Childhood Soft Tissue Sarcoma, part 2

Synovial sarcoma appears to be more sensitive to chemotherapy than many other soft tissue sarcomas. Children with synovial sarcoma seem to have a better prognosis than adults with synovial sarcoma.[11,28,32-37]

Sources: 11 · 28 · 32 · 37

The most commonly used chemotherapy regimens for the treatment of synovial sarcoma incorporate ifosfamide and doxorubicin.[19,35,38] Response rates to the ifosfamide and doxorubicin regimen are higher than in other NRSTS.[39]

Sources: 19 · 35 · 38 · 39

Evidence (surgery and chemotherapy with or without radiation therapy):

For patients with recurrent synovial sarcoma, the survival rate after relapse is poor (30%–40% at 5 years). Factors associated with outcome after relapse include duration of first remission (> or ≤ 18 months) and lack of a second remission.[46,47]

Sources: 46 · 47

In a German experience, surgical resection of metastatic disease was the most common way to achieve a second complete remission.[47] Maintenance chemotherapy with oral trofosfamide, idarubicin, and etoposide or oral cyclophosphamide and intravenous vinblastine was administered on an individual basis.

Sources: 47

A consortium of six European referral centers reported a retrospective review of patients younger than 21 years with recurrent synovial sarcoma. Among 41 patients, the first relapses occurred within 3 to 132 months (median, 18 months) after first diagnoses. The relapses were local in 34% of patients, metastatic in 54%, and both in 12%. Treatments at first relapse included surgery in 56% of patients, radiation therapy in 34%, and systemic therapy in 88%. In all, 36 patients received second-line medical treatment, which included chemotherapy in 32 patients (with 10 different regimens) and targeted therapy in 4 patients. No patient was included in early-phase clinical trials as second-line therapy. The overall response rate was 42%. The median EFS was 12 months, and the postrelapse 5-year EFS rate was 15.8%. The median OS was 30 months, and the postrelapse 5-year OS rate was 22.2%. In a Cox multivariable regression analysis, OS was significantly associated with time and type of relapse.[48]

Sources: 48

Radiation therapy (stereotactic body radiation therapy) can be used to target select pulmonary metastases. This is usually considered after a minimum of one resection to confirm metastatic disease. Radiation therapy is particularly appropriate for patients with lesions that threaten air exchange because of their location adjacent to bronchi or cause pain by invading the chest wall.[49]

Sources: stereotactic body radiation therapy · 49

Between 70% to 80% of synovial sarcomas express NY-ESO-1, an immunogenic cancer testis antigen.[50] NY-ESO-1 can be targeted with adoptive transfer of T cells engineered to express NY-ESO-1c259, an affinity-enhanced T-cell receptor (TCR) targeting NY-ESO-1/LAGE1a.[51] The procedure to produce the genetically engineered T cells restricts their reactivity to a single HLA type. All clinical trials of this technology chose HLA-A*02 as the initial target and limited eligibility to patients whose tumors expressed NY-ESO-1 and who had HLA-A*02. In a multi-institutional trial, confirmed antitumor responses occurred in 50% of patients (6 of 12) and were characterized by tumor shrinkage over several months. Circulating NY-ESO-1c259 T cells were present postinfusion in all patients, and the cells persisted for at least 6 months in all responders.[52]

Sources: 50 · 51 · 52

An open-label, international, phase II study enrolled patients with previously treated metastatic or unresectable synovial sarcoma and myxoid round cell liposarcoma.[53] Fifty-two patients with HLA-A*02 and tumors that expressed melanoma-associated antigen A4 (MAGE-A4) received a single intravenous dose of afamitresgene autoleucel (afami-cel) after lymphodepletion. Afami-cel is a MAGE-A4–directed, genetically modified, autologous T-cell immunotherapy. The overall response rate (the primary end point of the study) was 37% (19 of 52; 95% CI, 24%–51%), 39% (17 of 44; 95% CI, 24%–55%) for patients with synovial sarcoma, and 25% (2 of 8; 95% CI, 3%–65%) for patients with myxoid round cell liposarcoma. Cytokine release syndrome and cytopenias were the most frequent side effects. The authors concluded that afami-cel treatment resulted in durable responses in heavily pretreated eligible patients with synovial sarcoma.[53] These data led to FDA approval of afami-cel in adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02 positive, and whose tumors express the MAGE-A4 antigen.

Sources: 53 · 53

Information about National Cancer Institute (NCI)-supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

Sources: NCI website · ClinicalTrials.gov website

Epithelioid sarcoma is a rare mesenchymal tumor of uncertain histogenesis that displays multilineage differentiation.[54]

Sources: 54

Epithelioid sarcoma commonly presents as a slowly growing firm nodule based in the deep soft tissue. The proximal type predominantly affects adults and involves the axial skeleton and proximal sites. The tumor is highly aggressive and has a propensity for lymph node metastases.

Epithelioid sarcoma is characterized by inactivation of the SMARCB1 gene, which is present in both conventional and proximal types of epithelioid sarcoma.[55] This abnormality leads to increased dependence on EZH2 and tumor formation.[56]

Sources: 55 · 56

Treatment options for epithelioid sarcoma include the following:

Surgical removal of primary and recurrent tumor(s) is the most effective treatment.[57][Level of evidence C1] Because of the propensity of this disease to have occult metastasis to the lymph nodes, sentinel lymph node biopsy is recommended for epithelioid sarcoma of the extremities or buttocks in the absence of clinically (by imaging or physical examination) enlarged lymph nodes.[58]

Sources: 57 · Level of evidence C1 · 58

Evidence (surgery with or without chemotherapy and/or radiation therapy):

Evidence (tazemetostat):

In January 2020, the U.S. Food and Drug Administration (FDA) granted accelerated approval to tazemetostat for adult and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma who were not eligible for complete resection.

