Coverage Policy Manual
Policy #: 1997210
Category: Surgery
Initiated: July 1994
Last Review: July 2018
  Stereotactic Radiosurgery and Stereotactic Body Radiation Therapy Gamma Knife Surgery, Linear Accelerator, Cyberknife, TomoTherapy

Description:
Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) are techniques that use highly focused radiation beams to treat both neoplastic and non-neoplastic conditions, in contrast to traditional external radiation beam therapy, which involves the use of relatively broad fields of radiation over a number of sessions that may occur over weeks to months. SRS and SBRT rely on three dimensional imaging to localize the therapy target. Because they are more targeted than traditional external radiation therapy, SRS and SRBT are often used for treatment at sites that are difficult to reach via surgery, located close to other vital structures, or subject to movement within the body.
 
Both SRS and SBRT may be completed with 1 session (single-fraction) or less may require additional sessions (typically no more than 5) over a course of days, referred to as fractionated stereotactic radiotherapy. The fractionation used for SRS and SBRT is less than that used for conventional external beam radiotherapy, thus, “hypofractionated.”
 
SRS and SBRT can be administered by several types of devices that are distinguished by their source of radiation, including particle beams (proton), gamma rays from cobalt-60 sources, or high-energy photons from linear accelerator (LINAC) systems. The use of charged particle (proton beam) radiation therapies is addressed in a separate policy (Policy No. 8.01.10). The most commonly used gamma ray device is the
Gamma Knife® (Elekta, Inc., Stockholm), which is a fixed device used for intracranial lesions, typically for smaller lesions. Several brands of LINAC devices are available, including the Novalis Tx® (Novalis, Westchester, IL), the TrueBeamSTx (Varian Medical Systems, Palo Alto, CA), and the CyberKnife® system (Accuray, Sunnyvale, CA).
 
Non-Neoplastic Conditions Treated with SRS
Arteriovenous malformations consist of a tangled network of vessels in which blood passes from arteries to veins without intervening capillaries. They range in size from small, barely detectable lesions to huge lesions that can occupy an entire hemisphere. SRS incites an inflammatory response in the vessels, which results in ongoing fibrosis with eventual complete obliteration of the lesion over a course of months to years. This latency period is variable, depending on the size of the AVM and the dose distribution of the radiosurgery. During this latency period, there is an ongoing but declining risk of hemorrhage. In contrast, surgical excision provides an immediate effect on the risk of hemorrhage. Total surgical extirpation of the lesion, if possible, is the desired form of therapy to avoid future hemorrhage. However, a small subset of AVMs because of their size or location cannot be excised without serious neurologic sequelae. SRS is an important alternative in these patients.
 
Trigeminal neuralgia is a disorder of the fifth cranial (i.e. trigeminal) nerve that causes episodes of intense, stabbing pain in the face. Although trigeminal neuralgia is initially treated medically, in a substantial number of cases, drug treatment is either ineffective or the adverse effects become intolerable. Neurosurgical options include microvascular decompression, balloon compression, and rhizotomy. SRS has been investigated as an alternative to these neurosurgical treatments.
 
Seizure disorders are initially treated medically. Surgical treatment is only considered in those rare instances when the seizures have proven refractory to all attempts at aggressive medical management, when the seizures are so frequent and severe as to significantly diminish quality of life, and when the seizure focus can be localized to a focal lesion in a region of the brain that is amenable to resection. SRS has been investigated as an alternative to neurosurgical resection. For chronic pain that is refractory to a variety of medical and psychological treatments, there are a variety of surgical alternatives.
Neuro-destructive procedures include cordotomy, myelotomy, dorsal root entry zone (DREZ) lesions, and stereotactic radiofrequency thalamotomy. SRS targeting the thalamus has been considered an investigative alternative to these neuro-destructive procedures.
 
SRS, for the destruction of the thalamic nuclei (thalamotomy) has been proposed for a treatment of essential tremor and other forms of tremor (ie, secondary to Parkinson’s disease, multiple sclerosis, or other neurologic conditions), as an alternative to medical therapy or surgical therapy in extreme cases.
 
Neoplastic Conditions Treated with SRS
SRS is used for primary intracranial tumors and tumors that have metastasized to the central nervous system.
 
Primary intracranial tumors
Acoustic neuromas, also called vestibular schwannomas, are benign tumors originating on the eighth cranial nerve, sometimes seen in association with neurofibromatosis, which can be associated with significant morbidity and even death if their growth compresses vital structures. Treatment options include complete surgical excision using microsurgical techniques, but radiosurgery has also been used extensively, either as a primary treatment or as a treatment of recurrence after incomplete surgical resection.
 
SRS has been used for the treatment of other primary brain tumors, including gliomas, meningiomas, and primitive neuroectodermal tumors (ie, medulloblastoma, pineoblastoma).
 
Extracranial primary tumors treated with SBRT
SBRT has been studied for the treatment of lung cancers – specifically non-small cell lung cancer (NSCLC), with the greatest focus on inoperable, stage 1 NSCLC. Without the use of SBRT, local NSCLC would be treated with surgical resection, if possible, or conventional radiation therapy.
 
Extracranial metastatic tumors treated with SBRT
Metastases from NSCLC to the adrenal gland are common, and systemic treatment is the most frequent therapeutic option. Nevertheless, in patients suffering from an isolated adrenal metastasis, a survival benefit could be achieved after surgical resection.
 
Spinal primary and metastatic tumors treated with SBRT
Metastatic tumors to the spine have historically been treated with conventional radiotherapy. The need for retreatment is high due to morbidity from metastatic disease (eg, pain, myelopathy, spinal cord compression), but radiotherapy to the spine is often limited due to concern for radiation myelopathy and other adverse radiation effects. SBRT to the spine has been most widely studied in patients requiring reirradiation, but interest has also developed in the use of SBRT for the initial treatment of spinal tumors.
 
Regulatory Status
Several SRS and SBRT devices that use LINAC units to generate high-energy photons have been cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) premarket notification process, including the CyberKnife® System for Stereotactic Radiosurgery/Radiotherapy (Accuray, Inc.; approved December 1998, product code MUJ) and the TrueBeam™ Radiotherapy Delivery System (Varian Medical Systems; approved December 2012; product code IYE). Several devices that use cobalt 60 degradation (gamma ray devices) for SRS have been cleared for marketing by FDA through the 510(k) process, including the Leksell GammaKnife® (Elekta; approved May 1999, product code IWB). Gamma ray emitting devices that use cobalt 60 degradation are also regulated through the U.S. Nuclear Regulatory Commission.
 

Policy/
Coverage:
Effective November 2018
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Stereotactic radiosurgery using a gamma or LINAC unit meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the following indications:
 
    • arteriovenous malformations;  
    • acoustic neuromas;  
    • pituitary adenomas;  
    • non-resectable, residual, or recurrent meningiomas;  
    • solitary or multiple brain metastases in patients having good performance status (Karnofsky performance score of 70 or greater) and one of the following:    
        • no active systemic disease (extracranial disease that is stable or in remission); OR
        • newly diagnosed cancer (within past 3 months) and currently undergoing systemic chemotherapy; OR
        • no rapidly progressive disease (e.g. provider plans to treat brain metastases prior to treating primary site.  Primary site must not be rapidly progressing.)
    • primary malignancies of the CNS, including but not limited to high-grade gliomas (initial treatment or treatment of recurrence);  
    • trigeminal neuralgia refractory to medical management.  
    • craniopharyngiomas;  
    • glomus jugulare tumors.  
 
Stereotactic body radiotherapy meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the following indications:
 
    • Treatment of patients with stage 1 non-small cell lung cancer (not larger than 5 cm) showing no nodal or distant disease and who are not candidates for surgical resection;
    • Treatment of primary or metastatic malignant lesions of the spine or paraspinal regions;
    • Treatment of patients with malignant intracranial lesions who will receive 2 to 5 fractions of therapy.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Stereotactic radiosurgery or stereotactic body radiation therapy for the treatment of functional disorders other than trigeminal neuralgia, including epilepsy and chronic pain, or for any other condition not listed above as covered does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.  SRS for treatment of epilepsy or pain is the subject of ongoing clinical trials.
 
For members with contracts without primary coverage criteria, stereotactic radiosurgery or stereotactic body radiation therapy for the treatment of functional disorders other than trigeminal neuralgia, including epilepsy and chronic pain, or for any other condition not listed above as covered, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.  SRS for treatment of epilepsy or pain is the subject of ongoing clinical trials.
 
Extracranial stereotactic radiosurgery does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for many indications including but not limited to:  lesions of the pancreas, liver, lung (except in limited circumstances listed above), prostate, retroperitoneum, and pelvis.  Extracranial stereotactic radiosurgery for these indications is being studied clinical trials.
 
For members with contracts without primary coverage criteria, extracranial stereotactic radiosurgery is considered investigational for many indications including but not limited to:  lesions of the pancreas, liver, lung (except in limited circumstances listed above), prostate retroperitoneum, and pelvis.   Investigational services are specific contract exclusions in most member benefit certificates of coverage.  Extracranial stereotactic radiosurgery for these indications is being studied clinical trials.
 
 
Effective June 2015 - October 2018
 
Stereotactic radiosurgery using a gamma or LINAC unit meets member benefit certificate Primary Coverage Criteria for the following indications:
  • arteriovenous malformations;
  • acoustic neuromas;
  • pituitary adenomas;
  • non-resectable, residual, or recurrent meningiomas;
  • solitary or multiple brain metastases in patients having good performance status (Karnofsky performance score of 70 or greater) and no active systemic disease (defined as extracranial disease that is stable or in remission); or newly diagnosed cancer (within past 3 months) and currently undergoing systemic chemotherapy.
  • primary malignancies of the CNS, including but not limited to high-grade gliomas (initial treatment or treatment of recurrence);
  • trigeminal neuralgia refractory to medical management.
  • craniopharyngiomas;
  • glomus jugulare tumors.
 
