Medical Policies - Surgery


Adipose-Derived Stem-Cells in Autologous Fat Grafting to the Breast

Number:SUR716.021

Effective Date:06-15-2018

Coverage:

*CAREFULLY CHECK STATE REGULATIONS AND/OR THE MEMBER CONTRACT*

The use of adipose-derived stem-cells (ADSCs) in autologous fat grafting (AFG) to the breast is considered experimental, investigational and/or unproven.

NOTE: This policy does not address the use of autologous fat tissue in aesthetic breast augmentation (i.e., cosmesis).

Refer to Medical Policy - Reconstruction and Contralateral Mammaplasty (SUR716.011) for coverage explanation of harvesting and grafting autologous fat tissue when used during breast reconstruction.

Description:

Autologous fat grafting (AFG) to the breast has been used as an adjunct to reconstructive breast surgery, for postmastectomy pain and in irradiated skin. Adipose-derived stem-cells (ADSCs) have been proposed as a supplement to the fat graft in an attempt to improve graft survival.

Background

AFG to the Breast

AFG to the breast has been proposed for indications that include breast augmentation and following oncologic surgery. Proposed indications after oncologic surgery include as an adjunct to reconstruction post mastectomy or lumpectomy for contour deformities and improved shape and volume of the breast, for post mastectomy pain syndrome (neuropathic pain), and for irradiated skin to soften the skin and restore it to nonirradiated appearance and consistency which may reduce complication and failure rates of implant reconstruction. Variability in long-term results and oncologic concerns have limited its application in the breast.

Adipose-Derived Stem-Cells (ADSCs)

Stem-cell biology, and the related field of regenerative medicine, involves multipotent stem-cells that exist within a variety of tissues, including bone marrow and adipose tissue. Studies have shown that 1 gram of adipose tissue yields approximately 5x103 stem-cells, which are up to 500 times greater than the number of mesenchymal stem-cells in 1 gram of bone marrow. (1) Stem-cells, because of their pluripotentiality and unlimited capacity for self-renewal, offer promise for tissue engineering and advances in reconstructive procedures. Adipose tissue in particular represents an abundant and easily accessible source of ADSCs, which can differentiate along multiple mesodermal lineages. ADSCs may allow for improved graft survival and generation of new fat tissue after transfer from another site. (1)

This identification of several potentially beneficial therapeutic properties of ADSC has led to proposed novel techniques of fat grafting in conjunction with ADSC therapy for breast fat grafting, including the differentiation of ADSC into adipocytes as a reservoir for adipose tissue turnover, the differentiation of ADSC into endothelial cells and the subsequent increase in blood supply to the grafted fat tissue, thereby decreasing the rate of graft resorption, the release of angiogenic growth factors by ADSC and the induction of angiogenesis, protection of the graft from ischemic reperfusion injury by ADSC and acceleration of wound healing at the recipient site. (1)

Current methods for isolating ADSCs can involve a variety of processes which may include centrifugation and enzymatic techniques that rely on collagenase digestion followed by centrifugal separation to isolate the stem-cells from primary adipocytes. Isolated ADSCs can be expanded in monolayer on standard tissue culture plastic with a basal medium containing 10% fetal bovine serum, (2) and newly developed culture conditions provide an environment within which the study of ADSCs can be done without the interference of animal serum. They also allow rapid expansion of autologous ADSCs in culture for use in human clinical trials. A standard expansion method has not yet been established.

Yoshimura et al., in an effort to address the problems of unpredictability and low rates of fat graft survival, developed a technique known as cell-assisted lipotransfer (CAL), which produces autogenous fat rich in ADSCs. (3) In CAL, half of the lipoaspirate is centrifuged to obtain a fraction of concentrated ADSCs while the other half is washed, enzymatically digested, filtered and spun down to an ADSC-rich pellet. The latter is then mixed with the former, converting a relatively ADSC-poor aspirated fat to ADSC-rich fat.

Regulatory Status

There are several autologous fat grafting systems cleared for marketing by the U.S. Food and Drug Administration’s (FDA) Center for Devices and Radiological Health (CDRH) through the 510(k) process as a cell saver device.

