Is high dose rate brachyhtherapy in a 2x6Gy dose an effective treatment for keloid? S.C. STOKMANS -‐ 1746626 S.C. Stokmans
Auteur: S.C. Stokmans – studentnummer: 1746626 /
[email protected] Stagebegeleider: F.B. Niessen – afd. Plastische chirurgie VUMC /
[email protected] Stagecoordinator: M. Mullender – afd. Plastische chirurgie VUMC /
[email protected] Commissielid WVS: S.M. Peerdeman – afd. Neurochirurgie VUMC /
[email protected] Stageduur: 22 weken (wetenschappelijke stage zonder keuzestage)
Is high dose rate brachyhtherapy in a 2x6Gy dose an effective treatment for keloid? Abstract Background: The aim of this retrospective study was to assess the efficiency of keloidectomy followed by high dose rate (HDR) brachytherapy in the treatment of keloids. Methods and materials: Twenty-‐eight patients with in total 35 keloids who were treated in the VU medical center between 2003 and 2009 with keloidectomy followed by high dose rate brachytherapy were included in the study. Patients received a total dose of 12Gy in 2 fractions of 6 Gy. The first fraction was administered within 4 hours after surgery and the second dose within 24 hours after the first. Recurrence was defined as a visible presence of a new keloid at the location that was previously treated. Results: Twenty-‐five patients with 32 keloids completed the treatment according to protocol. After a follow-‐up of 2.3 years, 1 keloid (3.1%) recurred. All signs and symptoms improved after therapy and few side effects were observed; mainly skin pigmentation changes which occurred in six patients. Conclusion: Excision followed by high dose rate brachytherapy administered in a 2x6Gy dose is an efficient and safe treatment modality for patients suffering from keloids. Recurrence rate in this study is 3.1%, and except for hyper-‐ and hypopigmentation very few side effects occur. The treatment modality is safe and efficient and patients have very good cosmetic results and a high satisfaction.
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Introduction A keloid scar is a benign fibrous cutaneous tumour that arises as a result of abnormal healing of the dermis (1). The lesion does not improve over time and exceeds the boundaries of the wounded area by infiltrating into the surrounding normal tissue, but does not spread beyond the dermis, making it a benign disease (2,3,4). Keloids show some similarities with hypertrophic scars although hypertrophic scars do not exceed the boundaries of the original wound and tend to regress over time (1,6) (table 1). Excision can be used as a treatment for hypertrophic scars but keloidectomy shows 80-‐100% recurrence rate (5,1). Table 1: differences between hypertrophic scars and keloids (6)
Hypertrophic scar Develop soon (weeks) after trauma Do not exceed boundaries wounded area Regress spontaneously over time Surgery can be a curative treatment
Keloid May develop months or years after trauma Infiltrating normal surrounding tissue No spontaneous regression over time Surgery is contra indicated. No curative treatment yet. Associated with dark skin
No association with skin colour Etiology Men and women are equally affected although it seems clinically that women are more affected (7). This higher clinical incidence is probably due to a higher rate of ear piercing amongst women, and because women are more cosmetic concerned and more likely to seek help in case of a keloidal lesion (8,9). Incidence is higher in dark skinned individuals, (between 5 and 15 times more frequent) and relatively young people are mainly affected (the second to third decade is most affected)(1,7,10,11). Younger individuals are more exposed to traumas, have a higher collagen turnover and a higher skin tension (3.12). Keloids are more frequent on the anterior chest, shoulders, ear lobules, upper arms and cheeks, and far less frequent on the eyelids, genitalia, palms, soles, cornea and mucous membranes (1). More than 50% of all keloid cases have a positive family history, and familial keloid is associated with formation of keloids in multiple sites (13). They tend to have a genetic predisposition and likely to evolve aberrant interactions of one or more genes or gene pathways (14,15). Keloids can cause major physical complaints, mainly pain and pruritus, and can carry a major physiological burden as well. This impairs the quality of life (16,17,18,19). Pathology Keloids arise from an excessive deposit of collagen in the dermis and subcutaneous tissues after even the smallest skin injury in predisposed individuals (20).