Stereotactic body radiotherapy meets member benefit primary coverage criteria for the following indications:
  • Treatment of patients with stage 1 non-small cell lung cancer (not larger than 5 cm) showing no nodal or distant disease and who are not candidates for surgical resection;
  • Treatment of primary or metastatic malignant lesions of the spine or paraspinal regions;
  • Treatment of patients with malignant intracranial lesions who will receive 2 to 5 fractions of therapy.
 
Stereotactic radiosurgery or stereotactic body radiation therapy for the treatment of functional disorders other than trigeminal neuralgia, including epilepsy and chronic pain, or for any other condition not listed above as covered, do not meet member benefit certificate Primary Coverage Criteria requiring proof of effectiveness.  SRS for treatment of epilepsy or pain is the subject of ongoing clinical trials.
 
Extracranial stereotactic radiosurgery is not covered for, but not limited to, treatment of lesions including those of pancreas, liver, lung (except in limited circumstances as above), prostate, retroperitoneum and pelvis.  Extracranial stereotactic radiosurgery for these indications is being studied in clinical trials and is not covered based on benefit certificate Primary Coverage Criteria.
 
For members with contracts without Primary Coverage Criteria, stereotactic radiosurgery or stereotactic body radiation therapy for the treatment of functional disorders other than trigeminal neuralgia, including epilepsy and chronic pain, or for any other condition not listed above as covered, are considered investigational.  Investigational services are an exclusion in the member certificate of coverage.
 
Effective June 2012 - June 2015
 
Stereotactic radiosurgery using a gamma or LINAC unit meets member benefit certificate Primary Coverage Criteria for the following indications:
        • arteriovenous malformations;
        • acoustic neuromas;
        • pituitary adenomas;
        • non-resectable, residual, or recurrent meningiomas;
        • solitary or multiple brain metastases in patients having good performance status (Karnofsky performance score of 70 or greater) and no active systemic disease (defined as extracranial disease that is stable or in remission);
        • primary malignancies of the CNS, including but not limited to high-grade gliomas (initial treatment or treatment of recurrence);
        • trigeminal neuralgia refractory to medical management.
        • craniopharyngiomas;
        • glomus jugulare tumors.
 
Stereotactic body radiotherapy meets member benefit primary coverage criteria for the following indications:
    • Treatment of patients with stage 1 non-small cell lung cancer (not larger than 5 cm) showing no nodal or distant disease and who are not candidates for surgical resection;
    • Treatment of primary or metastatic malignant lesions of the spine or paraspinal regions;
    • Treatment of patients with malignant intracranial lesions who will receive 2 to 5 fractions of therapy.
 
Stereotactic radiosurgery or stereotactic body radiation therapy for the treatment of functional disorders other than trigeminal neuralgia, including epilepsy and chronic pain, or for any other condition not listed above as covered, do not meet member benefit certificate Primary Coverage Criteria requiring proof of effectiveness.  SRS for treatment of epilepsy or pain is the subject of ongoing clinical trials.
 
Extracranial stereotactic radiosurgery is not covered for, but not limited to, treatment of lesions including those of pancreas, liver, lung (except in limited circumstances as above), prostate, retroperitoneum and pelvis.  Extracranial stereotactic radiosurgery for these indications is being studied in clinical trials and is not covered based on benefit certificate Primary Coverage Criteria.
 
For members with contracts without Primary Coverage Criteria, stereotactic radiosurgery or stereotactic body radiation therapy for the treatment of functional disorders other than trigeminal neuralgia, including epilepsy and chronic pain, or for any other condition not listed above as covered, are considered investigational.  Investigational services are an exclusion in the member certificate of coverage.
 
 
 
Effective June 2012
Stereotactic radiosurgery using a gamma or LINAC unit meets member benefit certificate Primary Coverage Criteria for the following indications:
    • arteriovenous malformations;
    • acoustic neuromas;
    • pituitary adenomas;
    • non-resectable, residual, or recurrent meningiomas;
    • solitary or multiple brain metastases in patients having good performance status (Karnofsky performance score of 70 or greater) and no active systemic disease (defined as extracranial disease that is stable or in remission);
    • primary malignancies of the CNS, including but not limited to high-grade gliomas (initial treatment or treatment of recurrence);
    • trigeminal neuralgia refractory to medical management.
    • craniopharyngiomas;
    • glomus jugulare tumors.
 
Stereotactic body radiotherapy meets member benefit primary coverage criteria for the following indications:
        • patients with stage 1 non-small cell lung cancer (not larger than 5 cm) showing no nodal or distant disease and who are not candidates for surgical resection;
        • primary or metastatic malignant lesions of the spine or paraspinal regions.
 
Stereotactic radiosurgery or stereotactic body radiation therapy for the treatment of functional disorders other than trigeminal neuralgia, including epilepsy and chronic pain, or for any other condition not listed above as covered, do not meet member benefit certificate Primary Coverage Criteria requiring proof of effectiveness.  SRS for treatment of epilepsy or pain is the subject of ongoing clinical trials.
 
For members with contracts without Primary Coverage Criteria, stereotactic radiosurgery or stereotactic body radiation therapy for the treatment of functional disorders other than trigeminal neuralgia, including epilepsy and chronic pain, or for any other condition not listed above as covered, are considered investigational.  Investigational services are an exclusion in the member certificate of coverage.
 
Extracranial stereotactic radiosurgery is not covered for, but not limited to, treatment of lesions including those of pancreas, liver, lung, prostate, retroperitoneum and pelvis.  Extracranial stereotactic radiosurgery for these indications is being studied in clinical trials and is not covered based on benefit certificate Primary Coverage Criteria.
 
For members with contracts without Primary Coverage Criteria, extracranial stereotactic radiosurgery is considered investigational.  Investigational services are an exclusion in the member certificate of coverage.
 
Effective prior to June 2012
Stereotactic radiosurgery using a gamma or LINAC unit meets member benefit certificate Primary Coverage Criteria for the following indications:
    • arteriovenous malformations;
    • acoustic neuromas;
    • pituitary adenomas;
    • non-resectable, residual, or recurrent meningiomas;
    • solitary or multiple brain metastases in patients having good performance status (Karnofsky performance score of 70 or greater) and no active systemic disease (defined as extracranial disease that is stable or in remission);
    • primary malignancies of the CNS, including but not limited to high-grade gliomas (initial treatment or treatment of recurrence);
    • trigeminal neuralgia refractory to medical management.
 
Stereotactic body radiotherapy meets member benefit primary coverage criteria for the following indications:
    • patients with stage 1 non-small cell lung cancer (not larger than 5 cm) showing no nodal or distant disease and who are not candidates for surgical resection;
    • primary or metastatic malignant lesions of the spine or paraspinal regions.
 
Stereotactic radiosurgery or stereotactic body radiation therapy for the treatment of functional disorders other than trigeminal neuralgia, including epilepsy and chronic pain, or for any other condition not listed above as covered, do not meet member benefit certificate Primary Coverage Criteria requiring proof of effectiveness.  SRS for treatment of epilepsy or pain is the subject of ongoing clinical trials.
 
For members with contracts without Primary Coverage Criteria, stereotactic radiosurgery or stereotactic body radiation therapy for the treatment of functional disorders other than trigeminal neuralgia, including epilepsy and chronic pain, or for any other condition not listed above as covered, are considered investigational.  Investigational services are an exclusion in the member certificate of coverage.
 
Extracranial stereotactic radiosurgery is not covered for, but not limited to, treatment of lesions including those of pancreas, liver, lung, prostate, retroperitoneum and pelvis.  Extracranial stereotactic radiosurgery for these indications is being studied in clinical trials and is not covered based on benefit certificate Primary Coverage Criteria.
 
For members with contracts without Primary Coverage Criteria, extracranial stereotactic radiosurgery is considered investigational.  Investigational services are an exclusion in the member certificate of coverage.

Rationale:
Due to the detail of the rationale, the complete document is not online. If you would like a
hardcopy print, please email: codespecificinquiry@arkbluecross.com
 
The choice of energy source, i.e., gamma knife, LINAC, or charged-particle beam is frequently a local issue depending on availability of devices. LINAC devices, which can be adapted from existing linear accelerators, are the most common, while there are fewer gamma knife units. Due to their heavier mass, charged-particle accelerators are much larger and costlier than electron linear accelerators and thus have not been adapted for dedicated clinical use. With few exceptions these accelerators are located exclusively in dedicated physics research facilities (i.e., Lawrence Berkeley Laboratory and the Harvard Cyclotron Laboratory.)
 
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., <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 5 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., >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.
 
The latest Policy Update was based on review of a literature search covering MEDLINE references entered between January 1998 and July 2002. The search was aimed at identifying articles relevant to patient selection for radiosurgery of multiple brain metastases, as well as finding recent studies on use of radiosurgery for treating epilepsy and chronic pain. Studies presenting health outcome data for 10 or more patients were sought.  
 
Previous studies suggested that use of radiosurgery for brain metastases should be limited to patients with 3 or fewer lesions.  A recent randomized trial 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 the 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 volumes of tissue, this risk may be high enough to negate the advantage of radiosurgery plus WBRT over WBRT alone seen in patients with 4 or fewer metastases. Stereotactic radiosurgery centers commonly exclude patients with more than 5 metastases from undergoing radiosurgery.  It is difficult to identify a specific limit on the 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 larger metastases. The previous Policy Update stated that radiosurgery is medically necessary for between 1 and 3 metastases, but recent literature suggests that such a restriction is no longer justified.
 
