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

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[1-3] Childhood and adolescent cancer survivors require close monitoring because cancer therapy side effects may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Pediatric soft tissue sarcomas are a heterogenous group of malignant tumors that originate from primitive mesenchymal tissue and account for 6% of all childhood tumors (rhabdomyosarcomas, 3%; other soft tissue sarcomas, 3%).[2] For more information, see the Histopathological Classification of Childhood Soft Tissue Sarcoma section.

Rhabdomyosarcoma, a tumor of striated muscle, is the most common soft tissue sarcoma in children. It accounts for 50% of the soft tissue sarcomas in children aged 0 to 14 years.[2] For more information, see Childhood Rhabdomyosarcoma Treatment.

In pediatrics, the remaining soft tissue sarcomas are commonly referred to as nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS) and account for approximately 3.5% of all childhood tumors.[2,4] This summary discusses the treatment of NRSTS.

NRSTS are often classified according to the normal tissue types from which they are derived. These types include various connective tissues, peripheral nervous system tissue, smooth muscle tissue, and vascular tissue. The classification also includes undifferentiated tumors that are not clearly related to specific tissue types. For more information about vascular tumors in children, see Childhood Vascular Tumors Treatment.

Incidence of Soft Tissue Sarcoma by Age and Histology

The distribution of soft tissue sarcomas by histology and age, on the basis of the Surveillance, Epidemiology, and End Results (SEER) Program information from 2000 to 2015, is depicted in Table 1. The distribution of histological subtypes by age is also shown in Figure 2.

Table 1. Age Distribution of Soft Tissue Sarcomas in Children Aged 0 to 19 Years (SEER 2000–2015)a

		Age <5 y	Age 5–9 y	Age 10–14 y	Age 15–19 y	Age <20 y	All Ages (Including Adults)
pPNET = peripheral primitive neuroectodermal tumors; SEER = Surveillance, Epidemiology, and End Results.
aSource: SEER database.[5]
All soft tissue and other extraosseous sarcomas		1,124	773	1,201	1,558	4,656	80,269
Rhabdomyosarcomas		668	417	382	327	1,794	3,284
Fibrosarcomas, peripheral nerve, and other fibrous neoplasms		137	64	112	181	494	6,645
	Fibroblastic and myofibroblastic tumors	114	33	41	77	265		4,228
	Nerve sheath tumors	23	31	70	102	226		2,303
	Other fibromatous neoplasms	0	0	1	2	3		114
Kaposi sarcoma		2	1	2	10	15	7,722
Other specified soft tissue sarcomas		237	238	559	865	1,899	49,004
	Ewing tumor and Askin tumor of soft tissue	37	36	72	113	258		596
	pPNET of soft tissue	24	23	42	56	145		402
	Extrarenal rhabdoid tumor	75	8	9	4	96		205
	Liposarcomas	4	6	37	79	126		10,749
	Fibrohistiocytic tumors	43	73	142	223	481		13,531
	Leiomyosarcomas	11	14	19	41	85		14,107
	Synovial sarcomas	12	39	141	210	402		2,608
	Blood vessel tumors	12	9	11	32	64		4,238
	Osseous and chondromatous neoplasms of soft tissue	1	6	16	14	37		1,018
	Alveolar soft parts sarcoma	4	5	22	33	64		211
	Miscellaneous soft tissue sarcomas	14	19	48	60	141		1,339
Unspecified soft tissue sarcomas		80	53	146	175	454	13,614

Soft tissue sarcomas include both rhabdomyosarcomas and NRSTS. NRSTS are more common in adolescents and adults.[6] Most of the information regarding treatment and natural history of the disease in younger patients has been based on studies in adult patients. The distributions of soft tissue sarcomas by age according to stage (Figure 1), histological subtype (Figure 2), and tumor site (Figure 3) are shown below.[7]

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Prognosis and Prognostic Factors

The prognosis of NRSTS varies greatly depending on the following factors:[71-73]

• Site of the primary tumor.
• Tumor size.
• Tumor grade. For more information, see the Soft Tissue Sarcoma Tumor Pathological Grading System section.
• Tumor histology.
• Depth of tumor invasion.
• Presence of metastases and site of the metastatic tumor.
• Resectability of the tumor.
• Use of radiation therapy.

In a review of a large adult series of NRSTS, patients with superficial extremity sarcomas had a better prognosis than did patients with deep tumors. This may be a reflection of differences in resectability. Thus, in addition to grade and size, the depth of invasion of the tumor should be considered.[74]

Data specific to NRSTS in children and adolescents are difficult to separate. 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. A retrospective review of soft tissue sarcomas (rhabdomyosarcoma and NRSTS) in children and adolescents suggests that the 5-cm cutoff used for adults with soft tissue sarcoma may not be ideal for smaller children, especially infants. The review identified an interaction between tumor diameter and body surface area.[75] This relationship has been questioned in a rhabdomyosarcoma study and requires further study to determine the therapeutic implications of the observation.[76]

Some pediatric NRSTS are associated with a better outcome. For instance, patients with infantile fibrosarcoma who present at age 4 years or younger have an excellent prognosis. This excellent outcome occurs because surgery alone can cure a significant number of these patients and infantile fibrosarcoma is highly chemosensitive. This tumor also responds well to larotrectinib, a specific tropomyosin receptor kinase inhibitor.[22,77]

Prognosis based on the Children's Oncology Group (COG) ARST0332 trial

Soft tissue sarcomas in older children and adolescents often behave similarly to those in adult patients.[22,78] A large, prospective, multinational COG study (ARST0332 [NCT00346164]) enrolled newly diagnosed patients younger than 30 years. Patients were assigned to treatment based on their risk group. Risk groups were defined by the presence of metastasis, tumor resectability and margins, and tumor size and grade. For more information, see Figure 4.[79][Level of evidence B4]

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Each patient was assigned to one of three risk groups and one of four treatment groups. The risk groups were as follows:[79]

1. Low risk: Nonmetastatic R0 (resection was complete with negative microscopic margins) or R1 (microscopically positive margins) low-grade tumor, or ≤5 cm R1 high-grade tumor.
2. Intermediate risk: Nonmetastatic R0 or R1 >5 cm high-grade tumor, or unresected tumor of any size or grade.
3. High risk: Metastatic tumor.

The treatment groups were as follows:

1. Surgery alone (n = 205).
2. Radiation therapy (55.8 Gy) (n = 17).
3. Chemoradiation therapy (chemotherapy and 55.8 Gy radiation therapy) (n = 111).
4. Neoadjuvant chemoradiation therapy (chemotherapy and 45 Gy radiation therapy, then surgery and radiation therapy boost based on margins with continued chemotherapy) (n = 196).

Chemotherapy included six cycles of ifosfamide (3 g/m2 per dose) given intravenously on days 1 through 3 and five cycles of doxorubicin (37.5 mg/m2 per dose) given intravenously on days 1 to 2 every 3 weeks, with the sequence adjusted based on the timing of surgery or radiation therapy.

For the 550 patients enrolled, 529 evaluable patients were included in the analysis. At a median follow-up of 6.5 years (interquartile range [IQR], 4.9–7.9), the survival results are shown in Table 3.

Table 3. Survival Results for the Children's Oncology Group ARST0332 Trial

	5-Year Event-Free Survival		5-Year Overall Survival
Risk Group	Events/Patients	Estimate, % (95% CI)	Events/Patients	Estimate, % (95% CI)
CI = confidence interval; R0 = completely excised with negative microscopic margins; R1 = grossly excised but with positive microscopic margins; R2 = less than complete gross excision.
Low	26/222	88.9 (84.0–93.8)	10/222	96.2 (93.2–99.2)
Intermediate	84/227	65.0 (58.2–71.8)	55/227	79.2 (73.4–85.0)
High	63/80	21.2 (11.4–31.1)	52/80	35.5 (23.6–47.4)
Surgical Margin
R0	44/252	83.6 (78.3–89.0)	22/252	92.8 (89.1–96.5)
R1	29/81	66.2 (54.8–77.5)	17/81	79.7 (70.0–89.5)
R2	100/196	49.2 (41.4–57.0)	78/196	62.7 (55.2–70.3)

The COG ARST0332 trial was a risk-based stratification study. Overall, local control after radiation therapy was as follows: R0, 106 of 109 patients (97%); R1, 51 of 60 patients (85%); and R2/unresectable, 2 of 6 patients (33%). Local recurrence predictors included extent of delayed resection (P < .001), imaging response before delayed surgery (P < .001), histological subtype (P < .001), and no radiation therapy (P = .046). The 5-year EFS was significantly lower for patients unable to undergo R0 or R1 resection (P = .0003).[80]

Pediatric patients with unresected localized NRSTS have a poor outcome. Only about one-third of patients treated with multimodality therapy remain disease free.[71,81]; [82,83][Level of evidence C1] In an Italian review of 30 patients with NRSTS at visceral sites, only ten patients survived at 5 years. Unfavorable prognostic factors included inability to achieve complete resection, large tumor size, tumor invasion, histological subtype, and lung-pleura sites.[84][Level of evidence C1]

Prognosis based on the European paediatric Soft Tissue Sarcoma Study Group (EpSSG) NRSTS 2005 study

The EpSSG conducted a prospective trial for patients younger than 21 years with NRSTS. They reported an analysis of 206 patients with synovial sarcoma and 363 with adult-type NRSTS. Patients were treated according to assigned risk groups. For more information, see Figure 5.[85] With a median follow-up of 80 months (interquartile range, 54.3–111.3) for the 467 surviving patients, the 5-year EFS rate was 73.7% (95% CI, 69.7%–77.2%), and the OS rate was 83.8% (95% CI, 80.3%–86.7%). The survival by treatment groups are shown in Table 4.[85]

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Table 4. Survival Outcomes by Treatment Groups in the EpSSG NRSTS 2005 Study

