Table 2 Radiotherapy and outcome in major CUP studies

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