Radiation Therapy in the Treatment of Skin Cancers

Key Points

Radiation therapy is curative for >90% of primarily treated basal and squamous cell carcinomas of the skin; the cosmetic appearance years later is a function of the manner in which the treatment course is fractionated.
Malignant melanomas are the least sensitive type of skin tumor; however, 25% of metastatic malignant melanomas completely regress following radiation therapy. Elective irradiation of high-risk tumor beds substantially improves locoregional control of disease.
Kaposi sarcomas are universally responsive to radiation therapy in all clinical settings. The role and nature of radiation therapy depends on the overall health status of the patient.
The role of and response to radiation therapy for cutaneous lymphomas depends upon the stage of the disease. Both localized and total skin electron beam radiation therapy have roles and offer benefits.
Elective adjuvant radiation therapy decreases the local and regional risk of recurrence of resected Merkel cell carcinomas.

Introduction

Despite decades of success, radiation therapy currently is being selected for the treatment of skin cancer less often than in the past. In part, this appropriately reflects the increasing variety of effective alternative therapies for skin cancer and a realization that radiation therapy is not the best treatment for all skin cancers. However, radiation therapy does represent an effective and potentially optimal therapy. A substantial body of information exists to suggest radiation therapy as a possible treatment in situations where it offers a better alternative than other forms of skin cancer management.

Principles of radiation therapy

Physical factors

Radiation can be produced electronically (X-rays and electrons) or obtained from the disintegration of unstable isotopes (alpha, beta and gamma rays). In dermatology, the vast majority of lesions are better suited for treatment by radiations that are produced electronically and delivered at a distance from the radiation source (teletherapy). Isotope therapy essentially is limited to implantation techniques (brachytherapy) that result in less homogeneous dose patterns and, while a type of radiation therapy, are essentially as different from teletherapy as Mohs technique and electrodesiccation and curettage are as forms of surgery.

Superﬁcial-quality X-ray radiation (teletherapy)

X-rays are massless, chargeless, electromagnetic packages (photons) of energy that are generated when electrons, produced from an electrically excited ﬁlament and accelerated across an electric potential, interact with a heavy metal target. Superﬁcial-quality X-rays cannot penetrate very far into tissue because they are attenuated rapidly by interactions with atoms in the tissues traversed. Under typical circumstances, the intensity of a superﬁcial-quality X-ray beam (approximately 100 kVp, i.e. 100 kilovolt peak energy and 2 mm aluminum filtration, the type of radiation traditionally provided by dermatologists) decreases to approximately 80–85% (i.e. loses 15–20%, depending on field size) of its maximum deposited energy (surface dose) after traversing only 0.5 cm of tissue. It drops to 50% of its maximum intensity by 2 cm. Because most cutaneous tumors lie within a few millimeters of the skin surface, superﬁcial-quality X-rays more than adequately penetrate such neoplasms. However, tumors that are more than 5 mm thick are better iradiated with more penetrating electrons.

Electron beam radiation (teletherapy)

Electron beam-producing linear accelerators are now far more common than superﬁcial-quality X-ray-producing units. To some degree, a relatively low-energy electron beam (e.g. 6 MeV [million electron volt]) and a superﬁcial-quality X-ray (e.g. 100 kVp) penetrate tissue similarly. Because of their mass and charge, electrons can penetrate only limited distances through tissue before interacting and expending all of their energy and essentially stop. Most accelerators have the ability to produce electrons at several different energies, permitting selection of the depth of penetration that most closely matches the patient's needs; however, megavoltage electrons are more difficult to shield than are superficial X-rays.

Field size

Because it is not possible to examine the histologic margins of an irradiated tumor, normal-appearing tissue margins need to be slightly greater than is absolutely required for surgery. For the typical, well-demarcated lesion, a margin of 0.5 to 1.0 cm is adequate. Large tumors and those with less well-deﬁned edges may require up to 2 cm margins. Poorly demarcated tumors are usually better treated by Mohs surgery; in the odd circumstance when radiation therapy is chosen, small circumferential punch biopsies can be used to map the tumor edge, beyond which a generous margin should be applied. Choo et al. investigated the borders necessary to encompass microscopic tumor extension beyond the clinically detectable lesion in 64 consecutive patients who were selected for surgical excision with frozen- section-assisted assessment of the margins because they had features such as poorly defined edges and/or had diameters larger than 2 cm and/or had morpheaform or sclerotic patterns. In these patients, microscopic disease extended from 1 mm to 15 mm beyond the gross lesion, with a mean of 5.2 mm and larger tumors having further extension than small tumors. In this series, to have had a 95% likelihood of encompassing all disease, a margin of 10 mm beyond gross disease would have been required.

Anatomic site

The nature of the normal tissues in various anatomic sites also influences the response to radiation. Skin that is subjected to repeated physical trauma tends to blister and/or ulcerate following radiotherapy. Consequently, there are relatively few situations in which a small basal cell carcinoma (BCC) of the arms, legs or trunk would not be better treated by an alternative modality. In contrast, mucosal surfaces tolerate radiation therapy well. Squamous cell carcinomas (SCCs) of the lip are often good candidates for treatment by radiation therapy. Some sites are ideally suited for treatment by radiation therapy. Tumors of the eyelids or at the tip of the nose tend to have a better cosmetic result when treated by a well-fractionated course of radiotherapy than by surgery.

Biologic factors

Cellular changes in response to radiation therapy reflect both biologic processes and physical processes that determine the outcome of treatment. All tissues are less likely to be damaged or killed by the same dose of radiation when their cells are in speciﬁc phases of the cell cycle (cells in S, G1 and early G2 are less sensitive), when oxygen is less plentiful, when they have a relatively long time to repair radiation-induced damage before being damaged again, and when they have sufﬁcient time to grow and divide between fractions of treatment. The ‘4Rs’ of radiobiology (reassortment, reoxygenation, repair and repopulation) help explain why radiation therapy generally is most effective when a fractionated regimen is used. Regaud and Ferroux long ago performed a series of experiments in radiation fractionation, examining the effect of radiation on scrotal skin and testicular function. When radiation was administered in a single fraction, there was no dose that could be delivered to a rabbit's testes that would be sufﬁcient to cause sterility without producing unacceptable reactions in the scrotal skin as well. In contrast, when the radiation was given in a fractionated manner, it was possible to sterilize the animals without producing complications in the irradiated skin. Thus, to understand the literature, the reader must understand the precise implications of the dose-fractionation pattern employed.

For most human neoplasms, curative-intent external beam radiation therapy is delivered in one fraction per day, 180–200 cGy per fraction, 5 days per week, to total doses of 5000–7000 cGy. (Radiation is currently measured in ‘Gray’ or in units 1/100 as large, centiGray [cGy]. One cGy numerically equals one rad, the previous standard of dose.) However, skin tumors are among the smallest neoplasms at the time of discovery and are so superﬁcial that it is relatively easy to protect nearby normal tissues. Consequently, one can ‘get away’ with a wide variety of regimens that would not be tolerated in other anatomic sites and more variations have been used for the radio therapeutic management of cutaneous tumors than could be used for tumors arising in other tissues in the body. Each of these variations has a predictable influence on the outcome of treatment (both in the short term and in the long term).

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