Soft tissue sarcomas and rare soft tissue tumours – Brief information

Author:  Maria Yiallouros, Editor:  Maria Yiallouros, Reviewer:  PD Dr. med. Monika Sparber-Sauer, English Translation:  Dr. med. Gesche Riabowol (nee Tallen), Last modification: 2026/06/23 https://dx.doi.org/10.1591/poh.patinfo.weichteiltumor.kurz.20101215

General information on the disease

The term soft tissue tumours includes a variety of very different diseases that all share having developed due to a malignant transformation (degeneration) of immature precursor cells of soft tissue‎s.

Soft tissues, however, include different tissue types such as muscles, fatty and connective tissues as well as blood vessels and tissue of the peripheral nervous system‎. Therefore, different types of soft tissue tumours exist. They differ with regard to their histological‎ structure and the type of cell‎s they arise from, and they also have different frequencies and biological behaviour. This means, for example, that they present with different growth rates and spread patterns (metastasis), or respond to treatment, such as chemotherapy‎, differently.

Soft tissue tumours can be benign, malignant or medium-grade (intermediate-grade) malignant. Usually, malignant soft tissue tumours are called soft tissue sarcomas; the term “soft tissue tumour” is rather neutral and refers to any type of tumour behaviour. “Soft tissue tumours“ and "soft tissue sarcomas“ summarize at least 150 different histological tumour types (entities).

Most soft tissue sarcomas are highly malignant; they grow and spread rapidly and, hence, are lethal within a few weeks or months, if not treated appropriately. The majority of the less frequent soft tissue tumours, however, is of intermediate malignancy or partially even benign. The growth pattern of these tumours varies; they can do both, spontaneously regress or locally grow very aggressively.

Incidence

Soft tissue tumours account for about 5.4 % of all malignant diseases in childhood and adolescence, thereby representing one of the most frequent solid tumour‎ types in this age group, following tumours of the central nervous system‎ (CNS tumours, brain tumours). According to the German Childhood Cancer Registry (Mainz), about 10 out of 1,000,000 (a total of approximately 125) children and adolescents between 0 and 17 years are diagnosed with a soft tissue tumour each year. More than half of these patients present with rhabdomyosarcoma‎, the most frequent soft tissue sarcoma in childhood and adolescence.

Soft tissue tumours are most frequent in children younger than five or six years of age. The average age at diagnosis is 8.5 years. Boys are slightly more affected than girls (gender ratio: 1.2:1). However, both age distribution and gender ratio differ very much depending on the type of soft tissue tumour.

The most frequent soft tissue sarcomas – that is to say, malignant soft tissue tumours – in children and adolecents under 18 years of age are:

• rhabdomyosarcoma (RMS): 61 %
• extraosseal tumours of the Ewing-group: 16 %
• synovial sarcoma (SySa): 7 %
• fibrosarcoma (FS): etwa 3 %
• leiomyosarcoma (LMS): etwa 2 %
• undifferenciated sarcomas (UDS): 2 %

All other soft tissue sarcomas are rather rare in childhood and adolescence.

Tumour types

There are multiple variants of soft tissue tumours, including more than 20 different types of soft tissue sarcomas.

As per currently valid clinical classification, soft tissue tumours are divided into three large groups:

1. rhabdomyosarcomas (RMS)
2. non-rhabdomyosarcoma soft tissue sarcomas (NRSTS)
3. rare soft tissue tumours

In addition, there are also soft-tissue Ewing sarcoma‎s – that is, Ewing sarcomas that arise outside the bone (extraosseous). According to the WHO‎, these “extraosseous tumors of the Ewing group” belong to the overall group of Ewing sarcomas and are now generally treated according to the treatment protocols of the Ewing Study Group. For information on Ewing sarcoma please see here.

The following paragraphs will provide more information on the three groups of soft tissue sarcomas.

1. Rhabdomyosarcoma (RMS)

For a long time, rhabdomyosarcoma‎s (RMS) have been divided into two major groups based on their microscopic (histological) appearance: embryonal RMS (ERMS) and alveolar RMS (ARMS). Aside from their different histological‎ features, the two RMS types usually also show different characteristics regarding their growth pattern (localisation, extent, spread) as well as regarding age distribution and prognosis: embryonal RMS particularly affect children under 10 years of age and are mostly associated with a favourable outcome when compared to alveolar RMS, the incidence of which increases in children older than 10 years.

It is well-known by now that the course of the disease is mainly impacted by the molecular genetic‎ characteristics of the tumour cells. Hence, there are genetic alterations, so-called fusion genes, whose presence is associated with an unfavourable prognosis‎. This is, for example, the case for a typical fusion in the PAX-FOXO gene, which can be found in the majority of alveolar RMS (but not in embryonal RMS); the affected ARMS are also called fusion-positive RMS, whereas RMS lacking this specific PAX-FOXO gene fusion are called fusion-negative. However, in the meantime, additional alterations have been identified that can cause high malignancy in fusion-negative RMS, too.

