CyberKnife Radiosurgery for Glomus Jugulare Tumors

Transcription

1 C H A P T E R 20 CyberKnife Radiosurgery for Glomus Jugulare Tumors Michael Lim Iris C. Gibbs Steven D. Chang Abstract Glomus jugulare tumors (pargangliomas) are indolent well vascularized tumors that arise along the glossopharyngeal nerve or vagus nerve. Patients usually present with secondary symptoms due to the mass effect on neighboring structures. Traditional surgical interventions carry high morbidities, which is why radiation therapy was first considered as an option. Recently, radiosurgery has been shown to be an efficacious mode of therapy with little or no side effects. We discuss the history of radiation therapy that led to radiosurgery for the treatment of these tumors. We also present our own experience in treating glomus jugulare tumors with the CyberKnife. Introduction Glomus jugulare tumors, which are also termed paragangliomas, are indolent well vascularized tumors that arise along the glossopharyngeal nerve (Jacobson s nerve) or vagus nerve (Arnold s nerve). They were first described in 1840 by Valentin, who originally characterized the lesion as a ganglion. 1 The term glomus jugulare was coined a century later in 1941 by Guild. 2 These tumors account for only 0.6% of all cranial neoplasms and patients can present with cranial nerve deficits of the ninth, tenth, and eleventh nerves. The symptoms are thought to occur primarily from the mass effect on neighboring structures such as cranial nerves and vasculature. 3 Others present with thrombus of the nearby venous structures. Patients can also manifest labile blood pressures because of their intrinsic chromaffin cells, which can secrete catecholamines. 4, 5 Surgery Traditionally, glomus jugulare tumors were treated with surgery. However, surgical intervention, despite advances in surgical and microsurgical techniques, carries a high operative morbidity. Complications from surgical resection include stroke (8 20%), cranial nerve injury (33 44%), and an overall mortality rate of 5 13%. 4 The complex anatomy of critical cranial nerves and vessels in the approach and within the jugular bulb often prevents a complete resection. 213

2 2 1 4 PA RT I V: Non-Central Nervous System Applications Radiation Therapy: Historical Review External beam radiation was first used as adjuvant therapy for treatment of recurrent tumors or in situations of subtotal resections in the 1950s. 6, 7 The then-current opinion expressed in a 1955 textbook on British practice in radiotherapy 8 was as follows: This lesion is not amenable to surgical removal: indeed so vascular is the tumor and its surroundings that the obtaining of a biopsy specimen may test surgical skill. If encroachment on the posterior cranial fossa is causing intracranial pressure complications, these can be relieved by surgical decompression. Cure depends entirely on X-radiation. Experience, though still not extensive, suggests that the tumor is certainly radiosensitive and may be curable by that means. McWhirter & Dott 8 also stated that Glomus jugular tumors are compatible with four or five years survival and cause death finally, usually by encroachment on the posterior cranial fossa. In the same decade, Dalley 9 from the Royal Marsden Hospital, London, stated that this rare tumor presented with 50% related to the jugular bulb and 50% to the glomus body of the temporal bone. The Royal Marsden treatment technique was published in the 1960s by Lederman et al, 10 who grouped cancers of the middle ear, and proposed a range of treatment plans. By this time 110 cases had been seen in The three-year, five-year and 10-year results for 45 patients with previously untreated middle ear and mastoid tumors were 35%, 31% and 23%, respectively. 10 However, these figures were not computed using the now-familiar Kaplan-Meier life table method 11 and therefore cannot be directly compared with recent results. Nevertheless, they give a global indication of early treatment success in terms of overall survival. In 1955, Williams et al from the Mayo Clinic 12 considered that definite improvement resulted from doses of roentgen (~13 20 Gy) given to Figure 1. Example of a Royal Marsden Hospital, London, treatment plan from the early 1960s aiming to minimize radiation exposure to normal tissues. The 120% isodose line conforms to the petromastoid bone. At that time, when linear accelerators were not commonly available, the best use had to be made of existing technology. This plan combines a kilocurie telecobalt machine wedged field with a hectacurie telecobalt machine open field. 10 The hectacurie tele 60 cobalt machine was specifically developed for the treatment of head & neck cancers. The design was based on that of a radium bomb where the radium source was pneumatically transferred between a 47, 48 lead-protected safe and the machine head. the tumor in two weeks. In 1973, the M.D. Anderson Hospital, Houston experience was presented by Miller, 13 who reported on 14 patients treated in By 1973 only 1/14 had died. A total of 5/14 were treated in and received a minimum tumor

