Wednesday, August 21, 2019

Childhood Soft Tissue Sarcoma Treatment (PDQ®) 2/5 –Health Professional Version - National Cancer Institute

Childhood Soft Tissue Sarcoma Treatment (PDQ®)–Health Professional Version - National Cancer Institute

National Cancer Institute



Childhood Soft Tissue Sarcoma Treatment (PDQ®)–Health Professional Version






Histopathological Classification of Childhood Soft Tissue Sarcoma




World Health Organization (WHO) Classification of Soft Tissue Sarcomas

The WHO classification system for cancer represents the common nomenclature for cancer worldwide. In the United States, it has been adopted by the American Joint Committee on Cancer (AJCC) for sarcoma staging and the College of American Pathologists (CAP) cancer protocols for bone and soft tissue sarcomas. The fourth edition of the WHO Classification of Tumors of Soft Tissue and Bone was published in February 2013.[1]
The grading of soft tissue tumors has always been a controversial issue. While the WHO does not strictly state a preference in grading systems, one of the major modifications made to the WHO classification was the designation of two distinct types of intermediate malignancy in terms of biological potential—locally aggressive and rarely metastasizing.[1]
The WHO acknowledged the poorly defined nature of malignant fibrous histiocytoma (also known as undifferentiated pleomorphic sarcoma) and hemangiopericytoma (now considered within the spectrum of solitary fibrous tumors).[1]
With the current advances in molecular and genetic studies, a subset of tumors has been moved into new sections, including angiomatoid malignant fibrous histiocytoma and extraskeletal myxoid chondrosarcoma, which were previously classified as tumors of uncertain differentiation. Multiple entities were newly recognized, and a few entities belonging to tumors of skin were also added to this book. A few entities that were found to most likely represent morphologic variants of other tumors were deleted from the current classification or subsumed into other sections.[1]
  1. Adipocytic tumors.
    1. Benign.
      • Lipoma.
      • Lipomatosis.
      • Lipomatosis of nerve.
      • Lipoblastoma/lipoblastomatosis.
      • Angiolipoma.
      • Myolipoma.
      • Chondroid lipoma.
      • Extra-renal angiomyolipoma.
      • Extra-adrenal myelolipoma.
      • Spindle cell/pleomorphic lipoma.
      • Hibernoma.
    2. Intermediate (locally aggressive).
    3. Malignant.
  2. Chondro-osseous tumors.
  3. Fibroblastic/myofibroblastic tumors.
    1. Benign.
      • Nodular fasciitis.
      • Proliferative fasciitis.
      • Proliferative myositis.
      • Myositis ossificans.
      • Fibro-osseous pseudotumor of digits.
      • Ischemic fasciitis.
      • Elastofibroma.
      • Fibrous hamartoma of infancy.
      • Fibromatosis colli.
      • Juvenile hyaline fibromatosis.
      • Inclusion body fibromatosis.
      • Fibroma of tendon sheath.
      • Desmoplastic fibroblastoma.
      • Mammary-type myofibroblastoma.
      • Calcifying aponeurotic fibroma.
      • Angiomyofibroblastoma.
      • Cellular angiofibroma.
      • Nuchal-type fibroma.
      • Gardner fibroma.
      • Calcifying fibrous tumor.
    2. Intermediate (locally aggressive).
      • Palmar/plantar fibromatosis.
      • Desmoid-type fibromatosis (previously called desmoid tumor or aggressive fibromatoses).
      • Lipofibromatosis.
      • Giant cell fibroblastoma.
    3. Intermediate (rarely metastasizing).
    4. Malignant.
  4. Skeletal muscle tumors.
  5. Smooth muscle tumors.
    1. Benign.
      • Deep leiomyoma.
    2. Malignant.
      Angioleiomyoma was reclassified under perivascular tumors.
  6. So-called fibrohistiocytic tumors.
    1. Benign.
      • Tenosynovial giant cell tumor.
        • Localized type.
        • Diffuse type.
        • Malignant.
