eISSN: 1897-4309
ISSN: 1428-2526
Contemporary Oncology/Współczesna Onkologia
Current issue Archive Manuscripts accepted About the journal Supplements Addendum Special Issues Editorial board Abstracting and indexing Subscription Contact Instructions for authors Ethical standards and procedures
SCImago Journal & Country Rank
vol. 25
Original paper

High-dose-rate brachytherapy for non-melanoma skin cancer using tailored custom moulds – a single-centre experience

Concetta Laliscia
Taiusha Fuentes
Natalina Coccia
Roberto Mattioni
Franco Perrone
Fabiola Paiar

Division of Radiation Oncology, University of Pisa, Pisa, Italy
Medical Physics, University of Pisa, Pisa, Italy
Contemp Oncol (Pozn) 2021; 25 (1): 12–16
Online publish date: 2021/03/24
Article file
- High-dose.pdf  [0.11 MB]
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero


Skin cancer is the most common malignancy, especially for elderly patients [1]. Several studies have estimated that non-melanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), affects more than 3 million Americans a year [2, 3]. For BCC, the main carcinogenic factor is ultraviolet light, which explains why most tumours are located on sun-exposed sites and the risk of developing BCC for white-skinned people is about 30% [4]. Surgical excision is the preferred therapy for non-melanoma skin cancer, with a reported < 5% local recurrence rate. But other loco-regional approaches such as radiotherapy (RT), cryotherapy, and photodynamic therapy are also available. Radiotherapy, both external beam and brachytherapy (BT), may be considered as the primary definitive treatment in patients who are unfit for surgery (locally advanced disease, comorbidities, or refused surgery) or when curative surgery is not possible due to a significant risk of poor aesthetic outcome [5]. When excision is incomplete and re-excision is not feasible, adjuvant RT is considered an option [6]. BT through the superficial deposition of dose within the tumour with a great saving of normal tissues has been reported to have an excellent cosmetic outcome. High-dose-rate (HDR) BT is a highly tailored treatment for lesions ≤ 5 mm deep; otherwise, interstitial BT is preferred. Patients treated with HDR-BT for non-melanoma skin malignancies show 85–100% of local control (LC) [7]. The new emerging electronic BT provides an alternative to radioactive isotope sources (usually iridium-192 [192Ir]) [8].

Mould BT allows the delivery of radiation therapy with moulds that are made to better fit the patient’s external surface. Moulds are mostly indicated for larger lesions or for those localized in areas such as the face or the scalp, where the skin thickness is not sufficient to implant catheters [9, 10]. Hence, several companies have developed applicators for treating superficial skin lesions with surface BT, but the applicators can also be created in the same Radiation Oncology Divisions, mostly with a mould or wax (Fig. 1).

Fig. 1

Tailored custom surface mould for treating a basal cell carcinoma of the ear with basal cell carcinoma brachytherapy


The aim of this study was to analyse retrospectively tumour control, toxicity, and aesthetic events for patients affected by NMSC treated with 192Ir-based HDR-BT using tailored custom moulds.

Material and methods

From January 2014 to December 2019, 37 patients affected by NMSC were treated with surface moulds with 192Ir-based HDR-BT at the Division of Radiotherapy, University of Pisa. We analysed 40 lesions with a depth ≤ 5 mm, measuring a median 2 cm (range, 0.3–6.0), located in 40.0% scalp (n = 16), 17.5% nose (n = 7), 25.0% face (n = 10), and 17.5% ear (n =7). A tailored custom surface mould was created for each patient, following the contour of the skin surface and size of the lesion, with 0.5–1-cm-thick bolus material with a median of 5 catheters (range, 1–9) spaced 5–10 mm apart and affixed externally. All patients underwent computerized tomography (CT) simulation (GE LightSpeed RT, GE Healthcare, MediPhysics Inc., Arlington Heights, IL, USA). CT images were acquired with 2.5 mm slice thickness in supine position, for a better delineation of the clinical target volume (CTV) [11], and dose to the normal tissue and structures, and afterwards it was transmitted to the planning system. The treatment program was to deliver ≥ 95% of the prescribed dose to the planning target volume (PTV) [11] up to a median total dose of 40 Gy (range, 25–50 Gy). Hence, the modal prescribed total dose was 40 Gy (48.5% of cases) in 8 fractions of 5 Gy, 2/3 fractions/week, with a minimum interval of 24 hours between fractions and with a biological effective dose (α/β = 10) of 60 Gy.

The equivalent dose in 2-Gy fractions (EQD2) was calculated by using the following formula:

EQD2 = D [( d+ α /β)/( 2 Gy+ α/β)],

where D is the total dose in Gy, d is the dose per fraction in Gy, and the α/β ratio is considered 10 Gy for the tumour [12].

