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By Nita Sharma Das, PhD, ND
Radiotherapy and surgical interventions were the only two options available to treat Ewing's Sarcoma (ES), until the middle of the last century. However, several treatment options and many new chemotherapeutic agents have been introduced as a part of recent medical development.
The present treatment approach for ES is multidisciplinary, involving chemotherapy, radiotherapy, cheap provera coupons no prescription and surgery. The factors such as the site of the tumor and patient’s response towards the initial treatment help to further determine the appropriate treatment plan for the patient.
Clinicians usually recommend primary induction chemotherapy before any surgical intervention. The pre-surgical chemotherapy helps to destroy any existing micrometastases and may cause shrinkage of the tumor, thus facilitating complete removal of the tumor and a better surgical outcome. In addition, pre-operative chemotherapy can help to determine the patient’s tolerance to chemotherapy during post-operative treatment.
There are many chemotherapeutic agents available to treat ES, including vinca alkaloids, antitumor antibiotics, and alkylating agents. For optimum therapeutic efficacy, the oncologists combine several agents and design a customized regimen for the patients depending upon their conditions. Research evidence also shows that combination therapy comprising several therapeutic classes of drugs provide a better prognosis and an improved survival rate. Targeted therapy is also being developed. There are different mechanisms of actions for these drugs; however, the two most common among them are mentioned here:
- Insulin-like growth factor 1 (IGF1) signaling pathway to mTOR has a direct role on malignant transformation and cell progression. Chemotherapy can inhibit IGF1 and mTOR which further interferes with EWS-FLI1 fusion gene formation.
- Traditional chemotherapeutic agents may not be able to induce apoptosis due to the chemo-resistant nature of ES. However, novel chemotherapeutic agents induce non-apoptotic cell death techniques, such as necroptosis, autophagic cell death, and pyroptosis, which are different from regular apoptosis. Some of the chemotherapy regimens interfere with angiogenesis that normally accompanies malignant tumor growth, and thus restricts the malignant cell growth. Some newly invented chemotherapeutic regimens also inhibit tyrosine kinases and thus restrict tumor cell proliferation.
The intravenous administration of two or more chemotherapeutic agents in combination can improve the survival rate of patients with ES who have metastasis to the bone or boner marrow. A research study conducted on 32 patients with ES showed a 20% 2-year event-free survival. The success of such intensive chemotherapy depends upon how well the patient can tolerate it.
ES is very sensitive to radiotherapy; therefore treatment often begins with radiotherapy prior to chemotherapy. The dose selection of radiotherapy for treating ES varies between 36 Gy to 60 Gy. There are two different techniques applied in radiotherapy; definitive radiotherapy and pre-operative or postoperative adjuvant radiotherapy. Definitive radiotherapy is defined as radiotherapy intended to be the only local therapy, and is applied to treat centrally sited lesions and to destroy all the viable tumor cells. In such cases the tumor is typically large and difficult to excise. Pre-operative or postoperative adjuvant radiotherapy helps to facilitate prevent relapse because surgical tumor removal with negative surgical margins is difficult, and in case the surgical excision fails to eradicate all the malignant cells because of difficulties with the anatomy, respectively.
Research suggests that the combination of surgery and radiotherapy can provide better control over relapse rates than radiotherapy alone. However, radiotherapy alone may be preferred for better local control in ES patients who show a limited response to chemotherapy and a poor surgical prospects.
Immunotherapy is another mode of managing this malignancy, and is aimed at preventing the formation of the fusion gene which is responsible for the progression of ES. This is a novel treatment method which depends upon the utilization of tumor antigens to enhance the host immune recognition of tumor cells and expose the translocation products to immune surveillance. This leads to the destruction of peptide bonds present in the fusion protein peptides on the tumor cell surface.
Surgical intervention after pre-operative chemotherapy is the most common method to treat ES if the patient has a single resectable tumor after induction. Limb salvage is almost always attempted during surgical intervention. Intra-lesional resection, marginal resection, wide resection and radical resection are different surgical interventions that can be applied depending upon the position, nature, and size of the tumor. However, there is always a risk of tumor-positive margins, which must be treated by further radiotherapy or chemotherapy to correct it.
Post-surgical infection is very common in the patients affected by ES. Post-operative chemotherapy cannot be started till the infection at the site of surgical intervention has been fully eliminated. Treatment with high-dose chemotherapy can also trigger post-operative infection. Moreover, the selection of reconstruction method is very critical, as it can also encourage the development of infection at the affected site. Autogenous bone grafts, allografts and metal endoprostheses have all been recommended.
Liquid nitrogen-treated recycled bone is a novel reconstruction method, which is frequently used at the current time. In this method, the cryo-immunological response is stimulated which provides a greater increase in the survival rate than any other reconstructive method.
It is essential to perform iliac excision if the pelvis is affected, as is most common. Fibula strut grafts are used for pelvic reconstruction, typically non-vascularized. This helps the bones to unite within a few months of implantation.
Internal hemipelvectomy is another procedure used for the local control of pelvic ES, to assure a better postoperative quality of life of the patient.
The start of intensive chemotherapy soon after the diagnosis of ES is an essential part of disease management. There may be a need to implant a prosthesis after radical surgical intervention, in order to repair the skeletal defect. However, biological reconstruction methods are preferred for growing children who are being treated for ES.
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Last Updated: Feb 26, 2019
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