Intensity-modulated radiation therapy (IMRT)

Intensity modulated radiation therapy (IMRT) is an advanced radiation technique employing recent innovations in imaging and computer technology. Physicians at UCSF have used IMRT to treat cancer patients since 1997, giving us more experience with IMRT than most other centers in the United States and the rest of the world. IMRT planning starts with tumor target and normal tissue definition, followed by inverse planning. Using computer optimization, multiple small fields are designed to give a complex and conformal radiation dose distribution, which provides the prescription dose to the tumor target and minimizes dose to regional normal tissues.


When Policy Topic is covered
Intensity modulated radiation therapy may be considered medically necessary as an approach to delivering radiation therapy for patients with cancer of the anus/anal canal.
When dosimetric planning with standard 3-D conformal radiation predicts that the radiation dose to an adjacent organ would result in unacceptable normal tissue toxicity (see Considerations), intensity-modulated radiation therapy (IMRT) may be considered medically necessary for the treatment of cancer of the abdomen and pelvis, including but not limited to:  stomach (gastric);  hepatobiliary tract;  pancreas;  rectal locations; or  gynecologic tumors (including cervical, endometrial, and vulvar cancers).

When Policy Topic is not covered
Intensity-modulated radiation therapy (IMRT) would be considered investigational for all other uses in the abdomen and pelvis. Table PG1 outlines radiation doses generally considered tolerance thresholds for normal structures in the abdomen and pelvis. Dosimetry plans may be reviewed to demonstrate that radiation by 3-dimensional conformal radiotherapy (3D-CRT) would exceed tolerance doses to structures at risk.

Table PG1. Radiation Tolerance Doses for Normal Tissues of the Abdomen and Pelvis
For intensity-modulated radiotherapy (IMRT) to provide outcomes superior to 3D-CRT, there must be a clinically meaningful decrease in the radiation exposure to normal structures with IMRT compared with 3D-CRT. There is no standardized definition for a clinically meaningful decrease in radiation dose. In principle, a clinically meaningful decrease would signify a significant reduction in anticipated complications of radiation exposure. To document a clinically meaningful reduction in dose, dosimetry planning studies should demonstrate a significant decrease in the maximum dose of radiation delivered per unit of tissue, and/or a significant decrease in the volume of normal tissue exposed to potentially toxic radiation doses. While radiation tolerance dose levels for normal tissues are wellestablished, the decrease in the volume of tissue exposed that is needed to provide a clinically meaningful benefit has not been standardized. Therefore, precise parameters for a clinically meaningful decrease cannot be provided.
G6015 Intensity modulated treatment delivery, single or multiple fields/arcs, via narrow spatially and temporally modulated beams, binary, dynamic MLC [multileaf collimator], per treatment session G6016 Compensator-based beam modulation treatment delivery of inverse planned treatment using 3 or more high resolution (milled or cast) compensator, convergent beam modulated fields, per treatment session.
Code 77301 remains valid: 77301 Intensity-modulated radiotherapy plan, including dose-volume histograms for target and critical structure partial tolerance specifications.
The following CPT code may also be used and is to be reported only once per IMRT plan: 77338 Multi-leaf collimator (MLC) device(s) for intensity-modulated radiation therapy (IMRT), design and construction per IMRT plan. Radiotherapy may be an integral component of the treatment of cancers of the abdomen and pelvis. Intensity-modulated radiotherapy (IMRT) has been proposed as a method that allows adequate radiation to the tumor while minimizing the radiation dose to surrounding normal tissues and critical structures.