      • Deep benign fibrous histiocytoma.
    2. Intermediate (rarely metastasizing).
      The malignant counterpart of so-called fibrohistiocytic tumors, formerly known as malignant fibrous histiocytoma and its subtypes was renamed undifferentiated sarcoma and was previously classified under the undifferentiated/unclassified sarcomas section.
  7. Nerve sheath tumors.
    1. Benign.
      • Schwannoma (including variants).
      • Melanotic schwannoma.
      • Neurofibroma (including variants).
        • Plexiform neurofibroma.
      • Perineurioma.
        • Malignant perineurioma.
      • Granular cell tumor.
      • Dermal nerve sheath myxoma.
      • Solitary circumscribed neuroma.
      • Ectopic meningioma.
      • Nasal glial heterotopia.
      • Benign Triton tumor.
      • Hybrid nerve sheath tumor.
    2. Malignant.
  8. Pericytic (perivascular) tumors.
    • Glomus tumor (and variants).
      • Glomangiomatosis.
      • Malignant glomus tumor.
    • Myopericytoma.
    • Angioleiomyoma.
  9. Tumors of uncertain differentiation.
    1. Benign.
      • Acral fibromyxoma.
      • Intramuscular myxoma (including cellular variant).
      • Juxta-articular myxoma.
      • Deep (aggressive) angiomyxoma.
      • Pleomorphic hyalinizing angiectatic tumor.
      • Ectopic hamartomatous thymoma.
    2. Intermediate (locally aggressive).
      • Hemosiderotic fibrolipomatous tumor.
    3. Intermediate (rarely metastasizing).
      • Atypical fibroxanthoma.
      • Angiomatoid fibrous histiocytoma.
      • Ossifying fibromyxoid tumor.
        • Ossifying fibromyxoid tumor, malignant.
      • Mixed tumor NOS.
      • Mixed tumor NOS, malignant.
      • Myoepithelioma.
      • Myoepithelial carcinoma.
      • Phosphaturic mesenchymal tumor, benign.
      • Phosphaturic mesenchymal tumor, malignant.
    4. Malignant.
  10. Undifferentiated/unclassified sarcomas.
    Genetic subgroups are emerging within this family and this work is ongoing:
    • Undifferentiated round cell and spindle cell sarcoma.
      In this group, EWSR1 is involved in non-ETS fusions with genes such as PATZ1, POU5F1, SMARCA5, NFATC2, or SP3. Another recurrent rearrangement involves the CIC-DUX4 fusion gene resulting in the chimeric CIC-DUX4 protein, which upregulates genes of the PEA3 subclass of ETS family. (Refer to the Genomics of Ewing Sarcoma section of the PDQ summary on Ewing Sarcoma Treatment for more information.)
      It is unclear whether these cases represent one or more separate entities, or whether they are better classified as variants of Ewing sarcoma.
    • Undifferentiated pleomorphic sarcoma.
      Undifferentiated pleomorphic sarcoma was most often called malignant fibrous histiocytoma in the past. Historically, this entity has been difficult to evaluate because of the shifting diagnostic criteria. Analysis of 70 cases diagnosed as malignant fibrous histiocytosis of no specific type, storiform or pleomorphic malignant fibrous histiocytoma, pleomorphic sarcoma or undifferentiated pleomorphic sarcoma showed a highly complex karyotype with no specific recurrent aberrations.[6]
      Undifferentiated sarcomas with 12q13–15 amplification, including MDM2 and CDK4, are best classified as dedifferentiated liposarcomas;[6] the relationship between this tumor and the family of undifferentiated/unclassified tumors with spindle cell morphology remains relatively undefined.
  11. Vascular tumors.
    1. Benign.
      • Hemangioma. (Refer to the PDQ summary on Childhood Vascular Tumors Treatment for more information.)
        • Synovial.
        • Venous.
        • Arteriovenous hemangioma/malformation.
        • Intramuscular.
      • Epithelioid hemangioma.
      • Angiomatosis.
      • Lymphangioma.
    2. Intermediate (locally aggressive).
    3. Intermediate (rarely metastasizing).
    4. Malignant.


