Robotic Stereotactic Radiosurgery in Patients with Unresectable Glomus Jugulare Tumors

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1 Technology in Cancer Research and Treatment ISSN Volume 12, Number 2, April 2013 Adenine Press (2013) Robotic Stereotactic Radiosurgery in Patients with Unresectable Glomus Jugulare Tumors DOI: /tcrt We evaluated the treatment results of robotic stereotactic radiosurgery (SRS) in our patients with unresectable glomus jugulare tumors (GJTs). The medical charts of fourteen patients with GJT, who were treated with robotic SRS, were retrospectively evaluated. The gross tumor volume was described as the clinical target volume. The median dose to the tumor was 25 Gy in median 5 fractions. The dose was normalized to 80% isodose line. All patients were evaluated for tumor growth and clinical outcome every 6 months in the first 2 years and then annually. Median follow-up was 39 months (range, 7-60 months). Lesions were stable in 8 patients, and tumor regression was observed in 6 patients. We did not observe any treatment related toxicity in our patients. In conclusion, according to our early experience, robotic SRS seems to be successful treatment option in the management of unresectable GJTs. Key words: Glomus tumors; Glomus jugulare; Robotic stereotactic radiosurgery. P. Hurmuz, M.D. M. Cengiz, M.D. G. Ozyigit, M.D.* G. Yazici, M.D. F. Akyol, M.D. F. Yildiz, M.D. M. Gurkaynak, M.D. F. Zorlu, M.D. Hacettepe University Faculty of Medicine, Department of Radiation Oncology, 06100, Sihhiye, Ankara, Turkey Introduction Glomus tumors (GT) are rare and highly vascular tumors that arise from paraganglia. Depending on the location, glomus tumors can be classified as tympanic (middle ear), jugulare, or carotid vagal (1, 2). Although they are histologically benign they may cause symptoms due to their local mass effect on adjacent structures. The treatment options for GTs include surgery, conventional external beam radiotherapy (EBRT), stereotactic radio-surgery (SRS), or a combination of these modalities. Surgery is preferred for small lesions. The aim of surgery is complete removal of the tumor, and in 86 to 92% of patients tumor control has been reported (3-5). However, there is also considerable risk of postoperative complications such as cerebrospinal fluid leak, meningitis, bleeding, wound infections, pulmonary embolism and lower cranial nerve deficits (5-7). EBRT has been used to treat unresectable tumors and patients with residual or recurrent lesions after surgery (8). Tumor control rates ranges from 79 to 94% and complication rates are between 4-20% with EBRT (8-12). However due to the wide margins used in EBRT, there is the risk of neurovascular damage in long term period (12, 13). SRS with Gamma Knife or linear accelerators achieved 77-98% local control rates especially for small lesions (14, 15). SRS provides Abbreviations: GJT: Glomus Jugulare Tumor; GT: Glomus Tumor; EBRT: External Beam Radiotherapy; SRS: Stereotactic Radiosurgery, MRI: Magnetic Resonance Imaging. *Corresponding author: Gokhan Ozyigit, M.D. Phone: Fax: gozyigit@hacettepe.edu.tr 109

2 110 Hurmuz et al. us to deliver ablative radiation doses to tumor with high accuracy. However, there are only a few studies on the use of robotic SRS for GJTs. In this aspect, we retrospectively evaluated the effect and the toxicity of robotic SRS in the management of patients with unresectable GJTs. Materials and Methods Patients and Methods Between June 2007 and September 2010, 14 patients with GJTs were treated in our department using robotic SRS. Informed consent from all patients was obtained prior to treatment. One patient was male, and 13 were female. All patients had radiological diagnosis of GJTs. Median age was 68 years (range, years). One patient had undergone a previous surgery. Robotic SRS was delivered with CyberKnife (Accuray Incorporated, Sunnyvale, CA, USA). All patients underwent a pre-treatment contrast enhanced computerized tomography with a slice thickness of 1.25 mm. CT images were fused with T1 and T2 weighted fat suppression magnetic resonance imaging (MRI) sequences. The gross tumor volume (GTV) was described as the clinical target volume (CTV). An extra 1.0 mm was added to CTV for planning target volume (PTV). Then, treatment plan was generated with Multiplan (Accuray Incorporated, Sunnyvale, CA, USA) inverse planning system (Figure 1). All individual plans were evaluated and approved by the responsible physician. The median dose to the tumor was 25 Gy (range, Gy) in median 5 fractions (range, 1-5 fractions). Only one patient was treated with a single fraction. The GTV was median 15.8 cc (range, 2-64 cc). The dose was normalized to 80% isodose line (range, 70-88%). The median homogeneity and conformality indices were 1.24 ( ) and 1.61 ( ), respectively. Normal tissue dose tolerance varies in function of fraction number. Table I shows the critical organ doses in patients who received fractionated robotic SRS. The values of three patients who had 3 fractions of treatment are also included in the table. All of them were below the tolerance levels except the median value of the maximum doses to the ipsilateral cochlea that is Gy (range, Gy). Follow-up All patients were evaluated for tumor growth and clinical outcome every 6 months in the first 2 years and then annually. Figure 1: The treatment plan of a patient with glomus jugulare tumor.

