Role functioning before start of adjuvant treatment was an independent prognostic factor for survival and time to failure. A report from the Nordic adjuvant interferon trial for patients with high-risk melanoma

Figures & data

Table I. Clinical characteristics of 785 patients with information at baseline on any of the studied HRQoL variables.

Patient characteristics	N (%)
Allocated study arm:
A (control)	251 (32)
B (1 year treatment)	264 (34)
C (2 years treatment)	270 (34)
Age at randomization, mean (SD):	52 (18–77)
Sex:
Males	483 (62)
Females	302 (38)
AJJC Stage and positive nodes:
II	149 (19%)
IIIN1	343 (44)
IIIN2–3	187 (24)
IIIN4+	106 (14)
Tumor thickness^1, mean (SD):	3.6 (3.9)

¹For 45 patients, data on tumor thickness is not available.

Table II. Follow-up and number of events among patients included in the HRQoL study.

Characteristics	N (%)
The interferon trial
Recruitment to trial:	1996-11-11 to 2004-09-01
Total number of patients recruited:	855
Date for end of follow-up in the present analyses^1:	2009-10-15
Median follow-up time^2:	7.2 years
The HRQoL studya
Patients included in the study	785
Total number of deaths during follow-up:	400
Total number of events during follow-up:	479

^aNumber of patients with information on any of the studied HRQoL scales at baseline; ¹Last date for visit among patients still alive; ²Calculated using the reversed Kaplan-Meier technique.

Table III. Mean scores and standard deviations (SD) measured at baseline and expected values based on sex- and age-specific values from the normal Swedish population.

Variables	Number of patients	Mean (SD)	Expected
Global Quality of Life^1	771	74 (20)	77
Physical functioning^1	769	88 (20)	91
Role functioning^1	777	67 (32)	86
Emotional functioning^1	769	78 (20)	81
Cognitive functioning^1	771	91 (14)	89
Social functioning^1	765	83 (23)	90
Fatigue^2	768	21 (22)	21
Pain^2	765	10 (12)	19
Dyspnea^2	780	8 (17)	16
Appetite loss^2	783	6 (15)	4
Sleep disturbances^2	782	19 (26)	18

¹High scores indicate high levels of functioning and global quality of life; ²High scores indicate high levels of problems and symptoms.

Table IV. Univariate and multivariate prognostic factor analysis for survival.

	Unadjusted		Adjusted^a		Stepwise^b [backward, p = 0.01]		Bootstrap^c
Variable and coding	HR (99% CI)	p	HR (99% CI)	p	HR (99% CI)	p	Inclusion %
Clinical variables:
Age at randomization, years	1.15 (1.03–1.28)	0.002	1.15 (1.03–1.30)	0.002	1.20 (1.06–1.36)	< 0.001	83.9
Sex (Males vs. Females)	1.13 (0.87–1.48)	0.23	1.14 (0.86–1.50)	0.23			27.1
Stage/nodes (II, IIIN1, IIIN2–3, IIIN4+)	1.35 (1.17–1.55)	< 0.001	1.37 (1.19–1.57)	< 0.001	1.29 (1.12–1.50)	< 0.001	97.7
Thickness (Breslow), mm	1.17 (0.86–1.61)	0.19	1.30 (0.97–1.73)	0.020			19.0
Allocated treatment (B+ C vs. A)	0.86 (0.66–1.12)	0.16	0.85 (0.65–1.13)	0.14			9.5
HRQoL variables:
Global quality of life^d	0.97 (0.91–1.04)	0.27	0.96 (0.90–1.03)	0.14			4.0
Physical functioning^d	0.95 (0.90–1.01)	0.043	0.95 (0.89–1.02)	0.061			1.5
Role functioning^d	0.95 (0.91–0.99)	0.001	0.94 (0.90–0.98)	< 0.001	0.94 (0.90–0.99)	< 0.001	79.0
Emotional functioning^d	0.98 (0.92–1.05)	0.52	0.97 (0.91–1.04)	0.30			1.8
Cognitive functioning^d	0.98 (0.90–1.07)	0.62	0.98 (0.90–1.07)	0.55			4.1
Social functioning^d	0.96 (0.91–1.01)	0.039	0.95 (0.89–1.0)	0.016			2.5
Fatigue^e	1.03 (0.97–1.09)	0.18	1.05 (0.98–1.11)	0.071			5.9
Pain^e	1.08 (0.97–1.20)	0.064	1.08 (0.97–1.21)	0.060			2.2
Dyspnea^e	1.04 (0.97–1.11)	0.20	1.04 (0.97–1.12)	0.19			2.0
Appetite loss^e	1.03 (0.95–1.12)	0.37	1.06 (0.98–1.16)	0.069			3.3
Sleep disturbances^e	1.01 (0.96–1.06)	0.81	1.01 (0.96–1.06)	0.74			5.4

