Radiation effect in mouse skin: Dose fractionation and wound healing

Gorodetsky, Raphael; Mou, Xiaode; Fisher, David R.; Taylor, Jeremy M. G.

doi:10.1016/0360-3016(90)90443-n

Cited by 47 publications

(39 citation statements)

References 17 publications

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“…In a mouse model, Gorodetsky et al demonstrated that the effect of single-fraction radiation on wound strength recovery was dependent on dose per fraction when administered immediately before wounding of the skin. 7 The threshold for dose response was approximately 8 Gy, with a linear dose response up to approximately 20 Gy, at which the maximum decrease in wound strength was observed. Higher doses of up to 26 Gy showed no further decrease in wound strength.…”

Section: Discussionmentioning

confidence: 93%

No association between excessive wound complications and preoperative high-dose, hypofractionated, image-guided radiation therapy for spine metastasis

Keam

Bilsky²,

Laufer³

et al. 2014

SPI

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Object Radiation therapy is known to impair wound healing. Higher dose per fraction is believed to increase this risk. This study sought to quantify rates of wound complication in patients receiving preoperative conventionally fractionated radiotherapy (XRT) or high-dose hypofractionated image-guided radiation therapy (IGRT) for spinal metastasis, and to identify predictors of wound complication. Methods The records of 165 consecutive patients who underwent spine surgery for metastasis at Memorial Sloan–Kettering Cancer Center between 1999 and 2010, with a history of prior radiation therapy, were reviewed. Patients with primary spine tumors, 2 courses of prior radiation therapy to the surgical site, total dose < 9 Gy, or radiation therapy adjacent to or partially overlapping the surgical site, were excluded. One hundred thirty patients received XRT (≤ 3 Gy/fraction) and 35 received IGRT (> 3 Gy/fraction). The total dose prescribed to the 100% isodose line to treat the planning target volume was 18–30 Gy in 1–5 fractions. Clinical factors evaluated included age, Karnofsky Performance Scale score, body mass index, presence of diabetes, smoking, ambulatory status, prior surgery at same spinal site, preoperative laboratory results (hemoglobin, lymphocyte count, and albumin), perioperative chemotherapy or steroids, estimated blood loss, extent of stabilization hardware, time between radiation therapy and surgery, number of vertebral bodies irradiated, total radiation dose, and dose per fraction of radiation therapy. Wound complication was defined as poor healing, dehiscence, or infection. Potential predictors of wound complication were assessed by univariate analyses using competing-risk methods to adjust for risk of death. Results For XRT patients, median dose was 30 Gy (range 11.5–70 Gy) with 72% of them receiving 3 Gy × 10 fractions. For IGRT patients, 66% received 18–24 Gy × 1 fraction and 23% received 6 Gy × 5 fractions. Groups differed only by the mean number of vertebral bodies treated (4.6 XRT and 1.8 IGRT, p < 0.0001). Wound complications occurred at a median of 0.95 months (range 0.4–3.9 months). A total of 22 wound events occurred in the XRT group and 2 in the IGRT group. The 6-month cumulative incidence of wound complications for XRT was 17% and for IGRT was 6%. There was no significant difference in wound complications between groups (IGRT vs XRT: hazard ratio 0.31, 95% CI 0.08–1.3; p = 0.11). Higher dose per fraction appeared to be associated with a lower risk of wound complication (hazard ratio 0.27, 95% CI 0.06–1.15; p = 0.08), which trended toward significance. Univariate analyses did not reveal any significant predictors of wound complications. Conclusions Patients who underwent XRT or IGRT did not have significantly different rates of postoperative wound complications. This finding may be explained by the treatment of fewer vertebral bodies in IGRT patients, or by the low overall number of total events. With a wound complication rate of 6%, preoperative IGRT, a highly conformal treatment, resulted in a very low rate of surgical wound complication.

