Surgery Section - Stereotactic Radiosurgery and Stereotactic Body Radiation Therapy

IMPORTANT REMINDER

Regence Medical Policies are developed to provide guidance for members and providers regarding coverage in accordance with contract terms. Benefit determinations are based in all cases on the applicable contract language. To the extent there may be any conflict between the Medical Policy and contract language, the contract language takes precedence.

PLEASE NOTE: Contracts exclude from coverage, among other things, services or procedures that are considered investigational or cosmetic. Providers may bill members for services or procedures that are considered investigational or cosmetic. Providers are encouraged to inform members before rendering such services that the members are likely to be financially responsible for the cost of these services.

Description

Stereotactic Radiosurgery - The Technology

Stereotactic radiosurgery (SRS) is a method of delivering high doses of ionizing radiation to small intracranial targets. The technique differs from conventional radiotherapy, which involves exposing large areas of intracranial tissue to relatively broad fields of radiation over a number of sessions. SRS entails delivering highly focused convergent beams in a single session so that only the desired target is radiated, sparing adjacent structures.

Two main methods of this technology exist: gamma-ray radiosurgery (Gamma Knife®) and  linear-accelerator radiosurgery (e.g. LINAC and Cyberknife®). Differences in these  systems are summarized in the following table:

Note: Particle radiation can also be used without stereotactic guidance. In this setting, the use of particles is referred to as proton, helium, or neutron radiation therapy. This policy addresses only the use of gamma knife and the linear accelerator. Proton or helium ion radiation therapies are addressed in Medicine Policy No. 49.

As can be seen from the above table, the gamma knife and linear accelerator systems (including the Cyberknife®) are similar in concept; both use multiple photon radiation  beams that intersect at a stereotactically determined target, thus permitting higher doses of radiation delivery with sparing of surrounding normal tissues. The differences between the two relate to how the energy is produced (i.e., through decaying cobalt or from x-rays) and the number of energy sources used (i.e., multiple energy sources in the gamma knife versus one in the linear accelerator system).

Stereotactic Radiosurgery (SRS)- The Procedure

The stereotactic radiosurgical procedure is preceded by a process of localizing the target, which can be performed with one or more of the following techniques: cerebral angiography, computerized tomography, and magnetic resonance imaging. SRS is typically performed in one session, usually requiring no more than an overnight hospital stay.

Stereotactic Body Radiation Therapy (SBRT)

Stereotactic body radiation therapy refers to stereotactically guided radiation therapy applied over several days.  This fractionated form of radiation therapy is made possible by the recent availability of noninvasive repositioning devices that can be used in lieu of a head frame.  Stereotactic radiotherapy is based on the basic radiobiologic principle that fractionation decreases the short and long-term side effects of radiation therapy.  In some settings, this permits higher total dosage to be given.

Image-Guided Radiosurgery or Radiotherapy

Image-guided radiosurgery or radiotherapy is a relatively new development collectively describing  units with real-time guidance systems.   Examples include the Cyberknife® device, BrainLAB Novalis®, TomoTherapy®, and LINAC with computerized tomography (CT).

Applications of Stereotactic Radiosurgery and Stereotactic Radiotherapy

The most common applications of stereotactic radiosurgery include treatment of intracranial tumors and malignancies, including primary and metastatic tumors, acoustic neuromas, and other benign intracranial tumors such as meningiomas or pituitary adenomas. SRS has been used for trigeminal neuralgia that is resistant to other therapies. It is also an established treatment for arteriovenous malformations (AVMs). More recently, SRS has been investigated as a treatment of functional disorders, which are defined as conditions having no detectable organic cause. Examples of functional disorders include chronic pain.  In addition, SRS has been investigated as a treatment for movement disorders such as Parkinson’s disease and essential tremors. Using MRI for target localization, a stereotactic lesion is made in the area of the v.i.m. thalamus or internal globus pallidus. This approach has been proposed for patients considered to be poor candidates for more invasive pallidotomy or thalamotomy.  SRS is also being studied for treatment of extracranial sites including lung tumors, liver tumors, and spinal lesions.  SRS is being studied in order to better target lesions (sparing surrounding normal structures) and to shorten the length of time needed to complete the treatments.