A point-of-care system is available for concentrating ADSC from mature fat. The Celution™ System (Cytori Therapeutics, Inc., San Diego, CA) is designed to transfer a patient’s own adipose tissue from 1 part of the body to another in the same surgical procedure. In September 2006, Celution™ Cell Concentration System (Cytori Therapeutics, Inc.) was cleared for marketing by the FDA’s CDRH through the 510(k) process as a cell saver device. The system is cleared for the collection, concentration, washing, and reinfusion of a patient’s own cells for applications that may include, but are not limited to, cardiovascular, plastic and reconstructive, orthopedic, vascular, and urological surgeries and procedures. FDA product code: CAC.

The GID 700, also known as the Revolve™ System (LifeCell Corp., Bridgewater, NJ) is designed as a single use, sterile, and disposable high-volume fat processing system intended for use in cosmetic enhancement or reconstructive surgery procedures that require AFG. In August 2012, Revolve™ System (LifeCell Corp.) was cleared for marketing by the FDA’s CDRH through the 510(k) process as a suction lipoplasty system. The system is cleared for the aspiration, harvesting, filtering, and transferring of autologous adipose tissue for body contouring for applications that may include, but are not limited to, plastic and reconstructive surgery, gastrointestinal and affiliated organ surgery, neurological, urological, general, orthopedic, gynecological, thoracic, and laparoscopic surgeries and procedures. FDA product code: MUU.

Lipogems® System (Lipogems International, S.p.A., Rome, Italy) is a suction lipoplasty system, which is a sterile, closed-loop fat processing system intended for use in cosmetic enhancement or reconstructive surgery procedures that require AFG. In December 2014, Lipogems® System (Lipogems International, S.p.A.) was cleared for marketing by the FDA’s CDRH through the 510(k) process as a suction lipoplasty system. The system is cleared for the aspiration, harvesting, filtering, and transferring of autologous adipose tissue for body contouring for applications that may include, but are not limited to, plastic and reconstructive surgery, gastrointestinal and affiliated organ surgery, neurological, urological, general, orthopedic, gynecological, thoracic, and laparoscopic surgeries and procedures. FDA product code: MUU.

This is not an “all inclusive” list of autologous fat grafting systems. Refer to the FDA web site at www.fda.gov for the most current listing of autologous fat grafting systems.

Rationale:

The policy was created based on searches of MedLine database for peer-reviewed, published scientific literature of randomized controlled clinical trials, retrospective cohort studies, case series, and case reports. The most recent search was completed through April 20, 2017. The following is a summary of the key literature, including systematic reviews of the studies adipose-derived stem-cells (ADSCs) used in fat grafting to the breast. Several review articles summarize autologous fat grafting (AFG) and ADSCs. (1-4)

Clinical Studies

Pérez-Cano et al. conducted a single-arm, prospective, multicenter clinical trial of 71 women who underwent breast conserving surgery for breast cancer and autologous adipose-derived regenerative cell (ADRC)?enriched fat grafting for reconstruction of defects 150 mL or less (the RESTORE-2 [Autologous Fat Enhanced with Regenerative Cells Transplanted to Reconstruct Breast Deformities After Lumpectomy] trial). (5) Trial end points included patient and investigator satisfaction with functional and cosmetic results and improvement in overall breast deformity at 12 months after procedure. Female patients (age range, 18-75 years) presenting with partial mastectomy defects and without breast prosthesis were eligible. The RESTORE-2 protocol allowed for up to 2 treatment sessions, and 24 patients elected to undergo a second procedure following the 6-month follow-up visit. Of the 67 patients treated, 50 reported satisfaction with treatment results through 12 months. Sixty-one patients underwent radiation therapy as part of their treatment; 2 patients did not receive radiation, and the status of radiation treatment was not known for the other 4 patients. Using the same metric, investigators reported satisfaction with 57 out of 67 patients. There were no serious adverse events associated with the ADRC-enriched fat graft injection procedure. There were no reported local cancer recurrences. The LENT-SOMA scale included investigator and patient assessment of postradiation signs and symptoms. The investigators of the trial found that LENT-SOMA was insufficiently sensitive to adequately reflect the clinical improvements seen in the trial population. Patients with LENT-SOMA III and IV scores (most severe symptoms) were excluded during screening, which may have contributed to the subtle LENT-SOMA score changes observed in the trial. The investigators reported improvement from baseline through 12 months in the degree of retraction or atrophy in 29 of 67 patients, while 34 patients had no change and 4 patients reported worse symptoms. Postradiation fibrosis at 12 months was reported as improved in 29 patients, while 35 patients had no change and 3 patients had worse symptoms. Management of atrophy was reported as improved in 17 patients, with 48 patients having no change and 2 patients reporting worse symptoms. Improvement in these measures reached statistical significance. The authors concluded that future comparative studies are needed to determine the incremental benefit of ADRC-enriched fat grafting compared with traditional fat grafting in various clinical circumstances. The follow-up of the study is inadequate to draw conclusions on long-term risk of cancer recurrence.

