The Role of Radiation Therapy for Ewing’s Sarcoma

Overview

Radiation therapy (also known as radiotherapy) uses high-energy rays to damage or kill cancer cells by preventing them from growing and dividing. Similar to surgery, radiation therapy is a local treatment used to eliminate cancer in a specific area. Radiation therapy is not typically useful in eradicating cancer cells that have already spread to other parts of the body. Radiation therapy may be externally or internally delivered. External radiation delivers high-energy rays directly to the tumor site from a machine outside the body. Internal radiation, or brachytherapy, involves the implantation of a small amount of radioactive material in or near the cancer.

Optimal treatment of patients with Ewing’s sarcoma often requires more than one therapeutic approach. Thus, it is important for patients to be treated at a medical center that can offer multi-modality treatment involving radiation oncologists, orthopedic surgeons, pediatric oncologists, and rehabilitation specialists.

Ewing’s sarcoma is relatively sensitive to radiation, and conventional radiation therapy plays a major role in treatment. When radiation therapy is given to patients with Ewing’s it is usually given with chemotherapy.

External Beam Radiation Therapy

Radiation therapy is delivered to areas of cancer from a machine outside the body, called a linear accelerator, or from a shielded repository of a powerful isotope, such as cobalt 60. External beam radiation therapy is most often administered in conjunction with chemotherapy. In some instances, patients with advanced disease are treated with radiation therapy alone for relief of symptoms. Conventional radiation therapy is administered over a course of five to seven weeks.

The main effect of radiation therapy is to prevent local and regional recurrences (cancer recurrence in the area of the primary tumor). A recent review suggests that radiation therapy can prevent local cancer recurrence in 58 to 93 percent of patients.[1]

Surgery, Radiation Therapy and Chemotherapy for Localized Ewing’s Sarcoma

The most common approach for the treatment of localized Ewing’s sarcoma is to remove as much tumor as possible surgically, deliver local radiation to eradicate microscopic tumor not removed by surgery, and administer systemic (whole-body) combination chemotherapy to eradicate micrometastases (very small areas of cancer that may have spread to other parts of the body). Radiation therapy has no effect on distant metastatic disease.

Researchers from St Jude Children Research Center have reported the outcomes of 39 patients with localized Ewing’s sarcoma treated with definitive surgery, radiation therapy and chemotherapy.[2] They reported a five-year survival of 90 percent and a local recurrence rate of 11 percent. Patients who had positive surgical margins (evidence of cancer at the edge of the tissue that was surgically removed) had a local recurrence rate of 17 percent compared to 5.2 percent for those with no tumor in the surgical margins.

Radiation Therapy and Chemotherapy for Localized Ewing’s Sarcoma

Patients who have inoperable tumors or tumors in sites not suitable for surgery are treated with radiation therapy and chemotherapy. Researchers at St Jude Children’s Research Center have reported the outcomes of 79 patients with Ewing’s sarcoma treated with low-dose or high-dose radiation and chemotherapy with vincristine, actinomycin D, and cyclophosphamide with alternating cycles of ifosfamide and etoposide.[3] The local recurrence rate was 30 percent. Overall survival was 65 percent. Patients who were older or who had larger tumors had worse outcomes. In addition, radiation doses below 40 Gy were associated with an increased rate of local recurrence.

Side Effects of Radiation Therapy

Although patients do not feel anything while they are receiving radiation treatment, the effects of radiation gradually build up over time. Large doses of radiation can cause skin damage in the areas receiving radiation. Large doses of radiation to patients with Ewing’s sarcoma can damage blood vessels and nerves. Researchers from Emory University have described several late effects of radiation therapy in children including: atrophy, fibrosis, bone growth abnormalities, impairment of mobility, edema, and peripheral nerve injury.[4] The most worrisome side effect among long-term survivors is second cancers due to radiation. One Italian study involving 597 long-term survivors with Ewing’s sarcoma found that the risk of second cancer after radiation therapy for Ewing’s sarcoma was higher than after other childhood and adolescent cancers treated in the same manner.[5] Some researchers have suggested that postoperative radiotherapy should be avoided when surgery is accomplished with adequate margins (no evidence of cancer near the edge of the tissue that was removed).

