Postoperative radiotherapy of keloids: a twenty-year experience

ARTICLE

The management of keloids has always been a difficult problem: treatment by surgery alone is followed by recurrences in 50 to 80% of cases [1]. Therefore, adjuvant techniques have been proposed to improve therapeutic outcomes.

The use of radiotherapy in the treatment of keloids was first reported by De Beaurman and Gougerot [2] in 1906: they recommended combined excision and postoperative x-ray therapy. Cosman et al. [1], in 1961, introduced the immediate administration of x-ray therapy after surgical excision of the keloid. In the past four decades, many reports about radiotherapy of keloids have been published [3-12]: this kind of treatment, using various protocols, has been a safe and efficient way of reducing recurrences.

The purpose of our study was to evaluate the results of a twenty-year experience with postoperative radiotherapy in a group of 120 patients with keloids.

Material and methods

Case series

From 1981 to 2000, 124 patients with keloid lesions were treated with postoperative radiotherapy. Four cases were not included in the series presented, since their follow-up was less than six months, regarded as the minimum significant time length. Sixty-six patients were female and 54 male, aged 10 to 68 years (mean 37.12 years). One hundred and fifty-six lesions were surgically excised and irradiated. In all cases the clinical diagnosis of keloid was confirmed histologically. Family history was negative for a tendency to form keloids in 95 cases (79.16%) and positive in the remaining 25 (20.83%). The local etiologic factors are listed in Table I and the localization of the lesion is summarized in Table III. Table II reports previously administered treatments (in some lesions more than one treatment, while some keloids had not been previously treated). The time interval between the excision of the keloid lesions and the beginning of radiotherapy ranged from 24 hrs to 23 days: thirty-six lesions (23.07%) were treated within 48 hrs, 91 (58.33%) in 3-7 days and 29 (18.58%) in 8-23 days. All the patients were previously evaluated in collaboration with the surgeon in order to better define the size of the irradiation fields. In some cases radiotherapy was started before the stitches of the suture following the keloid excision had been completely removed. A wound dehiscence occurred in four patients; in two cases there was a failure of the spare skin graft.

We did not observe severe complications after x-ray therapy: only one patient showed a mild skin reaction (microvesicles and itching) that subsided spontaneously in a few days. No late stochastic nor non-stochastic damages which could be attributed to radiologic treatment was observed. It is well known, in fact, that the reactions to ionizing radiations may be classified into two groups: stochastic damage, which may also appear following very low doses of ionizing radiation, and non stochastic damage, occurring only when a certain dose threshold is surpassed. Genetic effects and radiogenic internal neoplasms belong to the first group, while in particular acute and chronic radiodermatitis, radiogenic skin cancer and cataract belong to the second. In the series studied, the employement of appropriate shields for critical organs (see "Radiotherapy technique") and the limitation of the total doses of ionizing radiations administered have prevented the occurrence of this kind of reaction up to now.

Most keloid lesions were photographed before being surgically removed, after the end of radiotherapy and during follow-up. The latter was planned so as to perform a first control one month from the end of treatment, then the patients were controlled every sixth months for 5 years and once a year afterwards.

Surgical technique

The keloid was usually excised by removing a lozenge of skin including the keloid, so that a flat and linear scar would be obtained. The deep layers were sutured with resorbable material, while the superficial layers were sutured by separate stitches with silk or other material. At the sites where there was no tension the superficial stitches were removed in the first few days (3rd day); at the latest on the 7th day the stitches were also removed from the central areas of the wound, where tension was greatest. When this method was not feasible for technical reasons (shape, size and site of the lesion) the wound was otherwise reconstructed, using rotation or transposition flaps, or again island-pedicle flaps. In some cases full thickness grafts were also used. In this last event the technique of spare skin graft was used [13, 14], which requires the grafting of skin surrounding the gap to be covered. Graft anchorage was similar to that used for full thickness grafts taken at a distance from the receiving area.

