Most people with Ewing sarcoma have chemotherapy to shrink the cancer and then surgery to remove as much of it as possible. This is often followed by further chemotherapy to kill any leftover cancer cells. If Ewing sarcoma affects your bones, you'll need surgery at a specialist bone cancer centre.
If you have an arm or leg amputated, you may need a prosthetic limb and support to help you regain the use of the affected limb. Ewing sarcoma can spread to other parts of the body quite quickly. The earlier it's diagnosed, the better the chance of treatment being successful. The cancer can also come back after treatment, so you'll be offered regular check-ups to look for any signs of this. Based on an analysis from the SEER database, regional lymph node involvement in patients is associated with an inferior overall outcome when compared with patients without regional lymph node involvement.
The following are not considered to be adverse prognostic factors for Ewing sarcoma:. Multiple studies have shown that patients with minimal or no residual viable tumor after presurgical chemotherapy have a significantly better EFS than do patients with larger amounts of viable tumor. Patients with poor response to presurgical chemotherapy have an increased risk of local recurrence.
A retrospective analysis of risk factors for recurrence was performed in patients who received initial chemotherapy and underwent surgical resection of the primary tumor. The addition of radiation therapy was associated with improved outcome HR, 0. Adverse risk factors for death included pulmonary metastasis HR, 8. Early local recurrence 0—24 months negatively influences survival HR, 3.
Several techniques to evaluate the presence of Ewing sarcoma in the peripheral blood have been proposed. Flow cytometry for cells that express the CD99 antigen was not sufficiently sensitive to serve as a reliable biomarker. A more sensitive technique that utilized patient-specific primers designed after identification of the specific translocation breakpoint in combination with droplet digital PCR reported a sensitivity of 0.
Additional study is required to determine whether circulating cell-free DNA will have clinical utility as a biomarker for Ewing sarcoma to monitor disease status and response to therapy. Ewing sarcoma belongs to the group of neoplasms commonly referred to as small round blue cell tumors of childhood. The individual cells of Ewing sarcoma contain round-to-oval nuclei, with fine dispersed chromatin without nucleoli. The cytoplasm varies in amount, but in the classic case, it is clear and contains glycogen, which can be highlighted with a periodic acid-Schiff stain.
The tumor cells are tightly packed and grow in a diffuse pattern without evidence of structural organization. Tumors with the requisite translocation that show neuronal differentiation are not considered a separate entity, but rather, part of a continuum of differentiation. CD99 is a surface membrane protein that is expressed in most cases of Ewing sarcoma and is useful in diagnosing these tumors when the results are interpreted in the context of clinical and pathologic parameters.
Refer to the Undifferentiated Small Round Cell [Ewing-like] Sarcomas section of this summary for more information about the cellular classification of other undifferentiated small round cell sarcomas.
The detection of a translocation involving the EWSR1 gene on chromosome 22 band q12 and any one of a number of partner chromosomes is the key feature in the diagnosis of Ewing sarcoma refer to Table 2. The significance of these alternate partners is not known. Besides these consistent aberrations involving the EWSR1 gene at 22q12, additional numerical and structural aberrations have been observed in Ewing sarcoma, including gains of chromosomes 2, 5, 8, 9, 12, and 15; the nonreciprocal translocation t 1;16 q12;q Trisomy 20 may be associated with a more aggressive subset of Ewing sarcoma.
Three papers have described the genomic landscape of Ewing sarcoma and all show that these tumors have a relatively silent genome, with a paucity of mutations in pathways that might be amenable to treatment with novel targeted therapies. Enlarge Figure 1. A comprehensive profile of the genetic abnormalities in Ewing sarcoma and associated clinical information.
Key clinical characteristics are indicated, including primary site, type of tissue, and metastatic status at diagnosis, follow-up, and last news.
The numbers of structural variants SV and single-nucleotide variants SNV as well as indels are reported in grayscale. The presence of the main copy-number changes, chr 1q gain, chr 16 loss, chr 8 gain, chr 12 gain, and interstitial CDKN2A deletion is indicated. Listed last are the most significant mutations and their types.
Ewing sarcoma translocations can all be found with standard cytogenetic analysis. A more rapid analysis looking for a break apart of the EWSR1 gene is now frequently done to confirm the diagnosis of Ewing sarcoma molecularly. In addition, other small round tumors also contain translocations of different ETS family members with EWSR1 , such as desmoplastic small round cell tumor, clear cell sarcoma, extraskeletal myxoid chondrosarcoma, and myxoid liposarcoma, all of which may be positive with a EWSR1 fluorescence in situ hybridization FISH break-apart probe.
The authors do not recommend relying solely on EWSR1 break-apart probes for analyzing small round blue cell tumors with strong immunohistochemical positivity for CD Small round blue cell tumors of bone and soft tissue that are histologically similar to Ewing sarcoma but do not have rearrangements of the EWSR1 gene have been analyzed and translocations have been identified. There are too few cases associated with each translocation to determine whether the prognosis for patients with these small round blue cell tumors is distinct from the prognosis of patients with Ewing sarcoma of similar stage and site.