Performance status is frequently used in oncology practice as a variable in determining prognosis and management strategies.  Either the Karnofsky Performance Status (KPS) or the Eastern Cooperative Oncology Group (ECOG) Performance Status scoring systems may be used.

Policy/Criteria

Stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) using   Gamma Knife®, LINAC, Cyberknife®, BrainLAB Novalis®, or TomoTherapy®  units may be considered medically necessary for the following indications:

1. Intracranial  arteriovenous malformations
2. Acoustic neuromas (also known as Vestibular Schwannomas)
3. Pituitary adenomas
4. Non-resectable, residual, or recurrent meningiomas
5. Solitary or multiple brain metastases in patients who have a Karnofsky Performance Status score equal to or greater than 70 (or an ECOG score equal to or less than 2) and no clinical or radiographic evidence of progression of extracranial disease in the month prior to SRS.  Patients who present with brain metastases at the time of initial diagnosis do not need to demonstrate one month of stable scans
6. Primary malignancies of the CNS, including but not limited to high-grade gliomas (initial treatment or treatment of recurrence)
7. Spinal or vertebral body tumors (metastatic or primary) in patients who have received prior radiation therapy
8. Trigeminal neuralgia (also known as tic douloureux) refractory to medical management
9. Patients with stage 1 non-small cell lung cancer showing no nodal or distant disease and who are not candidates for surgical resection.

Stereotactic radiosurgery and stereotactic body radiation therapy   are considered investigational for all other indications including but not limited to:

1. Functional disorders other than trigeminal neuralgia
2. Epilepsy
3. Chronic pain
4. Treatment of extracranial sites (e.g. prostate, ovaries), except for the cases of spinal tumors and stage 1 non-small cell lung cancer as noted above
5. Refractory symptoms of essential tremor or Parkinson's disease.

Note: See separate policy, Regence, Medicine,  Policy No. 49 for non-stereotactic applications of particle beam radiation therapy (i.e., proton or helium ion)

Scientific Background

Challenges to an Evidence Based Approach to Rapidly Evolving Technologies in Radiation Oncology

This policy groups together several different techniques for delivering stereotactic radiosurgery, i.e., the Gamma Knife, LINAC devices, and real-time image-guided devices (e.g.the Cyberknife® device, BrainLAB Novalis®, TomoTherapy®).  However, from an evidence-based approach, it is extremely difficult to compare these different devices to determine if one device is superior to another for a particular indication.  A literature search has failed to identify any controlled trials directly comparing different devices in homogeneous groups of patients.  In addition, the field of radiation oncology is rapidly evolving, with a current intense interest in emerging image guided technology.  A limited number of stereotactic radiosurgery options may be available in individual markets, and thus the choice among devices may be dictated primarily by geography.  The following summarizes different variables related to stereotactic radiosurgery and radiotherapy.

• Size of Lesion

In terms of stereotactic radiosurgery, the superiority of one energy source over another depends primarily on the dose distribution capabilities, which in turn depend on the target’s volume, location, and shape.  For small lesions (i.e., less than 5 cm3), the dose distributions produced by the gamma knife are essentially identical to those achievable with LINAC units.  When the target lesion is nonspherical or of intermediate size (e.g., between five and 25 cm3), LINAC units may have an advantage over Gamma Knife units, due to their ability to treat larger lesions without requiring multiple isocenters (which makes treatment planning difficult), and the ability to shape the dose using collimated fields.  However, when targeting large volumes (i.e., greater than 25 cm3), charged particle units that use a small fixed number of beams have the best ability to shape dose distributions and thus offer some advantages over both LINAC and Gamma Knife units.

