Palliative Therapy for Recalcitrant Cutaneous T-Cell Lymphoma of the Hands and Feet With Low-Dose, High Dose-Rate Brachytherapy

Importance  Cutaneous T-cell lymphoma (CTCL) of the hands and feet can be challenging to treat and cause significant disability for patients. Although CTCL is a highly radiosensitive tumor, the complex topography of acral surfaces presents challenges to achieving homogeneous superficial dosing of traditional electron beam therapy. In addition, traditional dosing may result in substantial acute cutaneous toxic effects. Recent reports demonstrate that low-dose palliative radiotherapy may be as effective as traditional regimens in CTCL. High dose-rate (HDR) brachytherapy allows for control of the depth of radiation penetration over complex curved surfaces. This study investigated the role of low-dose HDR brachytherapy for acral CTCL lesions.

Observations  Six patients with a total of 8 acral CTCL lesions received low-dose HDR brachytherapy during a 3-year period. Rapid improvement and clinical clearance were observed in all treated lesions with minimal to no acute cutaneous toxic effects. During a mean follow-up period of 15.8 months, 1 lesion recurred locally; the remaining 7 lesions had sustained clinical remission. No long-term sequelae were observed.

Conclusions and Relevance  This case series demonstrates that low-dose HDR brachytherapy provides excellent palliation for local control of acral CTCL lesions, offering homogeneous, controlled dosing for complex topographic sites with minimal to no cutaneous toxic effects.

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin lymphomas characterized by malignant skin-homing, mature-memory T lymphocytes with primary cutaneous involvement. The most common subtypes of CTCL are mycosis fungoides (MF) and Sézary syndrome.^1,2 Therapeutic options for CTCL encompass a broad spectrum of regimens, including skin-directed therapies for early-stage disease and systemic therapies for advanced-stage disease. The vast majority of patients with CTCL have early-stage disease presenting with heterogeneous cutaneous patches and plaques but without blood, nodal, or visceral involvement. Most patients receive skin-directed therapies with or without systemic therapy.³ Cutaneous T-cell lymphoma remains an incurable disease, and response to therapies is highly variable. Current treatment strategies aim to provide palliation of symptoms and, in some cases, can provide prolonged remission.

Radiotherapy has been shown^4,5 to be a highly effective modality for CTCL, both in the treatment of localized (isolated or oligolesional) disease and in more extensive skin disease, in which total skin electron-beam therapy (EBT) is often used. Common radiotherapy dosing regimens in CTCL range from 2000 to 4000 cGy administered in multiple fractions. In addition, studies report^4,5 excellent results with low-dose radiotherapy in CTCL, with reduced acute cutaneous toxic effects.

Brachytherapy, the administration of radiation through flexible catheters that can be secured within computer-optimized, fully customized surface molds, allows for control of the depth of radiation penetration over complex curved surfaces.⁶ The term brachytherapy is derived from the Greek word βραχυς (brachys) or “short” and refers to short-range radiotherapy directly inserted into a target lesion or applied directly onto the lesion surface. The most common brachytherapy systems use high dose-rate (HDR) iridium Ir 192.⁷ Brachytherapy has been used^7-10 successfully in the treatment of other tumors of the skin, including squamous cell and basal cell carcinomas, Merkel cell carcinoma, and complex facial lesions of CTCL.

In this case series, we describe 6 patients with 8 CTCL lesions involving the hands and/or feet that were considered recalcitrant to prior standard therapies. Clinical and histopathologic data were obtained from a medical record review of cases that were treated during a 3-year period (January 1, 2010, through December 31, 2012) in a single, multidisciplinary cutaneous oncology clinic. To our knowledge, we present the first series of patients who underwent low-dose HDR brachytherapy for acral CTCL lesions and describe our results, including response rates, toxic effects, and lesion recurrence–free survival. Each patient was seen in formal consultation, and written informed consent was obtained for treatment with radiation. Institutional review board approval was not required given this was a retrospective review of previously treated individuals.

