Total skin electron beam and total nodal irradiation for treatment of patients with cutaneous T-cell lymphoma

Sixteen patients with advanced cutaneous T-cell lymphoma (CTCL) with or without lymph node involvement, but without evidence of extranodal manifestations, were treated with a combination of total skin electron beam therapy (TSEB) and total nodal irradiation (TNI). Fourteen (87%) patients achieved a complete response (CR) lasting from 1 to 84+ months (median, 8+ months) from the completion of treatment. The best results occurred in 6 patients with pretumorous intracutaneous CTCL (Stages IB and IIA) where the CR has lasted in all patients from 8 to 84+ months (median about 27+ months). Conversely, a long-term CR occurred in only one of five patients with tumor-phase intracutaneous CTCL (Stage IIB) and in none of the 5 patients with histopathologically proven nodal involvement (Stage IVA). Radiotherapy was well tolerated with the major toxicity being bone marrow suppression. We conclude that combined TSEB and TNI is a relatively safe and effective treatment for patients with CTCL prior to the development of lymph node involvement. Long-term follow-up is needed to assess the curative potential of this treatment.     

A prospective, open-label study of low-dose total skin electron beam therapy in mycosis fungoides

PURPOSE: To determine the effect of low-dose (4 Gy) total skin electron beam therapy as a second-line treatment of Stage IB-II mycosis fungoides in a prospective, open-label study. METHODS AND MATERIALS: Ten patients (6 men, 4 women, average age 68.7 years [range, 55-82 years]) with histopathologically confirmed mycosis fungoides T2-T4 N0-N1 M0 who did not achieve complete remission or relapsed within 4 months after treatment with psoralen plus ultraviolet-A were included. Treatment consisted of low-dose total skin electron beam therapy administered at a total skin dose of 4 Gy given in 4 fractions over 4 successive days. RESULTS: Two patients had a complete clinical response but relapsed after 3.5 months. Six patients had partial clinical responses, with a mean duration of 2.0 months. One patient had no clinical response. Median time to relapse was 2.7 months. One patient died of unrelated causes and did not complete treatment. Acute side effects included desquamation, xerosis, and erythema of the skin. No severe side effects were observed. CONCLUSION: Low-dose total skin electron beam therapy can induce complete and partial responses in Stage IB-II mycosis fungoides; however, the duration of remission is short. Low-dose total skin electron beam therapy may find application in palliative treatment of mycosis fungoides because of limited toxicity and the possibility of repeating treatments for long-term disease control.     

全身皮肤电子束治疗蕈样霉菌病

目的分析全身皮肤电子束治疗蕈样霉菌病的疗效。材料与方法１９７７～１９９３年间以ＳａｇｉｔｔａｉｒｅＣＧＲＭｅＶ直线加速器８ＭｅＶ电子束加上一层有机玻璃将能量降为４ＭｅＶ治疗４８例蕈样霉菌病患者，剂量为４０天内３０Ｇｙ／１２次。结果Ａ，Ｂ及Ｃ期组中分别有１１／１４，５／１１及１４／２３例患者达完全消退，平均无复发生存期分别为４９．５，２２．８及１９．８月。结论全身皮肤电子束治疗可治愈Ａ期蕈样霉菌病，且可改善Ｂ－Ｃ期患者的生存质量。     

全身电子线照射治疗T3期蕈样霉菌病的近期疗效分析

目的:探讨全身电子线照射治疗肿瘤期蕈样霉菌病的近期疗效和不良反应.方法:我院2007-2016年收治的皮肤蕈样霉菌病患者11例,均经病理检查证实,中位年龄52岁,均为T3期患者,所有病人采用6Mev电子线全身照射,总剂量DT 36 Gy,残留病灶电子线局部加量放疗DT 10～20 Gy,放疗后有8例患者联合CHOP方案化疗2～4周期.结果:总有效率为100％,其中CR 72.7％ (8/11)、PR 27％(3/11)、平均生存时间10.8月,目前生存2例,不良反应主要有皮肤红斑、干燥脱屑、脱发、无汗、色素沉着及骨髓抑制等.结论:全身电子线照射治疗T3期蕈样霉菌病的效果是显著的,且不良反应可耐受,因此可作为局部晚期蕈样霉菌病的治疗选择.     

Granulomatous slack skin: report of a case with response to electron beam therapy

Granulomatous slack skin (GSS) is a rare form of cutaneous T-cell lymphoma, closely related to mycosis fungoides. It is characterized by pendulous skin folds with a predilection for flexural areas. Histology shows an elastolytic granulomatous infiltrate with atypical lymphoid cells. Granulomatous mycosis fungoides is an important histologic differential diagnosis to be considered. We present a 19-year-old man with a gradually enlarging erythematous, and bulky lesions on his body. Histologically, a dense atypical lymphoid cell infiltration with numerous multinucleated giant cells and elastolysis was observed. T-cell receptor gene rearrangement was detected in skin lesions. He was treated with PUVA and interferon α, but improvement in skin lesions was not observed. Marked regression of all lesions was achieved by using electron beam therapy. This case report supports that GSS is an indolent variant of mycosis fungoides due to clinical, histological and T-cell gene rearrangement results. However, there is no definitive data about prognosis of the disease. We suggest that further clinical studies are needed to understand this rare condition.     

