Radiotherapy as a part of management of keloidal lesions is well established. Common use is postoperative irradiation by external beam radiation in the management of hypertrophic scars and keloids [1] -[3] and interstitial irradiation [4] -[6] . Radiation has rarely been used as a primary modality by external beam [6] -[8] . Primary radiotherapy without surgical excision has mostly been unsatisfactory, from keloid resolution, symptomatic and cosmetic points of view [1] [4] [5] [7] [9] [10] -[13] . There has been a satisfactory response to primary radiation for surgically unrescectable, post-operative and post-radiotherapy recurrences, using high-dose hypo-fractio- nated radiotherapy [7] [10] in keloid regression and flattening, and resolution of symptoms and cosmetic benefits have been achieved. Efforts to treat unresectable keloids with primary brachytherapy have been mostly unsatisfactory with unacceptable outcomes [11] -[13] . Without surgical removal of keloids the results so far have been dismal. Unfortunately, with surgical resection only, keloids have up to 90% recurrence [14] [15] , frequently worse than their pre-excision state. Very large and multiple keloids are not amicable to surgical resection. For the same reason large keloids are unsuitable for repeated intra-lesional injection of steroids, instillation of proteolytic enzymes [16] or even oral Tamoxifen [17] .

Intra-lesional excision is a new approach to debulk keloid mass or achieve keloid core excision results in flattening of the lesion, relief of symptoms and cosmetic benefit, without the high degree of recurrence seen in classical excision [18] -[20] . Druitt [21] first laid the foundation of modern surgical excision of keloids. Several modifications have been adopted to reduce post-surgical recurrence since then, for example, keloid auto-grafts [22] -[24] . In reality, the biological effect of leaving behind a rim of keloid is more likely to cause relatively active, well oxygenated fibroblasts to move into the cycling and dividing phase, capable of further keloid proliferation [25] . None of the altered surgical excisions led to prevention of recurrences. Yet, surgical excision followed by post-operative radiotherapy remains the gold standard in treatment of keloids [26] [27] .

Keloids are a non-life threatening condition, yet patients seek assistance from doctors for various reasons, for example, mild to severe itching, pain, irritation, uncomfortable masses or lumps, unsightly appearance, func- tional impairment, cosmesis, social stigma, and depression [28] [29] . Of all these symptoms insatiable itching, cosmesis, and restriction of physical activities due to massive keloids are the most likely reasons for seeking medical attention. Irrespective of the modality of treatment, unless the keloid is significantly flattened the the- rapeutic effect should be considered inadequate, in spite of successful symptomatic relief [30] . In his extensive and exhaustive review of treatment of keloids, in seven (7) different categories—i.e., surgery alone; lasers alone; radiation alone; surgery plus radiation; intra-lesional steroids alone; surgery plus steroids; varieties of other agents and modalities with or without surgery—Lawrence [30] concluded that there is no consensus as to management of keloids. However, the majority of reports indicated results of the regimen showed “significant objective response” [31] . The tools for measurements of objective response remain unclear. Some investigators based their findings on symptomatic improvement, reduction of keloid thickness and the lesion being more supple and softer on palpation. Specifics of the objectivity are missing from most of the reports. Very few studies [7] reported complete flattening of the lesion, which should be our main objective aside from symptomatic relief in the management of keloids.

Once keloidal collagens are formed, they stay forever, only atrophying in synchrony with advancing age, along with the skin and its integuments [32] . The dynamics of the metabolism of established keloidal collagen is unclear [33] at this point in time, including that of non-keloidal collagens in wounds, scars or normal tissue, for that matter.

The above review and an extensive literature search confirms that if the keloid is surgically resectable, complete keloid resolution is best achieved by giving post-operative radiation [1] -[3] . To reduce post-surgical skin tension instead of performing extra keloidal resection, intra-keloidalcore resection or Cleido-cutaneous margin sparing surgery (CCMSS), followed by a course of radiotherapy, does provide excellent resolution and cosmetic benefits. Due to minimal or no tension of the skin flaps, this type of surgery has been shown to be more effective [57] - [59] .

In this surgical procedure the main benefit is the physical removal of the keloidal mass, which gives the best result for the treatment of keloids.

When the keloid removal or core resection is not practically feasible, then the alternative will be to search for a possible way to “lyse”, or liquefy, the keloid mass and then leave it to the body’s own disposal mechanisms, i.e., lymphatics, venous drainage and scavenging system to facilitate drainage or removal of the lysed or liquefied collagen and degradation products. This will take us close to achieving the goal of total or maximal keloid resolution.

