The use of ionizing radiation for benign disease has decreased considerably, due both to improvements in alternative therapy as well as an increasing awareness of the rare but serious side effects of radiotherapy.11 This includes not only fibrotic changes in the affected skin, but more significant is the risk of secondary malignancy. It is estimated that the relative risk of malignancy following radiation treatment increases by 10%–50%; the absolute risk remains very low. These malignancies occur at a median of 10 years following treatment. The risk appears to be greater in younger patients, and in those treated to anatomic areas at highest risk for malignancy (i.e., breast or thyroid tissue). For this reason, radiotherapy should be considered in benign disease only after other therapeutic options have been exhausted, should be avoided when possible in children and young adults, and should be delivered with attention to sparing radiation exposure to sensitive normal tissue.
Radiotherapy is effective symptomatic treatment of several inflammatory dermatoses, including eczema, psoriasis, and lichen planus at relatively low dose exposure (i.e., less than 10 Gy of fractionated treatment). These conditions are only rarely treated with radiation, given the number of other anti-inflammatory options. Benign lymphoproliferative disorders are sensitive in a similar fashion, and disorders such as lymphomatoid papulosis, lymphoid hyperplasia, and lymphocytoma cutis have an excellent response to radiotherapy. These may be treated with radiation after other options have been exhausted, and are approached using lymphoma regimens. Other benign proliferative processes that can be treated with radiotherapy include keratocanthomas, and hemangiomas. A list of diagnoses for which radiotherapy may be indicated can be found in Table 240-3.
Table 240-3 Cutaneous Indications for Primary or Adjuvant Radiotherapya ||Download (.pdf)
Table 240-3 Cutaneous Indications for Primary or Adjuvant Radiotherapya
Benign lymphoid hyperplasia
Basal cell carcinoma
Merkel cell carcinoma
Eccrine and apocrine carcinoma
Cutaneous T- and B-cell lymphoma
Erythroplasia of Queyrat
A number of large series and one randomized trial have examined the efficacy of localized, low-dose irradiation for the prevention of recurrence of hypertrophic scars or keloids following excision.12–14 This should be undertaken after failure of other therapies. The most common treatment regimen is to use kilovoltage X-rays or electrons to a total dose of 10–20 Gy delivered over several days. The treatment is usually initiated within 24–48 hours of excision. The recurrence risk after surgery and radiation is approximately 20% or less. The use of radiation without excision on existing keloids is not as effective.
Basal and Squamous Carcinoma
Radiation has been used as primary treatment for basal and squamous cell carcinoma, as an alternative to excision, with local control rates of 90% or greater for small lesions.15 There is concern for progressive late skin atrophy and necrosis decades after radiation, and for this reason surgical excision is usually felt to be a better option in younger patients (i.e., those less than 55). The control rate for primary treatment is a function of tumor size and T stage. For small lesions radiation is felt to offer local control that approximates that seen with excision.
Radiation is also an effective adjuvant treatment, following excision or Mohs micrographic surgery. The clearest indication for treatment is positive margins; other considerations include tumor depth greater than 4 mm in the case of squamous cell cancer and tumor size greater than 2 cm. Involvement of cartilage or bone is a strong predictor of local recurrence and consensus guidelines recommend adjuvant treatment. Perineural invasion has been correlated with both local and nodal recurrence following excision, and is an indication for treatment.16,17 Involvement of large, named nerves should prompt consideration of extension of the clinical target volume to include the proximal nerve tract. Other relative indications for treatment include poorly differentiated tumors, adenosquamous subtype, and limitations imposed on excision by anatomic location. Patient factors include the presence of neurologic symptoms, implying underlying nerve involvement, and immunosuppressed host status. For squamous cell carcinoma, locally advanced lesions may have a significant risk of nodal metastasis. In patients being treated adjuvantly or definitively for locally advanced primaries with risk factors, draining lymphatics should be electively included.
Dose fractionation schemes represent a balance between patient convenience and the relative risk of poor cosmesis. A total of 60–66 Gy in 2 Gy fractions is appropriate for gross disease, with higher doses indicated for lesions greater than 2–4 cm. Published experience with relatively hypofractionated treatment has shown equivalent locoregional control after 45–50 Gy in 2.5 Gy fractions, or radiobiologically equivalent doses in fraction sizes of 3 or 4 Gy.
Tumors or postoperative areas that are at superficial depth may be treated with orthovoltage radiation to spare the deeper normal tissue. An alternative is electron therapy, with the appropriate bolus to maximize the surface dose. When the target volume is deeper, then megavoltage X-rays, with appropriate bolus, may be required. Target structures such as lymph node basins or nerve tracts, in close proximity to critical normal structures, may require IMRT.
The role of radiotherapy in the management of localized melanoma has not been conclusively established. Radiotherapy is frequently used for palliation of unresectable lesions, and there is evidence that selected patients at increased risk of local or regional failure may benefit from adjuvant radiation.18 Risk factors such as tumor thickness greater than 4 mm, ulceration, satellitosis, positive surgical margins, mucosal origin, perineural invasion, and desmoplastic histology are predictive of local relapse after wide excision. Patients with positive lymph nodes at high risk of recurrence after node dissection may benefit from postoperative radiation directed at the nodal basin.19,20
Melanomas are frequently treated with hypofractionated radiation, with fraction sizes of 4–6 Gy (i.e., 30 Gy in five fractions) using megavoltage X-rays. The recurrence risk for melanoma after radiation is significantly higher than that for squamous or basal cell carcinoma.