References
  1. Fletcher CDM, Bridge JA, Hogendoorn P, et al., eds.: WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. Lyon, France: IARC Press, 2013.
  2. Dantonello TM, Int-Veen C, Leuschner I, et al.: Mesenchymal chondrosarcoma of soft tissues and bone in children, adolescents, and young adults: experiences of the CWS and COSS study groups. Cancer 112 (11): 2424-31, 2008. [PUBMED Abstract]
  3. Steelman C, Katzenstein H, Parham D, et al.: Unusual presentation of congenital infantile fibrosarcoma in seven infants with molecular-genetic analysis. Fetal Pediatr Pathol 30 (5): 329-37, 2011. [PUBMED Abstract]
  4. Evans HL: Low-grade fibromyxoid sarcoma: a clinicopathologic study of 33 cases with long-term follow-up. Am J Surg Pathol 35 (10): 1450-62, 2011. [PUBMED Abstract]
  5. Alaggio R, Collini P, Randall RL, et al.: Undifferentiated high-grade pleomorphic sarcomas in children: a clinicopathologic study of 10 cases and review of literature. Pediatr Dev Pathol 13 (3): 209-17, 2010 May-Jun. [PUBMED Abstract]
  6. Le Guellec S, Chibon F, Ouali M, et al.: Are peripheral purely undifferentiated pleomorphic sarcomas with MDM2 amplification dedifferentiated liposarcomas? Am J Surg Pathol 38 (3): 293-304, 2014. [PUBMED Abstract]

Staging and Grading Systems for Childhood Soft Tissue Sarcoma






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 Committee on Cancer (AJCC) that is used for adults has not been validated in pediatric studies.
Although a standardized staging system for pediatric nonrhabdomyosarcomatous soft tissue sarcoma does not exist, two systems are currently in use for staging pediatric nonrhabdomyosarcomatous soft tissue sarcoma:[1]
  • Surgico-pathologic staging system: The surgico-pathologic staging system used by the Intergroup Rhabdomyosarcoma Study is based on the amount, or extent, of tumor that remains after initial surgery and whether the disease has metastasized (refer to the Intergroup Rhabdomyosarcoma Study Staging System section of this summary for more information). This staging system was used in early pediatric trials.[2]
  • TNM staging system: The TNM staging system is a collaborative effort between the AJCC (United States) and the International Union Against Cancer (worldwide). Staging is based on the extent of the tumor (T), the extent of spread to the lymph nodes (N), and the presence of metastasis (M). Refer to Tables 3, 4, 5, and 6 for the staging of soft tissue sarcoma from the eighth edition of the AJCC Cancer Staging Manual.[3-7] The last Children's Oncology Group (COG) trial used the sixth edition AJCC Cancer Staging Manual for soft tissue sarcoma (with central pathology review).[1] A review of children with non-rhabdomyosarcoma soft tissue sarcomas was performed with data from the Surveillance, Epidemiology, and End Results (SEER) program and identified 941 patients between 1988 and 2007.[8] The COG risk stratification was validated in this cohort.



Intergroup Rhabdomyosarcoma Study Staging System

Nonmetastatic disease

  • Group I: Localized tumor completely resected with histologically negative margins.
  • Group II: Grossly resected tumor with microscopic residual tumor at the margin(s) and/or extension into regional lymph nodes.
    • Group IIA: Localized, grossly resected tumor with microscopic residual disease.
    • Group IIB: Regional disease with involved nodes completely resected with no microscopic disease. The most proximal (to the patient, most distal to the tumor) regional lymph node must be negative.
    • Group IIC: Regional disease with involved nodes grossly resected but with evidence of residual microscopic disease at the primary site and/or histologic involvement of the most proximal regional lymph node in the dissection.
  • Group III: Localized tumor, incompletely resected, or biopsy only, with gross residual tumor.

Metastatic disease

  • Group IV: Any localized or regional tumor with distant metastases present at the time of diagnosis. This includes the presence of malignant cells in effusions (pleural, peritoneal) and/or cerebrospinal fluid (rare).

