Peer-Review ReportStereotactic Radiosurgery as the Primary Treatment for New and Recurrent Paragangliomas: Is Open Surgical Resection Still the Treatment of Choice?
Introduction
Paragangliomas (PGs), glomus tumors, or chemodectomas are rare, indolent, vascular tumors that arise from the chief cells of the paraganglia (9, 20, 110). PGs most commonly occur in association with the jugular bulb and comprise 0.6% of intracranial tumors (135). They also arise along the vagus nerve or at the carotid body (56, 137) and have been reported elsewhere in association with rest of the paraganglia. They most commonly cause symptoms by compressing neighboring cranial nerves or vessels, or eroding bone (68). Two percent to 5% of PGs secrete catecholamines (20, 35, 111). Approximately 3%–5% of base-of-skull PGs and 10%–15% of those in the neck are malignant (28, 51, 52, 90). Most PGs are sporadic, but 7%–9% are familial (110). The inherited forms are more often multicentric, present at an earlier age, and have a higher risk of metastasis (50, 93, 103, 104, 140). Transmission is autosomal dominant (124) and related to at least four specific mutations affecting different subunits of the gene encoding for succinate dehydrogenase (11). PGs are uncommonly associated with other syndromes, including multiple endocrine neoplasia type 2, neurofibromatosis type 2, and von Hippel–Lindau disease (124, 131).
Surgical resection was the only treatment option before the availability of radiotherapy (RT) in the 1950s. Surgical recurrence rates as high as 80% and complication rates approaching 50% made RT more attractive for high-risk lesions (120). In the 1990s, stereotactic radiosurgery (SRS) emerged as a treatment alternative and eventually replaced RT in many centers (71). Studies using Gamma Knife (Elekta AB; Stockholm, Sweden) and LINAC-based systems described excellent results (32, 33, 36, 38, 68, 84), but debate continues as to specific indications for open resection, RT, and SRS (70). Some limited, single-institution reviews retrospectively evaluating more than one type of treatment are available (56), but PGs are so uncommon and slow growing that a prospective, randomized, controlled trial comparing SRS, RT, and surgery would be impractical. In the absence of class I data, we sought to derive treatment guidelines by combining our SRS experience with a review of the literature.
Section snippets
Materials and Methods: Clinical
After obtaining the approval of the Institutional Review Board, the CyberKnife Center database was searched. We identified 36 patients with 41 lesions, treated between July 1991 and November 2009. Patients were included if they received SRS alone or SRS as a salvage treatment. Age, sex, tumor location, dose, pre- and posttreatment symptoms and signs, lesion location and size by magnetic resonance imaging (MRI), recurrences, and complications were abstracted from the medical records. All living
Materials and Methods: Literature Review
Using various combinations of the keywords chemotherapy, CyberKnife, expectant, Gamma Knife, glomus, LINAC, paraganglioma, radiation therapy, radiotherapy, radiosurgery, resection, stereotactic, surgery, X-ray therapy, and XRT, we used PubMed to search the National Library of Medicine database through August 21, 2010. Additional clinical series, especially those in older publications, were identified in citations in the other review articles. There were no limits placed on the date of
Symptomatic Outcomes
One of the 26 patients with neurologic deficits before treatment had a lasting increase in vertigo (patient 2, Table 2), 2 had transiently increased cranial neuropathies (facial nerve deficits in one patient and dysphagia in one), 5 were unchanged, 10 recovered partially, and 8 recovered entirely following treatment. Of 6 patients with pretreatment complaints of pulsatile tinnitus, 4 reported resolution after SRS and in 3 the improvement occurred before the 3-month follow-up visit.
Tumor Control
Three
Expectant Management
Van der Mey et al. (140), who followed 108 patients with 175 tumors for up to 32 years, addressed expectant management in addition to outcomes following surgery. The morbidity of those who underwent radical surgery included multiple cranial neuropathies, strokes, meningitis, cerebrospinal fluid (CSF) leak, and other significant complications. Of their patients treated expectantly, or with limited resection, none died from recurrent or residual tumor and none developed metastases during the 32
A Treatment Algorithm
The ideal algorithm would maximize the likelihood of controlling tumor growth while minimizing risk. It would also be straightforward, easily implemented, and provide a standardized framework that would facilitate later study. Figure 2 summarizes the following treatment recommendations.
Because PGs are slow growing, and many never progress, one must first decide which PGs to treat and which to follow. The literature on expectant management is scant. Van der Mey et al. (140) have argued that only
Conclusions
Open surgery provides good local control rates, but published series describe a high rate of complications. The complications of open surgery are often disabling. RT offers higher local control rates than open surgery with far less risk. RT remains a good option. At our center, SRS provided a 100% local control rate with 3.9 years of clinical follow-up and minimal toxicity. Similar results have been published by numerous other authors. SRS is also delivered more quickly and conveniently than RT
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Conflict of interest statement: Dr. Adler was previously a principal in Accuray. Dr. Gibbs is a paid lecturer for Accuray. This work is in part supported by Robert C. and Jeannette Powell, Alan Wong and Sylvia Tang, and Paula and William Zappettini to Steven D. Chang, M.D.