Total skin electron beam therapy as palliative treatment for cutaneous manifestations of advanced, therapy-refractory cutaneous lymphoma and leukemia
© Hauswald et al.; licensee BioMed Central Ltd. 2012
Received: 30 March 2012
Accepted: 18 June 2012
Published: 29 July 2012
To retrospectively access the outcome and toxicity of a total skin electron beam therapy (TSEBT) in patients with cutaneous lymphoma (CL) or leukemia.
Patients and methods
Treatment results of 25 patients (median age 63 years; 5 female, 20 male) with cutaneous manifestations of advanced and therapy-refractory CL (n = 21; T-cell lymphomas n = 18, B-cell lymphomas n = 3) stage IIB-IV or leukemia (n = 4; AML n = 2, CLL n = 1, PDC n = 1) treated between 1993 and 2010 were reviewed. All patients were symptomatic. The median total dose was 29Gy, applied in 29 fractions of median 1 Gy each.
The median follow-up was 10 months. Palliation was achieved in 23 patients (92%). A clinical complete response was documented in 13 (52%) and a partial response in 10 patients (40%). The median time to skin progression was 5 months (range 1–18 months) and the actuarial one-year progression-free survival 35%. The median overall survival (OS) after the initiation of TSEBT was 10 months (range 1–46 months) and the actuarial one-year OS 45%. TSEBT related acute adverse events (grade 1 or 2) were observed in all patients during the treatment period. An acute grade 3 epitheliolysis developed in eight patients (32%). Long-term adverse events as a hyperpigmentation of the skin (grade 1 or 2) were documented in 19 patients (76%), and a hypohidrosis in seven patients (28%).
For palliation of symptomatic cutaneous manifestations of advanced cutaneous lymphoma or leukemia, total skin electron beam therapy is an efficient and well tolerated considerable treatment option.
classification of cutaneous T-cell lymphoma (CTCL)
Clinically and/or histopathologically suspicious lesions
Limited plaques, papules, or eczematous patches covering <10% of the skin surface
Generalized plaques, papules, or erythematous patches covering 10% or more of the skin surface
Tumors, one or more
No clinically abnormal peripheral lymph nodes; pathology negative for CTCL
Clinically abnormal peripheral lymph nodes; pathology negative for CTCL
No clinically abnormal peripheral lymph nodes; pathology positive for CTCL
Clinically abnormal peripheral lymph nodes; pathology positive for CTCL
No visceral organ involvement
Visceral involvement (must have pathology confirmation and organ involved should be specified)
Staging system of cutaneous T-cell lymphoma (CTCL) (original version)
Patients and methods
Characteristics of 25 patients with advanced and therapy-refractory CL
No. of patients
median, 63 years
range, 28-76 years
T-cell lymphoma (CTCL)
B-cell lymphoma (CBCL)
Acute myeloic leukemia
Chronic lymphatic leukemia (CLL)
Plasmacytoid dendritic cell leukemia (PDCL)
Radiotherapy was performed as total skin electron beam therapy and the patient standing in an upright position on a rotating base being irradiated by two electron fields with initial energies of 6 MeV that are reduced to 3.8 MeV by a Lucite moderator. Details on treatment setup were published by Funk et al. . It was our intention to perform a conventional TSEBT applying a total dose of 30–35 Gy. The median total dose applied was 29Gy (range 11–35 Gy), median single fraction size was 1 Gy (range 1–1.5 Gy). Additionally, 9 patients received a local boost irradiation using electron beams. During the course of radiotherapy, all patients were treated as inpatients to observe them closely and to avoid a tumor lysis syndrome.
The data was analysed regarding overall survival (OS) and skin-progression-free survival (PFS). Statistical analyses were carried out with SPSS statistical package (SPSS Inc., Chicago, IL, U.S.A.) using log-rank test (Mantel-Cox) and Kaplan-Meier’s estimation. Significance was defined as p-value <0.05. All time estimates began with the initiation of radiation treatment. Documented long-term side effects were classified according to the RTOG/EORTC Late Radiation Morbidity Scoring Scheme (Appendix IV, CTC Version 2.0). Approval of the ethics committee Heidelberg was obtained.
Response to treatment, tumor control and survival
Treatment related acute adverse events as mild to moderate fatigue, mild erythema, dry desquamation, mild edema and alopecia were observed in all patients during the treatment period and shortly after. None of the patients suffered from tumor lysis syndrome. An acute grade 3 epitheliolysis developed in eight patients (31%). Two patients died due to tumor progression and organ failure during the radiation treatment. One of these 2 patients suffered from a pneumonia finally causing fatal renal failure, the other patient developed fatal renal failure due to a blast crisis during TSEBT. Furthermore, following long-term adverse events were documented during follow-up visits: grade 1 or 2 hyperpigmentation of the skin developed in 19 patients (76%), and seven patients (28%) reported a hypohidrosis.
We report the treatment results in 25 patients treated with total skin electron beam therapy between 1993 and 2010 for cutaneous manifestations of advanced, extensively pretreated and therapy-refractory cutaneous lymphoma and leukemia. The overall treatment response with 92% symptom relief, especially of the pruritus and regression of cutaneous lesions, and 52% clinical complete remissions as well as 40% partial remissions demonstrate the efficacy in the setting of advanced and otherwise therapy-refractory disease. In the daily routine, treatment side effects as fatigue and skin reactions seem manageable.
A recent development to reduce the significant treatment-related side effects is to identify a lower possible treatment dose while keeping the effective treatment response. In this setting, Harrison et al. identified 102 patients treated for MF with low-dose (5- < 30Gy) TSEBT between 1958 and 1995. Patients had stage classifications T2-T4. The overall response rates were dose dependent with 90% in patients receiving 5 to <10 Gy (n = 19), 98% in 10 to <20Gy and 97% in 20 to <30Gy and efficacy measures as OS and PFS were comparable . In comparison to our results, these patients were treated with TSEBT median 4 months after initial diagnosis; in our cohort, patients were extensively pretreated and time from initial diagnosis to TSEBT was median 2 years. Besides this, the majority (51 patients) had T2 disease. The PFS was not given for the whole group, but the subgroup with T3 and T4 disease and >/= 30 Gy TSEBT had a median PFS of 2.9 years and 4.6 years, respectively. Kamstrup et al. evaluated prospectively the efficacy of low-dose (10Gy) TSEBT. Ten patients with stage IB-IV MF were treated with 4 fractions of 1 Gy each week to a total dose of 10Gy. Six patients had T2, 2 patients T3 and 2 patients T4 disease, all patients received prior therapies. The median time from initial diagnosis to TSEBT was 1 year. The achieved overall response rate was 90% with a rate of CR as high as 70%. Median PFS was 5.2 months. Treatment was well tolerated with transient alopecia (56%) and ocular irritation (33%) as most common side effects . In comparison to our data, the overall response rates as well as PFS are comparable; however the number of patients with limited disease is relatively high in this study and one would have expected better results in T2 stage.
Overview of literature
Type of radiation treatment
Lindahl et al.
High-dose (30 Gy) n = 25
High-dose: CR 68%
9 months median
Low-dose (4 Gy) n = 10
Navi et al.
TSEBT (+/- HN2)
36 Gy (range 30-40 Gy)
T2: CCR 75%
T2: 8.5 years
T2: 10.9 years
T3: CCR 47%
T3: 2.9 years
T3: 4.7 years
Kamstrup et al.
T2 n = 6
median response duration 5.2 months
T3 n = 2
T4 n = 2
Chinn et al.
T2 n = 55
TSEBT (+/- HN2)
Mostly 36 Gy
T2: CR 76%
Freedom from recurrence at 1 year 41%
T2: 10.7 years
T3 n = 27
T3: CR 44%
T3: 3.6 years
IIB n = 4
Median 29 Gy
III n = 1
IVA n = 10
IVB n = 7
In 2009 Neelis and co-workers published results on 18 patients with CBCL treated with palliative low-dose involved-field (IF) radiotherapy (4 Gy in 2 fractions) and 31 patients with MF treated with 4 Gy, later with 8 Gy in 2 fractions. In total 126 lymphoma sites were treated. All patients were previously treated with different approaches, 15 patients have already had TSEBT. In the group of patients with CBCL, the rate of complete remission (CR) was 75% (33/44 lesions). In patients suffering from CTCL and MF, the remission rate after application of 2 x 2 Gy was disappointing (70% failed to achieve a CR), so the treatment dose was increased to 2 x 4 Gy and a CR rate of 92% (60/65 lesions) was achieved. According to the authors, high-grade side effects were not seen. In conclusion, the authors recommended low-dose IF radiotherapy as standard treatment in patients with cutaneous lymphoma, with the option of re-irradiation at progression . From our point of view, this concept of low-dose IF-RT seems to be an option in localized CL, or in the situation of localized recurrence after TSEBT.
Literature on cutaneous manifestations of leukemia, e. g. leukemia cutis is very rare. Pepek and colleagues reported on 2 pediatric patients treated with TSEBT and recommended the consideration of TSEBT for palliation . Furthermore, Rubin et al. concluded in a case report on a pediatric patient treated with TSEBT for leukemia cutis, that TSEBT is feasible and potentially effective . Our experience supports the feasibility of TSEBT in cutaneous manifestations in leukemia, especially in palliative situations.
For palliation of symptomatic cutaneous manifestations of advanced, PUVA- and chemotherapy-refractory cutaneous lymphoma or leukemia, total skin electron beam therapy is an efficient and well tolerated considerable treatment option.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
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