| Coverage Policy Manual | |
| Policy #: | 2015033 |
| Category: | Medicine |
| Initiated: | November 2015 |
| Last Review: | February 2024 |
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| Adipose-Derived Stem Cells in Autologous Fat Grafting to the Breast | |
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| Description: |
Following a mastectomy, patients often experience pain and irradiated skin; as an adjunct to reconstructive breast surgery, surgeons will sometimes graft autologous fat to the breast. Adipose-derived stem cells (ADSCs) have been proposed as a supplement to the fat graft in an attempt to improve graft survival; however, whether ADSCs play a role in tumorigenesis is still relatively unknown.
Autologous Fat Grafting to the Breast
Autologous fat grafting to the breast has been proposed for indications that include breast augmentation following oncologic surgery. Grafting would be performed as an adjunct to reconstruction after mastectomy or lumpectomy for contouring improving shape and volume, for alleviating post-mastectomy pain syndrome (neuropathic pain), and for irradiated skin (thereby reducing complication and failure rates of implant reconstruction). Variability in long-term results and oncologic concerns have limited application of autologous fat grafting in the breast.
Note: This evidence review does not address the use of autologous fat tissue in aesthetic breast augmentation (i.e., cosmesis).
Adipose-Derived Stem Cells
Stem cell biology, and the related field of regenerative medicine involve multipotent stem cells that exist within a variety of tissues, including bone marrow and adipose tissue. A single gram of adipose tissue yields approximately 5000 stem cells; This is 100 to 500 times the number of mesenchymal stem cells found in an equivalent amount of bone marrow (Mizuno, 2010). Stem cells, because of their pluripotentiality and unlimited capacity for self-renewal, offer promise for tissue engineering and advances in reconstructive procedures. In particular, adipose tissue represents an abundant and easily accessible source of adipose-derived stem cells (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 (Mizuno, 2010; Wilson, 2011).
The potentially therapeutic properties of ADSC have led to novel techniques of fat grafting in conjunction with ADSC therapy for breast fat grafting. Differentiation of ADSC into adipocytes may provide a reservoir for adipose tissue turnover. Differentiation of ADSC into endothelial cells, with the release of angiogenic growth factors by ADSC, may decrease the rate of graft resorption by increasing blood supply to the grafted fat tissue. Further, ADSC may serve to accelerate wound healing and protect the graft from ischemia reperfusion injury (Mizuno, 2010). 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 (Sterodimas, 2010). Newly developed culture conditions provide an environment in which the study of ADSCs can be done without the interference of animal serum. They may also allow rapid expansion of autologous ADSCs in culture for use in human clinical trials. A standard expansion method has not yet been established.
To address the problems of unpredictability and low rates of fat graft survival, Yoshiumra et al developed a technique known as cell-assisted lipo-transfer (CAL), which produces autogenous fat rich in ADSCs (Yoshimura, 2011). 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.
A point-of care system is available for concentrating ADSC from mature fat. The Celution™ System
(Cytori Therapeutics) is designed to transfer a patient’s own adipose tissue from 1 part of the body to another in the same surgical procedure.
REGULATORY STATUS
In September 2006, Celution™ Cell Concentration System (Cytori Therapeutics) was cleared for marketing by the U.S. Food and Drug Administration’s (FDA) Center for Devices and Radiological Health 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 urologic surgeries and procedures. In 2007, Cytori Therapeutics received the FDA 510(k) clearance to market the Autologous Fat Transfer system, which transfers a patient’s own adipose tissue from one part of the patient’s body to another. FDA product code: CAC.
In 2017, the Revolve Envi 600 Advanced Adipose System (LifeCell Corporation, Branchburg, NJ) was cleared for marketing by the FDA through the 510(k) process. The system harvests, filters, and transfers autologous adipose tissue for fat grafting. Uses include reconstructive surgery. In May of 2020, the Revolve Envi 600 System underwent various design modifications (K163647). FDA product code: MUU.
Coding
There is no specific CPT code for this procedure. One of the following CPT codes might be used:
19366: Breast reconstruction with other technique
19380: Revision of reconstructed breast
19499: Unlisted procedure, breast
20926: Tissue grafts, other (e.g., paratenon, fat, dermis)
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Policy/ Coverage: |
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
The use of adipose-derived stem cells in autologous fat grafting to the breast does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For members with contracts without primary coverage criteria, the use of adipose-derived stem cells in autologous fat grafting to the breast is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
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| Rationale: |
This evidence review was created in October 2015, with the most recent literature search performed through September 13, 2015.
The literature on the use of fat grafting to the breast with the use of adipose-derived stem cells (ADSCs) consists of retrospective cohort studies, case series, and case reports. Following is a summary of the key literature to date, including systematic reviews of the studies using fat grafting to the breast and all identified case series using fat grafting to the breast with the supportive use of ADSCs.
Several review articles summarize autologous fat grafting and ADSCs (Mizuno, 2010; Sterodimas, 2010; Yoshimura, 2008; Wilson, 2011).
Pérez-Cano and colleagues 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 trial) (Pérez-Cano, 2012). 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 radiotherapy 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 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.