Description of Procedure or Service
For individuals who have gastrointestinal (GI) tract cancers who receive IMRT, the evidence includes nonrandomized comparative studies and retrospective series. The relevant outcomes are overall survival (OS), disease-specific survival, quality of life (QOL), and treatment-related morbidity. IMRT has been compared with 3-dimensional conformal radiotherapy (3D-CRT) for the treatment of stomach, hepatobiliary, and pancreatic cancers. Evidence has been inconsistent with the outcome of survival, with some studies reporting increased survival among patients receiving IMRT compared with patients receiving 3D-CRT, and other studies reporting no difference between groups. However, most studies found that patients receiving IMRT experienced significantly less GI toxicity compared with patients receiving 3D-CRT. The available comparative evidence, together with dosimetry studies of organs at risk, would suggest that IMRT decreases toxicity compared with 3D-CRT in patients who had GI cancers. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.
For individuals who have gynecologic cancers who receive IMRT, the evidence includes two small randomized controlled trials and several nonrandomized comparative studies. The relevant outcomes are OS, disease-specific survival, QOL, and treatment-related morbidity. There is limited comparative evidence on survival outcomes following IMRT or 3D-CRT. However, results are generally consistent that IMRT reduces GI and genitourinary toxicity. Based on evidence with other cancers of the pelvis and abdomen that are proximate to organs at risk, it is expected that OS with IMRT would be at least as good as 3D-CRT, with a decrease in toxicity. A reduction in GI toxicity is likely to improve the QOL in patients with gynecologic cancer. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.
For individuals who have anorectal cancer who receive IMRT, the evidence includes a small randomized controlled trial (n=20), nonrandomized comparative studies, and case series. The relevant outcomes are OS, disease-specific survival, QOL, and treatment-related morbidity. Survival outcomes have not differed significantly between patients receiving IMRT and 3D-CRT. However, studies have found that patients receiving IMRT plus chemotherapy for the treatment of anal cancer experience fewer acute and late adverse events than patients receiving 3D-CRT plus chemotherapy, primarily in GI toxicity. A reduction in GI toxicity is likely to improve the QOL in patients with anorectal cancer. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.
Input was obtained in 2010 and 2012. It supported the use of IMRT in tumors of the abdomen and pelvis when normal tissues would receive unacceptable doses of radiation. Through a chain of evidence, this reduced toxicity potentially lowers the risk of adverse events (acute and late effects of radiation toxicity). This input and a chain of evidence related to the potential to reduce harms led to the decision that IMRT may be considered medically necessary for the treatment of tumors of the abdomen and pelvis when dosimetric planning with standard 3D-CRT predicts that the radiation dose to an adjacent organ would result in unacceptable normal tissue toxicity.

Conventional External-Beam Radiotherapy
Methods to plan and deliver RT have evolved in ways that permit more precise targeting of tumors with complex geometries. Most early trials used 2-dimensional treatment planning, based on flat images and radiation beams with cross-sections of uniform intensity that were sequentially aimed at the tumor along two or three intersecting axes. Collectively, these methods are termed conventional external-beam radiotherapy.

Three-Dimensional Conformal Radiotherapy
Treatment planning evolved by using 3-dimensional images, usually from computed tomography (CT) scans, to delineate the boundaries of the tumor and discriminate tumor tissue from adjacent normal tissue and nearby organs at risk for radiation damage. Computer algorithms were developed to estimate cumulative radiation dose delivered to each volume of interest by summing the contribution from each shaped beam. Methods also were developed to position the patient and the radiation portal reproducibly for each fraction and immobilize the patient, thus maintaining consistent beam axes across treatment sessions. Collectively, these methods are termed3D-CRT.