• Dose Fractionation

Standard radiobiologic principles suggest that fractionating radiation therapy (i.e., delivery in multiple sessions) will reduce both early and late toxicities to surrounding normal tissues.  Radiosurgery (one treatment) or hypofractionation (limited number of treatments) may be considered when patient movement limits the use the use of conventional radiation therapy, or may be offered as a convenience to patients, particularly those that require rapid pain relief.  These two clinical indications are also associated with different outcomes that must be considered as part of an evidence-based analysis.  A more basic scientific issue is an underlying understanding of the radiosensitivity of surrounding normal tissues.

• Dose Escalation

Novel forms of radiation therapy have been/are being proposed as ways to provide dose escalation.  In this setting, clinical questions include whether or not dose escalation provides improved tumor control, which depends on the dose response rate of individual tumor types, and whether an increased dose is associated with increased toxicity to surrounding tissues.

• Decreased Toxicity

A variety of novel treatment planning and delivery are designed to reduce toxicity.     Evidence of reduced toxicity would require directly comparative studies.  Many of the potential benefits of delivery systems   have been based on modeling studies, or studies with phantoms, and limited clinical experience.

In summary, the lack of comparative studies of different techniques of radiation planning and delivery in homogeneous groups of patients limits any scientific analysis regarding the relative safety and efficacy of different systems for different clinical situations, i.e., reduction of fractionation, dose escalation reduced toxicity, or a combination of all three.  Therefore, the scientific evidence is inadequate to permit scientific conclusions regarding the superiority of one device over another.  The following discussion focuses on different general applications of stereotactic radiosurgery and radiotherapy.

Treatment of Acoustic Neuroma

One research focus has been on the treatment of acoustic neuromas, where the most significant side effect is functional preservation of the facial and auditory nerve.  For example, in a single institution study, Meijer and colleagues reported on the outcomes of single fraction vs. fractionated LINAC-based stereotactic radiosurgery in 129 patients with acoustic neuromas. ( 2) Among these patients, 49 were edentate and thus could not be fitted with a relocatable head frame that relies on dental impressions.  This group was treated with a single fraction, while the remaining 80 patients were treated with a fractionated schedule.  With an average follow-up of 33 months, there was no difference in outcome in terms of local tumor control, facial nerve preservation, and hearing preservation.  Chung and colleagues reported on the results of a single institution case series of 72 patients with acoustic neuromas, 45 who received single fraction therapy and 27 who received fractionated therapy. (3) Patients receiving single fraction treatment were functionally deaf, while those receiving fractionated therapy had useful hearing in the affected ear.  After a median follow-up of 26 months, there was no tumor recurrence in either group. Chang and colleagues reported that 74% of 61 patients with acoustic neuromas treated with CyberKnife using staged treatment who had serviceable hearing maintained serviceable hearing during at least 36 months of follow-up.(4)

Treatment of Brain Metastases

Previous studies suggested that use of radiosurgery for brain metastases should be limited to patients with three or fewer lesions. (5)  A randomized trial, published in 1999, compared whole-brain radiation therapy (WBRT) with WBRT plus radiosurgery boost to metastatic foci.  It found that the significant advantage of radiosurgery boost over WBRT alone in terms of freedom from local failure did not differ among patients with 2, 3, or 4 metastases. Survival also did not depend on number of metastases. As the number of metastases rises, so does the total volume of tissue receiving high-dose radiation, thus the morbidity risk of radiation necrosis associated with radiosurgery is likely to increase. For a large number of metastases, and for large volume of tissue, this risk may be high enough to negate the advantage of radiosurgery plus WBRT over WBRT alone seen in patients with four or fewer metastases. Stereotactic radiosurgery centers commonly exclude patients with more than five metastases from undergoing radiosurgery. ( 6,7) It is difficult to identify a specific number of metastases for which the use of stereotactic radiosurgery is advantageous. A large number of very small metastases may respond to radiosurgery as well as a small number of large metastases.