3 Robotic Stereotactic Radiosurgery in Glomus Jugulare Tumors 111 Table I Normal tissue dose-volume parameters in patients who received fractionated robotic radiosurgery. Parameter Median dose Min dose Maximum dose Ipsilateral cochlea Contralateral cochlea Brain stem Brain stem 1 cc vol max dose Ipsilateral optic nerve Ipsilateral optic nerve cc vol max dose Contralateral optic nerve Contralateral optic nerve cc vol max dose Chiasma Chiasma 0.2 cc vol max dose Abbreviations: 5 maximum dose; cc volume max dose 5 maximum dose received in given cc of volume. The lesions were evaluated via MRI. Local control was defined as the absence of progressive disease after robotic SRS on MRI. Tumor regression was defined as 20% decrease in tumor volume on the basis of the last available MRI. Clinical improvement was defined as any reduction in neurological symptoms compared to the symptoms prior to robotic SRS. Results The median follow-up was 39 months (range, 7-60 months). In 8 of our patients the lesions were stable on the basis of the last available MRI. We did not observe any disease progression at the time of reporting. Over the full length of follow up 6 of 14 lesions (43%) demonstrated tumor regression. On the basis of last follow up, the rate of local control was 100%. One patient was dead due to metastatic gastric cancer. The disease specific survival for the entire cohort was 100%. Prior to robotic SRS, 2 patients had headache, 7 patients had pulsatile tinnitus and 1 patient had loss of hearing functions at the lesion side. Complete clinical improvement according to our criteria was observed in 8 patients. The toxicities related to auditory, neurology and vascular categories were evaluated according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE). We did not observe any treatment related toxicity in this group of patients. Discussion Surgery is considered to be the primary treatment of GTs. However, tumors with destruction of the bone or patients with jugular foreman syndrome are generally managed with EBRT (16). Herein, we reported our early therapeutic results in unresectable GJTs homogenously treated in a single center, and we observed excellent local control with no toxicity after robotic SRS. Springate et al. reviewed the literature concerning the primary management of GTs. They showed local control rates are similar with surgery and radiotherapy (3). A recent meta-analysis by Guss et al. demonstrated that radiosurgery achieved 97% tumor control, and 95% clinical control in patients with GJTs. Because of its high effectiveness, they recommended radiosurgery as the primary treatment modality for GJTs (17). On the other hand, there are only a few studies on the use of robotic SRS in the management of GTs (12, 18, 19). Bianchi et al. evaluated the short term local control and the safety of robotic SRS in 9 patients with GTs. They treated 8 patients with a single fraction of 12.5 Gy, and one patient with 24 Gy in three fractions. After a mean follow-up of 20 months, they reported 100% local control with no serious toxicity (12). Tuniz et al. reported the therapeutic results of robotic SRS in the management of benign cranial base tumors. Only 4 among 35 patients had GTs. They delivered 24 Gy in 2 to 5 fractions. With a median follow-up time period of 31 months, tumor regression was observed in 44% of 35 patients (18). Lim et al. reported the results of radiosurgery in 21 GJTs. Sixteen tumors were treated with the CyberKnife and 5 tumors were treated with LINAC based system. The treatment doses ranged from 14 to 27 Gy. All but 5 patients were treated with one fraction. The remaining tumors were treated in 2 to 3 fractions. They