Radiotherapy technique

One hundred and sixteen patients received contact x-ray therapy according to Chaoul (potential 55-60 kV, intensity 4 mA, Focus Skin Distance [FSD] 1.5-5 cm, Half Value Depth [HVD] 2-12 mm). Four patients received soft x-ray therapy (potential 50 kV, intensity 25 mA, FSD 15 cm, filtration 1 mm Al, HVD 15 mm). The size of the irradiation field was adjusted to the keloid lesion to be treated: using a lead rubber shield (equivalent to 1 mm of Pb) a portion of skin of about 2 mm at the margin of the suturing line was included in the irradiation field. The critical organs were shielded with layers of lead rubber (equivalent to 6 mm of Pb). Treatment began within 48 hrs from the surgical excision in 36 lesions (23.07%), within 3-7 days in 91 lesions (58.33%) and within 8-23 days in the remaining 29 (18.58%) (Table IV). Weekly doses of 5 Gy were administered, up to total doses of 15 Gy in 7 cases, 20 Gy in 15 cases, 25 Gy in 31 cases, 27 Gy in 1 case, 30 Gy in 88 cases, 35 Gy in 35 cases and 40 Gy in 10 cases (mean total dose: 28.12 Gy).

The data obtained were processed by means of Access for Office 97 software (Microsoft Corporation). The statistical evaluation of the results was done using khi² analysis [15], setting the statistical level of significance at p < 0.05.

Results

The series of patients presented in this study had a follow-up ranging from 6 to 216 months (mean: 72.85 months). In 141 lesions (90.4%) the treatment administered resulted in a complete remission (CR) (Figs. 1 and 2), while in 15 cases (9.6%) the remission was partial. No ineffective result was obtained. In 17 lesions (10.89%) (15 patients) a recurrence occurred, defined, according to Cosman et al. [1], as the development of a growing and pruritic scar at the site of a previously excised keloid. Six of these lesions had first had a partial remission. In our series, the recurrences occurred in a period ranging from 1 to 72 months after the end of radiotherapy. The relapse-free rate, calculated according to the life table method, was 86.68% at 5 years from the end of radiotherapy (Fig. 3).

Relapses were treated as follows:

- eleven cases with intralesional corticosteroids, obtaining complete remission in 5 cases, a partial remission in 5 cases, but a progression in 1 case;

- two cases with surgical excision followed by a new course of radiotherapy resulting in a complete remission;

- one case underwent lasertherapy on his own decision, followed by a new relapse;

- one case with ointment containing allantoin, heparin and ethanolic onion extract: she was lost to follow-up.

Cosmetic results were evaluated according to 3 criteria in the lesions responsive to radiotherapy: they were defined as good when there was complete absence of telangiectasias and/or altered pigmentation in the irradiation field, as fairly good when there was presence of few telangiectasias and/or altered pigmentation, and as unsatisfactory, when there was presence of numerous telangiectasias and evident pigmentary changes. On the basis of these criteria, cosmetic results were judged as good in 98 lesions (70.50%), fairly good in 17 (12.23%) and unsatisfactory in 24 (17.26%).

A statistical analysis was used to evaluate the possible relation of the therapeutic outcome and other parameters. No statistically significant correlation was observed between the results of radiation therapy and the anatomical site of the keloids (Table III), or the post-surgical time interval (Table IV), or the total doses of ionizing radiation administered (Table V). A statistically significant correlation between the therapeutic results and the causes of keloids was found (p = 0.01): in fact the best results were obtained in keloids deriving from earlobe piercing (CR 100%), surgery (CR 93.33%) and acne (CR 88.88%).

As regards cosmetic results there was no significant correlation with localisation of keloids, or with total doses of ionizing radiation administered. The statistical analysis found a slight correlation (p = 0.05) between the cosmetic outcome and the post-surgical time interval, indicating an advantage for the group of lesions treated within 48 hrs.

The statistical analysis of the correlation between the rate of recurrence and the site of keloids was not significant. A significant correlation (p = 0.03) was observed between recurrence and the existence of one or more previous treatments (Table VI): in the group of recurrent keloids, in fact, there was a striking prevalence of previously treated ones (88.23%).

