Local radiotherapy was first described by Schultz in 1902. But the techniques of treatment were developed in late 1950s. There were practical problems in treating large field skin surface having oblique contours [28]. The cutaneous lesions are extremely radio responsive, and a dose-response relationship has been demonstrated [7, 23, 24, 39, 66]. Superficial, orthovoltage radiations as well as electrons in doses of 20–40 Gy are very effective in controlling the disease and have been used to treat localized primary or relapsed patches, plaques, and tumors. The fraction size may vary between 1 and 2 Gy, depending on the site and the size of the lesions. The complete remission rates with this therapy may be as high as 90–100 % in localized lesions. Local external beam radiation can be considered for patients having very localized disease. This is also very useful in the patients who either do not respond or have residual disease after PUVA/narrow band UVB therapy. Cotter et al. have even demonstrated 100 % remission with a radiation dose in excess of 30 Gy [7]. Wilson et al. have reported a remission rate of 97 % with external beam radiotherapy [73]. Isolated residual or relapsed lesions after PUVA therapy can also be effectively treated by this method with excellent results. In disseminated disease, a dose between 5 and 20 Gy provides adequate and effective palliation.

Although radiation as a therapy was used for the treatment of localized/limited lesions of MF in 1902, large areas of skin or the entire skin with low-energy X-rays or electrons could not be treated due to lack of equipment and technical shortcomings. Therefore, a technique was developed, as total skin electron irradiation therapy, which was first used in the clinical practice in 1952.

Teleroentgentherapy or total skin electron irradiation (TSEI) is still a technically and practically challenging procedure; hence not many centers around the world use it. The setup for performing TSEI requires a proper infrastructure, and the treatment procedure requires close coordination among the radiation oncologist, medical physicist, and dermatologist. A variety of technical and clinical issues related to TSEI and its effects were reviewed by Reavely et al. [63]. A model of TSEI treatment using the “six-dual-field” technique was reviewed by Faj et al. [14]. The procedure has been modified several times during the process of developing the TSEI program at Stanford University to make it more technically refined and clinician as well as patient friendly, which was widely accepted by many centers, and at the same time, many centers tried to improve upon the dose-schedule of the technique. Trump et al. first described the application of the TSEI in 1953 [66]. Since then, many modifications to the technique and dose fractionation have been done to obtain better results, which have been documented in many studies [15, 19, 25, 29, 31, 32, 34, 37, 38, 46, 51, 55, 64, 67, 68]. In a study by Jones, data of more than 2,000 patients is presented [31]. His subsequent publication on these patients included historical information, definition of target volume, different techniques, dosimetric aspects, updated clinical results from both Stanford University and Hamilton Regional Cancer Center and also an attempted meta-analysis of the worldwide literature [34]. At the Hamilton Regional Cancer Center, out of a total of 621 patients treated between 1956 and 1996, 401 patients received TSEI with/without any adjuvant modality of treatment or concurrent therapies, and another 52 patients received TSEI plus adjuvant mechlorethamine or concurrent systematic chemotherapy, retinoids or interferon [34, 36, 61].

A dose of 4–7 MeV is usually used to treat epidermal and dermal lesions homogeneously. As most of the dose (80 %) is delivered at a depth of 1 cm and less than 5 % beyond 2 cm, structures below the deep dermis are spared. Shadowed regions like the scalp, perineum, sole, and other skin folds are boosted later with local electron fields. TSEI produces excellent results in patients with diffuse cutaneous involvement with patches, plaques, or tumors and especially in such patient’s refractory to PUVA or other skin-directed therapies. The results are also good in symptomatic erythroderma. The stage of the disease and the total dose of the electron irradiation determine the end result, such as the response to therapy and diseases-free survival. In a study by Hoppe et al. the initial complete response ranged from 86 % in early-stage diseases to 44 % in the tumor stage. Kuten et al. have reported a cure rate of 95–100 % with TSEI [43]. Ysebeart et al. have described that TSEI produces excellent results in T1, T2 stage of MF [77]. The probability of complete remission is high with TSEI, and it offers good palliation in advanced disease [13]. Regardless of the technique used, the most important factors to get the best results in TSEI remain the electron energy, which should be 4 MeV and the total dose which should be more than 30 Gy [34, 57, 58]. Published literature also shows the benefit of TSEI on SS which reduces the burden of circulating T-cells in peripheral blood [30].