Important to know: Today, RMS are not primarily assessed based on their histological features, but rather on the presence or lack of genetic‎ alterations. Genetic characterization of the tumours therefore plays a major role when assessing the probability of survival and choosing the appropriate treatment approach.

2. Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS)

The non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) represent a rather heterogenous group of soft tissue sarcomas, which differ regarding multiple aspects, such as their growth behaviour, sensitivity to chemotherapy (chemosensitivity) and outcomes.

For example, alveolar soft tissue sarcoma, epitheloid sarcoma, malignant peripheral nerve sheath tumour, fibrosarcoma and leiomyosarcoma all belong to the group of NRSTS. Since these tumours may develop in adults, too, they are also known as "adult type NRSTS“. NRSTS meanwhile also include synovial sarcomas and undifferentiated sarcomas; previously, due to their sensitivity to chemotherapy and treatment similar to that of rhabdomyosarcomas, they were classified as “RMS-like” (rhabdomyosarcoma-like) and assigned to a separate group.

3. Rare tumours

The group of the "rare soft tissue tumours” includes tumour types with malignant, medium-grade (intermediate) malignant or benign biological behaviour. Due to their extreme rarity, they are summarized, despite of their different growth patterns and degrees of malignancies. Rare soft tissue tumours are myofibromatosis, desmoid-type fibromatosis (DTF), inflammatory myofibroblastic tumour (IMT), gastrointestinal stromal tumour (GIST) and many more. Based on the tumour type, there are individual treatment concepts for each of these rare diseases.

Location and spread

Soft tissue tumours may generally develop anywhere in the human body, since there is soft tissue everywhere. The tumours usually spread along certain anatomical structures, for example along muscle sheaths, ligaments or blood vessels. In the course of this, single cells may detach from the primary tumour‎ and spread to other body sites via the blood and/or lymph stream. They can settle there and start multiplying again; daughter tumours are developing (metastasis‎). Metastases of soft tissue sarcomas particularly occur in the lungs, in adjacent lymph nodes‎ and in the bones. Other organs can be affected as well.

Origin and growth behaviour of soft tissue tumours are strongly associated with the tumour type.

Rhabdomyosarcomas, for example, can generally develop in almost every organ, however, most frequently, they are found in the head-and-neck area, the urinary tract and reproductive organs as well as the extremities. Usually, fusion-positive alveolar rhabdomyosarcomas (ARMS) show a more aggressive behaviour compared to embryonal rhabdomyosarcomas (ERMS), meaning that they frequently grow and spread faster via the blood and/or lymph stream. Also, fusion-positive ARMS are associated with a higher risk of recurrent disease than most ERMS.

Synovial sarcomas occur most frequently close to joints in the extremities as well as in the head-and-neck area. All these tumour types tend to metastasize early. About 20 % of patients with a soft tissue sarcoma present with distant metastases already at the time of diagnosis.

Causes

The causes for the development of soft tissue tumours are not completely understood as of today. The assumption is that they originate from precursor cells of the connective tissue (soft tissue). In medical jargon, these cells are called "mesenchymal stem cells‎“. The malignant transformation is most certainly initiated by genetic‎ and/or chromosomal aberrations in these cells.

Different genetic and chromosomal aberrations have already been identified in the malignantly transformed cells, however, these happen to be quite heterogenous, do vary depending on the type of soft tissue tumour and are not regularly found in all tumours after all. Overall, multiple genetic alterations are most certainly responsible for the development of a soft tissue tumour. According to current research, most patients do not have any hereditary predisposition.

However, there are families presenting with high incidences of rhabdomyosarcoma in multiple generations. Also, children present with rhabdomyosarcoma more frequently in families with a frequent history of carcinoma‎. These observations indicate that those patients have a genetic predisposition to develop this disease, a so-called cancer predisposition syndrome‎ (CPS). These are complex diseases which are characterized by various kinds of developmental abnormalities and an elevated inherited risk to develop cancer. Cancer predisposition syndromes that are known to play a role in the development of a soft tissue tumour are, for example, neurofibromatosis‎, the Beckwith-Wiedemann syndrome‎, the Li-Fraumeni syndrome‎, the Gorlin-Goltz syndrome‎, the DICER1 syndrome‎, and the Werner`s syndrome‎.

Also, there are indications that certain external factors increase the risk to develop soft tissue tumour. These include radiation exposure‎ of the unborn (for example by X-rays‎ or radiation therapy‎ received by the mother), alcohol or other parental drug abuse prior to or during pregnancy, respectively, as well as early radiotherapy of the child. Associations with viral infection‎s have been reported as well. Hence, HIV‎-positive, thus immunosuppressed children have an increased risk of developing leiomyosarcoma following an infection with the Epstein-Barr virus‎ (EBV).