The most used immobilization systems were tapes or thermoplastic masks. HDR-BT was delivered using a 192Ir source, HDR afterloader microSelectron Elekta. Each RT daily fraction must be administered in the presence of a radiotherapist highly experienced in BT, who takes care of the accuracy of the procedures and dose delivery by continuously monitoring the treatment via a video camera and audio connection with the treatment room.

Acute and late toxicities were evaluated according to the common terminology criteria for adverse events (CTCAE vs. 5.0) [13]. The cosmetic results were assessed at each follow-up visit according to the Radiation Therapy Oncology Group – European Organization for Research and Treatment of Cancer scale [14]. Follow-up visits were scheduled every 3 to 4 months for the first 2 years after BT completion, every 6 months for the next 3 years, and once a year after 5 years.

Results are presented as median or mean value for quantitative parameters. Frequencies and percentages were computed for qualitative parameters. Local control was evaluated with the Kaplan-Meier method.

All patients were periodically followed-up, until they died or up to December 2019.


Non-melanoma skin cancer patients and lesions characteristics are shown in Table 1. Thirty-four lesions (85.0%) received a radical treatment and 6 lesions (15.0%) underwent adjuvant RT after surgery. Thirty-six lesions (90.0%) had a complete response (Fig. 2), and 4 (10.0%) had a partial response (PR) at clinical evaluation performed 3 months after treatment completion. Four (10.0%) PR were treated with HDR-BT after failed primary surgery and/or tailored chemotherapy.

Table 1

Patient and lesion characteristics

Age79 (31–91)
Male27 (73.0%)
Female10 (27.0%)
Histological subtype
Basal cell carcinoma23 (62.2%)
Squamous cell carcinoma14 (37.8%)
Lesion size (cm)
Lesion site
Scalp16 (40.0%)
Face10 (25.0%)
Nose7 (17.5%)
Ear7 (17.5%)
Fig. 2

A – An example of complete response of treatment of a basal cell carcinoma of the ear with high-dose-rate brachytherapy, using a tailored custom surface mould. B – After three months


Two (5.O%) PR lesions had local progression after a median time of 12 months (range, 6–23 months). Of these, 1 was affected by multifocal BCC of the face and 1 by multifocal BCC of the scalp, and both were treated with surgery and/or chemotherapy. The other 2 PR (5.0%) patients affected by multifocal BCC of the scalp had local and nodal progression and were treated with palliative RT and chemotherapy. No patients developed distant disease.

Four PR patients (10%) died of disease and 15 patients (40.5%) died of old age or comorbidities. The median follow-up of survivors was 25 months (range, 3–70 months). The 2-year LC rate was 90%. All 37 patients completed radiation treatment, and BT was well tolerated; no treatment was stopped for toxicity.

As shown in Table 2, the most common G1 toxicities were dermatitis (52%, n =21), pain (25%, n = 10), and ulceration (22%, n = 9). The only G2 acute toxicities were dermatitis and ulceration. The most common G1 late toxicities were fibrosis (17%, n =7), atrophy (15%, n = 6), and hypopigmentation (12%, n = 5). There was also no G3 or higher acute and late toxicity.

Table 2

Acute and late toxicity (CTCAE v. 5.0) in patients who underwent 192Ir–based HDR-BT, using customized surface moulds for NMSC

ToxicityG1G2G3-G4Any G
Dermatitis21 (52%)12 (30%)033 (82%))
Ulceration9 (22%)2 (5%)011 (27%)
Pain10 (25%)0010 (25%)
Dry skin5 (12%)005 (12%)
Infection1 (2%)001 (2%)
Fibrosis7 (17%)007(17%)
Telangiectasia3 (7%)003 (7%)
Atrophy6 (15%)006 (15%)
Hypopigmentation5 (12%)005 (12%)

[i] CTCAE – common terminology criteria for adverse events, 192Ir – radioactive isotope of iridium, HDR – high-dose-rate, BT – brachytherapy, NMSC – non melanoma skin cancer, G1 – grade 1, G2 – grade 2, G3 – grade 3, G4 – grade 4, G3–G4 – toxicities

Excellent cosmetic results were observed in 65.0% of lesions (n = 26); only 1 treated lesion (2.5%) presented a poor cosmetic result (skin ulceration) (Table 3).

