Clinical Investigation
The Role of Radiotherapy Alone in Patients With Merkel Cell Carcinoma: Reporting the Australian Experience of 43 Patients

https://doi.org/10.1016/j.ijrobp.2009.08.011Get rights and content

Purpose

To review the role of radiotherapy (RTx) alone in patients with Merkel cell carcinoma (MCC).

Methods and Materials

The records of 43 patients with MCC treated with RTx alone between 1993 and 2007 at the Westmead and Royal Brisbane/Mater Hospitals, Australia, were reviewed. Multivariate analysis was performed by use of Cox regression analysis.

Results

The median age was 79 years (range, 48–91 years) in 19 women (44%) and 24 men (56%). All patients were white, and 5 (12%) had immunosuppression. A majority (56%) underwent irradiation at initial diagnosis, with the remainder (44%) treated in the relapse setting. The median duration of follow-up was 39 months. The head and neck comprised the most frequently treated site (47%). The median maximum lesion size was 30 mm (range, 5–130 mm). Relapse developed in 60% of patients, with most being out-of-field relapses. The in-field control rate was 75%. Most out-of-field relapses were to visceral organs. Relapse developed outside the irradiated field in 53% of patients. On multivariate analysis, only nodal status (negative nodes vs. nodes present) was significantly associated with relapse-free survival, with p = 0.005 (hazard ratio, 0.25; 95% confidence interval, 0.96–0.663). Overall survival at 2 and 5 years was 58% and 37%, respectively.

Conclusions

Patients with MCC treated with RTx have a high likelihood of obtaining in-field control. Doses of 50 to 55 Gy in 20 to 25 fractions are recommended. A minority of patients are cured, with many dying of systemic relapse. Lower dose fractionation schedules (e.g., 25 Gy in 5 fractions) may be considered in patients with a very poor performance status.

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.

Section snippets

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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