Twenty-nine treatment courses for 24 patients diagnosed with MCC treated from 2018 to 2023 were identified that met study criteria, of which 19 (79.2%) were male and 10 (41.7%) were female. The patient cohort had a median age of 77 years, ranging from 51–93 years. Treatment details are provided in Table 1. The primary tumor site was located in the head and neck in 15 cases (51.7%). From this cohort, 13 received standard fractionation (2 Gy/day \(\times\) 25–30 fractions) with curative intent, 10 received hypofractionated radiotherapy (4 Gy/day \(\times\) 10 fractions) with curative intent, and 6 received single fraction (8 Gy) palliative radiation.
Table 1
Treatment parameters and patient characteristics for all treatment groups
| Stratification | |
| Palliative (N = 6) | Post-op and Def 2 Gy/fx (N = 13) | Post-op and Def 4 Gy/fx (N = 10) | Total (N = 29) | P-value |
Area, cm2 | | | | | 0.8701 |
N | 4 | 8 | 10 | 22 | |
Mean (SD) | 306.3 (464.09) | 94.8 (47.54) | 97.1 (30.60) | 134.3 (197.00) | |
Median | 102.5 | 76.6 | 92.1 | 92.1 | |
Range | 20.3, 1000.0 | 42.3, 183.8 | 52.0, 141.8 | 20.3, 1000.0 | |
RT Total Dose, Gy | | | | | < .0011 |
N | 6 | 13 | 10 | 29 | |
Mean (SD) | 8.0 (0.00) | 55.9 (4.27) | 36.4 (10.06) | 39.3 (19.53) | |
Median | 8.0 | 56.0 | 40.0 | 40.0 | |
Range | 8.0, 8.0 | 50.0, 60.0 | 16.0, 48.0 | 8.0, 60.0 | |
RT Total Fractions, fx | | | | | < .0011 |
N | 6 | 13 | 10 | 29 | |
Mean (SD) | 1.0 (0.00) | 28.4 (1.76) | 9.1 (2.51) | 16.1 (11.82) | |
Median | 1.0 | 28.0 | 10.0 | 10.0 | |
Range | 1.0, 1.0 | 25.0, 30.0 | 4.0, 12.0 | 1.0, 30.0 | |
RT Type, n (%) | | | | | < .0012 |
3D | 3 (50.0%) | 0 (0.0%) | 0 (0.0%) | 3 (10.3%) | |
Electrons + VMAT | 3 (50.0%) | 4 (30.8%) | 10 (100.0%) | 17 (58.6%) | |
Protons | 0 (0.0%) | 6 (46.2%) | 0 (0.0%) | 6 (20.7%) | |
VMAT | 0 (0.0%) | 3 (23.1%) | 0 (0.0%) | 3 (10.3%) | |
Location Category, n (%) | | | | | 0.6062 |
H&N | 3 (50.0%) | 8 (61.5%) | 4 (40.0%) | 15 (51.7%) | |
Lower Extremity | 0 (0.0%) | 1 (7.7%) | 2 (20.0%) | 3 (10.3%) | |
Trunk | 2 (33.3%) | 1 (7.7%) | 1 (10.0%) | 4 (13.8%) | |
Upper Extremity | 1 (16.7%) | 3 (23.1%) | 3 (30.0%) | 7 (24.1%) | |
Primary or recurrent, n (%) | | | | | 0.0232 |
Primary | 2 (33.3%) | 11 (84.6%) | 9 (90.0%) | 22 (75.9%) | |
Recurrent | 4 (66.7%) | 2 (15.4%) | 1 (10.0%) | 7 (24.1%) | |
Nodal Status, n (%) | | | | | < .0012 |
Negative | 0 (0.0%) | 2 (15.4%) | 6 (60.0%) | 8 (27.6%) | |
Positive | 1 (16.7%) | 11 (84.6%) | 1 (10.0%) | 13 (44.8%) | |
Unknown (Nx) | 5 (83.3%) | 0 (0.0%) | 3 (30.0%) | 8 (27.6%) | |
ECOG, n (%) | | | | | 0.2542 |
0 | 0 (0.0%) | 6 (46.2%) | 4 (40.0%) | 10 (34.5%) | |
1 | 3 (50.0%) | 6 (46.2%) | 2 (20.0%) | 11 (37.9%) | |
2 | 2 (33.3%) | 1 (7.7%) | 3 (30.0%) | 6 (20.7%) | |
3 | 1 (16.7%) | 0 (0.0%) | 1 (10.0%) | 2 (6.9%) | |
Acute Dermatits Grade, n (%) | | | | | 0.0062 |
0 | 5 (83.3%) | 0 (0.0%) | 3 (30.0%) | 8 (27.6%) | |
1 | 1 (16.7%) | 4 (30.8%) | 4 (40.0%) | 9 (31.0%) | |
