Number of patients Control primary without resection % (no) Control with adjuvant rdt primary (no)/vs. no radiotherapy 251 9 41 66 26 43 36%(30) 100%(9) 75%(43) 90%(32)/92% 100%(9)/(0) 91%(11) 44%(26)12%/(34) 93%(27)/0 CLINICS 2011;66(10):1817-1823 Reference (29) (43) (33) (47) (50) (51) Epidemiology and treatment of Merkel cell carcinoma Duprat JP et al. Table 3 - Radiotherapy: protocols and results. Author Allen Warner Boyle Gillenwater ## Mortier Veness ## Radiotherapy to primary and lymph node basin - head & neck. and angiolymphatic invasion.42 Comparison is very difficult because each study’s design and characteristics are different; some compare positive margins, some treat exclusively with radiotherapy, and some add the evaluation of the draining lymph node basin. Various protocols reported in reviews are applied to a large number of patients. Table 3 is an effort to compile these trends. In a study of 17 patients, Warner et al. did not observe a significant impact of a positive sentinel node on the prediction of regional recurrence. However, they did find that radio- therapy had an impact on local and regional control.43 Adjuvant radiotherapy is often suggested for large tumors and for cases in which regional disease is pre- sent.30,32,33,35,36,44,45 In a meta-analysis by Lewis et al.46 who compared surgery alone to surgery plus adjuvant radiation, the authors showed a reduction in local and regional recurrence in the combined therapy group. That study encompassed 1,254 patients, and if local radiotherapy was performed, a decrease in local (88 vs. 61%, respectively; p,0.001) and regional (77 vs. 44%, respectively; p,0.001) recurrence was observed, as was an increase in survival (HR 0.63, p = 0.02). It is very important to note that the group with primary tumors #2 cm benefitted the most from radiotherapy. Gillenwater et al. found a statistically sig- nificant difference in local recurrence in the head and neck region with radiotherapy (12% with vs. 44% without; p,0.01) and regional therapy (27 vs. 85%; p,0.01) but did not find a difference in overall survival.47 In a retrospective study, Meeuwissen et al. showed that all 38 patients treated with surgery alone relapsed, whereas only 10 in 34 patients treated with surgery plus radiotherapy relapsed.48 In that study, the patients treated with surgery plus radiotherapy were treated at a referred radiotherapy facility, therefore attending mostly the recurrences. It was not clear whether the surgeons who referred patients had the skills to treat the disease.3 A primary lesion that is not resectable can be treated with radiotherapy as an isolated treatment. The usual dose is 45- 70 Gy.49 Mortier et al. treated nine cases of primary lesions that could not be treated surgically. After a median follow- up of three years, there was no recurrence.50 In a larger series of 43 patients, Veness et al. treated patients who were non-operable because of clinical or local reasons; 77% of patients had nodal metastasis. In this particularly bad prognosis group, they had only 60% relapse, which commonly occurred out-of-field. The in-field control was 75%. The overall survival after two and five years was 58 and 37%, respectively.51 The Peter MacCallum Cancer Centre in Australia col- lected robust data on 176 patients. In that cohort, 94% of patients received radiotherapy. In the multivariate analysis, 1820 the dose of radiotherapy was significantly different for locoregional control. They divided their cohort into three groups: a) no radiotherapy, b) radiotherapy ,45 Gy and c) radiotherapy $45 Gy; Comparing the control achieved in the groups, respectively was 51 vs. 71 vs. 80 months p = 0.044 and overall survival, p = 0.005). However, only 11 patients received no radiotherapy.52 Regional Treatment In the absence of clinically positive lymph nodes, most centers will perform a sentinel lymph node biopsy (SLNB) to obtain accurate nodal staging. As stated previously, this is an important prognostic factor.3,6,43,53 The SLNB techni- que is conducted in the same manner as in melanoma patients. Immunohistochemistry for CK-20 is a valuable tool in identifying micrometastases. Allen et al. found 23% positivity of lymph nodes in patients who underwent pathologic staging of a clinically negative nodal basin (17 patients underwent elective lymph node dissection and 54 had sentinel lymph node biopsy). Paradoxically, if the primary lesion was less than 2 cm, the rate of positive nodes was 24%, and if the tumor was $2 cm, the rate of positive nodes was 20% (p = 0.71).29 Gupta et al. reviewed 122 patients with MCC who underwent SLNB and observed that 60% of those patients with a positive sentinel node recurred in three years (compared to a recurrence rate of 20% in those with negative SLNB).6 Warner et al. analyzed 22 papers involving the use of SLNB for MCC and found that among 241 patients, 31% had metastases. This group experienced recurrence in 19% of cases. In the negative sentinel node group, the recurrence was 7.5%.42 A positive node, either clinically or pathologically detected, requires the complete removal of all drainage basin lymph nodes. Patients who underwent a lymphadenectomy had longer disease-free survival (28.5 vs. 11.8 months, p = 0.04).41 Follow-up in small groups of patients reinforces this observation.36,38,53,54 Mehrany et al. performed a meta- analysis and showed that 15 of 20 patients with positive sentinel lymph nodes subsequently underwent a lympha- denectomy and had no regional recurrence after nine months. In contrast, three of four patients with positive nodes who did not subsequently undergo lymphadenect- omy had regional recurrences, with one patient absent from follow-up.53 Gupta et al. showed that a sentinel lymph node biopsy is not only important as a prognostic procedure but can also guide therapy. Data from Lemos et al. have shown that there is also a survival benefit in performing SLNB, as already shown in the stage chapter.12 There are some questions about false-negative sentinel nodes in MCC because compared to melanoma patients, the mean age is older, and there is a higher incidence in the