In 2008, Yoshimura et al. reported on the development of a novel strategy known as cell-assisted lipotransfer (CAL), in which autologous ADSCs are used in combination with lipoinjection. (3) From 2003 to 2007, the group performed CAL in 70 patients: in the breast in 60 patients (including 8 who had breast reconstruction after mastectomy). They reported outcomes for 40 patients with healthy thoraxes and breasts who underwent CAL for purely cosmetic breast augmentation; patients undergoing breast reconstruction for an inborn anomaly or after mastectomy were not included. Nineteen of the 40 patients had been followed for more than 6 months, with a maximum follow-up of 42 months. The authors observed that the transplanted adipose tissue was gradually absorbed during the first 2 postoperative months, and the breast volume showed a minimal change thereafter. Final breast volume showed augmentation by 100 to 200 mL after a mean fat amount of 270 mL was injected. The difference in breast circumference (defined as the chest circumference at the nipple minus the chest circumference at the inframammary fold) had increased in all cases by 4 to 8 cm at 6 months. Cyst formation or microcalcification was detected in 4 patients. The authors concluded that their preliminary results suggest that CAL is effective and safe for soft tissue augmentation and superior to conventional lipoinjection but that additional study is necessary to further evaluate the efficacy of this technique.

In 2007, Rigotti et al. reported the results of a pilot study on the presence and effectiveness of ADSCs in 20 consecutive patients undergoing therapy for side effects of radiation treatment to the breast, chest wall or supraclavicular region, with severe symptoms or irreversible function damage (LENT-SOMA scale grade 3 and 4). (6) (LENT-SOMA is one of the most common systems to assess the late effects of radiation therapy.) The mean patient age was 51 years (range, 37-71 years). The rationale behind the study was that the ADSCs, which have been shown to secrete angiogenic and antiapoptotic factors and to differentiate into endothelial cells, could promote neovascularization in ischemic tissue such as irradiated tissue. Targeted areas included the supraclavicular region, the anterior chest wall after mastectomy with or without breast prosthesis, and breast after quadrantectomy. Lipoaspirate purification procedure was performed by centrifugation to remove a large part of the triglyceride portion of the tissue and disrupt the cytoplasm of the mature adipocytes to favor their rapid clearance after injection. A stromal-vascular fraction was isolated by enzymatic digestion of extracellular matrix, centrifugation and filtration, and the fractions were cultured for 2 to 3 weeks to obtain a homogenous cell population. To assess the presence of mesenchymal stem-cells, the stromal-vascular fraction derived from the adipose tissue was cultured and characterized by flow cytometry. The number of procedures was 1 in 5 patients, 2 in 8, 3 in 6, and 6 in 1 patient. Clinical follow-up varied between 18 and 33 months (mean, 30 months). Clinical results after treatment with lipoaspirates were assessed by LENT-SOMA scoring. The 11 patients initially classified as LENT-SOMA grade 4 (irreversible functional damage) progressed to grade 0 (no symptoms), grade 1 and grade 2 in 4, 5 and 1 cases, respectively. In 1 case, no improvements were observed. In the 4 patients who had undergone mastectomy and had breast prostheses and areas of skin necrosis, the necrosis showed complete remission. In the group of 9 patients classified as LENT-SOMA grade 3, fibrosis, atrophy, and retraction progressed to grade 0 and 1 in 5 and 4 cases, respectively.

A November 2016 UpToDate overview of breast reconstruction addressed breast contour abnormalities in breast conserving surgeries. (7) They stated, “The most common contemporary reconstructive procedure performed to restore a breast contour is fat grafting (autologous fat transfer). Prospective studies have shown that fat grafting is an effective approach to correct these deformities.” The authors include mastopexy and reduction mammaplasty as other surgical approaches to address breast contour abnormalities. They cited a study comparing secondary procedures following breast conserving surgery (AFG was included), ipsilateral breast reduction or mastopexy were done 41%, augmentation or implant exchange was 18%, myocutaneous flaps were done 17%, local procedures (AFG) was 14%, and contralateral breast reduction were done 10%.

