The second most common malignant bone tumor after osteosarcoma in adolescents and young adults, Ewing’s sarcoma affects 100 to 150 new patients per year in Europe. In a third of cases, metastases are already present at diagnosis. Dr Nathalie Gaspar, pediatric oncologist and head of the SPIAJA program (Interdisciplinary Care for Adolescents and Young Adults) at the Gustave Roussy Institute, discusses the symptoms of this rare cancer, its diagnosis and its treatment.
What is Ewing sarcoma?
Definition of Ewing Sarcoma
Ewing’s sarcoma owes its name to the American doctor James Ewing who first described it in 1921. It is a primary bone tumor, that is to say it originates in the bone, and which invades the neighboring soft parts, notably the muscles, fat, nerves… “It is a rather lytic tumor, which destroys the bone., specifies Dr Nathalie Gaspar. Ewing sarcoma belongs to a group of tumors referred to as small round cell tumors which present a characteristic fusion transcript (molecular alterations following chromosomal rearrangements), most often EWS-Fli1.
Where is Ewing’s sarcoma located?
It preferentially affects flat bones such as those of the pelvis (30%), or the thorax (ribs, clavicle, scapula – 20%); when it affects the long bones (femur – 16%, tibia – 9%, humerus – 5%), it develops more at the level of their diaphysis, in other words the central part of the bone.
This cancer has the particularity of easily inducing metastasesmore particularly in the lungs, bones and bone marrow: in 30 to 35% of cases, these are already present at diagnosis.
How many people suffer from Ewing’s sarcoma in Europe?
According to estimates on the Orphanet website, the annual incidence of Ewing’s sarcoma is 1 case per 312,500 children under 15 years of age. With 100 to 150 new cases each year in Europe, this cancer represents the second malignant bone tumor in adolescents and young adults after osteosarcoma.
Who can be affected by Ewing’s sarcoma? Is there a higher risk age? Does it exist in adults?
It is mainly adolescents and young adults who are affected by Ewing’s sarcoma: the majority of cases occur between 5 and 25 years of age (70%), with a peak incidence between 12 and 18 years of age. But it is possible to develop this bone cancer outside of these ages, therefore in adults. Furthermore, Ewing’s sarcoma occurs more frequently in children of European origin and more rarely in African or Asian populations, underlines Dr. Nathalie Gaspar.
What causes Ewing’s sarcoma?
The causes of Ewing’s sarcoma are probably multiple but they remain poorly understood at the moment.
A somatic genetic anomaly identified
A fusion between two genes is characteristic of Ewing sarcoma tumor cells, it is a translocation between chromosomes 11 and 22, occurring in the tumor cells and which results in the production of an abnormal protein called EWS- FLI-1. This anomaly is not a genetic mutation and is therefore not transmissible: there is therefore no risk of transmission, in other words Ewing’s sarcoma is not hereditary.
No environmental cause
No environmental cause likely to favor the development of Ewing sarcoma has been identified to date.
What are the symptoms of Ewing sarcoma?
The symptoms of Ewing’s sarcoma remain poorly understood by non-specialist doctors and are not specific to this disease (pain, mass, pathological fracture, fever). Neuropathic pain such as sciatica or cruralgia can be seen in Ewing’s sarcoma of the spine or pelvis, but be careful in interpreting this pain: “This type of pain should immediately suggest a tumor until proven otherwise because herniated discs do not exist in children or adolescents.insists Dr. Gaspar.
How to recognize a sarcoma?
A bone sarcoma like Ewing’s sarcoma is characterized by pain continuous, resistant to analgesics, and swellings in the bones and surrounding soft tissues. The pain may worsen over time and cause the child to wake up at night. Over time and if left untreated, they can become disabling. Unlike osteosarcoma, Ewing’s sarcoma can also cause deterioration of general condition with in particular the fever but this symptom is not systematically present.
Localized swelling
Ewing’s sarcoma causes another more characteristic sign, continues the specialist, “a swelling which materializes by the appearance of a boule which originates on the bone; This lump is painful and firm.”
