Table 2.
Radiotherapy and outcome in major CUP studies
| Study (Data Aquired) — No. of Patients (Total No. In Study) |
Radiotherapy (No.) RT dosage median (range) |
Nodal State No.(%) |
Invasive Diagnostics — Surgical Treatment before RT No.(%) |
locoregional control — distant metastases (median time to appearance, months) |
overall survival — Head and Neck Mucosal Emergence No.(%) [most common site] |
|---|---|---|---|---|---|
| Bataini et al., 1987 [9] (1960–1980) — 138 |
dRT (90 pts): 70-80Gy pRT (48 pts): 50-60Gy bilateral 138, mucosa 43% |
N1 45 (33) N2 32 (23) N3 60 (44) 137/138 EC 60%, UC 40% |
FNAB/IB/EB 90 (65) — Adenectomy or RND 48 (35) |
neck failure: definitive RT: 43% RND + RT: 17% ultimately — ultimately 25% |
definitive RT: 22% RND + RT: 55% overall 33% at 5 years — 6 (4) [NR] |
| Jesse et al., 1973 [10] (1948–1968) — RT alone: 52 (210) |
dRT (52): 50-60Gy + 5-10Gy unilateral 0, bilateral + mucosa 52 |
N1 12 (23) N2-3 23 (77) SCC 62%, UC 28%, GCSO 10% |
EB 114/210 (52% total) — none in this group |
initial local control 79% — NR |
48% at 3 years — 3 (6) [oral cavity] |
| Weir et al., 1995 [11] (1970–1986) — 144 |
involved neck (85pts), bilateral + mucosa (59pts): 25 pts: 35-49Gy, 86 pts: 50-59Gy, 33 pts: 60-70Gy |
N1 11 (5) N2 67 (47) N3 55 (38) Nx 5 (3) 138/144 UC 30%, SCC 62%, others 8% |
EB 71 (50), IB 62 (43) FNAB 7 (7) — none |
initial local control 51% — ultimately 23% |
involved neck 37%, bilateral + mucosa 48%, overall 41%, at 5 years — 7 (5) [oropharynx] |
| Reddy et al., 1997 [12] (1974–1989) — 52 |
dRT (21): involved neck 70Gy (66–76) pRT (31): involved neck 64Gy (60–66) dRT/pRT: mucosa 60-66Gy, contralateral neck 46-50Gy unilateral 16, bilateral + mucosa 36 |
N1 9 (17) N2a 16 (31) N2b 7 (13) N2c 5 (10) N3 15 (29) |
EB/IB 21 (40) — RND 31 (60) |
NR — ultimately 15% |
40% at 5 years — 10 (19) [base of tongue] |
| Colletier et al., 1998 [13] (1968–1992) — 136 |
pRT (136): involved neck 63Gy (34-70) mucosa + uninvolved neck 50-54Gy unilateral 16, bilateral 120 |
N1 31 (23) N2a 49 (37) N2b 25 (18) N2c 3 (2) N3 18 (13) Nx 10 (7) SCC 93%, NS 7% |
EB 39 (29) — MND 64 (47) RND 33 (24) |
84% with ECE 100% without ECE neck control at 5 years — 15% at 5 years |
60% at 5 years 41% at 10 years — 14 (10) [oral cavity] |
| Fernández et al., 1998 [14] (1976-1996) — 67 |
dRT (3)/pRT (64): 50Gy bilateral + mucosa 67 |
N1 9 (13) N2 33 (49) N3 25 (37) |
FNAB 40 (60) — RND 50 (75) MND 14 (21) |
34% neck recurrence, mean 5 months — 22%, mean 17 months |
22% at 5 years 20% at 10 years — 10 (15) [oropharynx] |
| Grau et al., 2000 [15] (1975-1995) — RT ± ND 250 (352) |
dRT (250): neck 59Gy (28-93) neck + mucosa 66Gy (20-79) unilateral 26, bilateral + mucosa 224 |
N1 37 (15) N2 119 (48) N3 93 (37) Nx 1 (.4) |
FNAB (12) CB (1) EB/IB (85) — ND (2) |
local control 44% neck control 51% muscosal control 81% — NR |
36% — 17 (7) [oropharynx] |