Ongoing and Unpublished Clinical Trials

A search of ClinicalTrials.gov in April 2017 did not identify any ongoing or unpublished trials that would likely influence this medical policy.

Practice Guidelines and Position Statements

American Society for Aesthetic Plastic Surgery (ASAPS) and American Society of Plastic Surgeons (ASPS)

A joint task force of the ASAPS and the ASPS released a position statement on the use of stem-cells in aesthetic surgery during the 2011 annual meeting of ASAPS. (8) Based on a systematic review of the peer-reviewed literature, the task force concluded that while there is potential for the future use of stem-cells in aesthetic surgical procedures, the scientific evidence and other data are very limited in terms of assessing the safety or efficacy of stem-cell therapies in aesthetic medicine.

Summary of Evidence

The evidence for the use of ADSCs in patients who have breast cancer and are undergoing autologous fat grafting to the breast includes small single-arm studies, some of which are prospective. Relevant outcomes are overall survival, disease-specific survival, symptoms, change in disease severity, morbid events, functional outcomes, quality of life, resource utilization, and treatment-related morbidity. Studies have mainly reported patient and investigator satisfaction and functional and cosmetic results. Limitations of the data are small numbers of patients, short-term follow-up, and lack of understanding of the possible oncologic influence ADSC may have on the fat grafting procedure. Therefore, the evidence is insufficient to determine the effects of the technology on health outcomes.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

There is no specific CPT code for this procedure. One of the following codes might be used – 19366, 19380, 19499, and 20926.

CODING:

Disclaimer for coding information on Medical Policies

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.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

19366, 19380, 19499, 20926

HCPCS Codes

None

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.

A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

1. Mizuno H, Hyakusoku H. Fat grafting to the breast and adipose-derived stem-cells: recent scientific consensus and controversy. Aesthet Surg J. May-Jun 2010; 30(3):381-7. PMID 20601560

2. Sterodimas A, de Faria J, Nicaretta B, et al. Tissue engineering with adipose-derived stem-cells (ADSCs): current and future applications. J Plast Reconstr Aesthet Surg. Nov 2010; 63(11):1886-92. PMID 19969517

3. Yoshimura K, Sato K, Aoi N, et al. Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/stromal cells. Aesthetic Plast Surg. Jan 2008; 32(1):48-55; discussion 56-7. PMID 17763894

4. Wilson A, Butler PE, Seifalian AM. Adipose-derived stem-cells for clinical applications: a review. Cell Prolif. Feb 2011; 44(1):86-98. PMID 21199013

5. Perez-Cano R, Vranckx JJ, Lasso JM, et al. Prospective trial of adipose-derived regenerative cell (ADRC)-enriched fat grafting for partial mastectomy defects: the RESTORE-2 trial. Eur J Surg Oncol. 2012; 38(5):382-9. PMID 22425137

6. Rigotti G, Marchi A, Galie M, et al. Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adult stem-cells. Plast Reconstr Surg. Apr 15 2007; 119(5):1409-22; discussion 23-4. PMID 17415234

7. Nahabedian, Maurice, et al. Overview of breast reconstruction. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA. Available at <http://www.uptodate.com> (accessed April 19, 2017).

8. Joint ASPS & ASAPS Position Statement: Stem-cells and Fat Grafting (May 2011). Prepared by the American Society of Plastic Surgeons and the American Society for Aesthetic Plastic Surgery. Available at <http://www.surgery.org (accessed December 9, 2015).

9. ASPS Guiding Principles: Fat Transfer/Fat Graft and Fat Injection (January 2009). Prepared by the American Society of Plastic Surgeons. Available at <http://www.plasticsurgery.org> (accessed April 19, 2017).

10. Adipose-Derived Stem-Cells in Autologous Fat Grafting to the Breast. Chicago, Illinois: Blue Cross Blue Shield Association. Medical Policy Reference Manual (2015 October) Surgery 7.01.153.

Policy History:

Date Reason
6/15/2018 Reviewed. No changes.
7/15/2017 Document updated with literature review. Coverage unchanged. The following information was added: Refer to Medical Policy – Reconstruction and Contralateral Mammaplasty (SUR716.011) for coverage explanation of harvesting and grafting autologous fat tissue when used during breast reconstruction.
11/1/2016 Reviewed. No changes.
5/1/2016 New medical document. The use of adipose-derived stem-cells in autologous fat grafting to the breast is considered experimental, investigational and/or unproven.

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