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Section: Discussionmentioning

confidence: 93%

No association between excessive wound complications and preoperative high-dose, hypofractionated, image-guided radiation therapy for spine metastasis

Keam

Bilsky²,

Laufer³

et al. 2014

SPI

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“…1). In contrast, high-dose irradiation was shown to significantly reduce wound strength [14,15,16] with only minimal changes in histopathology and apparent collagen levels in the scar [15]. …”

Section: Discussionmentioning

confidence: 99%

“…A sharp parallel multiblade razor apparatus was used to cut the skin perpendicular to the wound to yield 7–8 equal skin samples from each wound, each containing an exactly 2-mm-wide section of the wound [14]. These skin strips were secured between small round paper reinforcement frames as previously described [14,15,16]. The samples were loaded on a computerized Ametek tensiometer (model 100 test system; Ametek, Mansfield, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Irradiated skin that underwent a significant stress should be more sensitive to any further insult, due to damages inflicted to the collagen-producing and collagen-reorganizing dermal cells. In previous studies we identified the dose of radiation that would delay wound healing with tolerable effect on intact skin [14,15,16]. Irradiation by these doses did not necessarily result in measurable depletion of the major skin collagen types I and III but in their remodeling by cells [15].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Halofuginone, a Collagen α1(I) Inhibitor, on Wound Healing in Normal and Irradiated Skin: Implication for Hematopoietic Stem Cell Transplantation

et al. 2007

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It is a major interest in the field of hematopoietic stem cell transplantation to reduce scarring of healing wounds with overdeposition of collagen due to radiation injury or graft-versus-host disease. Halofuginone (HF) inhibits collagen α1(I) gene expression and overdeposition of collagen. We examined the effect of HF on the healing of full-depth incision wounds inflicted in normal skin or skin areas compromised by local preirradiation with 18 Gy. Preirradiation significantly decreased the tensile strength of the healing wounds at day 14 (by ∼60%, p < 0.0001). In contrast, HF treatment did not significantly decrease the strength of wounds inflicted in both normal and preirradiated skin. Histological evaluation revealed that HF induced moderate thinning of the dermis accompanied by elevated thickness of the epidermis and enhanced rejoining of subdermal muscles in the wound area. HF only minimally reduced total collagen deposition in both groups, with minor changes in the level of more matured fibrillar collagen network. Our study demonstrates that HF does not significantly affect wound strength. This encourages the possible use of HF as an antifibrotic agent with minimal complications for post-hematopoietic stem cell transplantation complications including radiation toxicity and graft-versus-host disease.

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“…Choice of Irradiation Dose It is reported that the maximum decrease in wound strength occurs with a single dose of 20 Gy [7][8][9] and that skin graft changes are observed after at least 25 Gy [1] . Therefore, 25-Gy single doses were applied to the experimental groups in this study.…”

mentioning

confidence: 99%

The Effect of External Beam Irradiation Timing on Skin Graft Survival

et al. 2010

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Background: The purpose of this study was to evaluate skin graft integrity after external beam irradiation in a rat model. Methods: Forty-eight male Wistar rats were randomly assigned to 8 groups (A, B, C, D, A_c, B_c, C_c and D_c). A rectangular full-thickness skin graft was raised and reapplied to its original bed on the dorsum of each rat. Groups A_c, B_c, C_c and D_c were the control groups and were not given postoperative irradiation. After grafting, 25 Gy unfractioned cobalt⁶⁰ irradiation was administered to groups A, B, C and D on postoperative days 10, 20, 30 and 40, respectively. Histological samples were obtained 8 weeks after grafting. Dermal and epidermal thickness were measured by the KS-400 image analysis program. Results: The difference in the epidermal and/or dermal thickness between the irradiated groups was not found to be significant. Furthermore, when histological features and the image analysis of the irradiated groups were compared with each other, there were no significant differences between the groups. Conclusions: Although we are aware that experimental results may not directly translate to the clinical setting, the present study indicates that external radiotherapy can be performed to skin-grafted areas as early as 10 days postoperatively.

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Radiation effect in mouse skin: Dose fractionation and wound healing

Cited by 47 publications

References 17 publications

No association between excessive wound complications and preoperative high-dose, hypofractionated, image-guided radiation therapy for spine metastasis

No association between excessive wound complications and preoperative high-dose, hypofractionated, image-guided radiation therapy for spine metastasis

Effect of Halofuginone, a Collagen α1(I) Inhibitor, on Wound Healing in Normal and Irradiated Skin: Implication for Hematopoietic Stem Cell Transplantation

The Effect of External Beam Irradiation Timing on Skin Graft Survival

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