et al.: Desmoplastic small round-cell tumor: prolonged progression-free survival with aggressive multimodality therapy. J Clin Oncol 14 (5): 1526-31, 1996.
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Saab R, Khoury JD, Krasin M, et al.: Desmoplastic small round cell tumor in childhood: the St. Jude Children's Research Hospital experience. Pediatr Blood Cancer 49 (3): 274-9, 2007.
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Gerald WL, Ladanyi M, de Alava E, et al.: Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22)(p13;q12): desmoplastic small round-cell tumor and its variants. J Clin Oncol 16 (9): 3028-36, 1998.
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Schwarz RE, Gerald WL, Kushner BH, et al.: Desmoplastic small round cell tumors: prognostic indicators and results of surgical management. Ann Surg Oncol 5 (5): 416-22, 1998 Jul-Aug.
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Goodman KA, Wolden SL, La Quaglia MP, et al.: Whole abdominopelvic radiotherapy for desmoplastic small round-cell tumor. Int J Radiat Oncol Biol Phys 54 (1): 170-6, 2002.
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Lal DR, Su WT, Wolden SL, et al.: Results of multimodal treatment for desmoplastic small round cell tumors. J Pediatr Surg 40 (1): 251-5, 2005.
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Speleman F, Delattre O, Peter M, et al.: Malignant melanoma of the soft parts (clear-cell sarcoma): confirmation of EWS and ATF-1 gene fusion caused by a t(12;22) translocation. Mod Pathol 10 (5): 496-9, 1997.
[PUBMED Abstract]
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Coindre JM, Hostein I, Terrier P, et al.: Diagnosis of clear cell sarcoma by real-time reverse transcriptase-polymerase chain reaction analysis of paraffin embedded tissues: clinicopathologic and molecular analysis of 44 patients from the French sarcoma group. Cancer 107 (5): 1055-64, 2006.
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Ferrari A, Casanova M, Bisogno G, et al.: Clear cell sarcoma of tendons and aponeuroses in pediatric patients: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Cancer 94 (12): 3269-76, 2002.
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Daller JA, Bueno J, Gutierrez J, et al.: Hepatic hemangioendothelioma: clinical experience and management strategy. J Pediatr Surg 34 (1): 98-105; discussion 105-6, 1999.
[PUBMED Abstract]
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Lyons LL, North PE, Mac-Moune Lai F, et al.: Kaposiform hemangioendothelioma: a study of 33 cases emphasizing its pathologic, immunophenotypic, and biologic uniqueness from juvenile hemangioma. Am J Surg Pathol 28 (5): 559-68, 2004.
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Hu B, Lachman R, Phillips J, et al.: Kasabach-Merritt syndrome-associated kaposiform hemangioendothelioma successfully treated with cyclophosphamide, vincristine, and actinomycin D. J Pediatr Hematol Oncol 20 (6): 567-9, 1998 Nov-Dec.
[PUBMED Abstract]
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Deb G, Jenkner A, De Sio L, et al.: Spindle cell (Kaposiform) hemangioendothelioma with Kasabach-Merritt syndrome in an infant: successful treatment with alpha-2A interferon. Med Pediatr Oncol 28 (5): 358-61, 1997.
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Makhlouf HR, Ishak KG, Goodman ZD: Epithelioid hemangioendothelioma of the liver: a clinicopathologic study of 137 cases. Cancer 85 (3): 562-82, 1999.
[PUBMED Abstract]
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Pinet C, Magnan A, Garbe L, et al.: Aggressive form of pleural epithelioid haemangioendothelioma: complete response after chemotherapy. Eur Respir J 14 (1): 237-8, 1999.
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Coffin CM, Dehner LP: Vascular tumors in children and adolescents: a clinicopathologic study of 228 tumors in 222 patients. Pathol Annu 28 Pt 1: 97-120, 1993.
[PUBMED Abstract]
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Lezama-del Valle P, Gerald WL, Tsai J, et al.: Malignant vascular tumors in young patients. Cancer 83 (8): 1634-9, 1998.
[PUBMED Abstract]
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Fata F, O'Reilly E, Ilson D, et al.: Paclitaxel in the treatment of patients with angiosarcoma of the scalp or face. Cancer 86 (10): 2034-7, 1999.
[PUBMED Abstract]
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Ferrari A, Casanova M, Bisogno G, et al.: Malignant vascular tumors in children and adolescents: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Med Pediatr Oncol 39 (2): 109-14, 2002.
[PUBMED Abstract]
Back to Top Metastatic Childhood Soft Tissue Sarcoma
The prognosis for children with metastatic soft tissue sarcomas is poor,[1-6]
and these children should receive combined treatment with chemotherapy,
radiation therapy, and surgical resection of pulmonary metastases. In a
prospective randomized trial, chemotherapy with vincristine, dactinomycin,
doxorubicin, and cyclophosphamide with or without dacarbazine led to tumor
responses in one-third of patients with unresectable or metastatic disease.
The estimated 4-year survival rate, however, was poor, with fewer than one-third
of the children surviving.[6-8]
Standard Treatment Options
Children with isolated pulmonary metastases should undergo exploratory
thoracotomy in an attempt to resect all gross disease. The estimated 5-year
survival rate after thoracotomy for pulmonary metastasectomy has ranged from
10% to 58% in adult studies. Formal segmentectomy, lobectomy, and mediastinal
lymph node dissection are unnecessary.[9]
Treatment Options Under Clinical Evaluation
Vincristine, doxorubicin, and ifosfamide with granulocyte colony-stimulating
factor have been used in patients with unresected or metastatic tumors. The Pediatric
Oncology Group evaluated the combination of doxorubicin and
ifosfamide in children with unresected or metastatic soft tissue sarcomas
because several adult trials have suggested that ifosfamide-based regimens may
be superior to other chemotherapeutic regimens for soft tissue sarcomas.[10]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with metastatic childhood soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Demetri GD, Elias AD: Results of single-agent and combination chemotherapy for advanced soft tissue sarcomas. Implications for decision making in the clinic. Hematol Oncol Clin North Am 9 (4): 765-85, 1995.
