Chronic wounds are a significant burden on the healthcare system, contributing to morbidity and mortality.1,2 Bioengineered skin substitutes (SS) with a dermal component may improve healing outcomes in diabetic foot ulcers and venous leg ulcers.3 However, limited research exists on the use of SS for other difficult-to-treat wounds such as pyoderma gangrenosum, radiation dermatitis, or sclerotic cutaneous graft-versus-host disease. Furthermore, cancer patients are at risk of developing chronic wounds from their underlying disease or as a complication of medication, surgery, or radiation therapy. Wound healing may be complicated in these patients due to the oncologic disease process and/or anti-neoplastic treatments. This study characterizes the types of wounds prompting referrals for SS in patients with cancer and describes the efficacy of SS in the treatment of chronic wounds in this population.
Patients with cutaneous or non-cutaneous cancer who received a SS for a chronic wound by the Memorial Sloan Kettering Cancer Center Dermatology Service between 3/2017 – 12/2019 were included in this IRB-approved retrospective study. Response to treatment was defined by percent change in wound surface area, including complete response (CR) [≥95% decrease], partial response (PR) [50%–94% decrease], stable disease (<50% decrease) and progression of disease (increase in wound surface area). Recurrence was defined as development of a wound after complete closure or enlargement after PR. Cancer type, chronic wound risk factors, and other treatments were assessed (Supplemental Table I).
Thirty-two patients (53% female; mean [SD] age, 66 [16] years) received SS for chronic wounds (Table I). The most common wound was peristomal pyoderma gangrenosum (PPG; 22%). Median time from development of wound until application of first SS was 133 days (IQR 263). Clinical response was observed in 84% (n=27) of patients, including 16 patients (50%) with CR and 11 (34%) with PR. Median time to PR was 31 days, while median time to CR was 97 days. Nine (28%) patients had wound recurrence and seven (22%) received a second skin substitute. Patients requiring a second SS had slower healing times and worse outcomes (Table I). All seven patients with PPG had a clinical response, including six (86%) with CR (Table II). However, PPG recurred in 4/7 (57%) patients. There were no significant associations between wound healing outcomes and type of SS, anatomic location, laboratory values, or concurrent treatments. Limitations include the retrospective design, small number of patients, and single-institution setting.
Table I.
Baseline characteristics of patients receiving skin substitutes.
| Characteristic | n=32 |
|---|---|
| Age, years | |
| Mean (SD) | 66 (16) |
| Sex, n (%) | |
| Female | 17 (53) |
| Male | 15 (47) |
| Wound type, n (%) | |
| Pyoderma gangrenosum, peristomal | 7 (22) |
| Vasculopathic ulcer | 5 (16) |
| Venous stasis ulcer | 4 (13) |
| Radiation Dermatitis | 3 (9) |
| Sclerotic chronic cutaneous graft-versus-host disease | 3 (9) |
| Surgical wound | 3 (9) |
| Malignant wound | 3 (9) |
| Traumatic skin ulcer | 2 (6) |
| Pyoderma gangrenosum, breast | 1 (3) |
| Drug-induced ulcer | 1 (3) |
| Wound location, n (%) | |
| Abdomen | 8 (25) |
| Ankle | 6 (19) |
| Foot | 5 (16) |
| Leg | 5 (16) |
| Breast | 3 (9) |
| Inguinal fold | 2 (6) |
| Arm | 1 (3) |
| Orbit | 1 (3) |
| Trunk | 1 (3) |
| Wound duration prior to skin substitute, days | |
| Median (IQR) | 133 (263) |
| Wound size prior to skin substitute, cm2 | |
| Median (IQR) | 8.2 (23) |
| Wound size after skin substitute, cm2 | |
| Median (IQR) | 10 (9) |
| Type of skin substitute, n (%) | |
| Apligraf | 14 (44) |
| PuraPly AM | 12 (38) |
| AmnioFill | 4 (13) |
| Epifix | 1 (3) |
| Kerecis | 1 (3) |
| Number of applications of skin substitute, median (IQR) | 2 (2) |
| Apligraf | 2.5 (4) |
| PuraPly AM | 1.5 (1) |
| AmnioFill | 2.5 (1.5) |
| Epifix | 6 (0) |
| Kerecis | 1 (0) |
| Response in ulcer size, n (%) | |
| Complete response | 16 (50) |
| Partial response | 11 (34) |
| Stable disease | 3 (9) |
| Progression of disease | 2 (6) |
| Median time to response, days (IQR) | |
| Complete response | 97 (90) |
| Partial response | 31 (58) |
| Stable disease | 14 (227) |
| Progression of disease | 29 (7) |
| Recurrence of wound after response, n (%) | 9 (28) |
| Median time to recurrence, days (IQR) | 61 (74) |
| Developed infection after receiving skin substitute, n (%) | 2 (6) |
| Second type of skin substitute, n (%) | 7 (22) |
| PuraPly AM | 4 (13) |
| AmnioFill | 1 (3) |
| Epifix | 1 (3) |
| Kerecis | 1 (3) |
| Response to second type of skin substitute, n (%) | |
| Partial response | 3/7 (43) |
| Stable disease | 3/7 (43) |
| Complete response | 1/7 (14) |
| Median time to response to second type of skin substitute, days (IQR) | |
| Partial response | 109 (295) |
| Stable disease | 115 (161) |
| Complete response | 326 (0) |
| Follow-up, days | |
| Mean (SD) | 300 (298) |
SD, standard deviation; IQR, interquartile range
Table II.
