Advanced-Technology Radiation Therapy for Bone Sarcomas

Sarcomas of the Skull Base

Proton RT for skull base and cervical spine chordomas and chondrosarcomas has resulted in the best long-term outcome data ever reported for these entities.^[14] Proton irradiation is considered by many neurosurgeons and radiation oncologists around the world to be the treatment of choice following surgical resection. Fractionated proton radiotherapy allows the delivery of high radiation doses to tumors of the skull base while respecting normal tissue constraints. Relatively few significant complications have been observed, when considering the high doses delivered and when weighed against the certainty of major morbidity associated with otherwise uncontrollable tumor growth in such patients.

Outcome is substantially more favorable with chondrosarcomas than with chordomas,with local control at 10 years of 94% and 54%, respectively. In the MGH Harvard Cyclotron Laboratory (MGH/HCL) series of patients with chordomas, male patients had more favorable outcome that female patients, with local recurrence-free survival rates at 5 years of 81% vs 65% (P=.035) and at 10 years of 65% vs 42% (P=.007), respectively. Hug^[13] reported a more favorable outcome in skull base chordomas if the tumor volume at the time of proton radiotherapy was ≤25 cc. Patients with extensive abutment or compression of critical organs at risk (ie, brainstem, optic structures) by chordomas fare worse^[69] because normal tissue radiation constraints compromise the dose that can be delivered to the tumor target.^[70] Patients with chordomas also appear to have a favorable prognosis if they undergo proton radiotherapy at the time of primary disease,^[16] if they are of younger adult age,^[14] and if they have the non-chondroid variant.^[71]

Late, severe adverse events were reported by the MGH/HCL group^[14] in 8% of their patient population (20 patients), including 12 instances of symptomatic or asymptomatic brain changes, 3 patients with unilateral and 2 patients with bilateral blindness, and 4 instances of unilateral deafness. Several risk factors have been identified predicting severe adverse events. Debus et al^[72] found that a dose of >60 Gy (RBE) to a volume of brainstem ≥0.9 cc was more important in predicting brainstem damage than was the maximum dose. Diabetes, a history of smoking, hypertension, and repeat surgical resections led to reduced tolerance of the normal brainstem.

Prior to the advent of 3-dimensional treatment planning and highly conformal radiation techniques such as protons and IMRT, attempts to deliver tumoricidal radiation doses to tumors in the skull base were limited by critical normal tissue tolerance. In that era, photon radiation doses ranged between 50 and 60 Gy and, not surprisingly, tumors recurred locally in 70% to 100% of the patients treated.^[73,74] However, the recently published series of Hacettepe University in Ankara, Turkey, used modern imaging and radiation treatment techniques but at conventional doses.^[75] A 5-year progression-free survival rate of 23% and an overall survival rate of 35% in 18 patients with clival chordomas following 50 to 64 Gy confirm the poor outcome with these doses and emphasize the importance of high target doses.

In stark contrast, proton radiotherapy with mean doses of 71 CGE in the Loma Linda series^[13] and of doses up to 83 CGE at MGH/HCL resulted in improved tumor control.^[14] At present,almost all patients undergoing proton radiotherapy worldwide receive fractionated doses greater than 66 CGE.^[13] Stereotactic and IMRT photon techniques now permit the delivery of higher radiation doses to skull base tumors with photons than had been possible in the past. No phase III trial has been conducted that prospectively compares various photon-based radiation modalities with protons. The scientific value of comparing single institution data is limited, given for example the differences in patient selection criteria. Using 3-dimensional conformal, fractionated techniques under stereotactic guidance, Debus et al^[76] reported results of stereotactic photon radiotherapy in 45 patients with skull base chordomas or chondrosarcomas. Median dose levels were 66.6 Gy for chordomas and 64.9 Gy for chondrosarcomas,thus lower compared to protons but higher than historic, conventional photon techniques. All patients with chondrosarcomas remained locally controlled at 5 years. The local control rate for chordomas was 50% at 5 years and appeared to be improved compared to conventional photons but still inferior compared to protons.

The most mature data on Gamma knife radiosurgery have been reported by the Mayo Clinic. Krishnan et al^[77] analyzed 29 patients, 4 with chondrosarcomas and 25 with chordomas,treated radiosurgically and followed for a median 4.5 years. All 4 patients with chondrosarcomas remained locally controlled. However, the 5-year actuarial local control rate had dropped to 32% for patients with chordomas, despite the rather modest median pretreatment tumor volume of 14.4 cm^[3]. Ten patients (34%) experienced radiation-related complications.

Chang et al^[78] noted only 2 failures in 12 patients treated with either radiosurgery or hypofractionated stereotactic radiotherapy for chordomas of the skull base or cervical spine. Tumor volumes ranged from 1.1 to 21.5 mL and follow-up averaged 4 years. A similar report from Seoul, Korea, on the use of hypofractionated, stereotactic radiotherapy noted one failure in 9 patients at a median follow-up period of 24 months but also 2 occurrences of myelopathy.^[79] Several groups are currently exploring IMRT for use in skull base sarcomas, and it is anticipated that results with this technique will be reported in the near future.

Carbon-ion RT has been used by the German group at GSI. Four-year local control rates for chordomas and low-grade chondrosarcomas of the skull base in 67 patients were 74% and 87% at 4 years, respectively.^[26] This translated into overall survival rates at 4 years of 86% for chordomas and 100% for chondrosarcomas. Toxicity was reported to be mild.

Cancer Control. 2008;15(1):21-37. © 2008  H. Lee Moffitt Cancer Center and Research Institute, Inc.
© Copyright by H. Lee Moffitt Cancer Center & Research Institute. All rights reserved.

Cite this: Advanced-Technology Radiation Therapy for Bone Sarcomas - Medscape - Jan 01, 2008.