Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2025;15(2):4993 1 Unsealed 188Rhenium Resin Brachytherapy in Non-Surgical Candidates With Refractory Basal Cell Carcinoma: Clinical Outcomes Marco Adriano Chessa1,2, Carlotta Baraldi3, Francesco Savoia4, Lorenzo Maltoni1,2, Giacomo Clarizio1,2*, Federica Filippi1,2, BiancaMaria Piraccini1,2, Emi Dika2,3, Annalisa. Pitino5, Giovanni Tripepi6, Federico Zagni7, Lidia. Strigari7, Luigia Vetrone8, Stefano Fanti8, Paolo Castellucci8 1 Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy 2 Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy 3 Oncologic Dermatology Unit, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy 4 Skin Cancer Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy 5 IFC CNR Institute of clinical physiology of Reggio Calabria, Italy 6 IFC CNR Institute of clinical physiology of Rome, Italy 7 Department of Medical Physics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy 8 Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy Key words: Basal Cell Carcinoma, High-Dose Brachytherapy, 188rhenium, Non-Surgical Candidates, Refractory Skin Cancer Citation: Chessa MA, Baraldi C, Savoia F, et al. Unsealed 188Rhenium Resin Brachytherapy in Non-Surgical Candidates With Refractory Basal Cell Carcinoma: Clinical Outcomes. Dermatol Pract Concept. 2025;15(2):4993. DOI: https://doi.org/10.5826/dpc.1502a4933 Accepted: December 1, 2024; Published: April 2025 Copyright: ©2025 Chessa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Francesco Savoia; Skin Cancer Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Via P. Maroncelli 40, 47014 Meldola (FC), Italy. ORCID ID: 0000-0001-8833-2453. E-mail: francescosavoia76@virgilio.it Introduction: High-dose brachytherapy using a non-sealed 188Rhenium resin (188Re) is a new treatment option for difficult-to-treat basal cell carcinoma (BCC) that ensures a radical oncological outcome minimizing side effects. Objectives: The aim of this retrospective study was to evaluate the clinical efficacy of high-dose standardized brachytherapy using an unsealed 188Re in the management of difficult-to-treat BCCs and to evaluate the risk factors of relapses. Methods: Between October 2017 and December 2022, patients affected by difficult-to-treat BCC were selected. Inclusion criteria: histologically proven cutaneous BCC; thickness invasion no deeper than 3 mm; lesion located in the scalp, face, ears, or fingers or other areas in which surgery would have been difficult to perform or to destroy with scarce cosmetic-functional result; contraindication or refusal of surgery. All patients performed follow-up visits with videodermoscopy every 4–6 months. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2025;15(2):4993 Introduction Non-melanoma skin cancers (NMSCs) represent the most common form of cutaneous cancers in humans, account- ing for approximately 80% of all diagnosed cases [1]. Basal cell carcinoma (BCC) accounts for approximately 80% of NMSC diagnoses per year, as reported by the American Cancer Society [2]. Accordingly, more than 3 million patients, especially older adults, receive treatment each year, and about 5% of these patients are diagnosed with an advanced stage of the disease, showing a high locoregional recurrence risk [3]. The goal of the treatment of BCC, according to the National Comprehen- sive Cancer Network (NCCN), is to achieve complete cure and the highest preservation of function and cosmetics. [4] Early treatment of common BCC is curative in the vast majority of cases, and surgical excision is the first-line treatment in most cases [5] The European Association of Dermato- Oncology (EADO) classification divides BCCs into two categories, “easy-to-treat” (common) and “difficult-to-treat”6. More than 90% of BCCs are easy to treat through standard surgery or a range of alternative treatments during the initial months or years after diagnosis. Difficult-to-treat BCCs include all BCCs which, for any reason, pose specific management dif- ficulties. Six main reasons were classified by Peris et al. [7] defining a BCC as difficult-to-treat because of: (1) techni- cal difficulty of maintaining function and aesthetics due to the size or location (eyes, nose, lips, and