Does transfusion improve the outcome for HNSCC patients treated with radiotherapy? – Results from the randomized DAHANCA 5 and 7 trials

Figures & data

Figure 1. Study flow chart.

Table I. Patient and tumor characteristics.

Parameter		LowHb-transf		LowHb + transf		HighHb		All patients	p-value (low/high)	p-value (low +/−t)
Study/treatment^$	DAHANCA 5	89	39%	82	35%	243	35%	414
	DA5Pc5fx	45	20%	34	14%	116	17%	195	0.5*	0.4*
	DA5NiSx	44	19%	48	20%	127	18%	21S
	DAHANCA 7	141	61%	153	65%	458	65%	752
	DA7Ni5fx	68	30%	79	34%	222	32%	369	0.8^#	0.5^#
	DA7Ni6fx	73	32%	74	31%	236	34%	383
Age	< 60 years	115	50%	106	45%	375	53%	596	0.05	0.3
	> 60 years	115	50%	129	55%	326	47%	570
Gender	Female	35	15%	40	17%	226	32%	301	< 0.001	0.6
	Male	195	85%	195	83%	475	68%	865
Hb level median (range)	Female	12.1 (10.6–12.7)		12.2 (8.7–12.7)		13.8 (12.9–18.4)		13.5	< 0.001	0.3
	Male	13.7 (10.0–14.3)		13.4 (6.6–14.3)		15.1 (14.5–18.2)		144	< 0.001	0.6
Site	Oral cavity	21	9%	21	9%	83	12%	125
	Supraglottis	55	24%	57	24%	217	31%	329	0.004	1.0
	Pharynx	154	67%	157	67%	401	57%	712
HPV status	positive	51	22%	39	17%	134	19%	224	0.9	0.1
	neg + UK	179	73%	196	83%	567	81%	942
T-classification	T1 + T2	102	44%	104	44%	395	56%	601	< 0 001	1.0
	T3 + T4	128	56%	131	56%	306	44%	565
N-classification	N0	98	43%	93	42%	349	50%	545	0.01	0.8
	N^+	132	57%	137	58%	352	50%	621
Stage	I + II	43	19%	49	21%	200	29%	292	0.001	0.6
	III + IV	187	81%	186	79%	501	71%	874
Transfusion during RT	None	0	0%	154	66%	0	0%	154	No value	No value
	≥1	0	0%	81	34%	0	0%	81
Treatment	Nimorazole	185	80%	201	86%	585	83%	971	0.8	0.1
	Placebo	45	20%	34	14%	116	17%	195
	5 fx/week	157	68%	161	69%	465	66%	783	0.5	1.0
	6 fx/week	73	32%	74	31%	236	34%	383
Total		230		235		701		1166

^$Treatment groups:

1: DAHANCA 5, placebo, 5 fx/week (DA5Pc5fx)

2: DAHANCA 5, nimorazole, 5 fx/week (DA5Ni5fx)

3: DAHANCA 7, nimorazole, 5 fx/week (DA7Ni5fx)

4: DAHANCA 7, nimorazole, 6 fx/week (DA7Ni6fx)

*comparing difference between DAHANCA 5 and DAHANCA 7

^#comparing difference between the four treatment groups (DA5Pc5fx, DA5Ni5fx, DA7Ni5fx and DA7Ni6fx)

Figure 2. Time of transfusions.

Figure 3. Hemoglobin level during radiotherapy treatment as a function of hemoglobin group.

Figure 4. Locoregional control (a), disease-specific (b) and overall survival (c) probability curves (Kaplan-Meier method) according to hemoglobin group.

Table II. Univariate and multivariate analysis.