Table 3

Cosmetic results (RTOG-EORTC scale) in patients underwent to 192Ir–based HDR-BT, using customized surface moulds for NMSC

Cosmetic resultsLesions
Excellent26 (65.0%)
Good13 (32,5 %)
Fair0 (0.0 %)
Poor1 (2.5%)

[i] RTOG-EORTC – Radiation Therapy Oncology Group – European Organization for Research and Treatment of Cancer, 192Ir – radioactive isotope of iridium, HDR – high-dose-rate, BT – brachytherapy, NMSC – non melanoma skin cancer


The gold standard treatment for most primary NMSC cancer is surgical excision with histological control of excision margins, with recurrence rates for BCC from 2% to 8% at 5 years, as reviewed by Trakatelli et al. [6, 15]. Radiotherapy may be considered a primary definitive treatment in patients who are unfit for surgery (locally advanced disease, comorbidities, or refused surgery) or when curative surgery could lead to a poor aesthetics, but also RT could damage the surrounding normal tissues, resulting in toxicity or aesthetic changes, which are most often located within the radiation field [6]. Several RT techniques are used to treat skin cancer, such as superficial orthovoltage X-ray, electron beam, megavoltage photons, low-dose rate, or HDR-BT, and recently electronic BT [16]. In our study BT seems to be a highly effective and non-invasive therapeutic approach for NMSC, without high-grade toxicities, excellent cosmetic outcome, and good LC. We reported, as well as Jumeau et al., that no treatment was stopped for toxicity and there was no significant high-grade late skin toxicity [17]. The same results in terms of LC, late toxicity, and cosmetic effects, comparing BT with external beam radiation therapy (EBRT), were reported by Delishaj et al., with 62% excellent cosmetic results, 26% good results, and 5.5% poor results [18]. Guix et al. reported in 136 patients 10.3% G1 ulceration, 14% G2 erythema, and 92% good cosmetic results, 3 months after the completion of BT [9]. In a cohort of 200 patients of Gauden et al. G1 acute skin toxicity was detected in 168 treated lesions (71%), G2 in 81 (34%), and good or excellent cosmesis in 208 cases (88%). Late skin hypopigmentation was observed in 13 (5.5%) patients [19]. Unlike our cohort, a prospective study of Kalaghchi et al. reported, in 60 patients underwent radical or adjuvant BT, 6.7% G3 – 4 acute (3-month after BT) and no late toxicities (2 years after BT). The 2-year cosmetic results were good/excellent in 96.2% of patients [20].

The results of the studies on HDR-BT for NMSC showed LC rates from 83.3.% to 100%; the limit was due to few patients or different follow-up duration, cosmetic results, and toxicities reported. The different LC rates may be caused by tumour size (small vs. large), site (plain vs. curved surfaces), margin status, and histology (BCC vs. SCC) [1822]. In our study, we showed no statistically significant difference in LC rates between 2 histological groups, perhaps due to the small number of patients (data not shown).

Gauden et al. [19] compared the LC of HDR-BT-treated patients (98%) with the LC of EBRT-treated patients and reported both LC rates from 87% to 100% with follow-up from 2 to 5 years. Drucker et al. [23] estimated the equivalent LC (95%) for Mohs surgery and EBRT. Our study reported a 2-year LC rate of 90%, according to other BT papers.

As found in the literature, we showed no statistically significant difference between definitive and adjuvant treatment groups (data not shown).

Several studies reported various dose prescriptions and target volume contouring: Jumeau et al., for example, used a PTV equal to CTV and prescribed 25 Gy in 5 fractions of 5 Gy for adjuvant treatments, 30 Gy in 6 fractions for exclusive treatments, and 8 Gy (one fraction) for palliative treatments [17]. Gauden et al. prescribed 36 Gy in 12 fractions and used PTV equal to gross tumour volume (GTV) plus 5–10 mm [19]. Casey et al. [7] used several doses, but 40 Gy in 10 daily fractions was the most commonly used dose fractionation (48.2%). Also, in our cohort we used different fractionation schedules, but the most common prescribed total dose was 40 Gy in 8 daily fractions.

In accordance with the literature, we considered a surface HDR-BT particularly tailored for elderly patients, who are often unfit for surgery or longer radiation treatments, or for performance status and/or concomitant comorbidities. A French study [17] on patients with a median age of 80 years, poor performance status, and scalp and face skin lesions, treated with customized applicators, reported a 2-year LC rate of 91%, with no high-grade skin toxicity and only G1 dermatitis [1, 2426].


Our results suggest that surface mould HDR-BT is a safe and effective treatment modality for NMSC. BT is well tolerated with very poor high acute and late toxicities and good cosmesis. However, the limitation of our study as well as most literature studies is mainly due to the limited size and age of the population, because most late toxicity events can be noted only with a longer follow-up, while these frail patients did not continue follow-up or even died shortly after treatment was completed, limiting follow-up data.


[3] Conflicts of interest The authors declare no conflict of interest.



Lancellotta V, Kovács G, Tagliaferri L, et al. The role of personalized Interventional Radiotherapy (brachytherapy) in the management of older patients with non-melanoma skin cancer. J Geriatr Oncol 2019; 10: 514-517.


