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MP 8.01.13 Accelerated Breast Irradiation after Breast-Conserving Surgery for Early Stage Breast Cancer and Breast Brachytherapy as Boost with Whole-Breast Irradiation

Medical Policy    
Section
Therapy 
Original Policy Date
7/31/96
Last Review Status/Date
Reviewed with literature search/12:2014
Issue
12:2014
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Disclaimer

Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.


Description

 

Breast Conservation Therapy

For patients diagnosed with stage 1 or 2 breast tumors, survival after breast-conservation therapy (BCT) is equivalent to survival after mastectomy. BCT is a multimodality treatment that initially comprised BCS to excise the tumor with adequate margins, followed by whole-breast external-beam radiotherapy (EBRT) administered as 5 daily fractions per week over 5 to 6 weeks. Local boost irradiation to the tumor bed often is added to WBI to provide a higher dose of radiation at the site where recurrence most frequently occurs. For some patients, BCT also includes axillary lymph node dissection, sentinel lymph node biopsy, or irradiation of the axilla. A number of RCTs have demonstrated that the addition of radiotherapy after BCS reduces recurrences and mortality. In an expanded update of an individual-level meta-analysis, the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) reported that radiotherapy halved the annual recurrence rate after 10 years for women with node-negative disease (N=7287), from 31.0% for those not receiving radiotherapy to 15.6% for those receiving it.(1) It also reduced the 15-year risk of breast cancer death from 20.5% to 17.2% (p=0.005). For women with node-positive disease (n=1050), radiotherapy reduced the 1-year recurrence risk from 26.0% to 5.1%. Radiotherapy also reduced the 15- year risk of breast cancer death from 51.3% to 42.8% (p=0.01).

Consequently, radiotherapy is generally recommended following BCS. A potential exception is for older women at low risk of recurrence. For example, current National Comprehensive Cancer Network guidelines state that women aged 70 or older may omit radiotherapy if they have estrogen-receptor positive, T1 tumors, clinically negative lymph nodes, and plans to take adjuvant endocrine therapy.(2) However, a 2012 study has raised questions about this recommendation.(3)

Controversy continues on the length of follow-up needed to determine whether APBI is equivalent to WBI (for more information, see the 2013 TEC Assessment on Accelerated Radiotherapy After Breast-Conserving Surgery for Early Stage Breast Cancer(4). Because recurrences are relatively rare among lowrisk early breast cancer patients, it may take considerable time for enough recurrences to occur to provide sufficient power for comparing recurrence rates across radiotherapy approaches. Additionally, radiationinduced adverse cardiovascular effects and radiation-induced nonbreast cancers tend to occur 10 or more years after treatment.(5-7) For AWBI, some 10-year data are available. However, for newer approaches, the issue may be resolved by statistical issues rather than biological ones. For example, in the large NSABP-39/RTOG 0413 trial comparing WBI and APBI (see Table 2), enrollment has reached the revised target of 4216. Trial duration (barring early termination) is determined by the occurrence of a prespecified number (175) of in-breast recurrences. The researchers expect that reaching that number of recurrences will take approximately 10 years.

Currently, most patients diagnosed with stage 1 or 2 breast cancer are offered a choice of BCT or modified radical mastectomy, but BCT is selected less often than expected. Studies have shown that those living farthest from treatment facilities are least likely to select BCT instead of mastectomy and most likely to forgo radiotherapy after BCS.(8-10) A study using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results tumor registries from 1992 to 2002 examined how many women with early stage (1 or 2) breast cancer received radiotherapy within 4 months following BCS.(11) After adjusting for age, they found that, in 2002, 30.8% of Caucasian women and 44.7% of African-American women had not received radiotherapy. Furthermore, these rates had increased from 24.7% for Caucasian and 34.0% for African-American women in 1992.

Given that duration and logistics appear to be barriers to completion of treatment, there has been interest in developing shorter radiotherapy regimens. Two approaches have been explored.

The first method is to provide the same dose to the whole breast in a shorter time by increasing the dose provided per treatment (hypofractionation). This approach was initially avoided out of concern that increasing doses might induce more severe adverse events from radiation exposure, thus tipping the balance between benefits and harms. More recent research, some of which is highlighted below, has allayed most of these concerns. AWBI has been adopted widely in Canada and Europe.

The second approach to reducing radiotherapy treatment time is APBI. It differs from conventional WBI in several ways. First, the radiation only targets the segment of the breast surrounding the area where the tumor was removed, rather than the entire breast. This approach was based in part on the finding that recurrences are more likely to occur close to the tumor site rather than elsewhere in the breast. Second, the duration of treatment is 4 to 5 days (or 1 day with intraoperative radiotherapy) rather than 5 to 6 weeks, because radiation is delivered to the tumor bed in fewer fractions at larger doses per fraction. Third, radiation dose is intrinsically less uniform within the target volume when APBI uses brachytherapy (ie, the implantation of radioactive material directly in the breast tissue).

The major types of radiotherapy used after BCS are outlined in Table 1. They differ in their techniques, instrumentation, dose delivery, and possibly in their outcomes.

Table 1. Major Types of Radiation Therapy Following Breast-Conserving Surgerya

Radiation Type

Accelerated?

Whole or Partial Breast

External Beam or Brachytherapy

Approximate Duration of Treatment

Published RCTs; Length of Follow-Up

Conventional whole-breast irradiation

No

Whole

External beam

5-6 wk

Multiple; >15 y

Accelerated whole-breast irradiation

Yes

Whole

External beam

3 wk

4; 10 y

Interstitial APBIb

Yes

Partial

Brachytherapy

1 wk

2; 5.4 y

Balloon APBIc

Yes

Partial

Brachytherapy

1 wk

0

External-beam APBId

Yes

Partial

External beam

1 wk

0

Intraoperative APBIe

Yes

Partial

Not applicable

1 d

1; 5 y

a Noninvasive breast brachytherapy using Accuboost® has been described by the manufacturer as capable of delivering APBI, but no studies on this indication were found.

b Interstitial brachytherapy entails placement of multiple hollow needles and catheters to guide placement of the radioactive material by a remote afterloading device. It is more difficult to perform than other types of brachytherapy and has a steep learning curve.

c Balloon brachytherapy, eg, Mammosite®, entails inserting a balloon into the tumor bed, inflating the balloon, confirming its position radiographically, and then using a remote afterloader to irradiate the targeted area. Some brachytherapy systems combine aspects of interstitial and balloon brachytherapy.

d External-beam APBI is delivered in the same way as conventional or accelerated whole-breast radiotherapy but to a smaller area. All 3 external-beam regimens can use 3-dimensional, conformal radiation therapy or intensity-modulated radiation therapy.

e Intraoperative APBI is performed during breast-conserving surgery, when a single dose of radiation is delivered to the exposed tumor bed.

To appreciate the differences among radiotherapy techniques, it is useful to understand attributes of radiation delivery. The goals of cancer radiotherapy are usually to provide the tumor or tumor bed with a high dose of homogeneous radiation (eg, all parts of the tumor cavity receive close to the targeted dose). Areas adjacent to the tumor may be treated with a lower dose of radiation (eg, with whole-breast irradiation, to treat any unobserved cancerous lesions). Radiation outside the treatment area should be minimal or nonexistent. The goal is to target the tumor or adjacent areas at risk of harboring unseen cancer with an optimum dose, while avoiding healthy tissues.

