The Role of Radiation Therapy in Treating T Cell Lymphoma of the Skin

Local superficial radiotherapy in the management of minimal stage IA cutaneous T-cell lymphoma (Mycosis Fungoides).

Wilson LD, Kacinski BM, Jones GW ,Int J Radiat Oncol Biol Phys 1998 Jan 1;40(1):109-15 

Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06510, USA.

PURPOSE: To evaluate the impact of local superficial radiotherapy with respect to local control, survival, and toxicity for patients with "minimal" stage IA cutaneous T-cell lymphoma (Mycosis Fungoides). METHODS AND MATERIALS: Between 1954 and 1996 a total of 21 patients were identified as receiving curative local superficial radiation (LSR) for minimal stage IA Mycosis Fungoides. All patients had pathologic documentation at diagnosis and at the time of suspected recurrences and no patient received prior radiation. Ten patients were treated with 100-280 Kv (A1), and 11 with 4-12 Mev electrons. Nine patients had failed prior therapies (steroids: 4; PUVA: 3; BCNU: 1; UVB: 1) and six received adjuvant therapy after completion of LSR (PUVA: 5; steroids: 1). Minimum follow-up was 1 year. RESULTS: The median follow-up was 36 months (13-246), and the median age when commencing LSR was 55 years (27-73). All patients were Caucasian, and 11 were male. A total of 32 lesions were identified in 21 patients; 13 patients had unilesional disease, 5 patients had 2 lesions, and 3 had 3 lesions. A total of 33 fields were treated with a median treatment surface area of 107 cm2 (11-785). The median surface dose was 20 Gy (6-40), with 17 patients receiving a dose > or = 20 Gy. The median fraction number was 5 for all fields, but was 10 for the fields receiving 20-40 Gy. The complete response rate was 97%, and all patients were alive at last evaluation. All failures were cutaneous. One patient had persistent disease (treated with 6 Gy), and three failed locally at 52 months (8 Gy), 16 months (20 Gy), and 4 months (20 Gy). None of these patients received adjuvant therapy. Two patients failed in distant skin sites and were salvaged. The actuarial DFS for the entire group at 5 and 10 years was 75 and 64%, respectively, with local control of 75% at both time intervals. For the 13 patients with unilesional disease, the DFS was 85% at 10 years. For those treated with doses > or = 20 Gy, the DFS was 91% as was local control (no distant failures). Toxicity included mild erythema and dry desquamation acutely. Chronic toxicity included dermatitis [2], and telangiectasia [1]. No second cutaneous malignancies or hematologic toxicity was noted. CONCLUSION: Patients with minimal Stage IA Mycosis Fungoides may be managed effectively with local superficial radiation alone without adjuvant therapy. Distant failure is unusual and patients should receive a minimum surface dose of 20 Gy, which offers excellent local control. Sequalae of therapy are minimal.

Radiotherapy for unilesional mycosis fungoides.

Micaily B, Miyamoto C, Kantor G, Lessin S, Rook A, Brady L, Goodman R, Vonderheid EC , Int J Radiat Oncol Biol Phys 1998 Sep 1;42(2):361-4

Department of Radiation Oncology, Allegheny University Hospitals, Hahnemann, Philadelphia, PA 19102, USA.

