Th er ap eu tic s Evolution in the management of skin malignant lesions using new radiotherapy techniques

Introduction Radiotherapy plays an important role in the treatment of skin tumours. For skin carcinomas, external irradiation (kilovoltage X-rays or electrons according to clinical characteristics) is more preferable than interstitial brachytherapy, which is recommended for tumours of the lip and nasal vestibule. Electrons are usually used for treating superficial lesions and skin cancers, as well as in the orthovoltage radiotherapy. In order to treat mycosis fungoides, total cutaneous electron beam radiation therapy is efficient for patients with limited superficial plaques. In the treatment of classical form of Kaposi’s sarcoma, radiotherapy can achieve local control, whereas it gives good palliative results in the epidemic form. New radiotherapy techniques, such as helical tomotherapy, showed increased advantages, including dose escalation to the target tumour volume and the best protection of adjacent organs at risk. The aim of this work is to accurately evaluate the efficiency and tolerance of old and new radiotherapy techniques in the treatment of different skin tumours and to review the already existing techniques. Conclusion With all these new treatment modalities, the modern radiotherapy technique becomes a highly adapted treatment for different tumour types, which is a part of the multidisciplinary management. Introduction Radiotherapy plays an important role in the treatment of skin tumours, such as those arising from non-melanoma skin cancer and primary cutaneous lymphoma. For non-melanoma skin cancers, including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (CSC), Merkel cell carcinoma (MCC) and adnexal carcinoma (AC), complete surgical excision with a security margin is still the reference therapy. But, the choice of the treatment technique depends on various factors, such as the size of the tumour, the general condition of the patient, cosmetic considerations and recurrence. Radiotherapy is an effective option to control tumour growth and to improve quality of life of the patient. Histological confirmation is essential before radiotherapy initiation. For BCCs, radiotherapy is an alternative option if surgery is not preferred due to recurrence, incomplete excision, nodules of >2 cm in the head, or bone or cartilage involvement1. In such cases, 5–10-mm security margins are maintained depending on the tumour size, and superficial Xrays and electron beams are usually employed. A randomised controlled trial was conducted to compare radiotherapy with surgical excision of facial BCC of <4-cm diameter with 4-year failure rates of 7.5% and 0.7%, respectively (P = 0.003). Cosmetic outcomes significantly favoured surgical excision at 4 years in 87% of the surgery-treated patients, whereas 69% of the radiation-treated patients opined the cosmetic results to be satisfactory (P < 0.01). The study used different techniques of radiotherapy, including interstitial brachytherapy, contact therapy and conventional radiotherapy2. Despite these results, radiotherapy is still an option for BCCs that occur in areas where surgery would be technically difficult or would result in unacceptable tissue destruction, or for patients who would not be able to tolerate surgery3. In a study, the efficacy of electron beam radiotherapy for BCCs was evaluated; and 3-year local recurrence-free survival rates were found to be 97.6% for tumours treated with 54 Gy in 18 fractions and 96.9% with 44 Gy in 10 fractions4. Radiotherapy has also been compared with treatment with imiquimod 5% cream for nodular BCCs on the eyelid; in this study, remission rates were equivalent in both the groups, but tolerability was better in the radiotherapy group during the treatment5. For CSCs, radiotherapy is recommended when surgery is not possible, or it is used as an adjuvant in the treatment of high-risk tumours with 10–15-mm security margins6. The 3-year freedom from local recurrence was 97% with 54 Gy in 18 fractions, whereas it was 93.6% with 44 Gy in 10 fractions in a study about electron beam therapy4. Radiotherapy is particularly an option for CSCs overlying cartilage7, those with perineural invasion8,9, or with recurrence10. Adjuvant radiotherapy is also indicated of there is regional lymph node involvement11,12. For MCCs, radiotherapy is applied to the cavity of the excised primary or recurrent tumour13. Adjuvant regional radiotherapy on the tumour bed decreases regional recurrence, but * Corresponding author Email: youlia.kirova@curie.fr 1 Department of Radiation Oncology, Curie Institute, 26 Rue d’Ulm, 75005 Paris, France 2 Department of Dermatology, Cochin Hospital, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France


Introduction
Radiotherapy plays an important role in the treatment of skin tumours, such as those arising from non-melanoma skin cancer and primary cutaneous lymphoma.For non-melanoma skin cancers, including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (CSC), Merkel cell carcinoma (MCC) and adnexal carcinoma (AC), complete surgical excision with a security margin is still the reference therapy.But, the choice of the treatment technique depends on various factors, such as the size of the tumour, the general condition of the patient, cosmetic considerations and recurrence.Radiotherapy is an effective option to control tumour growth and to improve quality of life of the patient.Histological confirmation is essential before radiotherapy initiation.
