Advanced-Technology Radiation Therapy in the Management of Bone and Soft Tissue Sarcomas
Technically Advanced Radiotherapy in Selected Patients
Sarcomas of the Skull Base
Treatment of patients with these tumors is difficult and complex because of the proximity of the brain stem and the base of the brain. These factors have limited both surgical approaches and treatment with conventional RT. The rapid fall-off of dose at the end of the range of the proton beam was judged to be particularly suitable for treatment of these tumors from the days of the initial use of protons in the clinic. In fact, the physical advantage of protons allowed for significant dose escalation for these patients. Rosenberg et al[57] reported the actuarial 5- and 10-year actuarial local control rates of 99% and 98%, respectively, for 200 patients treated for chondrosarcomas of the base of the skull who received a median dose of 72.1 CGE in 38 fractions.Although some reports in the oncology literature note that chondrosarcomas are not sensitive to RT, these results clearly contradict that assertion. Interestingly, patients with chordomas of the skull base treated to a similar median dose of 68.9 CGE experience worse treatment outcome, with actuarial local control rates of 59% and 44% at 5 and 10 years, respectively.[58] Similar results were reported by Hug et al,[59] who noted local control in 92% of patients with chondrosarcomas and in 76% of patients with chordomas. They reported symptomatic grade 3-4 toxicities in 5% of patients. These results are better than those observed in cases where patients with chondrosarcomas and chordomas of the skull base were treated with photons to a median dose of 55 Gy in which the estimated local control was only 36%.[60] A randomized proton dose evaluation study for patients with chordomas of the cervical spine and base of skull is currently underway at the Northeast Proton Therapy Center. Higher-risk patients, ie, all patients with cervical spine tumors and women with base of skull lesions, are randomized to receive either 75.4 or 82.9 CGE, while lower-risk men with base of skull lesions are randomized to receive 69.7 or 75.4 CGE.
Sarcomas of the Spine and Paraspinal Tissues
Because of the proximity of the spinal cord, RT for treatment of tumors of the spine and paraspinal soft tissues is constrained by the radiation tolerance of the spinal cord, which is generally quoted at 45 Gy. This dose is below that necessary to reliably control most sarcomas, which require doses of approximately 60 Gy for subclinical microscopic disease, 66 Gy for microscopically positive margins, and more than 70 Gy for gross residual disease. With its ability to spare adjacent tissues, proton RT offers advantages for treatment of tumors in this location. Isacsson et al[61] compared conformal RT treatment plans with photons and protons for a patient with a cervical Ewing's sarcoma. Even when only the final 20% of the treatment -- the boost to the gross disease -- was given with protons, they noted a 5% improvement in local control for a comparable predicted risk of spinal cord injury. In a comparison of IMRT with IMPT treatment plans for spine and paraspinal sarcomas,Weber et al[50] noted that although the results were similar in levels of tumor conformation, IMPT reduced the integral (normal tissue) dose to organs at risk.
Hug and colleagues[9] presented results on combined photon/proton treatment of 47 patients with osteogenic and chondrogenic tumors of the axial skeleton. RT was delivered postoperatively in 23 patients, preoperatively and postoperatively in 17, and as sole treatment in 7 patients. Mean RT doses of 73.9 CGE, 69.8 CGE, and 61.8 CGE were delivered to group 1 (20 patients with recurrent/primary chordoma or chondrosarcoma), group 2 (15 patients with osteogenic sarcomas), and group 3 (12 patients with giant cell tumors, osteoblastomas, or chondroblastomas), respectively. For patients in group 1, the 5year actuarial local control and survival rates for patients with chondrosarcomas were both 100%, and for those with chordoma, these rates were 53% and 50%, respectively. For patients in group 2, the 5-year actuarial local control rate was 59%. For patients in group 3, the 5-year actuarial local control and survival rates were 76% and 87%, respectively. Overall, improved local control was noted for primary vs recurrent tumors, gross total resection, and target doses >77 CGE. Similar results have been reported with charged-particle therapy.[62] We currently are conducting an ongoing phase II study of combined photon and proton-beam RT in conjunction with maximal surgical resection (and dural plaque BT when possible) at the Northeast Proton Therapy Center for patients with spinal and paraspinal sarcomas.
Ewing's Sarcoma
Management of truncal, craniofacial, spinal, and pelvic Ewing's sarcomas is complex due to the critical importance of the normal structures in the vicinity of the tumor and also due to the frequent surgical resection with positive or close margins. For these sites, surgical resection and RT can be limited by the proximity of the tumor to critical organs. Local failure rates are often more than 50%.[63] Highly localized dose distributions offer the possibility of increasing local control as well as decreasing late effects. Smith et al[64] performed comparative treatment planning comparing IMRT with IMPT for a pelvic Ewing's sarcoma patient and noted sparing of the intestine, rectum, bladder, and femoral head with IMPT (Figure 3). These results demonstrate a significant potential for reduction of treatment morbidity with protons. In addition to less acute morbidity to bowel and marrow during concurrent chemoradiation, one would anticipate a reduction in late radiation-induced tumors, a problem with conventional photon radiotherapy for these patients.[65] Proton-beam RT has been approved for use in Children's Cooperative Oncology group protocols.
Retroperitoneal Sarcomas
Normal tissue, including bowel, liver, kidneys, and spinal cord, can limit the radiation doses that can be delivered for patients with retroperitoneal sarcomas. Treatment comparisons have shown a reduction in dose to normal tissue organs at risk with IMRT compared to 3-D conformal photons for patients with retroperitoneal sarcomas.[66] Additional dose reductions are anticipated with proton-beam RT. When combined with IORT, these techniques should result in improved outcomes.[15,55]
Extremity Sarcomas
Compared with postoperative RT, preoperative RT for extremity soft tissue sarcomas is associated with a higher rate of acute wound-healing complications but fewer late complications.[67] IMRT may reduce the dose delivered to the skin and subcutaneous tissues in some patients,[47] thereby reducing wound-healing complications associated with preoperative RT. Similar or greater advantages are to be expected with the proton beam. Potential late effects on bone, such as pathologic fractures following periosteal stripping, might also be reduced because of reductions in dose to the femur. These potential advantages need to be validated in clinical trials.[67]
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