Soft tissue sarcoma and rare soft tissue tumours – Brief information

Soft tissue sarcomas are malignancies originating in soft tissues such as muscles, joints, fibrous and nerve tissue. This text provides information about the characteristics of this disease group, its frequencies, causes, symptoms, diagnosis, treatment, and prognosis.

Author:  Maria Yiallouros, Dr. med. Stefanie Kube, erstellt am 2009/05/19, Editor:  Maria Yiallouros, Reviewer:  Prof. Dr. med. Ewa Koscielniak, PD Dr. med. Monika Sparber-Sauer, English Translation:  Dr. med. habil. Gesche Tallen, Last modification:  2022/09/29 DOI: 10.1591/poh.patinfo.weichteiltumor.kurz.20101215

General information on the disease

The term soft tissue sarcomas (also called malignant soft tissue tumours) includes a variety of very different malignant diseases that occur in muscles, ligaments, joints or nerve tissue. They all share having developed from a malignant transformation (degeneration) of immature precursor cells of soft tis-sues.

Soft tissues, however, include very different tissue types such as muscles, fatty and connective tissues as well as nerve tissues. Therefore, different types of soft tissue sarcomas and rare 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.

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 appropri-ately. 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 sarcomas and rare soft tissue tumours account for about 6 % 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 sarcoma / tumour each year. More than half of these patients present with rhabdomyosarcoma, the most frequent soft tissue sarcoma in childhood and adolescence.

Soft tissue sarcomas or 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: 1.3 : 1). However, both age distribution and gender ratio differ very much depending on the type of soft tissue sarcoma.

Tumour types

There are more than 20 different types of soft tissue sarcomas as well as multiple variants of soft tissue tumours.

The most frequent soft tissue sarcomas in children and adolecents under 18 years of age are:

  • rhabdomyosarcoma (RMS): 61 %
  • extraosseal tumours of the Ewing-group [extraosseal Ewing sarcoma (eEWS) / peripheral primitive neuroectodermal tumour (pPNET)]: 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.

Soft tissue sarcomas are divided into three large groups:

  • rhabdomyosarcomas (RMS)
  • non-rhabdomyosarcoma soft tissue sarcomas (NRSTS)
  • rare soft tissue tumours

Note: until recently, the „Cooperative Weichteilsarkom-Studiengruppe (CWS, German for „Cooperative Soft Tissue Sarcoma Study Group“) of the Society for Paediatric Oncology and Haematology (GPOH) differentiated an additional group based on their clinical behaviour and treatment approach: the so-called rhabdomyosarcoma-like soft tissue sarcomas. The tumours that were assigned to this group (extraosseal tumours of the Ewing group, synovial sarcomas and undifferentiated sarcomas) are now included in the NRSTS group.

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

Rhabdomyosarcoma (RMS)

For a long time, rhabdomyosarcomas (RMS) were divided into two major groups based on their microscopic (histological) appearance: embryonal RMS (eRMS) and alveolar RMS (aRMS). Aside from their different histological features, they also show different characteristics regarding their growth pattern (localization, extent, spread) as well as regarding age distribution and prognosis: embryonal RMS affect particularly 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 (although many different fusions have been identified as of today), whereas RMS lacking this specific PAX-FOXO gene fusion are called fusion-negative. However, in the meantime, additional alterations have been identified that can be associated with high malignancy of the so-called fusion-negative RMS.

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.

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. These tumours may also develop in adults and are therefore also known as „adult type NRSTS“ among specialists. NRSTS also include those tumours that were previously called “rhabdomyosarcoma-like soft tissue sarcomas” by the CWS Study Group (the extraosseal tumours of the Ewing group, the synovial sarcomas and the undifferentiated sarcomas), based on their chemosensitivity that is similar to that of RMS, as is the treatment.

Rare tumours

Rare soft tissue tumours (frequent or benign) are myofibromatosis, desmoid-type fibromatosis (DTF), inflammatory myofibroblastic tumour (IMT), gastro-intestinal stromal tumour (GIST) and many more.

Localisation and spread

Soft tissue sarcomas and rare 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 de-tach from the 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 (metastases). 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 sarcomas and rare 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. In general, alveolar rhabdomyosarcomas (or “fusion-positive RMS”, respectively) show a far more aggressive behaviour compared to embryonal rhabdomyosarcomas, meaning that they grow and spread much faster via the blood and/or lymph stream. Also, alveolar rhabdomyosarcomas are associated with a higher risk of recurrent disease than embryonal rhabdomyosarcomas.

Extraossear tumours of the Ewing group (including extraossear Ewing sarcomas and peripheral primitive neuroectodermal tumours) – which, according to their naming, grow outside any body tissue – mostly develop in the area of the trunc and extremities. 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 sarcomas and rare 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 sarcoma 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 sarcoma. 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 presdisposition 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, neurofibromatose, the Beckwith-Wiedemann syndrome, the Li-Fraumeni syndrome, the Gorlin-Goltz and the Werner syndrome.

Also, there are indications that certain external factors increase the risk to develop soft tissue sarcoma. These include radiation of the unborn (for example by x-rays or radiotherapy 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).

For most patients with soft tissue sarcoma or a rare soft tissue tumour, no risk factors have been identified yet.

Symptoms

The symptoms of patients with soft tissue sarcoma 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 sarcomas/-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 sarcoma/-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 sarcomas/-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 sarcomas or 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 sarcoma 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 sarcoma, 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 sarcoma or 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 sarcoma / 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 imaging

Apart from comprehensive medical history taking (anamnesis) and physical exam, imaging procedures – preferably a magnetic resonance imaging (MRI) with and without contrast agent – play a major role in soft tissue sarcoma / 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 hemangioma, 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 osteosarcoma and, once confirmed, to determine the subtype. For this, a very comprehensive characterization of soft tissue sarcomas 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 CWS Study Group of the GPOH in Bonn. The diagnosis is further confirmed by an additional molecular genetic analysis promoting superior tumour characterization, thereby providing relevant directions for the treatment.

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 and may be used for research aiming at treatment optimisation of these tumours.

Tests to assess spread of disease (staging)

Once the diagnosis of soft tissue sarcoma / 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 most metastases develop in the lungs, a chest x-ray as well as a computed tomography (CT) of the chest are indispensable. In addition, a magnetic resonance tomography (MRI) is performed to assess or, respectively, rule out metastases in the abdominal and pelvic region or the brain.

For all high-grade malignant soft tissue sarcomas (G3 sarcomas), a bone marrow puncture is done to rule out bone marrow involvement. 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 cerebrospinal fluid when dealing with skull base or spinal tumours), a total body MRI and/or a positron emission tomography (PET).

The positron emission tomography with 18-fluorodeoxyglucose (FDG-PET) is meanwhile increasingly used – combined with MRI (PET-MRI) or CT (PET-CT) – for children and adolescents with suspected metastases. Its advantage is that, aside from bone, it can also detect soft tissue metastases. So far, PET has not been established in every treatment centre, and its benefits for soft tissue sarcomas are still being examined.

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), a hearing test (audiometry), 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.

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 (there are 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 radiotherapy.
  • The patient’s age is also considered for the decision with regard to chemo- 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.

Patients with rhabdomyosarcoma are –– depending on whether their prognosis has been considered to be favourable or less favourable – assigned to different risk groups during therapy planning (low-risk group, standard-risk group, high-risk group), thus being treated according to different treatment plans. In Germany and other European countries, the differentiation according to risk groups with associated treatment plans is carried out according to the recommendations of the „European pediatric Soft tissue Sarcoma Study Group“ (EpSSG) and the „Cooperative Weichteilsarkom Studiengruppe“ (CWS Study Group).

Treatment

Treatment of children and adolescents with soft tissue sarcoma or soft tissue tumourshould 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 iis 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, chemotherapy 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 (see chapter „Treatment planning“ above). Since treatment of soft tissue sarcomas 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.

Chemotherapy

Chemotherapy includes treatment with agents (so-called cytostatic agents), 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 for rhabdomyosarcomas are, for example, actinomycin D (also known as dactinomycin), vincristine, cyclophosphamide, ifosfamide and doxorubicin (= adriamycin), in case of insufficient treatment response or in high-risk patients other agents, too. 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, 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 CWS study centre and the CWS reference experts will help the local caregiver team with decision-making regarding the treatment approaches for individual patients. For certain patient groups with rhabdomyosarcoma, the optimal treatment design will be evaluated in the framework of a new study (FaR-RMS).

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.

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. 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

Radiotherapy 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 sarcoma/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 radiotherapy. 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, 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.

Treatment of patients with rhabdomyosarcoma (RMS)

According to the currently valid guideline of the “Cooperative Weichteilsarkom-Studiengruppe” (CWS Guidance), patients with rhabdomyosarcoma (RMS) are divided into four different risk groups: one low-risk group, one standard-risk group and two high-risk groups. Patients with metastasized RMS currently receive a separate therapy according to CWS-Guidance (see chapter „Treatment of RMS patients with metastases or relapse“). The upcoming European treatment guideline (ERN Guidance) is considering one instead of two high-risk groups. In contrast to CWS Guidance, this one high-risk group will also include treatment of patients with metastasized RMS.

Treatment for the different risk groups is as follows:

  • Low-risk group: for the low-risk group, 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: in the standard-risk group, surgery and chemotherapy are also done; the latter includes, aside from vincristine and actinomycin D, additionally ifosfamide, and most patients also receive radiotherapy (time of therapy about 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. Chemotherapy includes ifosfamide, vincristine, actinomycin D, and sometimes doxorubicin (adriamycin) and takes about 25 weeks. As mentioned above, RMS patients with metastases will be included in the one high-risk group according to the ERN Guidance in the future.

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 extraosseal tumours of the Ewing group, the synovial sarcomas and the undifferentiated sarcomas. Patients with these tumour types (also called “RMS-like soft tissue sarcomas” in the past) are treated quite similarly to high-risk patients with RMS (see chapter „Treatment of patients with rhabdomyosarcoma“). The treatment takes about 25 weeks, depending on the therapy group. The extraosseal Ewing sarcoma is internationally often treated like a Ewing sarcoma of the bone.

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. New treatment options are currently tested for patients with these tumours, mainly in the framework of new trials. 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 metastases or relapse

According to the current CWS Guidance and the upcoming European ERN Guidance, patients with metastatic disease of rhabdomyosarcoma receive chemotherapy. Local treatment (radiotherapy, surgery) plays an important role.

According to the current CWS Guidance and the upcoming European ERN Guidance, patients with metastatic disease of rhabdomyosarcoma receive chemotherapy. Local treatment (radiotherapy, surgery) plays an important role. These are either given as pills (orally) or intravenously once a week, so that treatment can almost exclusively be done on an outpatient basis. Total duration of therapy takes about one year; the upcoming trial FaR-RMS is testing the efficacy of an extended maintenance to up to 24 months. In general, an oral-only maintenance therapy as per CWS Guidance with the agents trofosfamide and etoposide (in short: O-TIE) is also an option; in this case, treatment will take about a year or even longer in individual situations.

Patients with a particularly unfavourable prognosis can participate in so-called experimental trials. Your caregiver team will inform you whether one of those experimental treatment approaches is an option for your child. For patients whose disease does not respond to chemotherapy or with a recurrent disease, treatment is based on the frontline therapy. Usually, different and partially new agents are given that are not necessarily part of the standard treatment plans, but allow hope based on most recent research results.

Therapy optimising trials and registries

In the large paediatriac treatment centres, children and adolescents with a soft tissue sarcoma or 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 carried out within „therapy optimising trials“. These are controlled clinical trials, which have been developed, are monitored and continuously adjusted to the most recent research by the Society of Paediatric Oncology and Haematology (“Gesellschaft für Pädiatrische Onkologie und Hämatologie“, GPOH‎).

For patients who are not being treated within a trial (such as the upcoming trial FaR-RMS), there is a registry („SoTiSaR / opening 01.01.2023 SoTiSAR 2.0“) to collect all relevant patient data. These patients receive the currently recommended standard treatment, so far as per CWS Guidance, in the future as per ERN Guidance for patients with rhabdomyosarcoma. The opening of a new trial for patients with rhabdomyosarcoma or relapsed rhabdomyosarcoma is considered for the beginning of 2023 (FaR-RMS).

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

Prognosis

Prognosis for children and adolescents with a soft tissue sarcoma or a rare 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 sarcomas or rare soft tissue tumour has improved drastically due to standardised treatment based on treatment optimising studies. At the end of the 70s, still only 30 to 40 % of all children survived, while the 10-year survival rate is now a bit over 70 % due to continuous treatment optimisation.

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.

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. Please ask the doctor, who is responsible for your child, for competent information on the individual prognosis

References

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