For BCCs, radiotherapy is an alternative option if surgery is not preferred due to recurrence, incomplete excision, nodules of >2 cm in the head, or bone or cartilage involvement 1 .In such cases, 5-10-mm security margins are maintained depending on the tumour size, and superficial Xrays and electron beams are usually employed.A randomised controlled trial was conducted to compare radiotherapy with surgical excision of facial BCC of <4-cm diameter with 4-year failure rates of 7.5% and 0.7%, respectively (P = 0.003).Cosmetic outcomes significantly favoured surgical excision at 4 years in 87% of the surgery-treated patients, whereas 69% of the radiation-treated patients opined the cosmetic results to be satisfactory (P < 0.01).The study used different techniques of radiotherapy, including interstitial brachytherapy, contact therapy and conventional radiotherapy 2 .Despite these results, radiotherapy is still an option for BCCs that occur in areas where surgery would be technically difficult or would result in unacceptable tissue destruction, or for patients who would not be able to tolerate surgery 3 .In a study, the efficacy of electron beam radiotherapy for BCCs was evaluated; and 3-year local recurrence-free survival rates were found to be 97.6% for tumours treated with 54 Gy in 18 fractions and 96.9% with 44 Gy in 10 fractions 4 .Radiotherapy has also been compared with treatment with imiquimod 5% cream for nodular BCCs on the eyelid; in this study, remission rates were equivalent in both the groups, but tolerability was better in the radiotherapy group during the treatment 5 .
For CSCs, radiotherapy is recommended when surgery is not possible, or it is used as an adjuvant in the treatment of high-risk tumours with 10-15-mm security margins 6 .The 3-year freedom from local recurrence was 97% with 54 Gy in 18 fractions, whereas it was 93.6% with 44 Gy in 10 fractions in a study about electron beam therapy 4 .Radiotherapy is particularly an option for CSCs overlying cartilage 7 , those with perineural invasion 8,9 , or with recurrence 10 .Adjuvant radiotherapy is also indicated of there is regional lymph node involvement 11,12 .
For MCCs, radiotherapy is applied to the cavity of the excised primary or recurrent tumour 13 .Adjuvant regional radiotherapy on the tumour bed decreases regional recurrence, but Licensee OA Publishing London 2013.Creative Commons Attribution License (CC-BY) For citation purposes: Kirova YM, Kramkimel N. Evolution in the management of skin malignant lesions using new radiotherapy techniques.OA Dermatology 2013 Nov 22;1(1):6.
Competing interests: none declared.Conflict of interests: none declared.
All authors contributed to conception and design, manuscript preparation, read and approved the final manuscript.All authors abide by the Association for Medical Ethics (AME) ethical rules of disclosure.