Brachytherapy Boost with Whole-Breast Irradiation

Brachytherapy can also be used as an alternative to external-beam radiation therapy to deliver boost radiation therapy combined with whole-breast external-beam radiation therapy. Most of the studies of local boost brachytherapy use temporarily implanted needles, wires, or seeds after patients recovered from surgery and completed whole-breast radiation therapy.

Regulatory Status

The MammoSite® Radiation Therapy System (Proxima Therapeutics; Alpharetta, GA), the first device specifically designed for breast brachytherapy,(12) was FDA-cleared under a 510(k) premarket notification in 2002. Its intended use is ‘‘to provide brachytherapy when the physician chooses to deliver intracavitary radiation to the surgical margins following lumpectomy for breast cancer.’’(13)

Since 2002, several other devices for breast brachytherapy have been FDA-cleared for marketing through the 510(k) process as substantially equivalent to predicate devices (eg, Axxent® Electronic Brachytherapy System [Xoft; San Jose, CA], Strut-Adjusted Volume Implant [SAVI™] Applicator Kit [Biolucent (now Cianna Medical); Aliso Viejo, CA], Contura® Multi-Lumen Balloon Source Applicator for Brachytherapy [SenoRx; Aliso Viejo, CA], ClearPath™ Adjustable Multi-Catheter Source Applicator [North American Scientific; Chatsworth, CA], Intrabeam® System [Carl Zeiss Surgical, GmbH; Oberkochen, Germany]). Each includes an FDA-required warning that the safety and effectiveness of the device “as a
replacement for whole-breast irradiation in the treatment of breast cancer has not been established.”

Although the Intrabeam® System (discussed further below; see Intraoperative Brachytherapy subsection) is subject to FDA regulation, it does not fall under the regulatory purview of the U.S. Nuclear Regulatory Commission. In some states, participation of radiation oncologists in delivering radiation is not required.


Policy

 

When using radiation therapy after breast-conserving surgery (BCS) for early stage breast cancer:

Accelerated whole-breast irradiation (AWBI) may be considered medically necessary for patients who meet the following conditions:

  • invasive carcinoma of the breast. Exclude disease involving the margins of excision; tumors greater than 5 cm in diameter; breast width greater than 25 cm at posterior border of medial and lateral tangential beams.
  • negative lymph nodes
  • technically clear surgical margins

AWBI is considered investigational in all other situations involving treatment of early stage breast cancer after BCS.

Interstitial or balloon brachytherapy may be considered medically necessary for patients undergoing initial treatment for stage 1 or 2 breast cancer when used as local boost irradiation in patients who are also treated with BCS and whole-breast external-beam radiotherapy.

Accelerated partial-breast irradiation (APBI), including interstitial APBI, balloon APBI, external-beam APBI, noninvasive brachytherapy using Accuboost®, and intra-operative APBI, is considered investigational.

Noninvasive brachytherapy using Accuboost® for patients undergoing initial treatment for stage 1 or 2 breast cancer when used as local boost irradiation in patients who are also treated with BCS and wholebreast external-beam radiotherapy is considered investigational.


 

Policy Guidelines

Electronic brachytherapy is considered a type of balloon brachytherapy that can be used to deliver APBI.

There are CPT codes for placement of radiotherapy afterloading catheters:

19296: Placement of radiotherapy afterloading expandable catheter (single or multichannel) into the breast for interstitial radioelement application following partial mastectomy, includes imaging guidance; on date separate from partial mastectomy

19297: concurrent with partial mastectomy (List separately in addition to code for primary procedure)

19298: Placement of radiotherapy afterloading brachytherapy catheters (multiple tube and button type) into the breast for interstitial radioelement application following (at the time of or subsequent to) partial mastectomy, includes imaging guidance.

Specific CPT radiology codes exist for application of brachytherapy radiation sources (codes 77776-77787).

Since July 2007, there has been a CPT category III code specific to electronic brachytherapy:

0182T: High dose rate electronic brachytherapy, per fraction

 


Benefit Application

 

BlueCard/National Account Issues

State or federal mandates (e.g., FEP) may dictate that all devices approved by the U.S. Food and Drug Administration (FDA) may not be considered investigational. Therefore, FDA-approved devices may be assessed on the basis of their medical necessity.


Rationale

This policy, which addresses accelerated breast irradiation following breast-conserving surgery (BCS) for early stage breast cancer, is based on several TEC Assessments, the most recent of which was released in 2013.4 The most recent literature search update covered the period through November 3, 2014.

Accelerated Whole-Breast Irradiation

Four randomized controlled trials (RCTs) and 1 nonrandomized study compared accelerated whole-breast radiotherapy to 5-week whole-breast radiotherapy.(14-19) Two RCTs directly compared a 5-week to a 3-week regimen.(15,17,18) Both were prospective noninferiority trials with noninferiority margins of 5 percentage points for local or locoregional recurrence in the accelerated group at 5 (1-sided α=0.02515 or 0.0517 ) or 10 years (1-sided α=0.02518 ). Although the trials differed in specific fractionation schedules and patient characteristics, they reported similar ipsilateral local recurrence rates (ie, cancer recurrence in the same breast) across treatment arms.

The first RCT (Standardisation of Breast Radiotherapy [START] B; 2008), from the U.K., included women with stage 1-3 tumors (N=2215).(15) Approximately 75% of the women had negative lymph nodes, and approximately 42% had a radiation boost to the tumor bed. Randomization was stratified for hospital, type of surgery (8% underwent mastectomy), and plans for tumor bed boost. Systemic therapy, primarily tamoxifen, was used by some patients and appeared to be evenly distributed across treatment groups. Treatment arms compared a total dose of 40 Gy in 15 fractions over 3 weeks with 50 Gy in 25 fractions over 5 weeks. The primary efficacy outcome was locoregional relapse (relapse in ipsilateral breast or chest wall and or in ipsilateral axilla or supraclavicular fossa if previously irradiated) at 5 years. At median follow-up of 6.0 years (interquartile range [IQR], 5.0-6.2), estimated 5-year locoregional tumor relapse rate was 2.2% (95% confidence interval [CI], 1.3 to 3.1) in the 40 Gy group and 3.3% (95% CI, 2.2 to 4.5) in the 50 Gy group, for an absolute difference of -0.7% (95% CI, -1.7% to 0.9%). Hazard ratios (HRs) for 40 Gy accelerated whole-breast radiotherapy versus conventional whole-breast radiotherapy were not statistically significant (using the log-rank test) for local or locoregional relapse. There were statistically significant differences between the 2 treatment regimens for distant relapse and overall survival (OS), with relapse less frequent and survival longer for the 40 Gy accelerated whole-breast irradiation (AWBI) group. This unexpected difference between treatment arms began to appear at about 1 year; trial authors speculated that the difference may have been due to chance and may have changed with longer follow-up.