All patients with rhabdomyosarcoma should nowadays be tested for a genetic predisposition syndrome.

Symptoms

The symptoms of patients with soft tissue tumour depend on the site and the extent of the tumour and are therefore quite diverse. To name only a few of the frequent, representative symptoms here:

• Soft tissue tumours developing close to the surface often cause a continuously increasing swelling and/or pain. Both are not infrequently wrongly referred to as, for example, exercise-induced trauma. Also, they may cause a dysfunction of the affected organ, such as limited range of motion in arms and legs.
• A soft tissue tumour of the orbita may initially present with a painless bulging of the eye anteriorly out of the orbit (exophthalmus‎) and a swelling of the eyelid; later it usually causes pain because of the increased local pressure. Vision impairment is also possible.
• Soft tissue tumours of the nose are often associated with a long history of congestion or sniffle at the timepoint of diagnosis.
• In case the skull base is involved, cranial nerve impairments may occur, which present as facial nerve palsy or double vision.
• Tumours of the urinary tract and reproductive organs may present with general malaise, constipation and/or impaired urination, vaginal bleeds, blood in the urine and pain, however, usually once the tumour is already quite large

As for other parts of the body, soft tissue tumours are often getting noticed only because of their palpable or visible tumour mass, for example during a routine physical exam at the paediatrician or by imaging‎ diagnostics such as an ultrasound‎. They often do not cause any complaints, meaning that the patients feel good.

Children and adolescents with complaints as described above do, of course, not always necessarily have soft tissue tumour or any other malignant tumour. Nevertheless, it is strongly recommended to have the cause of such symptom‎s be evaluated by an experienced paediatrician.

Good to know: in case of suspected soft tissue tumour, the paediatrician should refer the patient to a treatment centre that is specialized on cancer in children and adolescents (paediatric oncology / haematology program). Initial diagnostic tests (imaging procedures or biopsy, respectively) that are done elsewhere often turn out insufficient and, thus, may negatively impact appropriate treatment and also the patient’s prognosis (chance of cure).

Diagnosis

If the doctor thinks that the young patient’s history and physical exam are suspicious of a soft tissue tumour, the child should immediately be referred to a hospital with a childhood cancer program (paediatric oncology unit), where further diagnostics can be initiated and performed by childhood cancer professionals. Very close collaboration between various specialists (such as paediatric oncologist‎s, paediatric surgeons, paediatric radiologist‎s, to name a few) is required both to find out whether the patient really suffers from a soft tissue tumour and, if so, to determine the tumour type and the extension of the disease.

Knowing these details is absolutely essential for optimal treatment planning and prognosis‎. Diagnostic management follows the European guidelines as well as the trial recommendations of the “Soft Tissue Sarcoma Study Group" of the Society of Paediatric Oncology and Haematology (GPOH‎ STS Study Group) and the "European pediatric Soft tissue Sarcoma Study Group“ (EpSSG), the latter of which is the merger of the European study groups.

Diagnostic imaging

Apart from comprehensive medical history taking (anamnesis‎) and physical examination‎, imaging‎ procedures – preferably a magnetic resonance imaging‎ (MRI) with and without contrast agent‎ – play a major role in soft tissue tumour diagnostics. First of all, they serve to assess or rule out a tumour. Also, the localization, size and volume of a tumour as well as its demarcation with regard to adjacent tissue (such as organs, blood vessels and nerves) or any tumour-induced changes of the bone system can be diagnosed by such imaging techniques very well.

Tissue extraction (biopsy) to confirm diagnosis

For final confirmation of the diagnosis, tumour tissue is required to be removed (biopsy), even if the tumour may be benign (as is the case with a lipoma‎ or haemangioma‎, for example). The biopsy‎ should only be performed by doctors who are specialized in surgery of sarcomas.

The obtained samples are subsequently analysed histological‎ly, immunohistochemical‎ly and genetic‎ally by specialists, with molecular genetic‎ tests becoming more and more important. The analyses serve to confirm the diagnosis of a soft tissue tumour and, once confirmed, to determine the subtype. For this, a very comprehensive characterization of soft tissue tumours will be available soon, which will make individualized (meaning tailored) therapies for single patients possible. Hence, analysis and research on tumour tissue is crucial.

Since the disease is overall rare, the obtained tissue samples should not only be studied by the local pathologist‎, but should also be sent to a reference centre for paediatric pathology – such as the reference pathologist of the Soft Tissue Sarcoma Study Group of the GPOH‎ (GPOH-STS-Study Group) in Bonn. Such a centre receives tissue samples of a certain tumours from all over Germany and therefore provides special experience with the assessment. The diagnosis is further confirmed by an additional molecular genetic analysis promoting superior tumour characterization, thereby providing relevant directions for the treatment. In many cases, however, research into unknown factors is still needed to gain a better understanding of these tumours.