We have been using this therapeutic modality in MF patients since 1985, and in our experience, TSEI is an excellent treatment modality in both early and advanced disease [57, 58]. Between 1985 and 1998, we have treated 14 such patients, all males between 27 and 82 years of age with a disease duration of 4 months to 2 years [57]. The duration of disease was <6 months in two patients, 6–12 months in four, and 1–2 years in the rest. Out of 14 patients, 7 had T2 and the other 7 had T3 stage disease. Seven patients had more than 90 % skin involvement, whereas the remaining patients had 60–90 % involvement. Nine patients had predominantly plaque lesions with diffuse involvement, while the rest had tumors and plaques. Two patients had lymph node involvement at the time of presentation. TESI was carried out using a high-energy linear accelerator (Clinac-20) with 6 MeV electrons. The patients were made to stand on a stationary platform with the legs wide apart behind a polystyrene screen (to reduce the beam energy to 4 MeV) at a distance of 10 ft from the isocenter of the accelerator. Two large overlapping fields were used to irradiate the whole length of the body. The central axis of the fields pointed 15^° upwards and downwards from the horizontal plane to minimize photon contamination, as described in the Stanford technique. All the patients were treated in six positions (anterior, posterior, left anterior oblique, left posterior oblique, right anterior oblique, and right posterior oblique). The total dose of radiation varied from 8 to 36 Gy with a daily fraction size of 120 cGy, given over 5 days in a week. During irradiation the eyes and nails were shielded with a 3 mm-thick lead shield. A supplementary boost dose of 10 Gy was given to self-shielding areas like the scalp, perineum, and soles. Only seven patients could tolerate a total dose of 36 Gy, while three patients received a dose between 24 and 36 Gy, and one patient was treated with a palliative dose of 8 Gy. Three patients did not come back for treatment after the initial eight treatment sessions; hence they were excluded from the analysis. The total follow-up period ranged between 4 and 110 months (median 52 months) [57]. Ten patients had complete remission with no evidence of disease following TSEI. Histopathology repeated in three patients also did not show any evidence of MF. Relapse of the cutaneous lesions occurred in three patients over the shaded area. All of them had received a total dose of less than 30 Gy. The relapse was noticed after a minimum follow-up period of 2 months. One patient developed visceral metastasis involving the liver 6 months after radiotherapy. Two patients died due to progression of the disease. Five patients were alive without any evidence of the disease at the end of 5 years of follow-up.

At present we perform TSEI using Elekta (SL-20) dual energy linear accelerator having a special attachment which delivers electron at a very high-dose rate (30 Gy/min) at the isocenter [58]. The high-dose-rate (HDR) mode delivers a 4 MeV electron beam with acceptable beam uniformity and adequate depth dose while maintaining a low level of X-ray contamination. The HDR mode is a useful treatment modality with good results and reduced treatment time while retaining proper functioning of the accelerator dosimetry systems and interlocks. Between 1998 and 2000, we have treated seven clinically diagnosed and histopathologically proven CTCL patients using HDR mode TSEI. All seven patients were male between 40 and 64 years of age, who had the disease for 9–18 months. Three patients had T2 and four patients had T3 stage disease with more than 90 % involvement. In three patients, the lesions were confluent, ulcerated and bleeding on manipulation. Extracutaneous sites were not involved in any of the patients. All patients were evaluated and treated with TSEI with a total radiation dose of 36 Gy. Thermo luminescent dosimeter (TLD) measurements of the prescribed skin dose were obtained in these patients at the lateral margins, dorsum of the foot, perineum, and scalp. The patients were given hydration before treatment and advised to take high calorie diet throughout the treatment. The treatment time taken for an individual setting with this modality was only about 15 min, which is significantly shorter than conventional TSEI time, which takes about 2 h. Four out of seven patients had complete remission both clinically and histopathologically following TSEI. In the other two patients, the lesions healed with a few ulcers, which healed within 2 months after TSEI. One patient died during the course of treatment owing to rapid progression of the disease. There were treatment interruptions for various durations in all patients because of radiation-associated morbidities such as the decrease in hemoglobin and total leucocytes count, development of blister, desquamation of the skin, and poor general condition of the patients. One patient developed pericardial effusion leading to generalized edema, who was managed for cardiac disease and treated like other patients. The patients were followed up at an interval of every 6 weeks in the first year, every 3 months during the second year, and every 6 months there after following TSEI. The total follow-up period ranged from 4 to 26 months (median 9 months) [58]. In one patient, the lesions relapsed on the trunk after 10 months, and in the other patient who did not received the boost treatment, the lesions relapsed over the eyelid and the perineum after 4 months. He was treated with 10 Gy of radiation dose to these regions. At the end of 2 years, all six patients were alive. The combined results have been outlined in Table 11.2.