Treatment Group	5-Year Event-Free Survival Rate (95% CI)	5-Year Overall Survival Rate (95% CI)	Local Recurrence Rate
CI = confidence interval; EpSSG = European paediatric Soft Tissue Sarcoma Study Group; NRSTS = nonrhabdomyosarcomatous soft tissue sarcomas.
Surgery alone	91.4% (87.0%–94.4%)	98.1% (95.0%–99.3%)	7.6% (19/250)
Adjuvant radiation therapy alone (n = 17)	75.5% (46.9%–90.1%)	88.2% (60.6%–96.9%)	6.7% (1/15)
Adjuvant chemotherapy ± radiation therapy (n = 93)	65.6% (54.8%–74.5%)	75.8% (65.3%–83.5%)	10.8% (7/65)
Neoadjuvant chemotherapy ± radiation therapy (n = 209)	56.4% (49.3%–63.0%)	70.4% (63.3%–76.4%)	14.2% (16/113)

Treatment failures specifically for the neoadjuvant therapy treatment groups are shown in Table 5.[85]

Table 5. Treatment Failures for Specific Neoadjuvant Therapy Groups in the EpSSG NRSTS 2005 Studya

Treatment	Local Failure (No. of Patients)	Local + Metastatic Failure (No. of Patients)	Metastatic Failure (No. of Patients)
EpSSG = European paediatric Soft Tissue Sarcoma Study Group; No. = number; NRSTS = nonrhabdomyosarcomatous soft tissue sarcomas.
aAdapted from Ferrari et al.[85]
Radiation therapy alone (n = 21)	7	2	4
Delayed surgery followed by radiation therapy (n = 104)	16	6	8
Delayed surgery alone (n = 48)	8	3	8
No local treatment (n = 16)	12	4	0
Preoperative radiation therapy followed by delayed surgery (n = 20)	4	0	6

The authors concluded that adjuvant therapy (radiation therapy and chemotherapy) could safely be omitted in the group of patients assigned to surgery alone. Their criteria included the following:[85]

• Synovial cell: Intergroup Rhabdomyosarcoma Study (IRS) group I tumor size <5 cm.
• Adult-type NRSTS: IRS group I tumor size <5 cm, any grade.
• Adult-type NRSTS: IRS group I tumor size >5 cm, tumor grade I.
• Adult-type NRSTS: IRS group II any tumor size, tumor grade I.

They also concluded that improving the outcome for patients with high-risk, initially resected, adult-type NRSTS and those with initially unresected disease remains a major clinical challenge.[85]

In a pooled analysis from U.S. and European pediatric centers, outcomes were better for patients whose tumor removal procedure was deemed complete than for patients whose tumor removal was incomplete. Outcomes were better for patients who received radiation therapy than for patients who did not.[82][Level of evidence C1]

Because long-term morbidity must be minimized while disease-free survival is maximized, the ideal therapy for each patient must be carefully and individually determined using these prognostic factors before initiating therapy.[29,86-90]

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74. 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]
75. Ferrari A, Miceli R, Meazza C, et al.: Soft tissue sarcomas of childhood and adolescence: the prognostic role of tumor size in relation to patient body size. J Clin Oncol 27 (3): 371-6, 2009. [PUBMED Abstract]
76. Rodeberg DA, Stoner JA, Garcia-Henriquez N, et al.: Tumor volume and patient weight as predictors of outcome in children with intermediate risk rhabdomyosarcoma: a report from the Children's Oncology Group. Cancer 117 (11): 2541-50, 2011. [PUBMED Abstract]
77. Hong DS, DuBois SG, Kummar S, et al.: Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 21 (4): 531-540, 2020. [PUBMED Abstract]
78. Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 4th ed. Mosby, 2001.
79. Spunt SL, Million L, Chi YY, et al.: A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study. Lancet Oncol 21 (1): 145-161, 2020. [PUBMED Abstract]
80. Million L, Hayes-Jordan A, Chi YY, et al.: Local Control For High-Grade Nonrhabdomyosarcoma Soft Tissue Sarcoma Assigned to Radiation Therapy on ARST0332: A Report From the Childrens Oncology Group. Int J Radiat Oncol Biol Phys 110 (3): 821-830, 2021. [PUBMED Abstract]
81. 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]
82. Ferrari A, Miceli R, Rey A, et al.: Non-metastatic unresected paediatric non-rhabdomyosarcoma soft tissue sarcomas: results of a pooled analysis from United States and European groups. Eur J Cancer 47 (5): 724-31, 2011. [PUBMED Abstract]
83. Smith KB, Indelicato DJ, Knapik JA, et al.: Definitive radiotherapy for unresectable pediatric and young adult nonrhabdomyosarcoma soft tissue sarcoma. Pediatr Blood Cancer 57 (2): 247-51, 2011. [PUBMED Abstract]
84. Ferrari A, Magni C, Bergamaschi L, et al.: Pediatric nonrhabdomyosarcoma soft tissue sarcomas arising at visceral sites. Pediatr Blood Cancer 64 (9): , 2017. [PUBMED Abstract]
85. Ferrari A, van Noesel MM, Brennan B, et al.: Paediatric non-rhabdomyosarcoma soft tissue sarcomas: the prospective NRSTS 2005 study by the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG). Lancet Child Adolesc Health 5 (8): 546-558, 2021. [PUBMED Abstract]
86. 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]
87. 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]
88. 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]
89. 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]
90. 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]

References

1. WHO Classification of Tumours Editorial Board: WHO Classification of Tumours. Volume 3: Soft Tissue and Bone Tumours. 5th ed., IARC Press, 2020.
2. 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]
3. 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]
4. Antonescu CR: Emerging soft tissue tumors with kinase fusions: An overview of the recent literature with an emphasis on diagnostic criteria. Genes Chromosomes Cancer 59 (8): 437-444, 2020. [PUBMED Abstract]
5. Ortiz MV, Gerdemann U, Raju SG, et al.: Activity of the Highly Specific RET Inhibitor Selpercatinib (LOXO-292) in Pediatric Patients With Tumors Harboring RET Gene Alterations. JCO Precis Oncol 4: , 2020. [PUBMED Abstract]

Assessment of disease extent 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 assessment 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.

No standardized staging system for pediatric nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS) exists, but two systems are currently in use for assessment of disease extent:[1]

References

1. American Joint Committee on Cancer: AJCC Cancer Staging Manual. 6th ed. 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. 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. 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. 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. 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. 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, 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. Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec. [PUBMED Abstract]
13. 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]
14. 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]
15. 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]
16. 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]
17. 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]
18. Spunt SL, Million L, Chi YY, et al.: A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study. Lancet Oncol 21 (1): 145-161, 2020. [PUBMED Abstract]
19. 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]
20. 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]

Because of the rarity of pediatric nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS), treatment should be coordinated by a multidisciplinary team that includes oncologists (pediatric or medical), pathologists, surgeons, and radiation oncologists for all children, adolescents, and young adults with these tumors. In addition, to better define the tumors' natural history and response to therapy, entry into national or institutional treatment protocols should be considered for children with rare neoplasms. Information about ongoing clinical trials is available from the NCI website.

The Children's Oncology Group (COG) performed a prospective nonrandomized trial (ARST0332 [NCT00346164]) for patients with soft tissue sarcomas.[1]

Surgical resection of the primary tumor was classified as follows:

Patients were assigned to one of the following three risk groups:

The treatment groups were as follows:

Chemotherapy included six cycles of intravenous (IV) ifosfamide (3 g/m2 per dose) on days 1 through 3 and five cycles of IV doxorubicin (37.5 mg/m2 per dose) on days 1 to 2 every 3 weeks, with the sequence adjusted on the basis of timing of surgery or radiation therapy.

The analysis included 529 evaluable patients: low risk (n = 222), intermediate risk (n = 227), and high risk (n = 80). Patients underwent surgery alone (n = 205), radiation therapy (n = 17), chemoradiation therapy (n = 111), and neoadjuvant chemoradiation therapy (n = 196).

At a median follow-up of 6.5 years (interquartile range [IQR], 4.9–7.9), the 5-year event-free survival (EFS) and overall survival (OS) rates, by risk group, were as follows:

The authors concluded that pretreatment clinical features can be used to effectively define treatment failure risk and stratify young patients with NRSTS for risk-adapted therapy. Most low-risk patients can be cured without adjuvant therapy, avoiding known long-term treatment complications. Survival remains suboptimal for intermediate-risk and high-risk patients, and novel therapies are needed for these patients.