Note: For molecular genetic analysis, fresh frozen tumour tissue is implicitly required. Therefore, it is crucial that the biopsy is taken in a centre that is specialized in paediatric oncology, where both the expertise and the facilities to process the tumour samples are adequately given. Remaining samples will be stored in the tumour bank (now biobank) and may be used for research aiming at treatment optimisation of these tumours. For more information on tumour banking see additional page on registries and studies of the GPOH-STS Study Center.

Tests to assess spread of disease (staging)

Once the diagnosis of "soft tissue sarcoma" or "(intermediate) malignant soft tissue tumour" has been confirmed, further tests are required to find out if and to which extent the cancer has spread and which organs are involved. Since especially soft tissue sarcomas predominantly develop metastases in the lungs [see metastasis‎], a chest X-ray examination‎ as well as a computed tomography‎ (CT) of the chest are indispensable.

In addition, a magnetic resonance imaging‎ (MRI) and also a positron emission tomography‎ with 18-fluorodeoxyglucose (FDG-PET) are performed to assess or, respectively, rule out metastases in the abdominal and pelvic region or the brain. PET is always combined with a MRI (PET-MRI) or CT (PET-CT) scan and, in accordance with ESCP guidelines (ESCP stands for ‘European Standard Clinical Practice’) and radiology guidelines, is currently being used increasingly in children and adolescents where metastases are suspected. The advantage is that it can detect not only soft-tissue metastases but also bone metastases.

For all high-grade malignant soft tissue sarcomas (G3 sarcomas), a bone marrow puncture‎ is done as a standard to rule out bone marrow‎ involvement. According to current data, a bone marrow aspiration is not necessary if the PET scan clearly shows bone or bone marrow involvement. This is taken into account in clinical trials (in particular the FaR-RMS trial, see chapter “Trials and registries”).

Depending on the disease and treatment situation, additional tests to diagnose and/or further assess metastases may be done, such as an ultrasoun‎d or a lumbar puncture‎ (to analyze the Ultraschall‎cerebrospinal fluid when dealing with skull base or spinal tumours), and/or a total body MRI‎.

Tests before treatment begins

Before treatment begins, further tests are needed in order to assess the condition of different organs. Therefore, the doctors will recommend an electrocardiography‎ (ECG) as well as an ultrasound of the heart (echocardiography‎), an electroencephalography‎ (EEC), a hearing test (such as audiometry‎, BERA hearing test‎ and/or otoacoustic emissions‎), special diagnostics for determining kidney and lung functions as well as various blood tests. Any changes occurring during the course of treatment can be assessed and managed better based on the results of those initial tests, which thus help to keep the risk of certain treatment-related side effects as low as possible.

Good to know: Not all the tests listed above need to be done for every patient. Contrariwise, the patient’s individual situation may require additional diagnostic procedures that have not been mentioned in this chapter. Therefore, you should always ask your doctor, based on the information above, which test your child needs and why.

Treatment planning

After the diagnosis has been confirmed and the spread of the disease has been assessed, therapy is planned. In order to design a highly individual, risk-adapted treatment regimen for the patient, certain individual factors influencing the patient’s prognosis‎ (called risk factors or prognostic factors‎) are being considered before and during treatment (risk-adapted treatment strategy).

Important prognostic factors are, for example, the type, the localisation, size and spread of the tumour. In addition, the patient’s age has an impact on treatment planning.

• The type of the tumour (meaning its fine tissue features (histology‎) and genetic‎ characteristics) impacts, amongst other factors, how fast the tumour grows and how the disease will respond to chemotherapy‎ or another kind of systemic‎ therapy (such as “new agent therapies”): there are, for example, chemosensitive and chemoinsensitive soft tissue sarcomas. The tumour type also impacts the risk of metastasis‎ and the probability of relapse. Experts accordingly differentiate between soft tissue sarcomas with favourable and with unfavourable histology or genetics, respectively (see also chapter “Tumour types”).
• The site, size and extent of the tumour (including potential lymph node involvement and metastases) determine the options of surgical tumour removal and radiation therapy‎ (radiotherapy).
• The patient’s age is also considered for the decision with regard to systemic and/or radiotherapy. Hence, younger patients usually tolerate chemotherapy better than older children. For children under the age of three years (in particular under one year), radiotherapy is only rarely given, but still an option in individual cases.

All these factors are included in treatment planning in order to achieve the best outcome possible for each patient, while keeping the risks of side effects and long-term sequelae as low as possible.

