Advanced-Technology Radiation Therapy for Bone Sarcomas

Samir Patel, MD; Thomas F. DeLaney, MD


Cancer Control. 2008;15(1):21-37. 

In This Article

Abstract and Introduction

Background: Bone sarcomas are rare primary tumors. Radiation therapy (RT) can be useful in securing local control in cases where negative surgical margins cannot be obtained or where tumors are not resected. Recent technical advances in RT offer the opportunity to deliver radiation to these tumors with higher precision, thus allowing higher doses to the tumor target with lower doses to critical normal tissues, which can improve local tumor control and/or reduce treatment-related morbidity.
Methods: The authors conducted a survey of recent technical developments that have been applied to the RT for bone sarcomas.
Results: RT techniques that show promise include intensity-modulated photon radiation therapy, 3-D conformal proton RT, intensity-modulated proton RT, heavy charged-particle RT, intraoperative RT, and brachytherapy.All of these techniques permit the delivery of higher radiation doses to the target and less dose to normal tissue than had been possible with conventional 3-D conformal radiation techniques. Protons deliver substantially less dose to normal tissues than photons.
Conclusions: Data from clinical studies using these advanced radiation techniques suggest that they can improve the therapeutic ratio (the ratio of local control efficacy to the risk of complications). This is expected to improve the treatment outcome for these challenging tumors.

Current management of bone sarcomas is based on a multidisciplinary approach using a combination of surgery, radiotherapy, and chemotherapy specific for tumor type, histologic grade, and stage of disease. Because these tumors are relatively uncommon and are present in a variety of anatomic locations, most clinicians see these tumors infrequently. However, because they can often be successfully treated with good functional outcome by sarcoma centers with appropriate multidisciplinary expertise, referral to centers with experienced sarcoma teams is the most appropriate management strategy.

Surgery is the preferred treatment for the primary site in most patients with bone sarcomas and results in high rates of local control in patients with extremity tumors. In the case of primary extremity osteosarcomas, for example, the rate of local control with chemotherapy and surgical resection is over 90%.[1] In contrast, in osteosarcoma lesions of the head and neck, spine, and pelvis, local control with surgery and chemotherapy is less favorable. The local recurrence rate for lesions in the pelvis was 70% in 67 patients reported by the Cooperative Osteosarcoma Study Group, with recurrence developing in 31 (62%) of 50 patients who underwent resection and in 16 (94%) of 17 who did not.[2] Of 22 patients with spinal osteosarcomas reported by Ozaki et al,[3] 15 (68%) experienced local failure. For patients with head and neck osteosarcomas, local control is achieved in approximately 50% of patients, with the mandible the most favorable site, followed by the maxilla and then extragnathic sites (zygoma, orbit, nasoethmoid, and cranial bones).[4,5]

RT can be useful in helping to secure local control in these unfavorable sites.[2,6] Radiation can be employed as neoadjuvant (preoperative), adjuvant (postoperative or intraoperative), or primary local therapy depending on the site and type of tumor,the availability and acceptability of the surgical option, and the efficacy of the chemotherapy. Neoadjuvant (preoperative) RT can be delivered prior to resection of sarcomas of the spine[7] or pelvis.[8] Adjuvant radiation is used for patients with bone sarcomas with positive or inadequate margins and in selected other situations that might include presentation with a pathologic fracture,[9] poor histologic response to chemotherapy,[10] inadvertent hematoma after biopsy, or intralesional excision of or intramedullary rod placement through a radiographically or cytologically benign-appearing lesion later found to be sarcoma on review of final pathologic material. RT as the primary local therapy without surgery is used for medically inoperable patients, for patients with axial Ewing's sarcomas or extremity Ewing's sarcomas where surgery would compromise function,[11] and for patients with primary bone tumors involving the upper sacrum,[12] portions of the pelvis, the base of skull, and the ethmoid/sphenoid sinus region where complete resection is either not technically possible or unacceptable to the patient.[13,14]

Ewing's sarcomas are quite radiation sensitive, and the original description of this tumor by James Ewing made note of the fact that the radiation sensitivity of this tumor was one of the features distinguishing it from other bone sarcomas.[15] Unresected tumor or gross residual disease is usually treated with 55.8 Gy in association with chemotherapy.[11] Consideration of higher doses for high-risk bulky axial tumors might be appropriate. Due to spinal cord constraints, vertebral lesions have often been treated with doses to 45 to 50 Gy. Microscopic residual disease is usually treated to 50.4 Gy.

Chondrosarcomas and osteogenic sarcomas require doses of approximately 66 Gy for control of microscopic residual disease and doses of ≥70 Gy for control of gross residual disease. Because most osteosarcomas are treated in conjunction with chemotherapy, our policy for patients (particularly for younger patients) with unresectable or gross residual disease has been to start treatment with induction chemotherapy using doxorubicin platinum and methotrexate per established protocols and then, after approximately 12 weeks of chemotherapy, deliver radiation of 70.2 Gy in 39 fractions of 1.8 Gy daily via shrinking field technique concurrent with chemotherapy, generally ifosfamide/ etoposide. Generally, chondrosarcomas in patients with gross disease have been managed with 70 to 77.4 Gy at 1.8 to 2 Gy daily, depending on the volume of disease and the RT tolerance of adjacent tissues. Chordomas require doses of approximately 70 Gy for microscopic residual disease and doses of >75 Gy for control of gross residual disease.[16]

Radiation is most commonly given by externally directed beams, but it can also be given by brachytherapy or intraoperative techniques. Brachytherapy has been most extensively employed in the adjuvant radiation of soft tissue sarcomas.[17] More recently it has been applied on the dura and paraspinal tissues for spine and paraspinal tumors[7,18,19] and for some Ewing's sarcomas with inadequate surgical margins.[20] Intraoperative RT with electron beam or orthovoltage is delivered to the tumor or tumor bed at the time of surgery and can be particularly useful to boost the dose to tumors around the pelvic girdle[21] and spine. Brachytherapy and intraoperative RT, although technically challenging, have been adopted in many specialized centers because of their dosimetric advantages over conventional external-beam therapy and reduction in integral dose to normal tissue.

Intensity-modulated photon radiation therapy (IMRT) is increasingly being employed for treatment of challenging bone sarcomas of the axial skeleton because of the higher conformality of dose and sparing of selected normal tissues from the high-dose region.[22] Because RT for sarcomas often requires high doses in close proximity to sensitive normal tissues,protons and other charged particles are an excellent treatment option for these patients when external-beam irradiation is part of the RT treatment plan. Sarcomas of the skull base and cervical spine were among the first tumors to be treated with protons on a concerted basis and one of the anatomic sites at which excellent clinical results have been achieved with this modality.[14,23] With an increasing number of proton therapy facilities, experience with this modality continues to grow. Interesting results have also been reported with heavier charged particles, initially helium and neon from Berkeley Laboratory[24] and more recently carbon ions from the National Institute of Radiological Sciences in Chiba, Japan,[25] and Gesellschaft für Schwerionenforschung (GSI) in Darmstadt, Germany.[26]


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