| Iganej et al., 2002 [16] (1969-1994) — 106 |
dRT: 66Gy (48-70) pRT: 60Gy (50-70) unilateral 16, bilateral + mucosa 163 |
N1 14 (13) N2a 27 (25) N2b 39 (37) N2c 2 (2) N3 24 (23) |
EB alone 12 EB + RT 15 — RND 29 RT alone 24 RND + RT 26 |
54% neck recurrence, median 7 months; ultimately 34% neck failure — 9% (4) |
53% at five years — 19 (18) [tonsil] |
| Yalin et al., 2002 [17] (1976-1988) — 114 |
UC: RT 50-70Gy SCC: RT 40-60Gy AC: 60Gy |
N1 33 (29) N2 51 (45) N3 30 (26) UC 62%, SCC 24%, AC 14% |
FNAB 111/EB 3 (100) — RND in case of bilateral disease (+thyrectomy in case of AC) |
NR — NR |
UC: 32%, SCC: 33% AC: 38% at 5 years — 12 (11) [tonsillar fossa] |
| Aslani et al., 2007 [18] (1987-2002) — 61 |
dRT (40): 64Gy (60-70) pRT (21): 60Gy (56-66) unilateral 11, bilateral 50 |
N1 16 (26) N2a 18 (31) N2b 13 (21) N2c 7 (11) N3 7 (11) UC 15% |
FNAB 9 (15) EB 32 (52) — MND 9 (15) RND 11 (18) |
neck control: with biopsy 76%, ND 85% at 5 years; 73% at 8 years — 11.5% (2-24 months) |
79% at 5 years 67% at 8 years — 4 (7) [base of tongue] |
| Boscolo-Rizzo et al., 2006 [19] (1980-2001) — 82 |
dRT (32 pts), pRT (47 pts): 60-70Gy before 1989; 50Gy + 10-20Gy after 1989 unilateral 37, bilateral 42 |
N1 10 (12) N2a 14 (17) N2b 23 (28) N2c 3 (4) N3 32 (39) |
FNAB/EB 82 (100) — RND 46 (56) MND 4 (5) |
NR — 23% at 10 years |
25% at 5 years 19% at 10 years — 10 (12) [base of tongue] |
| Beldi et al., 2007 [20] (1980-2004) — 113 (22/113 palliative intent) |
dRT (59), pRT (54): involved neck 50Gy*, 60Gy** bilateral neck + mucosa 50Gy*, 56Gy** unilateral 45, bilateral 67 |
N1 21 (19) N2a 12 (11) N2b 42 (37) N2c 10 (9) N3 28 (25) SCC 77%, AC 5%, UC 10%, others 8% |
FNAB 14 (12) EB 37 (33) — ND 62 (55) |
disease free survival 27% at 5 years — NR |
41% at 5 years — 19 (17) [NR] |
| Patel et al., 2007 [21] (1987-2006) — 70 |
pRT (60 pts): 50Gy or 54-60Gy unilateral 49, bilateral 11 |
N1 5 (7) N2a 13 (19) N2b 30 (43) N2c 4 (6) N3 18 (26) |
FNAB 68 (97) EB 2 (3) — MND 70 (100) |
ipsilateral control 84% contralateral control 93% at 5 years — 10% (9) |
56% at 5 years — 8 (11) [base of tongue] |
| Corry et al., 2008 [22] (1998-2002) — |
macroscopic disease 70Gy larger nodal masses 60Gy sites of suspected subclinical disease 50Gy |
N2a 12 (12) N2b 43 (42) N2c 27 (26) N3 20 (20) |
occult HNSCC\— ND 16 (16) |
neck failure ultimately 9% — ultimately 23% |
60% at 3 years (of 122 pts) — |
| Ligey et al., 2009 [29] (1990-2007) — 102 (122) |
pRT (95): involved neck 66Gy mucosa + uninvolved neck 50Gy unilateral 59, bilateral 36 |
N1 9 (9) N2a 22 (23) N2b 33 (35) N3 15 (16) Nx 16 (17) EC 100% |
EB 16 (17) — RND/MND 79 (83) |
neck control 66% at 5 years — ultimately 30% |
24% at 5 years — 9 (9) [tongue] |
| Lu et al., 2009 [23] (1989-2003) — 60 |
dRT (60): 69Gy (66-72) to mucosa; 62Gy (53-74) to involved areas; 51Gy (44-59) to uninvolved areas unilateral 25, bilateral 24, bilateral + mucosa 11 |
