Prognostic factors affecting survival after whole brain radiotherapy in patients with brain metastasized lung cancer

Figures & data

Table 1. RPA and GPA classification.

GPA score	0 points	0,5 points	1 point
Age	≥60	50–59	<50
KPS	<70	70–80	90–100
Number of brainmetastases	>3	2–3	1
Extracranial disease	Present	–	None
RPA class	Class 1	Class 2	Class 3
	<65 years, KPS ≥70, primary tumor under control, no extracranial metastases	All other patients	KPS <70

Table 2. Baseline demographics and disease characteristics.

Variables
Gender (% male)	46.8 [131/280]
Age (mean ± SD)	66.6 ± 10.2
Histology (%)  Adenocarcinoma  Squamous cell  SCLC  Large cell  NOS/mixed type	68.1 [188/276]  5.4 [15/276]  17.4 [48/276]  3.3 [9/276]  5.8 [16/276]
EGFR mutation status (%)  (Exon 19 del + Exon 21 L858R point mut)  Exon 20	20.6 [28/136]  3.7 [5/136]
ALK status (%)	9.6 [7/73]
KRAS status (%)	16.7 [5/30]
CNS metastasis at diagnosis (%)	45.4 [127/280]
Symptomatic CNS disease (%)	93.2 [261/280]
CNS therapy prior to salvage WBRT (%)  Surgery  Systemic therapy  Gamma knife	16.7 [22/132]  86.4 [114/132]  23.5 [31/132]
GPA class group (%)  0 (0–1)  1 (1.5–2.5)  2 (3–4)	60.2 [168/279]  35.1 [98/279]  4.7 [13/279]
RPA class (%)  1  2  3	4.7 [13/279]  59.1 [165/279]  36.2 [101/279]
Number of CNS metastases (%)  1  2–3  >3	8.6 [24/280]  15.4 [43/280]  76 [213/280]

In square brackets, the absolute number of patients in each subgroup and the total number of patients with available information is shown.

ALK: anaplastic lymphoma kinase; CNS: central nervous system; del: deletion; EGFR: epidermal growth factor; GPA: graded prognostic assessment; KRAS: Kirsten rat sarcoma; mut: mutation; NOS: nonotherwise specified; RPA: recursive partitioning analysis; SCLC: small-cell lung cancer; SD: standard deviation; WBRT: whole-brain radiotherapy.

Figure 1. OS whole cohort. Cumulative percent: 21.7% of patients died at the first month, 43.1% at 2 months and 54.7% at 3 months after WBRT.

Figure 2. (A) OS analysis for RPA classes, pairwise log rank test has shown statistically significant difference with p < .0001 between RPA classes 1 versus 3 and 2 versus 3. (B) OS analysis for GPA groups, pairwise log rank test has shown statistically significant difference with p < .0001 between GPA groups 0 versus 1. (C) OS according to GPA for RPA class 2 subgroup (165 patients), there was a statistically significant OS difference between GPA group 0 (79 patients) and GPA group 1 (78 patients) with p = .004. (D) OS according to GPA/age for RPA class 2 subgroup, Group A: Age ≤70, GPA group 0 [41/165], group B: Age ≤70, GPA group 1 or 2 [66/165], group C: Age> 70, GPA group 1 or 2 [20/165] and group D: Age >70, GPA group 0 [38/165]. The pairwise log rank test showed a statistically significant difference in OS between groups A versus D (p = .036), as well as B vs D (p < .0001).

Table 3. Univariate Cox regression analysis.

Variable	p value	HR (95% CI)
Gender(female vs. male)	.771	0.96 (0.76–1.23)
Age (>70 vs. ≤70)	<.0001	1.7 (1.31–2.17)
Age as continuous variable	<.0001	1.02 (1.01–1.04)
Histology (SCLC vs. NSCLC)	.637	0.93 (0.67–1.27)
Histology(non-adeno vs. adeno)	.443	1.11 (0.86–1.43)
CNS metastasis at diagnosis (Yes vs. No)	.404	0.90 (0.71–1.15)
Symptom CNS (Yes vs. No)	.06	1.57 (0.98–2.50)
EGFR (Exon19 + Exon21) (mut vs. WT)	.148	0.73 (0.48–1.12)
EGFR (Exon20) (mut vs. WT)	.802	0.89 (0.36–2.19)
ALK (mut vs. WT)	.87	0.94 (0.43–2.01)
KRAS (mut vs. WT)	.24	0.53 (0.18–1.53)
Upfront WBRT (Yes vs. No)	.076	1.24 (0.98–1.58)
Surgery CNS before WBRT (Yes vs. No)	.001	0.45 (0.28–0.72)
SRS before WBRT (Yes vs. No)	.778	0.95 (0.65–1.38)
Systemic treatment of BM before WBRT (Yes vs. No)	.66	0.95 (0.74–1.21)
RPA class  1  2  3	<.0001 <.0001 Ref	0.21 (0.12–0.39) 0.32 (0.24–0.41)
GPA class group  0 (0–1)  1 (1.5–2.5)  2 (3–4)	Ref <.0001 .088	0.48 (0.37–0.62) 0.6 (0.33–1.08)

ALK: anaplastic lymphoma kinase; BM: brain metastasis; CNS: central nervous system; del: deletion; EGFR: epidermal growth factor; GPA: graded prognostic assessment; KRAS: Kirsten rat sarcoma; mut: mutation; NOS: nonotherwise dpecified; NSCLC: nonsmall cell lung cancer; RPA: recursive partitioning analysis; SCLC: small-cell lung cancer; SRS: stereotactic radiosurgery; WBRT: whole-brain radiotherapy.

Table 4. Multivariate Cox-regression analyses for OS.

	p value	HR (95% CI)
A: Multivariate analysis including GPA
GPA class group 0 (0–1) 1 (1.5–2.5) 2 (3–4)	Ref <.0001 .552	0.48 (0.37–0.63) 0.83 (0.44–1.55)
Surgery CNS before WBRT (Yes vs. No)	.022	0.54 (0.32–0.91)
Age (>70 vs. ≤70)	.006	1.44 (1.11–1.87)
Symptomatic CNS disease (Yes vs. No)	.01	1.87 (1.16–3.00)
B: Multivariate analysis including RPA\
RPA class 1 2 3	<.0001 <.0001 ref	0.27 (0.15–0.49) 0.34 (0.26–0.45)
Surgery CNS before WBRT (Yes vs. No)	.14	0.68 (0.41–1.13)
Age (>70 vs. ≤70)	.007	1.43 (1.10–1.85)
C: RPA class 2 subgroup multivariate analysis
GPA class group 0 (0–1) 1 (1.5–2.5) 2 (3–4)	Ref .012 .42	0.65 (0.47–0.91) 1.40 (0.62–3.17)
Surgery CNS before WBRT	.022	0.47 (0.24–0.90)
Age >70	.028	1.47 (1.04–2.07)

A: Including GPA as an independent variable; B: Including RPA as independent variable; C: Multivariate analysis within RPA class 2 subgroup.

Figure 3. Diagram for the selection of brain metastasized lung cancer patients who should receive WBRT.