Stereotactic Radiosurgery for Chordomas

Although often referred to as a “low-grade“ malignancy, skull base chordomas are locally invasive and aggressive, making surgical resection challenging. It is widely agreed that safe, aggressive surgical resection should be the initial form of management when possible. Total resection is often not feasible due to deep central location, local invasion within normal-appearing bone, encasement of vessels and cranial nerves, as well as adherence to critical brain structures. Recurrence is common, even in cases where radiologic gross total resection (GTR) was achieved. Repeat surgery is challenging due to a scar tissue formation and prior high-dose radiation exposure. Many patients undergo adjuvant radiotherapy following initial resection either to control residual tumor volume or prevent recurrences due to undetected tumor invasion of surrounding tissues even after gross total tumor resection. ¹ Initial studies showing limited effect of radiation on chordomas have resulted in a misconception that chordomas are “radioresistant.” In most cases this has been due to limited radiation dose due to several factors, including technological limitations, proximity to critical neurovascular structures such as the brainstem, cranial nerves, or the optic apparatus. Stereotactic radiosurgery (SRS), with its intrinsic capability of precise targeting, steep dose gradient, and shielding techniques, allows exclusively high energy delivery to the tumor tissue and significant sparing of surrounding neurovascular structures and is an appealing adjunct in the multimodality treatment of skull base chordomas. This chapter discusses the role of SRS in the care of patients with chordoma, with a focus on how radiosurgery can augment existing treatment paradigms.

27.2 Technology and Technique

Most studies of SRS are limited to stereotactic Gamma Knife radiosurgery (Elekta AB, Stockholm, Sweden), which is a surgical procedure that delivers highly targeted, focused photon radiation from decay of 192 to 201 cobalt-60 sources. Magnetic resonance imaging (MRI) imaging is obtained with fine-cut slices (1–2 mm slice thickness) covering the entire region of the tumor and skull base. Because of bony destruction, tumor margins can be unclear on MRI alone, and computed tomography (CT) with CT-MRI image fusion can be used to assist tumor margin definition for dose planning. ² Radiation dose selection to the tumor margin has varied from 9 to 25 Gy in various series. Recent series have shown that doses of 15 Gy or higher are correlated with improved tumor control and progression-free survival (PFS). ³^,⁴ Higher doses are often feasible with lower tumor volume. There is evidence that SRS is correlated with better outcomes in patients with residual tumor volume of less than 20 cc. ⁵ Multiple isocenters are used to create irregular target plans, with one series describing a range from 1 to 30 with a median of 7 isocenters ³ ( ▶ Fig. 27.1, ▶ Fig. 27.2).

Fig. 27.1 Axial contrast-enhanced T1 (upper) and T2 (lower) images showing the radiosurgery dose plan for a 36-year-old man with a 2.8 cc chordoma within the left cavernous sinus. He had two prior resections, proton beam radiotherapy, and two prior radiosurgeries for tumor on the right side of the skull base. Following his second resection, this left cavernous sinus tumor was targeted. A tumor margin dose of 12 Gy. The steep dose falloff to 8 Gy is shown.

Fig. 27.2 This 37-year-old female underwent Gamma Knife radiosurgery without prior radiotherapy for her chordoma. The tumor volume was 3.4 cc, and the tumor margin dose was 16 Gy. Right image: at radiosurgery; middle image: radiosurgery plan; left image: 3 years after Gamma Knife radiosurgery.

At present, radiosurgery is typically initiated once there is documented clinical or imaging progression of disease, and Gamma Knife has been proven as an effective technique in such cases. Such success prompted reconsideration of treatment strategies and to include Gamma Knife radiosurgery in the treatment protocol as early as possible. Use of adjuvant SRS early after surgical resection is currently controversial and is only performed at few centers. However, our approach is to offer it as early as possible whenever residual or recurrent tumor is documented, as the results of SRS are better when the target volume is smallest and when there is limited local spread.