ears) of the tumor; (2) poorly defined borders often associated with the sclero- dermiform (sd) subtype or with a recurrence; (3) multiple re- currences on the face (often requiring much larger excision); (4) prior radiotherapy; (5) patient’s reluctance to accept the consequences of surgery; (6) patient’s comorbidities inter- fering with surgery. For the NCCN, the key risk factors for high-risk BBCs include tumor localization (especially in the head and neck), size (>6 mm in high-risk area and >10 mm in moderate-risk area), concomitant immunosuppression or prior radiotherapy, poorly defined borders, recurrent disease, and aggressive histopathological subtypes [8]. While surgery, particularly Mohs micrographic surgery, remains the gold standard for difficult BCC treatment, radiotherapy (RT), in- cluding brachytherapy, is a viable option for carefully selected patients with contraindications to surgery or those who de- cline surgical treatment. In recent years, brachytherapy with 188Re has been approved in Europe, and high-dose brachyther- apy using an unsealed 188Re, commercially identified as the medical device Rhenium-SCT (Oncobeta GmbH), offers a novel approach that allows radioactivity to be delivered as closely as possible to the entire surface of the lesion regardless of its shape and three-dimensional volume This brachyther- apy approach exploits the properties of 188Re to release high- energy (Beta (β) 2.2 MeV; Gamma (Ɣ) 155KeV: emission 85% β and 15% Ɣ radiation) in the superficial layers of the skin. Finally, it is noteworthy that 188Re physical characteristics are ideal for brachytherapy since about 75% of its energy is de- livered within 1 mm and 92% within 3 mm of depth, and only a negligible amount of energy is delivered below 3 mm. High-dose rate brachytherapy using iridium-192 (192Ir) or un- sealed 188Re-resin as a source for the treatment of skin cancers reported 98% efficacy up to five years of follow-up, excellent treatment tolerance, and no serious early or late complication [8-14]. Brachytherapy with 188Re could be a tailored solution in situations where (a) surgery or external beam radiation or other brachytherapy approaches could produce suboptimal results due to the location, size, or potential cosmetic outcome of the lesion after surgery; (b) the patient’s general health and comorbidities make him/her unsuitable for surgery; and (c) patients forgoing surgery. Several studies reported in the literature have evaluated the clinical efficacy of brachytherapy with 188Re or 192Ir without stratifying BCCs by histological type, size, and anatomical location9, [11-16]. Objectives In this retrospective study, we wanted to deepen and enrich with more data a previous work of our center in which we Results: Sixty-four consecutive patients affected by 82 histologically proven high-risk BCCs, were enrolled: 60 were nodular, 9 sclerodermiform, and 13 superficial. Average follow-up was 24 months. Brachytherapy with 188Re resin achieved a complete response in 93% of “difficult-to-treat” BCCs, with relapses occurring on average 24 months after the initial treatment. No statistically significant difference in response to brachytherapy was found in the ana- tomical area treated, size of the tumor, or previously treated vs. naive BCCs. The scleroder- miform histotype had a 7-fold higher risk of recurrence than nodular histotype; recurrence occurred approximately 12 weeks earlier. Conclusion: High-dose 188Re brachytherapy is a noninvasive, easy to perform, well-tolerated approach to treat difficult BCC when surgery or other therapy techniques are not feasible. Original Article | Dermatol Pract Concept. 