Radiotherapy, Radiosurgery, and Proton Beam

Authors

Patients no

Type of RT

Median dose Gy

Follow-up months

Tumor control (%)

Cummings et al. [7]

CRT

41 at 5 years

Chetiyawardana [8]

CRT

30–40

12–240

Amendola et al. [9]

CRT

40 at 5 years

Fuller and Bloom [10]

CRT

23 at 5 years

Forsyth et al. [11]

CRT

39 at 5 years

Romero et al. [4]

CRT

50.1

3.1 years

17 at 5 years

Watkins et al. [12]

CRT

50–60

34 at 5 years

Catton et al. [5]

CRT

23 at 5 years

Zorlu et al. [13]

CRT

23 at 5 years

Cho et al. [14]

CRT/GK

59.4

40 at 5 years

Sahgal et al. [15]

IMRT

65.3 at 5 years

Debus et al. [16]

FSRT

66.6

50 at 5 years

Bugoci et al. [17]

FSRT

66.6

37.5 at 5 years

RT radiotherapy, CRT conventional radiotherapy, NA not assessed, GK Gamma Knife, IMRT intensity-modulated radiation therapy, FSRT fractionated stereotactic radiotherapy

Despite conventional RT does not appear to increase survival rates in all published studies, its role in the palliative setting in advanced, unresectable, or recurrent tumors is well established [11–19]. Tumor shrinkage and improvement of neurological function were reported in about 10 % and up to 60 % of patients; however, the criteria used to evaluate the neurological improvement are subjective or not available in most series. Complication rates following RT were reported in 0–5 % of patients, being represented especially by an impairment of preexisting neurologic symptoms due to cranial nerve deficits.

The use of new radiation techniques, including both IMRT and FSRT, which allow higher doses of radiation to the tumor while sparing more surrounding normal tissue, has been associated with better outcome (Table 28.1) [15–17]. In a series of 37 patients with skull base chordomas irradiated with FSRT using a median dose of 66.6 Gy, Debus et al. [16] observed 5-year overall survival and local control rates of 82 % and 50 %, respectively, at a median follow-up of 27 months. The reported rate of permanent complications was 2.2 %, including one case of hemiparesis. Using a similar dose and fractionation, at a median follow-up of 42 months, Bugoci et al. [17] reported an overall survival rate of 76.4 % at 5 years. Using IMRT with a median dose of 76 Gy given in 2 Gy per fraction in 24 patients, Sahgal et al. [15] reported a 5-year survival and local control rates of 85.6 % and 65.3 %, respectively, at a median follow-up of 36 months.

In conclusion, conformal photon RT is associated with longer progression-free survival in comparison to surgery alone, although without clear survival benefit. Certainly, it is difficult to draw a clear conclusion on the efficacy of RT from these data because all studies are retrospective and include a small number of patients treated over many years with different techniques or using different radiation doses. IMRT and FSRT allow for a better 5-year local control and survival; however, only large series and longer follow-up may allow for definitive conclusions regarding the efficacy of new radiation techniques.

28.3 Stereotactic Radiosurgery

SRS may represent a convenient approach for small skull base chordomas after surgery or at recurrence with a reported local control rates of 21–72 % at 5 years [18–32] (Table 28.2). In clinical practice, SRS is usually offered to patients with tumors smaller than 30 mm in diameter and not in close proximity of organs at risk, such as the optic apparatus and brainstem. Kano et al. [28] have recently reported the results of a multicenter study of the North American Gamma Knife Consortium including 71 patients with small-sized chordomas of the skull base treated with Gamma Knife (GK) SRS. The median SRS target volume was 7.1 cm³ (range, 0.9–109 cm³), and median margin dose was 15.0 Gy (range, 9–25 Gy). With a median follow-up of 5 years, the 5-year actuarial overall survival and local control rates after SRS were 80 % and 66 %, respectively. Overall survival rates were 43 % for patients who had prior RT and 93 % for those who had no prior RT, and respective 5-year tumor control rates were 62 and 69 %. Older age, recurrent group, prior RT, and larger tumor volume were significantly associated with worse tumor control. In a small series of 15 patients who had undergone GK SRS between 1990 and 2007 at the University of Virginia using a mean dose of 12.7 Gy, Dassoulas et al. [29] observed actuarial tumor control rates of 50.3 % at 5 and 10 years, and similar results have been observed in other few series [18–20, 26, 30]. A similar tumor control up to 60 % at 5 years has been reported when SRS has been used in combination with conventional RT [14, 20, 23, 24]. Complications are reported from 0 to 33 % (median 3 %), being represented mainly by brain radionecrosis and cranial nerve deficits; however, serious radiation-related complications are rarely reported.