Good to know: As a rule, patients are assigned to different risk groups depending on their prognosis and are treated according to different treatment plans (see also chapter “Treatment of patients with rhabdomyosarcoma”). In Germany and other European countries, the classification into risk groups, each with its own associated treatment plan, is carried out in accordance with the recommendations of the “European Paediatric Soft Tissue Sarcoma Study Group” (EpSSG) and the “Soft Tissue Sarcoma Study Group” of the GPOH (GPOH-STS).

Treatment

Treatment of children and adolescents with soft tissue tumour should take place in a children's hospital with a paediatric oncology program. Only such a childhood cancer centre provides highly experienced and qualified staff (doctors, nurses and many more), since they are specialised and focussed on the diagnostics and treatment of children and teenagers with cancer according to the most advanced treatment concepts. The doctors in these centres collaborate closely with each other. Together, they treat their patients according to treatment plans (protocols) that are continuously optimised.

The goal of treatment is to eliminate the cancer while keeping the risk of side effects and late sequelae as low as possible.

Treatment methods

Treatment options for children and adolescents with soft tissue sarcomas or rare soft tissue tumours include surgery, radiotherapy, systemic therapy (such as chemotherapy or a so-called “new agent” therapy) or a combination of those, respectively.

Individual treatment (meaning which types of therapy to be applied and in which order) depends in particular on the microscopical and molecular genetic‎ tumour type, the localisation of the tumour, as well as on the patient’s age. Treatment is also adapted to the extent of the tumour as well as to its surgical accessibility and sensitivity to chemotherapy or any other systemic therapy (see chapter "Treatment planning“ above).

Since the treatment of soft tissue tumours can be associated with side effects, supportive treatment measures (supportive therapy‎) are also applied to prevent and/or treat these side effects. Here your will find further information on supportive care as well as on recommendations for home, the latter of which may be helpful during or after chemo- and radiotherapy.

The following information outlines the standard treatment options recommended in accordance with guidelines and international consensus recommendations (see also the chapters on diagnosis and treatment planning).

Chemotherapy

Chemotherapy includes treatment with agents (so-called cytostatic agents or cytostatics‎), which inhibit cell growth, thereby contributing to eliminating the tumour and potentially existent metastases. In order to eliminate as many of the cancer cells as possible (even those that cannot be detected by diagnostic imaging techniques such as magnetic resonance imaging‎), a combination of cell and, thus, tumour growth inhibiting agents that have proven to be efficient in treating soft tissue sarcomas/tumours are used.

Frequently-used agents are, for example, vincristine, actinomycin D (also known as dactinomycin), cyclophosphamide and ifosfamide, in case of insufficient treatment response or in high-risk patients often doxorubicin (= adriamycin) and, if necessary, other agents as well. The combination of agents as well as their dosages and the duration of treatment vary depending on treatment or risk group. The cytostatic agents are given in multiple chemotherapy‎ cycles with treatment pauses in between, which serve the patient’s recovery.

Local therapy

In addition to chemotherapy and/or other systemic treatment (see “New-agent therapy” below), local tumour control is provided by surgery‎ and sometimes radiotherapy‎. Surgical tumour removal may be performed both prior and after chemotherapy (primary or late resection, respectively), a potentially necessary radiotherapy either prior or after surgery (pre- or postoperative radiation). The GPOH-STS study centre and their reference experts will help the local caregiver team with decision-making regarding the treatment approaches for individual patients (where possible, the patient should be treated as part of a GPOH-STS study or registered in the registry).

Note regarding trial FaR-RMS: The study is currently investigating, amongst other things, the optimal se-quence of local treatment measures for patients with rhabdomyosarcoma (see chapters on the treatment of RMS patients as well as on trials and registries).

Surgery

Surgery aims at complete tumour removal. Hence, it is frequently scheduled later in the treatment plan, in fact, after the tumour volume has been decreased by chemotherapy (experts call this "late resection“). This particularly applies to soft tissue sarcomas that are known to be very responsive to chemotherapy, which hence allows to expect tumour shrinkage. These tumours include rhabdomyosarcomas and some other tumours behaving like RMS (such as synovial sarcomas and undifferentiated sarcomas).

Surgery as the first treatment choice (primary tumour resection) is usually per-formed only when, based on diagnostic imaging results, total gross tumour resection is possible without damaging healthy tissue. This is limited to very small tumours with favourable location. For patients with tumours less responsive to chemotherapy, primary surgery may also be an option as long as it is doable.

Surgery is carefully planned in the local treatment centre by representatives of all participating disciplines (paediatric oncologist‎s, surgeons, radiotherapists, radiologist‎s). The CWS study centre and the CWS reference expert group are standing by for advice. Since soft tissue sarcomas are rare, surgical treatments should only be performed in a centre with long-standing sarcoma experience.

Radiotherapy

Radiation therapy is done using energy-rich, electromagnetic‎ radiation, given through the skin to the tumour region. Radiation causes DNA‎ damage in tumour cells, thereby leading to cell death.

