Radiation Therapies

This local coverage determination (LCD) supplements but does not replace, modify or supersede existing Medicare applicable National Coverage Determinations (NCDs) or payment policy rules and regulations for the referenced radiation therapies. Medicare payment policy rules and this LCD do not replace, modify or supersede applicable state statutes regarding medical (or other health practice profession) practice acts, definitions and/or scopes of practice. All providers who report services for Medicare payment must fully understand and follow all existing laws, regulations and rules for Medicare payment for these referenced radiation therapy (RT) procedures and must properly submit only valid claims for them. Relevant CMS manual instructions and policies may be found in the following Internet-Only Manuals (IOMs) published on the CMS Web site.

Title XVIII of the Social Security Act, §1862(a)(1)(A) states that no Medicare payment shall be made for items or services which are not reasonable and necessary for the diagnosis or treatment of illness or injury.

Title XVIII of the Social Security Act, §1862(a)(7) excludes routine physical examinations.

42 CFR §410.32(b)(3) defines the levels of physician supervision for diagnostic tests.

42 CFR §410.32(b)(3)(ii) direct supervision means physical presence in the office suite in non-hospital locations; immediately available in other outpatient diagnostic services.

CMS Internet-Only Manual, Pub.100-08, Medicare Program Integrity Manual, Chapter 13, §13.5.4 Reasonable and Necessary Provision in an LCD

Overview

Intensity Modulated Radiation Therapy (IMRT)

IMRT is a form of 3D conformal radiation therapy (3D-CRT) that changes the intensity of radiation within different parts of single radiation beams while the treatment is delivered. Thus, IMRT can simultaneously treat multiple areas within the target to different dose levels. It most commonly utilizes 5, 7, or 9 treatment beams from different directions, with each field being from a stationary direction, but in which the radiation output varies across the field with time of irradiation. IMRT is especially useful in radiating treatment targets positioned near other normal tissues that need exposure to be minimized.

Volumetric modulation arc radiotherapy (VMAT) is a form of IMRT in which the radiation source moves in an arc around the patient while delivering the radiation treatment. VMAT delivery is more efficient and can be given in half the usual time as compared to IMRT.

IMRT utilizes a treatment-planning technique called inverse planning. IMRT treatment plans are tailored to the target volumes and are more precise than conventional or CRT plans. Through a computerized optimization process, the physicist or dosimetrist enters the anatomic information of tumors and organs at risk (OARs), as detailed by the radiation oncologist, specifies the desired dosimetric outcome and its constraint for each structure of interest and then lets the computerized treatment-planning system identify the best beam orientation and intensity pattern over the treatment fields. After inverse planning, an optimized treatment plan is developed.

Delivery of IMRT may be done with various combinations of gantry motion, table motion, slice-by-slice treatment (tomotherapy) and multi-leaf collimator (MLC) or solid compensators to modulate the beam or arc intensities.

The treatment plan for IMRT must be carefully followed with each session. The required precision and accuracy exceed that of conventional RT. The radiation team of oncologists, medical physicists, medical dosimetrists and radiation therapists must be well-coordinated. Drawbacks to IMRT include the potential for dose heterogeneity within a specific structure. This heterogeneity is the trade-off for improved dose conformity. Also, IMRT involves an increased “integral dose” resulting from unintended radiation outside the intended treatment volumes due to the use of multiple, fixed fields or rotating arcs. The long-term risk of second malignancies from this integral dose is still unclear.¹

Stereotactic Radiosurgery (SRS)

SRS combines anatomic accuracy and reproducibility with very high doses of highly precise, externally generated ionizing radiation to optimally ablate or eradicate the target(s) in the head while minimizing collateral damage to adjacent tissues. “Stereotactic” means a target lesion is localized relative to a known 3-dimensional (3D) reference system. Markers might be used on or in the body such as seeds, clips, or surface markers. Devices used in SRS for stereotactic guidance could include rigid head frames affixed to the patient, fixed bony landmarks, implanted fiducial markers, or mask-based systems. Imaging, planning and treatment typically are performed in close temporal proximity. The delivery of a high dose of ionizing radiation that conforms to the shape of the lesion mandates an overall accuracy of approximately 1 mm. To assure quality of patient care, the procedure involves a multidisciplinary team consisting of a neurosurgeon, radiation oncologist, medical physicist, and radiation therapist. For some tumors involving the skull base, the multidisciplinary team may include a head and neck surgeon with training in SRS.

All SRS procedures include the following: position stabilization with or without a frame, imaging for localization, computer-assisted tumor localization (i.e., “image guidance”), treatment planning, isodose distributions/dose prescription/dose calculation, setup and accuracy verification testing, simulation of prescribed arcs or fixed portals, and radiation delivery.

Stereotactic Body Radiation Therapy (SBRT)

SBRT is also known as stereotactic ablative radiotherapy (SABR) or ultrahypofractionated RT.

SBRT is a treatment that couples a high degree of anatomic targeting accuracy and reproducibility with very high doses of extremely precise, externally generated, ionizing radiation. The therapeutic intent of SBRT is to maximize cell-killing effect on the target(s) while minimizing radiation-related injury in adjacent normal tissues.

SBRT is used to treat extra-cranial sites as opposed to 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 1 form of image guidance to confirm proper patient positioning and tumor localization prior to delivery of each fraction.

SBRT may be delivered in 1 to 5 sessions (fractions). Each fraction requires an identical degree of precision, localization and image guidance. Since the goal of SBRT is to intensify 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 5 fractions is not considered SBRT.

Inverse treatment planning is used for IMRT/SRS/SBRT and involves multiple steps^1,2,3:

1. For SRS procedures, position stabilization would be needed via a patient affixed frame or a stereotactic mask fixation system (frameless).
2. Imaging: 3D image acquisition of the target area by simulation using computed tomography (CT), magnetic resonance (MR), positron emission tomography (PET) or similar image fusion technology is done. Usually, CT images will serve as the baseline image set for dose calculations. With IMRT or SBRT, when respiratory or organ motion is expected during radiation delivery, multi-phasic treatment planning imaging sets might also be done.
3. Contouring: This is done in multiple steps and defines the target and avoidance. The radiation oncologist reviews the 3D images and outlines the treatment target on each image slice. The sum of these contours equals the gross tumor volume (GTV). If SRS is being planned, the neurosurgeon may also be involved in the contouring process. Next, a margin may also be drawn around the GTV (if no previous surgical treatment has occurred) to also include areas at risk for microscopic disease. This is the clinical target volume (CTV). And then, to account for daily patient set-up variation and motion issues, a final may be added to create a planning target volume (PTV). Any combination of these volumes may be contoured depending on the clinical scenario and treatment intent. Proximate normal structures that could be harmed (OARs) must also be contoured.
4. Prescription: The radiation oncologist prescribes specific radiation doses. Usually, a prescribed dose must be given to at least 90-95% of the PTV. There is often a dose constraint describing an acceptable range of dose homogeneity. Dose constraints for the OARs should be present as an upper limit of mean dose and/or a maximum allowable point dose and/or a critical volume of the OAR that must not receive a dose above a certain limit. Prescribed doses to targets and OARs should maximize disease control and minimize radiation injury risk to normal tissue.
5. Dosimetric Planning, Calculations and Verification: The physicist or supervised dosimetrist will calculate a multiple static beam and/or modulated arc treatment plan to deliver the prescribed radiation doses to the PTV and also meet OAR dose constraints. Dose volume histograms must be prepared for the PTV and OARs. Continuously moving MLCs are used to deliver the optimized modulated radiation doses to the tumor and nearby organs within that patient. The distinguishing feature of an IMRT plan is that it demonstrates how treatment with non-uniform beam intensities will be delivered. Basic dose calculations are done on each of the modulated beams or arcs in order to verify the computerized calculations. The calculated beams or arcs are delivered to a phantom or a dosimetry measuring device to confirm the intended dose will be accurate and that delivery will be technically feasible. For SRS, the quality assurance must be quite stringent to ensure dose delivery within 1 mm accuracy.