3 C H A PTER 20 : CyberKnife Radiosurgery for Glomus Jugulare Tumors 215 Table 1. Glomus tympanicum and jugulare chemodectomas: local control with radiation therapy with or without surgery, , modified from Springate & Weischselbaum 15 and Million et al. 16 Taking all the data as a single group the result in terms of local control/total cases is 349/384 (91%). M = mean follow-up period. NS = not stated. Institution Treatment period Tumor dose (Gy) Local control/ Total cases Follow-up period (months) Publication year Massachusetts General / M Washington University / M University of Florida / M.D. Anderson Hospital / Geisinger Medical Center / Princess Margaret Hospital Toronto / University of California, San Francisco / University of Washington /14 92 M University of Virginia / University of Michigan / Mayo Clinic pre / Baylor University / University of Minnesota pre /14 NS Mount Sinai Hospital, New York / Queen Elizabeth Hospital, UK / University Hospital, Wales, UK / M University of Iowa / Aarhus, Denmark / University of Kansas / dose of less than 4500 rads (45 Gy) given over 35 days. The one case who died did so of a late brain necrosis 38 months after treatment, but had received a minimum dose of 4975 rads in 38 days. Two other brain necrosis deaths have been reported in the literature 14 and these occurred in the Christie Hospital, Manchester series and received doses of 5000 rads. It is also noted for the M.D. Anderson cases 13 that in 5/14 associated masses in the neck were considered probable carotid body tumors.

4 2 1 6 PA RT I V: Non-Central Nervous System Applications Table 1 summarizes local control results reported in 19 publications by Springate & Weischselbaum 15 and Million et al, 16 for patients treated during the period at centers in Canada, Denmark, the United Kingdom and the USA. Indications for external beam radiation were later expanded to include patients who were poor surgical candidates. By 1994, Mukherji et al 36 reported that institutions using external beam radiation achieved tumor control, defined as stable or decreased tumor size of about 60%, for more than 70% of their patients. Nevertheless, despite promising efficacy, the side effects of external beam radiation have historically been substantial, due in part to large field sizes often including the skull base and upper neck. Complications other than brain necrosis, 13, 14 such as radiation necrosis of bone, possible induction of secondary malignancies, skin changes and xerostomia, have been reported within the last 10 years. 3, 37 However, the advent of intensity-modulated radiation therapy (IMRT) has reduced the extent of normal tissue exposed to radiation and has produced a consequent decrease in side effects. Radiosurgery Before CyberKnife The utilization of radiosurgery using either the Gamma Knife or linear accelerators to treat glomus jugulare tumors began in the mid-1990s. 37 Radiosurgery offered a new technique to precisely deliver radiation. In addition, unlike conventional radiation therapy, the steep dose gradient achievable with radiosurgery minimizes irradiation of neighboring normal tissue. Therefore, a larger dose of radiation could be administered to the tumor without exceeding the radiation tolerance of normal tissues. Glomus jugulare tumors were considered ideally suited for radiosurgery because they were well defined, non-infiltrating, and usually presented with a reasonably small size. Since 1995, centers began reporting their experiences with radiosurgery. 3, One of the first studies was by Foote et al, who used Gamma Knife radiosurgery for nine patients with glomus tumors. 41,42 They demonstrated tumor-effective treatment with no long-term complications. Jordan et al confirmed Foote s results on a series of eight patients, also treated with Gamma Knife radiosurgery. They reported no tumor progression and no delayed cranial neuropathies. 3 With longer follow-up now available, the success of radiosurgery appears to be confirmed. The longest follow-up reported is from Bari et al, who treated eight patients with glomus jugulare tumors using the Gamma Knife. Their follow-up range was months. They reported that all patients were clinically stable and that 5/8 showed a decrease in the size of lesion at the time of follow-up. However, one can argue that at least a 10-year follow-up period is required to make any predictions for long-term efficacy and safety. 45 Eustacchio et al reported results for their series of 19 patients using the Gamma Knife, tumor control in 18/19 and no complications. 39 Feigenberg et al reported tumor control in 3/5 patients when using a linear accelerator, 40 whereas Liscak et al published higher complication rates in their study of 14 patients treated with the Gamma Knife, even though 100% control in tumor growth was achieved. A total of 3/14 patients complained of worsening hearing. 44 Although with only four cases in total, we nevertheless have long-term follow-up experience in treating glomus jugulare tumors using a linear accelerator. The median follow-up is 10.5 years radiographically and 13.2 years clinically. In all four cases, the size of the tumors remained unchanged over this period of

