Total-Skin Electron-Beam Irradiation
 
Various treatment techniques have been used since the introduction of TSEB therapy in the early 1950s. Initially, treatment was administered to the anterior and posterior skin surfaces by passing patients on a moving couch under a narrow radiation beam. More recent techniques have used stationary two-, four-, six-, and eight-field positions, as well as rotational techniques. In general, the uniformity of dose distribution improves as the number of fields increases, but at the expense of complexity and increased machine time for the treatment of each patient. The optimal technique with reasonable uniformity of dose appears to be a six–dual-field technique refined by Page. The electron beam with an effective central axis energy of 3 to 6 MeV and, rarely, 9 MeV is used to treat three anterior and three posterior stationary treatment fields, each having a superior and inferior portal with beam angulation 20 degrees above and 20 degrees below the horizontal axis. The patient is placed in front of the beam in six positions during treatment The straight anterior, right posterior oblique, and left posterior oblique fields are treated on the first day of each treatment cycle, and the straight posterior, right anterior oblique, and left anterior oblique fields are treated on the second day of each cycle.

The entire wide-field skin surface receives 1.5 to 2 Gy each 2-day cycle. The majority of patients can tolerate 2 Gy per cycle. However, patients with previous course of TSEB irradiation or atrophic skin tolerate 1.5 Gy per cycle better. Irradiation usually is administered on a 4-day/week dose schedule; the total dose depends on the intent (curative versus palliative). Doses of 30 to 40 Gy are delivered during an 8- to 10-week interval with a 1- to 2-week break at 18 to 20 Gy for patients treated with curative intent; 10 to 20 Gy is administered for palliation. The average skin dose is calculated as the product of the dose delivered to the center of the treatment plane for one of the dual fields multiplied by a correction factor (F). Factor F represents the fact that any given point on the surface receives some radiation from at least two of the six dual-exposure fields and is calculated from phantom measurements. The percentage of photon contamination for a single dual-field cycle should not exceed 0.3%. Machine calibration is performed daily, as are point-of-dose prescription and side-to-side flatness. Verification of delivered doses should be performed routinely using thermoluminescent dosimeters placed on skin surfaces.
 

During wide-field skin irradiation, internal or external eye shields are used routinely to protect the cornea and lens. The globe of the eye must not receive more than 15% of the prescribed skin surface dose. If internal eye shields are used, the energy build-up at the surface of the eye shields (if metallic uncoated shields are used) could result in significant overdosage of the eyelids. Shielding of the digits and lateral surfaces of the hands or feet may be necessary because of local skin reaction from overlapping treatment fields in these areas. In palliative setups, shielding of uninvolved skin is recommended. Areas not directly exposed to the path of the electron beam (soles of feet, perineum, medial upper thighs, axillae, posterior auricular areas, inframammary regions, vertex of scalp, and areas under the skin folds) are treated with separate electron beam fields (with appropriate energy) or individual 100-kV orthovoltage x-rays (0.4-mm aluminum filtration), usually at a rate of 1 Gy daily to a total dose of 20 Gy. Markedly infiltrated tumors may be treated with supplemental orthovoltage irradiation or higher-energy electrons to bring the total dose to 36 to 40 Gy. A comparison of published 10-year data from Yale, Stanford, and Hamilton suggests that progression-free survival might be improved by 10% to 20% by applying patch treatments.
 
In 1951, Trump used a modified Van de Graff accelerator to treat disseminated MF with a beam of 2.5-MeV electrons to a total dose of 6 to 8 Gy during an 8- to 10-day interval, and then repeated the treatment course as needed for recurrent disease. Of 220 patients with MF (50% in the tumoroulcerative phase) treated in this fashion during the next 10 years, 90 (40%) survived 2 to 7 years, but detailed actuarial survival rates are unavailable.

In 1971, Fuks and Bagshaw presented therapeutic results in 107 patients treated with 2.5-MeV electrons at Stanford University. They increased the total dose to 30 Gy and presented evidence indicating that the posttreatment disease-free intervals justified a more aggressive therapeutic approach than that used previously, particularly in patients with early manifestations of disease.A 1979 Stanford University report concerning TSEB irradiation described patients who had been treated with 4-MeV electrons to doses up to 40 Gy . A complete response occurred in 47%, 67%, and 94% of patients treated with low doses (8 to 19.99 Gy), moderate doses (20 to 29.99 Gy), and high doses (30 to 40 Gy), respectively. With initial doses exceeding 20 Gy, 118 of 140 patients (84%) achieved complete remission of disease overall, with clearance rates of 96%, 87%, 72%, and 71% for patients with limited plaque, generalized plaque, tumors, or erythrodermic disease, respectively. The actuarial 5-year survival rates for these patients were approximately 96% for those with limited plaque disease, 75% for those with generalized plaque disease, 28% for those with tumorous disease, and 54% those with for erythrodermic disease. Up to 40% of patients with early CTCL (stages Ia and Ib) who are treated with high-dose TSEB irradiation remain relapse-free for long intervals after treatment, a strong argument for the administration of TSEB irradiation for cure rather than for palliation in the management of early CTCL.
 
