World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Original Article

Volume 2, Number 4, August 2011, pages 181-190

Validation of a Predictive Model for Survival in Patients With Advanced Cancer: Secondary Analysis of RTOG 9714

**Table 1.** Risk Groups Previously Identified
Prognostic Factor	Partial Score Method	Risk Factor Score Method
Note: Sum of partial scores equal to survival prediction score (range 0 to 8).
KPS: Karnofsky performance score
Primary tumor site
Breast	0	0
Prostate	2	1
Lung	3	1
Others	3	1
Site of metastases
Bone only	0	0
Other	2	1
KPS
> 60	0	0
≤ 60	3	1
	Survival Prediction Score (SPS) determined by sum of partial scores	Number of Risk Factors Score (NRF) determined by sum of risk factors
	Risk Group A [SPS 0 - 4]	Risk Group I [NRF 0 - 1]
	Risk Group B [SPS 5]	Risk Group II [NRF 2]
	Risk Group C [SPS 6 - 8]	Risk Group III [NRF 3]

Table 1. Risk Groups Previously Identified

Prognostic Factor

Partial Score Method

Risk Factor Score Method

Note: Sum of partial scores equal to survival prediction score (range 0 to 8).

KPS: Karnofsky performance score

Primary tumor site

Breast

Prostate

Lung

Others

Site of metastases

Bone only

Other

KPS

> 60

≤ 60

Survival Prediction Score (SPS) determined by sum of partial scores

Number of Risk Factors Score (NRF) determined by sum of risk factors

Risk Group A [SPS 0 - 4]

Risk Group I [NRF 0 - 1]

Risk Group B [SPS 5]

Risk Group II [NRF 2]

Risk Group C [SPS 6 - 8]

Risk Group III [NRF 3]

**Table 2.** Patient Characteristics From RTOG Validation Set (N = 908)
Characteristic	n (%)
*BPI: Brief Pain Inventory
Gender
Male	447 (49)
Female	461 (51)
Age (years)
Mean ± SD	65 ± 12
Median (range)	67 (31 - 92)
Country of Residence
Canada	38 (4%)
USA	870 (96%)
Primary cancer site
Breast	462 (51)
Prostate	446 (49)
Karnofsky performance status (KPS)
40 - 60	214 (24)
70 - 100	694 (76)
Physician predicted survival time (months)
Mean ± SD	14.5 ± 14
Median (range)	12 (1 - 99)
Painful site(s)
Single	542 (60)
Multiple	366 (40)
Site of radiotherapy
Weight bearing	506 (56)
Non-weight bearing	402 (44)
BPI worst pain score at study entry*
< 5 with ≥ 60 mg/day morphine	17 (2)
5 - 6	254 (28)
7 - 10	637 (70)
Receiving biphosphanotes at study entry
No	688 (76)
Yes	220 (24)
Radiation treatment assignment
8 Gy	460 (49)
30 Gy	448 (51)

Table 2. Patient Characteristics From RTOG Validation Set (N = 908)

Characteristic

n (%)

*BPI: Brief Pain Inventory

Gender

Male

447 (49)

Female

461 (51)

Age (years)

Mean ± SD

65 ± 12

Median (range)

67 (31 - 92)

Country of Residence

Canada

38 (4%)

USA

870 (96%)

Primary cancer site

Breast

462 (51)

Prostate

446 (49)

Karnofsky performance status (KPS)

40 - 60

214 (24)

70 - 100

694 (76)

Physician predicted survival time (months)

Mean ± SD

14.5 ± 14

Median (range)

12 (1 - 99)

Painful site(s)

Single

542 (60)

Multiple

366 (40)

Site of radiotherapy

Weight bearing

506 (56)

Non-weight bearing

402 (44)

BPI worst pain score at study entry*

< 5 with ≥ 60 mg/day morphine

17 (2)

5 - 6

254 (28)

7 - 10

637 (70)

Receiving biphosphanotes at study entry

688 (76)

Yes

220 (24)

Radiation treatment assignment

8 Gy

460 (49)

30 Gy

448 (51)