Intensity-Modulated Radiotherapy
IMRT uses computer software and CT and magnetic resonance images, to offer better conformality than 3D-CRT because it modulates the intensity of the overlapping radiation beams projected on the target and uses multiple shaped treatment fields. Treatment planning and delivery are more complex, timeconsuming, and labor-intensive for IMRT than for 3D-CRT. The technique uses a multileaf collimator [MLC]), which, when coupled with a computer algorithm, allows for "inverse" treatment planning. The radiation oncologist delineates the target on each slice of a CT scan and specifies the target's prescribed radiation dose, acceptable limits of dose heterogeneity within the target volume, adjacent normal tissue volumes to avoid, and acceptable dose limits within the normal tissues. Based on these parameters and a digitally reconstructed radiographic image of the tumor, surrounding tissues, and organs at risk, computer software optimizes the location, shape, and intensities of the beam ports to achieve the treatment plan's goals.
Increased conformality may permit escalated tumor doses without increasing normal tissue toxicity and thus may improve local tumor control, with decreased exposure to surrounding, normal tissues, potentially reducing acute and late radiation toxicities. Better dose homogeneity within the target may also improve local tumor control by avoiding underdosing within the tumor and may decrease toxicity by avoiding overdosing.
Technologic development has produced advanced techniques that may further improve RT treatment by improving dose distribution. These techniques are considered variations of IMRT. Volumetric modulated arc therapy delivers radiation from a continuous rotation of the radiation source. The principal advantage of volumetric modulated arc therapy is greater efficiency in treatment delivery time, reducing radiation exposure and improving target radiation delivery due to less patient motion. Image-guided RT involves the incorporation of imaging before and/or during treatment to more precisely deliver RT to the target volume.
IMRT methods to plan and deliver RT are not uniform. IMRT may use beams that remain on as MLCs move around the patient (dynamic MLC) or that are off during movement and turn on once the MLC reaches prespecified positions ("step and shoot" technique). A third alternative uses a very narrow, single beam that moves spirally around the patient (tomotherapy). Each method uses different computer algorithms to plan treatment and yields somewhat different dose distributions in and outside the target. Patient position can alter target shape and thus affect treatment plans. Treatment plans are usually based on a single imaging scan, a static 3D-CT image. Current methods seek to reduce positional uncertainty for tumors and adjacent normal tissues by various techniques. Patient immobilization cradles and skin or bony markers are used to minimize day-to-day variability in patient positioning. In addition, many tumors have irregular edges that preclude drawing tight margins on CT scan slices when radiation oncologists contour the tumor volume. It is unknown whether omitting some tumor cells or including some normal cells in the resulting target affects outcomes of IMRT.
Note that the evidence for the following abdominal and pelvic cancers has not yet been reviewed and is beyond the scope of this review: bladder, kidney, ureter, and esophageal cancer and sarcoma.

Regulatory Status
In general, IMRT systems include intensity modulators which control, block, or filter the intensity of radiation; and RT planning systems which plan the radiation dose to be delivered. Fully integrated IMRT systems also are available. These devices are customizable and support all stages of IMRT delivery, including planning, treatment delivery, and health record management. Varian Medical Systems has several 510(k) marketing clearances for high-energy linear accelerator systems that can be used to deliver precision RT such as IMRT. FDA product code: IYE.

Rationale
This evidence review was created in April 2009 and has been updated regularly with searches of the MEDLINE database. The most recent literature update was performed through May 6, 2019.
Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life (QOL), and ability to function-including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.
To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, two domains are examined: the relevance, and the quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Intensity-Modulated Radiotherapy for Cancers of the Abdomen and Pelvis
Multiple-dose planning studies generate 3-dimensional conformal radiotherapy (3D-CRT) and IMRT treatment plans from the same scans and then compare predicted dose distributions within the target area and adjacent organs. Results of such planning studies have shown that IMRT is better than 3D-CRT with respect to conformality to the target and dose homogeneity within the target. Results have also demonstrated that IMRT delivers less radiation to nontarget areas. Dosimetry studies using stationary targets generally confirm these predictions. However, because patients move during treatment, dosimetry with stationary targets only approximate actual radiation doses received. Based on these dosimetry studies, radiation oncologists expect IMRT to improve treatment outcomes compared with those of 3D-CRT.
Comparative studies of radiation-induced adverse events from IMRT vs alternative radiation delivery would constitute definitive evidence of establishing the benefit of IMRT. Single-arm series of IMRT can give insights into the potential for benefit, particularly if an adverse event expected to occur at high rates is shown to decrease significantly. Studies of treatment benefit are also important to establish that IMRT is at least as good as other types of delivery, but absent such comparative trials, it is likely that benefit from IMRT is at least as good as with other types of delivery.
In general, when the indication for IMRT is to avoid radiation to sensitive areas, dosimetry studies have been considered sufficient evidence to demonstrate that harm would be avoided using IMRT. For other indications, such as using IMRT to provide better tumor control, comparative studies of health outcomes are needed to demonstrate such a benefit.

Clinical Context and Test Purpose
The purpose of IMRT in patients who have abdominal or pelvic cancers is to provide a treatment option that is an alternative to or an improvement on existing therapies.
The question addressed in this evidence review is: Does the use of IMRT for the treatment of patients with abdominal and pelvic cancers improve net health outcomes?
The following PICOTS were used to select literature to inform this review.