PURPOSE: To evaluate the treatment outcome and natural history of patients with the diagnosis of unilesional mycosis fungoides, treated according to a prospective radiotherapy protocol in our institution since July 1975. METHODS AND MATERIALS: A total of 325 patients with the diagnosis of mycosis fungoides have been referred to the Department of Radiation Oncology at Allegheny University of Health Sciences from July 1975 through September 1996. Of these, 18 patients (5%) were classified as having unilesional mycosis fungoides and were irradiated with a curative intent using local electron fields. One patient received 22 Gy; 1 patient received 40 Gy, and the rest of the patients 30.6 Gy. Daily fractions ranged from 1.8 to 2.0 Gy. Treatments prior to radiation consisted of topical steroids and/or antifungal creams in the majority of patients, with temporary partial responses. One patient had received 2 years of topical mechlorethamine (HN2) and another patient had received topical carmustine solution (BCNU) without response prior to irradiation. RESULTS: The responses were measured clinically; posttreatment skin biopsy was not performed routinely unless there was clinical evidence of disease persistence. Complete response rate was 100%; all treated lesions cleared completely within 4 to 8 weeks after the completion of radiation. With a median follow-up of 43 months (range 12 to 240 months), 2 relapses have occurred, 2 and 71 months after the completion of radiation. Both relapses were confined to the skin and were remote from the original site. Both relapses responded to topical application of HN2. There have been no recurrences in the irradiated field nor systemic dissemination. No long-term side effects were found related to treatment, and all the patients are currently alive and without evidence of disease. Actuarial relapse-free and overall survival at 10 years are, respectively, 86.2% and 100%. CONCLUSION: Unilesional mycosis fungoides has a long natural history, is possibly the earliest manifestation of a malignant process, and local treatments, including local radiotherapy, result in long-term disease-free intervals and, possibly, cure. Total skin electron beam radiotherapy is not indicated for this disease entity.

Radiotherapy of advanced mycosis fungoides: indications and results of total skin electron beam and photon beam irradiation.

Maingon P, Truc G, Dalac S, Barillot I, Lambert D, Petrella T, Naudy S, Horiot JC,  Radiother Oncol 2000 Jan;54(1):73-8

Radiotherapy Department, Centre G.F. Leclerc, Dijon, France.

BACKGROUND: The goals of this retrospective study of advanced mycosis fungoides are (1) to describe the indications of a combination of total skin electron beam and photon beam irradiation and (2) to analyze the results of total body or segmental photon irradiation for patients with extension beyond the skin. METHODS: From January 1975 to December 1995, 45 patients with pathologically-confirmed mycosis fungoides or Sezary syndrome received a combination of TSEB and photon beam irradiation for advanced disease: 34 males and 11 females, mean age 61 years (range 27-87 years). The mean follow-up was 111 months (range 18-244 months, median 85 months). Whole-skin irradiation treatment to a depth of 3-5 mm with a 6-MeV electron beam was produced by a linear accelerator to a total dose of 24-30 Gy in 8-15 fractions, 3-4 times a week. In cases of thick plaques or tumors that were beyond the scope of low energy electron beams or for treating nodal areas (especially in the head and neck area or axilla involvement), regional irradiation (RRT) with Co-60 photon beams was followed by whole-skin electron beam irradiation (15 patients). In cases of diffuse erythrodermia, Sezary syndrome, nodal or visceral involvement, total body irradiation was delivered with a 25-MV photon beam using a split-course regimen to prevent hematological toxicity (22 patients). The first course consisted of 1.25 Gy delivered in ten fractions and 10 days. Subsequently, patients received TSEB. Four to 6 weeks after TSEB, they received a second course of 1.25 Gy. The cumulative TBI dose ranged from 2.5 to 3 Gy in about 3 months. Hemi-body irradiation (HB) with Co-60 (and a bolus) was given in cases of multiple regional tumors with large and thick infiltration of the skin to a dose of 9-12 Gy (using fractions of 1-1.5 Gy/day) which, once flattened, were boosted with whole-skin electron beam therapy (8 patients). RESULTS: At 3 months, the overall response rate was 75% with 23/45 (51%) patients in complete response and 24% in partial response; one patient had stable lesions and 1 patient presented progressive disease. The overall response rate was 81% for T3 patients, 61% for T4, 79% for N1 and 70% for N3. The complete response rate was 67% for T3 and 28% for T4. Sixty-four percent of N1 patients and 41% of N3 had a complete response. The 5-year actuarial overall survival was 37% for T3 and 44% for T4 (P = 0.84). Patients with clinically abnormal lymph nodes that were pathologically negative (N1) presented a 5-year survival of 63%. Patients with pathologically positive lymph nodes (N3) experienced a 5-year survival rate of 32% (P = 0.040). CONCLUSIONS: TSEB provides an excellent quality of life by reducing itching and discharge from the skin. Patients with more advanced disease may be treated and cured by the addition of photon beams in combination with TSEB. A selection of patients with advanced skin disease and regional extension may be cured by a combination of TSEB and photon beam irradiation. The regional treatment allows the use of electrons after the reduction of the plaques or thick tumors and a prophylactic irradiation of the adjacent nodal area.

