Results of the whole-brain radiotherapy for patients with brain metastases from lung cancer: The RTOG RPA intra-classes analysis.

Figures & data

Table I.  Characteristics of patients.

Characteristic	Number (%)
Gender
Male	232 (72)
Female	90 (28)
Age
Range (Median)	31–79 (59)
< 65 years	241 (75)
≥ 65 years	81 (25)
Histology
SCLC	132 (41)
NSCLC	190 (59)
Squamous carcinoma	67 (35)
Adenocarcinoma	76 (40)
Large cell carcinoma	3 (2)
Without type specification	44 (23)
RTOG RPA prognostic class
Class 1	41 (13)
Class 2	215 (67)
Class 3	66 (20)
KPS
≥ 70	256 (80)
< 70	66 (20)
Previous surgery of BM
Yes	44 (14)
No	278 (86)
Presence of extracranial metastases
Yes	83 (26)
No	229 (71)
Unknown	10 (3)
Control of the primary tumour
Yes	88 (27)
No	222 (69)
Unknown	12 (4)
Number of BM
Single	124 (39)
Multiple	190 (59)
Unknown	8 (2)
Interval from diagnosis of the primary to development of BM
Synchronous	147 (46)
Metachronous	175 (54)
Surgery in the treatment of the primary
Yes	30 (9)
No	292 (91)

Table II.  Results of univariate analysis of 322 patients with brain metastases (BM) from lung cancer.

Analysed factor (number of patients)	1-year survival (%)	Median Survival (months)	p-value
Presence of extracranial metastases:
Yes (83)	4	2.0
No (229)	16	5.0	>0.00001
KPS
≥ 70 (256)	15	4.0
< 70 (66)	3	2.5	0.002
RTOG RPA prognostic class:
Class 1 (41)	12	5.2
Class 2 (215)	14	4.0
Class 3 (66)	3	2.5	0.003
Number of BM:
Single (124)	18	5.0
Multiple (190)	9	3.0	0.003
Control of the primary tumour:
Yes (88)	13	4.5
No (222)	12	3.0	0.03
Gender:
Female (90)	18	4.0
Male (232)	11	3.0	0.11
Age:
≥ 65 (81)	11	3.0
< 65 (241)	13	4.0	0.13
Interval from diagnosis of the primary to development of BM:
Synchronous (147)	10	3.5
Metachronous (175)	14	3.7	0.16
Histology:
NSCLC (190)	11	4.0
SCLC (132)	14	3.5	0.93

Table III.  Factors positively correlated with prognosis in the multivariate analysis of 322 patients with brain metastases (BM) from lung cancer (* in stepwise selection method, ˆ when tested independently).

Variable (number of patients)	Relative risk of death	95% confidence interval	p-value
Presence of extracranial metastases*:
Yes (83)	1.32	1.16–1.49	0.00002
No (229)	1.00
Karnofsky performance status*:
≥ 70 (256)	0.63	0.47–0.82	0.003
< 70 (66)	1.00
Control of the primary*:
Yes (88)	0.98	0.97–0.99	0.02
No (222)	1.00
RTOG RPA prognostic clasŝ:
Class 1 (41)	1.00
Class 2 (215)	1.27 (per Class)	1.02–1.59	0.03
Class 3 (66)

Table IV.  Results of univariate analysis of 190 patients with brain metastases (BM) from NSCLC.

Analysed factor (number of patients)	1-year survival (%)	Median Survival (months)	p-value
Control of the primary:
Yes (73)	16	5.0
No (117)	7	3.0	0.001
Presence of extracranial metastases:
Yes (39)	2	2.0
No (146)	13	4.0	0.002
Interval from diagnosis of the primary to the development of BM:
Synchronous (95)	5	3.0
Metachronous (95)	16	4.0	0.01
RTOG RPA Class:
Class 1 (34)	19	6.0
Class 2 (117)	11	3.5
Class 3 (39)	3	3.0	0.02
Histology:
Adenocarcinoma (76)	15	4.0
Squamous (67)	5	3.0	0.02
Histology:
Adenocarcinoma (76)	12	4.0
Other histologies (114)	9	3.0	0.06
Karnofsky performance status:
≥ 70 (151)	13	4.0
< 70 (39)	3	3.0	0.10
Number of BM:
single (94)	13	4.0
multiple (92)	8	3.0	0.10
Age:
≥ 65 (59)	11	3.5
< 65 (131)	11	4.0	0.29
Gender:
Female (44)	20	4.0
Male (146)	8	4.0	0.32

Table V.  Results of univariate analysis of 132 patients with brain metastases (BM) from SCLC.