2 | 0 (0.0%) | 5 (38.5%) | 3 (30.0%) | 8 (27.6%) | |
3 | 0 (0.0%) | 4 (30.8%) | 0 (0.0%) | 4 (13.8%) | |
Other Acute Toxicity G2+, n (%) | | | | | 0.1902 |
(G2) dysgeusia | 0 (0.0%) | 1 (7.7%) | 0 (0.0%) | 1 (3.4%) | |
(G2) fatigue | 0 (0.0%) | 0 (0.0%) | 1 (10.0%) | 1 (3.4%) | |
(G2) skin ulceration | 2 (33.3%) | 0 (0.0%) | 0 (0.0%) | 2 (6.9%) | |
Edema limbs (G3), (G2) esophagitis | 0 (0.0%) | 1 (7.7%) | 0 (0.0%) | 1 (3.4%) | |
G2 xerostomia, G2 dysgeusia | 0 (0.0%) | 0 (0.0%) | 1 (10.0%) | 1 (3.4%) | |
G3 skin ulceration, G2 pain | 1 (16.7%) | 0 (0.0%) | 0 (0.0%) | 1 (3.4%) | |
dental caries | 0 (0.0%) | 1 (7.7%) | 0 (0.0%) | 1 (3.4%) | |
fatigue (2) | 0 (0.0%) | 1 (7.7%) | 0 (0.0%) | 1 (3.4%) | |
n/a | 3 (50.0%) | 9 (69.2%) | 8 (80.0%) | 20 (69.0%) | |
Time duration of RT, days | | | | | < .0011 |
N | 6 | 13 | 9 | 28 | |
Mean (SD) | 0.0 (0.00) | 39.2 (3.37) | 41.4 (44.06) | 31.5 (29.37) | |
Median | 0.0 | 39.0 | 25.0 | 35.0 | |
Range | 0.0, 0.0 | 34.0, 45.0 | 14.0, 156.0 | 0.0, 156.0 | |
Time sim to end of RT, days | | | | | < .0011 |
N | 6 | 13 | 9 | 28 | |
Mean (SD) | 6.5 (4.59) | 55.5 (6.28) | 53.9 (44.31) | 44.5 (31.80) | |
Median | 7.0 | 54.0 | 39.0 | 50.0 | |
Range | 0.0, 13.0 | 46.0, 70.0 | 24.0, 167.0 | 0.0, 167.0 | |
Time surgery to sim, days | | | | | 0.0291 |
N | 3 | 11 | 10 | 24 | |
Mean (SD) | 662.3 (383.50) | 128.0 (234.51) | 30.6 (6.72) | 154.2 (278.15) | |
Median | 662.0 | 32.0 | 29.5 | 32.5 | |
Range | 279.0, 1046.0 | 18.0, 811.0 | 21.0, 41.0 | 18.0, 1046.0 | |
1Kruskal-Wallis p-value; 2Chi-Square p-value; |
Table 2
Treatment parameters and patient characteristics for adjuvant standard and hypofractionated groups
| Stratification | |
| Post-op 2 Gy/fx (N = 8) | Post-op 4 Gy/fx (N = 8) | Total (N = 16) | P-value |
Area, cm2 | | | | 0.3321 |
N | 6 | 8 | 14 | |
Mean (SD) | 101.4 (50.24) | 107.5 (24.26) | 104.9 (36.02) | |
Median | 76.6 | 98.1 | 92.1 | |
Range | 64.0, 183.8 | 81.3, 141.8 | 64.0, 183.8 | |
RT Total Dose, Gy | | | | < .0011 |
N | 8 | 8 | 16 | |
Mean (SD) | 53.6 (3.87) | 38.0 (9.32) | 45.8 (10.60) | |
Median | 53.2 | 40.0 | 49.0 | |
Range | 50.0, 60.0 | 16.0, 48.0 | 16.0, 60.0 | |
RT Total Fractions, fx | | | | < .0011 |
N | 8 | 8 | 16 | |
Mean (SD) | 27.5 (1.69) | 9.5 (2.33) | 18.5 (9.50) | |
Median | 28.0 | 10.0 | 18.5 | |
Range | 25.0, 30.0 | 4.0, 12.0 | 4.0, 30.0 | |
RT Type, n (%) | | | | 0.1212 |
Electrons + VMAT | 4 (50.0%) | 8 (100.0%) | 12 (75.0%) | |
Protons | 3 (37.5%) | 0 (0.0%) | 3 (18.8%) | |
VMAT | 1 (12.5%) | 0 (0.0%) | 1 (6.3%) | |
Location Category, n (%) | | | | 0.4542 |
H&N | 5 (62.5%) | 2 (25.0%) | 7 (43.8%) | |
Lower Extremity | 1 (12.5%) | 2 (25.0%) | 3 (18.8%) | |
Trunk | 1 (12.5%) | 1 (12.5%) | 2 (12.5%) | |
Upper Extremity | 1 (12.5%) | 3 (37.5%) | 4 (25.0%) | |
Nodal Status, n (%) | | | | 0.0372 |
Negative | 2 (25.0%) | 6 (75.0%) | 8 (50.0%) | |
Positive | 6 (75.0%) | 1 (12.5%) | 7 (43.8%) | |
Unknown (Nx) | 0 (0.0%) | 1 (12.5%) | 1 (6.3%) | |