Total skin electron radiation for patients with erythrodermic cutaneous T-cell lymphoma (mycosis fungoides and the Sezary syndrome).

Jones GW, Rosenthal D, Wilson LD,  Cancer 1999 May 1;85(9):1985-95

Department of Radiation Oncology, Cancer Care Ontario, Hamilton, Canada.

BACKGROUND: There is limited published evidence regarding the efficacy of total skin electron beam radiation for patients with the diffuse erythrodermic form of mycosis fungoides. METHODS: Forty-five patients with erythrodermic mycosis fungoides were managed at McMaster University in Hamilton, Ontario, Canada (n=34), and at Yale University (n=11) between 1970 and 1996. All received radiation without neoadjuvant, concomitant, or adjuvant therapies. The median age was 67 years (range, 42-84 years). The male-to-female ratio was 2.2. Fifteen received radiation for the treatment of newly diagnosed disease. There were 28 with Stage III (T4 N0-1 M0), 13 with Stage IVA (T4 N2-3 M0), and 4 with Stage IVB (T4 N0-3 M1) disease, and 21 had blood involvement. The median radiation dose was 32 gray (Gy) (range, 4.8-40 Gy). The median treatment time was 21 days (range, 3-125 days). A technically more intense method of radiation (32-40 Gy and 4-6 MeV electrons) was administered to 23 patients. RESULTS: All patients responded. The rate of complete cutaneous remission was 60%, with 26% remaining progression free at 5 years. Remission was associated with more intense radiation (P=0.014 in multivariate analysis with adjustment for blood and staging information). With the more intense radiation, 74% attained remission, with 36% remaining progression free at 5 years. For 8 patients with Stage III disease without blood involvement, all entered remission, with 69% remaining progression free at 5 years. Twenty of 30 deaths were related to mycosis fungoides. The median overall survival was 3.4 years, with a 10-year estimate of 28%. The median cause specific survival was 5 years, with a 10-year estimate of 43%. Both overall and cause specific survival were associated with an absence of blood involvement (both P<0.03 in multivariate analysis). Age was not a significant factor. Toxicities of radiation were acceptable when radiation was administered over 6-9 weeks at 5 fractions per week. CONCLUSIONS: Total skin radiation is an efficient monotherapy for patients with erythrodermic mycosis fungoides. With more intense radiation, the rate of cutaneous remission is 74%, and 27% remain progression free at 10 years. Radiation may be most efficacious in Stage III, with no blood involvement. When there is blood, lymph node, or visceral involvement, combined modality therapies should be explored.

Prognosis with newly diagnosed mycosis fungoides after total skin electron radiation of 30 or 35 GY.

Jones GW, Tadros A, Hodson DI, Rosenthal D, Roberts J, Thorson B,  Int J Radiat Oncol Biol Phys 1994 Mar 1;28(4):839-45

Hamilton Regional Cancer Centre, Ontario Cancer Foundation, Hamilton, Canada.

PURPOSE: To determine the prognosis of new patients with T1-4N0-1B0M0 mycosis fungoides treated with total skin electron beam radiation. METHODS AND MATERIALS: 25 consecutive patients received 30 Gy with 3 or 4 MeV electrons in 1977-1980; 121 received 35 Gy with 4 MeV in 1980-1992. Response rates, relapse-free survival, and overall and cause-specific survivals were assessed by explicit criteria. The relationships of T, N, gender, age, and radiation technique to prognosis were investigated by regression statistics. RESULTS: The average age was 55 years and the male:female ratio was 1:4. Forty-four percent were T1N0 and 34% were T2N0. The overall complete response rate was 82%, and lower T status, more radiation, and female gender were independently and positively associated with response. Median follow-up was 5.2 years. T1 patients who entered remission had a higher relapse-free survival compared to T2 through T4 patients. Thirty-four percent of T1 patients remained relapse-free at 6 years, compared to fewer than 20% of T2-4 patients. For all 146 patients the median overall survival was not reached at 15 years. Only 8 of 29 deaths were related to mycosis fungoides and these were significantly associated with higher T. The 54 T1N0 patients who had 35 Gy had a 10-year mycosis fungoides-specific survival of 100%. CONCLUSION: Total skin electron beam radiation gives good results with T1N0B0M0 disease. T3-4 disease is less likely to respond, it relapses more quickly, and it implies a poorer survival, but radiation offers palliation. T2 responds like T1, but relapses like T3-4. T2 also implies an intermediate survival. These results have implications for staging, informed consent, optimizing radiation treatment, and clinical trials.