Recurrent/progressive disease

  • Any soft tissue sarcoma that recurs after initial treatment or progresses after radiation therapy, chemotherapy, or initial surgery.

TNM Staging System

The eighth edition of the AJCC Cancer Staging Manual has designated staging by the four criteria of tumor size, nodal status, histologic grade, and metastasis and by anatomic primary tumor site (head and neck; trunk and extremities; abdomen and thoracic visceral organs; retroperitoneum; and unusual histologies and sites) (refer to Tables 3, 4, 5, and 6).[3-7] For information on unusual histologies and sites, refer to the AJCC Cancer Staging Manual.[7]
Table 3. Definition of Primary Tumor (T) for Soft Tissue Sarcoma of the Trunk, Extremities, and Retroperitoneum; Head and Neck; and Abdomen and Thoracic Visceral Organsa
T CategorySoft Tissue Sarcoma of the Trunk, Extremities, and RetroperitoneumSoft Tissue Sarcoma of the Head and NeckSoft Tissue Sarcoma of the Abdomen and Thoracic Visceral Organs
aAdapted from O'Sullivan et al.,[3] Yoon et al.,[4] Raut et al.,[5] and Pollock et al.[6]
TXPrimary tumor cannot be assessed.Primary tumor cannot be assessed.Primary tumor cannot be assessed.
T0No evidence of primary tumor.
T1Tumor ≤5 cm in greatest dimension.Tumor ≤2 cm.Organ confined.
T2Tumor >5 cm and ≤10 cm in greatest dimension.Tumor >2 to ≤4 cm.Tumor extension into tissue beyond organ.
T2aInvades serosa or visceral peritoneum.
T2bExtension beyond serosa (mesentery).
T3Tumor >10 cm and ≤15 cm in greatest dimension.Tumor >4 cm.Invades another organ.
T4Tumor >15 cm in greatest dimension.Tumor with invasion of adjoining structures.Multifocal involvement.
T4aTumor with orbital invasion, skull base/dural invasion, invasion of central compartment viscera, involvement of facial skeleton, or invasion of pterygoid muscles.Multifocal (2 sites).
T4bTumor with brain parenchymal invasion, carotid artery encasement, prevertebral muscle invasion, or central nervous system involvement via perineural spread.Multifocal (3–5 sites).
T4cMultifocal (>5 sites).
Table 4. Definition of Regional Lymph Node (N) for Soft Tissue Sarcoma of the Head and Neck; Trunk and Extremities; Abdomen and Thoracic Visceral Organs; and Retroperitoneuma
aAdapted from O'Sullivan et al.,[3] Yoon et al.,[4] Raut et al.,[5] and Pollock et al.[6]
bFor soft tissue sarcoma of the abdomen and thoracic visceral organs, N0 = no lymph node involvement or unknown lymph node status and N1 = lymph node involvement present.
N0No regional lymph node metastasis or unknown lymph node status.b
N1Regional lymph node metastasis.b
Table 5. Definition of Distant Metastasis (M) for Soft Tissue Sarcoma of the Head and Neck; Trunk and Extremities; Abdomen and Thoracic Visceral Organs; and Retroperitoneuma
aAdapted from O'Sullivan et al.,[3] Yoon et al.,[4] Raut et al.,[5] and Pollock et al.[6]
bFor soft tissue sarcoma of the abdomen and thoracic visceral organs, M0 = no metastases and M1 = metastases present.
M0No distant metastasis.b
M1Distant metastasis.b
Table 6. AJCC Prognostic Stage Groups for Soft Tissue Sarcoma of the Trunk, Extremities, and Retroperitoneuma
StageTNMGrade
T = primary tumor; N = regional lymph node; M = distant metastasis.
aAdapted from Yoon et al. [4] and Pollock et al.[6]
bStage IIIB for soft tissue sarcoma of the retroperitoneum; stage IV for soft tissue sarcoma of the trunk and extremities.
IAT1N0M0G1, GX
IBT2, T3, T4N0M0G1, GX
IIT1N0M0G2, G3
IIIAT2N0M0G2, G3
IIIBT3, T4N0M0G2, G3
IIIB/IVbAny TN1M0Any G
IVAny TAny NM1Any G