*** WHEN INVERSE TREATMENT PLANNING IS PERFORMED AND THAT PLAN IS UTILIZED, THE RADIATION ONCOLOGIST OR PHYSICIST MUST DOCUMENT THAT FACT. [Despite notations of optimization or use of certain computerized systems or other data, it is still necessary for the type of treatment planning either conventional forward planning or inverse planning to be specifically documented. Collaboration with one’s electronic medical record vendor is strongly recommended to help support meeting this documentation requirement.]

Image-guided radiation therapy (IGRT) uses imaging to maximize accuracy and precision throughout the process of full treatment delivery, not just during treatment planning. It is particularly applicable to highly conformal treatment modalities, such as CRT and IMRT. With SBRT and SRS, IGRT is considered a necessary and integral component of the entire procedure. IGRT techniques might use onboard kilovoltage radiation imaging, cone beam CT scanning, MRI or ultrasound alone or in combination. This allows smaller margins to account for day-to-day differences in positioning of the patient. It is often used in conjunction with IMRT and other advanced forms of RT. IGRT would typically be used with tumors in areas that move such as the lungs, liver, pancreas, cervix and prostate. Marked obesity in conjunction with deep tumors in the abdomen, pelvis or mediastinum might require the help of IGRT. The medical necessity for the imaging modality and frequency must be assessed and documented for each patient. If applicable, the methods used to minimize organ motion should be documented.

COVERAGE GUIDANCE

This limited LCD pertains to various types of RT treatment approaches.

Indications and Limitations of Coverage and/or Medical Necessity

IMRT

IMRT is clinically indicated when highly conformal dose planning is required to spare normal surrounding tissue as a specific clinical benefit to that individual beneficiary.

Based on medical necessity, disease sites that may support the use of IMRT include the following:

• Primary, metastatic or benign tumors of the central nervous system (CNS) including the brain, the brain stem, and spinal cord
• Primary or metastatic tumors of the spine where the spinal cord tolerance may be exceeded with conventional treatment or where the spinal cord has previously been irradiated
• Primary, metastatic, benign or recurrent head and neck malignancies, with treatment directly impacting the orbits, paranasal sinuses, skull base, aero-digestive tract-nasopharynx, oropharynx, hypopharynx, and larynx/glottic areas, salivary glands, oral cavity, nasal cavity
• Thoracic malignancies
• Abdominal malignancies when dose constraints to small bowel or other normal abdominal tissue are exceeded
• Pelvic malignancies including: prostatic, gynecologic and anal carcinomas
• Other pelvic or retroperitoneal malignancies
• Reirradiation that meets the requirements for medical necessity and which is duly documented

Documentation of the medical necessity for each unique, individual beneficiary is crucial for allowing coverage and must include the following (please see the related billing and coding article for further detail):

• The specific diagnosis and target volume requiring IMRT; the total dose and dose per fraction
• The type of treatment planning used must be specified (i.e., forward or inverse)
• The specific prior history of any RT related to site and total dose
• A narrative statement documenting the special need for IMRT rather than conventional or 3D RT relating to the individual specific beneficiary

Medical necessity documentation for IMRT should include 1 or more of the following clinical scenarios:

• • An immediately adjacent area has been previously irradiated and highly precise planning is needed for the current therapy with abutting portals
  • Dose escalation is planned to deliver radiation doses exceeding those commonly used for similar tumors with conventional treatment
  • The target volume is concave or convex, and the critical normal tissues are within or around that convexity or concavity
  • The target volume is very close to critical structures that must be protected
  • The volume of interest must be covered with narrow margins to adequately protect immediately adjacent structures

• With claimed delivery of prescribed IMRT, an easily identified, authenticated dose prescription must be present along with clearly labeled, color comparative treatment plans which include the dose volume histograms. Toward this requirement, collaboration with one’s electronic medical record vendor is strongly recommended.

Other malignancies not delineated above as potentially covered could be considered for coverage with submission of documentation for medical necessity should a denial occur. The determination of appropriateness and medical necessity for IMRT for any site shall be found in the documentation from the radiation oncologist and must be available when requested or submitted in the appeals process.

Limitations of Coverage:

IMRT is not considered reasonable and necessary when at least 1 of the above criteria relating to medical necessity are not documented as present.

Clinical scenarios that would not typically support the use of IMRT include:

• When conventional or CRT techniques can deliver good clinical outcomes and low toxicity
• In clinically urgent scenarios such as spinal cord compression, superior vena cava syndrome or airway obstruction
• For palliative treatment of metastatic disease where the prescribed dose does not approach normal tissue tolerances
• Inability to allow for organ motion, such as for a mobile lung tumor
• For a patient who cannot cooperate or who cannot tolerate immobilization to achieve accurate and reproducible delivery of doses

Non-Coverage

At this juncture, the following treatment is not considered reasonable and necessary due to insufficient evidence-based support:

• IMRT used in conjunction with proton beam RT⁶¹

SRS

SRS may be considered medically reasonable and necessary for the following indications:

1. Primary CNS malignancies, generally used as a boost or salvage therapy for lesions under 5 cm
2. As a boost treatment for larger cranial or spinal lesions that have been treated initially with external beam RT or surgery (e.g., sarcomas, chondrosarcomas, chordomas, and nasopharyngeal or paranasal sinus malignancies)
3. Primary and secondary tumors involving the brain parenchyma, meninges/dura, or immediately adjacent bony structures. For new brain metastases, the patient must have a documented Karnofsky Performance Status (KPS) score > 70% or an Eastern Cooperative Oncology Group (ECOG) status score of 0-2, be absent of leptomeningeal metastases, and not have a primary diagnosis of a lymphoma, germ cell tumor or small cell carcinoma. For repeat brain metastases therapy, the patient must have a KPS score > 70% or ECOG of 0-2, no leptomeningeal metastases, stable extra-cranial disease on restaging studies done within the prior 2 months, and a life expectancy of > 6 months. (In the case of brain metastases, this contractor will not attempt to calculate the performance scale score based on information pieced together from the record; the numeric scale specific score and the life expectancy must be documented in the patient’s record. Please see the additional information below under Associated Information and Sources of Information for KPS and ECOG scoring information.)
4. Benign brain tumors such as meningiomas, acoustic neuromas of Grade 3 or less, other schwannomas, pituitary adenomas, pineocytomas, craniopharyngiomas, glomus tumors, and hemangioblastomas
5. Cranial arteriovenous malformations (AVMs) and cavernous malformations
6. Trigeminal neuralgia, medically refractory epilepsy, severe Parkinson’s disease movement disorder, or severe and quality of life (QOL) impacting essential tremor that has not been responsive to medical management with at least 2 different agents at optimal doses. (The precise therapies, durations offered and responses to each therapy must be documented in the medical record.)
7. Uveal or ocular melanoma
8. Relapse in a previously irradiated cranial field where the additional stereotactic precision is required to avoid unacceptable vital tissue radiation

Limitations of Coverage:

SRS is not considered reasonable and necessary under the following clinical circumstances:

• When functional improvement is not expected
• When directed toward anything other than a severe symptom or serious threat to life or critical functions
• When clinically meaningful stabilization of the disease is not expected
• When other treatment could result in equally meaningful functional improvement or clinical stabilization
• Patients with poor performance status (KPS score < 40 or ECOG score > 3)
• Patients with widespread cerebral or extra-cranial metastases with limited life expectancy

SBRT

SBRT may be considered medically reasonable and necessary for the following indications:

1. Primary malignant tumors and tumors metastatic to the lung when the following criteria are met:
   • Early stage primary tumors in medically inoperable patients, OR
   • Recurrent early stage lung cancer in medically inoperable patients, OR
   • Early stage primary tumors in high operative risk patients, OR
   • Limited metastatic disease, good performance status, and the intention is eradicating all known active disease or greatly reducing the total disease burden in a manner that can extend progression-free survival (PFS).
2. Primary tumors and tumors metastatic to the liver when the following criteria are met:
   • Primary tumors when the patient is not a surgical candidate, OR
   • Limited metastatic disease, good performance status, and the intention is eradicating all known active disease or greatly reducing the total disease burden in a manner that can extend PFS.
3. Primary tumors and tumors metastatic to the kidney when the following criteria are met:
   • Primary tumors when the patient is not a surgical candidate, OR
   • Limited metastatic disease, good performance status, and the intention is eradicating all known active disease or greatly reducing the total disease burden in a manner that can extend PFS.
4. Primary tumors and tumors metastatic to the adrenal gland when the following criteria are met:
   • Primary tumors when the patient is not a surgical candidate, OR
   • Limited metastatic disease, good performance status, and the intention is eradicating all known active disease or greatly reducing the total disease burden in a manner that can extend PFS.
5. Primary tumors and tumors metastatic to the pancreas when the following criteria are met:
   • Primary tumors when the patient is not a surgical candidate, OR
   • Limited metastatic disease, good performance status, and the intention is eradicating all known active disease or greatly reducing the total disease burden in a manner that can extend PFS.
6. For treatment of pelvic and head and neck tumors that have recurred after primary irradiation when the following criteria are met:
   • The patient’s general medical condition (namely, the performance status) justifies aggressive, curative treatment to a primary, non-metastatic cancer, OR
   • Metastatic disease requiring palliation cannot be treated by conventional methods due to proximity of adjacent prior irradiated volumes and other measures are not appropriate or safe for the particular patient, OR
   • The patient’s general medical condition (namely, the performance status) justifies aggressive local therapy to 1 or more deposits of metastatic cancer in an effort either to achieve total disease clearance in the setting of oligometastatic disease or to reduce the patient’s overall burden of systemic disease for a specifically defined clinical benefit, AND
   • The targeted tumor(s) can be completely encompassed with acceptable risk to nearby critical normal structures.
7. Low- to intermediate-risk prostate cancer without a need for pelvic nodal irradiation (if nodal irradiation is needed, that area should be managed with conventional radiation fractions due to the risk for toxicity)
8. Bone metastases in the vertebral bodies or the paraspinous region where extra care must be taken to avoid excess irradiation of the spinal cord when tumor-ablative doses are administered and when the following criteria are met:
   • Limited metastatic disease, good performance status, and the intention is eradicating all known active disease or greatly reducing the total disease burden in a manner that can extend PFS.
9. Tumors arising in or near previously irradiated regions when a high level of precision and accuracy is required to minimize the risk of injury to surrounding normal tissues. (Medical records must describe the specific circumstances unique to the beneficiary.)
10. Tumors requiring a high dose per fraction treatment above the level obtainable with other methods of RT. (Medical records must describe the specific circumstances unique to the beneficiary.)

Limited coverage:

• SBRT of clinically localized prostate cancer or a primary spinal tumor may be covered on an individual case by case basis.
• For all SBRT therapy, the patient’s general medical condition (per the documented performance status scale score) must be sufficient to reasonably justify aggressive SBRT therapy to the primary or metastatic tumor. (For this purpose, an ECOG or KPS score must be documented and updated as necessary. These scales are noted under Associated Information section of this LCD.)

There is a genuine distinction between patients with primary or secondary tumors for whom curative intent or at least marked reduction in total disease burden that will extend PFS is sought vs those patients with metastatic disease in need of palliation. Palliative RT, when needed, can generally be accomplished with much less technically complex and more conventional approaches than SBRT.

Non-covered:

• Primary treatment of lesions of bone, breast, uterus, ovary and other internal organs not listed above as covered are not considered medically necessary.
• Treatment that is unlikely to result in clinical cancer control and/or functional improvement
• The tumor burden cannot be completely targeted with acceptable risk to nearby critical structures
• Patients with poor performance status scores (a KPS score < 40 or an ECOG status of 3 or worse)

The evolution of IMRT technology has demonstrated improved clinical outcomes to the point that many disease sites need to be considered as potentially appropriate for this therapy. Professional society and national clinical guidelines create the foundation for this LCD’s limited coverage related to evidence-based RT approaches.

Sources for this coverage LCD, such as American Society for Therapeutic Radiology and Oncology (ASTRO) and National Comprehensive Cancer Network^® (NCCN^®), have compiled many peer-reviewed publications which report clinical outcomes for these therapies related to cancer type and disease site. These publications have thus informed those credible specialty organization model policies and guidelines. In turn, these model policies and guidelines have all been reviewed for purposes of creating a foundation for this coverage LCD.

The ASTRO Model Policies for IMRT, SRS, and SBRT^1,2,3 address coverage and limitations based on a review of available literature.

IMRT Evidence Review

Anal Cancer

American College of Radiology (ACR^®) Appropriateness Criteria states that in terms of the dosage of ionizing radiation, IMRT can reduce the dose to normal structures and is associated with decreased acute toxicity when compared to CRT for anal carcinoma. They recommend IMRT use as “usually appropriate” if given outside of a protocol setting and note that further evaluations are underway.⁴

NCCN^® guidelines for the treatment of anal carcinoma state that IMRT is preferred over 3D-CRT, citing benefits of reduced toxicity while maintaining local control (LC) in multiple studies (2021).⁵

Breast Cancer

Jagsi et al⁶ conducted a randomized controlled trial (RCT) comparing IMRT and deep inspiration breath hold (DIBH) vs standard, free-breathing, forward-planned, 3D-CRT in individuals with left-sided, node-positive breast cancer in whom the internal mammary nodal region was targeted. The purpose of the study was to determine whether using these technologies reduces cardiac or pulmonary toxicity during breast RT. Endpoints included dosimetric parameters and changes in pulmonary and cardiac perfusion and function, measured by single photon emission computed tomography (SPECT) scans and pulmonary function testing performed at baseline and 1 year post treatment. Of 62 patients randomized, 54 who completed all follow-up procedures were analyzed. Mean doses to the ipsilateral lung, left ventricle, whole heart, and left anterior descending coronary artery were lower with IMRT-DIBH; the percent of left ventricle receiving ≥5 Gy averaged 15.8% with standard RT and 5.6% with IMRT-DIBH. SPECT revealed no differences in perfusion defects in the left anterior descending coronary artery territory, the study's primary endpoint, but did reveal statistically significant differences (P=0.02) in left ventricular ejection fraction (LVEF), a secondary endpoint. No differences were found for lung perfusion or function. The authors concluded that this study suggests a potential benefit in terms of preservation of cardiac ejection fraction among patients with left-sided disease in whom the internal mammary region was targeted. Future studies are essential, including comparative evaluation of outcomes and the impact of advances in radiation treatment planning and delivery, in order to inform and shape clinical practice and policy.

NCCN^® guidelines for breast cancer state that greater target dose homogeneity and sparing of normal tissues can be accomplished using compensators such as wedges, forward planning using segments and IMRT. Respiratory control techniques and prone positioning may be used to try to further reduce dose to adjacent normal tissues, particularly the heart and lungs (2021).⁷

Central Nervous System (CNS) Tumors

In its CNS Cancers guideline, NCCN^® states that lower doses of targeted conformal RT (including 3D-CRT and IMRT) are recommended for treatment of low-grade anaplastic gliomas, infiltrative astrocytomas, oligodendrogliomas, glioblastomas and meningiomas. Higher doses of RT are found to be no more effective than lower doses. For medulloblastomas, the guidelines state that for patients at average risk, a regimen of IMRT or proton craniospinal irradiation (CSI) alone or with chemotherapy are both viable treatment options (2021).⁸

Cervical Cancer

Tsuchida et al⁹ conducted a retrospective cohort analysis to compare clinical outcomes and toxicity incidence among patients diagnosed with cervical cancer that underwent radical hysterectomy and were treated with either 3D-CRT or IMRT. Concurrent chemotherapy was not given during the study. Outcomes of interest included gastrointestinal (GI), genitourinary (GU) and hematologic (HT) toxicities, and overall survival (OS), disease-free survival (DFS) and loco-regional control (LRC). A total of 73 patients (33 received 3D-CRT and 40 received IMRT) were included in the final analysis. The median follow-up period differed between the group with 82 months in the 3D-CRT group and 50 months in the IMRT group (P<0.001). After 4 years, there was no difference OS or DFS between the groups. Loco-regional recurrence was more frequent in patients with vaginal invasion reported in the post-operative pathological report (17% vs 2.3%; P=0.033). GI obstruction was more frequent in the group that received 3D-CRT vs IMRT (27% vs 7.5%; P=0.026) and surgical intervention for the obstruction was higher in the 3D-CRT group as well (18% vs 0%; P=0.005). There was no significant difference in acute GI, GU or HT toxicities; however, in the IMRT group, there were fewer late toxicities, GI ≥2 (P=0.026) and GU ≥G2 (P=0.038). The authors concluded that their results show that IMRT could reduce the incidence of late severe GI obstruction and that additional studies are warranted.