Two studies were completed prior to the 1998 review of this policy that included 11 and 9 patients in which radiosurgery was used to treat epilepsy. The subsequent literature search revealed 3 small studies on the use of radiosurgery for medically refractory epilepsy. Regis et. al.  Selected 25 patients with mesial temporal lobe epilepsy, of which 16 provided minimum 2-year follow-up. Seizure-free status was achieved in 13 patients, 2 patients were improved and 3 patients had radiosurgery-related visual field defects. Schrottner et. al.  Included 26 patients with tumoral epilepsy, associated mainly with low-grade astrocytomas. Mean follow-up among 24 available patients was 2.25 years. Tumor location varied across patients. Seizures were simple partial in 6 (3 with generalization) and complex partial in 18 (5 with generalization, 1 gelastic). Seizures were eliminated or nearly so in 13 patients.  Little improvement was observed in 4 patients and none in 7.  Whang and Kwon  performed radiosurgery in 31 patients with epilepsy associated with non-progressive lesions. A minimum of 1 year of follow-up was available in 23 patients, of whom 12 were seizure-free, 3 had antiseizure medications discontinued, 2 had seizures reduced in frequency, and 9 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 temporal 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 outcome. There is inadequate reporting of complications associated with radiosurgery. The studies published to date are preliminary in nature. Conclusions about the health outcome effects of radiosurgery await additional studies.  
 
Two studies were completed prior to the 1998 review of this policy that included 2 and 47 patients, who underwent radiosurgical thalamotomy for chronic pain. No new studies were found in the search of recent literature. The policy conclusions have not changed.
 
Treatment of Extracranial Sites Including Spinal Cord Lesions
A variety of applications have been proposed for the CyberKnife device. Published data are limited for most extracranial sites and thus this use is considered investigational.
 
The site most studied involves spinal 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.  The majority of patients were treated for pain control and also had received prior external beam irradiation. 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 IMRT 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. Conventional external beam radiation therapy typically is delivered over a course of 10 to 20 fractions. In contrast, in this study only 1 CyberKnife treatment session was used. In a 2005 study, Degen and colleagues reported on the outcomes of 51 patients with 72 spinal lesions who were treated with the CyberKnife.  Patients underwent a median of 3 treatments. Pain was improved, as measured by declining mean visual analog scale (VAS) score, and quality of life was maintained during the 1-year study period.
 
While these studies show that this approach was feasible, safe, and was able to provide pain relief with targeted radiation with few treatment sessions, studies comparing this approach to conventional treatments are needed to fully understand the impact of this treatment on pain relief, tumor control, and survival.
 
Stereotactic Radiotherapy
Stereotactic radiotherapy describes the delivery of multiple fractions over a course of several days. 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 versus fractionated LINAC-based stereotactic radiosurgery in 129 patients with acoustic neuromas.  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.  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  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. Three separate single-institution case series reported on 87 patients with metastatic disease, 143 patients with astrocytomas, and 36 patients with cerebral AVMs who were treated with fractionated stereotactic radiotherapy.  While all reported promising outcomes, the lack of a control group receiving stereotactic radiosurgery severely limits interpretation.
 
2009 Update
Input from several expert sources has uniformly supported the use of stereotactic radiation body therapy for the treatment of small non-small cell lung cancer, when there is no evidence of nodal or distant disease and when the patient is not a candidate for surgical resection.  There was limited support for use of this technique in some patients with liver (metastatic and primary) cancer.  There was very little support for its use in prostate cancer. Small trials of SBRT for liver and lung metastases have shown promise (Rusthoven, 2009-2 articles, Lee, 2009), although aneditorialists for these articles (Ben-josef, 2009) opined that “although SBRT seems to have given us a bigger hammer, we still have much to learn about how and when to strike the nails.”
 
There are many ongoing trials of stereotatactic radiosurgery, especially for extracranial applications.  Trials may include SRS alone or in combination with chemotherapy.
Lung cancer: NCT00643318, NCT00852644, NCT00238602, NCT00006456, NCT00687986
Pancreatic cancer: NCT00833859, NCT00547144, NCT00425841
Breast: NCT00529334, NCT00167414
Prostate: NCT00643617, NCT00643994, NCT00851916, NCT00619515
Liver, primary or metastatic: NCT00547677, NCT00006456
Spine, primary or metastatic: NCT00853528, NCT00593320
Pain: NCT00802659
Epilepsy: NCT00860145
 
2012 Update
Stereotactic Radiosurgery
This policy update includes information regarding SRS for the treatment of craniopharyngiomas and glomus jugulare tumors that lead to a change in the policy statement.
 
Hashizume and colleagues evaluated the results of the use of SRS in 10 patients with craniopharyngioma adjacent to optic pathways (Hashizume, 2010). Ten patients (six men, four women) with craniopharyngioma and median age of 56.5 years (range 10-74 years) were treated from 2006 through 2009. Median volume of tumor was 7.9 ml (range 1.1-21 ml). A total dose of 30-39 Gy in 10-15 fractions (median 33 Gy) was delivered to the target. Ten patients were followed up for 9-36 months (median 25.5 months). The response rate was 80% (8/10), and control rate was 100%. Improvement of neurological symptoms was observed in five patients. No serious complications due to SRS were found.
 
Hasegawa and colleagues determined the limiting dose to the optic apparatus in single-fraction irradiation in patients with craniopharyngioma treated with gamma knife radiosurgery (Hasegawa, 2010). One hundred patients with 109 craniopharyngiomas treated with radiosurgery were evaluated with a median follow-up period of 68 months. Tumor volume varied from 0.1 to 36.0 (median, 3.3) cm. The actuarial 5- and 10-year overall rates of survival of tumor progression after radiosurgery were 93% and 88%, respectively. The actuarial 5- and 10-year progression-free survival rates were 62% and 52%, respectively. Among 94 patients in whom visual function was evaluable, only 3 patients developed radiation-induced optic neuropathy, indicating an overall Kaplan-Meier radiation-induced optic neuropathy rate of 5%.
 
Combs and colleagues evaluated the long-term outcome in patients with craniopharyngiomas treated with fractionated stereotactic radiotherapy (Combs, 2007).  A total of 40 patients with craniopharyngiomas were treated between 1989 and 2006. Most patients were treated for tumor progression after surgery. A median target dose of 52.2 grays (Gy) (range, 50.4-56 Gy) was applied in a median conventional fractionation of 5 x 1.8 Gy per week. Follow-up examinations included thorough clinical assessment as well as contrast-enhanced magnetic resonance imaging scans, After a median follow-up of 98 months (range, 3-326 months), local control was 100% at both 5 years and 10 years. Overall survival rates at 5 years and 10 years were 97% and 89%, respectively. A complete response was observed in 4 patients and partial responses were noted in 25 patients. Eleven patients presented with stable disease during follow-up. Acute toxicity was mild in all patients. Long-term toxicity included enlargement of cysts requiring drainage 3 months after FSRT. No visual impairment, radionecrosis, or development of secondary malignancies were observed. The authors concluded that long-term outcome of fractionated radiosurgery for craniopharyngiomas is excellent with regard to local control as well as treatment-related side effects.
 
Ivan and colleagues conducted a meta-analysis of tumor control rates and treatment-related mortality for patients with glomus jugulare tumors (Ivan, 2011). In this study, the authors assessed data collected from 869 patients with glomus jugulare tumors from the published literature to identify treatment variables that impacted clinical outcomes and tumor control rates. A comprehensive search of the English-language literature identified 109 studies that collectively described outcomes for patients with glomus jugulare tumors. Univariate comparisons of demographic information between treatment cohorts were performed to detect differences in the sex distribution, age, and Fisch class of tumors among various treatment modalities. Meta-analyses were performed on calculated rates of recurrence and cranial neuropathy after subtotal resection (STR), gross-total resection (GTR), STR with adjuvant postoperative radiosurgery (STR+SRS), and stereotactic radiosurgery alone (SRS). The authors identified 869 patients who met their inclusion criteria. In these studies, the length of follow-up ranged from 6 to 256 months. Patients treated with STR were observed for 72 ± 7.9 months and had a tumor control rate of 69% (95% CI 57%-82%). Those who underwent GTR had a follow-up of 88 ± 5.0 months and a tumor control rate of 86% (95% CI 81%-91%). Those treated with STR+SRS were observed for 96 ± 4.4 months
 
Stereotactic Body Radiation Therapy
A search of the MEDLINE database through May 2012 did not reveal any new information that would prompt a change in the coverage statement regarding SBRT.
 
A Technical Brief was published on SBRT based on research conducted by the ECRI Institute for the Agency for Healthcare Research and Quality (Tipton, 2011). The report offered the following conclusions:
    • SBRT has been used for treatment of a variety of cancers with the majority of studies being done to treat cancers of the lung and thorax
    • None of the available studies involve comparison groups
    • “Comparative studies are needed to provide evidence that the theoretical advantages of SBRT over other radiotherapies actually occur in the clinical setting”
    • There is only one ongoing trial using a direct comparison to a different form of radiation therapy
    • “A full systemic review of the current literature cannot answer questions on the effectiveness and safety of SBRT compared to other radiotherapy interventions”
 
2014 Update
This policy is updated with a literature search through December 2013. There was no new literature that would prompt a change in the coverage statement. A summary of the key identified literature is included below.
 
Uveal melanoma
The literature on the use of SRS for uveal melanoma consists of case series; no studies directly comparing SRS with other, accepted radiation modalities used to treat uveal melanoma (brachytherapy, proton beam) are identified.
 