2025;15(2):4993 3 described the first results of our first experience on the ap- plication of brachytherapy with non-sealed 188Re in 50 con- secutive patients with non-melanoma skin cancers [13]. The primary endpoint was to evaluate the clinical efficacy of a sin- gle application of high-dose standardized brachytherapy us- ing an unsealed 188Re in the management of difficult-to-treat basal cell carcinoma. The secondary endpoint was to eval- uate the risk factors of recurrences and the timing of the recurrence after brachytherapy considering the following features: (1) the histological type of the BCC, (2) the size of the BCC, (3) the anatomical area involved, and (4) recurrent vs. naive BCC. Methods Inclusion Criteria and Reference Standards The study was performed according to the Helsinki Decla- ration; patients signed written informed consent to partici- pate, and the study was approved by local Ethics Committee (23/2019/Oss/AOUBo). Between October 2017 and Decem- ber 2022, patients affected by difficult-to-treat BCC (includ- ing both new diagnosis and relapses) were selected by the Dermatology Unit and Nuclear Medicine of the Azienda Ospedaliero-Universitaria di Bologna, Sant’Orsola-Malpighi Hospital. Inclusion criteria of our study were: (1) histologi- cally proven cutaneous BCC; (2) lesion thickness invasion not deeper than 3 mm (arbitrary cutoff based on 188Re charac- teristics) according to single or multiple diagnostic biopsies; (3) the presence of one or more criteria to define a patient with difficult-to-treat BCC [7]. Of the 152 lesions treated with Rhenium-SCT since October 2017, 64 consecutive pa- tients affected by 82 histologically proven difficult-to-treat BCCs were included in this study. Shared decision-making was a key part of the treatment program, and the treatment choice reflected patient preference when surgery posed risks or was not preferred. Patients were fully informed of surgical options and non-surgical alternatives, including brachyther- apy with the non-sealed 188Rhenium (188Re) resin for those who opted for a less invasive treatment. Patient Stratification The BCCs selected were all histologically confirmed and grouped into the following three histological subtypes: super- ficial, nodular, and sclerodermiform. According to the liter- ature, skin areas involved were stratified into high, medium, and low risk [16-17]. Area “H” included lesions of any size located in the central part of the face, eyelids, eyebrows, peri- orbital area, nose, lips, chin, jaw, preauricular area, temporal area, ears, genitals, hands, or feet. Area “L” included lesions located on the trunk and extremities, excluding hands and feet. Area “M” consisted of lesions on the cheeks, forehead, scalp, neck, and pretibial region. For all BCCs included, the cutaneous extension was specified in cm2. Twenty out of 82 recurrent cutaneous BCCs from previous treatments were also included: three BCCs had already been treated with sur- gery, six BCCs with photodynamic therapy and cryotherapy, 10 BCCs with cryotherapy, laser, and photodynamic therapy, and one BCC with imiquimod 5% cream. Follow-Up With Videodermoscopy Clinical and dermoscopic photographs before and after treatment were recorded with FotoFinder Vexia (FotoFinder Systems GmbH). All patients included in the study per- formed follow-up visits with videodermoscopy every 4–6 months at the skin cancer unit of the Azienda Ospedaliero- Universitaria di Bologna, Sant’Orsola-Malpighi Hospital. Patients were classified as complete responder (CR) if the videodermoscopy did not show any suspected area of relapse of the disease or if the biopsy guided by the dermos- copy resulted as negative or as non-responder (NR) in cases of relapses of disease evidenced by a positive histological ex- amination. The average follow-up of the patients included in the study was 24 months (range 2–24 months). The relapse rate was considered throughout the follow-up period. Standard of Treatment With 188Re-Based Resin Application The application of high-dose brachytherapy with unsealed 188Re resin followed the same procedure described in our previous papers [13-14]. Statistical Analysis Data are summarized as median and interquartile range or absolute number and percentage, as appropriate. Between-group comparisons were performed through Mann-Whitney or chi-squared tests depending on the data. The survival time was calculated on an individual basis as the weeks spanning from treatment to relapse or last obser- vation. To assess the relationship between time to relapse and characteristics of BCC (histological type, anatomical site affected, size and previous treatments) univariate and multivariate Cox analyses and restricted mean survival time (RMST) analyses were adopted to estimate the treatment ef- fect. RMST is defined as the area under the survival function curve up to a specific time (t*). When the median survival time is not calculable because event-free survival does not cross the 50% cutoff, the mean survival time, or the mean time to event, provides useful information about the time to event. Furthermore, the difference in RMST (ΔRMST) de- scribes the change (gain or loss) in event-free survival time between groups during a specific time frame. In Cox mod- els, data are expressed as hazard ratio (HR), 95% confident 4 Original Article | Dermatol Pract Concept. 