An update reported the outcome of 226 patients with MF limited to the skin treated with TSEB irradiation (>20 Gy) at Stanford University between 1966 and 1989. The median follow-up for all the patients was 9 years. The overall survival of all the patients calculated from the time of electron-beam irradiation was 10 years. Twenty-one of 44 patients (48%) with limited plaques, 14 of 105 (13%) with generalized plaques, 3 of 47 (7%) with tumors, and 2 of 30 (7%) with erythroderma have remained disease-free without any relapse since the completion of electron-beam irradiation. The median follow-up for patients with limited plaque was not stated
The high frequency of initial clearing after high-dose elec-tron-beam irradiation has been confirmed by other groups but most have reported a somewhat lower continuous disease-free survival rate for early CTCL (up to 30% in some series). Moreover, not all investigators agree that administration of high-dose TSEB irradiation is the method of choice Lo et al. at the Leahy Clinic found that the prognosis of patients with widespread CTCL who were treated with high-dose TSEB irradiation was not significantly different from that of patients treated with lower doses, and that long-term disease-free survival can be achieved with small-field megavoltage irradiation in patients with localized disease

Several radiation oncology groups have used more aggressive radiotherapeutic approaches for advanced CTCL. Micaily treated 19 patients with rapidly progressing plaque- or tumor-phase MF with high-dose TSEB irradiation (36 to 40 Gy during 8 to 10 weeks) and total nodal irradiation (25 to 30 Gy in 4 to 5 weeks). Fourteen patients had disease apparently confined to the skin (stages Ib, IIa, and IIb), and five patients had proven lymph node involvement (stage IVa). Although a complete response was recorded in nearly all instances, sustained disease-free intervals were recorded primarily for patients with stage Ib or IIa disease. These patients had an overall survival rate of 100% and a disease-free survival rate of 44% at 6 years. The acute effects of this treatment approach were well tolerated, but in three patients a second malignancy developed and one patient had myelodysplasia, possibly the result of radiation therapy.

Total-body photon irradiation (TBI) may play an important role in the management of advanced CTCL. Horriot JC, et al. have achieved promising results with low-dose, fractionated TBI . Five of 10 patients with extracutaneous CTCL have remained disease-free for >12 to 56 months after treatment. Bigler from Hahnemann University reported results in six patients with advanced CTCL treated with the combination of TSEB irradiation and TBI (one patient); TSEB irradiation, TBI, and high-dose cyclophosphamide (Cytoxan; one patient); TSEB irradiation and high-dose cyclophosphamide, BCNU (carmustine), and VP16 (etoposide; one patient); and TSEB irradiation and high-dose BCNU, etoposide, and cisplatin (two patients) supported by autologous bone marrow transplantation. There were no treatment-related deaths, and the two patients treated with TSEB irradiation and BCNU, etoposide, and cisplatin (BVP) were relapse-free 14 and 13 months after completion of treatment
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Sequelae of Treatment
The cutaneous complications of total-skin irradiation for CTCL depend primarily on the total dose of irradiation administered

Expected Adverse Effects With Total-Skin Electron Radiation
Mild erythema in some normal regions of skin with greater skin reaction in areas of prior ultraviolet exposure; the lesions of mycosis fungoides become erythematous, then pigmented
  • Complete, temporary scalp alopecia (100%)
  • Temporary nail stasis (100%)
  • Some edema of hands and feet (<50%)
  • Minor nosebleeds (<10%)
  • Blisters on fingers and feet (<5%)
  • Self-limiting anhidrosis, minor parotiditis, and gynecomastia in men (<3% each)
  • Corneal tears from internal eye shields (<1%)
  • Chronic nail dystrophy, chronic xerosis, partial but permanent alopecia of the scalp, and fingertip dysesthesias that persist for more than a year (<1% each)
  • Acute or late mortality attributable to total-skin electron-beam irradiation (0%)
Short-Term Radiation Therapy Sequelae
The skin of patients treated with TSEB irradiation at doses >10 Gy usually develops mild erythema and dry desquamation that may become uncomfortably symptomatic. Lesions frequently become more erythematous than clinically normal areas during the early phase of treatment and may later become hyperpigmented. At higher doses (>25 Gy), some patients experience transient swelling of the hands, edema of the ankles, and occasionally large blisters that may necessitate local shielding or temporary discontinuation of therapy. Unless hair and nails are shielded, loss of these skin appendages invariably occurs by the end of treatment, but they regenerate within 4 to 6 months (unless previously destroyed by the disease process). Gynecomastia also may develop; the mechanism for this is unknown.
 
With current methods, a mild leukopenia may develop during treatment in patients treated with TSEB irradiation, but they no longer are subject to severe bone marrow suppression from contaminating photon radiation. Other reported systemic sequelae such as arthralgias and nausea have not been observed in our patients.
 
Long-Term Radiation Therapy Sequelae
Chronic cutaneous damage from TSEB irradiation is unusual at doses of <10 Gy and is acceptably mild through 25 Gy. Superficial atrophy with wrinkling, telangiectases, xerosis, and uneven pigmentation are the most common changes. With higher total doses, frank poikiloderma, permanent alopecia, skin fragility, and subcutaneous fibrosis are more likely to occur but are uncommon. An increased incidence of radiation-induced cutaneous neoplasia has been noticed in patients receiving additional therapy along with TSEB. In general, the nature and severity of acute and chronic radiation effects are a function of technique, fractionation scheme, total dose, concomitant use of topical or systemic cytotoxic drugs, previous treatments, and the condition of the skin before irradiation