International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationsTemporal Lobe (TL) Damage Following Surgery and High-Dose Photon and Proton Irradiation in 96 Patients Affected by Chordomas and Chondrosarcomas of the Base of the Skull
Introduction
The physical properties of the proton beam that make it attractive for radiation therapy are represented by their finite range in tissues due to the Bragg peak and sharply defined lateral beam edges. These features provide the basis for proton dose distributions that are superior to those obtainable with photons in many tumor to healthy tissue relationships, particularly at the base of the skull. The dose delivered to a tumor using protons can, consequently, be increased to a certain extent, with proton beam therapy (PBT), relative to that which can be delivered with photon therapy while maintaining a comparable rate of treatment-related morbidity. This difference in volume of healthy tissues included in comparison to photons is primarily due to minimal dose beyond the target due to the Bragg peak of the proton radiation.
Chordomas and chondrosarcomas of the base of the skull present a worthy challenge to the neurosurgeon and the radiation oncologist and are judged to be a good example of tumors that may likely benefit from high-dose proton radiation. With photon radiation therapy, only moderate doses of radiation can be delivered to the primary target, and most of these patients die with locally progressive disease [1]. The total dose that can safely be delivered to the tumor is limited by the close proximity of healthy structures, such as the brain stem, temporal lobes, and optic chiasm and nerves. As a consequence of these particular tumor-healthy tissue relationships, and of the vital importance of the nervous structures, clinicians limit the radiation dose to levels tolerated by these structures (although the dose–response relationship for the central nervous system (CNS) has not yet been completely assessed) [2]. Irradiation of the CNS can, in fact, produce a wide range of clinically expressed, as well as silent, injuries in the brain 3, 4, 5, which have been described in patients receiving doses in excess of 45 Gy [6].
Identification of radiation damage as a distinct entity from the effects of the tumor growth, surgical procedures, or other incidental pathologies is crucial to devise new protocols for dose-escalation studies, and to evaluate retrospectively the cost-benefit of the clinical achievements. The knowledge of the tolerance dose of the healthy tissues is essential to maximize the dose prescribed to the targets and, thereby, achieve the highest tumor control with a low probability of damaging healthy surrounding tissues.
To contribute to the comprehension of CNS late effects, after high-dose irradiation, we report our experience based on an analysis of 96 consecutive patients affected by chordomas or chondrosarcomas of the base of the skull who were treated with high-dose proton and photon irradiation and were randomized to receive 66.6 or 72 CGE on a controlled, prospective dose-searching study. The aim of the present study was to examine the correlation between clinical and imaging signs of temporal lobe damage and dose, features of the tumor, distortion of the normal anatomy induced by the tumor, number of surgical procedures, and other host characteristics.
Section snippets
Methods and Materials
Ninety-six consecutive patients with chordomas and chondrosarcomas of the base of the skull were randomized to receive 66.6 or 72 CGE in a prospective dose-searching study (RTOG-Radiation Therapy Oncology Group #85-26) by proton and photon techniques at the Massachusetts General Hospital (MGH) and Harvard Cyclotron Laboratory (HCL) between July 1984 and July 1993.
The patients ranged in age from 11 to 80 years, with a median of 44 years; there were 51 males and 45 females. Of the tumors, 41 were
Results
The 2- and 5-year cumulative TL damage rates were 7.6 and 13.2%, respectively (standard errors 2.8 and 4.1, respectively). Ten patients with TL damage were identified, 1 with MRI white matter changes only, and 9 with both MRI changes and clinically evident TL injury. One had Grade 2 and 8 had Grade 3 injury. One patient developed multiple Grade 2 symptoms and 7 suffered Grade 3 symptoms (4 of 7 one Grade 3 only, 2 of 7 multiple Grade 3, and 1 of 7 Grade 3 and 2). Epilepsy and deterioration of
Discussion
The classical late adverse effect of therapeutic or incidental brain irradiation is localized necrotic reaction, which occurs typically at a few months to several years after irradiation and is usually associated with neurological symptoms that cannot be attributed to recurrent tumor [14].
After high-dose radiation therapy, “the specific endpoint chosen for complication of the brain is radionecrosis” [2]. Burger et al. [15]provided a clear description of the histological modifications associated
References (37)
- et al.
Tolerance of normal tissue to therapeutic irradiation
Int. J. Radiat. Oncol. Biol. Phys.
(1991) - et al.
Therapeutic irradiation and brain injury
Int. J. Radiat. Oncol. Biol. Phys.
(1980) - et al.
Cerebral radionecrosisincidence and risk in relation to dose, time, fractionation and volume
Int. J. Radiat. Oncol. Biol. Phys.
(1981) - et al.
Relative biological effectiveness of modulated proton beams in various murine tissues
Int. J. Radiat. Oncol. Biol. Phys.
(1984) - et al.
Multi-dimensional treatment planningI. Delineation of anatomy
Int. J. Radiat. Oncol. Biol. Phys.
(1983) - et al.
Multi-dimensional treatment planningII. Beam’s eye-view, back projection, and projection through CT sections
Int. J. Radiat. Oncol. Biol. Phys.
(1983) Compensation for inhomogeneities in charged particle radiotherapy using computed tomography
Int. J. Radiat. Oncol. Biol. Phys.
(1978)- et al.
Precise positioning of patients for radiation therapy
Int. J. Radiat. Oncol. Biol. Phys.
(1982) - et al.
Radiation response of the central nervous system
Int. J. Radiat. Oncol. Biol. Phys.
(1995) - et al.
Changes in early and late radiation responses with altered fractionationImplications for dose-survival relationships
Int. J. Radiat. Oncol. Biol. Phys.
(1982)