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The precise pathomechanism is unclear, but it seems that keloids are caused by a derailment in the wound healing process causing excessive scar tissue formation (1). Normal wound healing can be grouped into three different phases. The inflammatory phase, the proliferative or granulation phase, and the maturation or remodelling phase (3,20). In which phase keloid formation takes place is unknown. Some researchers think it occurs in the inflammatory phase, but others argue for the remodelling phase, since keloids can occur even years after wound closure (1). Histologically, keloids are characterized by hypo cellular collagen bundles, organized in swirls comprising closely bound fibrils. In comparison with normal scars the collagen fibres are larger and thicker and the keloidal fibroblasts produce as much as 20 times more collagen than normal scar fibroblasts. The collagen type I to III ratio is also elevated (3,7,20,21,22,23). This abnormal collagen turnover might be caused by increased density of keloidal fibroblasts (12,22,23). On top, these keloidal fibroblasts persist longer in the scar (due to less apoptosis) and show a greater capacity to proliferate and produce high levels of collagen, elastin, fibronectin and proteoglycans and overproduce certain grow factors (4,7,10,11,12,24). This overproduction might be caused by the higher responsiveness of keloid fibroblasts to certain proteins such as transforming growth factor ß (TGF-‐ ß) and insuline like growth factor-‐1 (9). These proteins are responsible for more collagen synthesis and prevent collagen breakdown (11). It is not yet demonstrated if the keloid fibroblasts are abnormal themselves, or if the keloid fibroblasts are intrinsically normal responding to abnormal extracellular signals. Evidence is directing towards the latter (17,25). Skin or wound tension is considered a critical role in the formation of keloids as well (26). Skin tension can cause fibroblast proliferation and therefore an upregulation of collagen production. Keloids develop more frequent in areas of high wound tension, such as the back or extremities (27). However, the importance of wound tension is questionable since keloids develop frequently as well in areas with very low wound tension, such as the ear lobules and appear rarely on the soles and palms where the wound tension is significant (21). Treatment No single treatment modality has proven widely effective, although multiple treatment modalities are used. (18,21,28) These include silicone-‐based therapy (29,30) with a relief of complaints in 60-‐100% of cases, intralesional steroids (31,35) with a recurrence rate between 9-‐50% , pressure therapy (31) with an 60-‐85% success rate, laser therapy (26,32,33) with recurrence rates between 16-‐94%, cryotherapy (22) with 51-‐76% response and antineoplastic agents (12,23,34). Up to now no curative treatment is found, merely due to the unknown pathogenesis. Monotherapy is insufficient in many
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cases and combination therapy has preference (1). Overall, normally excision is followed by one of the treatment modalities mentioned above (28,35). Brachytherapy Many studies have shown the efficacy of radiotherapy in the treatment of keloids with far better results than the treatment modalities mentioned before. External radiation therapy shows a recurrence rate between 12-‐27% (2,41,45), and brachytherapy shows even lower recurrence rates, between 3,4 and 23,6% (24,36,37,40). Guix et al. (36) treated 147 patients with a keloidectomy followed by high dose rate brachytherapy from 1991 to 1998. A total dose of 12Gy was given in four fractions of 300cGy. The first fraction was administered 30-‐60 minutes post-‐surgery, and the other 3 fractions followed within the next 24 hours. A 3,4% recurrence rate and a good or excellent cosmetic result was found in 130 patients. A recurrence rate of 3,4% is very low, but this might be due to patient selection bias, since most patients in this study came to the plastic surgeon with a small scar. Veen et al. (37) used three different high dose rate brachytherapy schemes in their group of 35 patients; 38 keloids were treated first with 1 x 6Gy and 2x 4Gy the next day, 7 keloids were treated with 3x 6Gy, and 9 keloids were treated with 1 x4 Gy first and 2x 3Gy the next day. The first dose was administered within 6 hours after surgery, and the two additional fractions were given the next day with an interval of at least 6 hours. One recurrence occurred in the first group, and 4 in the third group. The 3x6Gy group gave the best result, with a 0% recurrence rate. Their overall recurrence rate was 3,5%, although the groups were very small. De Lorenzi et al. (38) treated 24 patients with 30 keloids. They found that the thickness of the keloid after therapy was reduced with more than 2mm, a significant decrease. 