References

1. Spunt SL, Million L, Chi YY, et al.: A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study. Lancet Oncol 21 (1): 145-161, 2020. [PUBMED Abstract]
2. Douglass DP, Coffin CM, Randall RL, et al.: Clinical features and outcomes of young patients with low-grade non-rhabdomyosarcoma soft tissue sarcomas treated with a risk-based strategy: A report from Children's Oncology Group study ARST0332. Pediatr Blood Cancer 71 (8): e31062, 2024. [PUBMED Abstract]
3. Million L, Hayes-Jordan A, Chi YY, et al.: Local Control For High-Grade Nonrhabdomyosarcoma Soft Tissue Sarcoma Assigned to Radiation Therapy on ARST0332: A Report From the Childrens Oncology Group. Int J Radiat Oncol Biol Phys 110 (3): 821-830, 2021. [PUBMED Abstract]
4. Sugiura H, Takahashi M, Katagiri H, et al.: Additional wide resection of malignant soft tissue tumors. Clin Orthop (394): 201-10, 2002. [PUBMED Abstract]
5. 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]
6. 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]
7. 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]
8. 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]
9. Chandrasekar CR, Wafa H, Grimer RJ, et al.: The effect of an unplanned excision of a soft-tissue sarcoma on prognosis. J Bone Joint Surg Br 90 (2): 203-8, 2008. [PUBMED Abstract]
10. Daigeler A, Kuhnen C, Moritz R, et al.: Lymph node metastases in soft tissue sarcomas: a single center analysis of 1,597 patients. Langenbecks Arch Surg 394 (2): 321-9, 2009. [PUBMED Abstract]
11. Mazeron JJ, Suit HD: Lymph nodes as sites of metastases from sarcomas of soft tissue. Cancer 60 (8): 1800-8, 1987. [PUBMED Abstract]
12. 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]
13. 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]
14. Kayton ML, Delgado R, Busam K, et al.: Experience with 31 sentinel lymph node biopsies for sarcomas and carcinomas in pediatric patients. Cancer 112 (9): 2052-9, 2008. [PUBMED Abstract]
15. Dall'Igna P, De Corti F, Alaggio R, et al.: Sentinel node biopsy in pediatric patients: the experience in a single institution. Eur J Pediatr Surg 24 (6): 482-7, 2014. [PUBMED Abstract]
16. Parida L, Morrisson GT, Shammas A, et al.: Role of lymphoscintigraphy and sentinel lymph node biopsy in the management of pediatric melanoma and sarcoma. Pediatr Surg Int 28 (6): 571-8, 2012. [PUBMED Abstract]
17. Alcorn KM, Deans KJ, Congeni A, et al.: Sentinel lymph node biopsy in pediatric soft tissue sarcoma patients: utility and concordance with imaging. J Pediatr Surg 48 (9): 1903-6, 2013. [PUBMED Abstract]
18. Haas RL, Gronchi A, van de Sande MAJ, et al.: Perioperative Management of Extremity Soft Tissue Sarcomas. J Clin Oncol 36 (2): 118-124, 2018. [PUBMED Abstract]
19. Crompton JG, Ogura K, Bernthal NM, et al.: Local Control of Soft Tissue and Bone Sarcomas. J Clin Oncol 36 (2): 111-117, 2018. [PUBMED Abstract]
20. Nussbaum DP, Rushing CN, Lane WO, et al.: Preoperative or postoperative radiotherapy versus surgery alone for retroperitoneal sarcoma: a case-control, propensity score-matched analysis of a nationwide clinical oncology database. Lancet Oncol 17 (7): 966-975, 2016. [PUBMED Abstract]
21. 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]
22. 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]
23. 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]
24. Viani GA, Novaes PE, Jacinto AA, et al.: High-dose-rate brachytherapy for soft tissue sarcoma in children: a single institution experience. Radiat Oncol 3: 9, 2008. [PUBMED Abstract]
25. Virkus WW, Mollabashy A, Reith JD, et al.: Preoperative radiotherapy in the treatment of soft tissue sarcomas. Clin Orthop (397): 177-89, 2002. [PUBMED Abstract]
26. 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. [PUBMED Abstract]
27. Dickie C, Parent A, Griffin AM, et al.: The value of adaptive preoperative radiotherapy in management of soft tissue sarcoma. Radiother Oncol 122 (3): 458-463, 2017. [PUBMED Abstract]
28. 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]
29. Davis AM, O'Sullivan B, Turcotte R, et al.: Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma. Radiother Oncol 75 (1): 48-53, 2005. [PUBMED Abstract]
30. Rao AD, Chen Q, Million L, et al.: Preoperative Intensity Modulated Radiation Therapy Compared to Three-Dimensional Conformal Radiation Therapy for High-Grade Extremity Sarcomas in Children: Analysis of the Children's Oncology Group Study ARST0332. Int J Radiat Oncol Biol Phys 103 (1): 38-44, 2019. [PUBMED Abstract]
31. Seddon B, Grange FL, Simões R, et al.: The IMRiS Trial: A Phase 2 Study of Intensity Modulated Radiation Therapy in Extremity Soft Tissue Sarcoma. Int J Radiat Oncol Biol Phys 120 (4): 978-989, 2024. [PUBMED Abstract]
32. 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]
33. Delaney TF, Kepka L, Goldberg SI, et al.: Radiation therapy for control of soft-tissue sarcomas resected with positive margins. Int J Radiat Oncol Biol Phys 67 (5): 1460-9, 2007. [PUBMED Abstract]
34. 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]
35. Skytting B: Synovial sarcoma. A Scandinavian Sarcoma Group project. Acta Orthop Scand Suppl 291: 1-28, 2000. [PUBMED Abstract]
36. Hua C, Gray JM, Merchant TE, et al.: Treatment planning and delivery of external beam radiotherapy for pediatric sarcoma: the St. Jude Children's Research Hospital experience. Int J Radiat Oncol Biol Phys 70 (5): 1598-606, 2008. [PUBMED Abstract]
37. 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]
38. Karakousis CP, Driscoll DL: Treatment and local control of primary extremity soft tissue sarcomas. J Surg Oncol 71 (3): 155-61, 1999. [PUBMED Abstract]
39. 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]
40. Raut CP, Miceli R, Strauss DC, et al.: External validation of a multi-institutional retroperitoneal sarcoma nomogram. Cancer 122 (9): 1417-24, 2016. [PUBMED Abstract]
41. Baldini EH, Wang D, Haas RL, et al.: Treatment Guidelines for Preoperative Radiation Therapy for Retroperitoneal Sarcoma: Preliminary Consensus of an International Expert Panel. Int J Radiat Oncol Biol Phys 92 (3): 602-12, 2015. [PUBMED Abstract]
42. Bishop AJ, Zagars GK, Torres KE, et al.: Combined Modality Management of Retroperitoneal Sarcomas: A Single-Institution Series of 121 Patients. Int J Radiat Oncol Biol Phys 93 (1): 158-65, 2015. [PUBMED Abstract]
43. Al Yami A, Griffin AM, Ferguson PC, et al.: Positive surgical margins in soft tissue sarcoma treated with preoperative radiation: is a postoperative boost necessary? Int J Radiat Oncol Biol Phys 77 (4): 1191-7, 2010. [PUBMED Abstract]
44. Wang D, Bosch W, Kirsch DG, et al.: Variation in the gross tumor volume and clinical target volume for preoperative radiotherapy of primary large high-grade soft tissue sarcoma of the extremity among RTOG sarcoma radiation oncologists. Int J Radiat Oncol Biol Phys 81 (5): e775-80, 2011. [PUBMED Abstract]
45. Bahig H, Roberge D, Bosch W, et al.: Agreement among RTOG sarcoma radiation oncologists in contouring suspicious peritumoral edema for preoperative radiation therapy of soft tissue sarcoma of the extremity. Int J Radiat Oncol Biol Phys 86 (2): 298-303, 2013. [PUBMED Abstract]
46. Ferrari A: Role of chemotherapy in pediatric nonrhabdomyosarcoma soft-tissue sarcomas. Expert Rev Anticancer Ther 8 (6): 929-38, 2008. [PUBMED Abstract]
47. 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]
48. Woll PJ, Reichardt P, Le Cesne A, et al.: Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): a multicentre randomised controlled trial. Lancet Oncol 13 (10): 1045-54, 2012. [PUBMED Abstract]
49. Demetri GD, Chawla SP, Ray-Coquard I, et al.: Results of an international randomized phase III trial of the mammalian target of rapamycin inhibitor ridaforolimus versus placebo to control metastatic sarcomas in patients after benefit from prior chemotherapy. J Clin Oncol 31 (19): 2485-92, 2013. [PUBMED Abstract]
50. van der Graaf WT, Blay JY, Chawla SP, et al.: Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 379 (9829): 1879-86, 2012. [PUBMED Abstract]
51. Mir O, Brodowicz T, Italiano A, et al.: Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol 17 (12): 1732-1742, 2016. [PUBMED Abstract]
52. Weiss AR, Chen YL, Scharschmidt TJ, et al.: Pathological response in children and adults with large unresected intermediate-grade or high-grade soft tissue sarcoma receiving preoperative chemoradiotherapy with or without pazopanib (ARST1321): a multicentre, randomised, open-label, phase 2 trial. Lancet Oncol 21 (8): 1110-1122, 2020. [PUBMED Abstract]
53. Kayton ML, Weiss AR, Xue W, et al.: Neoadjuvant pazopanib in nonrhabdomyosarcoma soft tissue sarcomas (ARST1321): A report of major wound complications from the Children's Oncology Group and NRG Oncology. J Surg Oncol 127 (5): 871-881, 2023. [PUBMED Abstract]
54. Weiss AR, Chen YL, Scharschmidt TJ, et al.: Outcomes After Preoperative Chemoradiation With or Without Pazopanib in Non-Rhabdomyosarcoma Soft Tissue Sarcoma: A Report From Children's Oncology Group and NRG Oncology. J Clin Oncol 41 (31): 4842-4848, 2023. [PUBMED Abstract]

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] 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 following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Multidisciplinary evaluation in pediatric cancer centers that have surgical and radiotherapeutic expertise is of critical importance to ensure the best clinical outcome for these patients. Although surgery with or without radiation therapy can be curative for a significant proportion of patients, the addition of chemotherapy might benefit subsets of children with the disease. Therefore, enrollment in clinical trials is encouraged. Clinical trials for children and adolescents with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Many therapeutic strategies for children and adolescents with soft tissue tumors are similar to those for adult patients, although there are important differences. For example, the biology of the neoplasm in pediatric patients may differ dramatically from that of the adult lesion. Additionally, limb-sparing procedures are more difficult to perform in pediatric patients. The morbidity associated with radiation therapy, particularly in infants and young children, may be much greater than that observed in adults.[3]

Improved outcomes with multimodality therapy in adults and children with soft tissue sarcomas over the past 20 years have caused increasing concern about the potential long-term side effects of this therapy in children. To maximize tumor control and minimize long-term morbidity, treatment must be individualized for children and adolescents with nonrhabdomyosarcomatous soft tissue sarcoma. These patients should be enrolled in prospective studies that accurately assess any potential complications.[4]

References

1. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed August 23, 2024.
3. 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]
4. Hawkins DS, Black JO, Orbach D, et al.: Nonrhabdomyosarcoma soft-tissue sarcomas. In: Blaney SM, Helman LJ, Adamson PC, eds.: Pizzo and Poplack's Pediatric Oncology. 8th ed. Wolters Kluwer, 2020, pp 721-46.

Adipocytic tumors account for less than 10% of soft tissue lesions in patients younger than 20 years. The most common adipocytic tumors in children are lipomas and lipoblastomas.