27.3 Result of Major Studies

Studies have documented the use of SRS both in primary and adjuvant treatment of patients with skull base chordomas. The current work has consistently shown that SRS alone as the primary form of treatment does not provide adequate tumor control ( ▶ Table 27.1). There appears to be two main roles for SRS in the treatment of skull base chordomas. First, the addition of SRS has been shown to increase tumor control and prolong PFS in patients with recurrent tumors, who have already been treated surgically, by external beam radiotherapy or proton beam radiotherapy. Second, SRS was shown to be effective as a single treatment modality in management of small residual or recurrent chordomas after surgical resection. Due to the rarity of the disease, the literature on chordomas is quite limited and practical and valid conclusions cannot be drawn by considering the results of several studies. Therefore, major studies on different indications of SRS in management of chordomas will be individually analyzed here.

**Table 27.1** Studies of Gamma Knife radiosurgery for skull base chordomas
Study	No. of patients with chordoma	Median tumor volume (cc)	Median tumor margin dose (Gy)	Median no. of isocenters	Median follow-up after SRS (years)	Overall survival at 5, 10 years (%)	Tumor control at 5, 10 years (%)	Adverse radiation effects
Kim et al 2014 ²⁵	5	10.7	20	N/A	4.4	100, –	73, –	1
Kano et al 2011 ³	71	7.1	15	7	5	80, 73	66, –	4
Ito et al 2010 ⁹	19	3.3	17.8	–	5.9	100, –	100, –	0
Koga et al 2010 ¹¹	10	8.8	15	–	5.4	–, –	15, –	2
Dassoulas et al 2009 ⁸	15	5.8	12.7	N/A	5.8		50.3, –	N/A
Liu et al 2008 ⁶	31	11.4	12.7	N/A	5.8		50.3, –	2
Hasegawa et al 2007 ⁵	30	20	14	8	4.9	80, 53	76, 67	1
Martin et al 2007 ⁷	18	9.8	16	9	7.7	63, 63	63, 63	1
Krishnan et al 2005 ⁴	25	14.4	15	10	4.8	90, –	32, –	10

Kano et al, ³ representing the North American Gamma Knife Consortium (now International Gamma Knife Research Foundation), published a series of 71 patients who underwent SRS for skull base chordomas with a median follow-up 5 years. The median tumor volume was 7.1 cc, with a median tumor margin dose of 15 Gy. Treatment planning was based solely on MRI, and the median number of isocenters used was seven. Twenty-eight percent of patients had received prior radiotherapy. The 5-year actuarial overall survival (OS) and treated tumor control rates were 80% and 66%, respectively. Older age, patients with recurrent tumors, prior radiotherapy, and larger tumor volume were all significantly associated with worse tumor control. The authors concluded that SRS is a powerful, low-risk tool for care of small- to medium-sized chordomas, usually as a supplement to microsurgical resection.

Krishan et al ⁴ published a series of 29 patients with skull base tumors treated with SRS, 25 of whom had chordomas. Nineteen patients received concomitant radiotherapy. The median tumor volume was 14.4 cc, and the patients received a median tumor margin dose of 15 Gy. Treatment planning was based on MRI alone and employed a median of 10 isocenters. OS rate was 90% at a median clinical follow-up of 4.8 years. Eighteen of the chordoma patients had stable disease or tumor regression, and 79% were clinically stable or improved compared with pretreatment. Actuarial local tumor control rate was only 32% at 5 years. Sixteen percent of patients had out-of-field failures at 5 years, which demonstrated the challenges of defining the true tumors margins on MRI alone. Adverse radiation effects occurred in 34% of patients and included cranial nerve deficits in six, parenchyma effects in five, and pituitary dysfunction in three. None of the patients who received SRS alone had radiation-related complications. The authors concluded that SRS effectively provides tumor control as an adjunct to microsurgery, but they noted concerns regarding the relatively high complication rate in patients who had already received fractionated radiation therapy.

Hasegawa et al ⁵

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