Other undifferentiated round cell sarcomas are characterized by a CIC-DUX4 fusion resulting from a recurrent t 4;19 or t 10; Genome-wide association studies have identified susceptibility loci for Ewing sarcoma at 1p Three new susceptibility loci have been identified at 6p Pretreatment staging studies for Ewing sarcoma may include the following:.
Despite the fact that CT and MRI are both equivalent in terms of staging, use of both imaging modalities may help radiation therapy planning. In certain studies, determination of pretreatment tumor volume is an important variable. In one institutional study, 18F-FDG PET had a very high correlation with bone scan; the investigators suggested that it could replace bone scan for the initial extent of disease evaluation.
Bone marrow aspiration and biopsy have been considered the standard of care for Ewing sarcoma. The need for routine use of bone marrow aspirates and biopsies in patients without bone metastases is now in question. For Ewing sarcoma, the tumor is defined as localized when, by clinical and imaging techniques, there is no spread beyond the primary site or regional lymph node involvement.
Continuous extension into adjacent soft tissue may occur. If there is a question of regional lymph node involvement, pathologic confirmation is indicated. It is important that patients be evaluated by specialists from the appropriate disciplines e.
Appropriate imaging studies of the site are obtained before biopsy. To ensure that the incision is placed in an acceptable location, the surgical or orthopedic oncologist who will perform the definitive surgery is involved in the decision regarding biopsy-incision placement.
This is especially important if it is thought that the lesion can subsequently be totally excised after initial systemic therapy or if a limb salvage procedure may be attempted. It is almost never appropriate to attempt a primary resection of Ewing sarcoma. With rare exceptions, Ewing sarcoma is sensitive to chemotherapy and will respond to initial systemic therapy, which makes ultimate surgery easier and safer.
Primary surgery incurs the risk of tumor spread to surrounding tissues, which is reduced by the use of initial systemic therapy. Biopsy should be from soft tissue as often as possible to avoid increasing the risk of fracture. It is important to obtain fresh tissue, whenever possible, for cytogenetics and molecular pathology. A second option is to perform a needle biopsy, as long as adequate tissue is obtained for molecular biology and cytogenetics.
Table 3 describes the treatment options for localized, metastatic, and recurrent Ewing sarcoma. In patients who undergo surgery, surgical margins and histologic response are considered in planning postoperative therapy. Patients with metastatic disease often have a good initial response to preoperative chemotherapy, but in most cases, the disease is only partially controlled or recurs.
Adequate local control for metastatic sites, particularly bone metastases, may be an important issue. Multidrug chemotherapy for Ewing sarcoma always includes vincristine, doxorubicin, ifosfamide, and etoposide. Most protocols also use cyclophosphamide and some incorporate dactinomycin.
The mode of administration and dose intensity of cyclophosphamide within courses differs markedly between protocols. Protocols in the United States generally alternate courses of vincristine, cyclophosphamide, and doxorubicin VDC with courses of ifosfamide and etoposide IE ,[ 8 ] while, for many years, European protocols generally combined vincristine, doxorubicin, and an alkylating agent with or without etoposide in a single treatment cycle.
Treatment approaches for Ewing sarcoma and therapeutic aggressiveness must be adjusted in order to maximize local control while also minimizing morbidity. Surgery is the most commonly used form of local control. However, in the immature skeleton, radiation therapy can cause subsequent deformities that may be more morbid than deformities from surgery. When complete surgical resection with pathologically negative margins cannot be obtained, postoperative radiation therapy is indicated.
A multidisciplinary discussion between the experienced radiation oncologist and the surgeon is necessary to determine the best treatment options for local control for a given case. For some marginally resectable lesions, a combined approach of preoperative radiation therapy followed by resection can be used.
Timing of local control may impact outcome. A retrospective review from the National Cancer Database identified 1, patients with Ewing sarcoma. The difference in OS according to time to local therapy was more important in patients who received radiation therapy alone. For patients with metastatic Ewing sarcoma, any benefit of combined surgery and radiation therapy compared with either therapy alone for local control is relatively less substantial because the overall prognosis of these patients is much worse than the prognosis of patients who have localized disease.
Randomized trials that directly compare surgery and radiation therapy do not exist, and their relative roles remain controversial. Although retrospective institutional series suggest superior local control and survival with surgery than with radiation therapy, most of these studies are compromised by selection bias.
An analysis using propensity scoring to adjust for clinical features that may influence the preference for surgery only, radiation only, or combined surgery and radiation demonstrated that similar EFS is achieved with each mode of local therapy. The study did not prospectively define criteria for the selection of local-control modalities, and the investigators did not have access to information that would allow them to clarify why decisions for local-control modalities were made.
In patients with bone tumors who underwent surgical treatment— after controlling for tumor site in the pelvis, tumor volume, and surgical margin status—patients who did not undergo complete removal of the affected bone HR, 5.
For patients who undergo gross-total resection with microscopic residual disease, a radiation therapy dose of In summary, surgery is chosen as definitive local therapy for suitable patients, but radiation therapy is appropriate for patients with unresectable disease or those who would experience functional or cosmetic compromise by definitive surgery. The possibility of impaired function or cosmesis needs to be measured against the possibility of second tumors in the radiation field.
