Table 1 Studies with data on pituitary hormonal impairment after cranial radiotherapy in adult cancer patients

Lamba 2019

[13]

74

NR

Meningeoma

NR

Follow up: mean: 43 months

Mean time to develop hormone deficiency: 11–32 months

19% (14/74)

24% (18/74)

24% (18/74)

10% (7/74)

NR

Handisurya 2018

(prospective)

[14]

436

52 (19–83)

Brain

54–60 Gy

No statement on dose to the pituitary/hypothalamus

Baseline

3 months after RT

6 months after RT

1 years after RT

2 years after RT

3 years after RT

> 3 years after RT

NR

NR

21%

16.8%

11.3%

10.2%

1.4%

5.7%

10.9%

0% / 0%*

7.1% / 0%*

32.7% / 0%*

35.3% / 0%*

41.7% / 0%*

52.2% / 0%*

24% / 0%*

LH: always 0%

20% / 11%*

2% / 18.8%*

1.3% / 6.8%*

3.1% / 10.3%*

22.2% / 0%*

55.6% / 4.3%*

26% / 42.1%*

Kyriakakis 2016

[15]

107

40 ± 13.1

Brain

54Gy, estimated dose to the HP axis 35.9 ± 15.5Gy**

8 years 5.3–11 years

88%

86.9%

23.4%

11.2%

34.6%

15%

Ipekci 2014

[16]

30

45.2 ± 9.8

Nasopharyngeal

Mean dose to the pituitary: 46Gy (23–66)

Mean dose to the hypothalamus: 10Gy (4–41)

10–133 months

93% (28/30)

77% (23/30)

73% (22/30)

27% (8/30)

NR

43% (13/30)

Ratnasingam 2014 [17]

50

57 ± 12.2

Nasopharyngeal

No statement on dose to the pituitary/hypothalamus

Median: 8 years (3–21)

82% (41/50)

78% (39/50)

40% (20/50)

4% (4/50)

22% (11/50)

30% (15/50)

Seland 2014 [18]

140

42.5 (15–76)

Head and neck

Pituitary: 13Gy (0–68)

16 years (5–29)

73% (102/140)

25% (32/140)

34% (45/140)

34% (45/140)

55%

NR

Appelman-Dijstra 2014

[19]

80

47.5 (18.6–89.7)

Brain

Pituitary: 56.27 (40–70)

2 years after RT

5 years after RT

10 years after RT

15 years after RT

21% (17/80)

47% (23/49)

60% (27/45)

89% (31/35)

33% (27/80)

31% (25/80)

14% (11/80)

25% (20/80)

21% (17/80)

Madischi 2011 [20]

26

38.5 (33–47)

Brain

Mean dose to the pituitary and hypothalamus: 41.8 Gy (30.7–49.8)

< 32 months (median: 27 months)

38% (10/26)

29% (7/26)

22% (6/26)

14% (4/26)

4% (1/26)

NR

Snyders 2009

[21]

76, 21 with endocrine evaluation

56 (28–74)

Sinunasal

44-66Gy, estimated dose to the pituitary: 51–56, estimated dose to the hypothalamus: 44-52Gy

107 months (11–253)

62% (13/21)

24% (5/21)

19% (4/21)

14% (3/21)

19% (4/21)

10% (2/21)

Bhadare 2008 [22]

312, 112 with endocrine evaluation

NR

Nasopharyngeal

40-70Gy

63 months (6–365)

60% (67/112)

36% (16/44)

32% (14/44)

70% (31/44)

27% (12/44)

15% (10/68)

Schneider 2006 [23]

68, 44 with endocrine evaluation

20–79

Brain

NR

NR

38%

(17/44)

28%

(12/44)

19%

(8/44)

18%

(7/44)

29.5%

(13/44)

7%

(3/44)

Agha 2005 [24]

56

39.3 ± 11.9

Brain

Estimated dose to the pituitary: 54Gy (4–97)

6 years

41% (23/56)

32%

(18/56)

21%

(12/56)

9%

(5/56)

27%

(15/56)

32%

(18/56)

Johannesen 2003

[25]

33,

25 with endocrine evaluation

38 (14–68)

Brain

54 Gy (45–59)

13.1 years (6–25.6)

64% (16/25)