Strategies to Improve Treatment

Significant progress has been made in the treatment of Ewing’s sarcoma.  Future progress in the treatment of Ewing’s sarcoma will result from continued participation in appropriate clinical trials. There are several areas of active exploration aimed at improving the treatment of Ewing’s sarcoma with radiation therapy.

Intraoperative Radiation Therapy (IORT): Intraoperative radiation therapy (IORT) is a single dose of radiation therapy that is delivered directly to the area of surgery during the operation. IORT is performed in specially-equipped operating rooms. During IORT, the radiation doctor can see the area being treated, and sensitive normal structures, such as blood vessels and nerves, can be moved away from the radiation beam. Results from some studies evaluating IORT indicate that cancer may recur less often in the area of the surgery.[6]

Three-dimensional Conformal Radiation Therapy and Intensity Modulated Radiation Therapy: Three-dimensional conformal radiation therapy can precisely target radiation to the areas where cancer cells may be located and therefore, minimize side effects from radiation to normal structures such as the liver, stomach and kidneys.  Intensity modulated radiation therapy is a newer method of precisely delivering specified doses of radiation to cancer cells.  Neither of these techniques have been evaluated for treatment of Ewing’s sarcoma, although both techniques are probably utilized for this purpose in many radiation oncology centers.[7], [8]

Brachytherapy: Brachytherapy is the placement of a radioactive material directly into the cancer at the time of surgery.  This technique has not been systematically studied in patients with Ewing’s sarcoma.  However, promising results in controlling local disease have been reported.[9],[10]

References:


[1] Donaldson SS. Ewing sarcoma: radiation dose and target volume. Pediatr Blood Cancer 2004;42:471-476.

[2] Krasin MJ, Rodriguez-Galindo C, Davidoff AM, et al. Efficacy of combined surgery and irradiation for localized Ewings sarcoma family of tumors. Pediatric Blood Cancer. 2004;43:229-236.

[3] Krasin MJ, Rodriguez-Galindo C, Billups CA, et al. Definitive irradiation in mulitidisciplinary management of localized Ewing sarcoma family of tumors in pediatric patients: outcome and prognostic factors. International Journal of Oncology Biology Physics 2004;60:830-838.

[4] Paulino AC. Late effects of radiotherapy for pediatric extremity sarcomas. International Journal of Oncology, Biology, Physics. 2004;60:265-274.

[5] Bacci G, Longhi A, Barbieri E, et al. Second malignancy in 597 patients with Ewing’s sarcoma of bone treated at a single institution with adjuvant and neoadjuvant chemotherapy between 1972 and 1999. Journal of Pediatric Hematology and Oncology 2005;27:517-520.

[6] Sakayama K, Kidani T, Fujibuchi T, et al. Definitive intraoperative radiotherapy for musculoskeletal sarcomas and malignant lymphoma in combination with surgical excision. Int J Clin Oncol. 2003;8:174-179.

[7] DeLaney TF, Trofimov AV, Engelsman M, et al. Advanced-technology radiation therapy in the management of bone and soft tissue sarcomas. Cancer Control. 2005;12:27-35.

[8] Marec-Berard P, Philip T. Ewing sarcoma: the pediatrician’s point of view. Pediatr Blood Cancer. 2004;477-480.

[9] Ozaki T, Hillman A, Rube C, et al. The impact of introperative brachytherapy on surgery of Ewing’s sarcoma. J Cancer Res Clin Oncol. 1997;123:53-56.

[10] Merchant TE, Parsh N, del Valle PL, et al. Brachytherapy for pediatric soft-tissue sarcoma. Int J Radiat Oncol Biol Phys. 2000;46:427-432.