79,1% of their patients had no pain or irritation after treatment, and 79,2% would recommend the treatment to other patients. VU medical centre study In the VU medical centre brachytherapy is applied since 2002 and clinically good results are obtained. The given dose HDR brachytherapy is 2x6Gy. This dose scheme has not been described before (2,17,24,31,39,40,41). Guix (36) described a total dose of 12Gy too, but then in a 3x4Gy scheme. In the VU medical centre the first dose is administered within 4 hours after surgery, and the next dose within 24 hours after the first dose. Our hypothesis is that time between first dose and surgery is very important, although some articles report otherwise. (38,37) We evaluated this treatment modality retrospectively to determine its effectiveness in treating keloids.
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Material and Methods Between 2003 and 2009 a total of 48 patients with keloid were treated with keloidectomy followed by high dose rate (HDR) brachytherapy at the Plastic Surgery and Radiotherapy department of the VU University medical centre, Amsterdam, the Netherlands. All patients had received unsuccessful therapy before. The patients were located for follow up in 2011. Mean follow up time was 2.3 years and ranged from 1.5 to 8 years. All patients were invited by telephone and letter to attend for a consultation. Two patients refused cooperation, 14 patients were untraceable and 4 patients made an appointment but didn’t show up and refused to make another appointment. Finally 28 patients with 35 keloids were included in the study. Patient characteristics Twenty-‐eight patients showed up for re-‐examination by a researcher at the department of Plastic Surgery. Mean age at consultation was 38.6 years (18-‐85 years). There were 9 (32.1%) male patients and 19 (67.9%) females. Eleven patients were caucasian (39.3%) and 17 patients dark skinned. See table 2 for more patients’ characteristics. The treatment and the study characteristics were clearly explained to all patients. Table 2 Patient characteristics
Characteristic Median age at follow up (range) Sex Females Males Location Ear Lobules Sternum Shoulders Head Retro-‐Auriculair Upper Back Other Limb Abdomen Thorax Etiology Post-‐Operative Ear Piercing Trauma Unknown Acne Insect Bite Width pre-‐treatment(range) Width post-‐treatment (range) Length pre-‐treatment(range) Length post-‐treatment (range)
Frequency (Percent) 38.6 (18-‐85) 19 (67.9) 9 (32.1) 13 (37.1) 7 (20.0) 3 (8.6) 3 (8.6) 2 (5.7) 2 (5.7) 2 (5.7) 1 (2.9) 1 (2.9) 1 (2.9) 10 (28.6) 7 (20.0) 6 (17.1) 6 (17.1) 5 (14.3) 1 (2.9) 2,19 (0,5-‐10) 0,99 (0,0-‐6,0) 5,24 (1,0-‐24) 5,49 (0,0-‐24,0)
*N=28
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Outcome measures During follow up a researcher at the Department of Plastic Surgery re-‐examined the keloid location(s). First outcome measure is recurrence. The researcher and the patients independently rated the therapeutic response using the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver Scar Scale (VSS). The reason to use both the VSS and the POSAS are the higher validity and reliability obtained. Both scale measure roughly the same characteristics, but the inter-‐ rater reliability is higher when used both (42). See Table 3.1 and 3.2. Table 3.1: Patient and Observer scar assessment scale
Table 3.1: The POSAS scale incorporates both observer and patient scar ratings. The results were obtained after the therapy. The POSAS scale consists of the Observer Scar Assessment Scale (OSAS) and the Patient Scar Assessment Scale (PSAS). In the OSAS scale the observer scores the vascularity, pigmentation, thickness, relief, pliability, surface area and overall opinion. Each characteristic can be scored between 1 and 10, with 1 representing normal and 10 as the worst scar imaginable. The OSAS is combined with the Patient Scar
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Assessment Scale (PSAS), which contains six items: scar-related pain, itchiness, colour, stiffness, thickness and irregularity. The patient can also score between 1 and 10. The PSAS and OSAS items obtain a total score ranging from 7 to 70 in each scale.
