International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationThe Role of Radiotherapy Alone in Patients With Merkel Cell Carcinoma: Reporting the Australian Experience of 43 Patients
Introduction
Merkel cell carcinoma (MCC) is an uncommon and aggressive primary cutaneous neuroendocrine (small-cell) carcinoma originating from the basal epidermis and was first reported by Toker (1) in 1972. It frequently develops on the sun-exposed skin (head and neck/extremities) in patients who are older, often have immunosuppression, and are white (2). Unlike other cutaneous malignancies that are cured by local treatment, many patients with MCC have a poor prognosis characterized by locoregional and distant relapse despite multimodality treatment 3, 4. There is evidence that surgery to achieve negative margins (but respecting form and function), in combination with adjuvant wide-field radiotherapy (RTx), significantly improves locoregional control and survival compared with surgery alone 3, 4, 5, 6.
Despite this, patients may be technically or medically unfit for surgery or may refuse an operation. However, as a consequence of MCC's unique clinical radioresponsiveness, patients with macroscopic primary and/or nodal disease are still treatable with RTx alone with doses in the range of 45 to 60 Gy. Toxicity from such treatment, even in this patient population, is usually tolerable because of the often unilateral and relatively superficial techniques used (e.g., en bloc electron field). However, despite achieving in-field disease control, many patients will ultimately die of distant relapse or unrelated events. Achieving locoregional control and preventing symptoms such as tumor bleeding and discharge may improve the quality of life for both the patient and caregiver. A minority of patients will even be cured, and it should therefore not be assumed that patients treated with RTx alone are incurable and should only be offered palliative care.
In the largest series of patients treated with RTx alone, a French group reported the results of 9 patients with Stage I inoperable MCC treated by RTx alone (median dose, 60 Gy) (7). In this small study no patient had a relapse, with a median follow-up of 3 years. In our study we document 43 patients treated at the Departments of Radiation Oncology, Westmead Hospital, Sydney, and Royal Brisbane/Mater Hospitals, Brisbane, Australia, with RTx alone. Most (33 of 43) had clinically involved nodes at the time of treatment. The aims of this study were to document the clinical radioresponsiveness of patients with inoperable MCC treated with RTx and to review the patterns of relapse and outcome after treatment.
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Methods and Materials
Between 1993 and 2007, patients diagnosed with MCC and treated with RTx alone were identified from departmental computer databases. Ethics committee approval was obtained from both centers. All patients had a histologic diagnosis consistent with MCC (cytokeratin 20 positive, positive neuroendocrine markers, negative melanoma and lymphoma markers) without evidence of distant metastases. Pretreatment investigations were variable but included computed tomography (CT) scans of involved regions with
Patient characteristics
Of the 43 patients, 21 were treated at Westmead Hospital and 22 were treated at the Royal Brisbane/Mater Hospitals. The median age at diagnosis was 79 years (range, 48–91 years) in 19 women (44%) and 24 men (56%) (Table 1). All patients were white, and 5 (12%) had immunosuppression (3 transplant recipients and 2 with chronic lymphocytic leukemia). A majority (24 of 43 [56%]) underwent irradiation at initial diagnosis, with the remainder (19 of 43 [44%]) treated in the relapse setting, most
Discussion
The management of a patient diagnosed with MCC remains controversial, with randomized data lacking. Proponents of surgery (at least in the node-negative setting) suggest that patients are best served by an operation with or without sentinel node biopsy with a limited role for adjuvant treatment (9). Others support the important role of RTx based on the emerging evidence base 5, 10. Even relatively small MCCs exhibit a propensity for locoregional relapse and distant failure 11, 12. The addition
Conclusion
There remain many unanswered questions in managing patients with MCC. Most patients will present with locoregional disease, and the addition of RTx to any locoregional treatment is likely to benefit most. In patients considered unsuitable to undergo surgery and adjuvant RTx, we recommend doses of approximately 50 to 55 Gy in 20 to 25 daily fractions with wide fields encompassing macroscopic disease, in-transit tissues, and regional nodes, which offers a high likelihood of achieving locoregional
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Conflict of interest: none.