Description
INDICATIONS FOR RADIATION THERAPY AND TREATMENT OPTIONS
This guideline outlines several methods suitable for the employment of radiation therapy in conjunction with breast cancer treatment. These include the use of three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT) and internal radiation (brachytherapy). IMRT is not indicated as a standard treatment option for breast cancer but may be indicated for selected cases of breast cancer with close proximity to critical structures. Most external beam treatments are delivered using a high energy linear accelerator. Brachytherapy is generally delivered using temporary HDR sources such as 192-Iridium 
(192-Ir) or Cesium-137 (137-Cs). 

Whole Breast Radiation^{1, 2}
Three-dimensional conformal radiation therapy (3D-CRT) is the appropriate technique for treatment of the whole breast following breast conserving surgery (lumpectomy, breast conservation surgery). Electron beam or photon beam are the most commonly used techniques for delivering boost radiotherapy. Several randomized trials have confirmed the efficacy of a hypofractionated regimen in the adjuvant treatment of breast cancer.

Background   
Breast cancer is the second most commonly diagnosed cancer among women, after skin cancer, and it accounts for nearly 25% of cancer diagnoses in U.S. women. After a breast cancer diagnosis is made, it is followed by a staging evaluation to determine extent of disease (local, regional, or metastatic) and prognostic findings. Importance is placed on tumor size, lymph node involvement (sentinel node), the histo-pathological interpretation, margins of resection, and hormonal and growth-factor receptor status. Treatment for breast cancer may consist of one of several mastectomy options or breast-conserving surgery and radiation therapy. 

Radiation therapy is used to treat the breast and lymph node bearing areas after partial mastectomy or lumpectomy. Since breast cancers are relatively responsive to moderate doses of radiation therapy following tumor excision, treatment for cure may be achieved by external beam techniques or by partial breast irradiation techniques. 

The methods suitable for delivering breast radiation therapy have been established through clinical trials providing strong evidence in support of radiation therapy as an effective breast cancer treatment. The traditional approach utilizes tangential radiation fields to the breast and chest wall; based on the clinical and pathological factors, this may be followed by boost to the site of excision (tumor bed). The axilla and supra-clavicular regions also may be included in a separate field based on analysis of prognostic risk factors. Improvements in technology, the observation that local tumor recurrence is most frequently observed near the site of excision, and the desire to limit the extent of radiation have led to restriction of the radiation to the tumor bed (partial breast irradiation) for selected cases.

Policy
Hypofractionated Dosage Guidelines
The use of up to 16 fractions of 3DCRT followed by a boost of 4 – 8 fractions for patients at higher risk of recurrence is considered MEDICALLY NECESSARY.

Ultra-hypofractionated Dosage Guidelines¹
28.5 Gy delivered as 5 fractions, may be considered in selected patients aged ≥ 50 years following breast conservation surgery with pTis/T1/T2/N0 tumors. The optimal fractionation for the delivery of a boost is not known with this regimen.³

Other treatment regimens require physician review and clinical documentation that is considered MEDICALLY NECESSITY.

Partial Breast Irradiation^{1, 4}
Accelerated partial breast irradiation (APBI) may be considered as the sole form of radiation therapy, in lieu of whole breast radiation following lumpectomy for selected cases. Patients with a small tumor, clear surgical margins after lumpectomy, and no lymph nodes containing cancer are typically eligible for APBI. APBI is considered appropriate for patients who meet all of the following criteria (Suitable Group):

• Age 50 or older 
• Invasive Ductal Carcinoma or Low Grade-Intermediate Grade Ductal Carcinoma in Situ (DCIS)
• Lymph nodes negative 
• No or minimal lymphovascular invasion
• Positive Estrogen Receptor
• Negative surgical margins (more than or equal to 2mm for Invasive Ductal Carcinoma, more than or equal to 3mm for DCIS)
• Tumor size less than or equal to 2cm for Invasive Ductal Carcinoma and less than or equal to 2.5cm for Ductal Carcinoma In Situ
• Clinically or microscopically unifocal 
• Absence of BRCA in 1/2 mutation, if applicable 