Information about NCI-supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

Sources: NCI website · ClinicalTrials.gov website

The following is an example of a national and/or institutional clinical trial that is currently being conducted:

Alveolar soft part sarcomas account for 1.4% of soft tissue sarcomas in patients younger than 20 years (see Table 1).

Sources: Table 1

The median age at presentation is 25 years for patients with alveolar soft part sarcoma. This tumor most commonly arises in the extremities but can occur in the oral and maxillofacial region.[63-65] Alveolar soft part sarcoma in children can present with evidence of metastatic disease.[66] Delayed metastases to the brain and lung are uncommon.[63]

Sources: 63 · 65 · 66 · 63

In a series of 61 patients with alveolar soft part sarcoma who were treated in four consecutive CWS trials and the Soft Tissue Sarcoma Registry (SoTiSaR), 46 patients presented with localized disease and 15 patients had evidence of metastasis at diagnosis.[67]

Sources: 67

Sixty-nine patients younger than 30 years with alveolar soft part sarcoma were treated between 1980 and 2014 at four major institutions. The median age at diagnosis was 17 years, and 64% of patients were female. The most common site of disease was the lower extremity, and 26 patients had an ASPSCR1::TFE3 gene translocation.[68]

Sources: 68

This tumor of uncertain histogenesis is characterized by a consistent chromosomal translocation t(X;17)(p11.2;q25) that fuses the ASPSCR1 gene with the TFE3 gene.[69,70]

Sources: 69 · 70

Alveolar soft part sarcoma in children may have an indolent course.[66] Patients with alveolar soft part sarcoma may relapse several years after a prolonged period of apparent remission.[67,71]

Sources: 66 · 67 · 71

Treatment options for alveolar soft part sarcoma include the following:

The standard treatment approach is complete resection of the primary lesion.[72] If complete excision is not feasible, radiation therapy is administered.

Sources: 72

Evidence (surgery with or without chemotherapy):

Studies of targeted therapy (tyrosine kinase inhibitors and checkpoint inhibitors) have been done.

Sunitinib

Evidence (sunitinib):

Cediranib

Cediranib is an inhibitor of all three known vascular epidermal growth factor receptors.

Evidence (cediranib):

Pazopanib

Evidence (pazopanib):

Axitinib and pembrolizumab

Axitinib is a vascular endothelial growth factor receptor tyrosine kinase inhibitor. Pembrolizumab is an anti–PD-1 immune checkpoint inhibitor.

Evidence (axitinib and pembrolizumab):

Atezolizumab

Atezolizumab is a monoclonal antibody directed against PD-1 and PD-L1.

Evidence (atezolizumab):

There have been sporadic reports of objective responses to treatment with interferon-alpha and bevacizumab.[63,83,84]

Sources: 63 · 83 · 84

Because these tumors are rare, all children with alveolar soft part sarcoma should be considered for enrollment in prospective clinical trials. Information about ongoing clinical trials is available from the NCI website.

Sources: NCI website

Information about NCI-supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

Sources: NCI website · ClinicalTrials.gov website

Clear cell sarcoma (formerly called malignant melanoma of soft parts) is a rare soft tissue sarcoma that typically involves the deep soft tissues of the extremities. It is also called clear cell sarcoma of tendons and aponeuroses. The tumor often affects adolescents and young adults.

The tumor most commonly affects the lower extremity, particularly the foot, heel, and ankle.[85,86] It has a high propensity for nodal dissemination, especially metastases to regional lymph nodes (12%–43%).[86,87]

Sources: 85 · 86 · 86 · 87

The tumor typically has an indolent clinical course. Patients who have small, localized tumors with low mitotic rate and intermediate histological grade have the best outcomes.[88]

Sources: 88

Clear cell sarcoma of soft tissue is characterized by EWSR1::ATF1 or EWSR1::CREB1 gene fusions.[89,90]

Sources: 89 · 90

Treatment options for clear cell sarcoma of soft tissue include the following:

Surgery with or without radiation therapy is the treatment of choice and offers the best chance for cure.

Evidence (surgery with or without radiation therapy):

Evidence (targeted therapy):

Extraskeletal myxoid chondrosarcoma is relatively rare among soft tissue sarcomas, representing only 2.3% of all soft tissue sarcomas.[94] It has been reported in children and adolescents.[95]

Sources: 94 · 95

The tumor has traditionally been considered to have low-grade malignant potential.[96] However, reports from large institutions showed that extraskeletal myxoid chondrosarcoma has significant malignant potential, especially if patients are monitored for a long time.[97,98] Patients tend to have slow protracted courses. Nodal involvement has been well described. Local recurrence (57%) and metastatic spread to lungs (26%) have been reported.[98]

Sources: 96 · 97 · 98 · 98

Extraskeletal myxoid chondrosarcoma is a multinodular neoplasm. The rounded cells are arranged in cords and strands in a chondroitin sulfate myxoid background. Several cytogenetic abnormalities have been identified (see Table 2), with the most frequent being the EWSR1::NR4A3 gene fusion.[99]

Sources: Table 2 · 99

Treatment options for extraskeletal myxoid chondrosarcoma include the following:

Aggressive local control and resection of metastases led to OS rates of 87% at 5 years and 63% at 10 years. Tumors were relatively resistant to radiation therapy.[97] The therapeutic benefit of chemotherapy has not been established.

Sources: 97

There may be potential genetic targets for small molecules, but these need to be studied as part of a clinical trial. In an adult study, six of ten patients who received sunitinib achieved partial responses.[100]

Sources: 100

Almost one-fifth of patients with Ewing sarcoma will present with nonbone primary sites (extraosseous). Treatment for this tumor is the same as it is for patients with bone primary tumors.[101] For more information, see Ewing Sarcoma and Undifferentiated Small Round Cell Sarcomas of Bone and Soft Tissue Treatment.

Sources: 101 · Ewing Sarcoma and Undifferentiated Small Round Cell Sarcomas of Bone and Soft Tissue Treatment

Desmoplastic small round cell tumor is a rare primitive sarcoma.