Merkel cell carcinoma (MCC) is a rare tumor that carries high risk of local or nodal recurrence after resection. MCC is radiosensitive, and routine postoperative radiation is often recommended. These patients are treated with wide margins due to the high risk of local, in-transit metastases. The treatment volume often includes the draining lymphatics. Doses of 45–60 Gy in 1.8–2 Gy fractions result in excellent control.21
Sebaceous, eccrine, and apocrine carcinomas are rare, aggressive tumors arising from glandular elements. Apocrine tumors arise in the axilla, eccrine lesions are most prevalent in the head and neck region, and sebaceous carcinomas are most commonly found in the periorbital area. Surgery is the mainstay of treatment, and local and distant recurrences are common. Adjuvant radiotherapy is appropriate for advanced lesions, or following limited resection.
Radiotherapy is often used for palliative treatment of localized Kaposi Sarcoma. Abbreviated radiation regimens of 30 Gy in ten fractions or equivalent provide excellent relief of pain, bleeding, edema, or preservation of cosmesis. Angiosarcomas are frequently managed with resection and radiotherapy to wide postoperative fields. Marginal recurrences are unfortunately common.
Cutaneous T-cell lymphomas include numerous subtypes, the most common of which are mycosis fungoides (MF) and anaplastic large cell lymphoma. MF is exquisitely sensitive to radiotherapy and patients may present with localized or disseminated skin disease. Anaplastic large cell lymphoma (CD-30 positive) is also a common CTCL, but has an incidence which is less frequent than MF. The clinical presentation is also somewhat different, and these cells generally demonstrate a CD-4 positive phenotype (which can be seen in MF), and also express cutaneous lymphocyte antigen. As opposed to MF, these cells are typically not epidermotropic and do stain positive for CD-30. Lymphomatoid papulosis is also CD-30 positive and may be associated with anaplastic large cell lymphoma. Anaplastic lymphoma kinase (ALK) is usually not overexpressed in patients suffering specifically from cutaneous lymphoma of the CD-30 positive variety, though it may be expressed in patients with noncutaneous anaplastic large cell lymphoma.
There are also a variety of subtypes of cutaneous B-cell lymphoma, but the most commonly encountered are diffuse large B-cell, marginal zone, and follicular center cell. Diffuse large B-cell lymphoma may express CD-20 and CD-79 and lesions involving the lower extremities may express BCL-2, BCL-6, and MUM-1. Marginal zone lymphoma can be identified via expression of CD-20 and CD-79 and often BCL-2, but typically BCL-6 is not noted as a marker in this case. The follicular center cell variant may express CD-20 and CD-79, but expression of BCL-2 and MUM-1 is unusual.
Localized radiotherapy fields may be incorporated into the management of patients with limited disease but, in some cases, patients have extensive areas of skin which are involved and a total skin electron beam therapy (TSEBT) technique may be incorporated for adequate disease control.
Localized radiotherapy is typically provided utilizing an electron technique and bolus material is applied to the skin in an effort to maintain an appropriate deposition of dose at the skin surface. Typically the 90% isodose curve is utilized to provide homogeneous coverage of the area in question of the skin and margins of 2–3 cm radially are incorporated into the treatment plan. Doses of 30–36 Gy in 2 Gy fractions are used. With this type of regimen for most CBCLs, the complete response (CR) rate is greater than 95% with 5-year local control of approximately 75%.22,23 Some patients may not be able to logistically receive daily therapy over several weeks, but are in need of palliation of lesions which are bleeding, uncomfortable, unsightly, or impairing function. Such patients may be candidates for an abbreviated regimen of 2 Gy × 2 to a total of 4 Gy, which has been found to provide excellent response rates with reasonable durability in selected patients with low grade CBCL.24
TSEBT is significantly more complicated to provide and is typically utilized in patients suffering from extensive MF. It provides excellent response rates for patients with various levels of disease and has also been successful in patients with tumors of the skin, assuming that a supplemental boost be provided to the region involved by tumor. More superficial patches and plaques have an excellent response rate to TSEBT when it is used in the management of patients with MF and the response rate is 100%. The CR rate is variable and decreases with the degree of thickness associated with cutaneous lesions. A typical course of therapy is provided over approximately 8–10 weeks and, based on a Stanford technique, involves 36 fractions to the total skin utilizing six fields with blocking of the eyes, hands, fingernails and feet based on dosimetric parameters resulting from the individualized treatment program.25 The patient is treated in a variety of standing positions. TSEBT is best performed in centers that have a significant amount of experience with the technique given its degree of complexity. An important feature to be considered following response to TSEBT is a maintenance program, and such maintenance can be provided in a variety of forms. For MF patients with T1 and T2 level disease, effective regimens, which have been documented in the literature, include the use of PUVA and mechlorethamine.
Both cutaneous T- and B-cell lymphomas are very sensitive to radiotherapy, and it is generally accepted that all lesions will respond and that localized CBCL lesions have a CR rate approaching 100%. CTCL lesions have CR rates that are also excellent but are more dependent on extent of disease.