Dosage Guidelines¹

• Appropriate fractionation schemes for APBI are:
  • 30 Gy in 5 fractions once a day, preferred.^{5, 6}
  • 40 Gy in 15 fractions once a day.⁷
  • 34 Gy in 10 BID fractions balloon/interstitial brachytherapy.⁸
  • 38.5 Gy in 10 BID fractions.⁹

Chest Wall Radiation¹
Three-dimensional conformal radiation therapy (3D-CRT) is the appropriate technique for treatment of the chest wall following mastectomy. Chest wall scar boost may be delivered with or without bolus using electrons or photons.

Dosage Guidelines 

• 45 – 50.4 Gy up to 28 fractions with boost 59 – 66.4 Gy up to 37 fractions 

Other Considerations

• Re-irradiation following local or regional recurrence after prior mastectomy and prior breast or chest wall radiation may be appropriate.
• For inflammatory breast cancer, whole breast or chest wall radiation, consider nodal radiation with or without chest wall boost.

Dosage Guidelines 
• 45 – 50.4 Gy up to 28 fractions with boost 59 – 66.4 Gy up to 37 fractions. 

Standard radiation fractionation consists of 1.8 Gy to 2.0 Gy per day.

Whole Breast Irradiation (WBI)^{1, 2}
The use of up to 16 fractions of 3DCRT followed by a boost of 4 – 8 fractions for patients at higher risk of recurrence is considered medically necessary. Several randomized trials have confirmed the efficacy of a hypofractionated regimen in the adjuvant treatment of breast cancer. Other treatment regimens require physician review and clinical documentation that is considered MEDICALLY NECESSARY.

The use of up to 28 fractions of 3DCRT followed up with a boost of 4 – 8 fractions may be considered MEDICALLY NECESSARY if any of the following criteria are met: 

• Reirradiation
• Lymph node involvement requiring treatment the supraclavicular or internal mammary nodal regions 
• Concurrent chemotherapy will be administered (does not include trastuzumab or endocrine therapy)
• Collagen vascular disease
• Breast augmentation/reconstruction 
• Treatment will be delivered with 3D conformal radiotherapy and the treatment plan results in dose inhomogeneity of greater than 7% in the central axis (for example, if the plan is normalized to 95%, the maximum dose is greater than 120%)

Intraoperative radiation therapy (IORT) 

• Single Fraction Electron-beam IORT is considered medically necessary in accordance with ASTRO guidelines⁴ if the following criteria are met: 
  • Individual is 45 years of age or older with invasive cancer
  • T Stage: Tis or T1 (tumor up to 3.5 cm)
  • Clinically node negative
  • Negative surgical margins

The use of electronic brachytherapy for IORT (such as Intrabeam, Xoft and Papillon systems) is considered investigational/unproven therefore considered NOT MEDICALLY NECESSARY.

TREATMENT OPTIONS REQUIRING PHYSICIAN REVIEW
Intensity modulated radiation therapy (IMRT)¹
IMRT is not indicated as a standard treatment option and should not be used routinely for the delivery of radiation therapy for breast cancer. IMRT is strictly defined by the utilization of inverse planning modulation techniques. IMRT may be appropriate for limited circumstances in which radiation therapy is indicated and 3D conformal radiation therapy (3D-CRT) techniques cannot adequately deliver the radiation prescription without exceeding normal tissue radiation tolerance, the delivery is anticipated to contribute to potential late toxicity or tumor volume dose heterogeneity is such that unacceptable hot or cold spots are created. If IMRT is utilized, techniques to account for respiratory motion should be performed.

