Summary Of Evidence

Choroidal Melanoma

Aetna Stereotactic Radiosurgery Number: 0083. This is a commercial insurance policy, not peer-reviewed published literature. Of note, choroid melanomas are not addressed. This does not support the proposed LCD changes.

BlueCross Blue Shield of Massachusetts Medical Policy Stereotactic Radiosurgery and Stereotactic body Radiotherapy. Policy Number 277. This is a commercial insurance policy, not peer-reviewed published literature. While there is a bibliography at the end, not specific not peer-reviewed published literature is mentioned. This does not support the proposed LCD changes.

Local Coverage Determination (LCD): Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiation Therapy (SBRT) (L33410) from First Coast Service Options, Inc. There is no direct mention of choroidal melanomas in the LCD. However, the list of Group 2 Codes: ICD-10 Codes does include C69.00-C69.92 (Malignant neoplasm of unspecified conjunctiva—malignant neoplasm of unspecified site of left eye). However, this wide range, according to their overall medical director, is a result of a conversion of ICD-9 codes to ICD-10 codes. This gives some support to the proposed LCD changes.

NGS LCD for Stereotactic Radiation Therapy: Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiation Therapy (SBRT) (L35076). This is the current NGS LCD and this does not support the proposed LCD changes.

Reynolds M et al (2016) published a letter To the Editor reporting two patients with uveal melanomas who received carbon fiducials and were treated with gamma knife radiosurgery with good results. Supported, in part, by an unrestricted grant from Research to Prevent Blindness, Inc., NY, and from the Paul Family. This does support the proposed LCD changes.

Joye R et al (2014) reported on a retrospective, non-comparative case series of 23 patients with uveal melanoma treated with Gamma Knife Stereotactic radiosurgery. They were followed-up from 4 to 121 months (median: 41.5 months). Twenty patients had choroidal melanomas, two patients had ciliary body melanomas (one of which was a ring melanoma), and one patient had a ciliochoroidal melanoma. There was a 91% rate of local control. Unfortunately, the majority of patients experienced a decrease in visual acuity, and two patients (9%) eventually required enucleation due to secondary neovascular glaucoma. The authors noted, “Overall, the efficacy of Gamma Knife treatment for uveal melanoma reported here is similar to other studies in the literature.” They also noted, “The cosmetic benefits, the single treatment session, and the ability to perform the procedure without invasive surgery may be enough for some patients to choose Gamma Knife over enucleation in situations in which brachytherapy is contraindicated and proton beam is unavailable or undesired.” This does support the proposed LCD changes. Supported by the Massachusetts Lions Club and an unrestricted grant from Research to Prevent Blindness. The authors have no financial or proprietary interest in the materials presented herein. Dr. Duker did not participate in the editorial review of this article.

Reynolds M et al (2017) retrospectively analyzed 18 patients with primary uveal melanomas and uveal metastases who were treated with Gamma Knife at Mayo Clinic Rochester between 1/1/1990 and 6/1/2015. Comparing the study published in this paper to those discussed, it had a higher rate of recurrence (28.6%). Notably, patients included in this study had more rare metastatic cancers (as opposed to breast or lung cancer) and a lower survival rate (28.6%). Weaknesses of this study included retrospective design, a small patient size, limited follow-up, and limited information regarding dose to the macula and optic nerve.

Conclusions: In summary, GKR is a useful alternative to plaque brachytherapy and proton beam therapy. It is particularly useful for patients who cannot or prefer not to undergo the procedures required for plaque brachytherapy or for those whose tumor sizes disqualify them. It is also useful for patients who do not have access to proton beam therapy, which is geographically limited. Competing interests: The authors declare that they have no competing interests. Funding supported, in part, by an unrestricted grant from Research to Prevent Blindness Inc., NY; VRS Foundation, Minneapolis, MN; the Paul Family; and the Deshong Fund. This does support the proposed LCD changes.