Subsequent publications provided additional results for both START trials (ie, START A, which compared two 5-week whole breast radiotherapy regimens, and START B). Hopwood et al (2010) examined patient-reported breast, arm, and shoulder symptoms, as well as body image, over 5 years of follow-up.(20) There was no evidence that providing radiotherapy in fewer, larger fractions increased the incidence of these adverse events or adversely affected body image. Haviland et al (2013) reported 10-year relapse, survival, and adverse event outcomes (median follow-up, 9.9 years [IQR, 7.5-10.1]).(21) Locoregional relapse did not differ significantly between the 2 treatment groups: 4.3% (95% CI, 3.2 to 5.9) for the AWBI group and 5.5% (95% CI, 4.2 to 7.2) for the standard whole-breast radiotherapy group (HR=0.77 [95% CI, 0.51 to 1.16]; p=0.21). However, breast shrinkage, telangiectasia, and breast edema were significantly less common in the AWBI group. These effects were assessed by physician, photographic comparison with baseline, and patient report. Distant relapse (p=0.014), any breast-cancer-related event (local, regional, or distant relapse, breast cancer death, contralateral breast cancer; p=0.022), and all-cause mortality (p=0.042) were significantly less common in the AWBI group.

The second RCT, from Canada, compared AWBI and whole-breast irradiation (WBI) in women with lymph node‒negative stage 1-3 tumors.(17,18) Of 2429 eligible patients, 51% agreed to participate in the trial. Intention-to-treat (ITT) analysis was used. Treatment arms compared a total dose of 42.5 Gy in 16 fractions over 3 weeks with 50 Gy in 25 fractions over 5 weeks. Boost radiation was not used. Five-year local recurrence-free survival was 97.2% in the accelerated arm and 96.8% in the conventional arm (absolute difference: 0.4% [95% CI, -1.5% to 2.4%). Ten-year local recurrence was 6.2% for the accelerated arm and 6.7% for the conventional arm (absolute difference: -0.5% [95% CI, -2.5% to 3.5%). At 5 or 10 years, local recurrence rates with AWBI were not worse than conventional WBI, when applying a noninferiority margin of 5%. In prespecified subgroup analyses, treatment effects were similar by age, tumor size, estrogen-receptor status, and chemotherapy use (48% had no systemic therapy). However, local recurrence at 10 years for patients with high-grade tumors (post hoc analysis22 ) was 4.7% for the conventional WBI arm and 15.6% for the AWBI arm. The absolute difference was -10.9 percentage points (95% CI, -19.1 to -2.8; test for interaction, p=0.01).

A 2010 Cochrane review, entitled “Fraction Size in Radiation Treatment for Breast Conservation in Early Breast Cancer,”(23) included a systematic review based on the 4 RCTs described above. The authors concluded:

“We have evidence from four low to medium quality randomised trials that using unconventional fractionation regimens (greater than 2 Gy per fraction) does not affect local recurrence, is associated with decreased acute toxicity and does not seem to affect breast appearance or late toxicity for selected women treated with breast conserving surgery.”

A large retrospective study compared cardiac toxicity in patients with left-sided, early stage breast cancer who received conventional with accelerated whole-breast radiotherapy.(24,25) Chan et al (2014) in Canada reviewed medical database records of 2706 patients who received conventional (n=2221) or accelerated (n=485) WBI. Cardiotoxic chemotherapy regimens were similar between groups. At a median follow-up of 14.2 years, there was no statistical difference in cardiac hospitalization or cardiac mortality, breast cancer mortality, or overall mortality. Results were similar for 2628 patients with right-sided tumors. This study was not designed to capture outcomes of moderate or mild cardiac toxicity.

Several authors have examined AWBI in patients with ductal carcinoma in situ (prospective cohort studies(26) and retrospective reviews(27,28) [total N=2152]). With a median follow-up of 9 years, 1 retrospective study reported estimated 10-year local recurrence-free survival of 89% in 638 patients who received AWPI and 86% in 971 patients who received conventional WBI (log rank test, p=0.03).(27) This result requires replication in prospective, randomized trials before deviation from patient selection criteria derived from the Canadian study (described above) can be considered.

Section Summary

The overall body of evidence on AWBI compared with conventional WBI indicates that local recurrence rates with accelerated whole-breast radiotherapy were not worse than conventional WBI in patients meeting criteria of the Canadian trial, when applying a noninferiority margin of 5%. Longer follow-up is needed for the U.K. trial. Based on 14-year retrospective data, severe cardiac toxicity with AWBI for leftsided breast cancers may not be increased compared with conventional WBI.

Patient selection is key, and, at this point, only patients similar to those in the Canadian trial should be considered for this therapy. Outcomes could differ in women with other disease characteristics. Patients in this trial all had invasive carcinoma of the breast with negative lymph nodes and surgical margins, and they did not have a radiotherapy boost to the tumor site. Exclusion criteria included “invasive disease or ductal carcinoma in situ (DCIS) involving the margins of excision, tumors that were larger than 5 cm in diameter, and a breast width of more than 25 cm at the posterior border of the medial and lateral tangential beams, which could increase the heterogeneity of the radiation dose to the breast.” Lymph node status was determined by axillary dissection, but subsequent reports suggested that sentinel lymph node biopsy is likely to be as effective (eg, see James et al [2010](23) ). Despite the fact that 71% of women were estrogen-receptor positive, only 41% took tamoxifen.

Patients selecting accelerated whole-breast radiotherapy should be told that, although current evidence on this radiotherapy regimen is strong, it is not as strong as that for conventional WBI. Additional RCTs or longer follow-up could uncover additional concerns. Some potential adverse events, such as cardiac ischemia, may take longer to become evident. This accelerated whole-breast regimen has been widely used outside the United States without substantial reports of major adverse events. Potential patients should be carefully selected and given full information.

Accelerated Partial-Breast Irradiation

Six RCTs(29-38) and 9 nonrandomized comparative studies(39-50) evaluated interstitial, external-beam, or intraoperative accelerated partial-breast irradiation (APBI) compared with conventional WBI. Several of these studies were included in a 2014 meta-analysis by Kong et al that compared APBI (various methods) with WBI.(51)
Literature was searched through June 2012, and 11 comparative studies were included (4 RCTs, 2 retrospective and 5 prospective cohort studies). APBI methods included interstitial brachytherapy (5 studies), balloon brachytherapy (3 studies), intraoperative radiotherapy (1 study), external-beam radiotherapy (EBRT; 1 study), and multiple techniques (1 study). Median follow-up was 5 years (range, 5 months to 12 years). A small risk of publication bias was detected. Fixed effects meta-analysis of 10 studies (total N=4995) showed greater odds of local recurrence in patients who received APBI compared with patients who received WBI (pooled odds ratio [OR], 1.54 [95% CI, 1.15 to 2.06]; p=0.004; I2 =0%). Meta-analysis of 5 studies (total N not reported) showed greater odds of axillary failure in patients who received APBI (pooled OR=2.52 [95% CI, 1.72 to 3.68]; p<0.001; I2 not reported). Meta-analyses of other outcomes showed no statistical differences in odds of distant metastases, OS, and disease-free survival. Given the heterogeneity of APBI methods, comparative efficacy of which is currently unknown, and follow-up durations across studies, clinically informative conclusions that can be drawn from these results are limited.

Interstitial Brachytherapy

For a 2007 RCT, accrual was stopped before reaching the goal specified to evaluate differences in local recurrence, to allow patients to enroll in another trial.(31,32) The randomization process was unclear; patients deemed “technically unsuitable” for interstitial brachytherapy were given EBRT APBI; and patient characteristics and outcomes for each type of APBI were not reported separately. Finally, the sample size of 126 was relatively small; and longest reported follow-up was 66 months. Similar local and regional failure rates were found across treatment arms.

