Internal Medicine

Ewing sarcoma

All information given here is only of a general nature, tumor therapy always belongs in the hands of an experienced oncologist!

Synonyms

Bone sarcoma, PNET (primitive neuroectodermal tumor), Askin tumor, Ewing - bone sarcoma

English: Ewing´s sarcoma

definition

In which Ewing sarcoma it is a from Bone marrow outgoing Bone tumorthat can occur between the ages of 10 and 30. However, it mainly affects children and young people up to the age of 15. Ewing's sarcoma is less common than that Osteosarcoma.

Ewing's sarcoma is localized in the long ones Long bones (Femur (Thigh bone) and Tibia (Shin)), as well as in the pelvis or ribs. In principle, however, all bones of the trunk and limb skeleton can be affected, metastasis especially in the Lungs is possible.

frequency

The probability of developing Ewing sarcomas is <1: 1,000,000. Studies have shown that for every million people who live there, about 0.6 new patients develop Ewing sarcomas every year.

Compared with osteosarcoma (approx. 11%) and chondrosarcoma (approx. 6%), Ewing's sarcoma is in third place as another representative of primary malignant bone tumors. While Ewing's sarcoma occurs mainly between the ages of 10 and 30, a main manifestation could be established in the second decade of life (15 years of age). It is therefore mainly manifested in the growing skeleton, with boys (56%) suffering from Ewing sarcoma slightly more often than girls. If one compares the primary malignant bone tumors of children and adolescents, Ewing sarcoma is in second place: In childhood bone sarcomas, the proportion of so-called osteosarcomas is around 60%, the proportion of Ewing sarcomas around 25%. .

causes

As has already been explained and presented in the context of the summary, the cause that is responsible for the development of the Ewing sarcoma can not be fully clarified. It was found, however, that Ewing sarcomas often occur when there are familial skeletal abnormalities or patients under one from birth Retinoblastoma (= malignant retinal tumor occurring in adolescence). Research has shown that tumor cells in the so-called family of Ewing sarcomas have a change Chromosome # 22 exhibit. It is believed that this mutation is present in around 95% of all patients.

localization

The most common locations of Ewing's sarcoma can be found in the long tubular bones, especially in the tibia and fibula, or in flat bones. Nevertheless, as a malignant bone cancer, Ewing's sarcoma can affect all bones. The larger bones are most frequently affected, the smaller ones rarely. If the long tubular bones are affected, the tumor is usually found in the area of the so-called diaphysis, the shaft area.

Preferred locations:

approx. 30% femur (thigh bone)
approx. 12% tibia (shin)
approx. 10% humerus (upper arm bone)
approx. 9% basin
approx. 8% fibula (fibula).

Because of the severe haematogenic metastasis that occurs early on (see following section), localization in the soft tissues is also conceivable.

Localization in the pelvis

Ewing's sarcoma is localized in the pelvic bone as the primary tumor (site of origin of the tumor) in only about every fifth case. Much more often, however, the primary tumor is located in a long tubular bone.
The first symptoms can be swelling, pain and overheating in the pelvic area.

Localization in the foot

The foot is a rare location in a primary tumor. It is more common that primary tumors from the tibia or fibula favor a metastasis in the foot.
If there is an unclear painful swelling and overheating of the foot, especially in adolescence, Ewing's sarcoma should also be excluded in addition to juvenile arthritis. The worst does not necessarily have to be assumed here. Targeted diagnostics in the form of imaging can provide initial clarity about the causes of the complaints.

metastasis

As mentioned above, this applies Ewing's sarcoma as early hematogenous (= via the bloodstream) metastasizing. Metastases can therefore also settle in the soft tissue. Of these, primarily is the lung affected. However, the skeleton can also be affected by metastases via the bloodstream.

The fact that Ewing's sarcoma is to be classified as early metastatic has been proven by studies that show that metastases can be detected in around 25% of all cases at the time of diagnosis. Since metastases unfortunately cannot always be discovered, the dark rate is likely to be much higher.

diagnosis

Ewing sarcomas can cause a variety of symptoms. They should be listed below:

Pain of unknown cause
Swelling and usually pain in the affected region (s)
Swelling of the lymph nodes
local signs of inflammation (redness, swelling, overheating)
unwanted weight loss
Functional restrictions up to paralysis
Fracture without an accident event
Night sweats
moderate leukocytosis (= increase in the number of leukocytes in the blood)
decreased performance

A tumor can be ruled out with sufficient probability if the following criteria are met according to clinical, imaging and laboratory diagnostics:

There is no evidence of a mass
or

The visible swelling, the proven mass or unclear complaints can be clearly explained and documented by a non-tumorous disease.

Basic diagnostics:

In principle, imaging methods are used for basic diagnostics. these are
X-ray examination
X-ray examination in the area of the tumor localization (at least 2 levels)

Sonography
Sonography of the tumor (especially if a soft tissue tumor is suspected in the differential diagnosis)

In order to obtain additional information and to enable differential diagnostic delimitations, laboratory diagnostics (examination of laboratory values) is used. The following values are determined as part of this laboratory diagnostics:

Blood count
Iron (because decreased in tumors)
Electrolytes (to rule out hypercalcemia)
ESR (sedimentation rate)
CRP (C-reactive protein)
alkaline phosphatase (aP)
bone specific (AP)
Acid phosphatase (sP)
Prostate Specific Antigen (PSA)
Uric acid (HRS): increased with high cell turnover, e.g. in hemoblastosis
Total protein: decreased in consuming processes
Protein electrophoresis
Urine status: paraproteins - evidence of myeloma (plasmacytoma)
Tumor marker NSE = neuron-specific enolase in Ewing's sarcoma

Special tumor diagnostics

Magnetic resonance imaging (MRI)

In addition to the imaging methods mentioned in the context of basic diagnostics, magnetic resonance tomography is another option that can be used in individual cases.

Using MRI (magnetic resonance tomography), the soft tissue can be shown particularly well, whereby the tumor expansion to neighboring structures (nerves, vessels) of affected bones can be shown. Furthermore, the tumor volume can be estimated using MRI (magnetic resonance tomography) and the local extent of the tumor can be clarified.

As soon as a malignant bone tumor is suspected, the entire tumor-bearing bone should be imaged in order to exclude metastases (malignant settlements).

Computed Tomography (CT):
(especially for showing hard (cortical) bone structures)

Positron Emission Tomography (PET)
(Value not yet sufficiently valid)

Read more on the topic: Positron emission tomography

Digital subtraction angiography (DSA) or angiography to visualize the tumor vessels

Skeletal scintigraphy (3-phase scintigraphy)

biopsy
As mentioned several times above, the distinction between Ewing sarcoma and osteomyelitis, for example, can be quite difficult.In addition to the fact that the symptoms are similar, the X-ray as such cannot always provide direct information. If, after the so-called non-invasive diagnostics described above, there is still suspicion of a tumor or if there is uncertainty about the type and dignity of a tumor, a histopathological examination (= tissue examination) should be carried out.

Open procedures

Incisional biopsy

As part of the so-called incisional biopsy, the tumor is partially surgically exposed. Finally, a tissue sample is taken (if possible bone and soft tissue). The removed tumor tissue can be assessed directly.

Excisional biopsy (complete tumor removal)

It is only considered in exceptional cases, for example if there is a suspicion of malignancy (change from benign to malignant tumor) of smaller osteochondromas.

therapy

The therapeutic approach here is usually on several levels. On the one hand, the so-called therapy plan usually provides for chemotherapeutic treatment preoperatively (= neoadjuvant chemotherapy). Even after the surgical removal of Ewing's sarcoma, therapeutic follow-up treatment is provided through radiation therapy and, if necessary, renewed chemotherapy. Here a difference to osteosarcoma becomes noticeable: Compared to Ewing sarcoma, osteosarcoma has a lower radiation sensitivity.

Therapy goals:
A so-called curative (healing) therapeutic approach is given especially in patients whose Ewing sarcoma is localized and does not show any metastases. In the meantime, so-called neoadjuvant chemotherapy in combination with surgery and radiation therapy opens up further opportunities. If the Ewing sarcoma metastasizes outside of the lungs (= generalized tumor disease; extrapulmonary metastases), the therapy usually has a palliative (life-prolonging) character (see below).

Therapy modalities:
local:

preoperative chemotherapy
surgical therapy (wide or radical resection after Enneking)
radiotherapy

Systemic:
antineoplastic chemotherapy

Combination therapy (primarily (= "first line"): doxorubicin, ifosfamide, Methotrexate / Leukovorin, cisplatin; in the second line (= "second line"): etoposide and carboplatin)
(Protocols can change at short notice)

Curative therapy:

aggressive multi-substance chemotherapy pre- and postoperatively
Local treatment in the form of a surgical tumor resection or radiation alone
Supplement the therapy with Pre-irradiation (for example in the case of inoperable tumors, non-responders) or through post-irradiation
It is important to mention in the context of surgical therapy that, not least because of the further development of surgical methods, interventions that preserve extremities are possible in many cases. However, the prospect of a cure always has top priority, so that the focus should always be on radicality (= oncological quality) and not on possible loss of function.
The chemotherapy can then be continued (see above). One then speaks of a so-called consolidation.
In patients with lung metastases, additional interventions in the area of the lungs, such as partial removal of the lungs, may be necessary.

Palliative (life-prolonging) therapy:
Patients who have a generalized tumor disease (= extrapulmonary metastases) should locate the primary tumor on the trunk and / or the primary tumor proves to be inoperable. In such cases, only palliative therapy is usually possible. In such cases, the focus is usually on maintaining quality of life, so that the therapy focuses on pain relief and maintenance of function.

forecast

Whether or not recurrences occur is strongly dependent on the extent of metastasis, the response to preoperative chemotherapy and the "radical nature" of the tumor removal. It is currently believed that the five-year survival rate is around 50%. The operational improvements in particular have made it possible to improve the probability of survival over the past 25 years

The survival rate decreases with primary metastases. Here the survival rate is around 35%.