Note: HRs for age thickness and all HRQoL variables refers to a 10-unit increase. CI, confidence interval; HR, hazard ratio; HRQoL, health related quality of life. ^aEach of the clinical variables are adjusted for all the other clinical variables but ignoring the HRQoL variables. Each of the HRQoL variables are adjusted for all the clinical variables but ignoring the other HRQoL variables (i.e. the effect of the studied HRQoL variable on top of all the clinical variables); ^bStepwise model with backward-selection search. All the variables with a significance level < 0.01 remain in the final model. Estimation is based on observations with non-missing values for all specified variables; ^cTo assess the replication stability of the Stepwise model a bootstrap resampling procedure proposed by Sauerbrei et al. was used. This technique generates a number of samples (1000) each of the same size as the original data, by random sampling with replacement from the original data set. The frequency of inclusion is indicative for the prognostic importance of the factors; ^dHigh values indicate high level of functioning and global quality of life; ^eHigh values indicate high levels of problems and symptoms.

Table V. Univariate and multivariate prognostic factor analysis for time to recurrence.

	Unadjusted		Adjusted^a		Stepwise^b [backward, p = 0.01]		Bootstrap^c
Variable and coding	HR (99% CI)	p	HR (99% CI)	p	HR (99% CI)	p	Inclusion %
Clinical variables:
Age at randomization, years	1.09 (0.98–1.21)	0.032	1.09 (0.98–1.21)	0.040	1.14 (1.02–1.28)	0.003	55.7
Sex (Males vs. Females)	1.10 (0.86–1.41)	0.31	1.10 (0.85–1.42)	0.33			33.3
Stage/nodes (II, IIIN1, IIIN2–3, IIIN4+)	1.27 (1.11–1.44)	< 0.001	1.28 (1.12–1.46)	< 0.001	1.23 (1.07–1.40)	< 0.001	90.2
Thickness (Breslow), mm	1.17 (0.89–1.53)	0.14	1.26 (0.98–1.62)	0.018			28.0
Allocated treatment (B+ C vs. A)	0.80 (0.62–1.03)	0.020	0.79 (0.61–1.02)	0.016			37.0
HRQoL variables:
Global Health^d	0.96 (0.90–1.01)	0.047	0.94 (0.88–1.00)	0.008			2.4
Physical functioning^d	0.94 (0.89–0.99)	0.003	0.93 (0.87–0.99)	0.002			7.8
Role functioning^d	0.94 (0.91–0.98)	< 0.001	0.94 (0.90–0.97)	< 0.001	0.94 (0.90–0.98)	< 0.001	84.9
Emotional functioning^d	0.97 (0.92–1.03)	0.19	0.96 (0.90–1.02)	0.068			2.6
Cognitive functioning^d	0.99 (0.92–1.08)	0.83	0.99 (0.91–1.08)	0.73			12.1
Social functioning^d	0.96 (0.91–1.00)	0.017	0.94 (0.89–0.99)	0.004			2.0
Fatigue^e	1.04 (0.99–1.10)	0.046	1.06 (1.00–1.12)	0.010			5.2
Pain^e	1.08 (0.99–1.19)	0.031	1.10 (1.00–1.22)	0.014			3.9
Dyspnea^e	1.06 (1.00–1.13)	0.017	1.06 (1.00–1.13)	0.016			7.8
Appetite loss^e	1.05 (0.97–1.13)	0.10	1.07 (1.00–1.16)	0.015			2.4
Sleep disturbances^e	1.02 (0.97–1.06)	0.38	1.02 (0.97–1.07)	0.27			1.8

Note: HRs for age thickness and all HRQoL variables refers to a 10-unit increase. CI, confidence interval; HR, hazard ratio; HRQoL, health related quality of life. ^aEach of the clinical variables are adjusted for all the other clinical variables but ignoring the HRQoL variables. Each of the HRQoL variables are adjusted for all the clinical variables but ignoring the other HRQoL variables (i.e. the effect of the studied HRQoL variable on top of all the clinical variables). ^bStepwise model with backward-selection search. All the variables with a significance level < 0.01 remain in the final model. Estimation is based on observations with non-missing values for all specified variables; ^cTo assess the replication stability of the Stepwise model a bootstrap resampling procedure proposed by Sauerbrei et al. was used. This technique generates a number of samples (1000) each of the same size as the original data, by random sampling with replacement from the original data set. The frequency of inclusion is indicative for the prognostic importance of the factors; ^dHigh values indicate high level of functioning and global quality of life; ^eHigh values indicate high levels of problems and symptoms.

Unadjusted analysis: N = 740–785. Adjusted analysis: N = 719–740. Stepwise and Bootstap: N = 678.

Figure 1. Interaction between treatment and cognitive functioning in the survival analysis.