2025;15(2):4993 ones. On the contrary, different responses to treatment with brachytherapy were found in relation to the histological type. No recurrence was found for lesions of the superfi- cial histological subtype (100% efficacy). However, a sta- tistically significant difference was found between nodular and sdBCC (P=0.03) (Table 1). In fact, 3/9 (33%) sdBCC had recurrences compared to only 3/60 nodular BCCs (5%) (Table 1). Brachytherapy with the application of 188Re resin achieved a complete response in 93% (76/82) of treated BCCs, and only six recurrences were observed, with a mean time to recurrence of 102 weeks or 24 months (95% CI: 98.4–105.7) (Figure 4). The univariate RMST and Cox sur- vival analysis did not show any significant difference in the mean survival time nor in the hazard ratio (HR) for all the variables except for the histologic subtype (nodular VS sd- BCC). In this case, the HR for relapse of the sd histotype is about six times higher than that for the nodular type. SdBCC show a time to first relapseof about 90 weeks, while for the nodular one is 102 weeks (Table 2). Subsequently, amultivar- iate nalysis was performed, adjusted by known principal risk factors, histologic subtype, and its recurrence and location, on the subset of sd and nodular BCC (69 lesions). Results show that compared to the nodular subtype, the sd subtype had a seven-times higher risk of relapse (Cox model HR 7.2), and relapse occured about 12 weeks earlier than in the other group (ΔRMST) (Table 2). Conclusions The aim of this study was to enhance and substantiate with additional data a prior investigation from our center, wherein we detailed the preliminary outcomes of high-dose brachytherapy using an unsealed 188Re resin, Rhenium-SCT for NMSC. The focus was on locally advanced BCCs, with an expanded sample size and extended follow-up duration. Dermoscopic Cutaneous Features after Brachytherapy Throughout the follow-up, we observed multiple dermo- scopic manifestations indicative of potential local recurrence. Specifically, nine lesions exhibited the arborizing vessels and sclerotic skin areas characteristic of BCCs, hinting at a po- tential dermoscopic indication of relapse [18-20]. Conse- quently, biopsies were performed on these areas of concern, with only six out of the nine lesions being histologically verified as BCCs. We think that local inflammation and the subsequent scar tissue due to the brachytherapy can be con- sidered primary contributors to neo-angiogenesis and to the emergence of these arborizing-like vessels [21-25]. To better distinguish signs of relapse, confocal microscopy might be useful [26-27]. intervals (CI) and P<0.05 for statistical significance. Statisti- cal analyses were performed with the survRM2 and tempo- ral packages in the software R, version 3.6.3. Results Epidemiological Features Between October 2017 and December 2022, 64 consecu- tive patients, including 40 (62.5%) males and 24 (37.5%) females, affected by 82 histologically proven high-risk BCCs were enrolled; age ranged from 52 to 97 years, mean 81 years (Table 1). The average age of the patients was 81.6 years at the time of the treatment, and the peak of age according to frequency distribution was the eighth decade. Basal Cell Carcinomas Characteristics Of the 82 lesions included in the study, 13 were superfi- cial BCCs, 60 were nodular BCCs, and nine were sdBCCs, which included difficult-to-treat areas (such as the H area of the face) that would have required extensive surgical in- terventions (Figure 1). Three patients suffering from locally advanced BCC relapsed after surgery and were treated with brachytherapy