Yoshimura and colleagues reported on the development of a novel strategy known as cell-assisted lipo-transfer (CAL), in which autologous ADSCs are used in combination with lipo injection (Yioshimura, 2008). 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.
Rigotti and colleagues reported the results of a pilot study on the presence and effectiveness of ADSCs in 20 consecutive patients undergoing therapy for adverse 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) (Rigotti, 2007). (LENT-SOMA is one of the most common systems to assess the late effects of radiotherapy.) 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. A 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 lipo-aspirates 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.
Ongoing and Unpublished Clinical Trials
A search of ClinicalTrials.gov in September 2015 did not identify any ongoing or unpublished trials that would likely influence this review.
Summary of Evidence
The evidence for the use of adipose-derived stem cells (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.
Practice Guidelines and Position Statements
American Society for Aesthetic Plastic Surgery and American Society of Plastic Surgeons
A joint task force of the American Society for Aesthetic Plastic Surgery (ASAPS) and the American
Society of Plastic Surgeons released a position statement on the use of stem cells in aesthetic surgery during the 2011 annual meeting of ASAPS (Kamakura, 2011). 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
2017 Update
A literature search using the MEDLINE database through October 2017 did not reveal any new literature that would prompt a change in the coverage statement. The key identified literature is summarized below.
2018 Update
A literature search was conducted through October 2018. There was no new information identified that would prompt a change in the coverage statement.
2019 Update
Annual policy review completed with a literature search using the MEDLINE database through October 2019. No new literature was identified that would prompt a change in the coverage statement.
2020 Update
Annual policy review completed with a literature search using the MEDLINE database through October 2020. No new literature was identified that would prompt a change in the coverage statement.
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through October 2021. No new literature was identified that would prompt a change in the coverage statement.
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through October 2022. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
Jeon et al evaluated the efficacy of CAL on the fat graft retention rate in patients with volume deficit after undergoing autologous breast reconstruction following total mastectomy (Jeon, 2021). This 12-month prospective study included 20 patients (20 breasts) between 2017 and 2019. Patients were divided into 2 groups: autologous fat graft without stromal-vascular fraction (i.e., without ADSC) or autologous fat graft with stromal-vascular fraction of ADSC. The retention rate of the fat graft was higher in the group with ADSC than in the group without at both postoperative 6 months (73.8% vs 62.2%; p=.03) and 12 months (65.4% vs 48.4%; p=.03). Based on a modified BREAST-Q questionnaire at 12 months, the group who received fat graft with ADSC reported higher patient satisfaction (49.4 points out of 55 compared to 44.2 points out of 55), although this was not statistically significant. Fat necrosis occurred in 1 patient each in both groups, however, locoregional recurrence was not observed in any patient during follow-up. The authors concluded that CAL with stromal-vascular fraction provided better outcomes in terms of volume retention compared to CAL without ADSC.
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through October 2023. No new literature was identified that would prompt a change in the coverage statement.
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2024. No new literature was identified that would prompt a change in the coverage statement.
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| References: |
Agha RA, Pidgeon TE, Borrelli MR, et al.(2018) Validated Outcomes in the Grafting of Autologous Fat to the Breast: The VOGUE Study. Development of a Core Outcome Set for Research and Audit. Plast Reconstr Surg. May 2018;141(5):633e-638e. PMID 29697603 Jeon HJ, Choi DH, Lee JH, et al.(2021) A Prospective Study of the Efficacy of Cell-Assisted Lipotransfer with Stromal Vascular Fraction to Correct Contour Deformities of the Autologous Reconstructed Breast. Aesthetic Plast Surg. Jun 2021; 45(3): 853-863. PMID 32995982 Kamakura T, Ito K.(2011) Autologous cell-enriched fat grafting for breast augmentation. Aesthetic plastic surgery 2011; 35(6):1022-30. Mizuno H, Hyakusoku H.(2010) Fat grafting to the breast and adipose-derived stem cells: recent scientific consensus and controversy. Aesthetic surgery journal / the American Society for Aesthetic Plastic surgery 2010; 30(3):381-7. Perez-Cano R, Vranckx JJ, Lasso JM et al.(2012) Prospective trial of adipose-derived regenerative cell (ADRC)-enriched fat grafting for partial mastectomy defects: the RESTORE-2 trial. European journal of surgical oncology: Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 2012; 38(5):382-9. Rigotti G, Marchi A, Galie M et al.(2007) Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adult stem cells. Plastic and reconstructive surgery 2007; 119(5):1409-22; discussion 23-4. Sterodimas A, de Faria J, Nicaretta B et al.(2010) Tissue engineering with adipose-derived stem cells (ADSCs): current and future applications. Journal of plastic, reconstructive & aesthetic surgery: JPRAS 2010; 63(11):1886-92. Wilson A, Butler PE, Seifalian AM.(2011) Adipose-derived stem cells for clinical applications: a review. Cell proliferation 2011; 44(1):86-98. Yoshimura K, Sato K, Aoi N et al.(2008) Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/stromal cells. Aesthetic plastic surgery 2008; 32(1):48- 55; discussion 56-7. |
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Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2024 American Medical Association. |
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