Lin et al¹⁰ conducted a meta-analysis to compare the efficacies and toxicities of IMRT with 3D-CRT or 2D-RT for definitive treatment of cervical cancer. A search for relevant studies was conducted using PubMed^®, the Cochrane Library, Web of Science™, and Elsevier. Outcomes of interest included OS, DFS, and acute and chronic toxicities. The literature review yielded 2,808 publications and after screening and review, a total of 6 articles, with 1,008 participants (350 IMRT and 658 CRT) were included in the final analysis. Three-year OS and 3-year DFS revealed no significant differences between IMRT and 3D-CRT or 2D-RT (3-year OS: OR, 2.41, CI, 0.62 to 9.39, p=0.21; 3-year DFS: OR, 1.44, 95% CI, 0.69 to 3.01, p=0.33). The incidence of acute GI toxicity and GU toxicity in patients who received IMRT was significantly lower than that in the control group (GI: Grade 2: OR, 0.5, 95% CI, 0.28 to 0.89, p=0.02; Grade 3 or higher: OR, 0.55, 95% CI, 0.32 to 0.95, p=0.03; GU: Grade 2: OR, 0.41, 95% CI, 0.2 to 0.84, p=0.01; Grade 3 or higher: OR, 0.31, 95% CI, 0.14 to 0.67, p=0.003). Furthermore, patients who received IMRT experienced fewer incidences of chronic GU toxicity than patients in the control group (Grade 3: OR, 0.09, 95% CI, 0.01 to 0.67, p=0.02). The authors concluded that IMRT and CRT demonstrated equivalent efficacy in terms of 3-year OS and DFS, and that IMRT significantly reduced acute GI and GU toxicities as well as chronic GU toxicity in patients with cervical cancer.

Mell et al¹¹ conducted an international, multicenter, single-arm phase II clinical trial (NCT01554397, still ongoing) to evaluate the incidence of HT and GI toxicities in patients with stage IB-IVA, biopsy-proven invasive carcinoma of the cervix among patients who were treated with IMRT. All 83 patients received daily IMRT concurrently with weekly cisplatin for 6 weeks, with an intracavitary brachytherapy boost given at completion of the chemoradiation regimen. Additionally, the researchers conducted a subgroup analysis on whether the use of PET-based image-guided IMRT (IG-IMRT) had an influence on the development of neutropenia compared to standard IMRT. Post-simple hysterectomy patients were included, initiating the regimen within 8 weeks of surgery. Individuals who underwent radical hysterectomy with extensive nodal involvement were excluded. Primary outcome measures were either acute grade ≥3 neutropenia or clinically significant GI toxicity occurring within 30 days of regimen completion. The median follow-up was 26 months. The incidence of any primary event was 26.5%, significantly less than the 40% hypothesized in historical data. The incidence of grade ≥3 neutropenia and clinically significant GI toxicity was 19.3% and 12.0%, respectively. In the analysis on neutropenia, those treated with IG-IMRT (n=35) had a significantly lower incidence (8.6%) compared with the 48 patients who received standard IMRT (27.1%). The differences in the incidence of grade ≥3 leukopenia and any grade ≥3 HT toxicity were considered insignificant between the 2 types of IMRT delivery. The authors concluded that IMRT, compared with standard therapy, reduces both acute HT events and GI toxicity and that PET-based IG-IMRT reduces the incidence of acute neutropenia compared with historical data.

In a 2020 ASTRO Cervical Cancer Guideline, Chino et al recommended IMRT for women with cervical cancer treated with postoperative RT with or without chemotherapy to decrease acute and chronic toxicity (strength of recommendation: strong). For women with cervical cancer treated with definitive RT with or without chemotherapy, IMRT is conditionally recommended to decrease acute and chronic toxicity.¹²

NCCN^® guidelines for cervical cancer¹³ state that IMRT and similar highly conformal methods of dose delivery may be helpful in minimizing the dose to the bowel and other critical structures in the post-hysterectomy setting, in treating the para-aortic nodes when necessary, and when high doses are required to treat gross regional lymph nodes disease. IMRT should not be used as a routine alternative to brachytherapy for treatment of central disease in patients with an intact cervix. Very careful attention to detail and reproducibility is required for proper delivery (2021).

Endometrial Cancer

Klopp et al¹⁴ conducted a multicenter, phase III RCT (NCT01672892, still ongoing) to evaluate patient reported acute toxicity and QOL in patients with invasive cervical or endometrial cancer and treated with standard 4 field pelvic RT or pelvic IMRT. The primary end point, change in acute GI toxicity, was measured at baseline and end of RT (5 weeks) using the bowel domain of the Expanded Prostate Cancer Index Composite (EPIC). The secondary endpoints, measured at the same points in time, were change in GU toxicity and the extent to which it interfered with daily activities. To measure GU toxicity, the urinary domain of the EPIC was used and to determine the extent to which GU toxicity impacted daily activities, the Patient Reported Outcomes–Common Terminology Criteria for Adverse Events (PRO-CTCAE), Functional Assessment of Cancer Therapy-General (FACT-Cx), Functional Assessment of Cancer Therapy - General (FACT-G) and Trial Outcome Index were used. A total of 278 patients were included in the final analysis, 149 received standard RT and 129 received IMRT. Compared to baseline, the standard RT arm had larger mean EPIC bowel and urinary score declines compared with the IMRT arm (-26.3 vs -18.6; P=0.05 and -10.4 vs -5.3, P=0.03, respectively). The FACT-Cx mean scores showed a decline of 4.9 points in the standard RT group vs 2.7 points in the IMRT group (P=0.015). There was no difference between the arms in the FACT-G subscale or Trial Outcome Index scores. In addition, the PRO-CTCAE results showed that at the end of therapy, more patients in the standard RT arm experienced diarrhea frequently or almost constantly compared with the IMRT arm (51.9% vs 33.7%, respectively; P=0.01) and were taking antidiarrheal medications 4 or more times daily (20.4% vs 7.8%, respectively; P=0.04). The authors concluded based on the patient’s perspective, pelvic IMRT was associated with significantly less acute GI and urinary toxicity.

Wahl et al¹⁵ developed consensus guidelines on adjuvant radiotherapy for early-stage endometrial cancer from a multidisciplinary expert panel convened by the ACR^®. Per the ACR^® appropriateness criteria, IMRT has been shown to reduce dose to critical structures in dosimetric studies, and retrospective reviews of IMRT for early-stage endometrial cancer have shown excellent LC rates, with low GI toxicity rates. The ACR^® appropriateness criteria for advanced stage endometrial cancer states IMRT may further improve treatment of areas at risk for tumor recurrence while sparing adjacent normal tissues. The authors note that several studies of IMRT for gynecologic malignancies showed that, compared with external beam pelvic RT, IMRT improved target coverage, reduced the volume of normal tissues receiving the prescription dose, and that the reduction in dose resulted in a decrease in both acute and chronic GI side effects compared with historic controls.

Esophageal Cancer

Xu et al¹⁶ performed a systematic review and meta-analysis to compare IMRT and 3D-CRT in the treatment of esophageal cancer (EC) via analysis of dose-volume histograms and survival/toxicity outcomes. Overall, 7 studies were included. Of them, 5 studies (80 patients) were included in the dosimetric comparison, 3 studies (871 patients) were included in the OS analysis, and 2 studies (205 patients) were included in the irradiation toxicity analysis. For lungs and hearts, the average irradiated volumes of IMRT were less than those from 3D-CRT. IMRT resulted in a higher OS than 3D-CRT. However, no significant difference was observed in the incidence of radiation pneumonitis and radiation esophagitis between the 2 radiotherapy techniques.

NCCN^® guidelines for esophageal and esophagogastric junction cancers¹⁷ state that IMRT is appropriate in clinical settings where reduction in dose to OAR (e.g., heart and lungs) is required that cannot be achieved by 3D techniques (2021).