Aoyama and colleagues reported on a randomized trial of SRS plus whole brain radiation therapy (WBRT) vs. SRS alone for treatment of patients with 1 to 4 brain metastases.(8)  They found a 12-month intracranial tumor recurrence rate of 46.8% in the SRS+WBRT group compared to 76.4% in the group that received only SRS.  However, median survival times were not different at 7.5 and 8.0 months, respectively.  They also found no difference in neurological functional preservation.  In an accompanying editorial, Raizer comments that either treatment approach is a reasonable first step recognizing that those who select SRS alone are more likely to need subsequent salvage radiation treatments. (9) Raizer adds the additional comment that those who have a single brain metastasis from non-small cell lung cancer or RPA (recursive partitioning analysis) class 1 patients should initially receive SRS and WBRT.

Treatment of Epilepsy

The 1998 TEC Assessment (10) cited two studies of eleven and nine patients in which radiosurgery was used to treat epilepsy. The subsequent literature search revealed three small studies on the use of radiosurgery for medically refractory epilepsy. Regis and colleagues selected twenty-five patients with mesial temporal lobe epilepsy, of which sixteen provided minimum two-year follow-up. (11) Seizure free status was achieved in thirteen patients, two patients were improved and three patients had radiosurgery related visual field defects. Schrottner and colleagues included twenty-six patients with tumoral epilepsy, associated mainly with low-grade astrocytomas. (12) Mean follow-up among twenty-four available patients was 2.25 years. Tumor location varied among patients. Seizures were simple partial in six and complex partial in eighteen. Seizures were eliminated or nearly so in thirteen patients. Little improvement was observed in four patients and none in seven. Whang and Kwon performed radiosurgery in thirty-one patients with epilepsy associated with non-progressive lesions. (13) A minimum of one year of follow-up was available in twenty-three patients, of whom twelve were seizure-free, three had antiseizure medications discontinued, two had seizures reduced in frequency, and nine experienced no change. While the Regis series selected a fairly homogeneous clinical sample, the other two studies were heterogeneous. No confirmatory evidence is available on mesial lobe epilepsy. The available evidence from patients with epileptic lesions of various sizes and locations is insufficient to show what factors are associated with favorable outcomes.  The studies published to date are preliminary in nature. The 1998 TEC Assessment observed that evidence was insufficient to permit conclusions about the effects of radiosurgery on epilepsy on epilepsy. Conclusions about the health outcome effects of radiosurgery await additional studies.

Treatment of Chronic Pain

The TEC Assessment of 1998 (10) identified two papers, with two and forty-seven patients, who underwent radiosurgical thalamotomy for chronic pain. No new studies were found in the search of recent literature. Thus, the conclusions of the 1998 TEC Assessment have not changed.

Treatment of Parkinson’s Disease and Essential Tremors

Initially, based on promising preliminary evidence, a 2003 update to the policy added refractory symptoms of essential tremor and Parkinson’s disease as conditions that may be considered medically necessary in patients who are not surgical candidates. (14,15) Since that time, no further evidence has emerged that may permit conclusions about the effectiveness of stereotactic radiosurgery on Parkinson’s disease or other movement disorders. Specifically, radiofrequency ablation or deep brain stimulation are considered the therapies of choice for those with medically refractive disease and no data comparing stereotactic radiosurgery with deep brain stimulation or radiofrequency ablation are available.

Treatment of Spinal Cord Lesions and other Extracranial Sites

While a variety of extracranial applications for SRS and SBRT have been proposed (16), the most thoroughly studied has been the treatment of spinal cord lesions.  In the largest case series, Gerszten and colleagues reported on the outcomes of 115 patients with spinal tumors of varying etiologies (i.e., benign, metastatic, single, or multiple lesions) in a variety of locations (i.e., cervical, thoracic, lumbar, sacral) who were treated with the Cyberknife® in a single session. (17) The majority of patients were treated for pain control.  The authors point out that radiation therapy of the spinal cord is limited by its low tolerance and that if a radiation dose could be targeted more accurately at the lesions, higher doses could be delivered in a single fraction.  They further point out that conventional methods of delivering intensity modulated radiation therapy are limited due to lack of target immobilization.  Axial and radicular pain improved in 74 of the 79 symptomatic patients.  There was no acute radiation toxicity or new neurologic deficits.  The authors concluded that the treatment was feasible and safe.  Conventional external beam radiation therapy typically is delivered over a course of 10-20 fractions.  In contrast, in this study only one Cyberknife® treatment session was used.

In a 2005 study, Degen and colleagues reported on the outcomes of 51 patients with 72 spinal cord lesions who were treated with the Cyberknife®. (18) Patients underwent a median of three treatments.  Pain was improved, as measured by declining mean VAS score, and quality of life was maintained during the one year study period.

Additional reports on the use of stereotactic radiosurgery for spinal tumors have been published. Gerszten recently published results on a series of 500 cases from a single institution (334 tumors had previously undergone external beam irradiation) using the CyberKnife system. (19) In this series, the maximum intratumoral dose ranged from 12.5 to 25 Gy with a mean of 20 Gy. Long-term pain improvement occurred in 290 of 336 cases (86%). Long-term radiographic tumor control was demonstrated in 90% of lesions treated with radiosurgery as a primary treatment modality. Twenty-seven of 32 cases (84%) with a progressive neurologic deficit before treatment experienced at least some clinical improvement. Chang reported on phase I/II results of SBRT in 74 spinal lesions in 63 patients (55% had prior irradiation) with cancer. (20) The actuarial one-year tumor progression-free incidence was 84%. Pattern-of-failure analysis showed two primary mechanisms of failure: recurrence in the bone adjacent to the site of previous treatment; and recurrence in the epidural space adjacent to the spinal cord. The authors concluded that analysis of the data obtained in their study supports the safety and effectiveness of SBRT in cases of metastatic spinal tumors. They add that they consider it prudent to routinely treat the pedicles and posterior elements using a wide bone margin posterior to the diseased vertebrae because of the possible direct extension into these structures and for patients without a history of radiotherapy, more liberal spinal cord dose constraints than those used in the study.

The accumulating evidence suggests that SBRT can be used in patients with spinal, or vertebral body, tumors; the preponderance of the data are in patients who received prior irradiation. It is uncertain from the current literature about the outcomes of using SBRT in the initial treatment of these lesions. It is not certain if symptom relief occurs more rapidly or is more durable, since there have not been comparative studies of SBRT with other types of radiation therapy. In addition, there is the concern, perhaps theoretical, that the limited size of the SBRT field may result in more late recurrences at adjacent levels.

Treatment of non-small-cell lung cancer (NSCLC)

A number of studies of SBRT were identified in the treatment of non-small-cell lung cancer (NSCLC).  Timmerman concluded that prospective trials using SBRT in North America have been able to identify potent tolerant dose levels and confirm their efficacy, but also noted that sometimes debilitating toxicity has been observed for patients with tumors near the central airways. (21) Hof reported on outcomes (median follow-up 15 months) for 42 patients with stages I and II lung cancer who were not suitable for surgery and who were treated with stereotactic radiotherapy. (22) In this series, at 12 months overall survival was 75% and disease-free survival was 70%. Better local control was noted with higher doses of radiation.