Sarici A et al (2013) assessed the use of gamma-knife-based stereotactic radiosurgery in 50 consecutive patients for medium and large-sized posterior uveal melanoma treatment. The most common complication was cataracts (n=15), but the authors noted that 60% of the tumors were more anteriorly located... Neovascular glaucoma was noted in 7 patients. All of them underwent enucleation and this accounted to 45% of the enucleations. The authors concluded: “In conclusion, although GKRS does not offer better results for UM than brachytherapy or particle therapy, its results for local tumor control as well as eye retention and survival rates are favorable. However, the high complication rates, particularly the significant decrease in vision, highlight the need to use this treatment cautiously.”

“We believe that GKRS is an ocular-conserving option that may be considered for treatment of posterior UM in carefully selected patients, and must be saved only for cases where a patient cannot go to the operating room or access treatment by brachytherapy or PBRT.” Randomized controlled prospective studies, which compare GKRS with brachytherapy and/or PBRT, will provide us with additional data. “Conflict of interest: The authors have no proprietary interest.” This paper gives some support for the proposed LCD changes.

Kang D et al (2012) evaluated 22 patients with uveal melanoma and who were followed-up for a median period of 67 months (range 3-126). Five treated eyes resulted in enucleation. The overall 5-year survival rate was 90.9%. They noted that: “Besides the advantages of being less invasive and better tolerated by the patient, GKS can preserve the globe and restore visual function. In addition, it is a single-day treatment that can be completed within a few hours. On the other hand, GKS could deliver a dose to adjacent radiosensitive intraocular organs that is higher than they can tolerate, and it could potentially increase the chance of distant metastasis by not eliminating the melanoma itself. Previous retrospective series, in which the outcomes of GKS in the treatment of uveal melanoma were evaluated, have shown mixed results.” They concluded: “Gamma Knife surgery provides excellent local control of uveal melanomas with a decrease in volume over time. This procedure not only preserves the eyeball and its potential visual function, but also decreases the potential for hematological dissemination and achieves sufficient local tumor control with a gradual reduction in volume.” “The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.” This does support the proposed LCD changes.

Duker J et al (2016) reported one case of a patient with a diffuse juxtapapillary choroidal melanoma that originally was felt to be a small choroidal nevus. This transformation occurred six years later. At 5.5 years after gamma knife radiation therapy, visual acuity remained 20/20. “Supported in part by an Unrestricted Grant from the Research to Prevent Blindness and the Massachusetts Lions Clubs. None of the authors have any conflicting interests to disclose.” While this is a case report, it does support the proposed LCD changes.

Wackernagel W (2013) reported on a total of 189 patients with choroidal melanoma who were treated with Gamma-Knife stereotactic single-fraction radiosurgery at a single institution between June 1992 and May 2010. This reported on conservation of visual acuity after Gamma-Knife radiosurgery of choroidal melanomas. The majority of patients (84.7%) encountered a deterioration of vision after treatment. The most important risk factors for visual loss were tumour height, longest basal diameter, distance to the optic disk and/or foveola, and retinal detachment before treatment. Treatment dose, and patient characteristics (age, sex, and concurrent systemic diseases) were less important. Local tumour control rate was 94.4% after a median follow-up of 39.5 months. They concluded: “Visual outcome after single-fraction. Gamma-Knife radiotherapy is comparable with linear accelerator (LINAC) based fractionated stereotactic radiotherapy, inferior to proton beam radiotherapy, and depends primarily on tumour size, location and preexisting retinal detachment.” Funding: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Competing interests: All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work, no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years, no other relationships or activities that could appear to have influenced the submitted work.

Wackernagel W (2014) reported on the same 189 patients in their other publication concerning local tumour control and eye preservation after gamma knife radiosurgery (GK-RS) to treat choroidal melanomas. The authors are the same except there is now an eighth author... As stated in Wackernagel W (2013), they concluded that: “Visual outcome after single-fraction Gamma-Knife radiotherapy is comparable with linear accelerator (LINAC) based fractionated stereotactic radiotherapy, inferior to proton beam radiotherapy, and depends primarily on tumour size, location and preexisting retinal detachment.” “Competing interests: None.” This is really a duplicate publication of their prior paper and thus does not support any change to the LCD.

Analysis of Evidence

Choroidal Melanoma

The amount of literature submitted was not voluminous, but choroidal melanomas are not very common. Thus, to have large series of patients would not be possible. None of the papers suggest negative results on patients after the use of stereotactic radiosurgery choroidal melanomas and the outcomes were at least as good as other methods. Thus, this contractor will add choroidal melanomas as an indication for Stereotactic Radiosurgery.

