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.

We thank Drs Jones and Wilson for their interest in our recently published review on mycosis fungoides/Sezary syndrome (MF/SS).1-1 They raise several important issues. First, they suggest that modern total skin electron beam (TSEB) technique using 35 to 36 Gy delivered with electrons of at least 4 MeV energy (the MeV determines the depth of penetration) allows deeper penetration than older techniques, ie, to 2 to 3 cm, a difference that is important because it encompasses superficial lymph nodes. At our institute, we use a skin surface dose of 32 Gy delivered with electrons of 6 MeV. We agree that the optimal dose of penetration is up to 5 mm. However, despite the fact that the energy used here is higher than the 4 MeV quoted by Jones and Wilson, it does not significantly penetrate to 2 to 3 cm as they claim for 4 MeV. Indeed, at 2 cm, there is only 20% of the surface dose and, at 3 cm, it is negligible (Clinac 2100C-II HDTSe–Internal Release report, M.D. Anderson Cancer Center, 1994). These results are similar to those previously published by Fraass et al1-2 and indeed are consistent with the data reported by Jones et al.1-3 

In their letter, Jones and Wilson claim that overall survival is improved in patients who are treated with TSEB. The current literature does not adequately support such a claim. In the retrospective cohort analysis of the Stanford experience published in 1996,1-4 there was no improvement in survival in stage IA patients treated with TSEB as compared with those treated with mechlorethamine, despite the superior response rate to TSEB. Furthermore, a randomized trial conducted by the National Cancer Institute1-5 showed no difference in survival between patients treated with TSEB combined with chemotherapy versus those treated conservatively with topical agents. Finally, the increase in survival referred to by Jones and Wilson was recently published in a letter concerning a nonrandomized trial comparing patients who chose radiotherapy versus those who were managed with alternative therapies.1-6 Limited details of the study are available, but patients who chose TSEB were reported to have a superior overall survival, with this difference being most significant in the patients treated since 1980.

In conclusion, we agree that TSEB produces high response rates without severe toxicity. In our opinion, the outcome cited in our review1-1 for patients treated with this modality is not overly pessimistic. However, despite the high response rates, a well-controlled trial that supports a superior survival for patients treated with this modality has not yet been reported.

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