A 2012 review article summarizes the literature on the use of SRS for uveal melanoma, with long-term tumor control rates using the Gamma Knife reported to be around 90% (Zehetmayer, 2012). Initial studies using SRS for uveal melanoma reported secondary side effects from radiation to be common; however, more recent studies have reported lower incidences with lower total radiation doses (Zehetmayer, 2012).
The largest study to date consisted of 212 patients with choroidal melanoma, who were not suitable for brachytherapy or resection (Dunavoelgyi, 2011). Patients in the study received different doses of radiation ranging from 50 Gy to 70 Gy, in 5 fractions over 7 days. Ophthalmologic examination was performed at baseline and every 3 months in the first 2 years, every 6 months until 5 years, and once a year until 10 years after SRS. The study included measurement of tumor dimension and height using standardized methods, assessment of visual acuity and routine ophthalmologic examinations. Local tumor control was 96% at 5 years, and 93% at 10 years. Thirty-two patients developed metastases, and 22 of these patients died during the follow-up period. Median visual acuity decreased from 0.55 at baseline to hand motion (p<0.001). The authors concluded that SRS was sufficient to achieve excellent local tumor control in patients with melanoma of the choroid, and that disease outcome and vision were comparable to that achieved with proton beam radiotherapy.
 
Additional case series using SRS for uveal melanoma have suggested that it is a possible eye-sparing option for patients, with outcomes comparable to enucleation or other radiation modalities (Sarici, 2013; Muller, 2012; Furdova, 2010).
The published literature is insufficient to demonstrate improved outcomes with the use of stereotactic radiosurgery over other accepted radiation modalities in the treatment of uveal melanoma.
Hepatocellular carcinoma (HCC)
Bujold and colleagues reported on sequential phase I and II trials of SBRT for locally advanced hepatocellular carcinoma (Bujold, 2013). Two trials of SBRT for patients with HCC who were considered to be unsuitable for standard locoregional therapies were conducted from 2004 to 2010. All of the patients had Child-Turcotte-Pugh class A disease. The primary end points were toxicity and local control at 1 year, defined as no progressive disease of irradiated HCC by RECIST (Response Evaluation Criteria in Solid
Tumors). A total of 102 patients were evaluable (n=50 in trial 1, 2004 to 2007; n=52 in trial 2, 2007 to 2010). Underlying liver disease was hepatitis B in 38% of patients, hepatitis C in 38%, alcohol related in 25%, and other in 14%, and none in 7%. Fifty-two percent received prior therapies (excluding sorafenib). TNM stage was III in 66% of patients, and 61% had multiple lesions. Median gross tumor volume was 117.0 mL (range, 1.3 to 1,913.4 mL). Tumor vascular thrombosis (TVT) was present in 55%, and 12% of patients had extrahepatic disease. Local control at one year was 87% (95% CI, 78% to 93%). Toxicity ≥ grade 3 was seen in 30% of patients. In seven patients (two with TVT and progressive disease), death was possibly related to treatment (1.1 to 7.7 months after SBRT). Median overall survival was 17.0 months (95% CI, 10.4 to 21.3 months).
 
Meng and colleagues conducted a systematic review and meta-analysis of transcatheter arterial chemoembolization (TACE) in combination with radiotherapy compared to TACE alone for unresectable HCC using using meta-analysis of data from the literature involving available trials (Meng, 2009).  Seventeen trials involving 1,476 patients were identified. Five were RCTs, and 12 were non-randomized controlled clinical trials. In terms of quality, 5 RCTs were graded B, and the 12 non-randomized studies were graded C. Results showed that TACE plus RT significantly improved survival and tumor response over TACE alone. The authors concluded that considering the strength of the evidence, additional randomized controlled trials are needed before combination TACE and RT can be recommended routinely.
Ongoing trials
One Phase 3 trial is identified that compares the use of transarterial chemoembolization and SBRT for recurrent hepatocellular carcinoma (NCT01327521).
Prostate Cancer
Katz and colleagues performed SBRT on 304 patients with clinically localized prostate cancer (211 with high-risk disease, 81 with intermediate-risk and 12 with low-risk disease): Fifty received 5 fractions of 7 Gy (total dose 35 Gy) and 254 received 5 fractions of 7.25 Gy (total dose 36.25 Gy) (Katz, 2010). At a median 30-month (range 26-37 months) follow-up, there were no biochemical failures for the 35-Gy dose level. Acute grade II urinary and rectal toxicities occurred in 4% of patients with no higher grade acute toxicities. At a median 17-month (range: 8-27 months) follow-up, the 36.25-Gy dose level had 2 low- and 2 high-risk patients fail biochemically (biopsy showed 2 low- and 1 high-risk patients were disease-free in the gland). Acute grade II urinary and rectal toxicities occurred in 4.7% and 3.6% of patients, respectively. The authors concluded that the low toxicity was encouraging and that additional follow-up is needed to determine long-term biochemical control and maintenance of low toxicity.
At 6 years follow-up (Katz, 2013), late urinary grade II complications were seen in 4% of patients treated with 35 Gy and 9% of patients treated with 36.25 Gy. Five late grade III urinary toxicities occurred in patients treated with 36.25 Gy. Late grade II rectal complications were seen in 2% and 5% of patients treated with 35 Gy and 36.25 Gy, respectively. Initially, bowel and urinary QOL scores decreased, but returned to baseline levels. There was an overall 20% decrease in the sexual QOL score. For patients that were potent prior to SBRT, 75% remained potent. Actuarial 5-year biochemical recurrence-free survival was 97% for patients with low-risk disease, 90.7% for those with intermediate risk, and 74.1% for high-risk patients.
 
Ongoing Clinical Trials
A Phase 3 study is active, which is an international, multicenter, randomized study of organ confined low and intermediate risk prostate cancer and is composed of 2 parallel randomization schemes based on applicability of surgery as a treatment for the patient. Patients for whom surgery is a consideration are randomized to either laparoscopic or da Vinci prostatectomy or CyberKnife prostate SBRT. Patients for whom surgery is not a consideration are randomized to either conventionally fractionated radiation therapy or CyberKnife prostate SBRT. Efficacy, toxicity and quality-of-life outcomes will be compared across the pairs in each randomization. (NCT01584258).
 
A Phase III randomized open multicentre trial (ISRCTN45905321) is ongoing in Sweden comparing 78 Gy of intensity-modulated radiation therapy (IMRT) or 3-dimensional conformal RT (3D-CRT) in 39 2-Gy fractions to 42.7 Gy of SBRT in seven 6.1-Gy fractions, given every other day for men with T1c to T3a prostate cancer and up to 2 of the following risk factors: T3a, Gleason score 7 or higher, and/or PSA higher than 10 but lower than 20 ng/mL.
Kidney cancer
A 2012 systematic review on the use of stereotactic radiotherapy for primary renal cell carcinoma identified a total of 126 patients worldwide who had been treated using this modality (Siva, 2012). A systematic search performed in January 2012 identified 7 retrospective studies and 3 prospective studies that used a wide range of techniques, doses and dose fractionation schedules. Median or mean follow-up ranged from 9 months to 57.5 months. Local control was reported as 93.9% (range 84-100%) and the rate of severe grade 3 or higher adverse events was 3.8% (range 0-19%). The conclusions of the systematic review were that the current literature suggests that stereotactic radiotherapy for renal cell carcinoma can be delivered with good rates of local control and acceptable toxicity, but that there is insufficient evidence to recommend a consensus for dose fractionation or technique, and there is a need for further prospective studies.
Oligometastases
2012 and 2013 reviews on the use of SBRT for oligometastases summarize the data on local tumor control, and in a limited subset of patients, survival, for various anatomical sites. (Alongi, 2012; Tree, 2013; Corbin, 2013)
 
A 2012 long-term follow-up of a prospective study was reported on oligometastases treated with SBRT (Milano, 2012). The authors prospectively analyzed the long-term survival, tumor control outcomes and freedom from widespread distant metastases (FFDM) after SBRT in 121 patients with 5 or fewer clinically detectable metastases, from any primary site, metastatic to one to three organ sites, and treated with SBRT. For patients with breast cancer, the median follow-up was 4.5 years (7.1 years for 16 of 39 patients alive at the last follow-up visit). The 2-year OS, FFDM and local control (LC) rate was 74%, 52%, and 87%, respectively. 6-year OS, FFDM, and LC rate was 47%, 36%, and 87%, respectively. From the multivariate analyses, the variables of bone metastases (p = .057) and one vs. more than one metastasis (p = .055) were associated with a fourfold and threefold reduced hazard of death, respectively. None of the 17 bone lesions that were from breast cancer recurred after SBRT versus 10 of 68 lesions from other organs that recurred (p =.095). For patients with non-breast cancers, the median follow-up was 1.7 years
(7.3 years for 7 of 82 patients alive at the last follow-up visit). 2-year OS, FFDM, and LC rate was 39%, 28%, and 74%, respectively, and 6-year OS, FFDM, and LC rate was 9%, 13%, and 65%, respectively. For non-breast cancers, a greater SBRT target volume was significantly adverse for OS (p = .012) and lesion LC (p <.0001). Patients whose metastatic lesions demonstrated radiographic progression after systemic therapy but before SBRT, experienced significantly worse OS compared with patients with stable or regressing disease. The authors conclude that select patients with limited metastases treated with SBRT are long-term survivors.
 
Lung Oligometastases
For isolated or a few lung metastases (including less than 3 or less than 5 according to different selection criteria), the local control probability at 1 year has been reported in the range of 70%-100% (Alongi, 2012).In most series, the most common clinical presentation is a single lung metastasis. It is difficult to accurately evaluate survival estimates and clinical outcomes using SBRT for lung metastases due to an absence of randomized trials and because most phase 1 and 2 trials included heterogeneous patient populations (Alongi, 2012).
 