Radiotherapy in the management of mycosis fungoides: indications, results, prognosis. Twenty years experience.

Kirova YM, Piedbois Y, Haddad E, Levy E, Calitchi E, Marinello G, Le Bourgeois JP,  Radiother Oncol 1999 May;51(2):147-51

Department of Cancerology, Henri Mondor University Hospital, Creteil, France.

PURPOSE: To determine the role of total skin electron beam therapy (TSEBT) and the prognosis of patients with mycosis fungoides. MATERIALS AND METHODS: From 1978 to 1996, 66 consecutive patients with mycosis fungoides received 30 Gy TSEBT delivered in 12 fractions over 40 days as treatment of their relapsed after topical or/and systemic therapy. All patients were staged as follows: stage A, superficial lesions covering less than 50% of the body surface; stage B, superficial lesions covering more than 50% of the body surface; Stage C. tumors involving the skin, lymph nodes and/or visceral organs. RESULTS: The median age was 50 years (ranging from 13-78 years). There were 39 males and 27 females. The minimum follow-up was 12 months (range 12-192 months). There were 24 (36%) stage A patients, 22 (33%) stage B patients, and 20 (30%) stage C patients. The overall survival at 5 years for our series was as follows: 93% for stage A; 79% for stage B, and 44% for stage C disease (P = 0.002). For the entire cohort, the complete remission rate was 65%, the progression-free survival (PFS) at 5 years and 10 years was 30 and 18% respectively. For the group A, PFS was 62% at 5 years and 46% at 10 years; for group B, PFS was 19% at 5 years. CONCLUSIONS: This study suggests that TSEBT gives good results for relapsed stage A disease. Total skin electron beam therapy combined with local fields irradiation or other local treatment (puvatherapy or topical nitrogen mustard) might further improve permanent complete response for stage B patients. The most advanced stages of mycosis fungoides are not controlled by TSEBT, but the radiation therapy offers good palliation results.

Total skin electron beam therapy with or without adjuvant topical nitrogen mustard or nitrogen mustard alone as initial treatment of T2 and T3 mycosis fungoides.

Chinn DM, Chow S, Kim YH, Hoppe RT,  Int J Radiat Oncol Biol Phys 1999 Mar 15;43(5):951-8

Department of Radiation Oncology, Stanford University Medical Center, CA 94305, USA.

PURPOSE: To compare the efficacy of total skin electron beam therapy (TSEBT) with or without adjuvant topical nitrogen mustard (+/- HN2) with topical nitrogen mustard (HN2) alone as initial management of T2 and T3 mycosis fungoides (MF). METHODS AND MATERIALS: A retrospective analysis of 148 patients presenting to Stanford from January, 1970 through January, 1995 within 4 months of pathologic diagnosis of MF. Fifty-five patients with T2 and 27 with T3 disease received TSEBT +/- HN2. Fifty-four patients with T2 and 12 with T3 disease received HN2 alone. Boosts with radiotherapy were usually administered to cutaneous tumors of patients with T3 disease. RESULTS: TSEBT +/- HN2 yielded significantly higher complete response (CR) rates than did HN2 alone in patients with T2 and T3 disease (76% vs 39%, p = 0.03 for T2, and 44% vs 8%, p < 0.05 for T3, respectively). In T2 disease, treatment with adjuvant HN2 was associated with a longer freedom from relapse following TSEBT when compared to observation following a CR to TSEBT (p = 0.068). However, no significant differences in survival were observed for different management programs for T2 or T3 disease. In T2 disease, both TSEBT and HN2 were as effective as salvage therapy as when utilized as initial therapy. However, salvage therapy in T3 disease was rarely effective. Limited tumor involvement in T3 disease did not correlate with improved survival compared to more generalized tumorous disease. MF contributed to 27% and 68% of deaths in patients with T2 and T3 disease, respectively. CONCLUSION: Because of high response rates, management of significantly symptomatic or extensive T2 MF should include TSEBT, and adjuvant HN2 should be administered after a CR to TSEBT. Patients with T2 disease who fail TSEBT or HN2 can be salvaged with the other modality. TSEBT is also an effective treatment for T3 disease. The small subset of patients with limited T3 disease may also be treated with HN2 and local radiotherapy to the tumors. Further investigations are necessary to improve the overall outcome for T3 mycosis fungoides.