Response in ulcer size by treatment and wound type.
| Response | |||||
|---|---|---|---|---|---|
| Characteristic, n (%) | Complete response | Partial response | Stable disease | Progression of disease | Positive response (PR or CR) |
| Pyoderma gangrenosum, peristomal (n=7) | 6/7 (86) | 1/7 (14) | 0/7 (0) | 0/7 (0) | 7/7 (100) |
| PuraPly AM (n=7) | 6/7 (86) | 1/7 (14) | 0/7 (0) | 0/7 (0) | 7/7 (100) |
| Vasculopathic ulcer (n=5) | 3/5 (60) | 2/5 (40) | 0/5 (0) | 0/5 (0) | 5/5 (100) |
| Apligraf (n=4) | 3/4 (75) | 1/4 (25) | 0/4 (0) | 0/4 (0) | 4/4 (100) |
| PuraPly AM (n=1) | 0/1 (0) | 1/1 (100) | 0/1 (0) | 0/1 (0) | 1/1 (100) |
| Venous stasis ulcer (n=4) | 2/2 (100) | 2/2 (100) | 0/2 (0) | 0/2 (0) | 4/4 (100) |
| Apligraf (n=4) | 2/2 (100) | 2/2 (100) | 0/2 (0) | 0/2 (0) | 4/4 (100) |
| Malignant wound (n=3) | 0/3 (0) | 1/3 (33) | 1/3 (33) | 1/3 (33) | 1/3 (33) |
| PuraPly AM (n=3) | 0/3 (0) | 1/3 (33) | 1/3 (33) | 1/3 (33) | 1/3 (33) |
| Radiation Dermatitis (n=3) | 0/3 (0) | 1/3 (33) | 2/3 (67) | 0/3 (0) | 1/3 (33) |
| Apligraf (n=2) | 0/2 (0) | 1/2 (50) | 1/2 (50) | 0/2 (0) | 1/2 (50) |
| Kerecis (n=1) | 0/1 (0) | 0/1 (0) | 1/1 (100) | 0/1 (0) | 0/1 (0) |
| Sclerotic chronic cutaneous graft-versus-host disease (n=3) | 2/3 (67) | 1/3 (33) | 0/3 (0) | 0/3 (0) | 3/3 (100) |
| Amniofill (n=1) | 0/1 (0) | 1/1 (100) | 0/1 (0) | 0/1 (0) | 1/1 (100) |
| Apligraf (n=1) | 1/1 (100) | 0/1 (0) | 0/1 (0) | 0/1 (0) | 1/1 (100) |
| Epifix (n=1) | 1/1 (100) | 0/1 (0) | 0/1 (0) | 0/1 (0) | 1/1 (100) |
| Surgical wound (n=3) | 1/3 (33) | 1/3 (33) | 0/3 (0) | 1/3 (33) | 2/3 (67) |
| Apligraf (n=2) | 1/2 (50) | 0/2 (0) | 0/2 (0) | 1/2 (50) | 1/2 (50) |
| Amniofill (n=1) | 0/1 (0) | 1/1 (100) | 0/1 (0) | 0/1 (0) | 1/1 (100) |
| Traumatic skin ulcer (n=2) | 1/2 (50) | 1/2 (50) | 0/2 (0) | 0/2 (0) | 2/2 (100) |
| Amniofill (n=1) | 0/1 (0) | 1/1 (100) | 0/1 (0) | 0/1 (0) | 1/1 (100) |
| Apligraf (n=1) | 1/1 (100) | 0/1 (0) | 0/1 (0) | 0/1 (0) | 1/1 (100) |
| Pyoderma gangrenosum, breast (n=1) | 1/1 (100) | 0/1 (0) | 0/1 (0) | 0/1 (0) | 1/1 (100) |
| PuraPly AM (n=1) | 1/1 (100) | 0/1 (0) | 0/1 (0) | 0/1 (0) | 1/1 (100) |
| Drug-induced ulcer (n=1) | 0/1 (0) | 1/1 (100) | 0/1 (0) | 0/1 (0) | 1/1 (100) |
| Amniofill (n=1) | 0/1 (0) | 1/1 (100) | 0/1 (0) | 0/1 (0) | 1/1 (100) |
PR, partial response; CR, complete response
This study demonstrates the promise of SS in ten types of wounds that develop in cancer patients. The most common wound in our cohort was PPG. A recent systematic review found that systemic corticosteroids were the most commonly used systemic treatment for PPG.4 However, immunosuppressive treatments, such as systemic corticosteroids or cyclosporine, may reduce the anti-tumor effect of immune checkpoint inhibitors or increase the risk for infection in combination with targeted or cytotoxic chemotherapies.5 Therefore, SS represent a steroid-sparing alternative for difficult-to-manage wounds in this population. These data may help inform wound management to improve outcomes and to serve as a foundation for future randomized studies in this high-risk population.
Supplementary Material
Funding sources:
Dr. Markova is supported by a Dermatology Foundation Career Development Award. This study was also funded in part by a grant from the National Cancer Institute / National Institutes of Health (P30-CA008748) made to the Memorial Sloan Kettering Cancer Center.
Role of the funder/sponsor:
The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Conflicts of interest disclosure:
JRS and SWD do not have any conflicts of interest to disclose.
AM: advisory board of AstraZeneca. Dr. Markova also receives research funding from Incyte.
SJN: advisory board of Kyowa Kirin.
Footnotes
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IRB approval status: Approved by the Institutional Review Board of Memorial Sloan Kettering Cancer Center Protocol 16–458.
References
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