Ajkay et al (2014) reported a retrospective study of 5-year adverse events in patients with early stage breast cancer who were treated at a single U.S. center.(52) Of 417 patients who received BCS and radiotherapy, 271 received intracavitary brachytherapy (34 Gy in 10 fractions; 90% MammoSite®, 9% Contura®, 1% strut-adjusted volume implant [SAVI]) and 146 received WBI using 3-dimensional conformal radiotherapy (3D-CRT; 45-50.4 Gy in 25-28 fractions with 10-16 Gy boost). Median follow-up was 4.8 years in the brachytherapy group and 4.1 years in the WBI group. Estimated 5-year overall incidence of any adverse event was greater in the brachytherapy group than the WBI group (72% vs 52%; log rank test for all comparisons, p<0.001). For prespecified adverse events of interest, estimated 5-year incidence of infectious skin complications, abscess, telangiectasia, and breast pain was similar between groups. Estimated 5-year incidence of seroma (47% vs 19%, p<0.001) and fat necrosis (40% vs
24%, p<0.001) was greater in the brachytherapy group.

Intraoperative Brachytherapy

One RCT compared intraoperative radiotherapy (IORT) with WBI in 2232 women.(34,35) Radiotherapy was delivered to the tumor bed using the Intrabeam® device, which provides a point source of 50 kV energy xrays at the center of a spherical applicator, for 20 to 45 minutes. It was specifically developed for IORT. The TARGIT-A (Risk-adapted Targeted Intraoperative Radiotherapy) trial was a noninferiority trial with 28 centers in 9 countries and a sample size of 3451. (In 2010, the trial was extended for 2 more years to allow accrual in subprotocols.) An ITT approach was used. Patients were not blinded to treatment choice. As anticipated in advance, 14% of those in the IORT arm received EBRT as well, because of unfavorable pathologic features determined after surgery (eg, lobular carcinoma). The predefined noninferiority margin was an absolute difference of 2.5% between groups for pathologically confirmed, ipsilateral local recurrence. The most recent article reported 5-year results, defined as results for patients with 5-years of follow-up or “if they were seen the year before database lock.”35 Median follow-up for all patients was 2 years and 5 months (IQR, 12-52 months), and 1222 patients (35%) had a median follow-up of 5 years. Estimated 5-year risks for ipsilateral local recurrence were 3.3% (95% CI, 2.1 to 5.1) in the TARGIT group and 1.3% (95% CI, 0.7 to 2.5; p=0.042) in the whole-breast radiotherapy group. Mortality was similar between the 2 groups (2.6% TARGIT vs 1.9%; p=0.56). However, there were significantly fewer nonbreast cancer deaths in the TARGIT group than in the whole-breast radiotherapy group (1.4% [95% CI, 0.8 to 2.5] vs 3.5% [95% CI, 2.3 to 5.2]; p<0.001), with fewer deaths from cardiovascular causes and other cancers in the TARGIT group. Overall, there were 12 more local recurrences but 14 fewer deaths in the TARGIT group than in the whole-breast radiotherapy group. In the group that received IORT plus whole-breast radiotherapy, the mortality rate was higher at 8% (95% CI, 3.7 to 17.5), but the percentage of women with local recurrences (0.9%; 95% CI, 0.1 to 6.1) was similar to those who received only IORT. Noninferiority was established for the whole intraoperative cohort and for those who received IORT alone, but not for those patients who underwent both types of radiotherapy. There was no significant difference between the IORT and whole-breast radiotherapy groups in predefined 6-month wound-related complications. However, grade 3 or 4 radiotherapy-related skin complications were more common in the whole-breast radiotherapy group (13/1730 vs 4/1731; p=0.029). Five- and 10-year follow-up for the entire TARGIT-A cohort has yet to be accrued.

A number of reviews and editorials discussed results of the TARGIT-A trial.(5,6,53-59) While recognizing the potential benefits of intraoperative radiotherapy, including convenience, “excellent delineation of the tumour bed under visual control, very good dose homogeneity, and high sparing of normal tissue,”(53) a number of concerns have been expressed. They include the following:

  • If IORT is performed during the surgery to excise the tumor, definitive pathology is unavailable when radiotherapy is performed. Therefore, a subset of patients must also undergo whole-breast EBRT following surgery. In the trial, 14% of patients in the IORT arm also received whole-breast EBRT. When only those who received IORT during initial surgery (rather than during repeat surgery to clear positive margins) were considered, 21% received whole-breast EBRT. Limited data suggest that breast symptoms and pain after treatment may be greater for patients receiving both IORT and whole-breast external radiotherapy compared with those receiving IORT alone, and that patient satisfaction is greater with whole-breast external radiotherapy or IORT alone compared with combined treatment.(60) Therefore, IORT may result in harm for a subset of patients who receive both IORT and whole-breast external radiotherapy.
  • Whether radiation dose and type is actually equivalent to the standard radiotherapy regimen is unknown. Of particular concern is the rapid drop in dose with distance from the applicator and whether any residual disease will be eradicated. Some argue that the TARGIT-A trial alleviates this concern, but others disagree.
  • Because 93% of tumors included in the TARGIT trial were estrogen-receptor positive, and estrogen-receptor positive tumors tend to recur later, longer follow-up is needed. Further, because cardiovascular adverse events may occur more than 7 to 10 years after completion of radiation treatment, 10-year results are needed to assess net health benefit.(5,6)
  • Claims that IORT may improve OS due to fewer nonbreast cancer deaths may be premature due to short median follow-up (2.4 years) in TARGIT-A. Studies suggest that the latency period for radiation-induced nonbreast cancers is 15 to 20 years from breast treatment.(6)

A 2014 Cochrane review on partial breast irradiation for early breast cancer included the 3 RCTs discussed above plus a fourth RCT that compared conventional (not accelerated) WBI with conventional partial-breast irradiation by a variety of techniques.(61) The overall quality of evidence was considered low to very low, and conclusions could not be reached.

Another form of intraoperative radiotherapy, called electron intraoperative radiotherapy (ELIOT), uses electrons.(62) The 2013 ELIOT trial compared intraoperative radiotherapy with ELIOT to WBI.(36) With a sample size of 1305 patients and median follow-up of 5.8 years (IQR, 4.1-7.7), 35 patients in the intraoperative group (4.4%) and 4 patients in the WBI group (0.4%) developed ipsilateral breast tumor recurrences (HR=9.3 [95% CI, 3.3 to 26.3]; log-rank test, p<0.001). There was no statistically significant difference in 5-year OS. For women with data on adverse skin events (intraoperative radiotherapy=464; WBI=412), there were significantly fewer events among women who received intraoperative radiotherapy (p<0.001). This was an equivalence trial with a prespecified equivalence limit of 7.5% for local recurrence in the intraoperative radiotherapy group only. Therefore, although the criterion for equivalence was satisfied, ipsilateral breast recurrence rate was significantly higher in the intraoperative radiotherapy group. A subsequent review of the ELIOT trial noted that, of 69 women who had 4 or more positive lymph nodes, those randomized to WBI (n=38) received concurrent axillary radiation; for those randomized to ELIOT (n=31), axillary irradiation was delayed 6 to 12 weeks.(7) These reviewers also characterized ELIOT data as “still early” and noted that long-term results are needed to assess net health benefit.