Pathological fractures
Finally, the weakening of the bone can lead to so-called pathological fracturesoccurring following a slight trauma or, sometimes, spontaneously.
How to make the diagnosis of Ewing sarcoma?
An imaging assessment
The diagnostic process for Ewing’s sarcoma involves a consultation with your doctor who will prescribe either an X-ray of the whole bone or a thoraco-abdominal scan depending on the location of the suspicious lump and the pain. Depending on the results, an MRI of the whole bone should be performed in an expert center. This imaging assessment, carried out before the biopsy, serves to confirm the presence of a lesion in the bone, to measure its local extent, to guide the diagnosis and to guide the biopsy.
A tumor biopsy
An essential step in the diagnosis, the biopsy must be carried out by an expert sarcoma surgeon (belonging to the NETSARC+ or RESOS network) or by an interventional radiologist in an expert center; in this case, the radiologist and surgeon must ensure in advance that the biopsy path can be resected at the same time as the bone tumor later in the treatment. This collection is done under local or general anesthesia, depending on the age of the patient and the location of their tumor. “Analysis of the biopsy will confirm or refute the diagnosis; a review by an expert pathologist is required and molecular analysis of the tumor to identify the fusion transcript is essential”underlines Dr Gaspar.
Molecular analysis of the tumor
The existence of a specific marker for Ewing’s sarcoma, namely mutations involving the EWS gene, must lead to their search using molecular biology techniques (FISH, RT-PCR or RNA-seq). Molecular analysis consists of looking for the presence of the EWS-FL1 protein, overexpressed in more than 90% of patients, or the EWS-ERG protein, overexpressed by a minority of individuals.
How to treat Ewing sarcoma?
The general treatment plan for Ewing’s sarcoma includes three stages: induction chemotherapy or neoadjuvant chemotherapy, local treatment of the tumor (by surgery and/or radiotherapy), then post-operative chemotherapy or adjuvant chemotherapy. “Treatment choices must be discussed in a multidisciplinary consultation meeting (RCP) “sarcoma” for adult patients or “pediatric or AJA” for patients under 18 years of age.”we can read on the website of the Gustave Roussy Institute, a specialized cancer center.
What is the prognosis for Ewing’s sarcoma?
The success of the treatment depends on three factors: the location of the tumor, the presence of metastases at diagnosis and the response to induction chemotherapy. “In the case of localized sarcoma with a good response to neoadjuvant chemotherapy, the survival rate is 80% at 3-5 years. In the event of immediate pulmonary metastases or poor response to chemotherapy, it drops to 50%, and less than 30% if the metastases are extrapulmonary.reports Dr. Gaspar.
Neoadjuvant chemotherapy
It aims to slow down the growth of the bone tumor to facilitate its local treatment, explains the pediatric oncologist. This treatment also serves to prevent the development of metastases or to treat them if they were already there at diagnosis – which is the case in 25 to 30% of patients. 85 to 90% of these metastases are located in the lungs; the rest of the time, they are located on other bones or in the bone marrow. Finally, preoperative chemotherapy helps reduce pain and facilitates surgical intervention.
The chemotherapy currently used lasts between 4 and 5 months. But this duration can be extended in the event of metastases. “At the end of this treatment, the response of the tumor to chemotherapy will be evaluated by examining the tumor after the operation. This analysis makes it possible to determine the histological response which is considered good if less than 10% of living tumor cells remain. Histological response is one of the most important prognostic factors in children and young people with non-metastatic Ewing sarcoma.
Local treatment
The key element of local treatment is surgery, which aims to remove the entire portion of the diseased bone and then reconstruct it. It is a so-called “conservative” surgery with resection/reconstruction during the same operating time. Amputation may nevertheless be necessary when local invasion is significant.
Radiotherapy is often used in addition to surgery to limit the risk of local recurrence. In forms considered inoperable, exclusive radiotherapy may constitute the only local treatment.