Desmoplastic small round cell tumor most frequently involves the peritoneum in the abdomen, pelvis, and/or peritoneum into the scrotal sac, but it may occur in the kidney or other solid organs.[102-106] Dozens to hundreds of intraperitoneal implants are often found. The tumor occurs predominantly in males (85%) and may spread to the lungs and elsewhere.[106,107]

Sources: 102 · 106 · 106 · 107

A large single-institution series of 65 patients compared computed tomography (CT) scans (n = 54) with positron emission tomography (PET)-CT scans (n = 11). PET-CT scans produced very few false-negative results and detected metastatic sites missed on conventional CT scans.[107]

Sources: 107

Cytogenetic studies of these tumors have demonstrated the recurrent translocation t(11;22)(p13;q12), which has been characterized as a fusion of the WT1 and EWSR1 genes.[105,108] The EWSR1::WT1 fusion confirms the diagnosis of desmoplastic small round cell tumor. The average tumor variant burden is low for desmoplastic small round cell tumor (<1 variant per megabase), and recurring gene alterations other than the EWSR1::WT1 fusion are uncommon.[109] A small percentage of cases (approximately 3%) have activating variants in FGFR4, with amplification of FGFR4 observed at similar frequency.[109,110] Inactivating variants in TP53 and ARID1A are observed in a small percentage of desmoplastic small round cell tumor cases.[109,110]

Sources: 105 · 108 · 109 · 109 · 110 · 109 · 110

The overall prognosis for patients with desmoplastic small round cell tumor remains extremely poor, with reported rates of death at 90%. Greater than 90% tumor resection either at presentation or after preoperative chemotherapy may be a favorable prognostic factor for OS.[111,112]; [113][Level of evidence C1] Response to neoadjuvant chemotherapy and complete resection (near 100%) is associated with improved outcome.[106,114]

Sources: 111 · 112 · 113 · Level of evidence C1 · 106 · 114

There is no standard approach to the treatment of desmoplastic small round cell tumor.

Treatment options for desmoplastic small round cell tumor include the following:

Complete surgical resections are rare and usually performed in highly specialized centers, but are critical for any improved survival. Successful treatment modalities include neoadjuvant Ewing-type chemotherapy, followed by complete surgical resection of the extensive intra-abdominal tumors, followed by total abdominal radiation therapy. With this multimodality approach, survival can be achieved in 30% to 40% of patients at 5 years.[102,103,111,115-118]

Sources: 102 · 103 · 111 · 115 · 118

HIPEC is a local treatment method that may control more of the microscopic intra-abdominal disease. The theory is that the heated chemotherapy that is instilled in the abdominal cavity after surgical resection (at the time of surgery) provides synergistic cytotoxicity to any microscopic cells remaining in the abdomen.[119]

Sources: 119

The addition of HIPEC to complete surgical resection (cytoreductive surgery) is a new technique first applied to children in 2006 in a phase I clinical trial. Cytoreductive surgery and HIPEC for desmoplastic small round cell tumors is part of a multidisciplinary approach and is only being done in highly specialized centers. Surgeries can last more than 12 hours, and technical aspects of this unique tumor resection should be considered.[119]

Sources: 119

Evidence (surgery with HIPEC):

The Center for International Blood and Marrow Transplant Research analyzed patients with desmoplastic small round cell tumor in their registry who received consolidation with high-dose chemotherapy and autologous stem cell reconstitution.[123] While this retrospective registry analysis suggested some benefit to this approach, other investigators have abandoned the approach because of excessive toxicity and lack of efficacy.[111]

Sources: 123 · 111

A single-institution study reported that five of five patients with recurrent desmoplastic small round cell tumor had partial responses to treatment with the combination of vinorelbine, cyclophosphamide, and temsirolimus.[124]

Sources: 124

Malignant rhabdoid tumors were first described in children with renal tumors in 1981. These tumors were later found in a variety of extrarenal sites. These tumors are uncommon and highly malignant, especially in children younger than 2 years. For more information, see the Rhabdoid Tumors of the Kidney section in Wilms Tumor and Other Childhood Kidney Tumors Treatment.

Sources: Rhabdoid Tumors of the Kidney

Extrarenal (extracranial) rhabdoid tumors account for 2% of soft tissue sarcomas in patients younger than 20 years (see Table 1).

Sources: Table 1

The first sizeable series of children with extrarenal extracranial malignant rhabdoid tumor of soft tissues came from 26 patients enrolled on the IRS I through III studies during a review of pathology material. Only five patients (19%) were alive without disease beyond 2 years.[125]

Sources: 125

Investigation of children with atypical teratoid/rhabdoid tumors of the brain, as well as those with renal and extrarenal malignant rhabdoid tumors, found germline pathogenic variants and acquired variants of the SMARCB1 gene in all 29 tumors tested.[126] Rhabdoid tumors may be associated with germline pathogenic variants of the SMARCB1 gene and may be inherited from an apparently unaffected parent.[127] This observation was extended to 32 malignant rhabdoid tumors at all sites in patients whose mean age at diagnosis was 12 months.[128]

Sources: 126 · 127 · 128

Germline analysis should be considered for individuals of all ages with rhabdoid tumors. Genetic counseling is also part of the treatment plan, given the low-but-actual risk of familial recurrence. In cases of variants, parental screening should be considered, although such screening carries a low probability of positivity. Prenatal diagnosis can be performed in situations where a specific SMARCB1 variant or deletion has been documented in the family.[127]

Sources: 127

To date, there is little evidence regarding the effectiveness of surveillance for patients with rhabdoid tumor predisposition syndrome type 1 caused by loss-of-function germline SMARCB1 pathogenic variants. However, because of the aggressive nature of the tumors with significant lethality and young age of onset in SMARCB1 carriers with truncating variants, consensus recommendations have been developed. These recommendations were developed by a group of pediatric cancer genetic experts (including oncologists, radiologists, and geneticists). They have not been formally studied to confirm the benefit of monitoring patients with germline SMARCB1 pathogenic variants. Given the potential survival benefit of surgically resectable disease, it is postulated that early detection might improve OS.[129-131]

Sources: 129 · 131

Surveillance for patients with germline SMARCB1 pathogenic variants includes the following:

For information about SMARCB1 and rhabdoid tumor predisposition syndrome type 1, see Rhabdoid Tumor Predisposition Syndrome Type 1.