Total Skin Electron Beam Therapy for Mycosis Fungoides Revisited With Adjuvant Systemic Therapy

Background

Although standard-dose total skin electron beam therapy (TSEBT) has been thought to provide the greatest clinical benefit for mycosis fungoides, recent studies have shown that low-dose TSEBT may also provide high rates of disease control.

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

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 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.     

全身皮肤电子束照射急性毒性反应及剂量监测

目的分析全身皮肤电子线照射的急性毒性反应，探讨热释光剂量监测的临床意义。材料与方法自１９９５年底利用Ｖａｒｉａｎ－２１００ＣＨＤＴＳｅ－６ＭｅＶ电子束治疗模式治疗４例病人，分别用６ｍｍ和１０ｍｍ有机玻璃散射屏降低电子线能量，提高皮肤表面剂量。用热释光剂量计进行５人次１８个解剖部位的剂量监测，治疗周剂量５００～６００ｃＧｙ，总量３０００ｃＧｙ。结果全身皮肤电子线照射对各期皮肤Ｔ－细胞淋巴瘤均有良好控制效果；急性毒性反应限于皮肤及附属器，病人均能耐受；热释光监测结果与急性毒性反应相符。结论热释光剂量监测对疗中手指、足背屏蔽防护及治疗后头顶、腋下、会阴、足底补量照射有指导意义。对肥胖病人应行大腿内侧补量。     

Environmental factors and childhood acute leukemias and lymphomas

This review considers recent studies regarding the role of environmental factors in the etiology of childhood leukemia and lymphoma. Potential environmental risk factors identified for childhood leukemia include exposure to magnetic fields of more than 0.4 micro Tessla, exposure to pesticides, solvents, benzene and other hydrocarbons, maternal alcohol consumption (but only for certain genotypes), contaminated drinking water, infections, and high birth weight. The finding of space-time clustering and seasonal variation also supports a role for infections. There is little evidence linking childhood leukemia with lifetime exposure to ionizing radiation although fetal exposures to X-rays are associated with increased risk. Breast-feeding, consumption of fresh fruit and vegetables and having allergies all appear to be protective. Burkitt lymphoma (BL) is confined to areas of the world where malaria is endemic, with the additional involvement of the Epstein-Barr virus (EBV) as a co-factor. Environmental risk factors suggested for other types of non-Hodgkin lymphoma (NHL) include exposure to ionizing radiation (both lifetime and antenatal), pesticides, and, in utero exposure to cigarette smoke, benzene and nitrogen dioxide (via the mother). Hodgkin lymphoma (HL) is especially associated with higher levels of socioeconomic deprivation, but breast-feeding seems to confer lower risk. This is consistent with an infection or immune-response mediated etiology for HL.     

Pathology of peripheral T-cell lymphomas and leukemias

Peripheral T-cell lymphomas and leukemias have distinct histological and cytological characteristics although there are a variety of histological patterns even in a single lymph node. Histologic features are altered by the progression of the disease. There is no significant association between histology and prognosis. The variations in histologic features and clinical manifestations of peripheral T-cell lymphomas/leukemias can now be related to the presence of the retrovirus ATLV, and anti-ATLV antibodies as well as to the immunophenotypes of the lymphoma cells utilizing monoclonal antibodies. Changing concepts of peripheral T-cell lymphomas/leukemias are discussed.     

Total skin electron beam radiation therapy for mycosis fungoides.

Forty-nine patients with biopsy-proven mycosis fungoides, Stages I-IV were treated using total skin electron beam irradiation (TSEBI). Total dose ranged from 600 cGy to 3,200 cGy. To evaluate the dose response relationship, patients were retrospectively divided into two groups. In Group I, 18 patients received a dose of 2,000 cGy or less, and in Group II, 31 patients received more than 2,000 cGy. The overall response rate was 87.7% with a 75.7% complete response and 12.2% partial response. Complete response was higher among patients with early stage disease: (Stage IA 1/1, Stage IB 23/35 (92%), Stage IIA 3/4 (75%), Stage IIB 4/8 (50%), Stage III 3/6 (50%), Stage IVA 1/1, Stage IVB 0/1, and unstaged group 2/3 (66.6%)). Patients treated with a higher total dose had a higher overall 5-year survival rate (Group I 38%, Group II 68%), longer median duration of complete response (Group I, 27 months; Group II, 35.3 months), slightly better complete response rate (72.2% for Group I, 77.4% for Group II), and lower recurrence rate (Group I, 94%; Group II, 83.9%) compared to patients with lower total dose. Complications from TSEBI were minimal. Total skin electron beam irradiation is effective in controlling early stage mycosis fungoides; however, a prospective study to evaluate optimum total dose is needed.     

Total skin electron beam therapy in mycosis fungoides.