Table 11 summarizes the adipocytic neoplasms seen in pediatric patients and includes information about their corresponding clinico-pathological and molecular features.[1]

References

1. Putra J, Al-Ibraheemi A: Adipocytic tumors in Children: A contemporary review. Semin Diagn Pathol 36 (2): 95-104, 2019. [PUBMED Abstract]
2. Coffin CM, Alaggio R: Adipose and myxoid tumors of childhood and adolescence. Pediatr Dev Pathol 15 (1 Suppl): 239-54, 2012. [PUBMED Abstract]
3. Dehner LP, Gru AA: Nonepithelial Tumors and Tumor-like Lesions of the Skin and Subcutis in Children. Pediatr Dev Pathol 21 (2): 150-207, 2018 Mar-Apr. [PUBMED Abstract]
4. Yozu M, Symmans P, Dray M, et al.: Muir-Torre syndrome-associated pleomorphic liposarcoma arising in a previous radiation field. Virchows Arch 462 (3): 355-60, 2013. [PUBMED Abstract]
5. Palit A, Inamadar AC: Circumferential skin folds in a child: a case of Michelin tire baby syndrome. Indian J Dermatol Venereol Leprol 73 (1): 49-51, 2007 Jan-Feb. [PUBMED Abstract]
6. Goucha S, Khaled A, Zéglaoui F, et al.: Nevus lipomatosus cutaneous superficialis: Report of eight cases. Dermatol Ther (Heidelb) 1 (2): 25-30, 2011. [PUBMED Abstract]
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15. Han J, Murthy R, Wood B, et al.: ER stress signalling through eIF2α and CHOP, but not IRE1α, attenuates adipogenesis in mice. Diabetologia 56 (4): 911-24, 2013. [PUBMED Abstract]
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18. Creytens D, Folpe AL, Koelsche C, et al.: Myxoid pleomorphic liposarcoma-a clinicopathologic, immunohistochemical, molecular genetic and epigenetic study of 12 cases, suggesting a possible relationship with conventional pleomorphic liposarcoma. Mod Pathol 34 (11): 2043-2049, 2021. [PUBMED Abstract]
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23. 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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26. Bahig H, Roberge D, Bosch W, et al.: Agreement among RTOG sarcoma radiation oncologists in contouring suspicious peritumoral edema for preoperative radiation therapy of soft tissue sarcoma of the extremity. Int J Radiat Oncol Biol Phys 86 (2): 298-303, 2013. [PUBMED Abstract]
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Chondro-osseous tumors have several subtypes, including the following:

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6. Kawaguchi S, Weiss I, Lin PP, et al.: Radiation therapy is associated with fewer recurrences in mesenchymal chondrosarcoma. Clin Orthop Relat Res 472 (3): 856-64, 2014. [PUBMED Abstract]
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12. Jour G, Wang L, Middha S, et al.: The molecular landscape of extraskeletal osteosarcoma: A clinicopathological and molecular biomarker study. J Pathol Clin Res 2 (1): 9-20, 2016. [PUBMED Abstract]
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Fibroblastic and myofibroblastic tumors have several subtypes, including the following:

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73. Gaudichon J, Jeanne-Pasquier C, Deparis M, et al.: Complete and Repeated Response of a Metastatic ALK-rearranged Inflammatory Myofibroblastic Tumor to Crizotinib in a Teenage Girl. J Pediatr Hematol Oncol 38 (4): 308-11, 2016. [PUBMED Abstract]
74. Mossé YP, Voss SD, Lim MS, et al.: Targeting ALK With Crizotinib in Pediatric Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic Tumor: A Children's Oncology Group Study. J Clin Oncol 35 (28): 3215-3221, 2017. [PUBMED Abstract]
75. Butrynski JE, D'Adamo DR, Hornick JL, et al.: Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor. N Engl J Med 363 (18): 1727-33, 2010. [PUBMED Abstract]
76. Nakano K: Inflammatory myofibroblastic tumors: recent progress and future of targeted therapy. Jpn J Clin Oncol 53 (10): 885-892, 2023. [PUBMED Abstract]
77. Brivio E, Zwaan CM: ALK inhibition in two emblematic cases of pediatric inflammatory myofibroblastic tumor: Efficacy and side effects. Pediatr Blood Cancer 66 (5): e27645, 2019. [PUBMED Abstract]
78. Fischer M, Moreno L, Ziegler DS, et al.: Ceritinib in paediatric patients with anaplastic lymphoma kinase-positive malignancies: an open-label, multicentre, phase 1, dose-escalation and dose-expansion study. Lancet Oncol 22 (12): 1764-1776, 2021. [PUBMED Abstract]
79. Nishio M, Murakami H, Horiike A, et al.: Phase I Study of Ceritinib (LDK378) in Japanese Patients with Advanced, Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer or Other Tumors. J Thorac Oncol 10 (7): 1058-66, 2015. [PUBMED Abstract]
80. Fujiki T, Sakai Y, Ikawa Y, et al.: Pediatric inflammatory myofibroblastic tumor of the bladder with ALK-FN1 fusion successfully treated by alectinib. Pediatr Blood Cancer 70 (4): e30172, 2023. [PUBMED Abstract]
81. Gounder MM, Agaram NP, Trabucco SE, et al.: Clinical genomic profiling in the management of patients with soft tissue and bone sarcoma. Nat Commun 13 (1): 3406, 2022. [PUBMED Abstract]
82. Sulkowski JP, Raval MV, Browne M: Margin status and multimodal therapy in infantile fibrosarcoma. Pediatr Surg Int 29 (8): 771-6, 2013. [PUBMED Abstract]
83. Hirschfeld R, Welch JJG, Harrison DJ, et al.: Two cases of humoral hypercalcemia of malignancy complicating infantile fibrosarcoma. Pediatr Blood Cancer 64 (10): , 2017. [PUBMED Abstract]
84. Kao YC, Fletcher CDM, Alaggio R, et al.: Recurrent BRAF Gene Fusions in a Subset of Pediatric Spindle Cell Sarcomas: Expanding the Genetic Spectrum of Tumors With Overlapping Features With Infantile Fibrosarcoma. Am J Surg Pathol 42 (1): 28-38, 2018. [PUBMED Abstract]
85. Wegert J, Vokuhl C, Collord G, et al.: Recurrent intragenic rearrangements of EGFR and BRAF in soft tissue tumors of infants. Nat Commun 9 (1): 2378, 2018. [PUBMED Abstract]
86. Tan SY, Al-Ibraheemi A, Ahrens WA, et al.: ALK rearrangements in infantile fibrosarcoma-like spindle cell tumours of soft tissue and kidney. Histopathology 80 (4): 698-707, 2022. [PUBMED Abstract]
87. Motta M, Barresi S, Pizzi S, et al.: RAF1 gene fusions are recurrent driver events in infantile fibrosarcoma-like mesenchymal tumors. J Pathol 263 (2): 166-177, 2024. [PUBMED Abstract]
88. Orbach D, Rey A, Cecchetto G, et al.: Infantile fibrosarcoma: management based on the European experience. J Clin Oncol 28 (2): 318-23, 2010. [PUBMED Abstract]
89. Orbach D, Brennan B, De Paoli A, et al.: Conservative strategy in infantile fibrosarcoma is possible: The European paediatric Soft tissue sarcoma Study Group experience. Eur J Cancer 57: 1-9, 2016. [PUBMED Abstract]
90. Hawkins DS, Black JO, Orbach D, et al.: Nonrhabdomyosarcoma soft-tissue sarcomas. In: Blaney SM, Helman LJ, Adamson PC, eds.: Pizzo and Poplack's Pediatric Oncology. 8th ed. Wolters Kluwer, 2020, pp 721-46.
91. 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. [PUBMED Abstract]
92. Akyüz C, Küpeli S, Varan A, et al.: Infantile fibrosarcoma: retrospective analysis of eleven patients. Tumori 97 (2): 166-9, 2011 Mar-Apr. [PUBMED Abstract]
93. Gallego S, Pericas N, Barber I, et al.: Infantile fibrosarcoma of the retroperitoneum: a site of unfavorable prognosis? Pediatr Hematol Oncol 28 (5): 451-3, 2011. [PUBMED Abstract]
94. Parida L, Fernandez-Pineda I, Uffman JK, et al.: Clinical management of infantile fibrosarcoma: a retrospective single-institution review. Pediatr Surg Int 29 (7): 703-8, 2013. [PUBMED Abstract]
95. Laetsch TW, DuBois SG, Mascarenhas L, et al.: Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol 19 (5): 705-714, 2018. [PUBMED Abstract]
96. Kummar S, Lassen UN: TRK Inhibition: A New Tumor-Agnostic Treatment Strategy. Target Oncol 13 (5): 545-556, 2018. [PUBMED Abstract]
97. Drilon A, Laetsch TW, Kummar S, et al.: Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med 378 (8): 731-739, 2018. [PUBMED Abstract]
98. DuBois SG, Laetsch TW, Federman N, et al.: The use of neoadjuvant larotrectinib in the management of children with locally advanced TRK fusion sarcomas. Cancer 124 (21): 4241-4247, 2018. [PUBMED Abstract]
99. Hong DS, DuBois SG, Kummar S, et al.: Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 21 (4): 531-540, 2020. [PUBMED Abstract]
100. Drilon A, Nagasubramanian R, Blake JF, et al.: A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion-Positive Solid Tumors. Cancer Discov 7 (9): 963-972, 2017. [PUBMED Abstract]
101. Yanagisawa R, Noguchi M, Fujita K, et al.: Preoperative Treatment With Pazopanib in a Case of Chemotherapy-Resistant Infantile Fibrosarcoma. Pediatr Blood Cancer 63 (2): 348-51, 2016. [PUBMED Abstract]
102. 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]
103. Scheer M, Vokuhl C, Veit-Friedrich I, et al.: Low-grade fibromyxoid sarcoma: A report of the Cooperative Weichteilsarkom Studiengruppe (CWS). Pediatr Blood Cancer 67 (2): e28009, 2020. [PUBMED Abstract]
104. Fletcher CDM, Bridge JA, Hogendoorn P, et al., eds.: WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. IARC Press, 2013.
105. Sargar K, Kao SC, Spunt SL, et al.: MRI and CT of Low-Grade Fibromyxoid Sarcoma in Children: A Report From Children's Oncology Group Study ARST0332. AJR Am J Roentgenol 205 (2): 414-20, 2015. [PUBMED Abstract]
106. Guillou L, Benhattar J, Gengler C, et al.: Translocation-positive low-grade fibromyxoid sarcoma: clinicopathologic and molecular analysis of a series expanding the morphologic spectrum and suggesting potential relationship to sclerosing epithelioid fibrosarcoma: a study from the French Sarcoma Group. Am J Surg Pathol 31 (9): 1387-402, 2007. [PUBMED Abstract]
107. Mohamed M, Fisher C, Thway K: Low-grade fibromyxoid sarcoma: Clinical, morphologic and genetic features. Ann Diagn Pathol 28: 60-67, 2017. [PUBMED Abstract]
108. O'Sullivan MJ, Sirgi KE, Dehner LP: Low-grade fibrosarcoma (hyalinizing spindle cell tumor with giant rosettes) with pulmonary metastases at presentation: case report and review of the literature. Int J Surg Pathol 10 (3): 211-6, 2002. [PUBMED Abstract]
109. Folpe AL, Lane KL, Paull G, et al.: Low-grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes: a clinicopathologic study of 73 cases supporting their identity and assessing the impact of high-grade areas. Am J Surg Pathol 24 (10): 1353-60, 2000. [PUBMED Abstract]
110. Maretty-Nielsen K, Baerentzen S, Keller J, et al.: Low-Grade Fibromyxoid Sarcoma: Incidence, Treatment Strategy of Metastases, and Clinical Significance of the FUS Gene. Sarcoma 2013: 256280, 2013. [PUBMED Abstract]
111. Prieto-Granada C, Zhang L, Chen HW, et al.: A genetic dichotomy between pure sclerosing epithelioid fibrosarcoma (SEF) and hybrid SEF/low-grade fibromyxoid sarcoma: a pathologic and molecular study of 18 cases. Genes Chromosomes Cancer 54 (1): 28-38, 2015. [PUBMED Abstract]
112. Arbajian E, Puls F, Antonescu CR, et al.: In-depth Genetic Analysis of Sclerosing Epithelioid Fibrosarcoma Reveals Recurrent Genomic Alterations and Potential Treatment Targets. Clin Cancer Res 23 (23): 7426-7434, 2017. [PUBMED Abstract]
113. Arbajian E, Puls F, Magnusson L, et al.: Recurrent EWSR1-CREB3L1 gene fusions in sclerosing epithelioid fibrosarcoma. Am J Surg Pathol 38 (6): 801-8, 2014. [PUBMED Abstract]
114. Dewaele B, Libbrecht L, Levy G, et al.: A novel EWS-CREB3L3 gene fusion in a mesenteric sclerosing epithelioid fibrosarcoma. Genes Chromosomes Cancer 56 (9): 695-699, 2017. [PUBMED Abstract]
115. Porteus C, Gan Q, Gong Y, et al.: Sclerosing epithelioid fibrosarcoma: cytologic characterization with histologic, immunohistologic, molecular, and clinical correlation of 8 cases. J Am Soc Cytopathol 9 (6): 513-519, 2020 Nov - Dec. [PUBMED Abstract]
116. Puls F, Agaimy A, Flucke U, et al.: Recurrent Fusions Between YAP1 and KMT2A in Morphologically Distinct Neoplasms Within the Spectrum of Low-grade Fibromyxoid Sarcoma and Sclerosing Epithelioid Fibrosarcoma. Am J Surg Pathol 44 (5): 594-606, 2020. [PUBMED Abstract]
117. Warmke LM, Meis JM: Sclerosing Epithelioid Fibrosarcoma: A Distinct Sarcoma With Aggressive Features. Am J Surg Pathol 45 (3): 317-328, 2021. [PUBMED Abstract]
118. Chew W, Benson C, Thway K, et al.: Clinical Characteristics and efficacy of chemotherapy in sclerosing epithelioid fibrosarcoma. Med Oncol 35 (11): 138, 2018. [PUBMED Abstract]