Sources: Rhabdoid Tumor Predisposition Syndrome Type 1

Young age and metastatic disease at presentation are associated with poor outcomes in children with extracranial rhabdoid tumors.

One study that used data from the National Cancer Database identified 202 patients (aged younger than 18 years) with non–central nervous system (CNS) malignant rhabdoid tumors. The primary site of the malignant rhabdoid tumor was soft tissue (46%), kidney (45%), and liver (9%).[132]

Sources: 132

A SEER study examined 229 patients with renal, CNS, and extrarenal malignant rhabdoid tumor. Patients aged 2 to 18 years, patients with a limited extent of tumor, and patients who received radiation therapy had favorable outcomes compared with other patients (P < .002 for each comparison). Site of the primary tumor was not prognostically significant. The OS rate was 33% at 5 years.[133]

Sources: 133

A European registry for extracranial rhabdoid tumors identified 100 patients from 14 countries between 2009 and 2018.[134] Half of the patients were younger than 1 year at diagnosis. In 30 patients (30%), the tumor was located in the kidneys. Extracranial, extrarenal malignant rhabdoid tumor was found in 70% of patients (70 of 100), and the most common locations were in the cervical region, thoracic region, and liver. Nine patients demonstrated synchronous tumors. Distant metastases at diagnosis were present in 35% of patients (35 of 100). SMARCB1 germline pathogenic variants were detected in 21% of patients (17 of 81 evaluable). The 5-year OS rate was 45.8% (± 5.4%), and the EFS rate was 35.2% (± 5.1%). In an adjusted multivariate model, presence of a germline pathogenic variant, metastasis, and lack of a gross-total resection were the strongest significant negative predictors of outcome.

Sources: 134

Treatment options for extrarenal (extracranial) rhabdoid tumor include the following:[135-137][Level of evidence C1]

Sources: 135 · 137 · Level of evidence C1

Responses to alisertib have been documented in four patients with CNS atypical teratoid/rhabdoid tumors.[138] For more information about CNS atypical teratoid/rhabdoid tumors, see Childhood Central Nervous System Atypical Teratoid/Rhabdoid Tumor Treatment.

Sources: 138 · Childhood Central Nervous System Atypical Teratoid/Rhabdoid Tumor Treatment

Information about NCI-supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

Sources: NCI website · ClinicalTrials.gov website

The following is an example of a national and/or institutional clinical trial that is currently being conducted:

PEComas occur in various rare gastrointestinal, pulmonary, gynecological, and genitourinary sites. Soft tissue, visceral, and gynecological PEComas are more commonly seen in middle-aged female patients and are usually not associated with the tuberous sclerosis complex.[139] The disease course may be indolent.

Sources: 139

Benign PEComas are common in patients with tuberous sclerosis, an autosomal dominant syndrome that also predisposes to renal cell cancer and brain tumors. Tuberous sclerosis is caused by germline pathogenic inactivation of either TSC1 (9q34) or TSC2 (16p13.3), and the same tumor suppressor genes are inactivated somatically in sporadic PEComas.[140] Inactivation of either gene results in stimulation of the mTOR pathway, providing the basis for the treatment of nonsurgically curable tumors with similar genetic inactivation (lymphangioleiomyomatosis and angiomyolipoma) with mTOR inhibitors.[141,142] A small proportion of PEComas have TFE3 rearrangements with fusions involving various genes, including SFPQ and RAD51B.[143]

Sources: 140 · 141 · 142 · 143

Most PEComas have a benign clinical course, but malignant behavior has been reported and can be predicted based on the size of the tumor, mitotic rate, and presence of necrosis.[144]

Sources: 144

There are no standard treatment options. Treatment may include surgery or observation followed by surgery when the tumor is large.[145]

Sources: 145

In tumors with evidence of mTORC1 activation and TSC1 or TSC2 loss, including lymphangioleiomyomatosis and angiomyolipoma,[141] clinical activity using mTOR inhibitors, such as sirolimus, has been well documented. In a small case series, three adult patients with PEComas responded to sirolimus.[146]

Sources: 141 · 146

In a phase II trial, 34 patients with metastatic or locally advanced malignant PEComas were treated with sirolimus protein-bound particles for injectable suspension (albumin-bound) (nab-sirolimus). Of the 31 patients eligible for efficacy analysis, 12 (39%) had a response (1 complete response and 11 partial responses), 16 (52%) had stable disease, and 3 (10%) had progressive disease. Responses were rapid and durable. The median duration of response was not reached after a median follow-up of 2.5 years. Treatment was ongoing for 7 of 12 patients who responded to treatment (range, 5.6 months to longer than 47.2 months). Tumor variant profiling was completed for 25 specimens. Eight of nine patients with TSC2 variants responded to treatment, while only 2 of 16 patients without TSC2 variants responded. In addition, responses were noted in 10 of 17 patients with phospho-S6 (pS6) expression. No response was noted in eight patients without pS6 expression. The absence of pS6 expression reflects the lack of mTORC1 activation.[147][Level of evidence C1] In 2021, the FDA approved nab-sirolimus for adult patients with PEComas.

Sources: 147 · Level of evidence C1

From 1972 to 2006, patients with undifferentiated soft tissue sarcoma were eligible for participation in rhabdomyosarcoma trials coordinated by the IRS group and the COG. The rationale was that patients with undifferentiated soft tissue sarcoma had sites of disease and outcomes that were similar to those in patients with alveolar rhabdomyosarcoma. Therapeutic trials for adults with soft tissue sarcoma include patients with undifferentiated soft tissue sarcoma and other histologies, which are treated similarly, using ifosfamide and doxorubicin, and sometimes with other chemotherapy agents, surgery, and radiation therapy.