5 C H A PTER 20 : CyberKnife Radiosurgery for Glomus Jugulare Tumors 217 Table 2. Characteristics for the four patients treated using a linear accelerator (RT) at Stanford. All patients were still alive at the most recent follow-up. Previous surgical Size treatments before RT Follow-up (months) Dose Age (years) Side (cm) Sex (years) (Gy) Fractions MRI Clinical 43 Right 3.6 F 6, 12, 18 & Right 2.0 F None Right 1.2 F 13, Right 2.7 F None time and no permanent side effects were reported, Table 2. However, not every center has reported similar results with linear accelerator treatments. For instance, Feigenberg et al, who treated five patients, stated that 2/5 progressed in size at six months and at 40 months after irradiation. 40 In another small linear accelerator-treated series reported by Maarouf et al, all 12 patients had stable or decreased tumor size with stable or improved clinical symptoms at a median follow-up of four years. 46 It is noted that Feigenberg et al prescribed a higher median dose of 25 Gy when compared to Maarouf et al, where the median dose was 15 Gy. Our median dose was 21.5 Gy. CyberKnife Radiosurgery The CyberKnife offers an accurate and frameless method for radiosurgery in patients with glomus jugulare tumors, Figure 2. In our experience of treating 15 glomus jugulare tumors with stereotactic radiosurgery using the CyberKnife, we have found that our results are not significantly different from those reported for the Gamma Knife and for linear accelerators. We performed a retrospective analysis of our CyberKnife cases, and patient records were assessed for age, sex, tumor site (left or right), dose, number of isocenters, pre-treatment and post-treatment symptoms, maximum dimension of the tumor as assessed by MRI before and after therapy, and length of follow-up based on radiographs and clinical symptoms, Table 3. Radiation Dose Of the 15 glomus jugulare tumors treated with the CyberKnife, the prescribed doses (typically defined to the 80% isodose line) to the periphery of the tumor were in the range Gy. Our follow-up of patients was in the range 4 55 months (mean of 21 months), whereas it was months for clinical follow-up (mean of 27 months). Most patients in our study received radiosurgery as their first treatment, but 3/15 had prior open surgery for their tumors. Tumor sizes were in the range cm (mean of 3.1 cm) in terms of the maximum dimension of the tumor. Tumor Regression At the time of our latest follow-up, July 2004, a total of 4/15 patients treated with CyberKnife stereotactic radiosurgery alone had experienced a regression of their tumors. Case #5 in Table 3 had a pre-treatment

6 2 1 8 PA RT I V: Non-Central Nervous System Applications Figure 2. Example of a CyberKnife Stanford University treatment plan for a patient with a glomus jugulare tumor. Based on its location, patients can present with cranial nerve deficits of the 9 th, 10 th and 11 th nerves from the tumor mass effect. The tumor can also be responsible for symptoms by causing a thrombus in the neighboring venous structures.