Soft Tissue Sarcoma Tumor Pathological Grading System

In most cases, accurate histopathologic classification alone of soft tissue sarcomas does not yield optimal information about their clinical behavior. Therefore, several histologic parameters are evaluated in the grading process, including the following:
  • Degree of cellularity.
  • Cellular pleomorphism.
  • Mitotic activity.
  • Degree of necrosis.
  • Invasive growth.
This process is used to improve the correlation between histologic findings and clinical outcome.[9] In children, grading of soft tissue sarcoma is compromised by the good prognosis of certain tumors, such as infantile fibrosarcoma and hemangiopericytoma, which have a good prognosis in children younger than 4 years, and also angiomatoid fibrous histiocytoma and dermatofibrosarcoma protuberans, which may recur locally if incompletely excised, but usually do not metastasize.
Testing the validity of a grading system within the pediatric population is difficult because of the rarity of these neoplasms. In March 1986, the Pediatric Oncology Group (POG) conducted a prospective study on pediatric soft tissue sarcomas other than rhabdomyosarcoma and devised the POG grading system. Analysis of outcome for patients with localized soft tissue sarcomas other than rhabdomyosarcoma demonstrated that patients with grade 3 tumors fared significantly worse than those with grade 1 or grade 2 lesions. This finding suggests that this system can accurately predict the clinical behavior of nonrhabdomyosarcomatous soft tissue sarcoma.[9-11]
The grading systems developed by the POG and the French Federation of Comprehensive Cancer Centers (Fédération Nationale des Centres de Lutte Contre Le Cancer [FNCLCC]) Sarcoma Group are described below. These grading systems are being compared by the central review pathologists on the COG-ARST0332 study. The study has closed and results are pending.

POG grading system

The POG grading system is described below.[9] It is an older grading system of historical value that is no longer being used for treatment.
Grade I
Grade I lesions are based on histologic type, well-differentiated cytohistologic features, and/or age of the patient.
  • Angiomatoid fibrous histiocytoma.
  • Dermatofibrosarcoma protuberans.
  • Liposarcoma–myxoid or well-differentiated.
  • Myxoid chondrosarcoma.
  • Well-differentiated malignant peripheral nerve sheath tumor.
  • Well-differentiated or infantile (aged ≤4 years) fibrosarcoma.
  • Well-differentiated or infantile (aged ≤4 years) hemangiopericytoma.
Grade II
Grade II lesions are soft tissue sarcomas not included in grade I or III by histologic diagnosis (with <5 mitoses/10 high-power fields or <15% necrosis):
  • 15% or less of the surface area shows necrosis (primary criteria).
  • The mitotic count is <5 mitotic figures per 10 high-power fields (40X objective) (primary criteria).
  • Nuclear atypia is not marked (secondary criteria).
  • The tumor is not markedly cellular (secondary criteria).
Grade III
Grade III lesions are similar to grade II lesions and include certain tumors known to be clinically aggressive by virtue of histologic diagnosis and non-grade I tumors (with >4 mitoses per 10 high-power fields or >15% necrosis):
  • Alveolar soft part sarcoma.
  • Extraskeletal osteogenic sarcoma.
  • Malignant Triton tumor.
  • Mesenchymal chondrosarcoma.
  • Pleomorphic or round-cell liposarcoma.
  • Any other sarcoma not in grade I with >15% necrosis and/or ≥5 mitotic figures per 10 high-power fields (40X objective). Marked atypia and cellularity are less predictive but may assist in placing tumors in this category.