Radiotherapy is a very efficient treatment method for patients with eventually remaining soft tissue tumour tissue following surgery. It is a particularly favourable approach when surgery is not an option, for example for patients with rabdomyosarcoma in the head and neck area. Also, patients with a site-associated high risk of tumour spread (for example patients with rhabdomyosarcoma close to the meninges‎ or inside the orbita) should receive radiation therapy‎. Patients with rhabdomyosarcoma (RMS) or a non-RMS-like soft tissue sarcoma (NRSTS) whose tumour could be resected completely by primary surgery do not require radiotherapy.

The radiation dose is calculated based on the tumour type, its localisation and extent, its response to chemotherapy as well as its surgical resectability. Conventional treatment uses total radiation doses of about 40-50 gray‎ (Gy), given in single daily doses of 1.8-2 Gy. For individual cases, modern radiation techniques such as the so-called intensity-modulated radiotherapy‎ (IMRT) may be favourable. For certain tumour sites or age groups, proton therapy‎ is increasingly used.

New therapy options – "new agent“ therapies

The term “new-agent“ therapy summarizes new types of systemic‎ therapies (system therapies). These include targeted treatments with new agents that work in a different way compared to chemotherapy. These include substances which, in the presence of very specific genetic‎ alterations in tumour cells (such as an NRTK or ALK genetic alteration), can be used as inhibitor‎s. NRTK and ALK inhibitors are now approved for use in children and adolescents with certain conditions. However, there are a number of promising agents which, in children and adolescents, can so far only be used as part of individual treatment approaches or within clinical trials (see note on this below).

Example: An already licensed targeted therapy for soft tissue tumours is the use of the NTRK-inhibitor Larotrectinib for patients with a so-called NTRK-positive infantile fibrosarcoma (a non-rhabdomyosarcoma-like soft tissue sarcoma, NRSTS). These patients have a NTRK gene fusion (NTRK is the abbreviation for neurotrophic tyrosine receptor kinase), which can be inhibited by Larotrectinib. The agent is the treatment of choice for metastatic disease and is even an option for tumours that are not surgically resectable. However, since data regarding length of treatment, development of resistance‎ and long-term sequelae are still limited, the use of this agent versus the option of chemotherapy requires careful consideration. Children with this disease have been treated with chemotherapy and surgery for many years and show excellent prognosis.

Note: Future studies using these kinds of agents are being planned. Participation in clinical trials enables the effects and side effects of these medicines to be accurately recorded. For this reason, children and adolescents should, wherever possible, always receive such new active substances within the framework of clinical trials. In general, treatment within the context of clinical trials should always be given preference over any individualized treatment regimen. Only in this way can valid data be acquired that will serve to optimise future therapies.

Treatment of patients with rhabdomyosarcoma (RMS)

In Germany and other European countries, patients with rhabdomyosarcoma (RMS) are treated according to international guidelines for RMS (ESCP / ERN guideline / AWMF guideline), provided that no other treatment is planned as part of a study (currently FaR-RMS).

Depending on the patient’s risk factors, rhabdomyosarcoma are divided into four different risk groups: one low-risk group, one standard-risk group and two high-risk groups (“high-risk“ and “very high risk“, or HR and VHR for short). The intensity of treatment varies accordingly and also differs to some extent even within a single risk group.

Treatment for the different risk groups is as follows:

• Low-risk group: For patients with a low risk of relapse, treatment consists of total gross tumour resection and a chemotherapy with the agents vincristine and actinomycin D (dactinomycin) for about 22 weeks.
• Standard-risk group: For standard-risk patients, surgery and chemotherapy are also done. However, in addition to vincristine and actinomycin D (VA), this regimen also includes ifosfamide (IVA) in varying combinations. A total of nine cycles of chemotherapy are administered. Patients with residual tumour receive more intensive treatment than those without residual tumour, either in the form of higher-dose chemotherapy or adjuvant radiotherapy (treatment duration approximately 25 weeks). .
• High-risk groups: In both high-risk groups, surgical tumour removal is planned either prior to chemotherapy or later, depending on the site and extent of the tumour. All patients in these groups receive radiotherapy.
• a) Group “high risk”: For patients at high risk of relapse, chemotherapy consists of at least nine cycles of ifosfamide, vincristine and actinomycin (IVA) over a period of approximately 25 weeks. This is followed by approximately six months of maintenance therapy with vinorelbine and cyclophosphamide; this therapy phase consists of six chemotherapy cycles, each lasting four weeks.
• b) Group “very high risk”: In patients at very high risk of relapse, with lymph node or distant metastases, chemotherapy (total duration 25 weeks) is further intensified with an additional drug: doxorubicin is administered (IVADo) in addition to ifosfamide, vincristine and actinomycin. This is followed by twelve cycles of maintenance therapy. The highest-risk group also includes patients whose disease has relapsed (see chapter “Treatment of patients with recurrent diseases” below).