Chances of recovery

As with other cancers, the chances of recovery from Ewing's sarcoma are initially to be viewed as individually different, because statistics only ever show the average recovery and survival rates.
The chances of recovery are increased if the tumor can be completely removed surgically. Before this, chemotherapy should be done to shrink the tumor. After the tumor has been surgically removed, further chemotherapy should be carried out in order to kill any remaining tumor cells.
If the tumor cannot be completely removed surgically, the chances of recovery are much worse. Follow-up treatment with chemotherapy should also take place here.
A tumor that cannot be operated on should definitely be irradiated.
In general, it can be said that the prospect of a cure for Ewing's sarcoma is poorer if metastases are already present at the time of diagnosis. This means that the tumor has spread and is growing elsewhere in the body as well.

Survival rate

Survival rates in general are given in medicine as the statistical value of the “5-year survival rate”. This indicates in percent how large the number of survivors is after 5 years in a defined patient group. The reported survival rate for Ewing's sarcoma lies in a range between 40% and 60-70%. These broad areas result from the fact that the survival rate depends on the infestation of the respective bone region. For example, if the bones of the arms and / or legs are affected, the 5-year survival rate is 60-70%. If the pelvic bones are affected, it is 40%.

How high is the risk of relapse?

The 5-year survival rate averages 50%. Here one can assume that it is an aggressive and malignant cancer. The 5-year survival rate says that on average half of all diagnosed Ewing sarcomas lead to death.
However, if no further findings can be detected after 5 years after successful treatment of Ewing's sarcoma, it is said that the cancer is cured.

Aftercare

Recommendations:

in year 1 and 2:
A clinical examination should be carried out every three months. As a rule, a local X-ray check, laboratory tests, a CT of the thorax and a full-body skeletal scintigraphy performed. A local MRI is usually done once every six months.
in year 3 to 5:
A clinical examination should be carried out every six months. As a rule, a local X-ray check, laboratory tests, a CT of the thorax and a full-body skeletal scintigraphy performed. A local MRI is usually performed once a year.
From year 6 onwards, the following usually takes place once a year:
an X-ray check with laboratory examination and a CT of the chest as well as a whole-body skeletal scintigraphy and a local MRI.

Summary

The disease (Ewing sarcoma) got its name from the first description by James Ewing in 1921. These are highly malignant tumors that arise from degenerate primitive neuroectodermal cells (= immature precursor cells of nerve cells). Thus, Ewing sarcomas belong to the primitive, malignant, solid tumors.

As mentioned above, Ewing's sarcomas mainly affect the middle areas of the long tubular bones and the pelvis, but an affliction of the upper arm (= humerus) or the ribs is also conceivable, so that parallels to the osteosarcoma appear. Due to the accompanying signs of inflammation, confusion with osteomyelitis is possible.

Due to metastases that occur very quickly (approx. ¼ of all patients already show so-called daughter settlements at the time of diagnosis), Ewing sarcomas can also be found in soft tissue, similar to rhabdomyosarcomas. The lungs are usually most affected by metastasis.
The causes that could be held responsible for the development of Ewing's sarcoma are still unknown. However, it is currently assumed that neither the genetic component (heredity) nor radiation therapy that has already been carried out can be held responsible for the development. It was found, however, that Ewing sarcomas often occur when there are familial skeletal abnormalities or when patients suffer from retinoblastoma (= malignant retinal tumor occurring in adolescence) from birth. Research has shown that tumor cells of the so-called family of Ewing sarcomas show a change on chromosome number 22. It is assumed that this mutation (genetic change) is present in around 95% of all patients.

Ewing sarcomas can cause swelling and pain in the affected region (s), which can also be associated with functional impairments. Fever and moderate leukocytosis (= increase in the number of leukocytes in the blood) are also conceivable. Due to the possibility of confusion with osteomyelite, for example (see above), a diagnosis is not always easy and therefore, in addition to the imaging procedures (X-ray examination), a biopsy (= tissue examination of a tissue sample) may be necessary.

The therapeutic approach here is usually on several levels. On the one hand, the so-called therapy plan usually provides for chemotherapeutic treatment preoperatively (= neoadjuvant chemotherapy). Even after the surgical removal of Ewing's sarcoma, therapeutic follow-up treatment is provided through radiation therapy and, if necessary, renewed chemotherapy. Here a difference to osteosarcoma becomes noticeable: Compared to Ewing sarcoma, osteosarcoma has a lower radiation sensitivity.

Whether or not recurrences (renewed tumor growth) occur depends heavily on the extent of metastasis, the response to preoperative chemotherapy and the "radical nature" of the tumor removal. It is currently believed that the five-year survival rate is around 50%. The operational improvements in particular have made it possible to improve the probability of survival over the past 25 years