In the COG ARST0332 (NCT00346164) trial, patients with high-grade undifferentiated sarcoma were treated with an ifosfamide- and doxorubicin-based regimen. Results for the patients with high-grade undifferentiated sarcoma were reported together with all high-grade soft tissue sarcomas in the trial. The estimated 5-year EFS rate was 64% and the OS rate was 77% for sarcomas classified as high grade by the Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLC).[5][Level of evidence C1]

Sources: ARST0332 (NCT00346164) · 5 · Level of evidence C1

In a report of 32 patients with undifferentiated soft tissue sarcomas who were enrolled on the ARST0332 (NCT00346164) trial, the median age at enrollment was 13.6 years, and two-thirds of the patients were male. The most common primary sites were the paraspinal region and extremities. Five patients presented with metastatic disease.[148]

Sources: ARST0332 (NCT00346164) · 148

At one time, malignant fibrous histiocytoma was the single most common histotype among adults with soft tissue sarcomas. Since it was first recognized in the early 1960s, malignant fibrous histiocytoma has been controversial, in terms of both its histogenesis and its validity as a clinico-pathological entity. The World Health Organization (WHO) classification no longer includes malignant fibrous histiocytoma as a distinct diagnostic category but rather as a subtype of an undifferentiated pleomorphic sarcoma.[149,150]

Sources: 149 · 150

This entity accounts for 2% to 6% of all childhood soft tissue sarcomas.[151]

Sources: 151

These tumors occur mainly in the second decade of life. In a series of ten patients, the median age was 10 years, and the tumor was most commonly located in the extremities. In this series, all tumors were localized, and five of nine patients (for whom follow-up was available) were alive and in first remission.[151]

Sources: 151

In another series of 17 pediatric patients with malignant fibrous histiocytoma (now classified as undifferentiated pleomorphic sarcoma), the median age at diagnosis was 5 years and the extremities were involved in eight cases.[152] All patients with metastatic disease died, and two patients experienced a clinical response to a doxorubicin-based regimen.

Sources: 152

For more information about the treatment of malignant fibrous histiocytoma of bone, see Osteosarcoma and Undifferentiated Pleomorphic Sarcoma of Bone Treatment.

Sources: Osteosarcoma and Undifferentiated Pleomorphic Sarcoma of Bone Treatment

These tumors can arise in previously irradiated sites or as a second malignancy in patients with retinoblastoma.[153]

Sources: 153

An analysis of 70 patients who were diagnosed with 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.[154]

Sources: 154

Undifferentiated sarcomas with 12q13–15 amplification, including MDM2 and CDK4, are best classified as dedifferentiated liposarcomas.[154] The relationship between this tumor and the family of undifferentiated/unclassified tumors with spindle cell morphology remains relatively undefined.

Sources: 154

For information about the treatment of undifferentiated pleomorphic sarcoma of bone, see Osteosarcoma and Undifferentiated Pleomorphic Sarcoma of Bone Treatment.

Sources: Osteosarcoma and Undifferentiated Pleomorphic Sarcoma of Bone Treatment

Treatment options for recurrent or refractory pleomorphic sarcoma include the following:

The Sarcoma Alliance for Research through Collaboration conducted a phase II trial of the checkpoint inhibitor pembrolizumab in patients aged 18 years and older with recurrent soft tissue sarcoma.[155][Level of evidence C3]

Sources: 155 · Level of evidence C3

Intracranial mesenchymal tumor, with the FET::CREB gene fusion, has previously been called angiomatoid fibrous histiocytoma (AFP) or intracranial myxoid mesenchymal tumor. The molecular findings suggest that these tumors are histological variants of intracranial mesenchymal tumor.[156] In one study, the tumors of 20 patients were separated into two epigenetic subgroups. Group A tumors clustered nearest to but independent of solitary fibrous tumor and occurred in adolescents and young adults. Group B tumors clustered nearest to but independent of clear cell sarcoma and occurred in children. Patients with group B tumors had an inferior survival compared with patients with group A tumors (4.5 vs. 49 months; P = .001).[157]

Sources: 156 · 157

See the sections on Undifferentiated Small Round Cell Sarcomas With BCOR Genetic Alterations and Genomics of Ewing Sarcoma in Ewing Sarcoma and Undifferentiated Small Round Cell Sarcomas of Bone and Soft Tissue Treatment.

Sources: Undifferentiated Small Round Cell Sarcomas With BCOR Genetic Alterations · Genomics of Ewing Sarcoma

See the sections on Undifferentiated Small Round Cell Sarcomas With CIC Genetic Alterations and Genomics of Ewing Sarcoma in Ewing Sarcoma and Undifferentiated Small Round Cell Sarcomas of Bone and Soft Tissue Treatment.

Sources: Undifferentiated Small Round Cell Sarcomas With CIC Genetic Alterations · Genomics of Ewing Sarcoma

See the Undifferentiated Small Round Cell Sarcomas With EWSR1::non-ETS Fusions section in Ewing Sarcoma and Undifferentiated Small Round Cell Sarcomas of Bone and Soft Tissue Treatment.

Sources: Undifferentiated Small Round Cell Sarcomas With EWSR1::non-ETS Fusions

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

Sources: 1

Epithelioid hemangioendothelioma was first described in soft tissue by Weiss and Enzinger in 1982. These tumors can occur in younger patients, but the peak incidence is in the fourth and fifth decades of life. The number of pediatric patients reported in the literature is limited.

