Should brachytherapy play a key role in the treatment of adult malignant brain tumors?
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Yes.
Brachytherapy for the treatment of intracranial malignancies holds tremendous promise for optimal management of these frequently complex patients.
Adjuvant radiation therapy is necessary in several diseases of the central nervous system, including primary malignancies and metastases. Although most standard approaches utilize external beam radiotherapy (EBRT), brachytherapy presents an opportunity to improve patient care by increasing patient convenience and perhaps permitting effective escalation of therapy without increasing toxicity.
Completion of radiotherapy during surgery has an obvious practical advantage over sometimes weeks-long adjuvant radiotherapy courses, permitting patients to resume or initiate systemic therapy sooner after surgery and spend less time commuting to and from radiotherapy treatment centers. With implantation in the surgical cavity, risk to scalp wound healing is minimized, in contrast to EBRT or even stereotactic radiosurgery as the path of the radiation may be directly in line with the scar.
Tumor recurrence after previous surgery and radiation is a difficult challenge in the management of patients with gliomas, meningiomas and metastases. Brachytherapy performed at the time of resection of recurrent tumor gives the treating team a new radiation option after failed prior surgical, medical and radiation treatments. With practical advances and optimization of isotope selection such as GammaTile (GT Medical Technologies) brachytherapy with dosimetrically spaced cesium-131, a conformal dose can be delivered quickly over a few weeks due to the short half-life and rapid dose fall of the lower-energy gamma rays. In addition, early evidence with cesium-131 suggests there may be a lower incidence of radiation necrosis, especially beneficial in previously irradiated brain tissue. The immediate initiation and continuous dose delivery may offer higher local control for tumors located within 5 mm of the resection cavity by limiting tumor cell division during the normal time frame between surgery and adjuvant therapy, as well as limiting repopulation that may occur between radiotherapy fractions using conventional EBRT approaches.
Patients with recurrence of CNS disease after standard approaches are complex and require a thoughtful multidisciplinary team to develop treatment strategies. In such situations, intracranial brachytherapy is an important tool and should be considered when local control of a previously irradiated brain metastasis or primary neoplasm is clinically important. In settings where standards of care are well developed, such as initial adjuvant radiotherapy for primary CNS neoplasms or adjuvant therapy for brain metastases, enrolling patients in clinical trials evaluating whether brachytherapy can improve patient outcomes is our preferred approach.
Jeffrey S. Weinberg, MD, FAANS, FACS, is professor of neurosurgery and deputy chair and vice chair of clinical operations in the department of neurosurgery at The University of Texas MD Anderson Cancer Center.
Thomas H. Beckham, MD, PhD, is assistant professor of radiation oncology at The University of Texas MD Anderson Cancer Center.
No.
The role of brachytherapy for malignant gliomas has been well investigated and found to confer no survival benefit for patients when combined with best surgical resection and standard external radiotherapy. Two prospective randomized trials demonstrated this decades ago when compared with standard external beam dosing — although superior to substandard dosing in one study — despite earlier promising phase 2 studies with results skewed by selection bias. A higher risk for radiation necrosis and second surgeries related to this was a side effect experienced by the population that received the radioactive seeds.
Since then, numerous phase 1 or phase 2 trials have purported improved tumor control and/or survival using a myriad of different isotopes and delivery techniques, but none subjected to prospective randomization. In most cases, any gains were similar to those seen in the biased phase 2 studies with iodine-125. In fact, dose intensification, above the current standard external beam dose of 60 Gy in 30 treatments by any means, including radiosurgery, has never shown a survival advantage over standard of care when subjected to prospective randomized trials.
The role of brachytherapy at tumor recurrence or progression is murkier as brachytherapy has not been assessed in a randomized, prospective manner, and no standard of care exists in these situations.
- References:
- Laperriere NJ, et al. Int J Radiat Oncol Biol Phys. 1998;doi:10.1016/s0360-3016(98)00159-x.
- Selker RG, et al. Neurosurgery. 2002;51:343-355.
Gene Barnett, MD, MBA, FAANS, FACS, is professor and director of Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center at Cleveland Clinic. He can be reached at barnetg@ccf.org.
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