with 188Re to eradicate the BCC, with good cosmetic outcome (Figure 2). The H area was the most af- fected one (41/82, 50%), and the nose was the most common site of incidence, followed by the cheek. High incidence rates were also found in the M area (27/82, 32.9%). The L area showed the lowest incidence rates (14/82, 17,1%). Mean size area of the lesions was 5.96 cm2 (min 1- max 31). The most represented size range was between 1 and 4.9 cm2 (Table 1). Relapse at Follow-up All lesions that at follow-up with videodermoscopy were found to be suspicious for BCC relapse were subjected to multiple skin biopsies. After six months of follow-up, nine lesions suspected of relapse at dermoscopy showed arborizing-like vessels in the previously treated areas (Figure 3. Cancer cells were not found at histopathological examination (false positive) in 3/9 patients, while 6/9 sus- pected BCCs turned out to be true recurrences, highlighting the difficulty in differentiating arborizing-like vessels due to scarring (Figure 3A-F) from true arborizing vessels due to a relapse (Figure 3G-I). Risk Factors of Relapses In our sample, 23% (N=19) of lesions had already been treated without any significant association with subtype or location, nor with thickness or area treated; no statistically significant difference in relapse rate to brachytherapy was found in terms of the anatomical area treated, the size of the tumor, and the multi-treated BCCs compared to naive Original Article | Dermatol Pract Concept. 2025;15(2):4993 5 T ab le 1 . B as el in e C ha ra ct er is ti cs o f Pa ti en ts a nd o f L es io ns , G lo ba l a nd b y R el ap se . C hi -s qu ar ed f or C at eg or ic al V ar ia bl es an d M an n- W hi tn ey f or C on ti nu ou s V ar ia bl es . A ll (8 2) N o R el ap se ( 76 ) R el ap se ( 6) P V al ue s* N ( % ) M ea n (S D ) M ed ia n (I Q ) N ( % ) M ea n (S D ) M ed ia n (I Q ) N ( % ) M ea n (S D ) M ed ia n (I Q ) F 30 ( 36 .6 )     27 ( 35 .5 )     3 (5 0)     0. 48 M 52 ( 63 .4 )     49 ( 64 .5 )     3 (5 0)     A ge   81 .6 ( 8) 82 ( 78 -8 7)   81 .4 ( 7. 8) 81 .5 ( 78 -8 6. 5)   85 .2 ( 9. 4) 86 .5 ( 80 -9 1) 0. 26 H is to lo gi c su bt yp e N od ul ar 60 ( 73 .2 )     57 ( 75 )     3 (5 0)     0. 03 pe rf or m ed on ly 0 vs 1 Sc le ro de rm if or m 9 (1 1)     6 (7 .9 )     3 (5 0)     Su pe rfi ci al 13 ( 15 .9 )     13 ( 0)     0 (0 )     L oc at io n H 41 ( 50 .0 )     38 ( 50 .0 )     3 (5 0)     0. 99 ev en w he n L a nd M w er e ag gr eg at ed L 14 ( 17 .1 )     13 ( 17 .1 )     1 (1 6. 7)     M 27 ( 32 .9 )     25 ( 32 .9 )     2 (3 3. 3)     T hi ck ne ss ( m m )   1. 4 (0 .7 ) 1. 5 (1 -2 )   1. 4 (0 .7 ) 1. 5 (1 -2 )   1. 3 (0 .7 ) 1. 1 (1 -1 .6 ) 0. 26 A re a (c m 2)   6 (6 ) 3. 6 (2 -7 .3 )   5. 5 (5 .3 ) 3. 6 (2 -7 )   11 .8 ( 11 .2 ) 7. 8 (3 -1 9) 0. 09 Pr ev io us t re at m en t, ye s 19 ( 23 .2 ) 18 ( 23 .7 ) 1 (1 6. 7) Pr ev io us t re at m en t, no 63 ( 76 .8 ) 58 ( 76 .3 ) 5 (8 3. 3) 1. 00 A bb re vi at io ns : S D = s ta nd ar d de vi at io n. 6 Original Article | Dermatol Pract Concept. 2025;15(2):4993 BCCs by histological type [10-13, 24]. In our sample there was no recurrence in patients with superficial BCC. These data are probably related to the greater effectiveness of the radioactive isotope on superficial lesions. On the contrary, the sd histotype showed a risk of recurrence six times higher than the nodular subtype and had an earlier recurrence time Efficacy of Brachytherapy This is among the first studies in the literature that found statistically significant differences in relapse rates between the histological subtypes of BCC. In the literature there is a lack of data in relation to the efficacy of brachytherapy with 188Re or 192Iridium in difficult-to-treat BCC, stratifying the Figure 1. Sclerodermiform basal cell carcinoma of the auricle. (A) Before therapy and (B) six months after 188Re brachytherapy. Figure 2. (A) Basal cell carcinoma (BCC) relapsed after surgery over and under the surgical scar. (B, C) Dermoscopy and demarcation of the cutaneous area before treatment with 188Re brachytherapy. (D) Application of the 188Re. (E) Four weeks post-brachytherapy, skin redness and scaling. (F) Complete healing with excellent cosmetic result after six months. Original Article | Dermatol Pract Concept. 