Six patients with a total of 8 distinct patches, plaques, or tumors of CTCL displaying complex topography on curved and convex surfaces of the hands or feet were further evaluated for treatment with palliative EBT vs HDR surface-mold brachytherapy. Collective prior therapies were variable and included ultrapotent topical corticosteroids; topical mechlorethamine hydrochloride, 0.02%; ointment (nitrogen mustard); psoralen-UV-A phototherapy; narrowband UV-B phototherapy; systemic bexarotene; gemcitabine hydrochloride; vorinostat; methotrexate sodium; and pegylated doxorubicin hydrochloride (Table). Each lesion was determined to be fixed and recalcitrant to prior therapies. Patients reported pruritus and pain associated with their acral CTCL lesions and therefore desired alternative therapy. None of the patients had received prior radiotherapy within the intended treatment field.

The patient’s lesion was mapped as to the physical location of the tumor. The mapped lesional area then was marked with radiopaque copper wire, and a 2-cm margin was measured around this area that was then also marked using copper wire. This entire area was covered with a custom surface mold consisting of flexible catheters (Freiburg Flap; Elekta) with or without a thermoplastic base. Radiopaque dummy markers were placed in the channels of the catheters. The topography of the lesional area was also mapped out on transparency film, including landmarks such as nevi and nails, as well as bony landmarks. The patient then underwent a computed tomographic (CT) scan of the area (Figure 1). These data were entered into the brachytherapy treatment planning system, and a highly conformal, dose-optimized treatment plan was created. For patch-stage lesions, the 100% dose was set to a 3-mm tissue depth. For plaque- and tumor-stage lesions, the 100% dose was set to the base of the lesion as seen on magnified CT images of the area. Because the fingers and hands are relatively thin, significant dose painting was also used so as to provide dose sparing to the contralateral side of the hand or foot. The treatment plan for each lesion was 800 cGy administered in 2 fractions of 400 cGy each. These plans were approved by both the physician (P.M.D.) and medical physicist (D.A.O. and R.A.C.) before therapy. After appropriate safety checks, the patient was brought into the treatment room. The applicator was placed over the treatment region and affixed in place with tape or bandages. The flexible catheter channels were connected to the HDR afterloader, and treatment was delivered under the direct supervision of both the medical physicist and physician. The second treatment was delivered on a subsequent day, often with a single rest day between treatments. The treated area was managed with emollients.

All patients were evaluated for potential radiation toxic effects within 2 weeks of follow-up time and then returned to normal surveillance by the cutaneous oncology team and the referring dermatologist. Clinical photography was used at each stage to monitor response and assess for possible toxic effects. Most often, mild erythema was noted after the second treatment. One patient developed a small bulla within the radiation field that resolved with emollient application alone without long-term sequelae. Two lesions resolved with mild postinflammatory hyperpigmentation.

All 8 lesions demonstrated sustained reduction or clearance of erythema, scale, and induration (Figure 2). Pretreatment and posttreatment findings are delineated in the Table.

Cutaneous T-cell lymphoma is a highly radiosensitive tumor.^4,5,10 Traditionally, EBT has been used with good success in CTCL.^4,5 One limitation of EBT, however, is that it works most effectively on flat surfaces. In brachytherapy, flexible catheters and custom-made surface molds are conducive to providing homogeneous and precise dosing over areas with complex topography, such as the hands and feet.

Ideal dosing of traditional radiotherapy for cutaneous lymphomas has been investigated extensively.^4,5 Traditional doses range from 2000 to 4000 cGy compared with the 800-cGy dosing given in 2 fractions of 400 cGy administered in the present study. Lee et al¹¹ reported a single case of the use of 3-dimensional conformal radiotherapy, a technique using a photon beam that penetrates to a greater depth than EBT, for hyperkeratotic plantar MF, using 4000 cGy in normal fractionation with complete lesion clearance. Chan et al¹² reviewed 10 cases of unilesional or oligolesional CTCL and demonstrated that, in all 10 patients, the use of 3000 to 3600 cGy showed a disease-free survival of 70% at a mean follow-up time of 40 months; however, significant toxic effects were noted.

Two other studies^4,5 highlight the role of low-dose radiotherapy for palliation of recalcitrant CTCL lesions. A case series⁵ of 58 patients from Northwestern University demonstrated excellent effect, with a complete response rate of 95% at a mean follow-up time of 41 months, with single-fraction radiotherapy of 700 to 800 cGy, using either electrons or photons. A Dutch case series⁴ of 18 patients with either cutaneous B-cell lymphoma or CTCL treated with electrons at the 800-cGy level reported a complete response rate of 92% without notable toxic effects.