Patients
The relevant populations of interest are patients with gastrointestinal cancers (eg, stomach, hepatobiliary, and pancreatic cancers), gynecologic cancers (eg, cervical and endometrial cancers), and anorectal cancers who are recommended for radiotherapy (RT).

Interventions
The therapy being considered is IMRT. IMRT uses computer software and magnetic resonance imaging for increased conformality, permitting the delivery of higher doses of radiation to the tumor while limiting the exposure of surrounding normal tissues.

Comparators
The following therapy is currently being used: 3D-CRT. 3D-CRT uses 3dimensional images typically from computed tomography to discriminate tumor tissue from adjacent normal tissue and nearby organs. Computer algorithms are used to estimate radiation doses being delivered to each treatment segment.

Outcomes
The general outcomes of interest are overall survival (OS), recurrence (locoregional control), QOL, and treatment-related adverse events (eg, toxicity). Toxicity can be assessed using the U.S. Department of Health and Human Services grading criteria for adverse events (1=mild, 2=moderate, 3=severe or medically significant, 4=life-threatening, and 5=death).

Timing
Toxicity and recurrence can be assessed acutely and long-term.

Setting
IMRT is usually administered in a hospital or free-standing facility.

Gastrointestinal Tract Cancers Stomach
Boda-Heggemann et al (2009) evaluated the efficacy and safety of 2 different adjuvant chemoradiotherapy regimens using 3D-CRT or IMRT in 2 consecutive cohorts who underwent primarily D2 resection for gastric cancer. 1, A subsequent report (2013) from this group included 27 3D-CRT patients and 38 IMRT patients. 2, The cohorts were generally well-matched, with American Joint Committee on Cancer advanced stage (II-IV) disease. Most (96%) who received 3D-CRT were treated with 5-fluorouracil plus folinic acid. Patients in the IMRT cohort received capecitabine plus oxaliplatin (70%) or 5-fluorouracil plus folinic acid (30%). Radiation was delivered to a total prescribed dose of 45 gray (Gy) at 1.8 Gy per fraction. In the 3D-CRT cohort, 5 patients received less than 45 Gy because of treatment intolerance. Two patients in the IMRT cohort did not tolerate the full course, and 1 patient received 47 Gy. Overall, the IMRT plus chemotherapy regimen decreased renal toxicity with a trend toward improved survival (see Table  1). However, interpretation of the safety and efficacy of IMRT in this study is limited by differences in the chemotherapy regimens.  (2016) reported on a prospective comparative study of GI toxicity in patients treated with concurrent chemoradiotherapy plus IMRT or 3D-CRT for treatment of borderline resectable pancreatic cancer. 4, Treatment selection was by patient choice after consultation with a radiation oncologist. Symptoms of dyspepsia, nausea or vomiting, and diarrhea did not differ between groups. Upper endoscopy revealed more patients with gastroduodenal ulcers in the 3D-CRT group than in the IMRT group (see Table  2). OS was longer in the IMRT group than in the 3D-CRT group but the interpretation of survival results was limited by the risk of bias in this nonrandomized study.
Prasad et al (2016) retrospectively reviewed charts of patients with locally advanced pancreatic cancer who were treated with IMRT (n=134) or 3D-CRT (n=71). 5, Propensity score analysis was performed to account for potential confounding variables, including age, sex, radiation dose, RT field size, and concurrent RT. Grade 2 GI toxicity occurred in significantly more patients treated with 3D-CRT than with IMRT (propensity score odds ratio, 1.26; 95% confidence interval, 1.08 to 1.45; p=0.001; see Table 2). Hematologic toxicity and median survival were similar in the two groups.

Section Summary: GI Tract Cancers
The evidence on IMRT for GI tract cancers includes nonrandomized comparative studies. IMRT has been compared with 3D-CRT for the treatment of stomach, hepatobiliary, and pancreatic cancers, with some studies reporting longer OS and decreased toxicity with IMRT. For the treatment of stomach cancer, IMRT improved survival compared with 3D-CRT. However, this study also used different chemotherapy regimens, confounding the results. The evidence on hepatobiliary cancer includes a series of historical controls that found an increase in median survival with no difference in toxicity. Two comparative studies (one prospective, one retrospective) were identified on IMRT for pancreatic cancer. The prospective comparative study found an increase in survival with a reduction in GI toxicity, while the retrospective study found a decrease in GI toxicity. Although most studies were limited by their retrospective designs and changes in practice patterns over time, the available evidence would suggest that IMRT improves survival and decreases toxicity better than 3D-CRT in patients with GI cancers. vomiting and acute GI and genitourinary (GU) toxicity were significantly higher in the 3D-CRT group (see Table 3).

