Mycosis Fungoides and Total Skin Electron Beam Radiation

To the Editor:

We are writing to clarify comments concerning total skin electron beam radiation (TSE) made by Diamandidou et al1 in their comprehensive review of mycosis fungoides and the Sezary syndrome.

The technical description of TSE in the review did not distinguish between premodern and modern methods of TSE. Modern TSE is defined by a skin surface dose of 35 to 36 Gy delivered with electrons of at least 4 MeV energy.2-4 This TSE optimizes the distribution of dose within the main target volume (epidermis and dermis, to a depth of 5 mm; including blood present in the skin during radiation). It also increases the penetration of electrons to between 2 to 3 cm to encompass many superficial lymph nodes.2 These attributes are clinically significant. A meta-analysis of the main technical parameters of TSE showed that modern TSE is associated with very high rates of complete remission, with even advanced disease having a rate in excess of 70%.2 3 Of course, a key question is whether modern TSE improves survival as compared with premodern TSE or no TSE.

The survival experiences of patients receiving less optimal versions of TSE were compared with the experiences of patients managed with other topical therapies in 4 studies. These included contemporaneous,5 concurrent,4,6 and randomized7 controls. All 4 studies showed that premodern TSE achieved only moderate rates of complete remission and was not associated with improved survival. For example, in the randomized trial,7 combined premodern TSE and systemic chemotherapy was no better than conservative management in 103 randomized patients, although it should be noted that a majority of the patients in this trial had nodal and visceral disease (and were stage IV). In contrast, both Hoppe et al8,9 and Jones and Thorson4 have separately shown that more optimal versions of TSE are associated with improved progression-free and overall survivals.3,8 Kim et al10 have just reported a comparison of mechlorethamine versus a predominantly historical and essentially premodern TSE control group for only stage IA disease. None of 34 TSE patients and 3 of 73 mechlorethamine patients died of MF (5% difference at 10 years; P = .18). Recently, Jones and Thorson4 were able to demonstrate that modern TSE (when delivered early on in the course of disease) is highly associated with improved survival as compared with a concurrent control group that did not receive TSE in accordance with patient preferences. The survival improvement with TSE is estimated at approximately 10% for all T and N combinations. Clearly, all of the data just cited, now totaling more than a 1,000 patients, form an internally consistent pattern. This indicates that modern optimized TSE changes the natural history of MF and improves survival.

Modern TSE has little chronic toxicity,2 and treatment with TSE as first or second line therapy does not preclude another application of TSE later in the course of disease, if it is required.11 The role for TSE in the management of patients with mycosis fungoides should be predicated on modern data that support both palliative and survival benefits with acceptable toxicity.

Adjuvant therapies such as psoralen plus UV A (PUVA), interferon, or photophoresis might improve on the results of modern TSE. Data suggest that adjuvant PUVA significantly improves the duration of remissions when treating advanced patch/plaque disease, as compared with concurrent controls, and a trend toward improved survival is apparent.12 Such retrospective findings will now be prospectively evaluated by randomizing patients with patch/plaque disease to observation or adjuvant PUVA after TSE at both Yale University and Hamilton.