Table 3.2 Vancouver Scar Scale
Table 3.2: The VSS scores four physical characteristics of the scar: pigmentation, vascularity, pliability and height, and each variable include ranked subscales that are summed to obtain a total score ranging from 0 to 14, with 0 representing normal skin.
The symptoms of pain, pruritis, burning sensation, functional discomfort, dysesthesia, movement induction and psychological impairment before and after treatment were assessed and scored on a visual analogue scale (VAS) 0-‐10. The researcher took a picture of the keloid during the follow up session. The pictures were scored by an experienced plastic surgeon with the observer scale of the POSAS (the OSAS), excluding the pliability criteria. The professional scored between 6-‐60, 6 representing a normal scar. To compare the VSS, the PSAS and the OSAS and the scores were converted to percentages. Keloid sizes (with and length) were measured before and after treatment, to obtain the average reduction (or increase) of the keloid.
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Technique Surgery During the keloidectomy, as much scar tissue is removed as possible. Mostly all keloidal tissue can be removed, but sometimes some keloidal tissue is left for cosmetic reasons. This occurs especially on the ears, to prevent abnormal cosmetics and hearing loss. After surgery, a metal tipped Varisource catheter (150 cm) is positioned between the dermal edges of the wound. The wound edges need to be maximal approximated to lie directly against the catheter. At the level of in and outcome of the catheter at the end and beginning of the scar the catheter needs to be fixed on the skin using adhesive tape. The catheter must follow exactly the shape of the scar and must be at least one centimetre longer than the scar to avoid under dosage at the extremities of the scar. (see fig. 1) The catheter must be kept intact without any kinking and cutting or slicing. HDR Brachytherapy Within 4 hours of the operation the patient is transferred to the Radiotherapy department for the two HDR brachytherapy sessions. The catheter is loaded over the whole wound course with a dose of 6Gy at 0,5 cm around the axis of the catheter. Within 24 hours after the first fraction the second 6Gy is administered. A total dose of 12Gy is administered in two days. After the second fraction the catheter is removed, together with the radioactive material. The stitches are removed ten days post surgery. Fig 1: The fixed Varisource Catheter after keloidectomy.
Statistics Data analysis was performed using the software program IBM SPSS statistics version 18.0 for Mac. A dependent t-‐test is performed to compare the VAS scores before and after treatment. Descriptive statistical analyses were used to assess outcomes. A p-‐value < 0,05 was considered statistically significant. Recurrence was defined as a visible presence of new keloid at the location that was previously treated.