Experience with total skin electron beam therapy in combination with extracorporeal photopheresis in the management of patients with erythrodermic (T4) mycosis fungoides.

Wilson LD, Jones GW, Kim D, Rosenthal D, Christensen IR, Edelson RL, Heald PW, Kacinski BM,  J Am Acad Dermatol 2000 Jul;43(1 Pt 1):54-60

Departments of Therapeutic Radiology and Dermatology, Yale University School of Medicine, New Haven, CT 06520-8040, USA.

OBJECTIVE: We compared the prognosis of patients with erythrodermic mycosis fungoides (MF) administered total skin electron beam radiation (TSEB) plus neoadjuvant, concurrent, and adjuvant extracorporeal photopheresis (ECP) with the prognosis of patients administered only TSEB. Outcomes of clinical interest include disease-free survival (DFS), progression-free survival (PFS), overall survival (OS), and cause-specific survival (CSS). METHODS: This study was a retrospective nonrandomized series. Between 1974 and 1997, a total of 44 patients with erythrodermic MF from the Department of Therapeutic Radiology, Yale University School of Medicine, and the Department of Radiation Oncology, Cancer Care Ontario, Hamilton, Ontario, were collected and analyzed as a group (Hamilton = 15, Yale = 29). These patients received TSEB consisting of 32 to 40 Gy via 4 to 6 MeV. Twenty-one patients at Yale also received ECP treatment 2 days per month for a median of 6 months. Median age was 68 years (range, 29-82 years) at the commencement of TSEB, and 66% were male. Seventy-three percent of patients had received other therapies before TSEB, including 75 courses that failed to control disease (n = 15 systemic therapy, 16 biologicals, and 44 topical therapies). At TSEB, 59% had hematologic involvement (B1), 30% were stage IVA (N3), and 13% were IVB (M1). Median follow-up was 2.2 years (range, 0.3-13.9 years) subsequent to TSEB and 3.7 years from diagnosis (range, 0.8-16.8 years). RESULTS: All patients responded to TSEB within 2 months of completion, with a cutaneous complete response rate of 73%. For the 32 complete responders the 3-year DFS was 63%. It was 49% for those 17 patients who received only TSEB compared with 81% for those 15 patients who received TSEB + ECP. Cox regression analysis demonstrated that ECP was associated with prolonged remission (DFS multivariate P =.024, adjusting for B1 and stage). The 2-year PFS, CSS, and OS for the TSEB group were 36%, 69%, and 63%, respectively, compared with 66%, 100%, and 88% for the TSEB + ECP cohort. Cox regression demonstrated that ECP was associated with CSS (multivariate P =.048, adjusting for B1 and stage). For those who progressed, a total of 49 subsequent courses of therapy were administered (n = 20 chemotherapy, 10 biologicals, and 19 topical therapies). Thirteen patients died from MF-related causes, and 8 died from other causes. Acute and chronic toxicities were consistent with those previously reported. CONCLUSION: ECP given concurrently with, or immediately after, TSEB (32-40 Gy) significantly improves both PFS and CSS for patients with erythrodermic MF compared with TSEB without the addition of ECP.