4 112 Hurmuz et al. used MRI fusion in only 3 tumors during target delineation. After a median follow up of 66 months they showed 100% local control (19). In the current study, 93% of our patients received fractionated robotic SRS. To our knowledge, this is the largest number of patients with unresectable GJTs treated with fractionated robotic SRS. Our fractionation regimens were different than the doses reported in the literature (12, 18, 19). Arthur et al. reported excellent tumor control with conventional doses of 45 to 50 Gy (16). Therefore, we preferred to deliver a median dose of 25 Gy in 5 fractions. In terms of radiobiology, this is the equivalent dose to the conventional external radiotherapy dose to control the disease according to the linear-quadratic model. Furthermore, we used MRI fusion during the delineation of target and critical structures in all patients. Our GTV was CTV, according to ICRU recommendations for benign tumors. We added extra 1.0 mm for PTV to CTV (21). After 39 months of follow up, this protocol seems to be an effective regimen that shows excellent local control at the time of reporting. Cranial nerve palsy has been reported in 22-59% of patients after surgery (5-7). Surgical mortality rates range from 1.3 to 6.4% (7, 20). However, serious complication rate with radiotherapy is lower than surgery (2-3%) (16). The major complications of EBRT are mucositis, alopecia, parenchymal radionecrosis and temporal bone osteonecrosis (8, 9, 11). Bianchi et al. did not report any cranial nerve palsies in GTs after robotic SRS. In their series, all patients showed neurological stability or improvement (12). In the study of Tuniz et al., 4 patients used corticosteroids due to transient neurological worsening and radiographic signs of radiation injury (18). They did not observe permanent neurotoxicity. Lim et al. reported two transient ipsilateral tongue weakness and hearing loss which subsequently resolved in their patients with GJTs. One patient with previous EBRT history developed transient ipsilateral vocal cord paresis (19). We did not observe any treatment related neurological deficit in our patients with GJTs. In a recent meta-analysis, 869 patients with GJTs were evaluated in terms of local control and cranial neuropathy after subtotal resection (STR), gross total resection (GTR), STR 1 postoperative radiosurgery and SRS alone (22). The local control rate after SRS was 95% and that was significantly high compared to other 3 groups (p, 0.01). The patients who underwent GTR had high rates of cranial nerve IX-XI deficits than those who underwent SRS alone. It was concluded that higher rates of cranial nerve morbidity after surgery are not associated with improved local control rates compared with radiotherapy. SRS is able to deliver high dose to the tumor with a rapid dose fall off outside the target. We believe that fractionated robotic SRS is preferable versus single fraction treatment for skull base tumors for radiobiological reasons. It allows higher doses to be delivered to the tumor because of increased tolerance of the surrounding normal tissues. Unlike other SRS methods, robotic SRS is a frameless technique and does not require anesthesia. Therefore it allows performing hypofractionated radiosurgery. This is advantageous for treating lesions near sensitive structures with high accuracy. It can deliver a short, painless and effective radiation treatment without surgery related morbidities. Although our study has the limitations due to its retrospective nature, it is noteworthy to mention that GJTs are very rare tumors. Therefore, retrospective cohorts usually guide us in the decision making for the management of GTs. In this aspect, the early results of our series showed that robotic SRS seems to be an effective treatment option for unresectable GJTs in terms of high local control and low toxicity. It is obvious that longer follow-up time is necessary to see the late effects of high daily fraction doses delivered with SRS. Conflict of Interest We have no conflict of interest. Acknowledgement This study is supported by Hacettepe University Research Grant Project: 1-05 A The part of data in this manuscript was presented at the European Multidisciplinary Cancer Congress in Stockholm, Sweden, September References 1. Davidson, J., Gullane, P. Glomus vagale tumors. Otol Head Neck Surg 99, (1998). 2. Hotz, M. A., Schwaab, G., Bosq, J., Munck, J. N. Extramedullary solitary plasmacytoma of the head and neck. A clinicopathological study. Ann Otol Rhinol Laryngol 108, (1999). 3. Springate, S. C., Weichselbaum, R. R. 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