Clinical rationale and documentation for performing IMRT rather than 2D or 3D-CRT treatment planning and delivery will need to: 

• Demonstrate how 3D-CRT isodose planning cannot produce a satisfactory treatment plan (as stated above) via the use of a patient-specific dose volume histograms and isodose plans. 3D-CRT techniques such as step-and-shoot or field-in-field should be considered for the comparison.
• Confirm the IMRT requested will be inversely planned (forward plans or "field-in-field" plans are not considered IMRT).
• Provide tissue constraints for both the target and affected critical structures.
• Upon physician review, IMRT can be approved for accelerated partial breast irradiation using 30 Gy in 5 fractions once a day regimen.^{5, 6} Comparative 3D-CRT vs. IMRT plans are not required.

Brachytherapy
Interstitial brachytherapy boost treatment requires a peer review and documentation that improvement in dose delivery to the boost target cannot be delivered with external beam therapy. Other emerging techniques such as Non-invasive Image Guided Breast Brachytherapy (NIIGBB) techniques are being investigated and are not considered a medically necessary treatment option for the treatment of breast cancer.

Proton Beam Radiation Therapy
Proton beam is not an approved treatment option for breast cancer. There are limited clinical studies comparing proton beam therapy to 3-D conformal radiation or IMRT. Overall, studies have not shown clinical outcomes to be superior to conventional radiation therapy.

Intraoperative radiation therapy (IORT) 

• Single Fraction Electron-beam IORT is considered medically necessary in accordance with ASTRO guidelines⁴ if the following criteria are met: 
  • Individual is 45 years of age or older with invasive cancer
  • T Stage: Tis or T1 (tumor up to 3.5 cm)
  • Clinically node negative
  • Negative surgical margins
• The use of electronic brachytherapy for IORT (such as Intrabeam, Xoft and Papillon systems) is considered investigational/unproven therefore considered NOT MEDICALLY NECESSARY. 