All 8 nonrandomized, comparative studies included in the 2013 TEC Assessment were flawed, due to potential baseline differences in treatment groups, lack of multivariable analyses to account for them, inclusion of patients who did not meet eligibility criteria, variations in treatment within arms, and generally small sample sizes and insufficient follow-up.(39-49)

Other IORT modalities are being researched, eg, electronic brachytherapy using the Xoft® Axxent® eBx™ system (NCT01644669; see Ongoing and Unpublished Clinical Trials section). Use of the Xoft® Axxent® eBx™ system is not limited to intraoperative radiotherapy of the breast; it is also used in breast balloon brachytherapy and to treat other organs. Few studies have evaluated electronic brachytherapy devices (balloon and radiation source); no comparative studies were found. The purported advantage of using Axxent® is to eliminate the need for heavy shielding, as required when using a high-dose rate afterloader unit. (For more information on the Intrabeam® device and the Xoft® Axxent® eBx™ system,see Cox and Swanson.(63)

External-Beam APBI

Two RCTs compared EBRT APBI with whole-breast radiotherapy using 3D-CRT. In the first, 102 patients were randomized to either WBI, with or without a boost to the tumor bed, or APBI.(37) The primary end point was local recurrence within 5 years. In this noninferiority trial, the sample size was calculated to detect a 10% difference between treatment arms, with a power of 80% and a significance level of 0.05. The APBI group was significantly younger than the WBI group (mean age [SD], 67.1 [6.1] years vs 70.1 [5.2] years; p=0.009). After a median follow-up of 5 years, there were no recurrences in either group, nor was there a statistically significant difference in survival. Investigators noted that the sample size may have been insufficient to detect a true difference in local control. Ninety percent (46/51) of APBI patients had acute skin effects, mostly grade 1; all patients in the WBI group had acute skin effects, and most were grade 2. Grade 1 and 2 late effects were reported with some changes in the relative positions of the treatment groups over time.

The second RCT was the multicenter randomized RAPID trial (Randomized Trial of Accelerated Partial Breast Irradiation).(38) The sample size was 2135, and median follow-up was 3 years. Most patients were older than 50 years and had estrogen receptor‒positive tumors less than 1.5 cm in diameter. An interim article reported on cosmetic and toxicity results. An accelerated regimen was used for WBI, and 21% of these patients received a boost to the tumor bed. APBI patients were more likely than WBI patients to have adverse cosmesis at 3 years, whether reported by physicians (p<0.001), nurses (p<0.001), or patients (p<0.05). As for late toxicities, 1.4% of APBI patients had a grade 3 adverse event versus none of the WBI patients. Telangiectasia and breast induration were more common among APBI patients (p<0.001).

One RCT was reported in 1990 and 1993, and many changes in the care of patients with breast cancer have occurred since then.(29,30) The study was weakened by the fact that initial groups were potentially unbalanced, and nodal status was based on clinical exam, among other factors. Recurrence was higher for the “limited field” treatment arm (analogous to partial-breast irradiation) than for the “wide field” arm (analogous to WBI), but some of the “excess” recurrences in the limited field arm were axillary. This may be accounted for by the fact that the axillary area was included in the wide field radiotherapy but not in the limited field, and initial work-up for nodal involvement was limited. The follow-up was 65 months; the sample size was 708.

Smith et al (2012) analyzed Medicare data on 92,735 women, 67 years or older, diagnosed with breast cancer between 2003 and 2007, who underwent lumpectomy followed by radiotherapy.(64) The mean age (SD) was 74.8 (5.5) years. Use of brachytherapy increased from 3.5% in 2003-2004 to 12.5% in 2007 (p<0.001 for trend). Brachytherapy patients were more likely to undergo a subsequent mastectomy than matched WBI patients, even after adjusting for imbalanced covariates (HR=1.87 [95% CI, 1.36 to 2.58]; p<0.001). This finding held true when all WBI patients were compared with all brachytherapy patients using multivariable analysis (HR=2.19 [95% CI, 1.84 to 2.61]; p<0.001). Covariates that were significantly associated with subsequent mastectomy (besides brachytherapy) included age 75 to 79 (p=0.01), axillary lymph node involvement (p=0.004), and living in the southern United States (p=0.005). The cause of the mastectomies, eg, recurrence or treatment complications, could not be determined from the claims data. Breast brachytherapy also was associated with a higher risk of postoperative complications, both infectious and noninfectious (27.56% [95% CI, 26.51% to 28.63%] vs 16.92% for WBI patients [95% CI, 16.67% to 17.18%], p<0.001).

Czechura et al (2013) evaluated the frequency of APBI versus WBI in the National Cancer Data Base from 2003 to 2010.(65) The use of brachytherapy accounted for 3.4% of cases in 2003, 12.8% (p<0.001) in 2008, and 12.4% in 2010. The largest percentage-point increase by type of APBI was for brachytherapy (from 2.0% to 8.9%), followed by 3D-CRT (from 0.8% to 2.2%) and intensity-modulated radiotherapy (from 0.7% to 1.3%). Mean age was 58.7 years for WBI patients versus 61.6 years for APBI patients. Patients with managed care were most likely to use APBI (46.3% of all APBI), compared with 12.2% for private payers and 6.9% for Medicare. APBI was used most often in the southeastern United States. Considering invasive cancers, 43.6% of APBI patients met the ASTRO (American Society for Radiation Oncology) “suitable” guidelines; 47.0%, the “cautionary” guidelines; and 9.2%, the “unsuitable” guidelines.

Section Summary

Overall, the body of evidence on interstitial APBI compared with conventional WBI is weak; and it is extremely weak (ie, no randomized studies) for balloon brachytherapy. One small RCT compared EBRT APBI with whole-breast radiotherapy, and a second larger RCT reported on cosmesis and toxicity after a median of 3 years. The strongest published evidence is on intraoperative radiotherapy (the TARGIT trial); 5-year results showed increased ipsilateral local recurrence with APBI compared with whole-breast
radiotherapy, although a prespecified noninferiority criterion for this outcome was satisfied. Similarly, 5-year results of the ELIOT trial met a prespecified equivalence criterion; however, recurrence rate for intraoperative radiotherapy patients was statistically greater than for WBI patients. Furthermore, it is becoming increasingly clear that each type of APBI should be judged on its own merits, and studies comparing different APBI techniques with each other, as well as with WBI, are needed. Fortunately, a
number of large RCTs are underway.

Given the current level of evidence, it is important for patients to be aware of the uncertainty regarding the outcomes of this approach. This information should include failure rates for specific devices (eg, explantation for Mammosite®, incomplete expansion of the catheters for some of the hybrid devices), as well as the uncertainty regarding their comparative effectiveness. The intermediate alternative provided by AWBI also should be presented to women who meet criteria for the Canadian trial, as well as the critical importance of completing radiotherapy for the majority of patients undergoing BCS.

Use as Local Boost Radiotherapy

A 1996 TEC Assessment concluded that net health outcome with brachytherapy local boost were equivalent to outcomes with EBRT local boost in women who received BCS plus whole-breast radiotherapy as initial treatment for stage 1 or stage 2 breast cancer.(66) In 7 nonrandomized comparisons (total N=2022), the 5-year local control rate was 88% to 98% for those who received brachytherapy local boost, compared with 91% to 99% for those who received EBRT local boost.