[PUBMED Abstract]
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Elias A, Ryan L, Sulkes A, et al.: Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy. J Clin Oncol 7 (9): 1208-16, 1989.
[PUBMED Abstract]
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Edmonson JH, Ryan LM, Blum RH, et al.: Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol 11 (7): 1269-75, 1993.
[PUBMED Abstract]
-
Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec.
[PUBMED Abstract]
-
deCou JM, Rao BN, Parham DM, et al.: Malignant peripheral nerve sheath tumors: the St. Jude Children's Research Hospital experience. Ann Surg Oncol 2 (6): 524-9, 1995.
[PUBMED Abstract]
-
Pappo AS, Rao BN, Jenkins JJ, et al.: Metastatic nonrhabdomyosarcomatous soft-tissue sarcomas in children and adolescents: the St. Jude Children's Research Hospital experience. Med Pediatr Oncol 33 (2): 76-82, 1999.
[PUBMED Abstract]
-
Pratt CB, Pappo AS, Gieser P, et al.: Role of adjuvant chemotherapy in the treatment of surgically resected pediatric nonrhabdomyosarcomatous soft tissue sarcomas: A Pediatric Oncology Group Study. J Clin Oncol 17 (4): 1219, 1999.
[PUBMED Abstract]
-
Pratt CB, Maurer HM, Gieser P, et al.: Treatment of unresectable or metastatic pediatric soft tissue sarcomas with surgery, irradiation, and chemotherapy: a Pediatric Oncology Group study. Med Pediatr Oncol 30 (4): 201-9, 1998.
[PUBMED Abstract]
-
Putnam JB Jr, Roth JA: Surgical treatment for pulmonary metastases from sarcoma. Hematol Oncol Clin North Am 9 (4): 869-87, 1995.
[PUBMED Abstract]
-
Pappo AS, Devidas M, Jenkins J, et al.: Phase II trial of neoadjuvant vincristine, ifosfamide, and doxorubicin with granulocyte colony-stimulating factor support in children and adolescents with advanced-stage nonrhabdomyosarcomatous soft tissue sarcomas: a Pediatric Oncology Group Study. J Clin Oncol 23 (18): 4031-8, 2005.
[PUBMED Abstract]
Back to Top Recurrent/Progressive Childhood Soft Tissue Sarcoma
With the possible exception of infants with congenital fibrosarcoma, the
prognosis for patients with recurrent or progressive disease is poor. The
selection of further treatment depends on many factors, including the site of
recurrence, prior therapy, and individual patient considerations. Local
recurrence or isolated pulmonary recurrence should be treated with complete
resection. All patients with recurrent tumors should be offered enrollment in
current drug studies.
Standard Treatment Options
Resection is the standard treatment for recurrent pediatric
nonrhabdomyosarcomatous soft tissue sarcomas. If the patient has not yet
received radiation therapy, adjuvant radiation should be considered after local
excision of the recurrent tumor. Limb-sparing procedures with adjuvant
brachytherapy has been evaluated in adults but has not been studied extensively
in children. For some children with extremity sarcomas who have received
previous radiation therapy, amputation may be the only therapeutic option. No
prospective trial has been able to prove that enhanced local control of
pediatric soft tissue sarcomas will ultimately improve survival. Therefore,
treatment should be individualized for the site of recurrence and
biologic characteristics (e.g., grade, invasiveness, and size) of the tumor.
All patients should be considered for enrollment in clinical trials.
Pulmonary metastasectomy may achieve prolonged disease control for some patients.[1] A large, retrospective analysis of patients with recurrent soft tissue sarcoma showed that isolated local relapse had a better prognosis and that resection of pulmonary metastases improved the probability of survival.[2]
Treatment Options Under Clinical Evaluation
Different chemotherapy regimens are currently under investigation.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent childhood soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Belal A, Salah E, Hajjar W, et al.: Pulmonary metastatectomy for soft tissue sarcomas: is it valuable? J Cardiovasc Surg (Torino) 42 (6): 835-40, 2001.
[PUBMED Abstract]
-
Zagars GK, Ballo MT, Pisters PW, et al.: Prognostic factors for disease-specific survival after first relapse of soft-tissue sarcoma: analysis of 402 patients with disease relapse after initial conservative surgery and radiotherapy. Int J Radiat Oncol Biol Phys 57 (3): 739-47, 2003.
[PUBMED Abstract]
Back to Top Get More Information From NCI
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For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 a.m. to 4:30 p.m. Deaf and hard-of-hearing callers with TTY equipment may call 1-800-332-8615. The call is free and a trained Cancer Information Specialist is available to answer your questions.
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Back to Top Changes to This Summary (12/05/2008)
The PDQ cancer information summaries are reviewed regularly and updated as
new information becomes available. This section describes the latest
changes made to this summary as of the date above.
Cellular and Histopathologic Classification
Added Rekhi et al. as reference 8.
Nonmetastatic Childhood Soft Tissue Sarcoma
Added Pappo et al. as reference 47.
Back to Top More Information
About PDQ
Additional PDQ Summaries
Important:
This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
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