Abstract:

Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiation Therapy (SBRT) are methods of delivering ionizing radiation using highly focused convergent beams to target a lesion while limiting exposure of adjacent structures.

“Stereotactic” describes target lesion localization relative to a known three dimensional reference system that allows for a high degree of anatomic accuracy and precision. Devices used for stereotactic guidance may include a body frame with external reference markers in which a patient is positioned securely, a system of implanted fiducial markers that can be visualized with low-energy (kV) x-rays, and CT-imaging-based systems used to confirm the location of a tumor immediately prior to treatment.

SBRT is used to treat extra-cranial sites as opposed to stereotactic radiosurgery (SRS) which is used to treat intra-cranial and spinal targets. Treatment of extra-cranial sites excluding the spinal cord and related spinal structures requires accounting for internal organ motion as well as for patient motion. Thus, reliable immobilization or repositioning systems must often be combined with devices capable of decreasing organ motion or accounting for organ motion e.g. respiratory gating. Additionally, all SBRT is performed with at least one form of image guidance to confirm proper patient positioning and tumor localization prior to delivery of each fraction.

SBRT is only indicated as primary treatment for tumor types or locations where the available published literature supports an outcome advantage over other conventional radiation modalities.

SBRT may be delivered in one to five sessions (fractions). Each fraction requires an identical degree of precision, localization and image guidance.

SRS is typically performed in a single session, using a rigidly attached stereotactic guiding device, other immobilization technology and/or a stereotactic-guidance system.

The higher a Karnofsky Performance Status, the better a patient is doing.

The lower an Eastern Cooperative Oncology Group (ECOG) Performance Status is, the better a patient is doing. This is the opposite of the Karnofsky Performance scores where a lower score reflects a poorer status.

SRS/SBRT procedures include the following components:

1. Planning
2. Position stabilization (attachment of a frame or frameless)
3. Imaging for localization (CT, MRI, angiography, PET, etc.)
4. Computer assisted tumor localization (i.e. “Image Guidance”)
5. Treatment planning – number of isocenters, number, placement and length of arcs or angles, number of beams, beam size and weight, etc.
6. Isodose distributions, dosage prescription and calculation
7. Setup and accuracy verification testing
8. Simulation of prescribed arcs or fixed portals
9. Radiation treatment delivery

Indications for SRS/SBRT (for Cranial and Spinal Lesions):

1. Primary central nervous system malignancies, generally used as a boost or salvage therapy for lesions < 5 cm.
2. Primary and secondary tumors involving the brain or spine parenchyma, meninges/dura, or immediately adjacent bony structures.
3. Benign brain tumors and spinal tumors such as meningiomas, acoustic neuromas, other schwannomas, pituitary adenomas, pineocytomas, craniopharyngiomas, glomus tumors, hemangioblastomas.
4. Cranial arteriovenous malformations, cavernous malformations, and hemangiomas
5. Other cranial non-neoplastic conditions such as trigeminal neuralgia and select cases of medically refractory epilepsy. As a boost treatment for larger cranial or spinal lesions that have been treated initially with external beam radiation therapy or surgery (e.g. sarcomas, chondrosarcomas, chordomas, and nasopharyngeal or paranasal sinus malignancies).
6. Metastatic brain or spine lesions, with stable systemic disease, Karnofsky Performance Status 40 or greater (or expected to return to 70 or greater with treatment), and otherwise reasonable survival expectations, OR an Eastern Cooperative Oncology Group (ECOG) Performance Status of 3 or less (or expected to return to 2 or less with treatment). Note that the higher a Karnofsky Performance Status is, the better a patient is doing. However, the lower an Eastern Cooperative Oncology Group (ECOG) Performance Status is, the better a patient is doing.
7. Relapse in a previously irradiated cranial or spinal field where the additional stereotactic precision is required to avoid unacceptable vital tissue radiation.
8. Choroidal and other ocular melanomas

Limitations for SRS/SBRT (for Cranial and Spinal Lesions):

SRS is not considered medically necessary under the following circumstances:

1. Treatment for anything other than a severe symptom or serious threat to life or critical functions.
2. Treatment unlikely to result in functional improvement or clinically meaningful disease stabilization, not otherwise achievable.
3. Patients with wide-spread cerebral or extra-cranial metastases with limited life expectancy unlikely to gain clinical benefit within their remaining life.
4. Patients with poor performance status (Karnofsky Performance Status less than 40 or an ECOG Performance greater than 3) - see Karnofsky and ECOG Performance Status scales below. Note that the higher a Karnofsky Performance Status is, the better a patient is doing. However, the lower an Eastern Cooperative Oncology Group (ECOG) Performance Status is, the better a patient is doing.
5. Cobalt-60 pallidotomy is non-covered.

Indications for Stereotactic Body Radiation Therapy (SBRT):

1. SBRT is indicated for primary tumors and tumors metastatic to the lung, liver, kidney, adrenal gland, or pancreas.
2. SBRT is indicated for treatment of pelvic and head and neck tumors that have recurred after primary irradiation.
3. SBRT is indicated for patients with clinically localized, low- to intermediate-risk prostate cancer.
4. SBRT treatment, of any body site or internal organ, is indicated for treatment of recurrence in or near previously irradiated regions when a high level of precision and accuracy or a high dose per fraction is indicated to minimize the risk of injury to surrounding normal tissues and treatment with conventional methods is not appropriate or safe for the particular patient (medical records must describe the specific circumstances, see documentation requirements in the attached Billing and Coding Article).

Limitations for Stereotactic Body Radiation Therapy (SBRT):

1. Primary treatment of lesions of bone, breast, uterus, ovary, and other internal organs not listed earlier in this LCD as covered is not considered medically necessary.
2. SBRT is not considered medically necessary under the following circumstances for any condition:
   
   1. Treatment is unlikely to result in clinical cancer control and/or functional improvement.
   2. The tumor burden cannot be completely targeted with acceptable risk to critical normal structures.
   3. The patient has a poor performance status (Karnofsky Performance Status less than 40 or Eastern Cooperative Oncology Group (ECOG) Status of 3 or worse). Note that the higher a Karnofsky Performance Status is, the better a patient is doing. However, the lower an Eastern Cooperative Oncology Group (ECOG) Performance Status is, the better a patient is doing.
   4. Recurrent (other than pelvic and head and neck tumors) or metastatic disease could be treated by conventional methods (record must describe why other radiation therapy measures are not appropriate or safe for the particular patient).
   5. Since the goal of SBRT is to maximize the potency of the radiotherapy by completing an entire course of treatment within an extremely accelerated time frame, any course of radiation treatment extending beyond five fractions is not considered SBRT. SBRT is meant to represent a complete course of treatment and not to be used as a boost following a conventionally fractionated course of treatment.
      
      
   Karnofsky Performance Status Scale
   
   100 Normal; no complaints, no evidence of disease
   
   90 Able to carry on normal activity; minor signs or symptoms of disease
   
   80 Normal activity with effort; some signs or symptoms of disease
   
   70 Cares for self; unable to carry on normal activity or to do active work
   
   60 Requires occasional assistance but is able to care for most needs
   
   50 Requires considerable assistance and frequent medical care
   
   40 Disabled; requires special care and assistance
   
   30 Severely disabled; hospitalization is indicated although death not imminent
   
   20 Very sick; hospitalization necessary; active supportive treatment is necessary
   
   10 Moribund, fatal processes progressing rapidly
   
   0 Dead
   
   Karnofsky DA, Burchenal JH. (1949). “The Clinical Evaluation of Chemotherapeutic Agents in Cancer.” In: MacLeod CM (Ed), Evaluation of Chemotherapeutic Agents. Columbia Univ Press. Page 196.
   
   ECOG Performance Status Scale
   
   Grade 0: Fully active, able to carry on all pre-disease performance without restriction.
   
   Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light house work, office work.
   
   Grade 2: Ambulatory and capable of all self-care but unable to carry out and work activities. Up and about more than 50% of waking hours.
   
   Grade 3: Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
   
   Grade 4: Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
   
   Grade 5: Dead
   
   Am. J. Clin. Oncol.: Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carone, P.P.; Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649-655.