In terms of lung tumors, publications are reporting longer-term outcomes with SBRT for patients with early lung cancer who are not surgical candidates. These are patients with clinical stage 1 disease who currently might have been treated with “conventional” radiation therapy. These studies were summarized in a recent review by Nguyen. (23) This paper cites a number of studies of SBRT for early stage lung cancer receiving a biologic equivalent dose of 100 Gy or more. Three of the studies cited reported five-year survival that ranged from 30% to 83%; in the largest series of 257 patients the five-year survival was 42%. Koto reported on a phase II study of 31 patients with Stage 1 non-small-cell lung cancer. (24) Patients received 45 Gy in 3 fractions, but those with tumors close to an organ at-risk received 60 Gy in eight fractions. With a median follow-up of 32 months, the three-year overall survival was 72%, disease-free survival was 84%. Five patients developed grade two or greater pulmonary toxicity. While comparative studies were not identified, older studies have reported three-year disease-specific survival rates of 49% for those with stage 1 disease. (25) SBRT may not be appropriate for tumors in close proximity to the heart, mediastinum or spinal cord. In addition, centrally located proximal tumors may be associated with increased toxicity.  Based on the information reviewed above, SBRT may be considered medically necessary in patients with stage 1 non-small cell lung cancer (not larger than 5 cm in diameter) showing no nodal or distant disease and who are not candidates for surgical resection because of co-morbid conditions.

Treatment of Other Extracranial Sites

There are limited study data on the effectiveness of SRS or SBRT in other extracranial sites.  The published literature consists of single small, non-randomized case series in patients with liver,   prostate and pancreatic tumors. (26-31) One new citation was identified related to treatment planning in prostate cancer. (32) Recent studies on use in liver cancers describe feasibility studies and interim analysis.  Data for other extra-cranial uses of SBRT are limited.  Therefore, these clinical situations are still considered investigational.