Epithelioid hemangioendotheliomas can have an indolent or very aggressive course, with an overall survival rate of 73% at 5 years. There are case reports of patients with untreated multiple lesions who have a very benign course. However, other patients have a very aggressive course. Some pathologists have tried to stratify patients to evaluate risks and adjust treatment, but more research is needed.[2-8]

Sources: 2 · 8

A multi-institutional case series reported on 24 patients aged 2 to 26 years with epithelioid hemangioendotheliomas.[9][Level of evidence C2] Most patients presented with multiorgan disease. Progression was seen in 63% of patients, with a mean time to progression of 18.4 months (range, 0–72 months).

Sources: 9 · Level of evidence C2

The presence of effusions, tumor size larger than 3 cm, and a high mitotic index (>3 mitoses/50 high-power fields) have been associated with unfavorable outcomes.[4]

Sources: 4

Common sites of involvement are liver alone (21%), liver plus lung (18%), lung alone (12%), and bone alone (14%).[4,10,11] Clinical presentation depends on the site of involvement, as follows:

Sources: 4 · 10 · 11

WWTR1::CAMTA1 gene fusions have been found in most patients. Less commonly, YAP1::TFE3 gene fusions have been reported.[2] These gene fusions are not directly targetable with current medications. Monoclonality has been described in multiple liver lesions, suggesting a metastatic process.

Sources: 2

Histologically, these lesions are characterized as epithelioid lesions arranged in nests, strands, and trabecular patterns, with infrequent vascular spaces. Features that may be associated with aggressive clinical behavior include cellular atypia, one or more mitoses per 10 high-power fields, an increased proportion of spindled cells, focal necrosis, and metaplastic bone formation.[4]

Sources: 4

Treatment options for epithelioid hemangioendothelioma include the following:

For indolent cases, observation is warranted. Surgery is performed when resection is possible. Liver transplant has been used with aggressive liver lesions, both with and without metastases.[4,12-14]

Sources: 4 · 12 · 14

For more aggressive cases, several different drugs have been used, including interferon, thalidomide, sorafenib, pazopanib, and sirolimus.[12,15,16] The most aggressive cases are treated with angiosarcoma-type chemotherapy.

Sources: 12 · 15 · 16

A multi-institutional case series reported on 24 patients aged 2 to 26 years with epithelioid hemangioendothelioma.[9][Level of evidence C2]

Sources: 9 · Level of evidence C2

A report from 2020 that investigated sirolimus treatment in children aimed to add to the previous experience of sirolimus in adults. A retrospective review identified six pediatric patients with disseminated epithelioid hemangioendothelioma who were treated with sirolimus.[17]

Sources: 17

A report from the European paediatric Soft Tissue Sarcoma Study Group analyzed ten patients with localized disease and one patient with metastatic disease from two studies.[18] The median age was 14.3 years (range, 9.0–18.8 years). Local therapy was initial primary surgery in seven patients, and five patients received systemic therapy. No patients received radiation therapy.

Sources: 18

Patients or families who desire additional disease-directed therapy should consider entering trials of novel therapeutic approaches because no standard agents have demonstrated clinically significant activity.

Regardless of whether a decision is made to pursue disease-directed therapy at the time of progression, palliative care remains a central focus of management. This ensures that quality of life is maximized while attempting to reduce symptoms and stress related to the terminal illness.

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

Sources: NCI website · ClinicalTrials.gov website

Angiosarcomas are rare (accounting for 2% of sarcomas), aggressive, vascular tumors that can arise in any part of the body but is more common in soft tissues. Angiosarcoma has an estimated incidence of 2 cases per 1 million people. In the United States, it affects approximately 600 people annually, who are typically aged 60 to 70 years.[19]

Sources: 19

Angiosarcomas are extremely rare in children. It is unclear if the pathophysiology of angiosarcomas in children differs from that of angiosarcomas in adults. Cases have been reported in neonates and toddlers, with presentation of multiple cutaneous lesions and liver lesions, some of which are GLUT1 positive.[20-23] Most angiosarcomas involve the skin and superficial soft tissue, although the liver, spleen, and lung can be affected; bone is rarely affected.

Sources: 20 · 23

Nomenclature of these liver lesions has been difficult and confusing with use of outdated terminology proposed in 1971 (e.g., type I hemangioendothelioma: infantile hemangioma; type II hemangioendothelioma: low-grade angiosarcoma; type III hemangioendothelioma: high-grade angiosarcoma).[21] A report of eight cases of liver angiosarcomas in children highlighted the misuse of the term hemangioendothelioma and the importance of early diagnosis and treatment of these tumors.[24]

Sources: 21 · 24

Established risk factors include the following:[25]

Sources: 25

Angiosarcomas are largely aneuploid tumors. The rare cases of angiosarcoma that arise from benign lesions such as hemangiomas have a distinct pathway that needs to be investigated. MYC amplification is seen in radiation-induced angiosarcoma. KDR variants and FLT4 amplifications have been seen with a frequency of less than 50%.[25]

Sources: 25

Histopathological diagnosis can be very difficult because there can be areas of varied atypia. A common feature of angiosarcoma is an irregular network of channels in a dissective pattern along dermal collagen bundles. There is varied cellular shape, size, mitosis, endothelial multilayering, and papillary formation. Epithelioid cells can also be present. Necrosis and hemorrhage are common. Tumors stain for factor VIII, CD31, and CD34. Some liver lesions can mimic infantile hemangiomas and have focal GLUT1 positivity.[21]

Sources: 21

Treatment options for angiosarcoma include the following:

Localized disease can be cured by aggressive surgery. Complete surgical excision appears to be crucial for the long-term survival of patients with angiosarcomas and lymphangiosarcomas, despite evidence of tumor shrinkage in some patients who were treated with local or systemic therapy.[22,26-28] Data on liver transplant for localized angiosarcomas are limited.[29][Level of evidence C1]

Sources: 22 · 26 · 28 · 29 · Level of evidence C1

Evidence (surgery):

Localized disease, especially cutaneous angiosarcomas, can be treated with radiation therapy or combined chemotherapy (e.g., paclitaxel) and radiation therapy.[31] Most of these reported cases are in adults.[32] When radiation is used, the doses are high (50–70 Gy), the cutaneous volumes are extensive because of the infiltrating nature of the disease, and regional (draining) nodes are often included, even if clinically negative.[33,34] Because of these factors, radiation therapy is rarely used to treat children.