Analysed factor (number of patients)	1-year survival (%)	Median survival (months)	p-value
Presence of extracranial metastases:
Yes (44)	6	2.4
No (83)	20	5.4	0.0004
Karnofsky performance status:
≥ 70 (105)	17	4.0
< 70 (27)	4	2.0	0.003
RTOG RPA prognostic class:
Class 1 (7)	0	3.0
Class 2 (98)	18	4.5
Class 3 (27)	4	2.0	0.003
Number of BM:
single (30)	35	7.0
multiple (98)	9	2.9	0.005
Age:
≥ 65 (22)	14	2.5
< 65 (111)	15	3.5	0.24
Gender:
Female (45)	15	5.0
Male (87)	13	3.0	0.26
Control of the primary tumour:
Yes (15)	6	3.8
No (105)	16	3.5	0.53
Interval from diagnosis of the primary to development of BM:
Synchronous (52)	20	4.0
Metachronous (80)	11	3.0	0.60

Table VI.  Results of multivariate analysis performed separately for patients with brain metastases (BM) from NSCLC and SCLC.

Variable (number of patients)	Relative risk of death	95% confidence interval	p-value
NSCLC (190)
Presence of extracranial metastases:
Yes (39)	1.35
No (146)	1.00	1.23–1.62	0.001
Interval from diagnosis of the primary to development of BM:
synchronous (95)	1.00
metachronous (95)	0.68	0.59–0.92	0.01
SCLC (132)
Number of BM
Single (30)	1.00
Multiple (98)	1.82	1.55–2.83	0.007
Karnofsky performance status:
≥ 70 (105)	0.55
< 70 (27)	1.00	0.35–0.87	0.01
Presence of extracranial metastases:
Yes (44)	1.28
No (83)	1.00	1.06–1.56	0.01

Table VII.  Results of univariate analysis of 41 patients from RPA class 1.

Analysed factor (number of patients)	Median survival (months)	p-value
Surgery in the treatment of the primary
Yes (8)	5.0	0.58
No (33)	5.0
Gender
Female (9)	4.0
Male (32)	5.0	0.98
Histology
SCLC (7)	3.0
NSCLC (34)	6.0	0.32
Number of BM
Single (24)	6.5
Multiple (15)	3.5	0.08
Previous surgery of BM
Yes (19)	7.0
No (22)	4.0	0.03
Interval from diagnosis of the primary to development of BM:
synchronous (12)	5.0
metachronous (29)	5.0	0.4
Total dose
20 Gy (8)	3.0
30 Gy (29)	6.0
40 Gy (4)	6.0	0.24

Table VIII.  Results of univariate analysis of 215 patients from RPA class 2.

Analysed factor (number of patients)	Median survival (months)	p-value
Age
< 65 years (155)	3.0
≥ 65 years (60)	4.0	0.19
Control of the primary:
Yes (29)	6.0
No (180)	4.0	0.21
Presence of extracranial metastases:
Yes (61)	3.0
No (148)	5.0	0.0004
Surgery in the treatment of the primary
Yes (15)	3.0
No (200)	4.0	0.19
Gender
Female (62)	5.5
Male (153)	3.5	0.01
Histology
SCLC (99)	4.0
NSCLC (116)	3.5	0.25
Number of BM
Single (81)	4.0
Multiple (131)	4.0	0.22
Previous surgery of BM
Yes (17)	7.0
No (198)	3.0	0.007
Interval from diagnosis of the primary to development of BM:
synchronous (99)	3.5
metachronous (116)	4.0	0.4
Total dose
20 Gy (75)	2.5
30 Gy (116)	5.0
40 Gy (22)	5.5	0.00005

Table IX.  Results of univariate analysis of 66 patients from RPA class 3.

Analysed factor (number of patients)	Median survival (months)	p-value
Age
< 65 years (45)	3.0
≥ 65 years (21)	2.0	0.24
Control of the primary:
Yes (19)	3.5
No (42)	2.5	0.11
Presence of extracranial metastases:
Yes (22)	2.0
No (41)	3.0	0.009
Surgery in the treatment of the primary
Yes (5)	4.0
No (61)	3.0	0.06
Gender
Female (19)	2.5
Male (47)	3.0	0.56
Histology
SCLC (26)	2.0
NSCLC (40)	3.0	0.11
Number of BM
Single (17)	5.0
Multiple (46)	3.0	0.04
Previous surgery of BM
Yes (8)	4.0
No (58)	3.0	0.06
Interval from diagnosis of the primary to development of BM:
synchronous (36)	3.0
metachronous (30)	3.0	0.86
Total dose
20 Gy (22)	2.5
30 Gy (38)	3.0
40 Gy (6)	10.0	0.05

Table X.  Results of multivariate analyses performed separately for all three RPA classes.

Variable	Relative risk of death	95% confidence interval	p-value
RPA Class 1
Surgery of brain metastases
Yes (19)	1.00
No (22)	1.99	1.03–3.82	0.04
RPA Class 2
Total dose
20 Gy (75)
30 Gy (116)
40 Gy (22)	0.97 by Gy	0.95–0.99	0.002
Gender
Female (62)	0.62
Male (153)	1.00	0.46–0.81	0.003
Extracranial metastases
Yes (61)	1.27
No (148)	1.00	1.09–1.48	0.003
Surgery of BM
Yes (17)	1.00
No (198)	1.76	1.07–2.93	0.03
RPA Class 3
Extracranial metastases
Yes (22)	1.40
No (41)	1.00	1.07–1.82	0.01
Total dose
20 Gy (22)
30 Gy (38)
40 Gy (6)	0.96 by Gy	0.73–0.99	0.02