Radiotherapy for benign diseases started shortly after the x-ray discovery in 1896. Keloid is one of such diseases that showed decreased recurrence rate by adding postoperative radiotherapy (PORT) [1, 2]. The continuous abnormal healing that mostly exceeds the boundary of the initial wound edges characterizes post-traumatic keloid formation [3]. The ear is considered the commonest site affected by keloid scarring with cosmetic complaints and infrequent pain and pruritis [4, 5]. The proposed treatment approaches included non-invasive and invasive strategies, such as compression, intralesional injections of corticosteroids, intralesional injection of pharmaceutical agents like verapamil and bleomycin, topical therapy, laser treatment, intra-lesional cryotherapy, and surgical excision. However, it is an invasive option, resection remains the standard approach for recurrent cases following the failure of conservative measures [6,7,8,9,10,11,12].
Unfortunately, many studies showed that the incidence of postoperative local recurrence ranges from 50 to 80%. Moreover, multiple surgical resections led to bigger recurrences in most of the clinical scenarios [13,14,15]. Adjuvant PORT aiming to prevent local recurrence showed its effectiveness and superiority over other options [16,17,18]. Radiation targets immature fibroblasts which are relatively radiosensitive compared to normal fibroblasts leading to suppression of fibroblast proliferation and hence inhibition of collagen synthesis [15, 16]. Accordingly, radiation therapy (RT) should be considered as early as possible within 3 days following resection before fibroblast maturation [1, 13, 16]. This standard clinical practice of surgery followed by early PORT dated and proposed since 1981 by Ollestein et al. [19]. The proposed radiation dose varies in the literature with no consensus ranging from 7 Gray (Gy) to 13 Gy as a single dose or even fractionated ranging from 10 to 20 Gy. Most studies kept the high dose per fraction (fx) as a general concept regardless of the way of fractionation being keloids have low mitotic index [20,21,22,23,24,25,26,27]. Despite its rarity, radiation-induced second malignancy is a potentially serious side effect in such benign diseases that warrants RT optimization and discussion with the patients upon offering PORT [22, 23].
Aim of the study
The study aims to present our experience of using surgical excision with PORT for the treatment of recurrent ear keloids. The variables that possibly affect treatment outcomes were studied. The possible radiation-induced side effects and complications were evaluated.
Patients and methods
The patients presented by recurrent ear keloids (Fig. 1) and treated by surgical resection and PORT from 2006 till 2021 at our hospital were retrospectively reviewed. Institutional Review Board (IRB) approval was obtained before data collection. The medical records and radiation therapy files were used to collect the following information; disease laterality, radiation dose, number of fractions, dose per fraction, radiation energy, the interval between surgery and radiotherapy, local recurrence, early and late radiation-induced side effects. Our data were compared with other data published in the literature.
Surgical details
Excision of a keloid may stimulate additional collagen synthesis, prompting quick recurrence as a possible larger keloid than the initial one. So, the strategy of limiting tissue handling is followed. All adult patients underwent surgery under local anesthesia. The common practice at our institution is complete extramarginal excision leaving 5-mm margins of healthy skin as recommended worldwide. The incisions and wound edges are planned to be parallel to the main folding lines of the skin to decrease the recurrence rates. After undermining the surrounding skin for easy closure, the wound edges were closed under tension with absorbable subdermal and nonabsorbable subcuticular sutures.
Radiotherapy details
The radiation treatment was delivered at our department by using either electron beam therapy or orthovoltage x-ray beam. The linear accelerator is a dual-energy HDX machine (Varian Medical System, Palo Alto, USA). The orthovoltage machine is Xstrahl 300, SN Gm0372. This machine produces 9 clinical energies of x-ray beam from 60, 80, 100, 120, 150, 180, 200, 250 and 300 kilovoltage peak (kVp) with filters F1, F2, F3, F4, F5, F6, F7, F8, and F9 respectively. Patients were treated using open or closed applicators at focal spot distance 30 cm or 50 cm respectively. Open circular applicators are used with energies 60, 80, and 100 kilovolt (kV) while closed square or rectangular applicators are used with the remaining energies of more than 100 kV.
The patients were treated in the lateral position or supine position with the head turned to the other side so that the affected ear is facing up. A suitable head-rest device is used to allow proper comfortable reproducible positioning. The target volume was determined clinically including the scar plus a 1 to 1.5 cm margin (Fig. 2A). The depth was chosen clinically and mostly around 0.5–1.0 cm. Waxed lead cutout shields were positioned around the delineated target volume to block the normal tissue. Also, a waxed lead shield is placed behind the ear to protect the neck and brain and to avoid backscatter radiation (Fig. 2B). The gantry may be rotated so that the beam exits away from the inner and middle ear if applicable. In the case of treatment by 6 mega-electron volt (MeV) electron beam, a bolus of 0.5 cm thickness was applied to keep skin dose close to 100%. The dose was prescribed to 85–90% isodose line. In case of treatment with higher energies of electron beam, the skin dose was calculated, and mostly bolus is not applied. In case of orthovoltage treatment, the proper energy (filter) was used as per treatment depth with the dose prescribed to 90–95% isodose line. Different fractionation schedules were used as per the treating physician.
For the sake of comparison, we used the equivalent dose in 2-Gy fractions (EQD2) of 20 Gy with biological effective dose (BED) 40 to stratify the regimens used in our department. As a benign disease, we considered the α/β ratio for ear keloid to be 2.08 similar to late reacting tissues [28]. The regimens with EQD2 ≤ 20 Gy (BED ≤ 40) included 8 Gy/1fx and 10 Gy/2fx compared to regimens with EQD2 > 20 Gy ((BED > 40) that included 13 Gy/1fx, 15 Gy/3fx, 16 Gy/4fx, and 18 Gy/3fx.
The patients were followed up with radiation or plastic surgery departments every 3–6 months. We used telephone interviews for some patients who could not attend regular follow-up visits. Recurrence is defined as a reappearance of the keloid or progression of the residual scar elevation [16]. The recurrence-free duration is measured from the date of surgical excision till the date of local recurrence. The radiation-induced skin reactions were evaluated using Radiation Therapy Oncology Group (RTOG) grading scale [24].
Statistical analysis
Statistical package for social science version 21 (SPSS v21) was used for statistical analysis and the Kaplan-Meier method was used to estimate recurrence-free rate. The log-rank test was used to compare recurrence rates between groups. P values of < 0.05 were considered statistically significant. All different variables were studied and correlated with local recurrence. The student’s t test was used for the analysis of continuous variables. The chi-squared test and Fisher’s exact test for discrete variables were used to compare proportions.