**Table 3.** Derivation of Risk Groups From RTOG Validation Set
Prognostic Factor	Parameter Estimate*	Standard Error	Hazard Ratio [95% CI]	P-value	Partial Score	Risk Factor Score
*Cox Proportional Hazards Regression Model
Primary Cancer Site
Breast	0.00		1.00		0	0
Prostate	0.42	0.07	1.52 [1.33, 1.74]	< 0.0001	2	1

Site of metastases
Bone only	—	—	—	—	0	0

Karnofsky Performance Status
> 60	0.00				0	0
≤ 60	0.46	0.08	1.58 [1.35, 1.85]	< 0.0001	2	1
Survival Prediction Score (SPS) [sum of partial scores]	Risk Group A [SPS 0 - 4]
Number of Risk Factors Score (NRF) [sum of risk factors]	Risk Group I [NRF 0 - 1]
	Risk Group II [NRF 2]

Table 3. Derivation of Risk Groups From RTOG Validation Set

Prognostic Factor

Parameter Estimate*

Standard Error

Hazard Ratio [95% CI]

P-value

Partial Score

Risk Factor Score

*Cox Proportional Hazards Regression Model

Primary Cancer Site

Breast

0.00

1.00

Prostate

0.42

0.07

1.52 [1.33, 1.74]

< 0.0001

Site of metastases

Bone only

—

Karnofsky Performance Status

> 60

0.00

≤ 60

0.46

0.08

1.58 [1.35, 1.85]

< 0.0001

Survival Prediction Score (SPS) [sum of partial scores]

Risk Group A [SPS 0 - 4]

Number of Risk Factors Score (NRF) [sum of risk factors]

Risk Group I [NRF 0 - 1]

Risk Group II [NRF 2]

**Table 4.** Summary of Model Performance and Survival Estimates: Partial Score Method
Predictive Model	Training Set	Temporal Validation Set	External Validation Set [Single Institution]	RTOG External Validation Set [Multiple Institutions]
Model Performance
Harrel C index	0.66	0.65	0.63	0.96
Risk Group A
[Survival Prediction Score, 0 - 4]
n (%)	108 (27%)	126 (28%)	65 (14%)	908 (100%)
Median Survival (weeks)	60	53	64	42
95% CI	[41, 70]	[36, 75]	[28, undefined]	[38, 45]
Survival Probabilities
3 months	82%	86%	83%	84%
6 months	70%	72%	64%	66%
9 months	52%	51%	53%	43%

Table 4. Summary of Model Performance and Survival Estimates: Partial Score Method

Predictive Model

Training Set

Temporal Validation Set

External Validation Set [Single Institution]

RTOG External Validation Set [Multiple Institutions]

N = 395

N = 445

N = 467

N = 908

Model Performance

Harrel C index

0.66

0.65

0.63

0.96

Risk Group A

[Survival Prediction Score, 0 - 4]

n (%)

108 (27%)

126 (28%)

65 (14%)

908 (100%)

Median Survival (weeks)

95% CI

[41, 70]

[36, 75]

[28, undefined]

[38, 45]

Survival Probabilities

3 months

82%

86%

83%

84%

6 months

70%

72%

64%

66%

9 months

52%

51%

53%

43%

**Table 5.** Summary of Model Performance and Survival Estimates: Number of Risk Factors Method
Predictive Model	Training Set	Temporal Validation Set	External Validation Set [Single Institution]	RTOG External Validation Set [Multiple Institutions]
*Risk factors include prostate primary tumor and KPS ≤ 60.
Model Performance
Harrel C index	0.65	0.66	0.63	0.94
Royston and Sauerbrei D statistic	1.09	1.08	0.84	0.82
Risk Group I
Number of Risk Factors* ≤ 1
n (%)	98 (25%)	116 (26%)	64 (14%)	812 (89%)
Median Survival (weeks)	60	55	64	45
95% CI	[37, 70]	[37, 91]	[28, undefined]	[41, 51]
Survival Probabilities
3 months	80%	87%	83%	85%
6 months	68%	73%	63%	69%
9 months	53%	54%	53%	46%
Risk Group II
Number of Risk Factors = 2
n (%)	166 (42%)	193 (43%)	189 (40%)	96 (11%)
Median Survival (weeks)	26	19	28	23
95% CI	[20, 31]	[17, 28]	[22, 34]	[17, 31]
Survival Probabilities
3 months	73%	68%	76%	72%
6 months	51%	45%	52%	46%
9 months	26%	23%	25%	19%

Table 5. Summary of Model Performance and Survival Estimates: Number of Risk Factors Method

Predictive Model

Training Set

Temporal Validation Set

External Validation Set [Single Institution]

RTOG External Validation Set [Multiple Institutions]

N = 395

N = 445

N = 467

N = 908

*Risk factors include prostate primary tumor and KPS ≤ 60.