Randomized Controlled Trials
Gandhi et al (2013) reported on a prospective randomized study that compared whole-pelvis IMRT with whole-pelvis 2-dimensional RT in 44 patients with locally advanced cervical cancer. 7, Each treatment arm had 22 patients. The OS rate at 27 months was 88% with IMRT and 76% with 2-dimensional RT (p=0.645). However, fewer grade 2, 3, or 4 GI toxicities were experienced in the IMRT group than in the conventional RT group (see Table 3). There was no significant difference between IMRT and 2-dimensional RT in the incidence of acute hematologic toxicities. Overall, the IMRT patients had lower rates of chronic GI toxicities (p=0.002) than the 2-dimensional RT patients.

Section Summary: Gynecologic Cancers
The evidence on IMRT for gynecologic cancers includes 2 small RCTs (<50 patients each) and several nonrandomized comparative studies. There is limited comparative evidence on survival outcomes following IMRT or 3D-CRT. However, available results have generally been consistent that IMRT reduces GI and GU toxicity. Based on evidence with other cancers of the pelvis and abdomen in close proximity to organs at risk, it is expected that OS with IMRT would be at least as good as 3D-CRT, with a decrease in toxicity.

Randomized Controlled Trials
Rattan et al (2016) conducted a small (n=20) RCT assessing IMRT for the treatment of anal canal cancer. 11, Grade 3 GI toxicity during treatment was not observed in any patients in the IMRT group but was seen in 60% of patients treated with 3D-CRT (p=0.010). Hematologic grade 3 toxicity was not seen in any patients treated with IMRT but was noted in 20% of patients treated with 3D-CRT (p=0.228). Other parameters indicating better tolerance to treatment with IMRT were reduced need for parenteral fluid (10% vs 60%, p=0.019) and blood transfusion (0% vs 20%, p=0.060).

Nonrandomized Comparative Studies
Sun et al (2017) reported on a comparative analysis of the National Cancer Database of IMRT with 3D-CRT for the treatment of rectal adenocarcinoma. 12 Table 4). However, patients treated with IMRT had a higher risk of positive margins. Multivariate analysis found no significant differences between the treatments for pathologic downstaging, unplanned readmission, 30-day mortality, or long-term survival. This study used unplanned readmission as a surrogate measure of adverse events but could not assess acute or late toxicity.  Table 5). Four-year OS and disease-free survival did not differ between the two groups. Multivariate analysis found IMRT to be an independent predictor of local failure-free survival (hazard ratio, 0.35; 95% confidence interval, 0.11 to 0.95; p=0.042). In a retrospective review of 89 consecutive patients (52 IMRT, 37 3D-CRT), Chuong et al (2013) found that 3-year OS, progression-free survival, locoregional control, and colostomy-free survival did not differ significantly between patients treated with IMRT or with 3D-CRT (p>0.1). 14, Adverse events with 3D-CRT were more frequent and severe and required more treatment breaks than IMRT (11 days vs 4 days; p=0.006) even though the median duration of treatment breaks did not differ significantly ( 15, They reported that two-year OS, distant metastases-free survival, and locoregional recurrence-free survival did not differ significantly between patients in the IMRT and CRT groups.