It is also difficult to compare OS data from SBRT with that of historical surgical metastasectomy series, mainly because of the different clinical characteristics of the patients, as most patients referred for SBRT are felt to be inoperable due to medical comorbidities that affect OS outcomes (Alongi, 2012). Data from the International Registry of Lung Metastases reported OS of 70% at 2 years and 36% at 5 years in patients with a single metastasis who underwent surgical metastasectomy (International Registry of Lung Metastases, 1997).
A systematic review by Siva and colleagues on the use of SBRT for pulmonary oligometastases estimated from the largest studies included in the review a 2-year weighted OS rate of 54.5% (Siva, 2010), ranging from higher rates in a study by Norisha and colleagues of 84% (Norihisa, 2008) to lower rates, such as 39%, reported from a multi-institutional trial (Rusthoven, 2009).  
 
Liver Oligometastases
The liver is the most common site of metastatic spread of colorectal cancer (CRC). Data show that surgical resection of limited liver metastases can result in long-term survival in select patients. However, only 10-20% of patients with metastatic CRC to the liver are surgical candidates. In patients who are not considered to be candidates for surgery, a variety of locally ablative techniques have been developed, the most common of which are radiofrequency ablation (RFA) and transarterial chemoembolization. Retrospective analyses of RFA for liver metastases from CRC have shown wide variability in 5-year OS rates, ranging from 14% to 55% (Alongi, 2012).  
 
Retrospective series on the use of SBRT has reported local control rates ranging from 57-100% (Alongi, 2012).
 
Prospective studies have reported 1-year OS rates ranging from 61-85% and 2-year OS rates ranging from 30-62% (Alongi, 2012).  
 
One of the larger series that was reported by Chang et al. studied outcomes of SBRT for colorectal liver metastases in a pooled patient cohort from 3 institutions with colorectal liver metastases (Chang, 2011). Patients were included if they had 1 to 4 lesions, received 1 to 6 fractions of SBRT, and had radiologic imaging ≥3 months’ post-treatment. Sixty-five patients with 102 lesions treated from 2003 to 2009 were retrospectively analyzed. Forty-seven (72%) patients had ≥1 chemotherapy regimen before stereotactic body radiotherapy, and 27 (42%) patients had ≥2 regimens. The median follow-up was 1.2 years (range, 0.3-5.2 years). The median dose was 42 gray (Gy; range, 22-60 Gy). One- and 2-year local control rates were 67% and 55%, respectively. One- and 2-year OS rates were 72% and 38%, respectively.
These studies have had relatively short follow-up times, typically <18 months. They are also limited by relatively small numbers of patients in the studies and differences in the systemic therapies administered which may have affected treatment outcomes.
 
Adrenal gland oligometastases
The most frequent primary tumor that metastasizes to the adrenal glands is non-small cell lung cancer. Longer OS times have been reported with resection of clinically isolated adrenal metastases when compared with nonsurgical therapy, which has included locally ablative techniques, embolization and EBRT. Few studies on the use of SBRT in adrenal metastases have been published. Local control rates at 1 year ranging from 55% to 90% have been reported, and 1 year OS rates ranging from 40% to 56% and 2 year OS ranging from 14% to 33% (Alongi, 2012). Scorsetti et al. described the feasibility, tolerability and clinical outcomes of SBRT in the treatment of adrenal metastases in consecutive cancer patients (Scorsetti, 2012). Between 2004 and 2010, a total of 34 patients, accounting for 36 adrenal metastatic lesions, were treated with SBRT. All 34 patients were clinically and radiologically evaluated during and after completion of SBRT. The following outcomes were taken into account: best clinical response at any time, local control, time to systemic progression, time to local progression, overall survival and toxicity. The Kaplan-Meier method was used to estimate survival and factors that could potentially affect outcomes were analyzed with Cox regression analysis. No cases of Grade ≥3 toxicity were recorded. At a median follow-up of 41 months (range 12-75 months) 22 patients were alive. Eleven percent of lesions showed complete response, 46% partial response, 36% stable disease and 7% progressed in the treated area. Local failure was observed in 13 cases and actuarial local control rates at 1 and 2 years were 66% and 32%, respectively. Median time to local progression was 19 months and median survival was 22 months.
 
Holy et al. presented initial institutional experiences with SBRT for adrenal gland metastases (Holy, 2011). Between 2002 and 2009, 18 patients with non-small cell lung cancer and adrenal metastases received SBRT for the metastatic disease. Metastases were isolated in 13 patients and multiple in 5 patients. A median progression-free survival time of 4.2 months was seen in the entire patient group, with an increased PFS of 12 months in the 13 patients with isolated metastasis. After a median follow-up of 21 months, 77% of the patients with isolated adrenal metastasis achieved local control. In these patients, median OS was 23 months.
 
Casamassima et al. evaluated a retrospective single-institution outcome after hypofractionated SBRT for adrenal metastases (Casamassima, 2012). Between 2002 and 2009, 48 patients were treated with SBRT for adrenal metastases. Eight patients were treated with single-fraction SBRT and 40 patients with multi-fraction. Median follow up was 16.2 months (range 3-63 months). At time of analysis, 20 patients were alive and 28 patients were dead. One and 2-year actuarial OS rates were 39.7% and 14.5%, respectively. The median interval to local failure was 4.9 months. The actuarial 1-year disease control rate was 9%; the actuarial 1- and 2-year local control rates were both 90%.
 
Chawla et al. investigated the dosimetry and outcomes of patients undergoing SBRT for metastases to the adrenal glands (Chawla, 2009). A retrospective review of 30 patients who had undergone SBRT for adrenal metastases from various primary sites, including lung (n=20), liver (n=3), breast (n=3), melanoma (n=1), pancreas (n=1), head and neck (n=1), and unknown primary (n=1) was performed. Of the 30 patients, 14 with five or fewer metastatic lesions (including adrenal) underwent SBRT, with the intent of controlling all known sites of metastatic disease. Sixteen patients underwent SBRT for palliation or prophylactic
palliation of bulky adrenal metastases. 24 patients had >3 months of follow-up with serial computed tomography. Of these 24 patients, 1 achieved a complete response, 15 achieved a partial response, 4 had stable disease, and 4 developed progressive disease. No patients developed symptomatic progression of their adrenal metastases. Local control was poor, and most patients developed widespread metastases shortly after treatment, with one-year survival, local control, and distant control rates of 44%, 55%, and 13%, respectively. No patient developed grade 2 or greater toxicity.
Ongoing Clinical Trials
An active randomized clinical phase III trial is testing the efficacy of radiofrequency ablation and stereotactic body radiotherapy SBRT in the treatment of colorectal carcinoma liver metastases. Primary endpoint is local progression-free survival.
 
Conclusion
Systemic therapy is most frequently the preferred therapy for patients with liver metastases, but surgical excision or local tumor ablation strategies are often considered for patients with limited disease.
 
The role of SBRT in metastases to the liver is not clear. The optimal dose and fractionation is not known, nor is there consensus on the maximum size or number of lesions suitable to SBRT. The literature on the use of SBRT in liver metastases is limited by the small numbers of patients in the studies, retrospective analyses, and the inclusion of mixed tumor types in the local control and survival analyses. Therefore, the use of SBRT for hepatic metastases does not meet primary coverage criteria.
  
2015 Update
A literature search conducted through December 2014 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Data on the use of SRS and SBRT consists primarily of case series, registry data and early phase trials, with a limited number of randomized controlled trials (RCTs) and nonrandomized comparative trials.
 
The selection of variables used in the delivery of SRS and SBRT is complex and individualized, requiring selection of the device, radiation dose, and the size and shape of treatment margins, all of which depend on the location, shape, and radiosensitivity of the target tissue and the function and radiosensitivity of the surrounding tissue. Several ongoing questions exist in the evaluation of SRS and SBRT, related to most appropriate choices of:
  • Radiotherapy delivery device based on the size and shape of the target lesion.
  • Dose fractionation.
  • Methods to reduce toxicity.
 
Trials that would allow direct comparison of all of the possible variables involved in selecting specific SRS and SBRT methods do not currently exist. Therefore, the available evidence is inadequate to permit scientific conclusions about specific radiation planning and delivery techniques, including the specific number of fractions and methods of dose escalation or toxicity reduction. Therefore, the following discussion groups together several different techniques for delivering SRS and SBRT and does not attempt to compare specific radiation planning and delivery techniques.
 
Stereotactic Radiosurgery
Non-Neoplastic Conditions
 
Arteriovenous Malformations
In 2014, Mohr et al reported results of the ARUBA trial, a randomized, multicenter trial to compare medical therapy to medical therapy with interventional therapy (including any neurosurgical, endovascular, or stereotactic radiotherapy procedure) in patients with unruptured arteriovenous malformations (AVM) (Mohr, 2014). Two hundred and twenty-six patients were enrolled and randomized, 116 to interventional therapy and 110 to medical management. Among those randomized to interventional therapy, 91 received interventional therapy, 5 with neurosurgery alone, 30 with embolization alone, 31 with radiotherapy alone, 12 with embolization and neurosurgery, 15 with embolization and radiotherapy, and 1 with all three. The trial was stopped early by its data and safety monitoring board after interim analysis demonstrated superiority of medical management, after outcomes were available for 223 patients with mean follow up time of 33.3 months. The risk of death or stroke was lower in the medical management group than in the interventional therapy group (hazard ratio [HR] 0.27, 95% CI 0.14 to 0.54). Patients will continue to be followed to determine whether differences in outcomes persist. Although a high proportion of patients randomized to interventional therapy (40.5%) received at least some radiotherapy, outcomes are not reported by therapy type, making it difficult to assess the comparative effectiveness of SRS in AVM treatment.
 