Accuboost® for image-guided breast irradiation, also called noninvasive breast brachytherapy, has been used for local boost around the tumor bed. The Accuboost® system provides image-guided radiotherapy before each treatment to ensure that radiation is directed at the treatment target. The breast is placed between mammography paddles, where images are taken and radiation is delivered using a distinct applicator. The paddles prevent motion during treatment. Radiation is delivered from 1 side of the breast to the other or from the top of the breast to the bottom. This is proposed to reduce radiation exposure to adjacent tissues, including the heart and lung.(67) No long-term studies are available to confirm this. There is only 1 comparative study for this use, a matched retrospective study of patients receiving the boost dose using Accuboost® or electron beams (a type of EBRT).(68) Each of 47 Accuboost® patients was compared with 2 controls matched on age, stage, chemotherapy use, fractionation, and when possible, breast size, comorbidities, and smoking status. Main differences between the 2 treatment groups were in radiation dose received and timing of radiotherapy administration. The percentage of patients with a WBI dose (accompanying the boost dose) of 50 to 50.4 Gy was 68% in the Accuboost® group and 37% in the electron-treated group (p<0.001). Also, a greater proportion of patients in the electron-treated group received the boost dose after WBI, rather than during WBI or starting before and ending during WBI (99% for the electron-treated group vs 6% for the Accuboost® group). Approximately 60% of patients had stage 1 breast cancer, and approximately one-quarter, DCIS. With median follow-up of 13.6 months, skin/subcutaneous tissue toxicity occurred less often among patients treated with Accuboost® than among those treated with electron beam (p=0.046). Locoregional control rates were 99% or greater in both groups. Study limitations included the between-group differences in whole-breast radiation dose and timing of boost, as well as selection bias and the study’s retrospective design.

Section Summary

For women undergoing BCS plus WBI as initial treatment for stage 1 or stage 2 breast cancer, nonrandomized comparative studies have shown similar outcomes with brachytherapy local boost and with EBRT local boost.

One matched retrospective study of 141 patients who received noninvasive breast brachytherapy with Accuboost® or electron beam irradiation (a type of EBRT) to provide boost radiation to the tumor bed had a median follow-up of 14 months. This evidence is insufficient to form any conclusion about Accuboost®.

Ongoing and Unpublished Clinical Trials

A search of ClinicalTrials.gov found 12 ongoing comparative trials (10 randomized, 2 nonrandomized) of APBI (see Table 2). No comparative trials of AWBI or Accuboost® were identified.

Additionally, GEC-ESTRO (Groupe Européen de Curietherapie-European Society for Therapeutic Radiology and Oncology) is sponsoring a phase 3 multicenter trial to compare interstitial brachytherapy alone versus EBRT after BCS in patients with low-risk invasive carcinoma or low-risk DCIS.(69) This trial is not listed at ClinicalTrials.gov or the European Union Clinical Trials Register. Expected enrollment is 1170 patients, and 10-year follow-up is planned.

In 2009, Mannino and Yarnold (note Yarnold is a lead author on the START A and B trials) reviewed current ongoing APBI trials and raised several concerns regarding cross-trial variations.(70) The extent of initial BCS can vary substantially across studies, as well as the definition of the targeted tumor cavity. A larger margin is usually drawn around the tumor cavity for 3D-CRT, for example, because of the need to allow for variations in set-up and respiratory motion. Studies of APBI usually distinguish between “same site relapse,” ie, close to the irradiated area and “elsewhere relapse,” yet it is unclear whether what constitutes the same site varies across studies. The percentage of relapses occurring “elsewhere” in the ipsilateral breast in studies of whole-breast radiotherapy following BCS range from 18% to 42%; these studies may include some patients at higher risk of recurrence. Proponents of APBI have sometimes asserted that “elsewhere” tumors are rare, that they are mostly new primary tumors (rather than recurrence), or that earlier studies have shown that radiotherapy is not effective for these tumors in any case. Mannino and Yarnold challenged each of these points in turn, although they also concluded that results of trials currently underway will provide level-1 evidence for or against APBI.

Table 2. Ongoing Comparative Trials of APBI Listed at ClinicalTrials.gov

NCT Number

Title

Phase

Enrollmenta

Completion Dateb

WBI vs APBI ± tumor bed boost in DCIS

NCT00470236

Radiation Doses and Fractionation  Schedules in Non-low Risk Ductal Carcinoma In Situ (DCIS) of the Breast

(TROG)

3

1600

Nov 2024

Intraoperative brachytherapy

NCT01343459

Intra-Operative Electron Boost and Hypofractionated Whole-Breast Irradiation During Breast-conserving Treatment (BCT) (HIOB)

3

1000

Mar 2021

NCT01644669

Safety and Efficacy Study of the Xoft® Axxent® eBx™ IORT System

4

1000

Dec 2024

External-beam APBI

NCT01185132

Intensity Modulated Radiotherapy (IMRT) vs. 3D-conformal Accelerated Partial Breast Irradiation (APBI) for Early Stage Breast Cancer After Lumpectomy (2009-APBI)

3

660

Jul 2028

NCT01247233

Standard or Hypofractionated Radiotherapy Versus Accelerated Partial Breast Irradiation (APBI) for Breast Cancer (SHARE)

3

2796

Oct 2024

NCT01803958

Breast Cancer With Low Risk Of Local Recurrence: Partial and Accelerated Radiation With Three-Dimensional Conformal Radiotherapy (3DCRT) Vs. Standard Radiotherapy After Conserving Surgery (Phase III Study) (IRMA)

NR

3302

Dec 2017

NCT02104895

Accelerated Partial Breast Irradiation Using Intensity Modulated Radiotherapy Versus Whole Breast Irradiation

3

520

Feb 2014

APBI (multimodality)

NCT00103181

Radiation Therapy (WBI Versus PBIc ) in Treating Women Who Have Undergone Surgery For Ductal Carcinoma In Situ or Stage I or Stage II Breast Cancer (RTOG 0413/NSABP B39)

3

4216

Jun 2016

NCT00282035

Randomized Trial of Accelerated Partial Breast Irradiationd (RAPID)

3

2128

Dec 2020

NCT00892814

Partial Breaste Versus Whole Breast Irradiation in Elderly Women Operated on for Early Breast Cancer

2

628

May 2022

NCT00185744

Accelerated Partial Breast Irradiationf Following Lumpectomy for Breast Cancerg

NR

400

Dec 2015

NCT01185145

Accelerated Partial Breast Radiotherapy With Either Mammosite or Intensity Modulated Radiotherapy (APBI)g

2

291

Aug 2024

APBI: accelerated partial-breast irradiation; DCIS: ductal carcinoma in situ; NR: not reported; PBI: partial-breast irradiation; WBI: whole-breast irradiation.
aExpected.
bEstimated.
cAccelerated interstitial or balloon PBI, or 3-dimensional conformal accelerated PBI.
d3-dimensional conformal accelerated PBI.
ePBI mode of delivery unspecified.
fIntraoperative radiotherapy, balloon APBI, or stereotactic APBI.
gNonrandomized.

Clinical Input Received 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.

2011 Input

In response to requests, input was received from 1 physician specialty society and 4 academic medical centers while this policy was under review in 2011. There was near-unanimous support for the policy statement regarding AWBI. The input was mixed regarding APBI; those agreeing with the conclusion noted the need to define the risks and benefits of this approach in patient subgroups and noted that current data are inconclusive concerning the effectiveness of APBI compared with WBI.