2025;15(2):4993 7 Figure 3. Clinical and videodermoscopy images at six months of follow-up after 188Re brachytherapy. (A) Area affected by basal cell carci- noma (BCC) and treated with 188Re. (B) Arborizing-like vessels can be seen. (C) Polymorphic comma, harpin, and linear-irregular vessels in other points. (D) Bridge of the nose affected by BCC. (E, F) At dermoscopy, arborizing-like vessels can be seen on a background characterized by erythema and skin sclerosis. (G) Patient with large basal cell carcinoma of the mid pectoral region. (H, I) On dermoscopy, arborizing vessels with focus are seen, suspicious of recurrent BCC. Figure 4. Kaplan curve with the average time free-from-relapses after brachytherapy. 8 Original Article | Dermatol Pract Concept. 2025;15(2):4993 T ab le 2 . U ni va ri at e an d M ul ti pl e re st ri ct ed m ea n su rv iv al t im e (R M ST ) an d C ox A na ly si s at 1 06 w ee ks . R M ST 1 06 w ee ks ∆ R M ST P V al ue T im e W in do w H az ar d R at io P V al ue Sh oe nf el d (P V al ue ) M 10 2. 3 (9 9. 3- 10 5. 4) 6. 06 ( 2. 86 -1 4. 98 ) 0. 18 10 4 w ee ks 0. 52 ( 0. 11 -2 .6 0) 0. 43 0. 38 F 96 .3 ( 87 .9 -1 04 .6 ) A ge > 81 10 0. 6 (9 4. 7- 10 6. 4) -3 .0 8 (- 10 .2 7- 4. 11 ) 0. 40 10 6 w ee ks 1. 78 ( 0. 33 -9 .7 2) 0. 51 0. 83 A ge < =8 1 10 3. 7 (9 9. 5- 10 7. 8) H is to lo gi c su bt yp e Su pe rfi ci al nc N od ul ar 10 2. 1 (9 8. 3- 10 5. 9) Sc le ro de rm if or m 89 .8 ( 71 .4 -1 08 .1 ) -1 2. 36 ( -3 1. 08 -6 .3 6) 0. 20 10 5 w ee ks 6. 01 ( 1. 21 -2 9. 93 ) 0. 03 0. 79 L oc at io n L 10 4. 6 (1 03 .7 -1 05 .4 ) M 99 .8 ( 90 .7 -1 07 .4 ) -5 .7 1 (- 13 .9 4- 2. 53 ) 0. 17 0. 93 ( 0. 08 -1 0. 32 ) 0. 96 0. 19 H 10 1. 6 (9 7. 2- 10 6. 1) -2 .9 0 (- 7. 44 -1 .6 3) 0. 21 10 5 w ee ks 0. 88 ( 0. 09 -8 .4 5) 0. 91 T hi ck ne ss <1 m m 10 0. 84 ( 92 .9 1- 10 8- 77 ) 1. 0- 1. 4 m m 94 .2 3 (8 0. 63 -1 07 .8 2) -6 .6 2 (- 22 .3 6- 9. 13 ) 0. 41 10 5 w ee ks 4. 41 ( 0. 46 -4 2. 6) 0. 20 0. 66 1. 5- 1. 9 m m 10 2. 65 ( 98 .1 5- 10 7. 15 ) 1. 81 ( -7 .3 1- 10 .9 3) 0. 70 0. 84 ( 0. 05 -1 3. 52 ) 0. 90 => 2. 0 m m 10 4. 77 ( 10 4. 32 -1 05 -2 1) 3. 92 ( -4 .0 2- 11 .8 7) 0. 33 0. 89 ( 0. 06 -1 4. 29 ) 0. 94 Si ze <3 .7 c m 2 10 1. 5 (9 6. 69 -1 06 .3 1) => 3. 7 cm 2 10 0. 8 (9 5. 40 -1 06 .1 9) -0 .7 1 (- 7. 93 -6 .5 2) 0. 85 10 5 w ee ks 1. 86 ( 0. 34 -1 0. 19 ) 0. 47 0. 80 Pr ev io us t re at m en ts N o 10 1. 7 (9 7. 3- 10 6- 2) ye s 10 3. 1 (9 7. 6- 10 8. 6) 1. 35 ( -5 .7 4- 8. 45 ) 0. 71 10 6 w ee ks 0. 57 ( 0. 07 -4 .9 3) 0. 61 0. 76 M ul ti pl e m od el s N od ul ar Sc le ro de rm if or m -1 2. 60 ( -1 5. 9- - 9. 3) <0 .0 01 10 5 w ee ks 7. 27 ( 1. 38 -3 8. 21 ) 0. 02 0. 41 A bb re vi at io ns : R M ST = r es tr ic te d m ea n su rv iv al t im e; Δ R M ST = d if fe re nc e in M R ST Original Article | Dermatol Pract Concept. 2025;15(2):4993 9 3. Lubeek SF, van Vugt LJ, Aben KK, van de Kerkhof PC, Gerritsen MP. The Epidemiology and Clinicopathological Features of Basal Cell Carcinoma in Patients 80 Years and Older: A Systematic Review. JAMA Dermatol. 2017;153 (1): 71-78. DOI: 10.1001 /jamadermatol.2016.3628. PMID: 27732698 4. Schmults CD, Blitzblau R, Aasi SZ, et al. Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in On- cology. J Natl Compr Canc Netw. 2023; 21 (11): 1181-1203. DOI: 10.6004/jnccn.2023.0056. PMID: 37935106 5. Hernandez LE, Mohsin N, Levin N, Dreyfuss I, Frech F, Nouri K. Basal cell carcinoma: An updated review of pathogenesis and treatment options. Dermatol Ther. 2022; 35 (6): e15501. DOI: 10.1111/dth.15501. PMID: 35393669 6. Grob JJ, Guminski A, Malvehy J et al. Position statement on classification of basal cell carcinomas. Part 1: unsupervised clus- tering of experts as a way to build an operational classification of advanced basal cell carcinoma based on pattern recognition. J Eur Acad Dermatol Venereol. 2021; 35 (10): 1949-1956. DOI: 10.1111/jdv.17466. PMID: 34432327 7. Peris K, Fargnoli MC, Kaufmann R et al. EADO”A, EDF”B, ESTRO”C, UEMS”D and EADV”E. European consensus-based interdisciplinary guideline for diagnosis and treatment of basal cell carcinoma-update 2023. Eur J Cancer. 