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Results During the follow up period (mean 2,3 years ranging 1.5-‐8 years), 3 out of 35 keloids recurred (8.6%). Thirty-‐two keloids totally disappeared after the high dose rate brachyhtherapy. Three patients were not treated following protocol. Although these three patients did not follow protocol, they were included in the descriptive statistics. Two of those patients showed a recurrence. One patient had an overnight dislocation of the catheter. Instead of the 6Gy HDR brachytherapy, she underwent an extern radiation therapy of 6,6Gy at day 2. She did not develop a recurrence. Both other patients not treated following protocol did, however, recur. One patient had an overnight dislocation and did not receive any treatment at day two, so was only treated with one dosis of 6Gy HDR brachyhtherapy. The other patient whit a recurrence received, due to a technical deficiency, a lower dose HDR brachytherapy during his second session. When the patients not treated according to protocol are excluded, only 1 out of 32 keloids recurred (3.13%). Patients rated the symptoms associated with the keloid using the VAS score with a grade from 0-‐10. Pain, pruritus, movement induction, burning sensation, physical burden, functional discomfort and dysesthesia were evaluated before and after treatment. The initial signs and symptoms, as well as their responses to the treatment, are shown in table 4. Table 4: Signs and symptoms before and after treatment
Signs and symptoms Pain Pruritus Movement induction Burning Sensation Physical Burden Functional Discomfort Dysesthesie N=35, (*) = significant
Before treatment Mean (SD) 5.60 (3.77) 6.89 (2.72) 0.57 (1.99) 1.03 (2.76) 3.51 (3.94) 2.11 (3.53) 4.43 (3.91)
After treatment Mean (SD) Significance 1.17 (2.18) 0.06 1.37 (2.58) 0.06 0.06 (0.24) 0.03* 0.14 (0.85) 0.008* 0.97 (2.23) 0.001* 0.43 (1.65) 0.003* 1.31 (2.54) 0.005*
Pruritus followed by pain and physical burden were the most common symptoms observed. All signs and symptoms improved after therapy and except for pain and pruritus all improvement is significant.
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Cosmetic outcome was very good in the group without recurrence with a mean of 7.94 out of 10 (SD 2.31, range 1-‐10). The patients with a recurrence were not as satisfied with the cosmetic result; the mean score was 3,67 out of 10 (SD 3.06, range 1-‐7). Patient satisfaction about the treatment protocol was closer together when comparing the recurrence group and the group without recurrence. Patients without recurrence rated their satisfaction with a mean of 8,5 (SD 1.65, range 2-‐10) and the patients with recurrence with a mean of 6,67 (SD 4,16 range 2-‐10). Dissatisfied patients were mostly dissatisfied because they were not treated by the surgeon of their choice or felt not fully prepared for the treatment protocol. As a result of the brachytherapy 6 patients observed to have skin pigmentation changes; 3 patients were diagnosed with hypopigmentation and 3 patients with hyperpigmentation. In 1 case telangiectasy was noted. Two patients suffered from a possibly brachytherapy induced infection and 2 patients reported a decelerated wound healing. No other side effects such as alopecia or skin fibrosis were noted. (see table 5). Table 5: Side effects of Brachytherapy
Frequency % Hypopigmentation 3 8,6% Hyperpigmentation 3 8,6% Telangiectasia 1 2,9% Infection 2 5,7% Decelerated wound healing 2 5,7% Desquamation 2 5,7% No side effects 22 62,9% All patients underwent previous therapies. Corticosteroid injections were used in 85,7% of the patients, mostly Kenacort. Excision and silicone therapy was used in 60% of the cases. The mean period between appearance of the keloid and the first visit to a medical doctor was 2,17 years (SD 3.40, range 0-‐18 years). The mean time between the first consultation at VUmc and the brachytherapy treatment was 2,2 years (SD 3.68, range 0-‐ 14 years). This is important to distinguish between a keloid and a hypertrophic scar. Hypertrophic scars regress over time, keloids do not. Main reason for seeking help (60,7%) were complaints caused by the keloid, mainly pain and/or pruritus. For 21,4 % of patients the cosmetic burden was the main reason to seek treatment (see table 6).
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Table 6: The main reasons for patients to find help.