• Low-risk group: For patients with a low risk of relapse, treatment consists of total gross tumour resection and a chemotherapy with the agents vincristine and actinomycin D (abbreviated to VA) for about 22 weeks.
• Standard-risk group: For standard-risk patients, surgery and chemotherapy are also done. However, in addition to vincristine and actinomycin D (VA), this regimen also includes ifosfamide (IVA) in varying combinations. A total of nine cycles of chemotherapy are administered. Patients with residual tumour receive more intensive treatment than those without residual tumour, either in the form of higher-dose chemotherapy or adjuvant radiotherapy (treatment duration approximately 25 weeks).
• High-risk groups: In both high-risk groups, surgical tumour removal is planned either prior to chemotherapy or later, depending on the site and extent of the tumour. All patients in these groups receive radiotherapy.
• a) Group “high risk”: For patients at high risk of relapse, chemotherapy consists of at least nine cycles of ifosfamide, vincristine and actinomycin (IVA) over a period of approximately 25 weeks. This is followed by approximately six months of maintenance therapy with vinorelbine and cyclophosphamide; this therapy phase consists of six chemotherapy cycles, each lasting four weeks.
• b) Group “very high risk”: In patients at very high risk of relapse, with lymph node or distant metastases, chemotherapy (total duration 25 weeks) is further intensified with an additional drug: doxorubicin is administered (IVADo) in addition to ifosfamide, vincristine and actinomycin. This is followed by twelve cycles of maintenance therapy. The highest-risk group also includes patients whose disease has relapsed (see chapter “Treatment of patients with re-current diseases” below).

Note on the high-risk groups in the FaR-RMS trial: Within the framework of the FaR-RMS study, the respective standard treatment is being compared with a new treatment option in both high-risk groups:

“High-risk“ group: Here, standard chemotherapy (IVA) is being compared with a treatment comprising IVA plus irinotecan. The study is also investigating whether extending maintenance therapy by a further six cycles (to twelve cycles) can improve patients’ prognosis.

“Very high-risk“ group: The study is investigating whether standard therapy with doxorubicin (IVADo) can be replaced by a regimen consisting of IVA plus irinotecan. The use of doxorubicin is controversial, as it can have serious long-term effects. Furthermore, the study is investigating whether extending the current maintenance therapy from twelve cycles to a total of 24 cycles leads to better outcomes.

Treatment of patients with non-RMS soft tissue sarcoma (NRSTS)

The wide variety of tumours in the group of non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) is not only mirrored by their growth pattern, malignancy, operability and chemosensitivity; it also impacts the type of treatment to be considered for the individual patient:

There are NRSTS that are about as chemosensitive as rhabdomyosarcomas, for example the synovial sarcomas and the undifferentiated sarcomas. Patients with these tumour types are treated in accordance with the current ESCP/ERN guidelines. The current standard treatment involves ifosfamide and doxorubicin and lasts approximately 25 weeks, depending on the therapy group.

A large group of the rare NRSTS, the so-called "adult-type“ NRSTS (named that way because they also appear in adults) are often not chemosensitive. For patients with these tumours, new, personalised treatment options may in some cases (depending on the type of tumour) be used and/or tested in the framework of clinical trials (see chapter “New agent therapy” above). Some other of these rare NRSTS are rather benign; treatment in this case involves mainly a so-called extended resection, which is defined by surgical removal of the tumour with a certain safety distance, meaning removal of adjacent tissue surrounding the tumour. For some patients with NRSTS, the type of treatment also depends on the size of the tumour and the success of surgery.

Important to know: the treatment spectrum for this inhomogenous disease group is quite large, and new treatment options are being tested. Your caregiver team will explain to you, which therapy options exist for you/your child.

Treatment of patients with rare soft tissue tumours

Treatment of patients with a rare (frequently intermediate malignant or benign) soft tissue tumour mainly depends on its growth pattern. For tumours growing locally very aggressively (this can be the case for both benign and intermediate malignant tumours), surgery aiming at tumour removal is not always the first choice of treatment. For most of these tumours, the doctors will wait and see whether growth is ongoing, since spontaneous tumour regression is possible as well. If this does not happen or if the localisation of the tumour jeopardizes adjacent organs, a low-dose chemotherapy, depending on the tumor type, is indicated. By now, even newer, so-called targeted therapies (that consider the individual genetic alterations) are an option as well.