2023;192:113254. DOI: 10.1016/j.ejca.2023.113254. PMID: 37604067 8. Lancellotta V, Kovács G, Tagliaferri L et al. The role of personal- ized Interventional Radiotherapy (brachytherapy) in the manage- ment of older patients with non-melanoma skin cancer. J Geriatr Oncol. 2019; 10 (3): 514-517. doi: 10.1016/j.jgo.2018.09.009. PMID: 30314955 9. Cipriani C, Desantis M, Dahlhoff Get al. Personalized irradiation therapy for NMSC by rhenium-188 skin cancer therapy: a long-term retrospective study. J Dermatolog Treat. 2022; 33 (2): 969-975. DOI: 10.1080/09546634.2020.1793890. PMID: 32648530 10. Sedda AF, Rossi G, Carrozzo AM et al. Superficial brachyther- apy with beta emitting isotopes for the treatment of basal cell carcinoma. J Invest Dermatol. 2006; 126: S37. EADO Conjoint Symposium on Melanoma Therapy 11. Sedda AF, Rossi G, Cipriani C, Carrozzo AM, Donati P. Derma- tological high-dose-rate brachytherapy for the treatment of basal and squamous cell carcinoma. Clin Exp Dermatol. 2008; 33 (6): 745–749. DOI: 10.1111/j.1365-2230.2008.02852.x. PMID: 18681873 12. Doggett SW, Willoughby M, Miller KA, Mafong E. Long-term clinical outcomes of non-melanoma skin cancer patients treated with electronic brachytherapy. J Contemp Brachytherapy. 2023; 15 (1): 9-14. DOI: 10.5114/jcb.2023.125580. PMID: 3697043 13. Castellucci P, Savoia F, Farina A, et al. High dose brachyther- apy with non sealed 188Re (rhenium) resin in patients with non- melanoma skin cancers (NMSCs): single center preliminary results. Eur J Nucl Med Mol Imaging. 2021; 48 (5): 1511-1521. DOI: 10.1007/s00259-020-05088-z 14. Zagni F, Vichi S, Paolani G et al. A novel tool for predicting the dose distribution of non-sealed 188 Re (Rhenium) resin in non- melanoma skin cancers (NMSC) patients. Med Phys. 2023; 50 (7): 4600-4612. DOI: 10.1002/mp.16346. PMID: 36919341 15. Laliscia C, Coccia N, Fuentes T, Perrone F, Paiar F. Two differ- ent sizes of Valencia applicators in non-melanoma skin can- cer treatment with iridium-192 high-dose-rate brachytherapy. J Contemp Brachytherapy. 2021; 13 (6): 615-619. DOI: 10.5114 /jcb.2021.112111. PMID: 35079246 of approximately 12 weeks. SdBCC is considered a diffi- cult lesion to treat because it is characterized by deep tis- sue destruction and subclinical extension as well as by high rates of local recurrence [28]. Dermoscopy-guided biopsies performed pre-brachytherapy likely affected more superfi- cial areas of the sdBCC histotype, but the lesion probably extended deeper than 3 mm in others skin areas. Regard- ing lesion edges, at clinical and dermoscopic examination, these appeared more frequently poorly defined in sdBCCs and more frequently well defined in nodular and superficial BCCs [28-29]; from this point of view, brachytherapy could not be performed in all cutaneous area affected by sdBCC. Brachytherapy with 188Re proved to be an extremely ef- fective, fast, and painless method resulting in the healing of 93% of the difficult-to-treat BCCs included in the study at an average follow-up of 24 months, confirming the data pre- viously reported in the literature [8, 11, 13, 20]. The method also made it possible to treat multiple lesions simultaneously in the same patient [11]. Moreover, we recommend a more rigorous follow-up regimen for the sdBCC compared to the nodular type. Limitations The study has two main limitations: (1) limited sample of patients affected by BCC, heterogeneous in size, histological type, and location of the BCC, (2) limited follow-up time; most BCCs (60%) recur after five years, so longer follow-up is needed [16-17], and (3) in our study there was no compar- ison with other treatment options. Brachytherapy with 188Re is an effective, rapid, safe, painless treatment and mostly performed in a single ther- apeutic session, regardless of the complexity of the form, anatomical location, and number of lesions. For these rea- sons this technique may emerge as a treatment modality in specific scenarios such as advanced patient age, comorbidi- ties, or a patient who refuses surgery or for whom surgery may have high functional or cosmetic risk. Dermatologists should be aware of evaluating relapses with videodermos- copy in patients treated with 188Re brachytherapy because arborizing-like vessels could be due to fibrotic reaction and neo-angiogenesis. The histological type of sdBCC must alert dermatologists to both the efficacy of brachytherapy and the time to free-from-recurrence. References 1. Garcovich S, Colloca G, Sollena P et al. Skin Cancer Epidem- ics in the Elderly as An Emerging Issue in Geriatric Oncology. Aging Dis. 2017; 8 (5): 643-661. DOI: 10.14336/AD.2017.0503. PMID: 28966807 2. American Cancer Society Cancer Statistics 2021 Report. J Nucl Med. 2021; 62 (3): 12N. PMID: 33622967 10 Original Article | Dermatol Pract Concept. 