Adjuvant radiation therapy should be considered for patients with residual microscopic disease or inadequate margins. When preoperative assessment has suggested a high probability that surgical margins will be close or positive, preoperative radiation therapy has achieved tumor shrinkage and allowed surgical resection with clear margins. For patients with a high risk of relapse with conventional treatments, certain investigators have utilized high-dose chemotherapy with hematopoietic stem cell transplant HSCT as consolidation treatment, in an effort to improve outcome.
Both study arms were compromised by the potential for selection bias for patients who were eligible for and accepted randomization, which may limit the generalizability of the results. This regimen is less dose intensive than the regimen employed in COG studies. Results from this study include the following:. The advantage of high-dose therapy as consolidation for patients with a poor response to initial treatment with a less intensive regimen cannot be extrapolated to a population of patients who received a more intensive treatment regimen as initial therapy.
Multiple analyses have evaluated diagnostic findings, treatment, and outcome of patients with bone lesions at the following anatomic primary sites:. Extraosseous Ewing sarcoma is biologically similar to Ewing sarcoma arising in bone.
Historically, most children and young adults with extraosseous Ewing sarcoma were treated on protocols designed for the treatment of rhabdomyosarcoma. This is important because many of the treatment regimens for rhabdomyosarcoma do not include an anthracycline, which is a critical component of current treatment regimens for Ewing sarcoma. Currently, patients with extraosseous Ewing sarcoma are eligible for studies that include Ewing sarcoma of bone. Cutaneous Ewing sarcoma is a soft tissue tumor in the skin or subcutaneous tissue that seems to behave as a less-aggressive tumor than primary bone or soft tissue Ewing sarcoma.
Tumors can form throughout the body, although the extremity is the most common site, and they are almost always localized. Cancer in children and adolescents is rare, although the overall incidence has been slowly increasing since This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:. Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.
The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer. Clinical trials for children and adolescents with cancer are generally designed to compare potentially better therapy with current standard therapy. Most of the progress made in identifying curative therapies for childhood cancers has been achieved through clinical trials.
Information about ongoing clinical trials is available from the NCI website. Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.
Standard treatment options for localized Ewing sarcoma include the following:. There was no increase in toxicity observed with the every 2-week schedule. Decisions regarding the optimal modality for local control for an individual patient involve consideration of the following:. An analysis using propensity scoring a method that adjusts for the inherent selection bias of the location and size of the tumor to adjust for clinical features that may influence the preference for surgery only, radiation only, or combined surgery and radiation demonstrated that similar EFS rates are achieved with each mode of local therapy after propensity adjustment.
Surgery is generally the preferred approach if the lesion is resectable. The apparent superiority may represent selection bias. Pathologic fracture at the time of diagnosis does not preclude surgical resection and is not associated with adverse outcome.
Radiation therapy is delivered in a setting in which stringent planning techniques are applied by those experienced in the treatment of Ewing sarcoma. Such an approach will result in local control of the tumor with acceptable morbidity in most patients. The radiation dose may be adjusted depending on the extent of residual disease after the initial surgical procedure.
When no surgical resection is performed, radiation therapy is generally administered in fractionated doses totaling approximately A randomized study of 40 patients with Ewing sarcoma using For patients with residual disease after an attempt at surgical resection, the Intergroup Ewing Sarcoma Study INT recommended 45 Gy to the original disease site plus a No radiation therapy was recommended for those who have no evidence of microscopic residual disease after surgical resection.
Comparison of proton-beam radiation therapy and intensity-modulated radiation therapy IMRT treatment plans has shown that proton-beam radiation therapy can spare more normal tissue adjacent to Ewing sarcoma primary tumors than IMRT. The drugs may shrink the tumor and make it easier to remove the cancer with surgery or target with radiation therapy. After surgery or radiation therapy, chemotherapy treatments might continue in order to kill any cancer cells that might remain.
For advanced cancer that spreads to other areas of the body, chemotherapy might help relieve pain and slow the growth of the cancer. The goal of surgery is to remove all of the cancer cells. But planning the operation also takes into consideration how it will affect your ability to go about your daily life.
Surgery for Ewing sarcoma may involve removing a small portion of bone or removing an entire limb. Whether surgeons can remove all of the cancer without removing the entire limb depends on several factors, such as the size and location of the tumor and whether it shrinks after chemotherapy. During radiation therapy, the beams of energy are delivered from a machine that moves around you as you lie on a table.
The beams are carefully directed to the area of the Ewing sarcoma in order to reduce the risk of damage to surrounding healthy cells. Radiation therapy might be recommended after surgery to kill any cancer cells that remain. It can also be used instead of surgery if the Ewing sarcoma is located in a part of the body where surgery is not possible or would result in unacceptable functional outcomes such as loss of bowel or bladder function.
For advanced Ewing sarcomas, radiation therapy can slow the growth of the cancer and help relieve pain. There is a problem with information submitted for this request. Subscribe for free and receive an in-depth guide to coping with cancer, plus helpful advice on how to get a second opinion.
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