Thirty-nine patients with mycosis fungoides were treated with total skin electron beam irradiation from 1971 to 1976, and all received minimum follow-up of 12 months. Details of treatment technique and dosimetry are given. Sixteen patients cleared completely. Seven patients are in long-term remission (1 1/2 to 4 1/2 years). Eleven patients died. Those who failed are now being treated with topical therapy with varying degrees of control. Some have been retreated with local irradiation. Most of the patients had extensive disease; for this group, total skin electron beam therapy was especially useful, as many of those who failed developed only minimal disease that was well controlled by topical measures.     

Total skin electron beam and total nodal irradiation of cutaneous T-cell lymphoma

Nineteen patients with cutaneous T-cell lymphoma (CTCL) limited to the skin and/or lymph nodes were treated at Hahnemann University with a combination of total skin electron beam and total nodal irradiation (TSEB + TNI). The patients were classified as Stage Ib (1 patient), Stage IIa (8 patients), Stage IIb (5 patients), and Stage IVa (5 patients). Treatment resulted in a complete response in 100% (14/14) of patients with Stage Ib, IIa, and IIb disease, and a CR in 60% (3/5) of patients with Stage IVa disease. The Stage Ib and IIa patients had an overall survival of 100% and a disease-free survival of 44% at 6 years. Four of the five patients with Stage IIb CTCL relapsed within 3 months after completing TSEB + TNI with an overall survival in the group of 40% at 5 years. The Stage IVa patients all relapsed within 7 months and died of their disease within 50 months of completing treatment. The acute effects of TSEB + TNI were well tolerated, but three patients developed second malignancy (lung, kidney and skin) and one patient developed myelodysplasia, possibly the result of radiotherapy.     

Radiation therapy for localized low-grade non-Hodgkin's lymphomas

The most common low grade B-cell non-Hodgkin's lymphomas are follicular lymphomas, and extranodal marginal zone lymphomas, also known as mucosa-associated lymphoid tissue (MALT) lymphomas. Localized presentations of follicular lymphoma occur in 20-30% of cases, while for MALT lymphomas, stage I-II disease presentations occur in 70-90%. These are radiation-sensitive lymphomas. Following moderate dose local radiation treatment (30-35 Gy) for these stage I and II low grade lymphomas, the clinical results indicate long-term local control and possible cure. While local control is achieved with minimal morbidity with involved-field radiation therapy, a significant proportion of patients relapse with systemic disease outside of radiation fields. For follicular lymphoma, this occurs in approximately 50% of patients after 15 years, and for non-gastric MALT lymphoma, 30-40% after 10 years. Although patients with relapsed systemic disease are not curable with chemotherapy, the disease often behaves in an indolent fashion and prolonged survival is observed. For gastric MALT lymphomas, radiation therapy is indicated in patients whose lymphoma did not respond to Helicobacter pylori eradication therapy, or in gastric lymphoma not related to this microorganism. The subject of causative agents responsible for non-gastric MALT lymphomas is under active study and the identification of putative microorganisms will lead to improved treatment strategies for these unusual lymphomas, similar to the success in gastric lymphomas over the last decade.     

Treatment of primary cutaneous CD30+ anaplastic large-cell lymphoma with radiation therapy

PURPOSE: Primary cutaneous CD30+ anaplastic large-cell lymphoma (CALCL) is a relatively rare and indolent variant of cutaneous T-cell lymphoma (CTCL). This report examines the response of localized disease to radiation alone. METHODS: The Yale Cancer Center records were examined, and all patients with CTCL from January 1, 2001, to September 1, 2006, evaluated in the Department of Therapeutic Radiology were identified. Only those patients with localized or single CALCL lesions, no clinical evidence or history of lymphomatoid papulosis, no history of other CTCLs, no history of other skin disorders, lack of lymph node involvement, unambiguous pathology reports, and treatment with radiation alone were included. RESULTS: Eight patients were identified. Median age was 67 years, and gender was split evenly. Patients received radiation ranging from 34 to 44 Gy in 2-Gy fractions. Most patients (5 of 8) received 40 Gy, using 6 to 9 MeV electrons with 0.5 to 2 cm of bolus. All patients had a complete response. All patients were without evidence of disease at the most recent follow-up (median follow-up, 12 months). Radiation therapy was well tolerated, and the only recorded toxicity was Grade I to II dermatitis. CONCLUSIONS: Radiation therapy alone for localized CALCL is very well tolerated and clinical response is excellent. A dose of 40 Gy in 2-Gy fractions seems to be well tolerated and effective in inducing a complete response. Lower doses may be effective in achieving the same result, but data are not available. Longer follow-up is necessary before conclusions regarding durable disease-free survival can be made.     

Spleen tyrosine kinase as a molecular target for treatment of leukemias and lymphomas

Spleen tyrosine kinase (SYK) has emerged as a potential molecular target for the treatment of B-lineage leukemias and lymphomas. Here, we provide an overview of the current state of knowledge regarding the regulatory signaling function of SYK and its role in the pathogenesis of B-lineage lymphoid malignancies, available methods and drug candidates for targeting SYK, as well as compelling preclinical and clinical evidence regarding the clinical potential of inhibiting SYK. The further development of rationally designed SYK inhibitors may provide the foundation for therapeutic innovation against B-lineage leukemias and lymphomas.