Now there is enough evidence to suggest that TSEI alone can achieve remission rate of 80–97 % in newly diagnosed MF patients. The patients with stage IA, where the lesions persist or relapse after treatment, and in those with stage IB – IV disease also have reduced risk of clinically significant progression, transformation, and dissemination of disease following TSEI, leading to higher rates of cause-specific and overall survival.

TSEI is a well-tolerated therapy by most of the patients; however, radiation-associated acute toxicities like erythema, pruritus, alopecia, xerosis, edema of the lower limbs, hypohidrosis, bullae of the hands and feet, and loss of nails may occur in majority of the patients. On long- term follow-up, the most common symptoms observed are telangiectasia, atrophy, xerosis, alopecia, and hypohidrosis. Secondary cutaneous malignancies following TSEI have also been reported, which may be partly due to previous therapies used for the disease, particularly potent carcinogens like PUVA and mechlorethamine which may have contributed to the increased risk [1, 44]. Systemic side effects following TESI are usually not observed, as electrons do not penetrate beyond dermis.

At our centers, the therapy was tolerated well by most of the patients; however, radiation-associated changes like nausea, general fatigue, complete loose of hair, edema over the joints of the extremities, and tenderness over the hand and feet were observed in all patients who received more than 20 Gy of radiation. Patients receiving more than 20 Gy radiation also developed different grades of skin desquamation (grade III-3, grade II-7). Moist desquamations as well as blisters over the dorsa of the feet and lateral body surfaces were more often encountered with a higher dose. The desquamation was visible in the third week of the treatment. The treatment had to be interrupted for some periods in these patients to allow the desquamation to heal. The patients who developed acute toxicities were taken off the radiation therapy, admitted and managed with antibacterial therapy, parenteral nutrition, and blood transfusion where indicated and other conservative measures were instituted [57]. Four and two patients had edema of the hands and feet and conjunctivitis, respectively. One patient had dystrophy of the nails of the hands. However, none of the patients developed skin necrosis or a corneal ulcer.

The response to radiation therapy in MF is dependent on the total radiation dose and duration of treatment. Prolonged overall treatment duration can spare the tumor cells and lower the chance of cure, whereas delivering the total dose over a shorter duration provides greater radiobiological benefit and offers better tumor control [7, 25]. Hence, it is very important not to have more treatment interruptions and to complete the total treatment within shorter duration.

In order to reduce TSEI-related toxicities and treatment interruptions, we tried to modify the treatment schedule. The treatment was carried out using a HDR mode delivering 4 MeV electron at a dose rate of 30 Gy/min at isocenter. In this protocol, the patients were treated with Stanford technique, 120 cGy/field/day, to a total dose of 36 Gy. The treatment was delivered 5 days/week for first 2 weeks and then on alternate days until completion of total radiation dose. At the end of the treatment, a booster dose of 10 Gy was delivered to self-shielding areas such as sole, scalp, and perineum. Rest of the evaluation and follow-up protocols were similar to previous group of patients. This modification in the treatment protocol resulted in much less occurrence of radiation-associated toxicities like wet desquamation, swelling of joints, etc., with no treatment interruptions. The toxicities were limited to small blisters and mild swelling and pain of small joints. All the patients could complete the radiation treatment of total dose of 36 Gy within 10 weeks, compared to 14 weeks by conventional treatment schedule. Four patients were treated with this protocol and all of them had complete remission [59]. They were followed up for 60–84 months with no relapse of the disease. Comparative details of conventional Stanford technique and modified protocol are given in Table 11.3