Cosmetic Complaint (pain/ pruritus) Concerned Other
In table 7, recurrences (n=3) are compared with cases in which no recurrence occurred (n=32). In the comparison of the two groups, no significant differences were observed using independent sample t-‐test. Table 7: The recurrence group vs the no-recurrence group Recurrence No-recurrence group group Gender Male 66.67% 26.92% Female 33.33% 73.08% Race White 33.33% 38.46% Afro-‐American 66.67% 53.85% Other 0% 7.69% Age 26 (20-‐30) 39.38 (18-‐85) Location Ear Lobules 66.67% 34,38% Sternum 0% 21.88% Shoulders 0% 9.38% Genitalia 33.33% 0% Other 0% 34.38% Etiology Ear Piercing 66.67% 15.63% Trauma 33.33% 15.63% Post-‐operative 0% 31.25% Other 0% 37.5% Familiar Yes 66.67% 38.46% No 33.33% 61.54% Width Before 2.17 (SD 0.29) 2.18 (SD 1.75) Width After 1.66 (SD 0.58) 0.92 (SD 1.22)
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Lenght Before Lenght After PSAS VSS OSAS researcher OSAS professional Cosmetic Result Satisfaction Treatment Recommend to others
Again if neccessary
Treated as protocol
Yes No Yes No Yes No
2.5 (SD 0.5) 1.67 (SD 0.58) 51.85 (SD 30.63) 54.77 (SD 8.26) 49.21 (SD 5.72) 29.01 (SD 15.75) 3.67 (SD 3,06) 6.67 (SD 4.16) 33.33% 66.67% 33.33% 66.67% 33.33% 66.67%
5.5 (SD 5.04) 5.84 (SD 6.23) 17.36 (SD 19.12) 24.28 (SD 17.51) 16.21 (SD 11.56) 18.98 (11.84) 7.94 (SD 2.31) 8.5 (SD 1.65) 91.43% 8.57% 91.43% 8.57% 96.87% 3.13%
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Discussion This study shows that excision of a keloid followed by high dose rate brachytherapy represents an effective and safe treatment for keloids with a low recurrence rate of 3.1%. The treatment is a useful and effective method for keloid eradication, particularly in patients whose lesions have been resistant to other treatment modalities. Niessen et al have already largely discussed the necessity of complementary treatment following surgery of keloids since recurrence without additional treatment is very high (1). Radiotherapy in combination with surgery is a valuable treatment modality for keloidal scars and showed the best results. It offers better local control than other treatments, such as silicone therapy or corticosteroid injections with median recurrence rates of 50% (31,43). The exact mechanism by which radiotherapy prevents regrowth is unknown, although is it hypothesized that ionizing radiation destroys the fibroblasts by apoptosis and these fibroblasts are not replaced by blood borne cells from distant tissues. By destroying enough fibroblasts, a balance between collagen production and degradation may be created (44). The extracellular matrix gene expression seems to be affected as well and it may provoke damage to connective tissue stem cells (1). Radiotherapy Many studies using external radiotherapy are described. Viani et al (2) treated the largest number of patients so far. Six hundred and twelve patients with 892 keloids were treated using a strontium 90 surface applicator after keloidectomy. 12.4% patients showed a recurrence. Ragoowansi et al (41) treated 80 patients with surgical excision and immediate postoperative single fraction radiotherapy and reported 16% recurrence after 5 years. Kovalic et al (45) treated 113 keloids with superficial X ray therapy in a dose schedule of 12 Gy in three fractions. A recurrence rate of 27% was found. Low dose rate Brachytherapy The largest experience with low dose rate (LDR) brachyhterapy in the treatment of keloids was reported by Escarmant et al (46). In this study 855 keloids were treated with surgical excision followed by immediate interstitial implantation of 192 Iridium, reporting a 21% recurrence rate. This recurrence rate is about as high as the recurrence rate obtained with external radiation therapy but the authors favour low dose rate brachytherapy for practical reasons. Taken together, all of the above mentioned studies reported a recurrence rate approaching 19% when keloids are treated with external radiotherapy or LDR brachytherapy.