Summary of Evidence

Accelerated Whole-Breast Irradiation

The overall body of evidence on accelerated whole-breast irradiation (AWBI) compared with conventional whole-breast irradiation (WBI) suggests that local recurrence rates with AWBI are not worse than with conventional WBI in patients meeting criteria of the Canadian trial, with a noninferiority margin of 5%. Patient selection is important, and, at this point, only patients similar to those in the Canadian trial should be considered for this therapy. Thus, AWBI may be considered medically necessary for these patients with clinical characteristics noted in the medically necessary policy statement. Outcomes could differ in women with other disease characteristics.

Brachytherapy Boost With WBI

For patients treated with whole-breast external-beam radiotherapy (EBRT) and breast-conserving surgery (BCS), local boost irradiation via interstitial or balloon brachytherapy is likely to result in equivalent outcomes compared with local boost given by EBRT. This is based on results from nonrandomized comparative studies, a TEC Assessment, and specialty society guidelines. As a result, interstitial or balloon brachytherapy may be considered medically necessary for these patients when used as local boost irradiation.

Accelerated Partial-Breast Irradiation

Overall, the body of evidence on interstitial accelerated partial-breast irradiation (APBI) compared with conventional WBI is weak; evidence is extremely weak (ie, no randomized studies) for balloon brachytherapy. The strongest published evidence is on intraoperative radiotherapy. Five-year results of 1 randomized controlled trial (RCT; TARGIT-A) showed increased ipsilateral local recurrence with APBI compared with whole-breast radiotherapy. In another RCT that used a different technology (ELIOT),
recurrence rate with intraoperative radiotherapy was statistically greater than with WBI. It is becoming increasingly clear that each type of APBI should be judged on its own merits, and studies comparing different APBI techniques with each other, as well as with WBI, are needed. A number of large RCTs are underway. However, based on current evidence, APBI is considered investigational for treatment of early stage breast cancer after BCS, except when interstitial or balloon brachytherapy is used as local boost with whole-breast external-beam radiation after BCS, as described above.

Noninvasive Breast Brachytherapy

Evidence for noninvasive breast brachytherapy using Accuboost® to provide boost radiation to the tumor bed is very weak; therefore this technique is considered investigational.

Practice Guidelines and Position Statements

According to current National Comprehensive Cancer Network (NCCN) guidelines (version 3.2014)(2):

“Preliminary studies of APBI suggest rates of local control in selected patients with early stage breast cancer may be comparable to those treated with standard whole breast RT [radiotherapy]. However, compared with standard whole breast radiation, several recent studies documented an inferior cosmetic outcome with APBI. Follow-up is limited and studies are ongoing. Patients are encouraged to participate in clinical trials. If not trial eligible, per the consensus statement from the American Society for Radiation Oncology (ASTRO), patients who may be suitable are … [see ASTRO Criteria:Suitable in Table 3].”

For whole-breast radiotherapy, NCCN recommends either a conventional WBI regimen or a total dose of 42.5 Gy with 2.66 Gy per fraction, which equals 16 fractions. Although NCCN guidelines do not specify the duration of treatment, the latter is presumably an AWBI regimen. A boost to the tumor bed is recommended for higher risk patients receiving whole-breast radiotherapy, ie, those who are younger than 50 years old with high-grade disease.

The American College of Radiology (ACR) has ACR Appropriateness Criteria® for conservative surgery and radiation for stage 1 and 2 breast carcinoma, last reviewed in 2011. The document provides appropriateness criteria for the use of radiotherapy after BCS for specific cases.

The American Society of Breast Surgeons, ASTRO, and the American Brachytherapy Society have issued consensus statements for the selection of patients for APBI (summarized in Table 3). According to statement authors, the impetus for the publications was the increased use of APBI outside of clinical trials, even as results of those trials were awaited. The authors estimated that more than 32,000 women have already been treated with MammoSite®, a mechanism for delivering APBI. The statements are based on systematic reviews, which are not described in detail, and expert opinion. Several authors have questioned the validity of ASTRO consensus statement categories based on retrospective studies that showed inconsistent associations between ASTRO category and recurrence rates and no association between ASTRO category and survival outcomes.(50,71-73)

Table 3. Professional Medical Society Criteria for Performing APBI(74-77)

Factor

ASTRO
“Suitable”

ASTRO
“Cautionary”

ASTRO
“Unsuitable”

ASBS

ABS

Patient Factors

Age

≥60 y

50-59 y

<50 y

≥45 y
≥50 y for DCIS

≥50 y

BRCA 1I2 mutation

Not present

NR

Present

NR

NR

Pathologic factors

Tumor size

≤2cm

2.1-3.0 cm

>3cm

≤3cm

≤3cm

Tumor stage

T1

T0 or T2

T3-4

NR

 

Margins

Negative ≥2mm

Close (<2mm)

Positive

Microscopically negative

Negative

Grade

Any

NR

NR

NR

NR

LVSI

No

Limited/focal

Extensive

NR

NR

ER status

Positive

Negativea

NR

NR

Positive or negative

Multicentricity

Unicentric

NR

Present

NR

NR

Multifocality

Clinically unifocal; total size, ≤2.0cm

Clinically unifocal; total size, 2.1-3.0cm

Clinically multifocal or microscopically multifocal; total size, ≥3cm

NR

NR

Histology

Invasive ductal or other favorable subtypes

Invasive lobular

NR

Invasive ductal carcinoma or DCIS

All invasive subtypes and DCIS

Pure DCIS

Not allowed

≤3cm

>3cm

≤3cm

≤3cm

EIC

Not allowed

≤3cm

>3cm

NR

NR

Associated LCIS

Allowed

NR

NR

NR

NR

Nodal factors

Nodal stage

pN0 (i- ,i+)

NR

pN1, pN2, pN3

SN pN0

Pn0b

Nodal surgery

SN Bx, ALND

NR

None performed

NR

NR

Treatment factors

Neoadjuvant therapy

Not allowed

NR

If used

NR

NR


ABS: American Brachytherapy Society; ALND: axillary lymph node dissection; APBI: accelerated partial-breast irradiation; ASTRO: American Society for Radiation Oncology; ASBS: American Society of Breast Surgeons; DCIS: ductal carcinoma in situ; EIC: extensive intraductal component; ER status: estrogen receptor status; LCIS: lobular carcinoma in situ; LVSI: lymphovascular space invasion; NR: not reported; SN: sentinel node

aStrongly encouraged to enroll in NSABP B-39/RTOG 04-13 trial.
bLymphovascular space invasion is considered a contraindication for APBI.

ASTRO released guidelines on fractionation for WBI in 2010.(78) Guidelines are based on the Canadian trial,(17,18) START A16 and START B,(15) and a third RCT.(14,19) Guideline authors concluded that “Data are sufficient to support the use of HF-WBI [hypofractionated or accelerated, whole-breast irradiation] for patients with early breast cancer who meet all of the aforementioned criteria,” including age 50 years or older, disease stage pT1-2 pN0, no chemotherapy, and treatment with radiation dose homogeneity within ±7% in the central axis plane. The task force did not agree on whether HF-WBI is recommended for tumor boost.