Table 5. Grade 3 or Greater Toxicity Following Chemoradiotherapy for Rectal Cancer
Dewas et al (2012) retrospectively reviewed 51 patients with anal cancer treated with IMRT (n=24) or with 3D-CRT (n=27). 16, Outcomes also did not differ significantly between patients in the IMRT and 3D-CRT groups in two-year OS, locoregional relapse-free survival, and colostomy-free survival. Grade 3 acute toxicity occurred in 11 IMRT patients and in 10 3D-CRT patients. Pepek et al (2010) retrospectively analyzed of toxicity and disease outcomes associated with IMRT in 47 patients with anal cancer. 18, Thirty-one patients had squamous cell carcinoma. IMRT was prescribed to a dose of at least 54 Gy to areas of gross disease at 1.8 Gy per fraction. Forty (89%) patients received concurrent chemotherapy with various agents and combinations. The 2-year actutimes OS for all patients was 85%. Eight (18%) patients required treatment breaks. Toxicities included grade 4 leukopenia (7%) and thrombocytopenia (2%); grade 3 leukopenia (18%) and anemia (4%); and grade 2 skin toxicity (93%). These rates were lower than those reported in previous trials of chemoradiation, where grade 3 or 4 skin toxicity was noted in about 50% of patients and grade 3 or 4 GI toxicity noted in about 35%. In addition, the rate of treatment breaks was lower than in many studies; and some studies of chemoradiation included a break from RT.

Section Summary: Anorectal Cancer
The evidence on IMRT for anorectal cancer includes a small RCT with 20 patients, nonrandomized comparative studies, and case series. Survival outcomes have not differed significantly between IMRT and 3D-CRT. Studies have found that patients receiving IMRT plus chemotherapy for the treatment of anal cancer experience fewer acute and late adverse events than patients receiving 3D-CRT plus chemotherapy, primarily in GI toxicity.

Summary of Evidence
For individuals who have GI tract cancers who receive IMRT, the evidence includes nonrandomized comparative studies and retrospective series. The relevant outcomes are OS, disease-specific survival, QOL, and treatment-related morbidity. IMRT has been compared with 3D-CRT for the treatment of stomach, hepatobiliary, and pancreatic cancers. Evidence has been inconsistent with the outcome of survival, with some studies reporting increased survival among patients receiving IMRT compared with patients receiving 3D-CRT, and other studies reporting no difference between groups. However, most studies found that patients receiving IMRT experienced significantly less GI toxicity compared with patients receiving 3D-CRT. The available comparative evidence, together with dosimetry studies of organs at risk, would suggest that IMRT decreases toxicity compared with 3D-CRT in patients who had GI cancers. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.
For individuals who have gynecologic cancers who receive IMRT, the evidence includes two small RCTs and several nonrandomized comparative studies. The relevant outcomes are OS, disease-specific survival, QOL, and treatment-related morbidity. There is limited comparative evidence on survival outcomes following IMRT or 3D-CRT. However, results are generally consistent that IMRT reduces GI and genitourinary toxicity. Based on evidence with other cancers of the pelvis and abdomen that are proximate to organs at risk, it is expected that OS with IMRT would be at least as good as 3D-CRT, with a decrease in toxicity. A reduction in GI toxicity is likely to improve the QOL in patients with gynecologic cancer. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.
For individuals who have anorectal cancer who receive IMRT, the evidence includes a small RCT (n=20), nonrandomized comparative studies, and case series. The relevant outcomes are OS, disease-specific survival, QOL, and treatment-related morbidity. Survival outcomes have not differed significantly between patients receiving IMRT and 3D-CRT. However, studies have found that patients receiving IMRT plus chemotherapy for the treatment of anal cancer experience fewer acute and late adverse events than patients receiving 3D-CRT plus chemotherapy, primarily in GI toxicity. A reduction in GI toxicity is likely to improve the QOL in patients with anorectal cancer. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Clinical Input From Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

Input
In response to requests, input was received from 1 physician specialty society (4 reviewers) and 3 academic medical centers while this policy was under review in 2012. Input was mixed but there was support for use of intensity-modulated radiotherapy (IMRT) in a number of cancers discussed herein. In general, this support was based on normal tissue constraints for radiation doses and whether these dose constraints could not be met without IMRT.

Input
In response to requests, input was received from 1 physician specialty society (2 reviewers) and 3 academic medical centers while this policy was under review in 2010. There was support for use of IMRT in a number of cancers discussed herein. In general, this support was based on normal tissue constraints for radiation doses and whether these dose constraints could not be met without IMRT.