the tumour.Head and neck cancer is one of the best indications for tomotherapy.It has also already been used against sarcomas, gynaecological and lung tumours, and haematologic diseases [28][29][30] .HT has achieved better target coverage in the treatment of head and neck cancer with better protection of organs at risk by reducing xerostomia compared with step-andshoot intensity modulated radiotherapy (IMRT) 31 .We have shown that HT to be an effective option of radical treatment for advanced non-melanoma skin cancers as monotherapy or in combination with surgery.In our study, at a median 12-month followup, complete remission was observed in 88% of tumours: 100% in BCCs, 85.7% in CSCs, 80% in MCCs and 75% in ACs.This is a promising response rate, especially because our patients suffered from hard skin lesions; indeed, tumours treated in this study had poor prognoses either because of their localisation (face), incomplete surgical excision, recurrent or inoperable nature, or lymph node involvement.Early, late toxicity and cosmetic results were satisfactory.The method facilitates sparing of organs at risk (OARs).These results should be confirmed by larger prospective studies with longer follow-up 31 .To the best of our knowledge, this study is the largest cohort analysis of HT treatment of advanced non-melanoma skin cancer.Currently, only a few case reports have been published about the efficacy of tomotherapy for skin cancer: one case of multiple BCCs was treated simultaneously, one case of extensive BCC of the forehead and the scalp 32 , one case of sarcomatoid sarcoma of the scalp, one case of recurrent eccrine mucinous adenocarcinoma of the scalp, and three cases of skin malignancies [33][34][35][36] .
A few new indications have been reported about the decreasing tumour mass before stem cell transplantation in aggressive curaneous lymphomas 37 .in which they were performed.All human subjects, in these referenced studies, gave informed consent to participate in these studies.

Place of helical tomotherapy in the treatment of skin cancers
The choice of the most appropriate irradiation technique depends on tumour localisation and clinical target volume, as much as histology, and the size and thickness of the tumour.Three standard radiation techniques used for skin cancers are low-energy X-rays for tumours of <1 cm thickness, electron beams for thicker tumours, and brachytherapy for lesions of the lower lip and nasal pyramid.Helical TomoTherapy ® (HT; Accuray Incorporated, Sunnyvale, CA, USA) is a new technique of radiotherapy and little data have been published on nonmelanoma skin cancer.HT is an intensity-modulated radiation treatment using 6 MV photons combined with megavoltage computed tomography (CT) imaging allowing accurate patient positioning.This dynamic therapy has been developed at the University of Wisconsin in late 1980s 27 .The system is mounted upon a continuous rotating gantry coupled with translation of the patient through the gantry.The helical delivery minimises the risk of significant high-or low-dose deposition in the areas of overlap or junctioning.It is an adaptive radiotherapy with constant possibility to verify a therapeutic plan, that is, patient positioning, target tumour/organ registration and reconstruction of delivered dose.The dose is delivered slice by slice during an axial CT scan 28 .Advantages of this technique are increase in irradiation dose on the target tumour volume and the best protection of adjacent organs at risk 29 .Indeed, this technique allows targeting areas of disease while simultaneously minimising the dose to organ at risk 30 .It is useful for large-size tumours, complex-form tumours and when organs at risk are close or inside has no benefit on overall survival 14,15 .Radiotherapy alone can be a reasonable option for inoperable MCCs with similar overall and disease-free survival rates to combination of surgery and radiotherapy 16 .A recent study showed that radiation monotherapy could also be used for lymph node-positive MCC (for both microscopic and palpable lymph node disease), with comparable results to lymphadenectomy with or without adjunct radiotherapy 17,18 .
With regard to ACs, a few cases have been published about radiotherapy for sebaceous carcinoma.Sebaceous carcinomas have been considered radioresistant for years.But recently, reports of successful treatment of sebaceous carcinoma with radiotherapy have been published.Local control at the primary site after radiation and/or surgery was 90%, as observed in a study including 10 patients 19 .An appropriate radiotherapy delivery regimen (>55 Gy) seems to be an effective treatment for sebaceous carcinoma in combination or as an alternative to surgery [20][21][22] .
In mycosis fungoides, total cutaneous electron beam radiation therapy is efficient for patients with limited superficial plaques.In the classical form of Kaposi's sarcoma, radiotherapy can achieve local control, whereas it gives good palliative results in the epidemic form [22][23][24] .Radiation therapy is also a treatment of choice in the low-grade B-cell lymphomas 25,26 .The aim of this critical review was to discuss the evolution in the management of skin malignant lesions using new radiotherapy techniques.

Discussion
The authors have referenced some of their own studies in this review.These referenced studies have been conducted in accordance with the Declaration of Helsinki (1964) and the protocols of these studies have been approved by the relevant ethics committees related to the institution