Ewing’s sarcoma is a malignant tumor of bone tissue, which occurs mainly in children and young people aged 10-20 years. Ewing’s osteogenic sarcoma mainly affects long bones of limbs, although it can occur in any other bones (including flat ones).
Primary malignant bone tumors make up 5% of all childhood oncological diseases. Ewing’s sarcoma is the second most common bone tumor in this age group. Ewing’s sarcoma, although rare, can occur in infants as well as in elderly. The neoplasm affects men more often than women.
Ewing’s sarcoma is a serious malignant disease with a serious prognosis, but with timely diagnostics and competent comprehensive therapy, it is completely curable. It is extremely important to entrust the life and health of a patient with Ewing’s sarcoma in hands of an experienced specialist who will help to overcome this serious disease successfully. These are doctors who work in Pediatric Oncology Department of Tel Aviv Medical Clinic. Most of them have repeatedly trained at the best pediatric oncology centers in USA and Europe, so they have unique experience in managing such complicated patients and professional skills in dealing with children with cancer.
All medical and diagnostic procedures are prescribed by our specialists according to modern world protocols and clinical recommendations. Along with this, the approach to each child is individual. Developing a therapy scheme, oncologist does not use one template for everyone, but takes into account all the smallest features of patient and his illness.
An important advantage of Ewing’s sarcoma treating in TAMC is a multidisciplinary approach. One child with such a pathology is assisted by a whole team of narrow specialists: oncologists, orthopedists, traumatologists, surgeons, plastic surgeons, neurosurgeons, pediatricians, radiation therapists, chemotherapists, rehabilitators, physical therapists, psychologists and other specialists if necessary.
Causes of Ewing’s sarcoma in children
The exact causes that provoke Ewing’s sarcoma development have not yet been established. But there are several factors that can increase the risk of cancer developing.
Risk factors for bone tumor development:
- Genetic predisposition. If family members or close relatives are diagnosed with the disease, developmental risk of this oncology type increases significantly.
- As a result of injury. More than half of patients developed Ewing’s sarcoma after bone fractures.
- Congenital anomalies of bone structure. Congenital bone diseases (for example, bone enchondroma) significantly increase the risk of malignant neoplasm development.
- Genetic abnormalities during intrauterine development.
Genetic changes in patients with tumors of Ewing’s sarcoma family are by their nature chromosomal translocations that include Ewing’s sarcoma gene (EWS) on the 22nd chromosome. 18 different structural translocations with different types of hybrid genes associated with tumors development of Ewing sarcoma group were identified. More often, Ewing’s sarcoma occurs in people with a translocation between chromosomes 11 and 22, which leads to origination of a pathological protein called EWS-FLI13. This fact is actively used in molecular genetic diagnosis of tumors and confirms the diagnosis, which allows to avoid incorrect diagnosis and ineffective treatment.
Symptoms of Ewing’s sarcoma in children
The first sign that most often makes patients seek medical help is pain in a malignant tumor location. Ewing’s sarcoma is characterized by increased pain felt at night, which excludes the possibility of an inflammatory process. Anaesthetics do not help relieve pain.
Common symptoms of Ewing’s sarcoma:
- movement restriction in the joint located next to the tumor;
- appearance of noticeable deformation (bumps) in a certain area of skeleton;
- pain during palpation at the site of the lesion;
- local skin redness over affected area;
- increased tendency to fractures, pathological fractures development;
- an increase in temperature (both locally at the site of lesion and general fever);
- loss of appetite, rapid satiety during meals;
- general weakness, body ache;
- fast fatigue;
- rapid weight loss;
- anemia.
Specific symptoms may arise due to peculiarities of neoplasm location: sarcoma in lower extremities may lead to lameness and impaired gait development; sarcoma in chest becomes the cause of breathing disorders and can cause respiratory failure; when the hip joints are affected in the late stages of the disease, there is a violation of their motor function.
Diagnostic methods of Ewing’s sarcoma
The earlier the diagnosis is established, the more chances there are for a complete cure without negative health consequences. TAMC uses only modern diagnostic equipment of an expert class, thanks to which the diagnostic process becomes surprisingly comfortable and accurate.
An important sign of the disease is severe pain at the site of tumor development. As a rule, patients go to a traumatologist for an initial consultation. The reason for suspecting an oncological lesion of bone is pain that passes when the lesion is fixed and intensifies at night.
Diagnosing methods of Ewing’s sarcoma:
- Radiography. X-ray examination of affected area allows to exclude a bone injury. Also, X-ray images clearly reflect tissue changes that occur as a result of oncological bone damage.
- CT and/or MRI. These are the most accurate methods of visualization of soft tissues and bone structures. Layered scanning allows us to clearly and in detail consider tumor size, identify the boundaries and assess of oncological process spread to nearby tissues. CT and MRI are safe for body and painless procedures allowed for diagnostics of oncological diseases in children. The high accuracy of image makes it possible to detect regional and distant metastases.
- PET-CT or PET-MRI. Positron emission tomography is intended for metastases detection in bone marrow and internal organs.
- Biopsy. Tissues from bone marrow canal or tumor tissues are taken for research. The procedure allows us to determine tumor nature, its features and develop a further treatment plan.
We send all materials after biopsy for revision to the best histological laboratories in Israel. Thanks to such thorough checks, we are absolutely sure of diagnosis correctness and the next selected treatment tactics.
Molecular genetic studies can detect a translocation associated with an oncoprotein of any type, EWS-FLI1 or CD 99.