Several reviewed papers indicated that the best way to deliver radiation to keloids is to give fewer fractions and higher doses per fraction [60] . Malaker et al. have demonstrated, by treating unresectable and recurrent keloids with 750 cGy weekly, to a total dose of 3750 cGy in 5 fractions (Table 2). Similarly Guix, using high-dose rate brachytherapy, achieved very high cure rate (Table 2). The biological effect of high-dose rate brachytherapy is not fully cell cycle- or clonogenic cell death-dependent. A major component of keloid regression is due to radiolysis, as one can envisage from the rate and degree of reduction of keloidal collagen [61] .

The fundamental action of radiation is to induce ionization; hence it is called ionizing radiation, which is a radio-chemical phenomenon. But simple ionization of the ionizable component of an irradiated tissue does not deliver our objective of cellular damage for curing cancer, for which it is used. Processes beyond ionization, involving cell death and cure of cancer, depend on other biological factors, for example, tissue oxygen tension,

amount of cycling cells, inherent cellular radio-sensitivity, and quality of radiation, all of which are important contributors for the ultimate eradication of cancerous cells in order to achieve a cure. Body tissues comprise a small proportion of living cells compared to the much higher proportion of a-cellular products, which are made of basically either simple or complex molecules, i.e., the extra-cellular matrix, the ground substance, most of the connective tissue component and the water content of our body. Water, being an inanimate content of our tissue, does have a profound effect on cellular biology when subjected to ionizing radiation. The indirect effect of ionized charged radicals of water is to cause significant damage to various components of living cells including DNA, leading to small reversible or serious irreversible damage to the cell and ultimately manifesting the radiobiological effects of radiation. The initial process is radio-chemical and not radiobiological. Indeed to alter the radio-sensitivity of cells, attempts have been made to take advantage of this initial radiation-induced ionization or radiolysis process to facilitate or decelerate the biological effects using various chemicals or physical agents like “Hyperthermia”, etc.

While treating cancer with radiation our “target” is primarily the cancer cells and the supporting cells secondarily. Radiation can either directly hit the cellular genomic contents or indirectly affect them through the production of highly charged free radicals, i.e., O² radicals or HO radicals, which damage the genomic component of cells, or cellular integuments, leading to cell death. Damaging cancer cells is the targeted action.

In case of keloids, the bulk of the lesion is formed by collagen, which is a complex protein and not made of the cells. The bulk of the keloid must be removed to achieve our objective of keloid resolution (independent of its sparsely distributed hypoxic cells, which are relatively radio-resistant). Without dispersal of the keloidal mass, one can hardly achieve the objective of cosmoses of any degree. Surgical removal does it. Without any planned post-operative adjuvant therapy, the recurrence is guaranteed up to 90%. By using classical radiobiological techniques and principles of fractionated radiotherapy, treatment of keloid is essentially a failure, since very few “hypoxic”, “non cycling” and inherently radio-resistant fibroblasts are present in the interstices of a keloid that do not respond to classical fractionated radiotherapy regimen.

Keloids being protein, however complex, they are amenable to external beam radiation for “proteolytic” changes, a chemical event, eventual “radiolysis” leading to keloid resolution and a cure. Hence, treating keloids with radiation is a phenomenon of a “radio-chemical process” and not a “radiobiological” one (Figure 1).

High fraction size and low fraction number is likely to be the dictum for keloid radiation treatment, whether it is used as primary therapy or as an adjuvant, which works through “radiolysis”, a radio-chemical process, and not on radiobiological principles. We have manipulated the radiobiological aspect of radiotherapy in various ways, i.e., altering fractionation, concurrent boost, hyper-fractionation, using radio-sensitizers, radio-protectors, chemo-radiation, etc.

Although the radiolytic process is fundamental in the initiation of the radiobiological process, few or no innovative attempts have been made to alter or manipulate this fundamental action in radiotherapy to improve the therapeutic index. The success of treatment of keloids using the process of “radiolysis” is in our opinion an eye- opener. Other physical processes such as hyperthermia, ultrasound, and non-thermal radiofrequency all may have an impact on this initial process of “radiolysis” to enhance its biological or non-biological effect in curing tumors.

Ms. Joan Joseph provided secretarial assistance and Mr. Irus Toussaint provided all technical assistance.