January/February 2005, Vol. 12, No. 1

Authors: Thomas F. DeLaney, MD; Alexei V. Trofimov, PhD; Martijn Engelsman, PhD; Herman D. Suit, MD, DPhil

Abstract

Background: For patients with sarcomas, radiotherapy can be used as neoadjuvant, adjuvant, or primary local therapy, depending on the site and type of sarcoma, the surgical approach, and the efficacy of chemotherapy.
Methods: The authors review the current status of advanced technology radiation therapy in the management of bone and soft tissue sarcoma.
Results: Advances in radiotherapy have resulted in improved treatment for bone and soft tissue sarcomas. Intensity-modulated radiation therapy (IMRT) uses modifications in the intensity of the photon-beam from a linear accelerator across the irradiated fields to enhance dose conformation in three dimensions. For proton-beam radiation therapy, the nuclei of hydrogen atoms are accelerated in cyclotrons or synchrotrons, extracted, and transported to treatment rooms where the proton beam undergoes a series of modifications that conform the dose in a particular patient to the tumor target. Brachytherapy and intraoperative radiation therapy have generally been used to treat microscopic residual disease in patients with sarcomas. These technologies deliver dose to tumor cells with irradiation of limited volumes of normal tissue. Patients who may benefit from technically advanced radiotherapy include those with skull base and spine/paraspinal sarcomas, Ewing's sarcoma, and retroperitoneal/extremity sarcomas.
Conclusions: Advances in radiation therapy technology, particularly IMRT, proton-beam or other charged-particle radiation therapy, brachytherapy, and intraoperative radiation therapy, have led to improved treatment for patients with bone and soft tissue sarcomas.

Introduction

Contemporary management of sarcomas often includes a multidisciplinary approach using a combination of surgery, radiotherapy, and chemotherapy specific for tumor type, histologic grade, and stage of disease. Radiotherapy can be employed as neoadjuvant (preoperative), adjuvant (postoperative), 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 radiotherapy is frequently used for large, deep soft tissue sarcomas[1] and can also be delivered prior to resection of spine[2] or pelvic sarcomas.[3] Adjuvant radiation is utilized in many centers following resection of soft tissue sarcomas if tumor, or surgically contaminated tissues in patients with incomplete excision, cannot be excised with a minimum of 1 cm of healthy tissue or an intact fascial plane.[4] It is also used for patients with bone sarcomas with positive or inadequate margins and in selected other situations that might include presentation with a pathologic fracture,[5] poor histologic response to chemotherapy,[6] 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. Radiotherapy as the primary local therapy without surgery or in conjunction with subtotal resection is used for soft tissue sarcomas that are medically inoperable,[7] for axial Ewing's sarcomas or extremity Ewing's sarcomas where surgery would compromise function,[8] and for primary bone tumors involving the upper sacrum,[9] the base of skull, and some arising in the ethmoid/sphenoid sinus region.[10]

Radiation therapy (RT) is most commonly given by externally directed beams but can also be given by brachytherapy (BT) or intraoperative techniques. BT utilizes temporary or permanent radiation sources that are placed either into or adjacent to tumor tissue. BT has been used in the adjuvant radiation of soft tissue sarcomas.[11] More recently, it has been applied on the dura and paraspinal tissues for spine and paraspinal tumors[2,12,13] and for some Ewing's sarcomas with inadequate surgical margins.[14] Intraoperative radiotherapy (IORT) with electron beam or orthovoltage is delivered to the tumor bed at surgery to boost the dose to retroperitoneal,[15] paraspinal and spinal, and pelvic sarcomas.[16] BT and IORT, although technically challenging, have been adopted in many specialized centers because of their dosimetric advantages over conventional external RT. BT and IORT allow higher radiation doses to the tumor while sparing normal tissue, which results in higher tumor control and fewer normal tissue complications. In the case of BT, this is achieved by placing radiation sources in close contact with the tumor bed and the rapid fall-off in dose away from the radiation sources. Traditionally, this has been done with low-dose-rate iridium-192 (and occasionally less energetic iodine125), but more recently high-dose-rate sources have been employed.[17] In the case of IORT, this is achieved by moving critical normal tissues such as bowel, kidney, or lung out of the IORT beam at the time of surgery.