American Cancer Society. Cancer Facts & Figures 2020. American Cancer Society, Atlanta 2020.


Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020; 70: 7-30.


Dessinioti C, Antoniou C, Katsambas A, Stratigos AJ. Basal cell carcinoma: what’s new under the sun. Photochem Photobiol 2010; 86: 481-491.


Peris K, Fargnoli MC, Garbe C, et al. European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC). Diagnosis and treatment of basal cell carcinoma: European consensus-based interdisciplinary guidelines. Eur J Cancer 2019; 118: 10-34.


Garbutcheon-Singh KB , Veness MJ. The role of radiotherapy in the management of non-melanoma skin cancer. Australas J Dermatol 2019; 60: 265-272.


Casey S, Awotwi-Pratt J, Bahl G. Surface mould brachytherapy for skin cancers: the British Columbia cancer experience. Cureus 2019; 11: e6412.


Hennequin C, Rio E, Mahé MA. Radiotherapy of skin cancers. Cancer Radiother 2016; 20: S249-55.


Guix B, Finestres F, Tello J, Palma C, Martinez A, Guix JR, Guix R. Treatment of skin carcinomas of the face by high-dose-rate brachytherapy and custom-made surface molds. Int J Radiat Oncol Biol Phys 2000; 47: 95-102.


Ota K , Adar T , Dover L , Khachemoune A. Review: the reemergence of brachytherapy as treatment for non-melanoma skin cancer. J Dermatolog Treat 2018; 29: 170-175.


Guinot JL, Rembielak A, Perez-Calatayud J, et al. GEC-ESTRO ACROP recommendations in skin brachytherapy. Radiother Oncol 2018; 126: 377-385.


Withers HR, Thames HD Jr, Peters LJ. A new isoeffect curve for change in dose per fraction. Radiother Oncol 1983; 1: 187-191.


NCI. National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE vs. 5.0). https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.


Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995; 31: 1341-1346.


Trakatelli M, Morton C, Nagore E, Ulrich C, Del Marmol V, Peris K, Basset-Seguin N. Update of the European guidelines for basal cell carcinoma management. Eur J Dermatol 2014; 24: 312e29.


Bhatnagar A. Non melanoma skin cancer treated with electronic brachytherapy: results at 1 year. Brachytherapy 2013; 12: 134-140.


Jumeau R, Renard-Oldrini S, Courrech F, Buchheit I, Oldrini G, Vogin G, Peiffert D. High dose rate brachytherapy with customized applicators for malignant facial skin lesions. Cancer Radiother 2016; 20: 341-346.


Delishaj D, Rembielak A, Manfredi B, et al. Non-melanoma skin cancer treated with high-dose-rate brachytherapy: a review of literature. J Contemp Brachytherapy 2016; 8: 533-540.


Gauden R, Pracy M, Avery AM, Hodgetts I, Gauden S. HDR brachytherapy for superficial non-melanoma skin cancers. J Med Imaging Radiat Oncol 2013; 57: 212-217.


Kalaghchi B, Esmati E, Ghalehtaki R, et al. High-dose-rate brachytherapy in treatment of non-melanoma skin cancer of head and neck region: preliminary results of a prospective single institution study J Contemp Brachytherapy 2018; 10: 115-122.


Svoboda VH, Kovarik J, Morris F. High dose-rate microselectron molds in the treatment of skin tumors. Int J Radiat Oncol Biol Phys 1995; 31: 967-972.


Ghaly M, Zinkin H, Dannenberg M, et al. HDR brachytherapy with standardized surface applicators in the treatment of superficial malignant skin lesions. Int J Radiat Oncol Biol Phys 2008; 72: 505-506.


Drucker AM, Adam GP, Rofeberg V, Gazula A, Smith B, Moustafa F, Weinstock MA, Trikalinos TA. Treatments of primary basal cell carcinoma of the skin: a systematic review and network meta-analysis. Ann Intern Med 2018; 169: 456-466.


Bouhassir J, Bosc R, Greta L, et al. Factors associated with postoperative complications in elderly patients with skin cancer: a retrospective study of 241 patients. J Geriatr Oncol 2016; 7: 10-14.


Albert A, Knoll MA, Conti JA, Zbar RIS. Non-melanoma skin cancers in the older patient. Curr Oncol Rep 2019; 21: 79.


Veness MJ, Delishaj D, Barnes EA, Bezugly A, Rembielak A. Current role of radiotherapy in non-melanoma skin cancer. Clin Oncol (R Coll Radiol) 2019; 31: 749-758.

Copyright: © 2021 Termedia Sp. z o. o. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Quick links
© 2021 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe