Proton therapy and sarcomas

Introduction

Sarcomas are a rare and heterogenous group of malignant tumors that arise from soft tissues or bone. They constitute less than 1% of all adult malignancies and approximately 12% of pediatric cancers. Approximately 80% to 84% of sarcomas originate from soft tissues, and the rest originate from bone. ^, Given the histopathologic spectrum and ability of sarcomas to arise anywhere in the body, treatment paradigms are often dictated by the histology, grade, site of origin, stage, and age of the patient.

Surgical resection remains the mainstay of treatment when possible. For soft tissue sarcomas, radiation therapy (RT) has an integral role in the treatment approach. The combination of RT and a wide local excision (limb-sparing surgery) leads to better local control (LC) than does either modality alone for most soft tissue sarcomas. This was demonstrated in two randomized trials, both of which showed that combined-modality therapy resulted in a reduced risk of local recurrence by approximately 20% to 25%. RT can be administered preoperatively or postoperatively, and both have their advantages. Our practice consistently uses preoperative RT, which is endorsed by our multidisciplinary teams because of the lower rates of radiation-related late toxicities.

The use of RT for bone sarcomas depends strongly on the histology and resectability of the tumor. For bone sarcomas that are unresectable, primary RT is commonly used to achieve LC, with varying degrees of success; one study showed a 5-year LC rate of 56% among patients with nonmetastatic extremity osteosarcoma who refused resection. Postoperative radiation may also be used for sarcomas originating in bone, depending on the margin status and response of the tumor to chemotherapy.

Although the list of sarcoma histologies is too exhaustive to review in this chapter, readers should be aware of several of the more common types. Some of the most common types of soft tissue sarcomas include undifferentiated pleomorphic sarcoma (historically called malignant fibrous histiocytoma), liposarcoma, leiomyosarcoma, and synovial sarcoma. Unusual but important subtypes also include desmoid tumors and dermatofibrosarcoma protuberans, both of which can be locally aggressive. Several of the more common bone sarcomas include osteosarcoma, Ewing sarcoma, and chondrosarcoma.

Much of the treatment paradigm, consisting of surgery and RT, with or without chemotherapy, is based on histology. However, the anatomic site of origin is also a critical factor to consider, particularly for the choice of local therapy. For instance, the strategy to treat a sarcoma in the distal leg is often different than that for a sarcoma that arises in the base of skull or retroperitoneum. Not only does the site of origin matter from a surgical standpoint, but also it factors into the approach taken by the radiation oncologist. Different anatomic sites require thoughtful radiation planning because of treatment volumes, neighboring critical structures, and toxicity considerations.

One radiation modalities with increasing applicability for the treatment of sarcomas is proton beam radiation. The goal of this chapter is to provide some perspective on the use of proton beam RT and summarize the available data supporting its use in the treatment of sarcomas.