Gynecologic Cancers
For cervical cancer, the NCCN guidelines (v.4.2019) indicate IMRT "may be helpful in minimizing the dose to the bowel and other critical structures in the posthysterectomy setting and in treating the para-aortic nodes when necessary" such as "when high doses are required to treat gross disease in regional lymph nodes." 22, IMRT "should not be used as routine alternatives to brachytherapy for treatment of central disease in patients with an intact cervix." The guidelines also mention that "very careful attention to detail and reproducibility (including consideration of target and normal tissue definitions, patient and internal organ motion, soft tissue deformation, and rigorous dosimetric and physics quality assurance) is required for proper delivery of IMRT and related highly conformal technologies." The NCCN guidelines (v.3.2019) on uterine endometrial cancer state that radiotherapy for uterine neoplasms includes external-beam radiotherapy and/or brachytherapy but that IMRT may be considered "for normal tissue sparing." 23

American College of Radiology
The American College of Radiology Appropriateness Criteria (2014) recommended that IMRT is usually appropriate to treat anal cancer if performed outside of a protocol setting but is still undergoing study. 27, The College also noted the most appropriate radiation dose for anal cancer has not been determined and quality control and technical problems are considered challenging with IMRT (eg, in target volume contouring).

U.S. Preventive Services Task Force Recommendations
Not applicable.

Medicare National Coverage
There is no national coverage determination. In the absence of a national coverage determination, coverage decisions are left to the discretion of local Medicare carriers.

Ongoing and Unpublished Clinical Trials
Some currently ongoing and unpublished trials that might influence this review are listed in Table 6. Billing Coding/Physician Documentation Information 77301 Intensity modulated radiotherapy plan, including dose-volume histograms for target and critical structure partial tolerance specifications 77338 Multi-leaf collimator (MLC) device(s) for intensity modulated radiation therapy (IMRT), design and construction per IMRT plan 77385 Intensity modulated radiation treatment delivery (IMRT), includes guidance and tracking, when performed; simple 77386 Intensity modulated radiation treatment delivery (IMRT), includes guidance and tracking, when performed; complex 77387 Guidance for localization of target volume for delivery of radiation treatment delivery, includes intrafraction tracking, when performed G6001 Ultrasonic guidance for placement of radiation therapy fields G6002 Stereoscopic x-ray guidance for localization of target volume for the delivery of radiation therapy G6015 Intensity modulated treatment delivery, single or multiple fields/arcs, via narrow spatially and temporally modulated beams, binary, dynamic MLC, per treatment session G6016 Compensator-based beam modulation treatment delivery of inverse planned treatment using 3 or more high resolution (milled or cast) compensator, convergent beam modulated fields, per treatment session The Centers for Medicare and Medicaid Services (CMS) decided not to implement this change for 2015 and instead created HCPCS G codes for the radiotherapy codes being deleted 12/31/14. So the following codes may be used for IMRT: G6015: Intensity modulated treatment delivery, single or multiple fields/arcs, via narrow spatially and temporally modulated beams, binary, dynamic MLC [multileaf collimator], per treatment session G6016: Compensator-based beam modulation treatment delivery of inverse planned treatment using 3 or more high resolution (milled or cast) compensator, convergent beam modulated fields, per treatment session.
Code 77301 remains valid: 77301: Intensity-modulated radiotherapy plan, including dose-volume histograms for target and critical structure partial tolerance specifications. No policy statement changes. 11/1/12 No policy statement changes. 12/13/12 Policy statement changed to state that IMRT may be considered medically necessary for all anal cancers (not limited to squamous cell carcinoma). Policy statement changed to state that IMRT may be considered medically necessary for the treatment of tumors of the abdomen and pelvis when dosimetric planning predicts the volume of small intestine receiving doses >45 Gy with standard 3-D conformal radiation would result in unacceptable risk of small intestine injury. Added a policy statement that IMRT would be considered investigational for all other uses in the abdomen and pelvis. Paragraph added to policy guidelines regarding toxic radiation dose to tissues and definition of a clinically significant decrease in radiation dose. 2 State and Federal mandates and health plan contract language, including specific provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The medical policies contained herein are for informational purposes. The medical policies do not constitute medical advice or medical care. Treating health care providers are independent contractors and are neither employees nor agents Blue KC and are solely responsible for diagnosis, treatment and medical advice. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, photocopying, or otherwise, without permission from Blue KC.