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

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


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  45. Shah C, Antonucci JV, Wilkinson JB, et al. Twelve-year clinical outcomes and patterns of failure with accelerated partial breast irradiation versus whole-breast irradiation: results of a matched-pair analysis. Radiother Oncol. Aug 2011;100(2):210-214. PMID 21497927
  46. Shah C, Wilkinson JB, Lyden M, et al. Comparison of survival and regional failure between accelerated partial breast irradiation and whole breast irradiation. Brachytherapy. Jul-Aug 2012;11(4):311-315. PMID 22381652
  47. Vicini FA, Baglan KL, Kestin LL, et al. Accelerated treatment of breast cancer. J Clin Oncol. 2001;19(7):1993-2001.
  48. Vicini FA, Kestin L, Chen P, et al. Limited-field radiation therapy in the management of early-stage breast cancer. J Natl Cancer Inst. 2003;95(16):1205-1211.
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Codes

Number

Description

CPT  19296  Placement of radiotherapy afterloading catheter (single or multichannel)  into the breast for interstitial radioelement application following partial mastectomy, includes imaging guidance; on date separate from partial mastectomy
  19297  Concurrent with partial mastectomy (List separately in addition to code for primary procedure)
  19298  Placement of radiotherapy afterloading brachytherapy catheters (multiple tube and butt on type) into the breast for interstitial radioelement application following (at the time or subsequent to) partial mastectomy, includes imaging guidance
  77261, 77262, 77263  Therapeutic radiology treatment planning code range 
  77280, 77285, 77290, 77295  Therapeutic radiology simulation-aided field-setting code range 
  77326  Brachytherapy isodose calculation; simple (calculation made from single plane, 1 to 4 sources/ribbon application, remote afterloading brachytherapy, 1 to 8 sources) 
  77327  Intermediate (multiplane dosage calculations, application involving 5 to 10 sources/ribbons, remote afterloading brachytherapy, 9 to 12 sources) 
  77328  Complex (multiplane isodose plan, volume implant calculations, over 10 sources/ribbons used, special spatial reconstruction, remote afterloading brachytherapy, over 12 sources) 
  77776, 77777, 77778  Interstitial radioelement application code range 
  77785, 77786, 77787 Remote afterloading high dose rate ardionuclide brachytherapy code range
  0182T High dose rate electronic brachytherapy, per fraction
ICD-9 Procedure  85.0  Mastotomy 
  92.27  Implantation/insertion of radioactive elements 
ICD-9 Diagnosis  174.0–174.9  Primary malignant neoplasm of breast, female 
  175.0–175.9  Primary malignant neoplasm of breast, male 
  198.81  Secondary malignant neoplasm of breast (male/female) 
HCPCS C1717 Brachytherapy source, high dose rate iridium 192, per source
  C9726 Placement and removal (if performed) or applicator into breast for radiation therapy
  Q3001  Radioelements for brachytherapy, any type, each
ICD-10-CM (effective 10/1/15) C50.011-C50.929 Malignant neoplasm male and female breast code range
   C79.81 Secondary malignant neoplasm of breast
ICD-10-PCS (effective 10/1/15)   ICD-10-PCS codes are only used for inpatient services.There is no specific ICD-10-PCS code for this procedure.
    DM1097Z, DM1098Z, DM1099Z, DM109BZ, DM109CZ, DM109YZ, DM10B7Z, DM10B8Z, DM10B9Z, DM10BBZ, DM10BCZ, DM10BYZ, DM1197Z, DM1198Z, DM1199Z, DM119BZ, DM119CZ, DM119YZ,
DM11B7Z, DM11B8Z, DM11B9Z, DM11BBZ, DM11BCZ, DM11BYZ
Radiation oncology, breast, brachytherapy, code by body part (right or left), modality qualifier (high dose rate or low dose rate), and isotope (Cesium 137, Iridium 192, Iodine 125, Palladium 103, Californium 252, or other isotope)
    0HHT01Z, 0HHT31Z, 0HHT71Z, 0HHT81Z, 0HHTX1Z, 0HHU01Z, 0HHU31Z, 0HHU71Z, 0HHU81Z, 0HHUX1Z, 0HHV01Z, 0HHV31Z, 0HHV71Z, 0HHV81Z, 0HHVX1Z Surgical, skin & breast, insertion, radioactive element, code by body part (right, left or bilateral), and approach (open, percutaneous, via natural or artificial opening, via natural or artificial opening endoscopic, or external)
   0HCT0ZZ, 0HCT3ZZ, 0HCU0ZZ, 0HCU3ZZ, 0HCV0ZZ, 0HCV3ZZ Surgical, skin & breast, extirpation, breast, code by body part (right, left or bilateral) and approach (open or percutaneous)
Type of Service  Radiotherapy 
Place of Service  Inpatient 

 


Index

 

Breast Brachytherapy
Brachytherapy, Breast
Mammosite
Partial Breast Brachytherapy
Intraoperative Radiotherapy


Policy History
Date Action Reason
7/31/96 Add to Therapy section New policy
5/15/02 Replace policy Policy updated but unchanged; rationale added to source section
12/18/02 Replace policy Policy updated to include conclusions of 2002 TEC Assessment; policy statement unchanged
11/9/04 Replace policy Policy updated; new references added; no change to policy statement
12/14/05 Replace policy Policy updated; new references added; no change to policy statement. Reference numbers 10–21 added
04/25/06 Replace policy Added updated NCCN statement and one reference. No change to policy statement
10/10/06 Replace policy Policy updated with literature search; new references added (new 13-24). No change to policy statement.
05/08/08 Replace policy Policy updated with literature search; reference citations from the 2007 update corrected and references 30, 35, and 40-48 added. No change to policy statement
4/14/11 Replace policy Policy updated with literature review and TEC Assessment; clinical input reviewed; policy extensively edited; new references added. Title changed to “Accelerated Breast Irradiation after Breast-Conserving Surgery for Early Stage Breast Cancer and Breast Brachytherapy as Boost with Whole-Breast Irradiation” (from Brachytherapy-Accelerated Partial Breast Irradiation); accelerated whole breast irradiation may be considered medically necessary in specific situations; accelerated partial breast irradiation (APBI), including intraoperative APBI, remains investigational.
12/13/12 Replace Policy Policy updated with literature review. References 1, 16, 28-30, 35-41 added. Policy statement on criteria for accelerated whole breast radiation changed from “negative surgical margins” to “technically clear surgical margins”; no change to intent of policy statement.
12/12/13 Replace policy Policy updated with literature review through November 2013. Two references were updated (2-3). Nine references were added (15, 34, 41-44, 46, 48, 49) and one was deleted (TEC 2010 Report). Policy statement clarified. Changed “Following breast-conserving surgery for early stage breast cancer” to “When using radiation therapy after breast-conserving surgery for early stage breast cancer.” Also added text at the end of the following statement: Accelerated whole-breast irradiation is considered investigational in all other situations involving treatment of early stage breast cancer after breast-conserving surgery. Added noninvasive brachytherapy Accuboost to policy statements as investigational.
2/13/14 Replace policy - correction only Policy statement “Accelerated whole-breast irradiation (AWBI) may be considered medically necessary for patients who meet the following conditions:” moved back up above the bulleted list of conditions.
12/11/14 Replace policy Policy updated with literature review through November 3, 2014; references 3, 5-7, 12-13, 22-28, 50-52, 57-59, 61, 69, 73, and 77 added; references 2 and 76 updated. Rationale reorganized and references renumbered. No change to policy statements.