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DOI 10.1245/s10434-014-3757-8
ABSTRACT
Background. Achieving clear surgical margins in Merkel
cell carcinoma (MCC) can be difficult due to tumor location or patient comorbidity. Clinical impression suggests
that radiation treatment achieves good control of macroscopic disease.
Methods. A retrospective chart review was undertaken of
all patients with pathological evidence of MCC and treated
with curative intent at the BC Cancer Agency between
1979 and 2007. This is a report on the outcomes of those
with gross disease treated with radiotherapy, without radical surgery.
Results. Fifty-seven patients received definitive radiotherapy to the primary and/or nodal disease. Median age
was 75 years and median follow-up was 34 months
(84.5 months for those alive at last follow-up). American
Joint Committee on Cancer (AJCC) stage distribution was
23, 19, and 58 % for stages I, II, and III, respectively.
Tumor control at sites treated for macroscopic disease was
88 % at 12 months and 82 % at 2 years, and 5-year local
relapse-free survival (RFS) was 90 %. Five-year RFS,
cancer-specific survival (CSS), and overall survival were
57, 68, and 39 %, respectively. On univariate and multivariate analyses, only male sex was associated with a worse
RFS, and a radiotherapy dose [50 Gy was associated with
a better CSS.
Limitations. The retrospective nature of the study and
small sample size limit the strength of the conclusions.
Conclusions. Radical radiotherapy is effective in the
curative treatment of MCC, especially in patients who
3402
C. Harrington, W. Kwan
TABLE 1 Baseline characteristics
N
57
75 (3694)
Male/female (%)
54/46
15 (4104)
T stage [n (%)]
T0
9 (16)
T1 (tumor B 2 cm)
19 (33)
14 (25)
15 (26)
13 (23)
II (T2/3N0M0)
III (any T, N1 M0)
11 (19)
33 (58)
33 (58)
Upper limb
6 (11)
10 (17)
No primary
9 (16)
Comorbidity [n (%)]
Previous non-melanoma skin cancer
14 (25)
Previous melanoma
3 (5.3)
15 (26)
4 (7)
Cardiovascular disease
11 (19)
Neurodegenerative disease
3 (5.3)
Renal transplant
2 (3.5)
3403
TABLE 2 Comparison of patients treated with radical RT versus
radical surgery
Survival Function
Censored
1.0
0.8
0.6
0.4
0.2
0.0
0
50
100
150
200
250
Radical RT
Radical surgery
57
122
Male (%)
65
49
75
74
Stage 1 (%)
23
59
Stage 2 (%)
19
33.6
Stage 3 (%)
58
7.4
11
21
8.2
33
57
62
68
77
39
49
Time (months)
RT radiation treatment
FIG. 1 Local recurrence-free survival after radical irradiation of the
primary tumor
1.0
Proportion Surviving
0.8
0.6
0.4
0.2
0.0
0
50
100
150
200
250
Time (months)
Cancer Control
Tumor control at sites treated for macroscopic disease
was 88 % at 12 months and 82 % at 2 years. Four patients
developed local recurrence as first site of failure after
radical RT to the primary tumor (11 %). Local RFS was
90 % at 5 years (Fig. 1).
After RT to grossly involved nodes, 7 of the 33 patients
(21 %) recurred first at nodal sites. Three recurred at nodal
sites outside the original field and four patients (12 %)
relapsed within (two) or at the edge (two) of the irradiated
field. Five-year nodal RFS amongst those treated with
radical nodal RT was 75 %.
Treatment to EQD2 of C50 Gy was associated with
improved RFS (p = 0.01) and cancer-specific survival
3404
C. Harrington, W. Kwan
TABLE 3 Published reports of radiotherapy to macroscopic merkel cell carcinoma with outcome data specific to these patients
Author
Year
Dose (Gy)
Stage
12
Survival (%)b
Elliot12
1981
38
NA
NA
100
Pacella et al.13
1988
19
3650
18
95
2-year OS 63
Pilotti et al.14
1988
NA
NA
NA
100
100
Ashby et al.15
1989
3945
100
100
Morrison et al.16
1990
NA
100
Hasle17
1991
40
100
Meeuwissen et al.8
Suntharalingam et al.18
1995
1995
8
2
4560
7077.5
1
2
7
0
50
50
25
50
Poulsen et al.19
2003
15
50 median
NA
1415
71
3-year OS 45
Mortier et al.20
2003
60
100
67
2009
50 median
87.5
12.5
Fang et al.22
2010
NA
5-year NRFS 78
2-year OS 63
Foote et al.23
2010
13
NA
13
NA
5-year OS 51
Pape et al.
2010
25
65 median
25
92
60
Veness et al.25
2010
43
51 median
10
33
75
5-year OS 37
Fields et al.26
2011
22
C50
21
NA
NA
Ghadjar et al.7
2011
13
60 median
5-year LRFS 82
NA
Kukko et al.27
2011
NA
NA
NA
67
NA
100
NA
NA
24
Lok et al.28
2011
10
6070
29
2012
60 median
67
Sundaresan et al.30
2012
16
50 median
NA
1012
85
NA
Santamaria-Barria et al.31
2013
12
NA
83
NA
Mendenhall et al.
NA data not available, OS overall survival, NRFS nodal relapse-free survival, LRFS local relapse-free survival
a
Percent without recurrence at treated site at study end, unless otherwise stated
stage 3 disease) [Table 2]. Yet, the local and nodal relapse
rates are comparable (11 vs. 8.2 % local relapse; 21 vs.
33 % nodal relapse). The 5-year OS and CSS of the
patients who had radical radiation are lower, consistent
with their more advanced disease at presentation.
DISCUSSION
The current series is one of the largest examining the role
of radical RT in MCC. In keeping with other series,10,11 these
patients are elderly and had a relatively high prevalence of
comorbidities, including immunosuppressive states and
previous treatments for other cancers. We found that control
at sites treated with radical radiation without aggressive
surgery was high for both primary and nodal disease, in
keeping with previous reports in the literature (Table 3).1231
With local relapse rate only at 11 % at 5 years, radical
RT to the primary tumor can be considered an alternative
to surgery, especially when the required operation would
be extensive, or likely to have a poor functional or cosmetic result.
14.
15.
16.
CONCLUSION
The current series adds to the literature supporting
radiotherapy to gross residual disease as an option for
management of local and regional disease in MCC, especially in situations where extensive surgery is not favored.
A radiotherapy dose of 50 Gy (in 2.5 Gy fractions) or more
is recommended. Field edge recurrences suggest that irradiating the whole nodal region should be considered when
treating involved nodes.
CONFLICTS OF INTEREST
3405
None declared.
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