2025;15(2):4993 23. Jin H, Yang MY, Kim JM, Kim GW, Kim HS, Ko HC, Kim BS, Kim MB. Arborizing Vessels on Dermoscopy in Various Skin Dis- eases Other Than Basal Cell Carcinoma. Ann Dermatol. 2017; 29 (3): 288-294. DOI: 10.5021/ad.2017.29.3.288. PMID:28566904 24. Ghaly M, Zinkin H, Dannenberg M et al. HDR Brachytherapy with Standardized Surface Applicators in the Treatment of Su- perficial Malignant Skin Lesions. Int J Radiat Oncol Biol Phys 2008; 72: S505-S506. Proceedings of the 50th Annual ASTRO Meeting 25. Zou Y, Zhu X, Xia R. Reflectance Confocal Microscopy Follow-up of Multifocal Superficial Basal Cell Carcinomas Treated With Imiquimod 5% Cream. Dermatol Pract Concept. 2022; 12 (4): e2022207. DOI: 10.5826/dpc.1204a207. PMID: 36534551 26. Navarrete-Dechent C, Cordova M et al. In vivo imaging char- acterization of basal cell carcinoma and cutaneous response to high-dose ionizing radiation therapy: A prospective study of reflectance confocal microscopy, dermoscopy, and ultra- sonography. J Am Acad Dermatol. 2021; 84 (6): 1575-1584. DOI: 10.1016/j.jaad.2020.07.130. PMID: 32827607 27. Eberle FC, Kanyildiz M, Schnabl SM, et al. Three dimensional (3D) histology in daily routine: practical implementation and its evaluation. J Dtsch Dermatol Ges. 2014; 12 (11): 1028-35. doi: 10.1111/ddg.12466. PMID: 25354011 28. Conforti C, Pizzichetta MA, Vichi S, et al. Sclerodermiform basal cell carcinomas vs. other histotypes: analysis of specific demo- graphic, clinical and dermatoscopic features. J Eur Acad Der- matol Venereol. 2021; 35 (1): 79-87. doi: 10.1111/ddg.12466. PMID: 25354011 29. van Loo E, Mosterd K, Krekels GA, et al. Surgical excision versus Mohs’ micrographic surgery for basal cell carcinoma of the face: A randomised clinical trial with 10 year follow-up. Eur J Cancer. 2014; 50 (17): 3011-20. DOI: 10.1016/j.ejca.2014.08.018. PMID: 25262378 16. Stanganelli I, Spagnolo F, Argenziano G, et al, On Behalf Of Italian Melanoma Intergroup Imi. The Multidisciplinary Management of Cutaneous Squamous Cell Carcinoma: A Comprehensive Review and Clinical Recommendations by a Panel of Experts. Cancers (Basel). 2022; 13; 14 (2): 377. DOI: 10.3390/cancers 14020377. PMID: 35053539 17. Tchernev G, Wollina U, Temelkova I. High-Risk Basal Cell Carcinomas of the Head and Neck: Selected Successful Surgical Approach in Three Bulgarian Patients. Open Access Maced J Med Sci. 2019;7 (10): 1665-1668. DOI: 10.3889/oamjms.2019.360. PMID: 31210819 18. Suppa M, Micantonio T, Di Stefani A et al. Dermoscopic variabil- ity of basal cell carcinoma according to clinical type and anatomic location. J Eur Acad Dermatol Venereol. 2015; 29 (9): 1732-41. DOI: 10.1111/jdv.12980. PMID: 25627865 19. Emiroglu N, Cengiz FP, Kemeriz F. The relation between dermos- copy and histopathology of basal cell carcinoma. An Bras Derma- tol. 2015; 90: 351–6. DOI: 10.1590/abd1806-4841.20153446. PMID: 26131865 20. Lallas A, Apalla Z, Ioannides D, et al. Dermoscopy in the diagnosis and management of basal cell carcinoma. Future Oncol. 2015; 11 (22): 2975-84. DOI: 10.2217/fon.15.193. PMID: 26450622 21. Navarrete-Dechent C, Cordova M et al. In vivo imaging char- acterization of basal cell carcinoma and cutaneous response to high-dose ionizing radiation therapy: A prospective study of reflectance confocal microscopy, dermoscopy, and ultrasonog- raphy. J Am Acad Dermatol. 2021; 84 (6): 1575-1584 DOI: 10.1016/j.jaad.2020.07.130. PMID: 32827607.22 22. Krzysztofiak T, Suchorzepka M, Tukiendorf A, Wojcieszek P, Kamińska-Winciorek G. Basal Cell Carcinoma After High Dose Rate Brachytherapy: Medium-term Dermoscopic Evaluation of Cancer’s Response. Dermatol Ther (Heidelb). 2023; 13 (9): 2063-2078. DOI: 10.1007/s13555-023-00981-5. PMID: 37558829