The final diagnosis is made mainly based on the results of tumor material biopsy. A sample of affected tissue is obtained by an incision without puncture needle application. This method provides a sufficient amount of material for pathohistological research and necessary molecular genetic research.
Foundation One and Caris Molecular Testing test systems are an example of innovative molecular genetic diagnostics for Ewing’s sarcoma. These tests allow to find certain types of mutations in malignant cells, as well as presence of specific receptor molecules on the surface of these cells. Such information can be used in future to create individual medications of immunobiological therapy or to select drugs with a targeted effect.
On the basis of obtained data about tumor location, its size and spread, metastases presence, and tumor cells characteristics based on biopsy results, oncologist forms a final diagnosis with an indication of process stage. In accordance with this diagnosis, an individual scheme of complex treatment is developed, based on modern therapy protocols and individual characteristics of patient and his disease.
Prognosis for Ewing’s sarcoma in children
The prognosis for Ewing sarcoma depends on several factors:
- Tumor size and location.
- Age and gender of the patient.
- Tumor spread and the stage of disease at which it was detected.
- Tumor response to modern treatment protocols.
- This is the primary process or relapse.
Patients with a localized Ewing’s tumor, which can be completely removed surgically, have a 5-year survival rate of over 70%. In patients with metastatic disease, in whom the tumor has spread to distant parts of the body at the time of diagnosis, the 5-year survival rate is 15–30%.
Ewing’s sarcoma modern treatment
Treatment of Ewing’s sarcoma includes various combinations of surgery, chemotherapy and radiation therapy (complex approach). Currently, more than 60% of patients with primary localized Ewing’s sarcoma can be cured using such a comprehensive approach. In some cases, radical treatment is possible even in metastases presence.
Chemotherapy is one of the main methods of treatment for Ewing’s sarcoma. The action of the method is based on intravenous administration of combined cytostatic drugs, under the influence of which neoplasm size significantly decreases, which facilitates surgical intervention and improves the prognosis. In postoperative period, the reception of special antitumor drugs is continued to prevent relapse and metastasis.
The number of chemotherapy courses depends on sarcoma stage and the degree of its spread, on average, treatment lasts up to 12 months. Chemotherapy treatment of patients with Ewing’s sarcoma is carried out according to the world standard protocols AEWS 1031 and EURO-W.W.I.NG. 99. Also, patients are often given auxiliary drugs that allow them to cope with negative consequences of polychyotherapy.
The standard protocol of AEWS 1031 includesapplication of following antitumor drugs: vincristine, doxorubicin, cyclophosphamide, infosfamide, etoposide. Standard protocol EURO-W.W.I.N.G. 99 includes the use of the following antitumor drugs: vincristine, infosfamide, doxorubicin, etoposide.
Then, patients with localized disease receive anti-relapse chemotherapy courses according to VAI protocol (vincristine, actinomycin, ifosfamide) for 8 courses.
If timely diagnosis was carried out and primary tumor did not reach large sizes, the use of high-dose chemotherapy is inappropriate. In case of an initial large tumor, high-dose chemotherapy is mandatory. The next step in treatment may be a bone marrow transplantation, as a rule, autologous (the patient is transplanted with stem hematopoietic cells prepared before treatment start). High-dose chemotherapy is also prescribed for recurrence of Ewing’s sarcoma, providing an intensive effect on tumor and metastases.
Radiation therapy consists in impact of ionizing radiation on tumor location, if no metastases were detected during the diagnosis. Radiation therapy is used in several stages:
- before surgical intervention for effective growth retardation and reduction in neoplasm diameter;
- after surgical treatment to reduce the likelihood of tumor recurrence;
- as a palliative treatment for an inoperable neoplasm or for multiple metastases (to reduce symptoms and improve quality of life).
Radiation therapy may be prescribed together with chemotherapy for complex treatment. Conducting therapy courses requires careful and detailed planning. Before prescribing radiation therapy to patient, X-ray or MRI is performed to accurately determine the lesions.
To reduce the side effects of radiation therapy, TAMC specialists use modern types of radiation therapy, in particular, radiation therapy with modulated radiation intensity (IMRT). This method of cancer treatment involves the targeted influence of radiation on neoplasms and minimal impact on healthy organs and tissues. The duration and extend of irradiation by IMRT method is significantly less than with standard remote radiotherapy.
Surgical treatment of Ewing’s sarcoma involves complete or partial removal of bone affected part. If we are talking about flat bones, they are removed completely, when the tubular bone is damaged, a partial resection is performed followed by reconstruction.
More recently, they acted radically – they amputated a limb. Today, TAMC specialists, thanks to the latest technologies introduction, perform amputation in very rare cases. During resection, surgeons of our medical center try to remove changed tissue as much as possible while preserving the healthy bone. Removing a large amount of biomaterial, reconstructive and restorative surgeries are performed – reconstruction with the help of artificial implants printed on a 3D printer or autografts.
After an organ-preserving surgery, in future the child will be able to lead an active lifestyle, engage in sports, avoiding contact injuries. If during surgical treatment the damaged area was replaced with an implant, the following surgical interventions for replacement or correction may be required as the child grows. Such corrective interventions do not require long-term inpatient treatment, sometimes they are performed in conditions of one day hospital.
Immunobiological and targeted therapy drugs are new drugs that have a targeted effect on cancer cells, blocking their growth and reproduction. Kinase inhibitors (cabozantinib) and monoclonal antibodies (ganitumab) are being studied for treatment of Ewing’s sarcoma. Kinase inhibitors block protein responsible for tumor cells growth.
Many children are offered treatment for Ewing’s sarcoma as part of clinical research. For some of them, this is the only chance to continue a healthy life.
