Maarten van der Doelen

Chapter 7

distributions between subgroups, by calculating hazard ratios (HR) and 95% confidence intervals (CI). All statistical tests were two-sided, with P values of <0.05 considered to be statistically significant.

RESULTS Patient cohort

In total, 93 patients received radium-223 therapy, underwent somatic and/or germline NGS testing, and were included in this two-centre retrospective study. The 28 patients described previously were included in this cohort study, with updated outcomes and longer follow-up. (11) Of the 93 included patients, 28 (30.1%) patients were identified with (likely) pathogenic mutations in DDR genes (Figure 1). Thirty-five different alterations were found, consisting of 27 (77.1%) somatic and eight (22.9%) germline mutations. Mutations were most frequently found in ATM (8.6%), BRCA2 (7.5%), and CDK12 (4.3%) genes.

0

8

29%

ATM

25%

BRCA2

14%

CDK12

7%

BRCA1

7%

CHEK2

4%

BRIP1

4%

CHEK1

4%

FANCG

4%

FANCI

4%

NBN

4%

PALB2

4%

RAD51B

4%

RAD51C

4%

RAD54L

17

16

02

05

34

44

64

80

08

20

61

66

76

35

46

83

21

36

27

70

26

77

53

43

73

12

18

30

Nonsense Splice site

Missense Frameshift CNV - deletion

Figure 1. Next-generation sequencing data of patients with pathogenic DNA damage response (DDR) alterations.

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