Paul et al conducted a retrospective cohort study that included 697 SRS treatments in 662 patients treated with SRS for brain AVMs at a single institution (Paul, 2014). The obliteration rate after a single or multiple SRS procedures was 69.3% and 75%, respectively. The obliteration rates were significantly associated with AVMs that were compact (odds ratio [OR] 3.16, 95% CI 1.92 to 5.22), with undilated feeders (OR 0.36, 95% CI 0.23 to 0.57), with smaller volume (OR 0.95, 95% CI 0.92 to 0.99) and that were treated with higher marginal dose (OR 1.16, 95% CI 1.06 to 1.27).
 
Bowden et al reported outcomes from a retrospective cohort study of patients with cerebellar AVM treated with SRS at a single institution (Bowden, 2014). Sixty-four patients were included, 73% of whom had presented with intracranial hemorrhage and 19% of whom had undergone prior embolization. Total obliteration was achieved at 3, 4, and 5-10 years in 52%, 69%, and 75%, respectively, of subjects. Obliteration was more likely in smaller AVMs but less likely in patients who had undergone prior embolization. Symptomatic adverse radiation events, defined by MRI changes and new neurologic deficits in the absence of hemorrhage, occurred in 3 patients.
 
Fokas et al reported long-term follow up of a cohort of patients who underwent SRS for cerebral AVMs at a single institution (Fokas, 2014). One hundred sixty-four patients were identified, with a median follow up of 93 months (range 12-140 months). Thirty-nine percent of subjects had experienced a prior intracranial hemorrhage, and 43.3% and 8.0%, respectively, had undergone prior embolization or neurosurgical procedures. Complete obliteration was seen in 61% of patients at a median time of 29 months. Complete obliteration was achieved at 3 and 5 years in 61% and 88%, respectively. In multivariable models, higher radiation dosage and smaller target volumes were associated with higher rates of complete obliteration. The annual bleeding risk was 1.3% per year during follow up.
 
Matsuo et al reported outcomes from a cohort of 51 patients with intracranial AVMs treated with SRS at a single institution (Matsuo. 2014). Rates of obliteration after a single SRS at 3, 5, 10, and 15 years were 46.9%, 54.%, 64,%, and 68%, respectively; rates of obliteration after multiple SRS sessions at 3, 5, 10, and 15 years were 46.9%, 61.3%, 74.2%, and 90.3%, respectively. The adverse radiation events occurred in 9 cases (17.6%), with 4 cases (3 symptomatic cysts and 1 intracranial hemorrhage) not occurring until 10 years after the SRS treatment.
 
Potts et al summarized outcomes for 80 children treated with SRS for intracranial AVMs, most of whom (56%) had intracranial hemorrhage at the time of presentation (Potts, 2014). Among the 47% of subjects with available angiograms 3 years after treatment, AVM obliteration occurred in 52% of patients treated with higherdose SRS (18-20 Gy) and in 16% treated with lower-dose SRS (<18 Gy).
 
The evidence related to the use of SRS for AVM consists primarily of noncomparative cohort studies, which demonstrate relatively high rates of complete obliteration of AVM after SRS, in the range of approximately 40% in some studies to greater than 70% in others. Isolating the effect of the SRS therapy in and of itself can be challenging, as many patients are treated with more than one therapy, including endovascular treatments and surgery. Recently, an RCT that compared medical therapy to a variety of interventions in the treatment for AVM showed no significant improvement in outcomes with interventional therapy. However, given that the interventional therapies included a variety of therapies, it is difficult to assess whether one particular component of the intervention has benefit or lacks benefit. Longer-term follow up will be forthcoming from this study.
 
Epilepsy
In the most recent literature review (2014), no new comparative studies evaluating SRS for the treatment of epilepsy were identified.
 
The currently-available research related to the use of SRS for epilepsy treatment is preliminary. There is inadequate information to determine the risk: benefit ratio of SRS compared with other therapies for epilepsy treatment.
 
Tremor
SRS has been used to for the treatment of tremor through stereotactic radiofrequency thalamotomy. In 2008, Kondziolka et al reported outcomes for 31 patients who underwent SRS thalamotomy for disabling essential tremor (Kondziolka, 2008). Among 26 patients with follow-up data available, score on the Fahn-Tolosa-Marin tremor score improved compared with baseline from 3.7 (pre-SRS) to 1.7 (post-SRS; P=<0.000015) and score on the Fahn-Tolosa-Marin handwriting score improved compared with baseline from 2.8 (pre-SRS) to 1.7 (post-SRS; P<0.0002). One patient developed transient mild right hemiparesis and dysphagia and one patient developed mild right hemiparesis and speech impairment.
 
Kooshkabadi et al reported outcomes for 86 patients with tremor treated over a 15 year period, including 48 with essential tremor, 27 with Parkinson disease, and 11 with multiple sclerosis (Kondziolka, 2013). Fahn-Tolosa-Marin tremor scores were used to compare symptoms pre- and post-procedure: the mean tremor score improved from 3.28 (pre-SRS) to 1.81 (post-SRS; P<0.0001), the mean handwriting score improved from 2.78 (pre-SRS) to 1.62 (post-SRS; P<0.0001), and the mean drinking score improved from 3.14 (pre- SRS) to 1.8 (post-SRS, P<0.0001). Complications included temporary hemiparesis in 2 patients, dysphagia in 1 patient, and sustained facial sensory loss in 1 patient.
 
Lim et al reported outcomes for a small cohort of 18 patients who underwent SRS treatment for essential tremor (Lim. 2010). For the 14 patients with videotaped evaluations allowing blinded evaluation of tremor severity and at least 6 months of follow up (N=11 with essential tremor and N=3 with Parkinson disease), Fahn-Tolosa-Marin Tremor Rating Scale activities of daily living scores improved significantly after SRS (mean change score 2.7 points; P = .03). However, there was no significant improvement in other Fahn-Tolosa-Marin Tremor Rating Scale items (P=0.53 for resting tremor, P= 0.24 for postural tremor, P=0.62 for action tremor, P=0.40 for drawing, P >.99 for pouring water, P= 0.89 for head tremor). Mild neurologic complications occurred in 2 patients (lip and finger numbness), and severe neurologic complications occurred in 1 patient (edema surrounding thalamic lesion with subsequent hemorrhage at the lesion site, with speech difficulty and hemiparesis.)
 
Ohye et al conducted a prospective study of SRS for tremor that included 72 patients, 59 with Parkinson disease and 13 with essential tremor) (Ohye, 2012). Among 52 patients who had follow up at 24 months, tremor scores measured using the unified Parkinson’s disease rating scale (P<0.001; approximate score decrease extrapolated from graph from 1.5 at baseline to 0.75 at 24 months follow up).
 
Young et al reported outcomes for a cohort of 158 patients with tremor who underwent SRS, including
102 patients with Parkinson’s disease, 52 with essential tremor, and 4 with tremor due to other conditions (Young, 2000). Among patients with a parkinsonian tremor, at latest follow up (mean 47 months), blinded assessments on unified Parkinson’s disease rating scale demonstrated improvements in several specific items, including overall tremor (from 3.3 pre-treatment to 1.2 at last follow-up; P<0.05) and action tremor (from 2.3 pre-treatment to 1.3 at last follow-up; P<0.05. Among patients with Essential tremor, blinded assessments were conducted using the Fahn-Tolosa-Marin Tremor Rating Scale. At 1 year of follow up,
92.1% of patients with essential tremor were completely or nearly tremor-free. Improvements were reported in components of the Fahn-Tolosa-Marin Tremor Rating Scale, but statistical comparisons are not presented. Three patients developed new neurological symptoms attributed to the SRS.
 
The evidence related to the use of SRS for tremor consists of uncontrolled cohort studies, many of which report outcomes from the treatment of tremor of varying etiologies. Most studies report improvements in standardized tremor scores, although few studies used a blinded evaluation of tremor score, allowing for bias in assessment. No studies that compared SRS to alternative methods of treatment or a control group were identified. Limited long-term follow up is available, making the long-term risk: benefit ratio of an invasive therapy uncertain.
 
Central Nervous System Neoplasms
Acoustic Neuromas
SRS is widely used for the treatment of acoustic neuromas (vestibular schwannomas). Case series report generally high rates of local control. For example, Badahshi et al reported a 3-year local tumor control rate of 88.9% in a study of 250 patients with vestibular schwannoma who underwent SRS or fractionated SRS (Badakhshi, 2014). Williams et al reported rates of tumor progression-free survival for patients with large vestibular schwannomas treated with SRS of 95.2% and 81.8% at 3 and 5 years, respectively (Williams, 2013). For patients with small vestibular schwannomas treated with SRS, tumor progression-free survival was 97% and 90% at 3 and 5 years, respectively. In a retrospective case series of 93 patients with vestibular schwannomas treated with SRS, 83 of whom had long-term follow up, Woolf et al. reported an overall control rate of 92% at a median follow up of 5.7 years. A small study from 2006 that compared microsurgical resection (N=36) with SRS (N=46) for the management of small (<3 cm) vestibular schwannomas showed better hearing preservation at last follow up in the SRS group (P<0.01) and no difference in tumor control between the groups (100% vs 96%, P=0.50) (Pollock, 2006).
 
The evidence related to the use of SRS for acoustic neuroma (vestibular schwannoma) consists primarily of case series and cohort studies, which report high rates of freedom from tumor progression. Given that vestibular schwannoma is a slow-growing tumor with symptoms most often related to local compression, demonstration of slowing of progression is a reasonable outcome. A single comparative study was identified that demonstrated comparable tumor control outcomes between SRS and surgical therapy for small vestibular schwannomas.
 
Craniopharyngioma
The evidence related to the use of SRS for craniopharyngioma consists primarily of case series and cohort studies, which report high rates overall survival. There is a lack of comparative studies evaluating the treatment of pituitary adenomas with SRS versus surgery or traditional radiotherapy.
 
Glomus Jugulare Tumors
The evidence review related to the use of SRS for glomus jugulare tumors identified includes a large meta-analysis, which suggested that SRS treatment is associated with improved patient outcomes.
 
Pituitary Adenoma
In 2013, Chen et al reported results from a systematic review and meta-analysis of studies evaluating SRS (specifically gamma-knife surgery) for the treatment of nonfunctioning pituitary adenoma that included a volumetric classification (Chen, 2013). Seventeen studies met the inclusion criteria, including 7 prospective cohort studies and 10 retrospective cohort studies, with 925 patients included in the meta-analysis. Outcomes were reported related to the rate of tumor control, rate of radiosurgery-induced optic neuropathy injury, and the rate of radiosurgery-induced endocrinologic deficits. In patients with tumor volume <2mL, the rate of tumor control was 99% (95% CI 96 to 100%), the rate of radiosurgery-induced optic neuropathy injury was 1% (95% CI 0 to 4%), and the rate of radiosurgery-induced endocrinologic deficits was 1% (95% CI 0 to 4%). In patients with volumes from 2 to 4 mL, the comparable rates were 96% (95% CI 92 to 99%), 0 (95% CI 0 to 2%), and 7% (95% CI 2 to 14%), respectively, and in patients with volumes larger than 4 mL was 91% (95% CI 89 to 94%), 2% (95% 0 to 5%) and 22% (95% CI 14- 31%), respectively. The rates of tumor control and rates of radiosurgery-induced optic neuropathy injury differed significantly across the three groups.
 
In 2014, Lee et al retrospectively reported outcomes for 41 patients treated with SRS in a cohort of 569 patients treated for nonfunctioning pituitary adenomas at three institutions (Lee, 2014). At a median follow up of 48 months, on neuroimaging 34 patients (82.9%) had a decrease in tumor volume, 4 patients had tumor stability (9.8%), and 3 patients had a tumor increase (7.3%). Progression-free survival was 94% at 5 years and 85% at 10 years post-SRS. New onset or worsened pituitary deficiencies were found in 10 patients (24.4%) at a median follow up of 52 months. The authors conclude that initial treatment with SRS for nonfunctioning pituitary adenomas may be appropriate in certain clinical settings, such as in older patients (70 or more years); in patients with multiple comorbidities in whom an operation would involve a high risk; in patients with clear neuroimaging and neuro-endocrine evidence of an NFA, no mass effect on the optic apparatus, and progressive tumor on neuroimaging follow-up; or in patients who wish to avoid resection. Sheehan et al reported results from a multicenter registry of 512 patients who underwent SRS for nonfunctional pituitary adenomas (Sheehan, 2013). Four hundred seventy-nine (93.6%) had undergone prior resection, and 34 (6.6%) had undergone prior external-beam radiotherapy. Median follow up was 36 months. At last follow up, 31 of 469 patients with available follow up (6.6%) had tumor progression, leading to an actuarial progression-free survival of 98%, 95%, 91%, and 85% at 3, 5, 8, and 10 years post-SRS, respectively. Forty-one (9.3%) of 442 patients had worsened or new CNS deficits, more commonly in patients with tumor progression (P=0.038).
 
Noncomparative studies demonstrate high rates of tumor control (85% and better) for pituitary adenomas with SRS treatment, with better tumor control with smaller lesions. There is a lack of comparative studies evaluating the treatment of pituitary adenomas with SRS versus surgery or traditional radiotherapy.
 
Randomized Controlled Trials
Since the publication of the systematic reviews, several RCTs have been published.
 
Nonrandomized, Comparative Studies
Tian et al reported results from a retrospective, single-institution cohort study comparing neurosurgical resection to SRS for solitary brain metastases from NSCLC. Seventy-six patients were included, 38 of whom underwent neurosurgery (Tian, 2013). Median survival was 14.2 months for the SRS group and 10.7 months for the neurosurgery group. In multivariable analysis, treatment mode was not significantly associated with differences in OS.
 
Noncomparative Studies
Noncomparative studies continue to evaluate the use of SRS without WBRT for the management of brain metastases, and the role of SRS for the management of larger numbers of brain metastases. Yamamoto et al conducted a prospective observational study to evaluate primary SRS in patients with 1-10 newly diagnosed brain metastases (Yamamoto, 2014). Inclusion criteria included largest tumor volume less than 10 mL and less than 3 cm in the longest diameter, a total cumulative volume less than or equal to 15 mL, and a Karnofsky performance status score of 70 or higher. Among total 1,194 patients, the median OS after SRS was 13.9 (95% CI 12.0 to 15.6) in the 455 patients with 1 tumor, 10.8 months (95% CI 9.4 to 12.4) in the 531 patients with 2-4 tumors, and 10.8 months (95% CI 9.1 to 12.7) in the 208 patients with 5-10 tumors. Rava et al, in a cohort study including 53 patients with at least 10 brain metastases, described the feasibility of SRS treatment ((Rava, 2013). Median survival was 6.5 months in this cohort. Raldow et al, in a cohort of 103 patients with at least 5 brain metastases who were treated with SRS alone, demonstrated a median OS of 8.3 months, comparable to historical controls.46 OS was similar for patients with 5-9 and with at least 10 metastases (7.6 months and 8.3 months, respectively).
 
Yomo et al reported outcomes for 41 consecutive patients with 10 or fewer brain metastases from NSCLC who received SRS as primary treatment (Yomo, 2014). The study reported 1- and 2-year OS rates of 44% and 17%, respectively, with a median survival time of 8.1 months. Distant brain metastases occurred in 44% by 1 year, with 18 patients requiring repeat SRS, 7 requiring WBRT, and 1 requiring microsurgery.
 
For cases of brain metastases, evidence from RCTs and systematic reviews indicates that the use of
SRS improves outcomes in the treatment of brain metastases. SRS appears to be feasible in the treatment of larger numbers (e.g. >10) of brain metastases, and outcomes after SRS treatment do not appear to be worse for patients with larger numbers of metastases, et least for patients with 10 or fewer metastases.
 
Uveal Melanoma
Since the publication of the 2012 review, several studies have reported outcomes from SRS for intraocular melanoma. Wackernagel et al reported outcomes for 189 patients with choroidal melanoma treated with SRS (Gamma Knife) (Wackernagel, 2014). All patients with choroidal melanoma at the authors’ institution were offered SRS as an alternative to enucleation if they wished to retain their eye, and other globe-preserving treatment options were not feasible because of tumor size or location or the patient’s general health. Sixty-six patients (37.3%), all treated before 2003, received high-dose SRS (35-80 Gy); subsequently, all patients received low-dose SRS (30 Gy in 87 patients and 25 Gy in 24 patients). The median overall follow-up was 39.5 months. During follow-up, local tumor control was achieved in 167 patients (94.4%). Enucleation was required in 25 patients, 7 due to tumor reoccurrence and 18 due to radiation-induced adverse effects. Overall survival and distant metastasis rates are not reported.
 
Furdova et al reported outcomes for a cohort of 96 patients who underwent SRS at a single center in Slovakia for stage T2/T3 uveal melanoma (Furdova, 2014). Local tumor control occurred in 95% of patients at 3 years of follow up and in 85% of patients at 5 years of follow up. Eleven patients (11.5%) required secondary enucleation between 3 and 5 years post-SRS due to radiation neuropathy or secondary glaucoma.
 
The evidence related to SRS for the treatment of uveal melanoma is limited to case series. The published literature is insufficient to demonstrate improved outcomes with the use of stereotactic radiosurgery over other accepted radiation modalities in the treatment of uveal melanoma.
 
Stereotactic Body Radiation Therapy
 
Spinal Tumors
Sahgal et al evaluated rates of vertebral compression fractures after SBRT in 252 patients with 410 spinal segments treated with SBRT (Shagal, 2013). Fifty-seven fractures were observed (13.9% of spinal segments treated), with 27 de novo fractures and 30 cases of existing fracture progression. Most fractures occurred relatively early post-treatment, with a median and mean time to fracture of 2.46 months and 6.33 months, respectively. Radiation dose per fraction, baseline vertebral compression fracture, lytic tumor, and baseline spinal misalignment were predictive of fracture risk.
 
Non-Small-Cell Lung Cancer
 
Systematic Reviews
In 2014, Zheng et al reported results from a systematic review and meta-analysis comparing survival afterSBRT with survival after surgical resection for the treatment of stage I NSCLC (Zheng, 2014). The authors included 40 studies reporting outcomes from SBRT, including 4850 patients, and 23 studies reporting outcomes after surgery published in the same time period, including 7071 patients. For patients treated with SBRT, the mean unadjusted OS rates at 1, 3, and 5 years were 83.4%, 56.6%, and 41.2%, respectively. The mean unadjusted OS rates at 1, 3, and 5 years were 92.5%, 77.9%, and 66.1%, respectively, with lobectomy, and 93.2%, 80.7%, and 71.7% with limited lung resections. After adjustment for surgical eligibility (for the 27 SBRT studies which reported surgical eligibility) and age, in a multivariable regression model, the treatment modality (SBRT vs surgical therapy) was not significantly associated with OS (P=0.36).
 
Nonrandomized, Comparative Studies
In a matched-cohort study design, Crabtree et al retrospectively compared outcomes between SBRT and surgical therapy in patients with stage 1 NSCLC (Crabtree, 2014). Four hundred fifty-eight patients underwent primary surgical resection and 151were treated with SBRT. Surgical and SBRT patients differed significantly on several baseline clinical and demographic characteristics, with SBRT patients having an older mean age, higher comorbidity scores, a greater proportion of peripheral tumors, and worse lung function at baseline. For the surgical group, 3-year OS and disease-free survival were 78% and 72%, respectively. Of note, among the 458 patients with clinical stage I lung cancer, 14.8% (68/458) were upstaged at surgery and found to have occult N1 or N2 disease. For patients with occult nodal disease, 3-year and 5-year OS were 66% and 43%, respectively. For patients without occult nodal disease, 3- and 5-year OS were 80% and 68%, respectively. For the SBRT group, 3-year OS and disease-free survival were 47% and 42%, respectively.
 