Sources: 31 · 32 · 33 · 34

Multimodal treatment with surgery, systemic chemotherapy, and radiation therapy is used for metastatic disease, although it is rarely curative.[34,35] Disease control is the objective in patients with metastatic angiosarcomas. Published progression-free survival is between 3 months and 7 months,[36] and the median overall survival (OS) is 14 to 18 months.[37] In both adults and children, the 5-year OS rates are between 20% and 35%.[22,23,38]

Sources: 34 · 35 · 36 · 37 · 22 · 23 · 38

One child who was diagnosed with angiosarcoma secondary to malignant transformation from infantile hemangioma responded to treatment with bevacizumab (a monoclonal antibody against vascular endothelial growth factor) combined with systemic chemotherapy.[20,35]

Sources: 20 · 35

Biologic agents that inhibit angiogenesis have shown activity in adults with angiosarcomas.[21,38]

Sources: 21 · 38

There is one case report of a pediatric patient with metastatic cardiac angiosarcoma who was successfully treated with conventional chemotherapy, radiation, surgery, and targeted therapies, including pazopanib.[39]

Sources: 39

Regardless of whether a decision is made to pursue disease-directed therapy at the time of progression, palliative care remains a central focus of management. This ensures that quality of life is maximized while attempting to reduce symptoms and stress related to the terminal illness.

Patients or families who desire additional disease-directed therapy should consider entering trials of novel therapeutic approaches because no standard agents have demonstrated clinically significant activity.

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

Sources: NCI website · ClinicalTrials.gov website

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]

Sources: 1 · 6 · 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]

Sources: 9 · 10 · 11 · 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.

Sources: 12

Generally, a surgical procedure, with resection of all gross disease, should be considered for children with isolated pulmonary metastases.[13] For patients with multiple or recurrent pulmonary metastases, additional surgical procedures can be performed if the morbidity is deemed acceptable. In a retrospective review, patients with synovial sarcoma and pulmonary metastases who underwent complete resection of all metastatic lung lesions had better survival than patients who did not undergo complete resections.[13][Level of evidence C1] Formal segmentectomy, lobectomy, and mediastinal lymph node dissection are unnecessary.[14]

Sources: 13 · 13 · Level of evidence C1 · 14

An alternative approach is focused radiation therapy (fractionated stereotactic radiation therapy), which has been successfully used in adults to control lesions. The estimated 5-year survival rate after thoracotomy for pulmonary metastasectomy has ranged from 10% to 58% in adult studies.[9]

Sources: stereotactic radiation therapy · 9

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.

Sources: 1 · 2

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:

Evidence (surgery):

Chemotherapy agents that have been used to treat recurrent soft tissue sarcomas include the following:

Evidence (tyrosine kinase inhibitors):

Evidence (immune checkpoint inhibitors):

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

Sources: NCI website · ClinicalTrials.gov website

A pediatric oncologist, a doctor who specializes in treating children with cancer, oversees treatment for soft tissue sarcoma. The pediatric oncologist works with other health care providers who are experts in treating children with soft tissue sarcoma and who specialize in certain areas of medicine. These may include a pediatric surgeon with special training in the removal of soft tissue sarcomas. Other specialists may include:

Sources: pediatric surgeon

There are different types of treatment for children and adolescents with soft tissue sarcoma. You and your child's cancer care team will work together to decide treatment. Often, the treatments depend on the type of soft tissue sarcoma. Many other factors will be considered, such as your child's overall health and whether the cancer is newly diagnosed or has come back.

Your child's treatment plan will include information about the cancer, the goals of treatment, treatment options, and the possible side effects. It will be helpful to talk with your child's cancer care team before treatment begins about what to expect. For help every step of the way, visit our booklet, Children with Cancer: A Guide for Parents.

Sources: Children with Cancer: A Guide for Parents

Types of treatment your child might have include:

Surgery to completely remove the soft tissue sarcoma is done when possible. If the tumor is very large, radiation therapy or chemotherapy may be given first, to make the tumor smaller and decrease the amount of tissue that needs to be removed during surgery. This is called neoadjuvant (preoperative) therapy.

Sources: radiation therapy · chemotherapy · neoadjuvant (preoperative) therapy

The following types of surgery may be used:

A second-look surgery may be needed to:

Sources: second-look surgery

After the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Sources: adjuvant therapy

Learn more about Surgery to Treat Cancer.

Sources: Surgery to Treat Cancer

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are different types of radiation therapy:

Sources: x-rays · radiation

The way radiation therapy is given depends on the type and stage of the cancer being treated, if any cancer cells remain after surgery, and the expected side effects of treatment. External and internal radiation therapy are used to treat childhood soft tissue sarcoma.

Sources: stage

Learn more about Radiation Therapy to Treat Cancer.

Sources: Radiation Therapy to Treat Cancer

Chemotherapy (also called chemo) uses drugs to stop the growth of cancer cells. Chemotherapy either kills the cancer cells or stops them from dividing. Chemotherapy may be given alone or with other types of treatment, such as radiation therapy.

For children with soft tissue sarcoma, chemotherapy is taken by mouth or injected into a vein. When given this way, the drugs enter the bloodstream to reach cancer cells throughout the body.

Sources: injected

The way the chemotherapy is given depends on the type of soft tissue sarcoma being treated. Some types of soft tissue sarcoma may respond to treatment with chemotherapy.

Sources: respond

Chemotherapy that may be used alone or in combination includes:

Other chemotherapy drugs not listed here may also be used.

Learn more about how chemotherapy works, how it is given, common side effects, and more at Chemotherapy to Treat Cancer.