Treatment of RMS patients with recurrent disease

Patients who experience a relapse (recurrence‎) or progression of the disease during treatment have a particularly poor prognosis‎. The standard chemotherapy regimen for recurrent RMS involves the administration of the cytostatics‎ vincristine, irinotecan and temozolomide. (Replacing temozolomide with regorafenib did not show any improvement in prognosis in the FaR-RMS trial.) Due to the generally very poor prognosis, affected patients may take part in clinical trials (so-called phase I/II trials). If such experimental treatment approaches are an option for your child, your treatment team will inform you accordingly.

For example, there is a phase I/II vaccine trial (PerVision) for patients with fusion-positive sarcoma‎. The trial is investigating whether targeted vaccination‎ can prevent a recurrence of the sarcoma. The treating doctor will assess whether a patient is eligible for inclusion in the PerVision vaccine trial.

Therapy trials and registries

In the large paediatriac treatment centres, children and adolescents with a soft tissue tumour receive therapy according to standardised treatment plans (protocols). These protocols are designed by experts and aim at steadily improving the patients’ survival rates while also reducing the risk of therapy-related late effects. Therapy according to such treatment protocols is usually carried out within controlled clinical trials, which are developed, monitored and regularly updated in line with the current state of scientific knowledge, either within the framework of the Society of Paediatric Oncology and Haematology (“Gesellschaft für Pädiatrische Onkologie und Hämatologie“, GPOH‎‎) or at European level.

For patients who are not being treated as part of a clinical trial – either because no trial was available at the time of their diagnosis or because they do not meet the inclusion criteria for an existing trial – a registry is available for recording all relevant patient data. However, these days, even patients receiving treatment within the framework of clinical trials are recorded in the registry with a limited set of data and, particularly at the end of a trial, are transferred to a registry wherever possible so that long-term effects and late complications can be recorded. To ensure the best possible treatment, the study group (with international participation) draws up detailed recommendations and advises treating doctors on selecting the most appropriate treatment for each individual patient.

In Germany, the following trials and registries are currently available for patients with soft tissue tumours:

• Trial FaR-RMS: In April 2025, the international, multicentre FaR-RMS trial (phases I and III) for children, adolescents and young adults with a first-time diagnosis or relapse of rhabdomyosarcoma (RMS) was launched at the first centre in Germany. Among other things, the trial is investigating whether new chemotherapy regimens and an extension of maintenance therapy can improve the chances of cure in high-risk patients. Various radiotherapy options are also to be compared with one another. Numerous treatment centres in Europe and beyond are participating in the trial. The national study coordination is based at the University Children’s Hospital in Tübingen, under the direction of Prof. Dr. med. Monika Sparber-Sauer.
• Registry SoTiSaR 2.0-NIS: Since the end of 2024, the registry has been recording all children, adolescents and young adults with soft tissue sarcomas and other soft tissue tumours; it replaces the CWS-SoTiSaR registry, which was closed at the end of 2025. Patients included in the SoTiSaR 2.0-NIS registry who are not being treated as part of a clinical trial receive, depending on the type of soft tissue tumour (RMS, NRSTS, rare soft tissue tumour), the respective standard treatment based on European guidelines / consensus recommendations (ESCP guidelines for patients with rhabdomyosarcoma or NRSTS). The registry is headed by Prof. Dr Monika Sparber-Sauer (Olgahospital, Stuttgart) and Prof. Dr Martin Ebinger (University Children’s Hospital, Tübingen).

For further information on above-mentioned registries and guidelines, please see here. Details are available on the website of the CWS Study Group: https://www.klinikum-stuttgart.de/cws/home

Prognosis

Prognosis for children and adolescents with a soft tissue tumour depends on multiple factors. Most relevant are the type, localisation and size of the tumour, its spread, operability (resectability) and the patient’s age.

Over the past four decades, prognosis‎ for patients with soft tissue tumour has improved drastically due to standardised treatment based on therapy optimising trial‎s. At the end of the 70s, still only 30 to 40 % of all children survived, while the 10-year survival rate is now around 70 % due to continuous treatment optimisation (see note below).

In favourable constellations, long-term survival can be observed in over 80 % of patients, while the chance of long-term cure decreases for patients with large, inoperable tumours at diagnosis. Similar, even more unfavourable outcomes have been reported for patients presenting with lymph node‎ involvement and/or spread into other body sites at the time of diagnosis. For example, for patients with a metastasis‎ed RMS-like soft tissue sarcoma, the 5-year-survival rate is currently 30 %. Various studies aim at improving the prognosis for these patients as well.

Important note: The above-mentioned numbers are statistical values. Therefore, they only provide information on the total cohort of patients with these types of tumour. They do not predict individual outcomes. It should also be noted that soft tissue tumours constitute a highly heterogeneous group of diseases, meaning that general figures, such as those mentioned above, are not particularly meaningful. Please ask the doctor, who is responsible for your child, for competent information on the individual prognosis

Brief information on soft tissue sarcomas and soft tissue tumours (532KB)
Author: Maria Yiallouros
23/06/2026