Skeletal muscle tumors have several subtypes, including the following:

References

1. Huang SC, Alaggio R, Sung YS, et al.: Frequent HRAS Mutations in Malignant Ectomesenchymoma: Overlapping Genetic Abnormalities With Embryonal Rhabdomyosarcoma. Am J Surg Pathol 40 (7): 876-85, 2016. [PUBMED Abstract]
2. Griffin BB, Chou PM, George D, et al.: Malignant Ectomesenchymoma: Series Analysis of a Histologically and Genetically Heterogeneous Tumor. Int J Surg Pathol 26 (3): 200-212, 2018. [PUBMED Abstract]
3. Dantonello TM, Leuschner I, Vokuhl C, et al.: Malignant ectomesenchymoma in children and adolescents: report from the Cooperative Weichteilsarkom Studiengruppe (CWS). Pediatr Blood Cancer 60 (2): 224-9, 2013. [PUBMED Abstract]
4. Milano GM, Orbach D, Casanova M, et al.: Malignant ectomesenchymoma in children: The European pediatric Soft tissue sarcoma Study Group experience. Pediatr Blood Cancer 70 (2): e30116, 2023. [PUBMED Abstract]

References

1. Pollock BH, Jenson HB, Leach CT, et al.: Risk factors for pediatric human immunodeficiency virus-related malignancy. JAMA 289 (18): 2393-9, 2003. [PUBMED Abstract]
2. Kleinerman RA, Tucker MA, Abramson DH, et al.: Risk of soft tissue sarcomas by individual subtype in survivors of hereditary retinoblastoma. J Natl Cancer Inst 99 (1): 24-31, 2007. [PUBMED Abstract]
3. Samuels BL, Chawla S, Patel S, et al.: Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: results of a worldwide expanded access program study. Ann Oncol 24 (6): 1703-9, 2013. [PUBMED Abstract]
4. Demetri GD, von Mehren M, Jones RL, et al.: Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial. J Clin Oncol 34 (8): 786-93, 2016. [PUBMED Abstract]
5. Pautier P, Italiano A, Piperno-Neumann S, et al.: Doxorubicin-Trabectedin with Trabectedin Maintenance in Leiomyosarcoma. N Engl J Med 391 (9): 789-799, 2024. [PUBMED Abstract]

References

1. Enzinger FM, Zhang RY: Plexiform fibrohistiocytic tumor presenting in children and young adults. An analysis of 65 cases. Am J Surg Pathol 12 (11): 818-26, 1988. [PUBMED Abstract]
2. Black J, Coffin CM, Dehner LP: Fibrohistiocytic tumors and related neoplasms in children and adolescents. Pediatr Dev Pathol 15 (1 Suppl): 181-210, 2012. [PUBMED Abstract]
3. Moosavi C, Jha P, Fanburg-Smith JC: An update on plexiform fibrohistiocytic tumor and addition of 66 new cases from the Armed Forces Institute of Pathology, in honor of Franz M. Enzinger, MD. Ann Diagn Pathol 11 (5): 313-9, 2007. [PUBMED Abstract]
4. Billings SD, Folpe AL: Cutaneous and subcutaneous fibrohistiocytic tumors of intermediate malignancy: an update. Am J Dermatopathol 26 (2): 141-55, 2004. [PUBMED Abstract]
5. Remstein ED, Arndt CA, Nascimento AG: Plexiform fibrohistiocytic tumor: clinicopathologic analysis of 22 cases. Am J Surg Pathol 23 (6): 662-70, 1999. [PUBMED Abstract]
6. Salomao DR, Nascimento AG: Plexiform fibrohistiocytic tumor with systemic metastases: a case report. Am J Surg Pathol 21 (4): 469-76, 1997. [PUBMED Abstract]
7. Redlich GC, Montgomery KD, Allgood GA, et al.: Plexiform fibrohistiocytic tumor with a clonal cytogenetic anomaly. Cancer Genet Cytogenet 108 (2): 141-3, 1999. [PUBMED Abstract]
8. Luzar B, Calonje E: Cutaneous fibrohistiocytic tumours - an update. Histopathology 56 (1): 148-65, 2010. [PUBMED Abstract]

Peripheral nerve sheath tumors have several subtypes, including the following:

References

1. 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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3. Agresta L, Salloum R, Hummel TR, et al.: Malignant peripheral nerve sheath tumor: Transformation in a patient with neurofibromatosis type 2. Pediatr Blood Cancer 66 (2): e27520, 2019. [PUBMED Abstract]
4. Agaram NP, Wexler LH, Chi P, et al.: Malignant peripheral nerve sheath tumor in children: A clinicopathologic and molecular study with parallels to the adult counterpart. Genes Chromosomes Cancer 62 (3): 131-138, 2023. [PUBMED Abstract]
5. Zhang M, Wang Y, Jones S, et al.: Somatic mutations of SUZ12 in malignant peripheral nerve sheath tumors. Nat Genet 46 (11): 1170-2, 2014. [PUBMED Abstract]
6. Röhrich M, Koelsche C, Schrimpf D, et al.: Methylation-based classification of benign and malignant peripheral nerve sheath tumors. Acta Neuropathol 131 (6): 877-87, 2016. [PUBMED Abstract]
7. Kaplan HG, Rostad S, Ross JS, et al.: Genomic Profiling in Patients With Malignant Peripheral Nerve Sheath Tumors Reveals Multiple Pathways With Targetable Mutations. J Natl Compr Canc Netw 16 (8): 967-974, 2018. [PUBMED Abstract]
8. 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]
9. Zou C, Smith KD, Liu J, et al.: Clinical, pathological, and molecular variables predictive of malignant peripheral nerve sheath tumor outcome. Ann Surg 249 (6): 1014-22, 2009. [PUBMED Abstract]
10. 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]
11. Amirian ES, Goodman JC, New P, et al.: Pediatric and adult malignant peripheral nerve sheath tumors: an analysis of data from the surveillance, epidemiology, and end results program. J Neurooncol 116 (3): 609-16, 2014. [PUBMED Abstract]
12. Valentin T, Le Cesne A, Ray-Coquard I, et al.: Management and prognosis of malignant peripheral nerve sheath tumors: The experience of the French Sarcoma Group (GSF-GETO). Eur J Cancer 56: 77-84, 2016. [PUBMED Abstract]
13. Høland M, Kolberg M, Danielsen SA, et al.: Inferior survival for patients with malignant peripheral nerve sheath tumors defined by aberrant TP53. Mod Pathol 31 (11): 1694-1707, 2018. [PUBMED Abstract]
14. Krawczyk MA, Karpinsky G, Izycka-Swieszewska E, et al.: Immunohistochemical assessment of cyclin D1 and p53 is associated with survival in childhood malignant peripheral nerve sheath tumor. Cancer Biomark 24 (3): 351-361, 2019. [PUBMED Abstract]
15. Akshintala S, Mallory NC, Lu Y, et al.: Outcome of Patients With Malignant Peripheral Nerve Sheath Tumors Enrolled on Sarcoma Alliance for Research Through Collaboration (SARC) Phase II Trials. Oncologist 28 (5): 453-459, 2023. [PUBMED Abstract]
16. Martin E, Coert JH, Flucke UE, et al.: Neurofibromatosis-associated malignant peripheral nerve sheath tumors in children have a worse prognosis: A nationwide cohort study. Pediatr Blood Cancer 67 (4): e28138, 2020. [PUBMED Abstract]
17. Meister MT, Scheer M, Hallmen E, et al.: Malignant peripheral nerve sheath tumors in children, adolescents, and young adults: Treatment results of five Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry. J Surg Oncol 122 (7): 1337-1347, 2020. [PUBMED Abstract]
18. Bahig H, Roberge D, Bosch W, et al.: Agreement among RTOG sarcoma radiation oncologists in contouring suspicious peritumoral edema for preoperative radiation therapy of soft tissue sarcoma of the extremity. Int J Radiat Oncol Biol Phys 86 (2): 298-303, 2013. [PUBMED Abstract]
19. Baldini EH, Wang D, Haas RL, et al.: Treatment Guidelines for Preoperative Radiation Therapy for Retroperitoneal Sarcoma: Preliminary Consensus of an International Expert Panel. Int J Radiat Oncol Biol Phys 92 (3): 602-12, 2015. [PUBMED Abstract]
20. 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]
21. van Noesel MM, Orbach D, Brennan B, et al.: Outcome and prognostic factors in pediatric malignant peripheral nerve sheath tumors: An analysis of the European Pediatric Soft Tissue Sarcoma Group (EpSSG) NRSTS-2005 prospective study. Pediatr Blood Cancer 66 (10): e27833, 2019. [PUBMED Abstract]
22. Higham CS, Steinberg SM, Dombi E, et al.: SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors. Sarcoma 2017: 8685638, 2017. [PUBMED Abstract]
23. Bergamaschi L, Bisogno G, Manzitti C, et al.: Salvage rates and prognostic factors after relapse in children and adolescents with malignant peripheral nerve sheath tumors. Pediatr Blood Cancer 65 (2): , 2018. [PUBMED Abstract]
24. Al-Ezzi E, Gounder M, Watson G, et al.: Selinexor, a First in Class, Nuclear Export Inhibitor for the Treatment of Advanced Malignant Peripheral Nerve Sheath Tumor. Oncologist 26 (4): e710-e714, 2021. [PUBMED Abstract]
25. WHO Classification of Tumours Editorial Board: WHO Classification of Tumours. Volume 3: Soft Tissue and Bone Tumours. 5th ed., IARC Press, 2020.
26. de Traux de Wardin H, Dermawan JK, Vanoli F, et al.: NF1-Driven Rhabdomyosarcoma Phenotypes: A Comparative Clinical and Molecular Study of NF1-Mutant Rhabdomyosarcoma and NF1-Associated Malignant Triton Tumor. JCO Precis Oncol 8: e2300597, 2024. [PUBMED Abstract]
27. Schaefer IM, Fletcher CD, Hornick JL: Loss of H3K27 trimethylation distinguishes malignant peripheral nerve sheath tumors from histologic mimics. Mod Pathol 29 (1): 4-13, 2016. [PUBMED Abstract]
28. Hornick JL, Nielsen GP: Beyond "Triton": Malignant Peripheral Nerve Sheath Tumors With Complete Heterologous Rhabdomyoblastic Differentiation Mimicking Spindle Cell Rhabdomyosarcoma. Am J Surg Pathol 43 (10): 1323-1330, 2019. [PUBMED Abstract]

Pericytic (perivascular) tumors have several subtypes, including the following:

References

1. Rodriguez-Galindo C, Ramsey K, Jenkins JJ, et al.: Hemangiopericytoma in children and infants. Cancer 88 (1): 198-204, 2000. [PUBMED Abstract]
2. Ferrari A, Casanova M, Bisogno G, et al.: Hemangiopericytoma in pediatric ages: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Cancer 92 (10): 2692-8, 2001. [PUBMED Abstract]
3. Bien E, Stachowicz-Stencel T, Godzinski J, et al.: Retrospective multi-institutional study on hemangiopericytoma in Polish children. Pediatr Int 51 (1): 19-24, 2009. [PUBMED Abstract]
4. Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 5th ed. Mosby, 2008.
5. Fernandez-Pineda I, Parida L, Jenkins JJ, et al.: Childhood hemangiopericytoma: review of St Jude Children's Research Hospital. J Pediatr Hematol Oncol 33 (5): 356-9, 2011. [PUBMED Abstract]
6. Haller F, Knopf J, Ackermann A, et al.: Paediatric and adult soft tissue sarcomas with NTRK1 gene fusions: a subset of spindle cell sarcomas unified by a prominent myopericytic/haemangiopericytic pattern. J Pathol 238 (5): 700-10, 2016. [PUBMED Abstract]
7. Wong V, Pavlick D, Brennan T, et al.: Evaluation of a Congenital Infantile Fibrosarcoma by Comprehensive Genomic Profiling Reveals an LMNA-NTRK1 Gene Fusion Responsive to Crizotinib. J Natl Cancer Inst 108 (1): , 2016. [PUBMED Abstract]
8. Doebele RC, Davis LE, Vaishnavi A, et al.: An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101. Cancer Discov 5 (10): 1049-57, 2015. [PUBMED Abstract]
9. Wiswell TE, Davis J, Cunningham BE, et al.: Infantile myofibromatosis: the most common fibrous tumor of infancy. J Pediatr Surg 23 (4): 315-8, 1988. [PUBMED Abstract]
10. Chung EB, Enzinger FM: Infantile myofibromatosis. Cancer 48 (8): 1807-18, 1981. [PUBMED Abstract]
11. Modi N: Congenital generalised fibromatosis. Arch Dis Child 57 (11): 881-2, 1982. [PUBMED Abstract]
12. Levine E, Fréneaux P, Schleiermacher G, et al.: Risk-adapted therapy for infantile myofibromatosis in children. Pediatr Blood Cancer 59 (1): 115-20, 2012. [PUBMED Abstract]
13. Larralde M, Hoffner MV, Boggio P, et al.: Infantile myofibromatosis: report of nine patients. Pediatr Dermatol 27 (1): 29-33, 2010 Jan-Feb. [PUBMED Abstract]
14. Agaimy A, Bieg M, Michal M, et al.: Recurrent Somatic PDGFRB Mutations in Sporadic Infantile/Solitary Adult Myofibromas But Not in Angioleiomyomas and Myopericytomas. Am J Surg Pathol 41 (2): 195-203, 2017. [PUBMED Abstract]
15. Arts FA, Sciot R, Brichard B, et al.: PDGFRB gain-of-function mutations in sporadic infantile myofibromatosis. Hum Mol Genet 26 (10): 1801-1810, 2017. [PUBMED Abstract]
16. Dachy G, de Krijger RR, Fraitag S, et al.: Association of PDGFRB Mutations With Pediatric Myofibroma and Myofibromatosis. JAMA Dermatol 155 (8): 946-950, 2019. [PUBMED Abstract]
17. Cheung YH, Gayden T, Campeau PM, et al.: A recurrent PDGFRB mutation causes familial infantile myofibromatosis. Am J Hum Genet 92 (6): 996-1000, 2013. [PUBMED Abstract]
18. Martignetti JA, Tian L, Li D, et al.: Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis. Am J Hum Genet 92 (6): 1001-7, 2013. [PUBMED Abstract]
19. Murray N, Hanna B, Graf N, et al.: The spectrum of infantile myofibromatosis includes both non-penetrance and adult recurrence. Eur J Med Genet 60 (7): 353-358, 2017. [PUBMED Abstract]
20. Hettmer S, Dachy G, Seitz G, et al.: Genetic testing and surveillance in infantile myofibromatosis: a report from the SIOPE Host Genome Working Group. Fam Cancer 20 (4): 327-336, 2021. [PUBMED Abstract]
21. Gopal M, Chahal G, Al-Rifai Z, et al.: Infantile myofibromatosis. Pediatr Surg Int 24 (3): 287-91, 2008. [PUBMED Abstract]
22. Sparber-Sauer M, Vokuhl C, Seitz G, et al.: Infantile myofibromatosis: Excellent prognosis but also rare fatal progressive disease. Treatment results of five Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry. Pediatr Blood Cancer 69 (3): e29403, 2022. [PUBMED Abstract]
23. Weaver MS, Navid F, Huppmann A, et al.: Vincristine and Dactinomycin in Infantile Myofibromatosis With a Review of Treatment Options. J Pediatr Hematol Oncol 37 (3): 237-41, 2015. [PUBMED Abstract]
24. Weller JM, Keil VC, Gielen GH, et al.: PDGRFB mutation-associated myofibromatosis: Response to targeted therapy with imatinib. Am J Med Genet A 179 (9): 1895-1897, 2019. [PUBMED Abstract]
25. Wenger TL, Bly RA, Wu N, et al.: Activating variants in PDGFRB result in a spectrum of disorders responsive to imatinib monotherapy. Am J Med Genet A 182 (7): 1576-1591, 2020. [PUBMED Abstract]
26. Mudry P, Slaby O, Neradil J, et al.: Case report: rapid and durable response to PDGFR targeted therapy in a child with refractory multiple infantile myofibromatosis and a heterozygous germline mutation of the PDGFRB gene. BMC Cancer 17 (1): 119, 2017. [PUBMED Abstract]
27. Pond D, Arts FA, Mendelsohn NJ, et al.: A patient with germ-line gain-of-function PDGFRB p.N666H mutation and marked clinical response to imatinib. Genet Med 20 (1): 142-150, 2018. [PUBMED Abstract]

Tumors of uncertain differentiation have many subtypes, including the following:

References

1. Wilkes D, Charitakis K, Basson CT: Inherited disposition to cardiac myxoma development. Nat Rev Cancer 6 (2): 157-65, 2006. [PUBMED Abstract]
2. Carney JA, Young WF: Primary pigmented nodular adrenocortical disease and its associated conditions. Endocrinologist 2: 6-21, 1992.
3. Ryan MW, Cunningham S, Xiao SY: Maxillary sinus melanoma as the presenting feature of Carney complex. Int J Pediatr Otorhinolaryngol 72 (3): 405-8, 2008. [PUBMED Abstract]
4. Sultan I, Rodriguez-Galindo C, Saab R, et al.: Comparing children and adults with synovial sarcoma in the Surveillance, Epidemiology, and End Results program, 1983 to 2005: an analysis of 1268 patients. Cancer 115 (15): 3537-47, 2009. [PUBMED Abstract]
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129. Foulkes WD, Kamihara J, Evans DGR, et al.: Cancer Surveillance in Gorlin Syndrome and Rhabdoid Tumor Predisposition Syndrome. Clin Cancer Res 23 (12): e62-e67, 2017. [PUBMED Abstract]
130. Morgan KM, Siow VS, Strotmeyer S, et al.: Characteristics and Outcomes in Pediatric Non-Central Nervous System Malignant Rhabdoid Tumors: A Report from the National Cancer Database. Ann Surg Oncol 29 (1): 671-678, 2022. [PUBMED Abstract]
131. Sultan I, Qaddoumi I, Rodríguez-Galindo C, et al.: Age, stage, and radiotherapy, but not primary tumor site, affects the outcome of patients with malignant rhabdoid tumors. Pediatr Blood Cancer 54 (1): 35-40, 2010. [PUBMED Abstract]
132. Nemes K, Bens S, Kachanov D, et al.: Clinical and genetic risk factors define two risk groups of extracranial malignant rhabdoid tumours (eMRT/RTK). Eur J Cancer 142: 112-122, 2021. [PUBMED Abstract]
133. Puri DR, Meyers PA, Kraus DH, et al.: Radiotherapy in the multimodal treatment of extrarenal extracranial malignant rhabdoid tumors. Pediatr Blood Cancer 50 (1): 167-9, 2008. [PUBMED Abstract]
134. Madigan CE, Armenian SH, Malogolowkin MH, et al.: Extracranial malignant rhabdoid tumors in childhood: the Childrens Hospital Los Angeles experience. Cancer 110 (9): 2061-6, 2007. [PUBMED Abstract]
135. Bourdeaut F, Fréneaux P, Thuille B, et al.: Extra-renal non-cerebral rhabdoid tumours. Pediatr Blood Cancer 51 (3): 363-8, 2008. [PUBMED Abstract]
136. Wetmore C, Boyett J, Li S, et al.: Alisertib is active as single agent in recurrent atypical teratoid rhabdoid tumors in 4 children. Neuro Oncol 17 (6): 882-8, 2015. [PUBMED Abstract]
137. Folpe A, Inwards C, eds.: Bone and Soft Tissue Pathology: A Volume in the Foundations in Diagnostic Pathology. WB Saunders Co, 2010.
138. Martignoni G, Pea M, Reghellin D, et al.: Molecular pathology of lymphangioleiomyomatosis and other perivascular epithelioid cell tumors. Arch Pathol Lab Med 134 (1): 33-40, 2010. [PUBMED Abstract]
139. Bissler JJ, McCormack FX, Young LR, et al.: Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med 358 (2): 140-51, 2008. [PUBMED Abstract]
140. Davies DM, Johnson SR, Tattersfield AE, et al.: Sirolimus therapy in tuberous sclerosis or sporadic lymphangioleiomyomatosis. N Engl J Med 358 (2): 200-3, 2008. [PUBMED Abstract]
141. Agaram NP, Sung YS, Zhang L, et al.: Dichotomy of Genetic Abnormalities in PEComas With Therapeutic Implications. Am J Surg Pathol 39 (6): 813-25, 2015. [PUBMED Abstract]
142. Armah HB, Parwani AV: Perivascular epithelioid cell tumor. Arch Pathol Lab Med 133 (4): 648-54, 2009. [PUBMED Abstract]
143. Alaggio R, Cecchetto G, Martignoni G, et al.: Malignant perivascular epithelioid cell tumor in children: description of a case and review of the literature. J Pediatr Surg 47 (6): e31-40, 2012. [PUBMED Abstract]
144. Wagner AJ, Malinowska-Kolodziej I, Morgan JA, et al.: Clinical activity of mTOR inhibition with sirolimus in malignant perivascular epithelioid cell tumors: targeting the pathogenic activation of mTORC1 in tumors. J Clin Oncol 28 (5): 835-40, 2010. [PUBMED Abstract]
145. Wagner AJ, Ravi V, Riedel RF, et al.: nab-Sirolimus for Patients With Malignant Perivascular Epithelioid Cell Tumors. J Clin Oncol 39 (33): 3660-3670, 2021. [PUBMED Abstract]
146. Laetsch TW, Roy A, Xu L, et al.: Undifferentiated Sarcomas in Children Harbor Clinically Relevant Oncogenic Fusions and Gene Copy-Number Alterations: A Report from the Children's Oncology Group. Clin Cancer Res 24 (16): 3888-3897, 2018. [PUBMED Abstract]
147. Randall RL, Albritton KH, Ferney BJ, et al.: Malignant fibrous histiocytoma of soft tissue: an abandoned diagnosis. Am J Orthop 33 (12): 602-8, 2004. [PUBMED Abstract]
148. Fletcher CDM, Bridge JA, Hogendoorn P, et al., eds.: WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. IARC Press, 2013.
149. 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]
150. Daw NC, Billups CA, Pappo AS, et al.: Malignant fibrous histiocytoma and other fibrohistiocytic tumors in pediatric patients: the St. Jude Children's Research Hospital experience. Cancer 97 (11): 2839-47, 2003. [PUBMED Abstract]
151. Bjerkehagen B, Smeland S, Walberg L, et al.: Radiation-induced sarcoma: 25-year experience from the Norwegian Radium Hospital. Acta Oncol 47 (8): 1475-82, 2008. [PUBMED Abstract]
152. 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]
153. Tawbi HA, Burgess M, Bolejack V, et al.: Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol 18 (11): 1493-1501, 2017. [PUBMED Abstract]

Vascular tumors vary from hemangiomas, which are always considered benign, to angiosarcomas, which are highly malignant.[1] Malignant vascular tumors include the following subtypes:

References

1. 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]
2. Mehrabi A, Kashfi A, Fonouni H, et al.: Primary malignant hepatic epithelioid hemangioendothelioma: a comprehensive review of the literature with emphasis on the surgical therapy. Cancer 107 (9): 2108-21, 2006. [PUBMED Abstract]
3. Haro A, Saitoh G, Tamiya S, et al.: Four-year natural clinical course of pulmonary epithelioid hemangioendothelioma without therapy. Thorac Cancer 6 (4): 544-7, 2015. [PUBMED Abstract]
4. Sardaro A, Bardoscia L, Petruzzelli MF, et al.: Epithelioid hemangioendothelioma: an overview and update on a rare vascular tumor. Oncol Rev 8 (2): 259, 2014. [PUBMED Abstract]
5. Dong K, Wang XX, Feng JL, et al.: Pathological characteristics of liver biopsies in eight patients with hepatic epithelioid hemangioendothelioma. Int J Clin Exp Pathol 8 (9): 11015-23, 2015. [PUBMED Abstract]
6. Adams DM, Hammill A: Other vascular tumors. Semin Pediatr Surg 23 (4): 173-7, 2014. [PUBMED Abstract]
7. Xiao Y, Wang C, Song Y, et al.: Primary epithelioid hemangioendothelioma of the kidney: the first case report in a child and literature review. Urology 82 (4): 925-7, 2013. [PUBMED Abstract]
8. Reich S, Ringe H, Uhlenberg B, et al.: Epithelioid hemangioendothelioma of the lung presenting with pneumonia and heart rhythm disturbances in a teenage girl. J Pediatr Hematol Oncol 32 (4): 274-6, 2010. [PUBMED Abstract]
9. Cournoyer E, Al-Ibraheemi A, Engel E, et al.: Clinical characterization and long-term outcomes in pediatric epithelioid hemangioendothelioma. Pediatr Blood Cancer 67 (2): e28045, 2020. [PUBMED Abstract]
10. 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]
11. Ackermann O, Fabre M, Franchi S, et al.: Widening spectrum of liver angiosarcoma in children. J Pediatr Gastroenterol Nutr 53 (6): 615-9, 2011. [PUBMED Abstract]
12. Raheja A, Suri A, Singh S, et al.: Multimodality management of a giant skull base hemangioendothelioma of the sphenopetroclival region. J Clin Neurosci 22 (9): 1495-8, 2015. [PUBMED Abstract]
13. Ahmad N, Adams DM, Wang J, et al.: Hepatic epithelioid hemangioendothelioma in a patient with hemochromatosis. J Natl Compr Canc Netw 12 (9): 1203-7, 2014. [PUBMED Abstract]
14. Otte JB, Zimmerman A: The role of liver transplantation for pediatric epithelioid hemangioendothelioma. Pediatr Transplant 14 (3): 295-7, 2010. [PUBMED Abstract]
15. Stacchiotti S, Provenzano S, Dagrada G, et al.: Sirolimus in Advanced Epithelioid Hemangioendothelioma: A Retrospective Case-Series Analysis from the Italian Rare Cancer Network Database. Ann Surg Oncol 23 (9): 2735-44, 2016. [PUBMED Abstract]
16. Semenisty V, Naroditsky I, Keidar Z, et al.: Pazopanib for metastatic pulmonary epithelioid hemangioendothelioma-a suitable treatment option: case report and review of anti-angiogenic treatment options. BMC Cancer 15: 402, 2015. [PUBMED Abstract]
17. Engel ER, Cournoyer E, Adams DM, et al.: A Retrospective Review of the Use of Sirolimus for Pediatric Patients With Epithelioid Hemangioendothelioma. J Pediatr Hematol Oncol 42 (8): e826-e829, 2020. [PUBMED Abstract]
18. Orbach D, Van Noesel MM, Brennan B, et al.: Epithelioid hemangioendothelioma in children: The European Pediatric Soft Tissue Sarcoma Study Group experience. Pediatr Blood Cancer 69 (10): e29882, 2022. [PUBMED Abstract]
19. Cioffi A, Reichert S, Antonescu CR, et al.: Angiosarcomas and other sarcomas of endothelial origin. Hematol Oncol Clin North Am 27 (5): 975-88, 2013. [PUBMED Abstract]
20. Jeng MR, Fuh B, Blatt J, et al.: Malignant transformation of infantile hemangioma to angiosarcoma: response to chemotherapy with bevacizumab. Pediatr Blood Cancer 61 (11): 2115-7, 2014. [PUBMED Abstract]
21. Dehner LP, Ishak KG: Vascular tumors of the liver in infants and children. A study of 30 cases and review of the literature. Arch Pathol 92 (2): 101-11, 1971. [PUBMED Abstract]
22. 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]
23. Deyrup AT, Miettinen M, North PE, et al.: Pediatric cutaneous angiosarcomas: a clinicopathologic study of 10 cases. Am J Surg Pathol 35 (1): 70-5, 2011. [PUBMED Abstract]
24. Grassia KL, Peterman CM, Iacobas I, et al.: Clinical case series of pediatric hepatic angiosarcoma. Pediatr Blood Cancer 64 (11): , 2017. [PUBMED Abstract]
25. Elliott P, Kleinschmidt I: Angiosarcoma of the liver in Great Britain in proximity to vinyl chloride sites. Occup Environ Med 54 (1): 14-8, 1997. [PUBMED Abstract]
26. Lezama-del Valle P, Gerald WL, Tsai J, et al.: Malignant vascular tumors in young patients. Cancer 83 (8): 1634-9, 1998. [PUBMED Abstract]
27. 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]
28. Lahat G, Dhuka AR, Hallevi H, et al.: Angiosarcoma: clinical and molecular insights. Ann Surg 251 (6): 1098-106, 2010. [PUBMED Abstract]
29. Orlando G, Adam R, Mirza D, et al.: Hepatic hemangiosarcoma: an absolute contraindication to liver transplantation--the European Liver Transplant Registry experience. Transplantation 95 (6): 872-7, 2013. [PUBMED Abstract]
30. Aldén J, Baecklund F, Psaros Einberg A, et al.: Is primary hepatic angiosarcoma in children an indication for liver transplantation?-A single-centre experience and review of the literature. Pediatr Transplant 25 (8): e14095, 2021. [PUBMED Abstract]
31. Roy A, Gabani P, Davis EJ, et al.: Concurrent paclitaxel and radiation therapy for the treatment of cutaneous angiosarcoma. Clin Transl Radiat Oncol 27: 114-120, 2021. [PUBMED Abstract]
32. Sanada T, Nakayama H, Irisawa R, et al.: Clinical outcome and dose volume evaluation in patients who undergo brachytherapy for angiosarcoma of the scalp and face. Mol Clin Oncol 6 (3): 334-340, 2017. [PUBMED Abstract]
33. Guadagnolo BA, Zagars GK, Araujo D, et al.: Outcomes after definitive treatment for cutaneous angiosarcoma of the face and scalp. Head Neck 33 (5): 661-7, 2011. [PUBMED Abstract]
34. Scott MT, Portnow LH, Morris CG, et al.: Radiation therapy for angiosarcoma: the 35-year University of Florida experience. Am J Clin Oncol 36 (2): 174-80, 2013. [PUBMED Abstract]
35. Dickson MA, D'Adamo DR, Keohan ML, et al.: Phase II Trial of Gemcitabine and Docetaxel with Bevacizumab in Soft Tissue Sarcoma. Sarcoma 2015: 532478, 2015. [PUBMED Abstract]
36. North PE, Waner M, Mizeracki A, et al.: A unique microvascular phenotype shared by juvenile hemangiomas and human placenta. Arch Dermatol 137 (5): 559-70, 2001. [PUBMED Abstract]
37. Boye E, Yu Y, Paranya G, et al.: Clonality and altered behavior of endothelial cells from hemangiomas. J Clin Invest 107 (6): 745-52, 2001. [PUBMED Abstract]
38. Ravi V, Patel S: Vascular sarcomas. Curr Oncol Rep 15 (4): 347-55, 2013. [PUBMED Abstract]
39. Koo J, Knight-Perry J, Galambos C, et al.: Pediatric Metastatic Cardiac Angiosarcoma Successfully Treated With Multimodal Therapy: Case Report and Review of Literature. J Pediatr Hematol Oncol 43 (2): e203-e206, 2021. [PUBMED Abstract]