N1 10 (17) N2 39 (65) N3 11 (18) |
FNAB 51 (85) EB 9 (15) — none |
neck control 66% at 5 years — ultimately 18% |
69% at 5 years — 10 (21) [nasopharynx] |
| Chen et al., 2011 [24] (2001-2009) — 60 |
dRT (15): involved neck 60-74Gy uninvolved neck 54-66Gy pRT (45): involved neck 63Gy (60-66) uninvolved neck 56Gy (54-60) bilateral + mucosa 60 |
N1 5 (8) N2a 26 (43) N2b 20 (33) N2c 0 (0) N3 9 (15) |
FNAB 15 (25) EB 5 (8) — ND 8 (13) MND 32 (53) |
locoregional control 89% at 2 years — 13% (9) |
89% at 2 years — NR |
| Wallace et al., 2011 [25] (1964-2006) — 179 |
dRT (179): mucosa 57Gy (24-74) neck 65Gy (50-86) unilateral 5, bilateral + mucosa 174 |
N1 18 (10) N2a 48 (27) N2b 46 (26) N2c 11 (6) N3 56 (31) |
none — ND 65 (36) before RT ND 44 (25) after RT |
mucosal control 92% and neck control 81% at 5 years — 14% at 5 years |
52% at 5 years — NR |
| Fakhrian et al., 2012 [26] (1988-2009) — 65 |
unilateral RT (17 pts): 60Gy (50-66) bilateral RT + mucosa (48 pts): 65Gy (28-70) |
N1 14 (21) N2a 9 (14) N2b 34 (52) N2c 2 (3) N3 5 (8) UC 14% |
EB 10 (15) — RND 27 (42) MND 24 (37) |
locoregional lymph node recurrence, ultimately 14% — 28% (23) |
48% at 5 years — 10 (15) [nasopharynx] |
| Tribius et al., 2012 [67] (2002-2011) — 63 |
dRT (63): involved neck 60-68Gy mucosa 60 Gy uninvolved neck 50-54Gy unilateral 7, bilateral 47 |
N1 6 (10) N2 38 (57) N3 19 (30) |
FNAB 63 (100) — none |
neck recurrence 25%, median 7 months — 13% (10) |
76% at 2 years — 4 (6) [base of tongue] |
| Demiroz et al., 2014 [27] (1994-2009) — 41 |
dRT (19 pts): involved neck 70Gy univovled neck 50-59Gy pRT (22 pts): formerly inv. neck 60Gy (ECE 66Gy) univolved neck 54Gy bilateral + mucosa 67 |
N1 4 (10) N2a 10 (24) N2b 18 (44) N2c 0 (0) N3 9 (22) |
FNAB/EB 41 (100) — RND 5 (12) MND 17 (41) |
LRFS:dRT: 75% ND + RT: 76% at 4 years — definitve RT: 11% ND + RT: 28% ultimately |
definitve RT: 85% ND + RT: 85% at 4 years — 2 (5) tonsillar fossa] |
| Straetmans et al., 2015 [28] (1997-2010) — 51 |
pRT (46 pts): univolved neck 50.4Gy or 46-50Gy involved neck 59.4-63Gy or 60-66Gy unilateral 32, bilateral 14 |
N1 4 (9) N2a 7 (15) N2b 28 (52) N3 12 (24) |
FNAB (22) — MND 51 (100) |
neck recurrence ultimately 18% — ultimately 18% (<24) |
55% at 5 years — 0 |
Abbrevations: UC undifferentiated carcinoma, AC adenocarcinoma, EC epidermoid carcinoma, GCSO glandular carcinoma of salavary origin, IB incision biopsy, CB core biopsy, EB exicision biospy, ND neck dissection, MND modified neck dissection, RND radical neck dissection, pts patients, dRT definitive radiotherapy, pRT postoperative radiotherapy, LRFS locoregional relapse-free survival, NS not specified; *median dose in the 1980s, **median dose in the 1990s; TNM staging referring to UICC/AJCC classification actual when published; Tumor entity SCC if not described otherwise; adapted from references [9–28]