In a propensity score-matched analysis, 56 patients were matched based on clinical characteristics, including age, tumor size, ACE comorbidity score, FEV1%, and tumor location (central versus peripheral). In the final matched comparison, 3-year overall survival was 52% versus 68% for SBRT and surgery, respectively (P=0.05), while disease-free survival was 47% versus 65% (P=0.01). Two-, 3-, 4-, and 5-year local recurrence-free survival for SBRT was 91%, 91%, 81%, and 40%, respectively, versus 98%, 92%, 92%, and 92% for surgery (P=0.07).
 
Jepperson et al compared SBRT with conventional radiation therapy for patients with medically inoperable NSCLC (T1-2N0M0) (Jeppesen, 2013). The study included 100 subjects treated with SBRT and 32 treated with conventional radiation therapy. At baseline, the SBRT-treated patients had smaller tumor volume, lower FEV1, and a greater proportion of T1 stage disease. The median overall survival was 36.1 months versus 24.4 months for SBRT and conventional RT, respectively (p =0.015). Local failure-free survival rates at one year were in SBRT group 93% versus 89% in the conventional RT group and at five years 69% versus 66%, SBRT and conventional RT respectively (P =0.99).
 
Port et al compared SBRT with wedge resection for patients with clinical stage IA NSCLC using data from a prospectively maintained database (Port, 2014).  One hundred sixty-four patients were identified, 99 of whom were matched based on age, sex, and tumor histology. Thirty-eight patients underwent a wedge resection only, 38 patients underwent a wedge resection with brachytherapy, and 23 patients had SBRT. SBRT patients were more likely to have local or distant recurrences than surgically-treated patients (9% vs 30%, P=0.016), but there were no differences between the groups in disease-free 3-year survival (77% for wedge resection vs 59% for SBRT, P=0.066).
 
Varlotta et al compared surgical therapy (N=132 with lobectomy and N=48 with sublobar resection) with SBRT (N=137) in the treatment of stage I NSCLC.67 Mortality was 54% in the SBRT group, 27.1% in the sublobar resection group, and 20.4% in the lobar resection group. After matching for pathology, age, sex, tumor diameter, aspirin use, and Charlson comorbidity index, patients with SBRT had lower OS than patients treated with either wedge resection (P=0.003) or lobectomy (P<0.0001).
 
Noncomparative Studies
In a prospective evaluation of 185 medically inoperable patients with early (T1-T2N0M0) NSCL treated with SBRT, Allibhai et al evaluated the influence of tumor size on outcomes (Allibhai, 2013). Over a median follow up of 15.2 months, tumor size (maximum gross tumor diameter) was not associated with local failure but was associated with regional failure (P=0.011) and distant failure (P=0.021). Poorer overall survival (P=0.001), disease-free survival (P=9.001), and cause-specific survival (P=0.005) were also significantly associated with tumor volume more significant than diameter.
 
Noncomparative Studies
 
Yoon et al reported outcomes for 93 patients with primary non-metastatic HCC treated with SBRT at a single institution (Yoon, 2013).  The median follow up was 25.6 months. OS at 1 and 3 years was 86% and 53.8%, respectively. The main cause of treatment failure was intrahepatic (i.e., out-of-field) metastases. At 1 and 3 years, local control rates were 94.8% and 92.1%, respectively, and distant metastasis-free survival rates were 87.9% and 72.2%, respectively. However, intrahepatic recurrence-free survival rates at 1 and 3 years were 51.9% and 32.4%, respectively.
 
Jung et al reported rates of radiation-induced liver disease in patients with HCC treated with SBRT for small (<6 cm), non-metastatic HCC that was not amenable to surgery or percutaneous ablative therapy (Jung, 2014). Ninety-two patients were included, 17 of whom (18.5%) developed grade 2 or worse radiation-induced liver disease within 3 months of SBRT. In multivariable analysis, Child-Pugh class was the only significant predictor of radiation-induced liver injury. The 1- and 3-year survival rates were 86.9% and 54.4% respectively; with the median survival of 53.6 months. The presence of radiation-induced liver disease was not associated with survival.
 
Prostate Cancer
 
 

CPT/HCPCS:
32701Thoracic target(s) delineation for stereotactic body radiation therapy (SRS/SBRT), (photon or particle beam), entire course of treatment
61796Stereotactic radiosurgery (particle beam, gamma ray, or linear accelerator); 1 simple cranial lesion
61797Stereotactic radiosurgery (particle beam, gamma ray, or linear accelerator); each additional cranial lesion, simple (List separately in addition to code for primary procedure)
61798Stereotactic radiosurgery (particle beam, gamma ray, or linear accelerator); 1 complex cranial lesion
61799Stereotactic radiosurgery (particle beam, gamma ray, or linear accelerator); each additional cranial lesion, complex (List separately in addition to code for primary procedure)
61800Application of stereotactic headframe for stereotactic radiosurgery (List separately in addition to code for primary procedure)
63620Stereotactic radiosurgery (particle beam, gamma ray, or linear accelerator); 1 spinal lesion
63621Stereotactic radiosurgery (particle beam, gamma ray, or linear accelerator); each additional spinal lesion (List separately in addition to code for primary procedure)
77261Therapeutic radiology treatment planning; simple
77262Therapeutic radiology treatment planning; intermediate
77263Therapeutic radiology treatment planning; complex
77280Therapeutic radiology simulation-aided field setting; simple
77285Therapeutic radiology simulation-aided field setting; intermediate
77290Therapeutic radiology simulation-aided field setting; complex
772953-dimensional radiotherapy plan, including dose-volume histograms
77299Unlisted procedure, therapeutic radiology clinical treatment planning
77300Basic radiation dosimetry calculation, central axis depth dose calculation, TDF, NSD, gap calculation, off axis factor, tissue inhomogeneity factors, calculation of non-ionizing radiation surface and depth dose, as required during course of treatment, only when prescribed by the treating physician
77301Intensity modulated radiotherapy plan, including dose-volume histograms for target and critical structure partial tolerance specifications
77306Teletherapy isodose plan; simple (1 or 2 unmodified ports directed to a single area of interest), includes basic dosimetry calculation(s)
77307Teletherapy isodose plan; complex (multiple treatment areas, tangential ports, the use of wedges, blocking, rotational beam, or special beam considerations), includes basic dosimetry calculation(s)
77316Brachytherapy isodose plan; simple (calculation[s] made from 1 to 4 sources, or remote afterloading brachytherapy, 1 channel), includes basic dosimetry calculation(s)
77317Brachytherapy isodose plan; intermediate (calculation[s] made from 5 to 10 sources, or remote afterloading brachytherapy, 2-12 channels), includes basic dosimetry calculation(s)
77318Brachytherapy isodose plan; complex (calculation[s] made from over 10 sources, or remote afterloading brachytherapy, over 12 channels), includes basic dosimetry calculation(s)
77321Special teletherapy port plan, particles, hemibody, total body
77331Special dosimetry (eg, TLD, microdosimetry) (specify), only when prescribed by the treating physician
77332Treatment devices, design and construction; simple (simple block, simple bolus)
77333Treatment devices, design and construction; intermediate (multiple blocks, stents, bite blocks, special bolus)
77334Treatment devices, design and construction; complex (irregular blocks, special shields, compensators, wedges, molds or casts)
77336Continuing medical physics consultation, including assessment of treatment parameters, quality assurance of dose delivery, and review of patient treatment documentation in support of the radiation oncologist, reported per week of therapy
77338Multi-leaf collimator (MLC) device(s) for intensity modulated radiation therapy (IMRT), design and construction per IMRT plan
77370Special medical radiation physics consultation
77371Radiation treatment delivery, stereotactic radiosurgery (SRS), complete course of treatment of cranial lesion(s) consisting of 1 session; multi-source Cobalt 60 based
77372Radiation treatment delivery, stereotactic radiosurgery (SRS), complete course of treatment of cranial lesion(s) consisting of 1 session; linear accelerator based
77373Stereotactic body radiation therapy, treatment delivery, per fraction to 1 or more lesions, including image guidance, entire course not to exceed 5 fractions
77432Stereotactic radiation treatment management of cranial lesion(s) (complete course of treatment consisting of 1 session)
77435Stereotactic body radiation therapy, treatment management, per treatment course, to 1 or more lesions, including image guidance, entire course not to exceed 5 fractions
G0339Image guided robotic linear accelerator-based stereotactic radiosurgery, complete course of therapy in one session or first session of fractionated treatment
G0340Image guided robotic linear accelerator-based stereotactic radiosurgery, delivery including collimator changes and custom plugging, fractionated treatment, all lesions, per session, second through fifth sessions, maximum 5 sessions per course of treatment

References: 1994 Blue Cross Blue Shield Association Technology Evaluation Center Assessment; Tab 38.

1995 Blue Cross Blue Shield Association Technology Evaluation Center Assessment; Tab 5.

1995 Blue Cross Blue Shield Association Technology Evaluation Center Assessment; Tab 6.

1995 Blue Cross Blue Shield Association Technology Evaluation Center Assessment; Tab 7.

1997 Blue Cross Blue Shield Association Technology Evaluation Center Assessment; Tab 24.

1998 Blue Cross Blue Shield Association Technology Evaluation Center Assessment; Tab 28.

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