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High dose rate brachytherapy Better results were obtained using high dose rate (HDR) brachytherapy. Brachytherapy’s biggest advantages are dose optimatization and better dose distribution, rapid dose fall off and better radioprotection. The same dose of radiation is given to the patient in a shorter amount of time. Compared with external radiotherapy, HDR brachytherapy involves less normal tissue in the treated area and it’s costs compare favourably with those of external radiotherapy. HDR Brachytherapy also compares favourably with LDR brachytherapy. It is more convenient for patients because there is no need for hospitalisation in a shielded room and it decreases the radiation exposure for health care workers. Garg et al (40) already proved the higher effectiveness of brachytherapy in comparision with conventional radiotherapy showing that patients who failed surgery and postoperative external radiotherapy had a low recurrence rate (12%) when treated with keloidectomy following HDR Brachytherapy of 15Gy in three fractions. The first fraction was delivered within 24 hours after surgery and the other two fractions were administered on day two and day three. Veen et al (37) used three different HDR brachytherapy schemes in their group of 35 patients. He reported an overall recurrence rate of 3.5%. The first fraction was administered within 6 hours after the surgery and the next fractions were administered at day two, with a six hours interval between the doses. Guix et al (36) treated 147 patients with four fractions of 3Gy. A 3.4% recurrence rate was found. The first fraction administered within 30-‐60 minutes post surgery and the total of 4 fractions were administered within 24 hours. Arnault et al (24) reported a 23.6% recurrence rate when treating 32 patients with Iridium 192 brachytherapy in an average dose scheme of 17.9Gy. The exact time/delivery scheme was not described in this study. All these studies offered much better local control rates than did those with other techniques like radiotherapy, corticosteroid injections, silicone therapy or laser therapy which had a median recurrence rate of 50%. Nowadays surgical excision followed by radiotherapy is considered the treatment of choice for keloid scars, especially keloids that recurred after previous therapies. In our series we found a local recurrence rate of 3.1% suggesting that 12Gy is a good dosage. Kal et al (47 and 48) recommend a BED value of 30 Gy (for instance obtained with 1x13Gy, 2x8Gy or 3x6Gy) for the lowest recurrence rate. Our lower dose seems to work as well even resulting in a lower recurrence rate (3.1% vs. 3.5%) and off course less radiance for the patient. Guix used a total dose of 12Gy too and found 3.4% recurrence, but Veen’s group (37) recommends a 3x 6Gy scheme with 3.5% recurrence. As mentioned above, not only brachytherapy dose is important but also the time between the surgery and the first administration of the brachytherapy. In the studies
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mentioned above, this interval varies between 30-‐60 minutes up to within 24 hours after surgery. In our study the surgery-‐first HDR brachyhtherapy treatment interval is 4 hours and our hypothesis is that the shorter the interval, the better the result. Veen (37) and Guix (36) both used short intervals, within 6 hours and within 30-‐60 minutes respectively, and both studies had very low recurrence rates of 3.5% and 3.4%. The risk of carcinogenesis from radiation exposure is well known, leading to a discussion about the suitability of treating a benign disease with radiotherapy. The use of radiation as a therapeutic modality in the control of a benign disease merits caution, especially in children and carcinogenic sensitive areas such as the breasts and thyroid gland. Extensive large studies of this treatment have shown a 0% carcinogenetic rate, despite theoretical risks. Therefore it can be concluded that radiotherapy is acceptable as keloid treatment modality (49,50). We conclude that the results of this study prove the effectiveness of HDR brachytherapy after keloidectomy. The 2x6Gy scheme seems to be sufficiently high and the surgical technique used seems to be adequate. This treatment protocol has minimal side effects and no serious complications. Conclusion Excision followed by high dose rate brachytherapy in a 2x6Gy dose is an efficient and safe treatment modality for patients suffering for keloids. Recurrence rate is 3.1% and except for hyper-‐ and hypopigmentation very few side effects occur. The treatment modality is safe and efficient and patients have very good cosmetic results and a high satisfaction.
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