Table 28.2

Summary of published studies on SRS/HSRT for chordoma

Authors	Patients no	Type of RT	Median dose Gy	Follow-up months	Tumor control (%)
Miller et al. [18]	8	GK	15	2.3 years	100 at 2 years
Muthukumar et al. [19]	9	GK	18	48	NA
Crockard et al. [20]	26	GK^a	15	51	NA
Krishnan et al. [23]	25	GK^a	15	56	32 at 5 years
Hasegawa et al. [24]	30	GK^a	14	59	72 at 5 years
Martin et al. [25]	18	GK	16.5	88	63 at 5 years
Liu et al. [26]	31	GK	12.7	30.2	21.4 at 5 years
Ito et al. [27]	19	GK	15	87.2	47.9 at 5 years
Kano et al. [28]	71	GK	15	60	66 at 5 years
Dassoulas et al. [29]	15	GK	12.7	88	50.3 at 5 years
Kondziolka et al. [30]	4	GK	20	22	100
Chang et al. [21]	10	CK^b	19.4	4	80^c
Gwak et al. [22]	4	CK	35–43.6	24	NA
Henderson et al. [31]	18	CK	35	46	59.1^c
Zorlu et al. [32]	11	CK	30	42	73

SRS stereotactic radiosurgery, HSRT hypofractionated stereotactic radiotherapy, RT radiotherapy, GK Gamma Knife, CK CyberKnife, NA not assessed

^aIn conjunction with conventional radiotherapy

^bFive patients treated with LINAC radiosurgery

^cSeries include both skull and cervical spine chordomas

Only a few series report on the use of hypofractionated stereotactic radiotherapy (HSRT) in patients with small-to-moderate-sized chordomas of skull base [21, 22, 31, 32]. In a small series of 11 patients with a chordoma of skull base treated with CyberKnife multi-fraction SRS (30 Gy in 5 daily fractions), Zorlu et al. [32] reported 2-year overall survival and tumor control rates of 91 % and 82 %, respectively, at a median follow-up time of 42 months. A similar tumor control has been observed in a few other small series using doses of 20–43.6 Gy delivered in 2 to 5 fractions [21, 22, 31], with a low incidence of serious radiation-induced complications. Although promising, available results on either photon-based single-fraction SRS or multi-fraction SRS are of difficult interpretation. The limited experience, the relatively small size of treated lesions, and the short follow-up periods do not allow for meaningful conclusions.

28.4 Proton Beam Radiotherapy

Protons represent a major advance in radiation therapy, because of their ability to concentrate dose in the tumor while simultaneously sparing surrounding healthy tissue. Surgery followed by proton beam RT has then considered the standard treatment for skull base chordomas. Several studies have reported the safety and efficacy using doses ranging between 63 and 83 CGE (Cobalt Gray Equivalent) at fractionation of 1.8–2.0 CGE for either adults or children with residual or recurrent chordomas of any size [33–47] (Table 28.3). Of these series, the largest one included 169 patients treated with proton beam RT at Massachusetts General Hospital [35]. At a median follow-up of 41 months, 5- and 10-year local control rates were 73 and 54 %, and respective overall survival rates were 80 and 54 %. Using a combination of FSRT and proton beam RT, Noël et al. [39] reported 2- and 4-year local control rates of 86.3 % and 53.8 %, respectively, in 100 patients with skull base and cervical spine chordomas. More recently, Deraniyagala et al. [46] found a 2-year local control rate of 86 % in 33 patients with skull base chordomas. Comparable results have been shown also by other authors, with reported 5-year tumor control and survival rates ranging from 46 % to 81 % and from 66.7 % to 89 %, respectively [33, 34, 36–38, 40–45, 47]. No differences have been observed in terms of local control and survival between children and adult patients.

Table 28.3

Summary of published studies on proton beam radiotherapy for chordomas

Authors	Patients no	Type of RT	Median dose CGE	Follow-up months	Tumor control (%)
Benk et al. [33]	18 (pediatric)	PhT/PBT	69	72	63 at 5 years^a
Hug et al. [34]	33	PBT	71.9	33	76
Munzenrider and Liebsch [35]	169	PhT/PBT	66–83	41	73 at 5 years, 54 at 10 years
Terahara et al. [36]	115	PhT/PBT	68.9	41	59 at 5 years, 44 at 10 years Only gold members can continue reading. Log In or Register to continue Share this: Click to share on Twitter (Opens in new window) Click to share on Facebook (Opens in new window) Related Related posts: Introduction Introduction Endoventricular Cystic Craniopharyngiomas Skull Base Approaches to Clival Chordomas Supraorbital Approach Endoscopic Endonasal Transsphenoidal Approach Stay updated, free articles. Join our Telegram channel Tags: Midline Skull Base Surgery May 26, 2017 \| Posted by admin in NEUROSURGERY \| Comments Off on Radiotherapy, Radiosurgery, and Proton Beam Full access? Get Clinical Tree Get Clinical Tree app for offline access Get Clinical Tree app for offline access