Head and Neck Cancer

Gupta et al¹⁸ compared long-term disease-related outcomes and late radiation morbidity between IMRT and 3D-CRT in head and neck squamous cell carcinoma (HNSCC) in a prospective RCT. The primary endpoint was the incidence of physician rated acute salivary gland toxicity (≥grade 2). Secondary endpoints included other acute toxicity (mucositis, dermatitis, dysphagia), late radiation morbidity, patterns of failure, loco-regional disease status, and OS. Patients (n=60) who were previously untreated and had early to moderately advanced non-metastatic squamous carcinoma of the oropharynx, larynx, or hypopharynx planned for comprehensive irradiation of primary site and bilateral neck nodes were randomly assigned to either IMRT or 3D-CRT. Treatment consisted of 6MV photons to a total dose of 70 Gy/35 fractions over 7 weeks (3D-CRT) or 66 Gy/30 fractions over 6 weeks (IMRT). At a median follow-up of 140 months for surviving patients, 10-year Kaplan-Meier estimates of locoregional control (LRC), PFS, and OS with 95% confidence interval were 73.6%, 45.2%, and 50.3% respectively. There were no significant differences in 10-year disease-related outcomes between 3D-CRT and IMRT for LRC 79.2% vs 68.7%; PFS 41.3% vs 48.6%; or OS 44.9% vs 55.0%. Significantly lesser proportion of patients in the IMRT arm experienced ≥ grade 2 late xerostomia and subcutaneous fibrosis at all time-points. At longer follow-up, fewer patients remained evaluable for late radiation toxicity reducing statistical power and precision. The authors concluded IMRT provides sustained clinically meaningful benefit compared to 3D-CRT in reducing the late morbidity of radiation without compromising disease-related outcomes in long-term survivors of non-nasopharyngeal HNSCC. Limitations include lack of blinding to treatment arm and small study size with even much lesser numbers on long-term follow-up (between 5 and 10 years).

In 2018, the International Lymphoma Radiation Oncology Group conducted a literature review and developed guidelines covering staging, work-up, and RT management of patients with plasma cell neoplasms. With a localized plasmacytoma in the bone or in extramedullary (extraosseous) soft tissues, definitive RT is the standard treatment. It provides long-term LC in solitary bone plasmacytomas and is potentially curative in the extramedullary cases. On the basis of comparative treatment planning (comparison dose-volume histogram) and determination of the priority of the OARs to protect, the radiation oncology team should make a clinical judgment as to which treatment technique to use. In some situations, more conformal techniques such as IMRT, helical-IMRT, or VMAT approaches may offer significantly better sparing of critical normal structures, usually at the cost of a larger total volume of normal tissue irradiated, but with a lower dose.¹⁹

Nutting et al²⁰ assessed whether parotid-sparing IMRT reduced the incidence of severe xerostomia, a common late side effect of RT to the head and neck. Ninety-four patients with pharyngeal squamous cell carcinoma were randomly assigned to receive IMRT (n=47) or CRT (n=47). The primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months. Median follow-up was 44 months. Six patients from each group died before 12 months; 7 patients from the CRT and 2 from the IMRT group were not assessed at 12 months. At 12 months, xerostomia side effects were reported in 73 of 82 patients. Grade 2 or worse xerostomia at 12 months was significantly lower in the IMRT group (38%) than in the CRT group (74%). The only recorded acute AE of grade 2 or worse that differed significantly between the treatment groups was fatigue, which was more prevalent in the IMRT group. At 24 months, grade 2 or worse xerostomia was significantly less common with IMRT than with CRT. At 12 and 24 months, significant benefits were seen in recovery of saliva secretion with IMRT compared with CRT, as were clinically significant improvements in dry-mouth-specific and global QOL scores. At 24 months, no significant differences were seen between randomized groups in non-xerostomia late toxicities, LRC or OS. The authors concluded that sparing the parotid glands with IMRT significantly reduces the incidence of xerostomia and leads to recovery of saliva secretion and improvements in associated QOL.

NCCN^® guidelines for head and neck cancers state that IMRT is appropriate and may offer clinically relevant advantages to spare important OARs, such as brain, brain stem, cochlea, semicircular canals, optic chiasm, cranial nerves, retina, lacrimal glands, cornea, spinal cord, brachial plexus, mucosa, salivary glands, bone, pharyngeal constrictors, larynx, esophagus, and decrease the risk for late, normal tissue damage and toxicity while still achieving the primary goal of local tumor control (2022).²¹

Hippocampal-Avoidance Whole Brain Radiation Therapy (HA-WBRT)

Brown et al²² conducted a phase III trial to determine if hippocampal avoidance using IMRT during whole-brain radiotherapy (WBRT) preserves cognition. Between July 2015 and March 2018, 518 patients were randomly assigned to 2 groups, 1 group with brain metastases to HA-WBRT plus memantine, and 1 group with WBRT plus memantine. Time to cognitive function failure, defined as decline using the reliable change index on at least 1 of the cognitive tests was the primary endpoint. OS, intracranial PFS, toxicity, and patient-reported symptom burden, were secondary endpoints. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine vs WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; P=0.02). This difference was attributable to less deterioration in executive function at 4 months, and learning and memory at 6 months. Treatment arms did not differ significantly in OS, intracranial PFS, or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue (P=0.04), less difficulty with remembering things (P=0.01), and less difficulty with speaking (P=0.049) and using imputed data, less interference of neurologic symptoms in daily activities (P=0.008) and fewer cognitive symptoms (P=0.01). The authors concluded HA-WBRT plus memantine effectively spares the hippocampal neuroregenerative niche to better preserve cognitive function and patient-reported symptoms and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region. Additionally, no differences were observed in intracranial PFS, toxicity, or OS. Limitations include lack of blinding.

The American Society of Clinical Oncology (ASCO)/Society for NeuroOncology (SNO)/ASTRO guidelines for patients with brain metastases from solid tumors recommends memantine and hippocampal avoidance should be offered to patients who receive WBRT, and have no hippocampal lesions, and 4 months or more expected survival. Patients with asymptomatic brain metastases with either KPS ≤ 50 or KPS < 70 with systemic therapy options do not derive benefit from RT.²³

NCCN^® guidelines for CNS cancers state that HA-WBRT (plus memantine) 30 Gy in 10 fractions is preferred for patients with a better prognosis (≥4) and no metastases within 5 mm of the hippocampi (2021).⁸

Mediastinal Tumors

Besson et al²⁴ evaluated toxicities secondary to different RT modalities and the evolution of those modalities in the treatment of mediastinal tumors associated with Hodgkin’s (HL) and non-Hodgkin's lymphoma (NHL). Between 2003 and 2015, 173 individuals with Stage I-III nodal lymphoma were treated at a single institution with either 3D-CRT or IMRT as part of a chemoradiotherapy protocol (HL=64, NHL=5). Of interest, between 2003 and 2006, 16 patients were treated by 3D-CRT vs zero patients treated by IMRT. Between 2007-2009, 16 patients were treated by 3D-CRT vs 1 patient receiving IMRT. Between 2010- 2015, 19 patients were treated by IMRT, and zero received 3D-CRT. All patients were followed for 5 years alternately by a radiation oncologist or a hematologist. Results demonstrated LC at 100% in both groups and acute (grade 1 or 2) toxicities of 55% and 71.4% with IMRT vs 3D-CRT, respectively. Authors concluded that the use of IMRT as an improved RT technique over 3D-CRT has promoted the evolution of improved acute and late outcomes for HL and NHL patients. Longer follow-up is necessary to evaluate very late toxicities, as this study only evaluated acute (grade 1 and 2) toxicities.