A poorly significant correlation (p = 0.05) was found between recurrence and total dose of ionizing radiation administered (Table VII): however, the percentage of non-relapsing cases would indicate more favourable results in the range of 25-35 Gy of total dose. Nevertheless, we must remember that most of the treated lesions had received a total dose in that range.

Finally, no significant correlation was found (p > 0.05) between recurrence rate and age of the patients.

Discussion

The employment of radiotherapy in the treatment of benign skin disorders, including keloids, is presently allowed only under certain conditions [3] and subject to compliance with strict protection rules [16, 17]. The series of patients described in this study and the characteristics of tissue absorption of the ionizing radiation beams, together with the measures taken, assured full compliance with such rules and conditions.

The purpose of the combined surgical-radiotherapeutic treatment is to favourably affect the healing of the surgical wound, at a time when connective tissue is more radiosensitive, by decreasing fibroblast proliferation and causing a rapid mast cell degranulation. As a consequence, a reduction occurs in the levels of histamine, which is considered capable of accelerating collagen formation [18]. The total doses of ionizing radiation administered were in most cases among the highest reported in the literature. Such doses were chosen in order to reduce the risk of recurrences, since most of the keloid lesions treated by us had proved resistant to, or relapsed after, previous treatments. In addition, keloids represented a functional, even more than a cosmetic problem for our patients. Even if such increase of the total doses of ionizing radiations administered could theoretically enhance the risk of radiogenic skin cancer for the patients treated, we tried to minimize such consequence in the following way:

- the maximum dose of 40 Gy was administered only to 10 patients, whose age ranged from 56 to 68 years;

- in these cases the irradiation fields had an extremely small size (diameter 1 cm) and the radiation energy was limited (50 kV);

- in all cases the sites treated were not in photoexposed areas.

Since we were also able to successfully irradiate areas covered with spare skin grafts, favourable results were also obtained with regard to quite large keloid lesions. In fact, in such instances the graft might potentially favor fibroblast proliferation, while on the other hand the ionizing radiation might impair its taking.

For a better evaluation of the results obtained and the eventual side effects, we only included patients with a minimum follow-up period of six months in our study.

The results of our twenty-year experience in postoperative radiotherapy of keloids appear better than those obtained in our previous report based on a ten-year study [7], even if the number of patients has nearly doubled (120 versus 70): in fact a complete remission has been obtained in 90.4% of the lesions respect to the previous 78.5%.

An attempt to reliably compare our series with those from the literature regarding postoperative radiotherapy of keloids is very difficult: in fact the numbers of lesions treated are very different and as is the period of follow-up (and often not indicated). On the whole, however, it is possible to state that our results are in the mean of those reported by other Authors (ranging from 72 to 90% of favourable results) [4-6]. On the basis of the available data, it seems possible also to argue that orthovoltage postoperative radiotherapy is not less effective than interstitial radiotherapy [19], high energy electron therapy [10], and brachytherapy with Sr90 [12].

It is even more difficult to compare postoperative radiotherapy with the various other therapeutic modalities employed in the management of keloids.

However, the results obtained in our cases contribute to demonstrate that postoperative radiotherapy is a very effective therapeutic choice: as a matter of fact, we observed a complete resolution of 141 lesions (90.4%) and a partial resolution in the remaining ones, with a five-year cure-rate of 86.68%. In no case the treatment resulted ineffective. We did not find a significant correlation between therapeutic results and the site of the lesions, or the interval between excision and radiotherapy, or the dose.

We have also considered the cosmetic outcome of the treatment which was favourable in 82.73% of the lesions, with slightly better results in keloids irradiated within 48 hrs after excision.

Seventeen keloids (10.89%) recurred after radiotherapy, at a period after the treatment ranging between 1 and 72 months. Recurring keloids had more often been previously treated.

