Chemotherapy Regimen for Ewing’s Sarcoma

What Is Ewing’s Sarcoma?

Ewing's sarcomas are rare neuroectodermal tumors that affect teenagers or young adults, with the majority under 30. Ewing's sarcomas are much higher in Caucasians than in Africans or Asians. The most common locations for Ewing's sarcoma are the chest, head, and neck; however, it can occur in any soft tissue. There have also been some cases of Ewing's sarcoma of the uterus, ovaries, vagina, and vulva. The treatments for Ewing’s sarcoma include surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, and radiotherapy.

How Is Ewing’s Sarcoma Diagnosed?

Approximately 85 % of Ewing’s sarcomas have a translocation (11;22) (q24;q12) genetic alteration, which results in a chimeric fusion of the EWS-FLI1 gene. Molecular techniques critical for detecting these translocations and, consequently, diagnosing Ewing's sarcoma are as follows:

1. Fluorescence in situ hybridization (FISH).

2. Reverse transcriptase polymerase chain reaction (RT-PCR).

3. Next-generation sequencing(NGS).

What Is the Treatment of Ewing’s Sarcoma?

The treatments for Ewing’s sarcoma include surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, and radiotherapy, mainly based on the location and extent of the tumor. A localized Ewing’s tumor is limited to specific tissues such as muscles or tendons. However, even with localized Ewing's sarcoma, there is often cancer spread to other places of the body that imaging studies cannot detect. When an Ewing tumor is discovered and staged, the first treatment is neoadjuvant chemotherapy, which is administered before any surgery or radiation therapy. After at least nine weeks of chemotherapy, imaging tests such as magnetic resonance imaging(MRI), positron emission tomography (PET), computed tomography(CT), or bone scans are performed to determine if the tumor can be surgically removed. The surgical specimen removed is subsequently examined by a pathologist.

• Radiation Therapy and Chemotherapy - If cancer cells are discovered at or near the boundaries of the surgical specimen, indicating the need for radiation therapy and chemotherapy to be utilized for several months.

• Chemotherapy - Chemotherapy can be used instead of radiation therapy if the cancer cells are at or near the borders of the surgical specimen.

What Is Chemotherapy?

Chemotherapy is a treatment that uses medications to circulate through the bloodstream and kill rapidly growing cells, such as cancer cells. Ewing's sarcoma, with no visible cancer spread detected in bone marrow biopsy samples and imaging tests, is likely to have very modest areas of cancer dissemination (micrometastases). These microscopic metastases will grow into more extensive tumors if chemotherapy is not administered. However, chemotherapy simultaneously affects the normal cells as a side effect.

When Is Chemotherapy Used for Ewing Sarcoma?

Chemotherapy is the initial treatment for Ewing sarcoma, regardless of how far it has spread to other places in the body. Chemotherapy can frequently shrink the primary tumor and make surgery or radiation less painful. It can also eliminate cancer cells that have spread throughout the body. The remaining tumor is removed or destroyed following chemotherapy using surgery or radiation, which reduces the likelihood of cancer reoccurring later.

How Is Chemotherapy Administered for Ewing’s Sarcoma?

An oncologist formulates the chemotherapy treatment plan at the beginning of the therapy. The doctor will also discuss the treatment choices and side effects. Chemotherapy is administered directly into the bloodstream via an IV (intravenous) line through a small plastic tube inserted into the hand or arm vein. The drug is then administered gradually over several hours. Chemotherapy is typically administered as an outpatient procedure at a hospital infusion facility, clinic, or healthcare provider's office.

How Many Cycles of Chemotherapy Are Required?

Chemotherapy is administered in cycles for a specified period, followed by rest. Each treatment and rest time is one cycle. Treatment in cycles aids in killing more cancer cells and enables the drug to combat more cells. Because cells do not divide at the same rate, the drug can kill more cancer cells over time. Other cells that divide quickly are more vulnerable to treatment. Most people receive four to six cycles as part of their initial treatment, which typically lasts several months. Chemotherapy is administered again after surgery or radiation.

Which Chemotherapy Drugs Are Used to Treat Ewing’s Sarcoma?

The chemotherapy drugs used to treat Ewing sarcoma are:

1. Cyclophosphamide.

2. Doxorubicin.

3. Etoposide.

4. Ifosfamide.

5. Vincristine.

6. Actinomycin D.

Chemotherapy for Ewing sarcoma is a mix of medications. The most common combination is Vincristine, Doxorubicin, and Cyclophosphamide, alternating with Ifosfamide and Etoposide (VDC/IE). The VDC-IE treatment (Vincristine, Doxorubicin, Cyclophosphamide, Ifosfamide, Etoposide) improved survival in patients with non-metastatic Ewing's sarcoma family tumors.

What Are the Different Chemotherapy Regimens for Ewing’s Sarcoma?

The chemotherapy regimens are as follows:

1. VDC-IE (Vincristine, Doxorubicin, and Cyclophosphamide, alternating with Ifosfamide and Etoposide).

2. DIE (Doxorubicin, Ifosfamide and Etoposide).

3. CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone.

4. Pirarubicin, Cisplatin and Ifosfamide.

What Are the Side Effects of Chemotherapy Drugs?

Cyclophosphamide and Ifosfamide both cause bladder issues, such as blood in the urine. Vincristine can cause nerve injury and result in numbness and tingling in the hands and feet. It can also cause constipation by disrupting nerves involved in bowel function. Doxorubicin has the potential to harm heart muscles and impair fertility in later life. Some medications may increase the risk of developing another malignancy, such as leukemia, in the future.

What Are the Most Prevalent Chemotherapy Side Effects?

During treatment, blood counts are tested regularly. The white blood cell (WBC) count may drop with chemotherapy, leading to a decrease in immune system functioning. Signs of infection, such as a fever, sore throat, a new cough, or a burning sensation during urination, must be attended to immediately. Bleeding and bruising are also easily caused by a reduced blood platelet count after chemotherapy. Chemotherapy side effects vary from person to person and are determined by the medications utilized. These are some of the more common chemotherapy adverse effects:

1. Loss of hair.

2. Vomiting and nausea.

3. Difficulty eating or swallowing.

4. Sores in the mouth.

5. Loose motions.

6. Extreme exhaustion.

7. Appetite loss.

8. Enhanced risk of infection.

What Care Should Be Taken During Chemotherapy?

Collaboration with healthcare providers is critical to understanding the medications and their potential adverse effects. It is essential to discuss any symptoms that are susceptible to infections. Body temperature must be recorded in case of developing fever or chills. A side effect diary may be beneficial as a written list will help remember the questions before appointments.

What Is the Differential Diagnosis of Ewing’s Sarcoma?

Ewing's sarcoma is a type of small cell tumor that can be difficult to distinguish from:

1. Neuroblastoma.

2. Rhabdomyosarcoma.

3. Small cell carcinoma.

Ewing's sarcoma can be only distinguished by hematoxylin and eosin staining alone. The presence of CD99 immunohistochemistry staining also suggests Ewing's sarcoma. Also, vimentin, neuron-specific enolase (NSE), S-100 protein, CD57, and synaptophysin are frequently positive in Ewing’s sarcoma in addition to CD99.

Conclusion:

Ewing’s sarcoma is a rare neuroectodermal tumor. The immunohistochemical marker CD99 and EWS-FLI1 gene translocations by using fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction (RT-PCR) are required for a proper diagnosis. VDC-IE therapy is proven to be a successful treatment regimen.