7 C H A PTER 20 : CyberKnife Radiosurgery for Glomus Jugulare Tumors 219 Table 3. Stanford CyberKnife radiosurgery patients. The size quoted in the table is the tumor s maximum dimension. Tumor reduction details for #5, #6, #7 and #14 are given in the text. All other cases were stable at the last follow-up. Case # Age Side Size (cm) Sex Previous treatment Dose (Gy) Number of fractions Follow-up (months) 1 75 Left 2.8 M Yes Left 1.5 F Yes Right 2.5 F No 18 1 None Left 2.5 M No Right 3.9 F No Left 2.0 M No Left 3.8 F No Right 2.3 M No Left 1.7 M No Left 6.2 F No Right 2.8 F No Right 3.1 F No Right 3.6 F No Left 6.2 M Yes Left 2.2 F No Mean MRI Clinical tumor maximum diameter of 3.9 cm and within five months this had decreased to 3.0 cm. Case #6 had a pre-treatment tumor maximum diameter of 2 cm, and post-treatment no tumor was visible on MRI at six months follow-up. Case #7 had a pre-treatment tumor maximum diameters radiographically of 3.8 cm but at 15 months follow-up this had decreased to 3.4 cm. Case #14 had a pre-treatment tumor maximum diameter radiographically of 6.2 cm, but at eight months follow-up this had decreased to 5.0 cm. Side Effects We found that patients experienced only transient symptoms. However, 2/15 experienced transient worsening of pre-procedural cranial nerve deficits. The first complained of transient ipsilateral tongue

8 2 2 0 PA RT I V: Non-Central Nervous System Applications atrophy and hearing loss and the second reported worsened post-procedure voice hoarseness that was confirmed via laryngoscopy. However, this resolved over eight months. The remaining patients experienced no side effects. What is notable is the implied radiation resistance of the cranial nerves. Our results confirmed the low rate of cranial nerve injury seen in 3, 42, 44 the majority of studies. Discussion & Conclusions Our results are exciting in that we have had 100% tumor control with no permanent morbidity. One possible reason for this success could be the high accuracy of the CyberKnife. Precise target delineation is critical for treating glomus jugulare tumors because of the neighboring critical structures; the CyberKnife has small treatment delivery errors of less than 2 mm. This translates into minimizing the radiation dose to normal neighboring tissues. While we are encouraged by the results of the CyberKnife, we stress the importance of long-term follow-up. Glomus jugulare tumors are slow-growing and a more accurate assessment of radiosurgery for these tumors can only be made after 10-year follow-up. Also, it is inevitable that a long time will be necessary to accrue sufficient numbers of cases because of the extremely low incidence of this particular tumor. However, we remain optimistic that the CyberKnife will offer an efficacious and safe mode of therapy for tumor control and preservation of cranial nerves, with minimal side effects, in patients with glomus jugulare tumors. References 1. Bickerstaff ER, Howell JS. The neurological importance of tumours of the glomus jugulare. Brain 1953;76: Guild SR. Hitherto unrecognized structure, the glomus jugulare in man. Anat Rec 1941; 79: Jordan JA, Roland PS, McManus C et al. Stereotactic radiosurgery for glomus jugulare tumors. Laryngoscope 2000;110: Chretien PB, Engelman K, Hoye RC et al. Surgical management of intravascular glomus jugulare tumors. Am J Surg 1971;122: Lundgren N. Tympanic body tumors in the middle ear: tumors of carotid body type. Acta Otolaryngol 1949;37: Leroux-Robert J, Ennuyer A. Malignant tumors of the ear. Rev Laryngol Otol Rhinol (Bordeaux) 1958;79: , discussion Boland J, Paterson R. Cancer of the middle ear and external auditory meatus. J Laryngol Otol 1955;69: McWhirter R, Dott NM. Tumours of the brain and spinal cord. In: Rock Carling E, Windeyer B, Smithers DW, eds. British Practice in Radiotherapy. London: Butterworth, 1955, 335, Dalley VM. Malignant tumours of the eye and ear. In: Raven RW, ed. Cancer Vol 5. London: Butterworth, 1959, Lederman M, Jones CH, Mould RF. Cancer of the middle ear: technique of radiation treatment. Br J Radiol 1965;38: Kaplan EL, Meier P. Non-parametric estimation from incomplete observations. J Am Stat Assoc 1958;53: Williams HL, Childs DS, Parkhill EM et al. Chemodectomas of the glomus jugulare with special reference to their response to Roentgen therapy. Ann Otol (St. Louis) 1955;64:

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