Sources: Chemotherapy to Treat Cancer

Observation is closely monitoring a person's condition without giving any treatment until signs or symptoms appear or change. Observation may be done when:

Observation may be used for epithelioid hemangioendothelioma, infantile fibrosarcoma, or PEComa.

Sources: epithelioid hemangioendothelioma · infantile fibrosarcoma · PEComa

Targeted therapy uses drugs or other substances to block the action of specific enzymes, proteins, and other molecules involved in the growth and spread of cancer cells. Targeted therapies used to treat soft tissue sarcoma include:

Learn more about Targeted Therapy to Treat Cancer.

Sources: Targeted Therapy to Treat Cancer

Immunotherapy is a treatment that uses the person's immune system to fight cancer. Pembrolizumab may be used to treat undifferentiated pleomorphic sarcoma (malignant fibrous histiocytoma) and progressive and recurrent soft tissue sarcoma.

Learn more about Immunotherapy to Treat Cancer.

Sources: Immunotherapy to Treat Cancer

For some children, joining a clinical trial may be an option. There are different types of clinical trials for childhood cancer. For example, a treatment trial tests new treatments or new ways of using current treatments. Supportive care and palliative care trials look at ways to improve quality of life, especially for those who have side effects from cancer and its treatment.

You can use the clinical trial search to find NCI-supported cancer clinical trials accepting participants. The search allows you to filter trials based on the type of cancer, your child's age, and where the trials are being done. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

Sources: clinical trial search · ClinicalTrials.gov

Learn more about clinical trials, including how to find and join one, at Clinical Trials Information for Patients and Caregivers.

Sources: Clinical Trials Information for Patients and Caregivers

To learn about the treatments listed below, visit Types of treatment for childhood soft tissue sarcoma.

Sources: Types of treatment for childhood soft tissue sarcoma

Treatment of newly diagnosed epithelioid hemangioendothelioma may include:

Sources: epithelioid hemangioendothelioma

Treatment of newly diagnosed angiosarcoma may include:

Sources: angiosarcoma

Treatment of newly diagnosed extraskeletal osteosarcoma is surgery to completely remove the tumor, followed by chemotherapy.

Sources: extraskeletal osteosarcoma

Learn more at Osteosarcoma Treatment.

Sources: Osteosarcoma Treatment

Treatment of newly diagnosed extraskeletal mesenchymal chondrosarcoma may include:

Sources: extraskeletal mesenchymal chondrosarcoma

Treatment of newly diagnosed liposarcoma may include:

Sources: liposarcoma

Treatment of newly diagnosed dermatofibrosarcoma protuberans may include:

Sources: dermatofibrosarcoma protuberans

Treatment of newly diagnosed infantile fibrosarcoma may include:

Sources: infantile fibrosarcoma

Treatment of adult-type newly diagnosed fibrosarcoma is surgery to completely remove the tumor, when possible.

Sources: fibrosarcoma

Treatment of newly diagnosed myxofibrosarcoma is surgery to completely remove the tumor.

Sources: myxofibrosarcoma

Treatment of newly diagnosed low-grade fibromyxoid sarcoma is surgery to completely remove the tumor.

Sources: low-grade fibromyxoid sarcoma

Treatment of newly diagnosed infantile hemangiopericytoma is usually chemotherapy.

Sources: infantile hemangiopericytoma

Learn more at Childhood Rhabdomyosarcoma Treatment.

Sources: Childhood Rhabdomyosarcoma Treatment

Treatment of newly diagnosed ectomesenchymoma may include:

Sources: ectomesenchymoma

Treatment of newly diagnosed plexiform fibrohistiocytic tumor is surgery to completely remove the tumor.

Sources: plexiform fibrohistiocytic tumor

Other summaries with information related to Carney complex include:

Sources: Carney complex

Treatment of newly diagnosed epithelioid sarcoma may include:

Sources: epithelioid sarcoma

Treatment of newly diagnosed extraskeletal myxoid chondrosarcoma may include:

Sources: extraskeletal myxoid chondrosarcoma

Learn more at Ewing Sarcoma Treatment.

Sources: Ewing Sarcoma Treatment

Treatment of newly diagnosed perivascular epithelioid cell tumors may include:

Sources: perivascular epithelioid cell tumors

Treatment of newly diagnosed undifferentiated pleomorphic sarcoma may include surgery. Treatment of recurrent or refractory undifferentiated pleomorphic sarcoma may include immunotherapy (pembrolizumab).

Sources: pembrolizumab

Learn more about the treatment of malignant fibrous histiocytoma of bone at Osteosarcoma Treatment.

Sources: malignant fibrous histiocytoma · Osteosarcoma Treatment

Treatment of childhood soft tissue sarcoma that has spread to other parts of the body at diagnosis is chemotherapy and radiation therapy. Surgery may be done to remove tumors that have spread to the lung.

To learn more about the treatment of specific tumor types, visit Treatment of Childhood Soft Tissue Sarcoma.

Sources: Treatment of Childhood Soft Tissue Sarcoma

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

Sources: clinical trial search · General information

To learn about the treatments listed below, visit Types of treatment for childhood soft tissue sarcoma.

Sources: Types of treatment for childhood soft tissue sarcoma

Treatment of progressive or recurrent childhood soft tissue sarcoma may include:

Sources: progressive · recurrent

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

Sources: clinical trial search · General information

Cancer treatments can cause side effects. Which side effects your child might have depends on the type of treatment they receive, the dose, and how their body reacts. Talk with your child's treatment team about which side effects to look for and ways to manage them.

To learn more about side effects that begin during treatment for cancer, visit Side Effects.

Sources: Side Effects

Problems from cancer treatment that begin 6 months or later after treatment and continue for months or years are called late effects. Late effects of cancer treatment may include:

Some late effects may be treated or controlled. It is important to talk with your child's doctors about the effects cancer treatment can have on your child. Learn more about Late Effects of Treatment for Childhood Cancer.

Sources: Late Effects of Treatment for Childhood Cancer