		Locoregional Control			Disease-Specific Survival			Overall Survival
Univariate parameter		HR	CI	p-value	HR	CI	p-value	HR	CI	p-value
Age	>60 vs <60	1.09	(0.92–1.29)	0.3	1.10	(0.92–1.30)	0.3	1.23	(1.07–1.42)	0.004
Gender	female vs male	0.77	(0.63–0.94)	0.009	0.78	(0.63–0.96)	0.02	0.78	(0.66–0.92)	0.004
Site	Supraglottic vs pharynx	0.79	(0.64–0.96)	0.02	0.58	(0.47–0.72)	<0.001	0.71	(0.60–0.84)	0.0001
	Oral cavity vs pharynx	1.43	(1.11–1.85)	0.005	1.12	(0.86–1.46)	0.4	1.06	(0.84–1.33)	0.6
	Supraglottic oral cavity	0.55	(0.41–0.73)	<0.001	0.52	(0.38–0.71)	<0.001	0.67	(0.52–0.86)	0.002
HPV status	pos vs neg+UK	0.51	(0.40–0.65)	<0.001	0.38	(0.28–0.50)	<0.001	0.46	(0.37–0.57)	<0.001
T-classification	Tl + T2 vs T3 + T4	0.60	(0.51–0.71)	<0.001	0.60	(0.51–0.72)	<0.001	0.67	(0.58–0.78)	<0.001
N-classification	N0 vs N+	0.59	(0.50–0.70)	<0.001	0.49	(0.41–0.59)	<0.001	0.65	(0.56–0.75)	<0.001
Stage	I + II vs III + IV	0.55	(0.44–0.68)	<0.001	0.49	(0.38–0.61)	<0.001	0.68	(0.57–0.81)	<0.001
Treatment	DA5Pc5fx vs DA5Ni5fx	1.43	(1.10–1.86)	0.007	1.32	(1.00–1.74)	0.05	1.04	(0.82–1.32)	0.7
	DA7Ni5fx vs DA5Ni5fx	1.01	(0.79–1.29)	0.9	1.06	(0.83–1.36)	0.6	1.00	(0.81–1.22)	1.0
	DA7Ni6fx vs DA5Ni5fx	0.81	(0.63–1.04)	0.1	0.84	(0.65–1.09)	0.2	0.91	(0.74–1.12)	0.4
Hemoglobin level	High vs low all	0.83	(0.70–0.98)	0.03	0.77	(0.64–0.91)	0.003	0.77	(0.67–0.89)	0.0004
	High vs low−t	0.85	(0.69–1.06)	0.1	0.87	(0.69–1.09)	0.2	0.86	(0.71–1.04)	0.1
	Low+t vs low−t	1.06	(0.82–1.38)	0.7	1.27	(0.97–1.65)	0.1	1.24	(0.99–1.54)	0.08
Transfusion during radiotherapy		1.14	(0.78–1.67)	0.5	1.35	(0.94–1.95)	0.1	1.18	(0.86–1.61)	0.3

		Locoregional Control			Disease-Specific Survival			Overall Survival
Univariate parameter		HR	CI	p-value	HR	CI	p-value	HR	CI	p-value
Age	>60 vs <60	1.10	(0.93–1.30)	0.3	1.11	(0.93–1.33)	0.2	1.24	(1.07–1.44)	0.004
Gender	female vs male	0.84	(0.68–1.03)	0.1	0.87	(0.71–1.08)	0.2	0.84	(0.70–1.00)	0.05
Site	Supraglottic vs pharynx	0.89	(0.72–1.09)	0.3	0.68	(0.54–0.86)	0.001	0.75	(0.63–0.90)	0.002
	Oral cavity vs pharynx	1.71	(1.30–2.25)	<0.001	1.27	(0.96–1.68)	0.1	1.07	(0.84–1.36)	0.6
	Supraglottic vs oral cavity	0.51	(0.38–0.70)	<0.001	0.54	(0.39–0.74)	<0.001	0.7	(0.54–0.92)	0.009
HPV status	pos vs neg + UK	0.53	(0.41–0.68)	<0.001	0.36	(0.27–0.49)	<0.001	0.45	(0.36–0.56)	<0.001
T-classification	Tl +T2 vsT3 +T4	0.63	(0.54–0.76)	<0.001	0.65	(0.54–0.77)	<0.001	0.72	(0.62–0.83)	<0.001
N-classification	N0 vs N^+	0.57	(0.47–0.68)	<0.001	0.49	(0.41–0.60)	<0.001	0.64	(0.55–0.74)	<0.001
Treatment	DA5Pc5fx vs DA5Ni5fx	1.37	(1.05–1.78)	0.02	1.22	(0.92–1.60)	0.2	0.99	(0.78–1.26)	0.9
	DA7Ni5fx vs DA5Ni5fx	0.88	(0.68–1.13)	0.3	0.91	(0.71–1.19)	0.5	0.91	(0.74–1.13)	0.4
	DA7Ni6fx vs DA5Ni5fx	0.74	(0.57–0.96)	0.03	0.83	(0.63–1.08)	0.2	0.92	(0.74–1.14)	0.4
Hemoglobin level	High vs low all*	0.92	(0.77–1.11)	0.4	0.86	(0.72–1.03)	0.1	0.85	(0.73–0.99)	0.04
	High vs low−t	0.93	(0.74–1.15)	0.5	0.93	(0.73–1.17)	0.5	0.91	(0.75–1.10)	0.3
	Low+t vs low−t	1.00	(0.77–1.29)	1.0	1.15	(0.88–1.50)	0.3	1.14	(0.91–1.43)	0.2

*When including the high vs. low all parameter in the multivariate model the other parameters HRs are only slightly different from this analysis, which is based on a multivariate model including all three hemoglobin groups. P-values are the same.