In our view, however, another favourable feature was that, in the event of partial failure of the combined surgical-radiotherapeutic treatment, other therapies that had previously proved ineffective (intralesional corticosteroids) were in most cases able to block the growth of the keloid tissue, and often led to its complete regression. This fact has to be evaluated as positive, considering the type of lesion treated (resistant, relapsing or extensive lesions).

Article accepted on 15/10/01

REFERENCES

1. Cosman B, Crikelair GF, Ju MC, Gaulin JC. Lattes R. The surgical treatment of keloids. Plast Reconstr Surg 1961; 27: 335-45.

2. De Beaurman R, Gougerot H. Chéloïdes des muqueuses. Ann Dermatol Syph 1906; 7: 151-2.

3. Caccialanza M, Dal Pozzo V, Di Pietro A, et al. Radioterapia post-operatoria dei cheloidi. Risultati preliminari della nostra casistica. G Ital Dermatol Venereol 1987; 122: 471-5.

4. Borok TL, Bray M, Sinclair I, et al. Role of ionizing irradiation for 393 keloids. Int J Radiation Oncology Biol Phys 1988; 15: 865-70.

5. Kovalic JJ, Perez AC. Radiation therapy following keloidectomy: a 20-year experience. Int J Radiation Oncology Biol Phys 1989; 17: 77-80.

6. Doornbos JF, Stoffel TJ, Hass AC, et al. The role of kilovoltage irradiation in the treatment of keloids. Int J Radiation Oncology Biol Phys 1990; 18: 833-9.

7. Caccialanza M, Dal Pozzo V, Piccinno R, et al. Postoperative radiotherapy of keloids. Ten years'experience. G Ital Dermatol Venereol 1992; 127: 129-34.

8. Darzi MA, Chowdri NA, Kaul SK, Kahn M. Evaluation of various methods of treating keloids and hypertrophic scars: 10 year follow-up study. Br J Plast Surg 1992; 45: 374-9.

9. Chaudhry MR, Akhar S, Duvalsaint F, et al. Ear lobe keloids, surgical excision followed by radiation therapy: a 10-year experience. Ear Nose Throat J 1994; 73: 779-81.

10. Klumpar DI, Murray JC, Anscher M. Keloids treated with excision followed by radiation therapy. J Am Acad Dermatol 1994; 31: 225-31.

11. Caccialanza M, Dal Pozzo V, Piccinno R, et al. Postoperative radiotherapy of earlobe keloids. G Ital Dermatol Venereol 1998; 133: 399-404.

12. Wagner W, Alfrink M, Micke O, et al. Results of prophylactic irradiation in patients with resected keloids. A retrospective analysis. Acta Oncol 2000; 39: 217-20.

13. Dal Pozzo V, Di Pietro A. In tema di tecniche chirurgiche: lembi di avanzamento associati a "innesti di recupero". G Ital Chir Derm Onc 1986; 1: 55-65.

14. Dal Pozzo V, Podenzani AS, Cavicchini S. Spare skin grafting: a new technique. G Ital Dermatol Venereol 1991; 126: 403-9.

15. Colton T. Inference on proportions. In: Statistics in medicine. 1st ed. Boston: Little, Brown and Company, 1974: 151-88.

16. ICRP Publication 60. Recommandations of the International Commission on Radiological Protection. Ann ICRP 1991; 21: 1-3.

17. Panizzon RG. Radiation therapy of benign tumors, hyperplasias, and dermatoses. In: Goldschmidt H, Panizzon RG, eds. Modern Dermatologic Radiation Therapy. New York: Springer-Verlag, 1991: 139-41.

18. Topol BR, Lewis UL, Benveniste K. The use of anthistamine to retard the growth of fibroblast derived from human skin, scar, and keloid. Plast Reconstr Surg 1981; 68: 227-32.

19. Escarmant P, Zimmermann S, Amar A, Ratoanna JL, Moris A, Azaloux H, Francis H, Gosserez O, Michel M, G'Baguidi R. The treatment of 783 keloid scar by iridium 192 interstitial irradiation after surgical excision. Int J Radiation Oncol Biol Phys 1993; 26: 245-51.