References

1. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Breast Cancer Version 1.2022. National Comprehensive Cancer Network (NCCN). Updated November 24, 2021. Accessed December 10, 2021. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
2. Smith BD, Bellon JR, Blitzblau R, et al. Radiation therapy for the whole breast: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Pract Radiat Oncol. May-Jun 2018;8(3):145-152. doi:10.1016/j.prro.2018.01.012
3. Brunt AM, Haviland JS, Sydenham M, et al. Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer. J Clin Oncol. Oct 1 2020;38(28):3261-3272. doi:10.1200/jco.19.02750
4. Correa C, Harris EE, Leonardi MC, et al. Accelerated Partial Breast Irradiation: Executive summary for the update of an ASTRO Evidence-Based Consensus Statement. Pract Radiat Oncol. Mar-Apr 2017;7(2):73-79. doi:10.1016/j.prro.2016.09.007
5. Meattini I, Marrazzo L, Saieva C, et al. Accelerated Partial-Breast Irradiation Compared With Whole-Breast Irradiation for Early Breast Cancer: Long-Term Results of the Randomized Phase III APBI-IMRT-Florence Trial. J Clin Oncol. Dec 10 2020;38(35):4175-4183. doi:10.1200/jco.20.00650
6. Livi L, Meattini I, Marrazzo L, et al. Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial. Eur J Cancer. Mar 2015;51(4):451-463. doi:10.1016/j.ejca.2014.12.013
7. Coles CE, Griffin CL, Kirby AM, et al. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial. Lancet. Sep 9 2017;390(10099):1048-1060.doi:10.1016/s0140-6736(17)31145-5
8. Vicini FA, Cecchini RS, White JR, et al. Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial. Lancet. Dec 14 2019;394(10215):2155-2164. doi:10.1016/s0140-6736(19)32514-0
9. Whelan TJ, Julian JA, Berrang TS, et al. External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial. Lancet. Dec 14 2019;394(10215):2165-2172. doi:10.1016/s0140-6736(19)32515-2
10. ACR Appropriateness Criteria®: Conservative Surgery and Radiation – Stage I and II Breast Cancer. American College of Radiology Updated 2015. Accessed December 16, 2021. https://acsearch.acr.org/docs/69351/Narrative/
11. ACR Appropriateness Criteria®: Locally and Advanced Breast Cancer. American College of Radiology. Updated 2016. Accessed December 16, 2021. https://acsearch.acr.org/docs/69346/Narrative/
12. American Society for Radiation Oncology. Ten Things Physicians and Patients Should Question. ABIM Foundation. Updated 2019. Accessed December 7, 2021. https://www.choosingwisely.org/societies/american-society-for-radiation-oncology/9—Breast Cancer© 2019-2022 National Imaging Associates, Inc., All Rights Reserved 
13. American Society for Radiation Oncology. Model Policies: Intensity modulated radiation therapy (IMRT). American Society for Radiation Oncology (ASTRO). Updated June 6, 2019. Accessed December 13, 2021. https://www.astro.org/ASTRO/media/ASTRO/Daily%20Practice/PDFs/IMRTMP.pdf
14. Breast Cancer Facts & Figures. American Cancer Society. Updated 2020. Accessed December 16, 2021. https://www.cancer.org/research/cancer-facts-statistics/breast-cancer-facts-figures.html
15. Bentzen SM, Constine LS, Deasy JO, et al. Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): an introduction to the scientific issues. Int J Radiat Oncol Biol Phys. Mar 1 2010;76(3 Suppl):S3-9. doi:10.1016/j.ijrobp.2009.09.040
16. Jackson A, Marks LB, Bentzen SM, et al. The lessons of QUANTEC: recommendations for reporting and gathering data on dose-volume dependencies of treatment outcome. Int J Radiat Oncol Biol Phys. Mar 1 2010;76(3 Suppl):S155-60. doi:10.1016/j.ijrobp.2009.08.074
17. Shah C, Vicini F, Shaitelman SF, et al. The American Brachytherapy Society consensus statement for accelerated partial-breast irradiation. Brachytherapy. Jan-Feb 2018;17(1):154-170. doi:10.1016/j.brachy.2017.09.004
18. Smith BD, Arthur DW, Buchholz TA, et al. Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). Int J Radiat Oncol Biol Phys. Jul 15 2009;74(4):987-1001. doi:10.1016/j.ijrobp.2009.02.031
19. Vicini F, Arthur D, Wazer D, et al. Limitations of the American Society of Therapeutic Radiology and Oncology Consensus Panel guidelines on the use of accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys. Mar 15 2011;79(4):977-84. doi:10.1016/j.ijrobp.2009.12.047
20. Vicini F, Beitsch P, Quiet C, et al. Five-year analysis of treatment efficacy and cosmesis by the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial in patients treated with accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys. Mar 1 2011;79(3):808-17. doi:10.1016/j.ijrobp.2009.11.043
21. Wang EH, Mougalian SS, Soulos PR, et al. Adoption of intensity modulated radiation therapy for early-stage breast cancer from 2004 through 2011. Int J Radiat Oncol Biol Phys. Feb 1 2015;91(2):303-11. doi:10.1016/j.ijrobp.2014.09.011
22. Whelan TJ, Pignol JP, Levine MN, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. Feb 11 2010;362(6):513-20. doi:10.1056/NEJMoa0906260
23. Wong WW, Pockaj BA, Vora SA, Halyard MY, Gray RJ, Schild SE. Six-year outcome of a prospective study evaluating tumor bed boost with intra-operative electron irradiation followed by whole-breast irradiation for early-stage breast cancer. Breast J. Mar-Apr 2014;20(2):125-30. doi:10.1111/tbj.12235
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25. Zauls AJ, Watkins JM, Wahlquist AE, et al. Outcomes in women treated with MammoSite brachytherapy or whole breast irradiation stratified by ASTRO Accelerated Partial Breast Irradiation Consensus Statement Groups. Int J Radiat Oncol Biol Phys. Jan 1 2012;82(1):21-9. doi:10.1016/j.ijrobp.2010.08.034

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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