literature of malignancies following treatment of keloids with radiotherapy. ... reports and discuss the safety of this approach to the management of keloid scars.
The British Journal of Radiology, 72 (1999), 1222±1224
E
1999 The British Institute of Radiology
Case report
The risks of treating keloids with radiotherapy N BOTWOOD, BSc, MRCP, C LEWANSKI, MRCP, FRCR and C LOWDELL, MRCP, FRCR Department of Radiology, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK
Abstract. The risk of carcinogenesis from radiation exposure is well known. It has been questioned for some time therefore, whether it is wise to treat benign disease with radiotherapy. We report a case of a patient who developed bilateral breast carcinomas almost 30 years after treatment of chest wall keloids with radiotherapy. There are only anecdotal reports in the literature of malignancies following treatment of keloids with radiotherapy. We review these reports and discuss the safety of this approach to the management of keloid scars.
Case report A 57-year-old woman suffered severe chest wall burns in 1959, aged 20 years, following an accident where her night clothes caught ®re. She subsequently developed severe keloids over the burns sites. In 1965 she received radiotherapy treatment to the scars, an area that included the right and left chest walls and lower breast tissue. Radiotherapy was given twice a week, delivering a total of 13 Gy in ®ve fractions (2.6 Gy per fraction) using super®cial X-rays of 75 kV with a focus-to-skin distance of 25.5 cm. In 1994, when the patient was 54-years-old, a lump in the left breast was found on routine screening, within the previous radiotherapy ®eld (Figure 1). She proceeded to lumpectomy for a moderately differentiated invasive ductal carcinoma with carcinoma in situ (comedo type). The lymph nodes were negative. Staging investigations were all negative. The patient received adjuvant radiotherapy of 50 Gy in 25 fractions and a boost of 10 Gy to the tumour bed. In view of a history of retinitis pigmentosa, it was decided not to start her on tamoxifen. In December 1996, mammography revealed an opacity in the right breast inferior to the nipple, again in an area within the previous radiotherapy ®eld. She proceeded to lumpectomy and axillary clearance. Multiple small foci of moderately invasive ductal carcinoma were found with intermediate grade ductal carcinoma in situ. The overall size of the tumour was 3 cm. The axilla showed no metastatic spread. The tumour was oestrogen and progesterone receptor positive. She was given adjuvant radiotherapy of 50 Gy in 25 fractions with a 10 Gy boost to the tumour bed Received 4 February 1999 and in revised form 23 July 1999, accepted 5 August 1999. 1222
and was commenced on formestane (lentaron) 250 mg every 2 weeks. There was no family history of breast cancer. The patient took hormone replacement therapy between 1987 and 1994. Her menarche was at aged 14 years and her menopause occurred aged 46 years. To date there has been no further evidence of metastatic spread or reccurence.
Discussion Keloid scars are the commonest type of benign disease treated by radiotherapy. The reason for this lies in the fact that keloid scars are particularly refractory to most other therapeutic modalities. Those that have been tried, with limited success, include cryosurgery, laser destruction, hyaluronidase, nitrogen mustard, methotrexate, steroid in®ltration, retinoic acid, zinc, colchicine, antihistamines, tetrahydroxyquinone, compression splints and dermabrasion. Radiotherapy was ®rst introduced as a treatment in 1906 [1], yet 93 years later there is still debate about whether it is a safe treatment modality. It has been shown in many epidemiological studies that ionizing radiation carries a risk of carcinogenesis. In particular, an increased incidence of breast cancer has been observed in women given radiotherapy for post-partum mastitis [2]. An increased incidence of malignancies has been found in the survivors of the Hiroshima/ Nagasaki bombs [3]. It is also well known that radiotherapy carries the risk of second malignancies in the treatment of many common tumours such as Hodgkin's disease, testicular seminomas, breast cancer, gynaecological disorders and in patients irradiated for ankylosing spondylitis [4]. It has been dif®cult to establish a ``safe'' lower limit of exposure from such data. The cloning of the ataxia telangiectasia gene [5], which is associated with intrinsic radiosensitivity and The British Journal of Radiology, December 1999
Case report: Risks of treating keloids with radiotherapy
Figure 1. Mammogram showing site of disease in left breast at time of ®rst diagnosis in 1994.
cancer predeliction, with a prevelance of approximately 0.5% of the population, has only emphasized the potential risks of, for example, mammography for certain individuals. Adding to this concern is the biphasic relationship between second cancer risk and radiation dose. At lower radiation doses the tumorigenic potential appears to be paradoxically enhanced, and then diminishes at higher doses that appear to ``sterilize'' the carcinogenic potential, by increased apoptosis proportional to DNA double-strand break induction [6]. There is a balance between this apoptotic process and the integration of potentially transforming mutations. This relationship is far from being characterized, but is dependent partly on the tissue's ability to repair sublethal damage, a process involving a number of identi®ed molecular intermediaries, such as the p53 phosphoprotein. Despite the complexity of the interrelationship between apoptosis, repair and genetic instability, most data suggest that tumour induction increases in a supralinear fashion with sublethal dose, this dose being considered ``inef®ciently tumorigenic''. As the dose is increased beyond a certain ``ef®ciently cell-lethal'' intensity the incidence of tumours declines accordingly [7, 8]. Breast tissue is at increased risk with doses between 0.2 and 0.5 Gy, but above 10 Gy the risk of tumorigenesis diminishes [8, 9]. However, scatter from the radiation ®eld can expose areas of the breast to potentially hazardous doses considered to be tumorigenic. Despite the potential risks, however, there are very few reports in the literature of malignancies arising from the treatment of keloids with radiotherapy. Hoffman reported a case of carcinoma arising in the thyroid of a 19-year-old man 8 years The British Journal of Radiology, December 1999
after receiving X-ray treatment of 12 Gy to his chin [10]. However, subsequent written communication with this author created some doubt as to the exact causal relationship between the treatment and the disease [S Hoffman, personal communication, 1988]. Bilbey reports a case of a 36-year-old woman who received radiotherapy to a chest wall keloid (dose unknown) when aged 13 years, and who subsequently developed both a hypoplastic right breast and a poorly differentiated ductal carcinoma in situ with lymph node metastases [11]. This patient also developed a localized pleural mesothelioma directly beneath the area of previous radiotherapy, although it is suspected she may have received a dose that exceeds today's standards. The optimal dosage schedule for the radiotherapy is unclear, with authors disagreeing about total dose, fractionation, the time interval between surgery and radiotherapy and whether electrons are preferable to photons. However, a number of large studies report a 0% carcinogenicity rate although there is some concern regarding length of follow-up, with some reports being as short as 2 years [12].
Conclusion Radiotherapy following surgical excision is the most effective treatment available in the management of keloid scars and remains the treatment of choice for most patients. Extensive large studies of this treatment have shown a 0% carcinogenicity rate, despite the potential theoretical risks outlined. We have described, however, a case where a causal relationship between the treatment of a keloid and the subsequent development of bilateral breast carcinomas within the irradiated ®eld is particularly strong, and discussed other reports where this may be the case. The use of radiation as a therapeutic modality in the control of benign disease merits caution, especially in children and young adults, particularly in areas that have been shown to be at increased risk such as breast and thyroid through their inherent radiosensitivity. However, whilst there continue to be few other satisfactory solutions to this often troublesome condition, radiotherapy seems destined to remain the mainstay of treatment.
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The British Journal of Radiology, December 1999
