First recurrence characteristics | All N=71 (%) | No adjuvant RT at first recurrence N=47 (%) | Adjuvant RT at first recurrence N=24 (%) | P value* |
Median time to first recurrence—months (range) | 7 (1–44) | 7 (1–44) | 7 (4–19) | 0.63 |
ECOG—no. (%) | 0.77 | |||
0 | 58 (82) | 38 (81) | 20 (83) | |
1 | 12 (17) | 8 (17) | 4 (17) | |
2 | 1 (1) | 1 (2) | 0 | |
Stage (AJCC eighth edition)—no. (%) | 0.38 | |||
IIIB | 9 (13) | 6 (13) | 3 (13) | |
IIIC | 55 (77) | 38 (81) | 17 (71) | |
IIID | 7 (10) | 3 (6) | 4 (17) | |
Recurrence detected by—no. (%) | 0.41 | |||
Symptoms | 7 (10) | 5 (11) | 2 (8) | |
Clinical examination | 39 (55) | 28 (60) | 11 (46) | |
Imaging | 25 (35) | 14 (30) | 11 (46) | |
Recurrence and adjuvant IO—no. (%) | 0.61 | |||
During | 49 (69) | 31 (66) | 18 (75) | |
After | 22 (31) | 16 (34) | 6 (25) | |
0–3 months | 10 (46) | 8 (50) | 2 (33) | |
3–6 months | 6 (27) | 3 (19) | 3 (50) | |
>6 months | 6 (27) | 5 (31) | 1 (17) | |
Surgical resection margins—no. (%) | 0.01 | |||
Clear | 63 (89) | 45 (96) | 18 (75) | |
Involved | 8 (11) | 2 (4) | 6 (25) | |
Locoregional recurrence site—no. (%) | 0.0016 | |||
LN only | 27 (38) | 13 (28) | 14 (58) | |
In-transit only | 38 (54) | 32 (68) | 6 (25) | |
LN and in-transit | 6 (8) | 2 (4) | 4 (17) | |
Site of LN involvement (n=33)—no. (%) | 0.04 | |||
Neck | 6 (18) | 0 (0) | 6 (33) | |
Axillary | 13 (39) | 8 (53) | 5 (28) | |
Inguinal | 14 (42) | 7 (47) | 7 (39) | |
If LN is involved (n=33)—no. (%) | 0.28 | |||
Median number LN involved, (range) | 1 (1–6) | 1 (1–3) | 1 (1–6) | |
ENE: yes | 16 (48) | 5 (33) | 11 (61) | |
ENE: no | 17 (52) | 10 (66) | 7 (39) | |
Median size largest LN, mm (range) | 15 (4–60) | 13 (4–60) | 19 (4–54) | |
Recurrence within RT field—no. (%) | 0.99 | |||
Yes | 2 (67) | 2 (67) | 0 | |
No | 1 (33) | 1 (33) | 0 | |
Adjuvant systemic therapy—no. (%) | 0.25 | |||
Prior adjuvant IO continued | 8 (11) | 7 (15) | 1 (4) | |
Anti-PD-1 restarted | 5 (7) | 2 (4) | 3 (13) | |
New therapy commenced | 26 (37) | 19 (40) | 7 (29) | |
BRAF/MEK inhibition | 23 | 16 | 7 | |
Ipilimumab-nivolumab | 1 | 1 | 0 | |
Other† | 2 | 2 | 0 | |
No therapy | 32 (45) | 19 (40) | 13 (54) | |
High risk‡—no. (%) (n=33): | 23 (70) | 9 (60) | 14 (78) | 0.0021 |
Bold text signifies p<0.05
*Pearson’s χ2 test; Fisher’s exact test.
†One patient received imatinib, one patient received ipilimumab. Both patients did not receive adjuvant RT at first recurrence.
‡Refers to TROG criteria where high-risk patients are those with: at least one parotid, two cervical or axillary or three inguinal LNs; maximum size of involved LNs (≥3 cm cervical or ≥4 cm axillary or inguinal LN); or the presence of ENE.
AJCC, American Joint Committee on Cancer; ECOG, Eastern Cooperative Oncology Group; ENE, extranodal extension; IO, immunotherapy; LN, lymph node; PD-1, programmed cell death protein-1 ; RT, radiotherapy.