NCCN^® guidelines for lymphomas state that advanced RT technologies, such as IMRT, breath hold or respiratory gating, and/or IGRT or Proton Beam Therapy (PBT), may offer significant and clinically relevant advantages in specific instances to spare OAR and decrease the risk for late, normal tissue damage while still achieving the primary goal of local tumor control. Randomized studies to test these concepts are unlikely to be done since these techniques are designed to decrease late effects which take 10+ years to evolve. Therefore, the guidelines recommend that RT delivery techniques that are found to best reduce the doses to the OAR in a clinically meaningful way without compromising target coverage should be considered in these patients, who are likely to enjoy long life expectancies following treatment (2022).²⁵

NCCN^® guidelines for thymomas and thymic carcinomas state that RT should be given by 3D conformal technique to reduce surrounding normal tissue damage (e.g., heart, lungs, esophagus, spinal cord). The guideline states that since these patients are younger and mostly long-term survivors, the mean total dose to the heart should be as low as reasonably achievable to potentially maximize survival. IMRT is preferred over 3D-CRT and may further improve the dose distribution and decrease the dose to the normal tissue as indicated (2022).²⁶

Non-Small Cell Lung Cancers (NSCLC), Stage III

NCCN^® guidelines for NSCLC state that in a prospective trial of definitive/consolidative chemo/RT for patients with stage III NSCLC (RTOG 0617), IMRT was associated with a nearly 60% decrease in high-grade radiation pneumonitis as well as similar survival and tumor control outcomes despite a higher proportion of stage IIIB and larger treatment volumes compared to 3D-CRT; as such, IMRT is preferred over 3D-CRT in this setting (2022).²⁷

Pancreatic Cancer

Bittner et al²⁸ conducted a systematic review to determine whether toxicities can be reduced by using IMRT rather than 3D-CRT in patients with pancreatic cancer, and to compare OS and PFS between the 2 techniques. A search for relevant studies was conducted using PubMed^®/Medline. Outcomes of interest included details regarding the therapy given, acute and late toxicities, and patient survival (OS and PFS). A total of 13 IMRT and 7 3D-CRT studies were included in the final analysis. For acute toxicities, nausea and vomiting ≥ grade 3 were 13.4% (109/747 patients) vs 7.8% (35/446 patients) for 3D-CRT and IMRT, respectively (p<0.001). Late toxicities were predominantly GI: toxicities ≥ grade 3 were 10.6% (22/207) and 5.0% (19/381), for 3D-CRT and IMRT, respectively (p=0.017). However, those were mainly attributed to the group of patients with GI bleeding/duodenal ulcer. There were no differences in HT, OS and PFS between the 2 techniques. The authors concluded that when comparing 3D-CRT and IMRT in the treatment of pancreatic cancer, there is no significant differences in OS and PFS, however; treatment-related toxicities (i.e., nausea, vomiting, diarrhea and late GI toxicity) are significantly reduced with IMRT.

ASTRO’s 2019 clinical practice guideline states that modulated treatment techniques such as IMRT and VMAT for planning and delivery of both conventionally fractionated and hypofractionated RT are recommended for treatment of localized pancreatic cancer (Strength of recommendation: Strong).²⁹

NCCN^® guidelines for pancreatic adenocarcinoma state that IMRT with breath hold/gating techniques can result in improved PTV coverage with decreased dose to OAR. IMRT is increasingly being applied in treatment of locally advanced pancreatic adenocarcinoma and in the adjuvant setting with the aim of increasing radiation dose to the gross tumor while minimizing toxicity to surrounding tissues. There is no clear consensus on appropriate maximum dose of radiation when IMRT is used (2021).³⁰

Prostate Cancer

Viani et al³¹ compared IMRT with 3D-CRT for the treatment of prostate cancer through a randomized, phase III clinical trial (NCT02257827). In total, 215 patients were enrolled in the study, randomly selected into the IMRT group (n=109) or the 3D-CRT group (n=106). Primary outcome measures included early and late GU and GI toxicities as well as freedom from biochemical failure, determined through use of Phoenix criteria (PSA + 2 ng/mLnadir). The median follow-up period was 3 years. The 3D-CRT arm reported incidences of grade ≥ 2 acute GU and GI toxicities at 27% and 24%, respectively, compared with 9% and 7%, respectively, in the IMRT group. In assessing the rate of grade ≥2 late GU and GI toxicities spanning the entire follow-up period, the 3D-CRT group reported 12.3% and 21%, respectively, compared to the IMRT arm which reported 3.7% and 6.4%, respectively. The 5-year rate of freedom from biochemical failure was 95.4% in the IMRT arm and 94.3% in the 3D-CRT arm (P=0.678). The authors concluded that the use of IMRT resulted in significantly less acute and late toxicities than 3D-CRT when used in the treatment of prostate cancer.

NCCN^® guidelines state that highly CRT, such as IMRT, should be used to treat prostate cancer. IMRT significantly reduces the risk of GI toxicities and rates of salvage therapy compared to 3D-CRT in some but not all older studies. Moderately hypofractionated image guided IMRT regimens have been tested in randomized trials with similar efficacy and toxicity to conventionally fractionated IMRT in some studies, and they can be considered as an alternative to conventionally fractionated regimens when clinically indicated (2022).³²

At the time of this evidence review, no evidence was identified in the clinical literature supporting the combined use of IMRT and proton beam RT in a single treatment plan.

SRS Evidence Review

SRS is limited to 1 to 5 fractions delivered to intracranial targets and selected tumors around the base of the skull. According to the Skeie³³ article, nearly all glioblastoma multiforme (GBM) patients suffer a relapse after the initial treatment. In this study, 77 consecutive patients with recurrent GBM treated with Gamma Knife^® surgery (GKS), reoperation, or both were reviewed. Thirty-two patients were treated with GKS, 26 patients underwent reoperation, and 19 patients were treated with both. Patients treated with GKS at the time of tumor progression had significantly better local tumor control and significantly longer survival than patients not treated with GKS.

Three articles evaluated SRS for brain metastases. Yomo et al³⁴ noted that patients treated with SRS for limited brain metastases from small cell lung cancer survived slightly more than 8 months following SRS. Although SRS provided durable local tumor control, repeat treatment was required in nearly half of the patients to control distant brain metastases. Soike et al³⁵ conducted a review of nonrandomized prospective and retrospective data supporting the use of SRS in patients with 4 or more brain metastases. The absolute number of brain metastases was not as prognostic as other factors such as the KPS, age, histology of the tumors, and presence of mutations that could be targeted. WBRT has been the standard treatment for brain metastases. However, new technology has allowed use of SRS to treat 4 or more brain metastases, but there has been a lack of randomized evidence supporting its use. The authors concluded the role of SRS in brain metastases should be carefully considered on an individual basis. More multi-institutional trials were recommended to determine whether SRS is the most appropriate treatment in such patients. Badiyan et al³⁶ noted that brain metastases are the most common intracranial malignancy. Surgery and SRS are both commonly used to treat patients with brain metastases. Surgery is preferred for patients with a single brain metastasis. Surgery also has the advantage of treating metastases greater than 4 cm and those that abut critical structures. SRS has the advantage of being noninvasive, with the ability to treat multiple tumors simultaneously. Some patients receive both treatments. SRS is also sometimes used post operatively to treat the residual tumor cavity to decrease the risk of local recurrence. Although the 2 treatments have never been compared in a randomized trial, data point to potentially poorer LC with surgery alone. The ASTRO SRS Model Policy does recommend coverage for metastatic brain lesions, independent of the number of such lesions assuming other positive clinical factors exist such as decent performance status and stable systemic disease.²

A systematic review and meta-analysis was performed to evaluate the safety and efficacy of fractionated stereotactic radiotherapy (FSRT) and SRS for pituitary adenomas.³⁷ The authors concluded SRS and FSRT have comparable clinical outcomes and are in agreement with current reviews in the literature. FSRT and SRS have similar efficacy and safety profiles. In the Przybylowski³⁸ study, a retrospective review was performed regarding SRS for acoustic neuromas. It was concluded that SRS affords effective tumor control for acoustic neuromas with an acceptable rate of hearing preservation. Koos grade IV tumors were significantly less likely to respond to SRS than grades I to III tumors and should be strongly considered for surgical resection when possible. Two studies evaluated SRS for intracranial AVMs. Gupta et al³⁹ conducted a retrospective review of 114 patients with intracranial AVMs treated with the CyberKnife^® device. Interdisciplinary treatment regimens that may involve endovascular embolization, surgical resection and SRS are increasingly being used. The multimodal treatment approach is believed to ensure obliteration of the AVM while minimizing AVM rupture. This article presented single institution data on a series of patients whose AVMs proved resistant to radiosurgery with the CyberKnife^® device over a 10-year period. The average follow-up was over 7 years. The incidence of delayed hemorrhage after CyberKnife^® treatment was 11 percent. Functional and clinical outcomes after radiosurgery remained the same in most cases. Two thirds of these AVMs were eventually completely obliterated at last imaging follow-up. Even AVMs persisting for over 4 years following CyberKnife^® radiosurgery might eventually obliterate, with or without adjunctive endovascular and/or radiosurgical treatment. In the Ding⁴⁰ article, 11 patients' diagnoses with large localized cerebral AVMs were selected for multi-stage robotic SRS. The CyberKnife^® and MultiPlan^® radiation delivery and treatment planning systems were concluded to be practical for multi-stage SRS of large cerebral AVMs. The ASTRO SRS Model Policy does recommend coverage for AVMs and cavernous malformations; the evidence for SRS, particularly as part of a multidisciplinary approach to assure success appears to be reasonable and necessary.²