References

1. BlueCross and BlueShield Association Medical Policy Reference Manual, Policy No. 6.01.10
2. Meijer OW, Vandertop WP, Baayen JC et al. Single-fraction vs. fractionated LINAC-based stereotactic radiosurgery for vestibular schwannoma: a single-institution study. Int J Radiat Oncol Biol Phys 2003;56(5):1390-6
3. Chung HT, Ma R, Toyota B et al. Audiologic and treatment outcomes after linear accelerator-based stereotactic irradiation for acoustic neuroma. Int J Radiat Oncol Biol Phys 2004;59(4):1116-21
4. Chang SD, Gibbs IC, Sakamoto GT et al. Staged stereotactic irradiation for acoustic neuroma. Neurosurgery 2005;56(6):1254-61
5. Kondziolka D, Patel A, Lunsford LD et al. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys 1999;45(2):427-34
6. Weltman E, Salvajoli JV, Brandt RA et al. Radiosurgery for brain metastases: a score index for predicting prognosis. Int J Radiat Oncol Biol Phys 2000;46(5):1155-61
7. Yu C, Chen JC, Apuzzo ML et al. Metastatic melanoma to the brain: prognostic factors after gamma knife radiosurgery. Int J Radiat Oncol Biol Phys 2002;52(5):1277-87
8. Aoyama H, Shirato H, Tago M et al. Stereotactic radiosurgery plus whole brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: A randomized controlled trial. JAMA 2006;295:2483-91
9. Raizer J. Radiosurgery and whole-brain radiation therapy for brain metastasis: Either or both as the optimal treatment. JAMA 2006;295:2535-6
10. BlueCross and BlueShield Association Technology Evaluation Center Assessment.  Special Report: SRS for Intracranial Lesions by Gamma Beam, Linear Accelerator, and Proton Beam Methods, 1998;  Vol. 13 No. 28
11. Regis J, Bartolomei F, Rey M et al. Gamma knife surgery for mesial temporal lobe epilepsy. J Neurosurg 2000;93(Suppl 3):141-6
12. Schrottner O, Eder HG, Unger F et al. Radiosurgery in lesional epilepsy: brain tumors. Stereotact Funct Neurosurg 1998;70(Suppl 1):50-6
13. Whang CJ, Kwon Y. Long term follow-up of stereotactic Gamma Knife radiosurgery in epilepsy. Stereotact Funct Neurosurg 1996;66(Suppl 1):349-56
14. Ohye C, Shibazaki T, Zhang J et al. Thalamic lesions produced by gamma thalamotomy for movement disorders. J Neurosurg 2002;97(5 suppl):600-6
15. Kondziolka D, Ong JG, Lee JY et al. Gamma Knife thalamotomy for essential tremor. J Neurosurg. 2008;108(1):111-7)
16. Chang SD, Adler JR. Robotic and radiosurgery-the Cyberknife®. Stereotact Funct Radiosurg 2001;76(3-4):204-8
17. Gerszten PC, Ozhasoglu C, Burton SA et al. Cyberknife® frameless stereotactic radiosurgery for spinal cord lesions: clinical experience in 125 cases. Neurosurgery 2004;55(1):89-99
18. Degen JW, Gagnon GJ, Voyadzis JM et al. Cyberknife® stereotactic radiosurgical treatment of spinal cord tumors for pain control and quality of life. J Neurosurg Spine 2005;2(5):5540-9
19. Gerszten PC, Burton SA, Ozhasoglu C et al. Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution. Spine 2007; 32(2):193-9
20. Chang EL, Shiu AS, Mendel E et al. Phase I/II study of stereotactic body radiotherapy for spinal metastasis and its pattern of failure. J Neurosurg Spine 2007; 7(2):151-60
21. Timmerman RD, Park C, Kavanagh BD. The North American experience with stereotactic body radiation therapy in non-small cell lung cancer. J Thorac Oncol 2007; 2(7 suppl 3):S101-12
22. Hof H, Muenter M, Oetzel D et al. Stereotactic single-dose radiotherapy (radiosurgery) of early stage nonsmall-cell lung cancer (NSCLC). Cancer 2007; 110(1):148-55
23. Nguyen NP, Garland L, Welsh J et al. Can stereotactic fractionated radiation therapy become the standard of care for early stage non-small cell lung carcinoma. Cancer Treat Rev 2008; 34(8):719-27
24. Koto M, Takai Y, Ogawa Y et al. A phase II study on stereotactic body radiotherapy for stage I non-small cell lung cancer. Radiother Oncol 2007; 85(3):429-34
25. Kupelian PA, Komaki R, Allen P. Prognostic factors in the treatment of node-negative nonsmall cell lung carcinoma with radiotherapy alone. Int J Radiat Oncol Biol Phys 1996; 36(3):607-13
26. Mendez Romero A, Wunderink W, Hussain SM et al. Stereotactic body radiation therapy for primary and metastatic liver tumors: a single institution phase i-ii study. Acta Oncol 2006; 45(7):831-7
27. Svedman C, Sandstrom P, Pisa P et al. A prospective phase II trial of using extracranial stereotactic radiotherapy in primary and metastatic renal cell carcinoma. Acta Oncol 2007; 45(7):870-5
28. Madsen BL, Hsi RA, Pham HT et al. Stereotactic hypofractionated accurate radiotherapy of the prostate (SHARP), 33.5 Gy in five fractions for localized disease: first clinical trial results. Int J Radiat Oncol Biol Phys 2007; 67(4):1099-105
29. Wulf J, Hädinger U, Oppitz U, Thiele W et al.  Stereotactic radiotherapy of targets in the lung and liver.  Strahlenther Onkol. 2001 Dec;177(12):645-55
30. Herfarth KK, Debus J, Lohr F et al.  Stereotactic single-dose radiation therapy of liver tumors: results of a phase I/II trial.  J Clin Oncol. 2001 Jan 1;19(1):164-70
31. Blomgren H, Lax I, Näslund I et al.  Stereotactic high dose fraction radiation therapy of extracranial tumors using an accelerator. Clinical experience of the first thirty-one patients.  Acta Oncol. 1995;34(6):861-70
32. Fuller DB, Naitoh J, Lee C et al. Virtual HDR CyberKnife treatment for localized prostatic carcinoma: dosimetry comparison with HDR brachytherapy and preliminary clinical observations. Int J Radiat Oncol Biol Phys 2008; 70(5):1588-97

Cross References

Charged Particle (Proton or Helium Ion) Radiation Therapy, Regence Medical Policy Manual,  Medicine, Policy No. 49

Vagus Nerve Stimulation, Regence Medical Policy Manual, Surgery, Policy No. 74

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