ECOG, n (%) | | | | 0.7662 |
0 | 4 (50.0%) | 4 (50.0%) | 8 (50.0%) | |
1 | 3 (37.5%) | 2 (25.0%) | 5 (31.3%) | |
2 | 1 (12.5%) | 2 (25.0%) | 3 (18.8%) | |
Acute Dermatits Grade, n (%) | | | | 0.3192 |
0 | 0 (0.0%) | 2 (25.0%) | 2 (12.5%) | |
1 | 4 (50.0%) | 3 (37.5%) | 7 (43.8%) | |
2 | 4 (50.0%) | 3 (37.5%) | 7 (43.8%) | |
Other Acute Toxicity G2+, n (%) | | | | 0.3682 |
G2 xerostomia, G2 dysgeusia | 0 (0.0%) | 1 (12.5%) | 1 (6.3%) | |
dental caries | 1 (12.5%) | 0 (0.0%) | 1 (6.3%) | |
n/a | 7 (87.5%) | 7 (87.5%) | 14 (87.5%) | |
Time duration of RT, days | | | | 0.0441 |
N | 8 | 8 | 16 | |
Mean (SD) | 38.8 (4.10) | 27.9 (9.49) | 33.3 (9.02) | |
Median | 38.5 | 24.5 | 35.0 | |
Range | 34.0, 45.0 | 21.0, 43.0 | 21.0, 45.0 | |
Time sim to end of RT, days | | | | 0.0241 |
N | 8 | 8 | 16 | |
Mean (SD) | 56.9 (7.14) | 39.9 (13.20) | 48.4 (13.50) | |
Median | 55.0 | 34.0 | 52.5 | |
Range | 48.0, 70.0 | 28.0, 64.0 | 28.0, 70.0 | |
Time surgery to sim, days | | | | 0.7131 |
N | 8 | 8 | 16 | |
Mean (SD) | 32.1 (16.88) | 29.6 (6.37) | 30.9 (12.39) | |
Median | 29.0 | 29.5 | 29.0 | |
Range | 18.0, 70.0 | 21.0, 39.0 | 18.0, 70.0 | |
1Kruskal-Wallis p-value; 2Chi-Square p-value |
A subset of patients treated adjuvantly with curative intent included 8 standard fractionation and 8 hypofractionated radiotherapy patients. Median treatment time was 39 days versus 25 days for standard fractionation versus hypofractionated radiotherapy patients, respectively (Table 1).
At a median 10-month follow up, no locoregional failures occurred in the standard fractionation group, and 1 regional failure occurred in an untreated nodal basin in the hypofractionated radiotherapy group. For these patients, initial treatment consisted of wide local excision and SLNB or neck dissection followed by adjuvant RT. No patients had a history of prior radiation therapy to sites treated, while 3 had a history of prior systemic therapy.
At a median follow-up time of 12 months, the survival probability for patients who received adjuvant RT in standard fractionation was 100% and 83.3% (95% CI, 53.5%-100.0%) for individuals in the adjuvant hypofractionated group (Fig. 1). For patients treated definitively and post-operatively, the 12-month survival probability at standard fractionation was 90.9% (95% CI, 73.9%-100.0) and 71.4% (95% CI, 38.0%-100.0%) hypofractionated; for palliative radiation therapy, a 12-month survival probability of 41.7% (95% CI, 0.0%-100.0%) was observed (Fig. 2). There were 5 patient deaths noted during the follow-up period. No statistically significant differences in locoregional and distant failure or overall survival were observed between the patient groups.
No RTOG grade 4 + acute toxicity was reported. Acute dermatitis toxicity was minimal with hypofractionated treatment, with 0% of hypofractionated patients experiencing grade 3 + toxicity compared to 30.8% (4 patients) of patients receiving standard fractionation (Table 1).