FNCLCC grading system

The FNCLCC histologic grading system was developed for adults with soft tissue sarcoma. The purpose of the grading system is to predict which patients will develop metastasis and subsequently benefit from postoperative chemotherapy.[12,13] The system is described in Table 7 and Table 8.
Table 7. FNCLCC Histologic Grading System
FNCLCC = Fédération Nationale des Centres de Lutte Contre Le Cancer; HPF = high-power field.
Tumor Differentiation
Score 1Sarcoma closely resembling normal adult mesenchymal tissue (e.g., well-differentiated liposarcoma)
Score 2Sarcomas for which histologic typing is certain (e.g., myxoid liposarcoma)
Score 3Embryonal and undifferentiated sarcomas, sarcomas of doubtful type, and synovial sarcomas
Mitotic Count
Score 10–9 mitoses per 10 HPF
Score 210–19 mitoses per 10 HPF
Score 3≥20 mitoses per 10 HPF
Tumor Necrosis
Score 0No necrosis
Score 1<50% tumor necrosis
Score 2≥50% tumor necrosis
Table 8. Histologic Grade Determined by Total Score
Total ScoreHistologic Grade
2–3Grade I
4–5Grade II
6–8Grade III

Prognostic Significance of Tumor Grading

The POG and FNCLCC grading systems have proven to be of prognostic value in pediatric and adult nonrhabdomyosarcomatous soft tissue sarcomas.[14-18] In a study of 130 tumors from children and adolescents with nonrhabdomyosarcomatous soft tissue sarcoma enrolled in three prospective clinical trials, a correlation was found between the POG-assigned grade and the FNCLCC-assigned grade. However, grading did not correlate in all cases; 44 patients whose tumors received discrepant grades (POG grade 3, FNCLCC grade 1 or 2) had outcomes between concurrent grade 3 and grades 1 and 2. A mitotic index of 10 or greater emerged as an important prognostic factor.[19]
The completed COG-ARST0332 trial will analyze data comparing the POG and FNCLCC pathologic grading systems to determine which system better correlates with clinical outcomes. The closed COG trial (ARST1321 [NCT02180867]) used the FNCLCC system to assign histological grade.


References
  1. American Joint Committee on Cancer: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002.
  2. Maurer HM, Beltangady M, Gehan EA, et al.: The Intergroup Rhabdomyosarcoma Study-I. A final report. Cancer 61 (2): 209-20, 1988. [PUBMED Abstract]
  3. O'Sullivan B, Maki RG, Agulnik M, et al.: Soft tissue sarcoma of the head and neck. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 499-505.
  4. Yoon SS, Maki RG, Asare EA, et al.: Soft tissue sarcoma of the trunk and extremities. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 507-15.
  5. Raut CP, Maki RG, Baldini EH, et al.: Soft tissue sarcoma of the abdomen and thoracic visceral organs. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 517-21.
  6. Pollock RE, Maki RG, Baldini EH, et al.: Soft tissue sarcoma of the retroperitoneum. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 531-7.
  7. Maki RG, Folpe AL, Guadagnolo BA, et al.: Soft tissue sarcoma - unusual histologies and sites. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 539-45.
  8. Waxweiler TV, Rusthoven CG, Proper MS, et al.: Non-Rhabdomyosarcoma Soft Tissue Sarcomas in Children: A Surveillance, Epidemiology, and End Results Analysis Validating COG Risk Stratifications. Int J Radiat Oncol Biol Phys 92 (2): 339-48, 2015. [PUBMED Abstract]
  9. 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]
  10. Recommendations for the reporting of soft tissue sarcomas. Association of Directors of Anatomic and Surgical Pathology. Mod Pathol 11 (12): 1257-61, 1998. [PUBMED Abstract]
  11. 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]
  12. Coindre JM, Terrier P, Guillou L, et al.: Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer 91 (10): 1914-26, 2001. [PUBMED Abstract]
  13. Guillou L, Coindre JM, Bonichon F, et al.: Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma. J Clin Oncol 15 (1): 350-62, 1997. [PUBMED Abstract]
  14. Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec. [PUBMED Abstract]
  15. 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]
  16. 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]
  17. 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]
  18. 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]
  19. Khoury JD, Coffin CM, Spunt SL, et al.: Grading of nonrhabdomyosarcoma soft tissue sarcoma in children and adolescents: a comparison of parameters used for the Fédération Nationale des Centers de Lutte Contre le Cancer and Pediatric Oncology Group Systems. Cancer 116 (9): 2266-74, 2010. [PUBMED Abstract]
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