Model Performance

Harrel C index

0.65

0.66

0.63

0.94

Royston and Sauerbrei D statistic

1.09

1.08

0.84

0.82

Risk Group I

Number of Risk Factors* ≤ 1

n (%)

98 (25%)

116 (26%)

64 (14%)

812 (89%)

Median Survival (weeks)

95% CI

[37, 70]

[37, 91]

[28, undefined]

[41, 51]

Survival Probabilities

3 months

80%

87%

83%

85%

6 months

68%

73%

63%

69%

9 months

53%

54%

53%

46%

Risk Group II

Number of Risk Factors = 2

n (%)

166 (42%)

193 (43%)

189 (40%)

96 (11%)

Median Survival (weeks)

95% CI

[20, 31]

[17, 28]

[22, 34]

[17, 31]

Survival Probabilities

3 months

73%

68%

76%

72%

6 months

51%

45%

52%

46%

9 months

26%

23%

25%

19%

**Table 6.** Summary of Patient Characteristics From Two Previous Survival Prediction Investigations
	1999, RRRP (n = 395)	2000, RRRP (n = 445)	2002, PMH (n = 468)
Gender	N (%)	N (%)	N (%)
Male	198 (50%)	243 (56%)	246 (53%)
Female	197 (50%)	202 (45%)	222 (47%)
Age (years)
Median	68	69	66
Range	31 - 93	24 - 93	24 - 91
Primary cancer site
Lung	143 (36%)	132 (30%)	266 (55%)
Breast	80 (20%)	99 (22%)	62 (13%)
Prostate	56 (14%)	70 (16%)	24 (5%)
Others	116 (30%)	144 (32%)	126 (27%)
Weight loss
≥ 10% over the last 6 months	132 (33%)	141 (32%)	108 (23%)
Site of metastases
Bone only	113 (29%)	164 (37%)	80 (17%)
Others	282 (71%)	281 (63%)	388 (83%)
Karnofsky performance score
10 - 20, ECOG 4	2 (0.5%)	2 (0.4%)	32 (7%)
30 - 40, ECOG 3	44 (11%)	56 (13%)	112 (24%)
50 - 60, ECOG 2	163 (41%)	208 (47%)	140 (30%)
70 - 80, ECOG 1	167 (42%)	152 (34%)	160 (34%)
90 - 100, ECOG 0	19 (5%)	27 (6%)	23 (5%)
Median	60	60	2
Range	10 - 100	10 - 100	0 - 4

Table 6. Summary of Patient Characteristics From Two Previous Survival Prediction Investigations

1999, RRRP (n = 395)

2000, RRRP (n = 445)

2002, PMH (n = 468)

Gender

N (%)

Male

198 (50%)

243 (56%)

246 (53%)

Female

197 (50%)

202 (45%)

222 (47%)

Age (years)

Median

Range

31 - 93

24 - 93

24 - 91

Primary cancer site

Lung

143 (36%)

132 (30%)

266 (55%)

Breast

80 (20%)

99 (22%)

62 (13%)

Prostate

56 (14%)

70 (16%)

24 (5%)

Others

116 (30%)

144 (32%)

126 (27%)

Weight loss

≥ 10% over the last 6 months

132 (33%)

141 (32%)

108 (23%)

Site of metastases

Bone only

113 (29%)

164 (37%)

80 (17%)

Others

282 (71%)

281 (63%)

388 (83%)

Karnofsky performance score

10 - 20, ECOG 4

2 (0.5%)

2 (0.4%)

32 (7%)

30 - 40, ECOG 3

44 (11%)

56 (13%)

112 (24%)

50 - 60, ECOG 2

163 (41%)

208 (47%)

140 (30%)

70 - 80, ECOG 1

167 (42%)

152 (34%)

160 (34%)

90 - 100, ECOG 0

19 (5%)

27 (6%)

23 (5%)

Median

Range

10 - 100

0 - 4