NR

4%

(1/25)

56%

(14/25)

16%

(4/25)

0%

(0/25)

Popovic 2002 [26]

22

6 > 18y

NR

Brain

56 Gy, estimated dose to the pituitary: 25-30Gy

7.6 ± 0.7 years (2–3)

67%

(4/6)

67%

(4/6)

NR

NR

NR

NR

Pai 2001 [27]

107

41.2 (17–75)

Chordoma/ chondrosarcoma

Estimated dose to pituitary and hypothalamus: < 50-70Gy

5.5 years

87%

NR

19%

30%

29%

72%

Arlt 1997

[28]

31

26–66

Brain

Mean dose pituitary: 51.1Gy (±12.1) mean dose hypothalamus: 57Gy (±7.8)

1.5–11 years

77% (24/31)

NR

29% (9/31)

Taphoorn 1995 [29]

13

24–66

Brain

45–61 Gy, mean pituitary dose: 36.1 Gy (0–50)

3 years (1–11.5)

77%

(10/13)

31%

(4/13)

62%

(8/13)

0%

(0/13)

15%

(2/13)

23%

(3/13)

Constine 1993 [30]

32

6–65

Brain

39.6–70.2Gy

2–13 years

91% (28/32)

NR

NR

NR

NR

NR

Lam 1991 [31]

20

43.7 ± 8.4 (male)

36.8 ± 9 (female)

Nasopharyngeal

Estimated dose to the pituitary 62Gy, estimated dose to the hypothalamus: 40Gy

60 months

75% (15/20)

55% (11/20)

25% (5/20)

15% (3/20)

35% (7/20)

30% (6/20)

Woo 1988 [32]

11

33–64

Nasopharyngeal

Estimated dose to pituitary 62-67Gy, estimated dose to the hypothalamus: 41-45Gy

72–240 months

82% (9/11)

90% (9/10)

18% (2/11)

45% (5/11)

55% (6/11)

27% (3/11)

Samaan 1987 [33]

166

47 (6–80)

Nasopharyngeal

and paranasal sinus

Estimated dose to the pituitary: 57 (4–75), estimated dose to the hypothalamus: 50 (11–75)

12–312 months

75% (124/166)

75% (124/166)

18% (30/166)

20% (33/166)

20% LH (33/166)

35% FSH (58/166)

36% (60/166)

Lam 1987 [34]

32

27–50

Nasopharyngeal

46–60

60–204 months

25% (8/32)

19% (6/32)

6% (2/32)

13% (4/32)

16% (5/32)

19% (6/32)

Mechanik 1986 [35]

15

22–59

Brain

40–50 to whole brain

2–9 years

93%

(14/15)

NR

NR

14.3%

(1/7)

NR

100%

(9/9)

Lam 1986 [36]

8

27–52

Nasopharyngeal

46–61, estimated to the pituitary 55–67

> 60 months

100% (8/8)

100% (8/8)

50% (4/8)

50% (4/8)

25% (2/8)

88% (7/8)

Huang 1979

(prospective) [37]

37

16–65

Nasopharyngeal

estimated dose to pituitary/hypothalamus: 46–56 Gy

Before RT

6 months after RT

1 years after RT

2 years after RT

NR

8.1%

18.9%

18.9%

21.6%

NS

46%

73%

83.8%

83.8%

p = < 0.01

0%

21.6%

27%

37.8%

p = < 0.01

10.8% / 48.6%

56.8% / 83.8%

51.4% / 83.8%

56.8% / 81.1%

(LH/FSH)

p < 0.01

NR

Harrop 1976 [38]

17

8 < 18y

8 < 18

Brain

40–52

6 years (1–15)

62.5%

(5/8)

50%

(4/8)

12.5%

(1/8)

12.5%

(1/8)

37.5%

(3/8)

NR

Rosenthal 1976 [39]

6

35–66

Nasopharyngeal

55–65

12–96 months

67% (4/6)

100% (2/2)

50% (1/2)

67% (4/6)

NR

NR

Samaan 1975 [40]

10

26–55

Nasopharyngeal

Estimated dose to pituitary: 50–83

60–240 months

100% (10/10)

60% (6/10)

50% (5/10)

40% (4/10)

30% (3/10)

50% (5/10)