SBRT Evidence Review

The ASTRO Model Policy for SBRT³ addresses coverage and limitations based on a review of available literature. SBRT is used to treat extracranial sites. ASTRO also has an evidence-based guideline for SBRT for early stage NSCLC.⁶³ It notes indications for SBRT in early stage lung cancer for medically inoperable or high surgical risk patients and for patients with limited metastatic disease, good performance status with the intention of eradicating all known active disease or greatly reducing the total disease burden in a manner that can extend PFS. Cao et al⁴¹ performed a systematic review and meta-analysis of SBRT vs surgery for patients with NSCLC. The authors found that current evidence suggests surgery is superior to SBRT in terms of mid- and long-term clinical outcomes, but SBRT is associated with lower perioperative mortality. It was also noted that the data on improved outcomes after surgery might be skewed due to an imbalance of baseline characteristics. Future studies were recommended that would confirm malignancy histopathology and then compare SBRT with minimally invasive anatomical resections. Rosen et al⁴² found that among healthy patients with clinical stage I NSCLC in the National Cancer Database, lobectomy was associated with a significantly better outcome than SBRT. This was also found in the Li⁴³ article which noted a superior OS and long-term distant control for early stage NSCLC after surgery compared with SBRT after propensity score matching. Lischalk et al⁴⁴ noted SBRT in 5 fractions to a total dose of 35 or 40 Gy was a safe and effective management strategy for high-risk central pulmonary metastatic lesions, though care had to be taken to limit the maximum point dose to the mainstem bronchus. In the Lodeweges⁴⁵ article, pulmonary metastasectomy (PME) with clear margins was compared to SABR. The authors found despite higher age and shorter metastasis-free interval suggesting higher baseline risk for death after SABR, unadjusted reanalysis at almost 6 years of follow-up actually did not support that surgery for pulmonary oligometastases would result in better survival or LC compared with SABR. Nikitas et al⁴⁶ noted that patients who received either synchronous or metachronous SBRT had no significant reduction in OS or toxicity when compared to single-course patients.

Yeung et al⁴⁷ looked at the use of SBRT in hepatocellular carcinoma (HCC). They reported that SBRT provided good LC to small inoperable HCC. Also, SBRT could be delivered safely even after previous liver-directed therapies. It also did not preclude later additional alternative liver therapies. Although overall 32 percent of patients experienced greater than or equal to 3 plus toxicities, and 19 percent had a deterioration in Child-Pugh score of 2 or more points, these changes were mainly transient. The authors noted that excellent LC existed while disease progression outside of the irradiated site was prominent. Further studies were urged to examine combined therapy approaches to maximize disease control. The Onal⁴⁸ study was designed to evaluate the feasibility of SBRT to breast cancer metastasized to the liver. They concluded SBRT was a conservative approach with excellent LC and limited toxicities. The Brunner⁴⁹ study is the largest reported series on SBRT in cholangiocarcinoma. OS and LC were significantly improved after higher doses and tolerance was excellent.

Francolini et al⁵⁰ noted that surgical resection was the treatment of choice for localized renal cell carcinoma (RCC) as nephron-sparing is so important. But it was also noted that RCC patients are often unfit for surgery due to multiple comorbidities. Therefore, active surveillance or ablative techniques are often suggested. This author notes that SBRT might be considered as an alternative treatment in these inoperable patients with primary RCC. Dose escalation to 48 Gy in 3 to 4 fractions was effective and well tolerated. Further studies to explore interactions between SBRT and immune therapy in the approach to RCC.

Draulans et al⁵¹ finds that SBRT is a valid treatment option for patients with low- and intermediate-risk prostate cancer. A study by King et al⁵² notes that prostate specific antigen (PSA) relapse-free survival rates after SBRT compared favorably with other definitive treatments for low- and intermediate-risk patients. The authors concluded that current evidence supports consideration of SBRT among the therapeutic options for low- and intermediate-risk patients. Freeman et al⁵³ reported 5-year results for SBRT in localized prostate cancer demonstrating efficacy and safety for shorter course high fraction dose SBRT. ASTRO/ASCO/AUA have published an evidence-based guideline concerning hypofractionated RT for localized prostate cancer. Based on high-quality evidence, strong consensus was reached for offering moderate hypofractionation across risk groups to patients who opted to have external beam RT. The task force only conditionally recommended ultrahypofractionated radiation for low- and intermediate-risk prostate cancer. The task force strongly encouraged treatment of intermediate-risk patients to occur within the construct of a clinical trial or multi-institutional registry. And for high-risk patients, the task force conditionally recommended against routine use of ultrahypofractionated external beam RT.⁶¹

Zhan et al⁵⁴ conducted a systematic review of the literature related to treatment for spinal AVMs. The authors identified 11 studies associated with radiosurgery or fractionated radiotherapy treatments for spinal vascular malformations. Four were done at the same institution and included overlapping patients. So there were truly 8 total articles that qualified. In this review, microsurgery and transarterial embolization were the mainstays of treatment for spinal AVMs. The use of SRS and fractionated radiotherapy for spinal AVM management has very limited associated literature.

Yazici et al⁶⁵ recently reported (2022) on long term results of retrospective analysis regarding both stereotactic surgery and FSRT in 443 patients with 445 uveal melanomas who underwent CyberKnife^® treatment between 2007 and 2019. 70% of the tumors were small/medium and 30% were large. The primary endpoints were LC, local recurrence-free survival (LRFS), enucleation-free survival (EFS) and treatment toxicity. After a median 74 month follow-up, SRS/FSRT demonstrated an 83% overall LC rate. The 5- and 10-year LRFS rate was 74% and 56% respectively. An increased dose was associated with higher LRFS and higher EFS rates. Related toxicity was noted in 49% of the eyes. Overall eye preservation rate was 62% and the 5- and 10-year EFS rate was 64% and 36% respectively. The authors also noted that the delivery of FSRT every other day resulted in a significantly lower rate of toxicity and enucleation compared to FSRT on consecutive days. Akbaba et al⁶⁴ retrospectively analyzed the clinical outcomes, visual acuity and enucleation rates for 24 patients with primary uveal melanoma who were treated with linear accelerator-based SFRT during a period between 1991 and 2015. This therapy offered good LC rates with a local PFS of 82% after 5 years. Of all local progressions, 80% happened within the first 5 years post radiotherapy. In 1 case, enucleation was eventually needed. EFS was related to the radiotherapy dose (p<0.0001). A 2-year sight preservation rate of 75% was achieved which was comparable to brachytherapy or PBT and which was available in small center. Six late toxicities were observed. The ASTRO Model Policy for SRS² does recommend coverage for uveal or ocular melanoma. That policy lists numerous evidence-based resources underlying that recommendation. While toxicity of RT to the eye is a concern, the risk of enucleation is not remarkably higher with other therapy approaches. Overall, the evidentiary support indicates that SRS is likely reasonable and necessary.

Regarding PBT, ASTRO reviewed this treatment via its emerging technology committee in 2012. Data was reviewed for PBT in CNS tumors, GI malignancies, lung, head and neck, prostate and pediatric tumors. There was not sufficient evidence to recommend it in lung cancer, head and neck cancer, and GI malignancies. There did appear to be some efficacy for PBT in HCC and prostate cancer, but there was no suggestion that it was superior to photon based approaches. Investigation is ongoing for use of PBT in large ocular melanomas and chordomas. More robust prospective clinical trials are needed to determine the appropriate clinical setting for PBT.⁶⁰

The literature supports the use of SRS for intracranial targets and lesions at the base of the skull. The articles included primary brain tumors and metastatic brain tumors. The studies also included pituitary adenomas, acoustic neuromas and intracranial AVMs. Both NCCN^® and ASTRO model policies were given weight regarding recommendations for potential coverage, if reasonable and necessary, for a wide expanse of IMRT indications and for non-cancer related diagnoses such as some refractory epilepsy, movement disorders and essential tremor. Likewise, the ASTRO Model Policy recommended consideration for potential coverage related to uveal melanoma indications was accepted. The entirety of the ASTRO Model Policy was not incorporated into this coverage LCD based on overall evidence review. For SBRT, the literature supports its use for patients who are not surgical candidates and have early-stage NSCLC, HCC, and RCC. The studies also supported low- and intermediate-risk prostate cancer treatment. The studies were not felt to support SBRT for spinal AVMs.

