26 2011
IMAGING & ONCOLOGY
INTRA-CRANIAL STEREOTACTIC RADIOTHERAPY Radiosurgery is an established form of treatment for both benign and malignant intra- cranial lesions and has shown good results with minimal side-effects. Surgical resection remains the gold standard for treatment and aggressive resection offers the best results. However, in many cases surgery may be contraindicated. Radiosurgery has been used as both a primary and adjuvant treatment modality following surgical excision. Whole brain radiation therapy and/or chemotherapy are used in many cases following surgical resection. As whole brain radiotherapy and chemotherapy have significant side- effects, stereotactic radiosurgery may be used as an alternative adjuvant treatment. Moreover, for inoperable patients, stereotactic radiosurgery is the only available ablative procedure targeted directly at the tumour, whilst sparing surrounding healthy tissue. Phase III randomised clinical trials comparing stereotactic radiotherapy alone with stereotactic radiotherapy, plus whole brain radiotherapy, had comparable overall survival rates17
. However, local relapse was higher in patients treated with stereotactic radiotherapy alone. Neurologic preservation was similar between both groups.
EXTRA-CRANIAL STEREOTACTIC RADIOTHERAPY Invasive immobilisation frames are used with many stereotactic systems. The CyberKnife system however, does not require the use of any invasive frames due to its unique ability to track throughout treatment. Similarly, alternative methods such as abdominal compression, are not required to assist in minimising motion.
LUNG Stereotactic radiotherapy is not the primary treatment option for lung cancer and surgery remains the gold standard for early stage, non-small cell lung cancer NSCLC, providing excellent local control and survival outcomes2
Study
Baumann et al, 2006 [33]
Lagerwaard et al, 2008 [34]
Nagata et al, 2005 [35]
Onishi et al, 2007 [21]
Timmerman et al, 2006 [36]
Xia et al, 2006 [37]
Number of patients
138
Dose Median FU (months)
30-48 Gy in 2-4 #
206 3 x 20 Gy 45 4 x 12 Gy
257 18-75 Gy in 1-22 #
70 3 x 20 Gy 3 x 22 Gy
43 5 x 10 Gy 33 12 30 38 18 27 Table 1: Recent studies investigating outcomes from the use of SBRT
Local control
85% (3 yr) 97% (3yr)
2 yr
survival 65%
65%
98% (2 yr) 90% stage 1A 72% stage 1B
84% 96% (2 yr) 95% (3 yr) 70% 55% 78%
dose, as large lesions have demonstrated local and distant failure24
. . However, radiotherapy is an alternative for
patients who are poor surgical candidates, or who are inoperable due to the stage or the location of the tumour. Conventional radiotherapy has proved to be a poor alternative. Dose escalation is limited when using conventional external beam radiotherapy, mainly because large margins are applied routinely, which result in large treated volumes and increased side effects. Hence, results with external beam radiotherapy have been disappointing with long-term survival rates of just 15-30 per cent, and local failure in excess of 50 per cent in stage I NSCLC18,19
. Complication rates are also high 20 .
There is substantial published literature supporting the use of stereotactic radiotherapy (see table 1). Stereotactic lung radiotherapy allows the delivery of high dose radiotherapy, giving excellent local control, potentially resulting in improved overall survival compared to conventional radiotherapy21
. SRT has been widely accepted for
medically inoperable early stage NSCLC and has shown comparable outcomes to surgical series22,23
.
Delivered doses vary from 45-60Gy, usually given in three fractions. Tumour size is important when considering SRT because an increase in tumour size requires a higher
Delivery of stereotactic radiotherapy to lung tumours does, however, present a number of challenges. Primarily, the continuous respiratory induced motion has to be taken into account and the dose to normal healthy tissue needs to be limited. The ability to track the tumour with high accuracy using the CyberKnife system addresses these challenges and allows the use of smaller margins25
. In contrast, gantry based imaging systems
such as cone-beam CT may provide useful 3D or 4D information prior to treatment delivery, but are unable to account for target movements during treatment delivery, although the information can be used to design patient specific margins.
A drawback of the CyberKnife tracking system is that fiducials are required in many cases and they come with their own associated risks. Delivery also comes at the expense of longer treatment times (averaging approximately 90 minutes). Treatment times over 60 minutes could be associated with loss of biological equivalent dose (BED) of >10-15 per cent, which will impact on tumour control26
. The number of beams should therefore be kept to a minimum when using CyberKnife, without compromising tumour coverage.
Numerous Radiation Therapy Oncology Group (RTOG) studies are currently investigating toxicity and efficacy of SBRT for early stage NSCLC. Additional studies investigating both inoperable and operable patients (RTOG 0236, RTOG 0618) and a phase III randomised multi- centre trial have been initiated in the Netherlands comparing surgery and SBRT in stage IA NSCLC27
. Encouraging results have also been reported for lung metastases,28 however further randomised trials using SBRT are required for both primary and oligometastatic lung disease.
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