Standard treatment options for metastatic childhood soft tissue sarcoma include the following:

For treatment options, see the individual tumor type sections of the summary.

The prognosis for children with metastatic soft tissue sarcomas is poor.[1-6] 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. However, the estimated 4-year survival rate was poor. Less than one-third of children survived.[6-8]

Targeted (stereotactic body) radiation therapy is an option for sites of metastasis, particularly the lung.[9] Targeted radiation therapy is also an option for local control or sites of metastasis, including the lungs, bones, and brain,[10,11] particularly in patients for whom the morbidity of resection is a concern or whose life expectancy is limited.[9]

In a prospective trial of children with metastatic soft tissue sarcoma, patients were randomly assigned to receive multiagent chemotherapy with or without the addition of bevacizumab.[12] There was no difference in event-free survival or overall survival between the two study arms.

References

1. 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]
2. 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]
3. 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]
4. Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec. [PUBMED Abstract]
5. 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]
6. 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]
7. 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]
8. 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]
9. Dhakal S, Corbin KS, Milano MT, et al.: Stereotactic body radiotherapy for pulmonary metastases from soft-tissue sarcomas: excellent local lesion control and improved patient survival. Int J Radiat Oncol Biol Phys 82 (2): 940-5, 2012. [PUBMED Abstract]
10. Howard TP, Boyle PJ, Marcus KJ, et al.: Clinical outcomes for pediatric patients receiving radiotherapy for solid tumor central nervous system metastases. Pediatr Blood Cancer 68 (12): e29331, 2021. [PUBMED Abstract]
11. Cameron AL, Elze MC, Casanova M, et al.: The Impact of Radiation Therapy in Children and Adolescents With Metastatic Rhabdomyosarcoma. Int J Radiat Oncol Biol Phys 111 (4): 968-978, 2021. [PUBMED Abstract]
12. Ferrari A, Merks JHM, Chisholm JC, et al.: Outcomes of metastatic non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) treated within the BERNIE study: a randomised, phase II study evaluating the addition of bevacizumab to chemotherapy. Eur J Cancer 130: 72-80, 2020. [PUBMED Abstract]
13. Stanelle EJ, Christison-Lagay ER, Wolden SL, et al.: Pulmonary metastasectomy in pediatric/adolescent patients with synovial sarcoma: an institutional review. J Pediatr Surg 48 (4): 757-63, 2013. [PUBMED Abstract]
14. Putnam JB, Roth JA: Surgical treatment for pulmonary metastases from sarcoma. Hematol Oncol Clin North Am 9 (4): 869-87, 1995. [PUBMED Abstract]

With the possible exception of infants with infantile fibrosarcoma, the prognosis for patients with progressive or recurrent disease is poor. No prospective trial has demonstrated that enhanced local control of pediatric soft tissue sarcomas will ultimately improve survival. Therefore, treatment should be individualized for the site of recurrence, biological characteristics of the tumor (e.g., grade, invasiveness, and size), previous therapies, and individual patient considerations. All patients with recurrent tumors should consider participating in clinical trials.

Published results of two studies addressed the outcomes of children with relapsed synovial sarcoma. Most patients in one study had distant relapse (29 of 44 patients),[1] while most patients in the second study had local relapse (27 of 37 patients).[2] Distant recurrence was a poor prognostic variable, while tumor resectability at relapse (as manifested by extremity recurrence) was associated with a better outcome in both studies.

Resection is the standard treatment for recurrent pediatric nonrhabdomyosarcomatous soft tissue sarcomas. If the patient has not yet received radiation therapy, postoperative radiation should be considered after local excision of the recurrent tumor. Limb-sparing procedures with postoperative brachytherapy have been evaluated in adults but have 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.

Treatment options for progressive or recurrent disease include the following:

References

1. Ferrari A, De Salvo GL, Dall'Igna P, et al.: Salvage rates and prognostic factors after relapse in children and adolescents with initially localised synovial sarcoma. Eur J Cancer 48 (18): 3448-55, 2012. [PUBMED Abstract]
2. Soole F, Maupain C, Defachelles AS, et al.: Synovial sarcoma relapses in children and adolescents: prognostic factors, treatment, and outcome. Pediatr Blood Cancer 61 (8): 1387-93, 2014. [PUBMED Abstract]
3. Bergamaschi L, Bisogno G, Manzitti C, et al.: Salvage rates and prognostic factors after relapse in children and adolescents with malignant peripheral nerve sheath tumors. Pediatr Blood Cancer 65 (2): , 2018. [PUBMED Abstract]
4. 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]
5. 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]
6. Stanelle EJ, Christison-Lagay ER, Wolden SL, et al.: Pulmonary metastasectomy in pediatric/adolescent patients with synovial sarcoma: an institutional review. J Pediatr Surg 48 (4): 757-63, 2013. [PUBMED Abstract]
7. Maki RG, Wathen JK, Patel SR, et al.: Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002 [corrected]. J Clin Oncol 25 (19): 2755-63, 2007. [PUBMED Abstract]
8. Le Cesne A, Cresta S, Maki RG, et al.: A retrospective analysis of antitumour activity with trabectedin in translocation-related sarcomas. Eur J Cancer 48 (16): 3036-44, 2012. [PUBMED Abstract]
9. Garcia-Carbonero R, Supko JG, Maki RG, et al.: Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study. J Clin Oncol 23 (24): 5484-92, 2005. [PUBMED Abstract]
10. Garcia-Carbonero R, Supko JG, Manola J, et al.: Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy. J Clin Oncol 22 (8): 1480-90, 2004. [PUBMED Abstract]
11. van der Graaf WT, Blay JY, Chawla SP, et al.: Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 379 (9829): 1879-86, 2012. [PUBMED Abstract]
12. Glade Bender JL, Lee A, Reid JM, et al.: Phase I pharmacokinetic and pharmacodynamic study of pazopanib in children with soft tissue sarcoma and other refractory solid tumors: a children's oncology group phase I consortium report. J Clin Oncol 31 (24): 3034-43, 2013. [PUBMED Abstract]
13. Casanova M, Basso E, Magni C, et al.: Response to pazopanib in two pediatric patients with pretreated relapsing synovial sarcoma. Tumori 103 (1): e1-e3, 2017. [PUBMED Abstract]
14. Tawbi HA, Burgess M, Bolejack V, et al.: Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol 18 (11): 1493-1501, 2017. [PUBMED Abstract]

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.

This summary was comprehensively reviewed.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.