To our knowledge, only a single report focusing on brachytherapy for CTCL currently exists. In that series, DeSimone et al¹⁰ described successful treatment in 10 patients with facial CTCL lesions with lose-dose, 800-cGy, surface-applicator brachytherapy administered in 2 fractions. Brachytherapy was used in this series because of its ability to provide precise dosing over complex topographic areas of the face.

Given its effectiveness over sites with complex topography, brachytherapy offers a unique and highly efficacious treatment option for recalcitrant and fixed lesions of CTCL on the hands and feet. Ultrapotent topical corticosteroids, topical nitrogen mustard, and topical bexarotene gel are the most frequently used therapies for limited CTCL but often are ineffective at penetrating the thick stratum corneum of acral surfaces. Patients also frequently find that keeping topical preparations in place on acral surfaces is challenging owing to handwashing, manual tasks, and the mechanical friction of walking. Treatment with UV phototherapy has been used but can be cumbersome, requiring multiple visits per week, often with costly insurance co-payments. Acral CTCL lesions, similar to other chronic dermatoses of the hands and feet, can be debilitating. Patients may experience pain with walking or with the use of their hands, and the disease can significantly affect quality of life.¹³ Although, to our knowledge, no study investigating quality of life or disability measures specifically in acral CTCL has been reported, extensive data exist on other hand and foot dermatoses, such as palmoplantar psoriasis and contact hand dermatitis.¹⁴ The patients with palmar or plantar involvement described in the present series reported associated pain and functional disability. Lesions on the dorsal hands may also be of cosmetic concern for patients. These issues underscore the need for effective treatment options for acral CTCL, ideally with minimal adverse effects.

Our findings are limited by the small number of patients and the retrospective nature of this case series. In addition, lack of pretreatment and posttreatment disability and/or quality-of-life indices is a limiting factor; such data would be important in future prospective studies. Although long-term information on lesion recurrence–free survival is lacking, our patients were monitored for a mean of 15.8 months (range, 10.3-23.3 months) of follow-up, with sustained clearance of disease within the treatment field noted in 7 of 8 lesions. One palmar CTCL lesion recurred at 12 months. The recurrence was later treated with full-dose (2000 cGy) EBT, which also failed to provide lesion remission.

To our knowledge, this is the first case series reported of low-dose HDR brachytherapy for the treatment of acral lesions of CTCL. Computer-optimized, surface-applicator brachytherapy is unique in its ability to deliver homogeneous doses over complex and curved surfaces, such as the hands and feet. Additional beneficial characteristics of this delivery method and dosing strategy are that the entire treatment, including consultation, can be completed in 2 to 3 outpatient visits; the treatment-associated adverse effects are minimal to none and typically include only mild, transient erythema and/or postinflammatory hyperpigmentation, and the response is rapid and sustained in most patients. This study highlights the potential use of low-dose HDR brachytherapy for treatment of refractory acral CTCL lesions. Future systematic investigation is warranted to further define the role of this therapy for recalcitrant acral CTCL.

Accepted for Publication: July 17, 2015.

Corresponding Author: Allison L. Goddard, MD, Department of Dermatology, Brigham and Women’s Hospital, 221 Longwood Ave, Boston, MA 02115 (agoddard@partners.org).

Published Online: September 23, 2015. doi:10.1001/jamadermatol.2015.3028.

Author Contributions: Drs Goddard and Devlin had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Goddard, LeBoeuf, O’Farrell, Cormack, Kupper, Devlin.

Acquisition, analysis, or interpretation of data: Goddard, Vleugels, Hansen, Kupper, Devlin.

Drafting of the manuscript: Goddard, Vleugels, Hansen, Devlin.

Critical revision of the manuscript for important intellectual content: Goddard, Vleugels, LeBoeuf, O’Farrell, Cormack, Kupper, Devlin.

Administrative, technical, or material support: Cormack, Hansen, Kupper, Devlin.

Study supervision: Kupper, Devlin.

Conflict of Interest Disclosures: None reported.