Particular attention was given to the use of SRS and SBRT in spinal cord tumor treatment. While preliminary evidence suggests that SBRT and SRS may be effective and safe for treating intradural and intramedullary spinal cord disease, it is clear that surgical resection remains the best approach for both primary and metastatic spinal cord lesions. Limited coverage, via this LCD, is available regarding the common occurrence of vertebral metastases and for spinal cord tumors that remain after resection or reside in or near previously irradiated tissue. For primary spinal lesions, which certainly encompass a large proportion of benign slow-growing tumors, the long-term consequences of spinal injury secondary to RT impact might have much greater impact in a setting with prolonged life expectancies. Again, it is quite likely that primary surgical resection would be the better approach. Though some guidelines and other literature have been published regarding spine tumors and stereotactic RT, the accepted tolerance for radiation to the spinal cord remains debated. Furthermore, all incidences of radiation-injury do not necessarily correlate with the degree of stereotactic radiation intensity. The risk of injury from RT is likely multifactorial. It is possible that radiation-related injury is oversimplified when only the maximum tumor dose is considered. A much greater understanding of the implications of radiation-induced injury in the spine after SRS or SBRT is necessary and strong evidence supporting these therapies in primary spinal nerve sheath tumors or meningiomas or hemangioblastomas is judged insufficient.⁶²

Documentation Requirements

Documentation of all aspects of the treatment planning processes for radiation oncology must be present in the record. This A/B Medicare Administrative Contractor (MAC) notes that the radiation oncology medical record systems frequently utilized by providers create unnecessary confusion/difficulties for medical review or external auditors as follows:

• May not allow for appropriate authenticating signatures to be applied,
• Do not identify personnel performing a service by name and with credentials,
• Do not clearly identify what type of treatment planning was employed (the use of inverse planning should be clearly documented),
• Do not clearly identify steps in the treatment planning process which often leads to confusion for non-radiation oncology professionals as to what type of therapy and/or treatment planning was done,
• Unintentionally support a failure to include freely entered, valuable narrative that should be present in order to clearly document the reasonable and necessary basis for the chosen RT approach(es)

The prescription defining the type, medical necessity, goals and requirements of the treatment plan, including the specific dose constraints to the target and OARs (critical structures) must be present and authenticated by the radiation oncologist. It is strongly recommended that the prescription be labeled as such and easily identifiable within the medical record.

The ultimate decision regarding the medical necessity for a type of RT by the treating radiation oncologist must be documented to justify that therapy.

The IMRT inverse treatment plan must meet prescribed PTV and OAR constraints. It must be signed by the medical physicist or dosimetrist with credentials. It is strongly recommended that the planning document be labeled as such and easily identifiable within the medical record.

Please review this LCD in its entirety for other references to necessary documentation.

The type of treatment planning done and utilized (e.g., forward planned, inverse planned, etc.) must be clearly stated within the medical record.

Target verification must include documentation of the CTV and the PTV as well as documentation of immobilization and patient positioning.

Basic radiation dosimetry is a separate and distinct service. Independent basic dose calculations and verifications for each beam or arc before the patient’s first treatment must be present in the record.

Please see the related billing and coding article for helpful guidance regarding the documentation needed to support the allowable coverage in this LCD as well as the coding for the services provided. Following this guidance is considered necessary to fully operationalize this coverage LCD.

The patient’s record must support the necessity and frequency of treatment. The patient’s past history, chronologic history of their cancer, and recent imaging results must be documented. Also, the patient’s functional status and current performance status (per Karnofsky or ECOG) must be documented. For SRS, the radiosurgery physician must document the clinical aspects of the treatment and the management decisions. A radiation oncologist and medical physicist must document the technical aspects of the treatment and resulting management decisions and authenticate their documentation with an inclusion of their credentials. SRS treatment is to be performed under the direct supervision of a qualified medical physicist and a radiation oncologist. Per CMS guidelines, direct supervision is defined as physician presence in the suite during diagnostic testing services.

Treatment planning for SBRT generally is the same as the processes used for IMRT and 3-D conformal therapy. SBRT treatment planning determines the field size(s), gantry angles and other beam modifications that are needed to properly administer the prescribed dose(s). SBRT may be delivered in 1-5 fractions with each fraction (session) requiring the same precision and localization and image guidance. Any RT course extending beyond 5 sessions is not considered SBRT. SBRT is meant to be a complete course of treatment and not to be used as a boost following a course of conventional fractionated RT.

SBRT might be an alternative to surgery and it might be safer and more effective than conventional RT for certain cancers or target areas. The patient’s medical record must support the reasonable and necessary nature of the treatment. Therefore, supporting clinical records must include not only the patient’s medical history and exam findings, but also current functional status by a performance status score obtained from the KPS scale or the ECOG Performance Status scale. The patient’s general medical condition must reasonably justify aggressive, curative intent RT. The radiation oncologist must evaluate and document the clinical and technical aspects of the planned treatment and the resulting management decisions that have been made for an individual beneficiary. It is obviously also important that the medical record document the technical aspects of treatment planning and delivery, the prescription for the treatment dose to the target and the constraints to any OARs, the actual dose delivered, and the dates of treatment delivery. All of this documentation is key to supporting the reasonable and necessary standard required for coverage.

It is expected that all personnel involved in administering, supervising, and treating patients for the indications outlined in this LCD meet the regulations set forth by each state or district, as well as for Medicare and the Nuclear Regulatory Commission (NRC), as applicable. These personnel include the radiation oncologist or other qualified physician radiation/medical physicist, radiation technologist and radiation assistant. These compliances must be made available when requested.

All radiation oncology therapeutic services will be considered reasonable and necessary only when performed by appropriately trained providers. Hence, a qualified physician for this service is defined as follows: Training and expertise must have been acquired within the framework of an accredited residency and/or fellowship program in the applicable specialty/subspecialty, i.e., Radiation Oncology.

Free standing facilities (office or clinic), hospital based practices, and mobile delivery units affiliated with a place of service (POS) must meet federal and local (state) radiation protection guidelines in regard to patient safety and quality assurance as well as the physician supervision requirements.

Utilization

Performance Scales

ACR^®-ASTRO Practice Parameter for Intensity Modulated Radiation Therapy (IMRT). Practice Guideline. Amended 2014 (Resolution 39); 1-11.

ASTRO Model Policies for Intensity Modulated Radiation Therapy (IMRT), 2015

ASTRO Radiation Oncology Coding Resource, Updated April 1, 2016 (E-Book)

Other Medicare Administrative Contractor LCDs

ACR^®-ASTRO Practice Parameter for Image-Guided Radiation Therapy (IGRT) Revised 2019.

KPS Scale (as above)

ECOG Performance Status Score (as above)

1. ASTRO. Model Policies Intensity Modulated Radiation Therapy (IMRT). Accessed September 7, 2023.

2. ASTRO. Model Policies Stereotactic Radiosurgery (SRS). Accessed September 7, 2023.

3. ASTRO. Model Policies Stereotactic Body Radiation Therapy (SBRT). Accessed September 7, 2023.

4. Hong TS, Pretz JL, Herman JM, et al. ACR appropriateness criteria^®. Anal cancer. Gastrointest Cancer Res. 2014;7(1):4-14.

5. National Comprehensive Cancer Network^® (NCCN^®). Clinical Practice Guidelines in Oncology. Anal carcinoma. V2.2021. Updated V1.2023. Accessed September 7, 2023.

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66. ACR Practice Parameter for Intensity-Modulated Radiation Therapy (IMRT). Accessed September 7, 2023.

• IMRT
• SRS
• SBRT
• SABR