Prolonged radiation time and low nadir hemoglobin during postoperative concurrent chemoradiotherapy are both poor prognostic factors with synergistic effect on locally advanced head and neck cancer patients

Figures & data

Table 1 Patient characteristics and treatment outcome

	N=140, number (%)	Overall survival		Disease-free survival		Locoregional control rate
		5-year (%)	P-value*	5-year (%)	P-value*	5-year (%)	P-value*
Age (years)
<50	64 (45.7)	45.8	0.194	37.6	0.185	66.0	0.233
50+	76 (54.3)	57.5		51.1		78.5
Primary tumor site
Oral cavity	106 (75.7)	60.3	0.001	54.1	<0.001	79.1	0.002
Pharynx/larynx	34 (24.3)	26.4		15.1		52.4
Surgical margin
Positive	32 (22.9)	43.8	0.184	31.7	0.064	66.5	0.202
Negative	108 (77.1)	54.6		48.9		75.2
Extracapsular extension
No	120 (85.7)	53.6	0.278	45.4	0.438	73.3	0.612
Yes	20 (14.3)	42.9		45.0		73.7
Pathological T stage
2	36 (25.7)	55.6	0.915	46.3	0.779	67.6	0.470
3–4	104 (74.3)	50.7		44.3		75.6
Pathologic N stage
N0–N2a	69 (49.3)	67.1	<0.001	55.7	0.001	78.7	0.060
≥N2b	71 (50.7)	35.1		34.2		67.3
Histology differentiation
Well moderate	125 (89.3)	52.0	0.572	45.4	0.573	74.8	0.664
Poor	15 (10.7)	53.3		42.7		62.7
Lymphovascular invasion
No	83 (59.3)	59.3	0.045	52.9	0.019	80.8	0.022
Yes	57 (40.7)	41.6		32.4		60.4
Perineural invasion
No	93 (66.4)	52.5	0.697	45.8	0.705	79.1	0.083
Yes	47 (33.6)	51.5		43.7		62.2
OP–RT interval (weeks)
≦6	66 (47.1)	51.1	0.962	47.6	0.667	72.5	0.961
>6	74 (52.9)	53.2		41.0		74.9
RTT (weeks)
≦7	49 (35.0)	64.6	0.039	62.0	0.020	87.2	0.020
>7	91 (65.0)	45.2		36.1		65.5
Pre-op Hb (g/dL)
≦13.0	34 (24.3)	29.1	<0.001	20.7	<0.001	61.4	0.019
>13.0	106 (75.7)	59.5		51.2		77.0
Pre-CCRT Hb (g/dL)
≦13.0	112 (80.0)	49.2	0.151	41.5	0.110	73.1	0.995
>13.0	28 (20.0)	62.6		60.3		74.4
Nadir Hb (g/dL)
≦11.0	82 (58.6)	42.4	0.004	36.6	0.012	70.0	0.224
11.1–12.0	31 (22.1)	61.6		49.1		86.4
>12.0	27 (19.3)	70.6		54.9		61.7
Transfusion status during CCRT**
Not transfused	61 (74.4)	47.3	0.095	41.6	0.166	71.7	0.558
Received transfusion	21 (25.6)	28.6		22.9		64.0

Notes:

* P-value based on the Log-rank test;

** including only 82 patients with Hb ≦11.0 g/dL during CCRT.

Abbreviations: OP–RT interval, interval between operation and radiotherapy; RTT, radiation treatment time; Hb, hemoglobin; pre-op Hb, preoperative hemoglobin – hemoglobin within 1 week before operation; CCRT, concurrent chemoradiotherapy; pre-CCRT Hb, hemoglobin within 1 week before CCRT; nadir Hb, the lowest hemoglobin concentration during CCRT.

Table 2 Association of preoperative hemoglobin level with pathological T, N stage, and primary tumor site

	Pre-op Hb (g/dL)		P-value*
	≦13.0 (N=34), number (%)	>13.0 (N=106), number (%)
Pathological T stage
2	7 (20.6)	29 (27.4)	0.713
3	8 (23.5)	21 (19.8)
4	19 (55.9)	56 (52.8)
Pathological N stage
0	3 (8.8)	32 (30.2)	0.009
1	6 (17.6)	21 (19.8)
2	21 (61.8)	51 (48.1)
3	4 (11.8)	2 (1.9)
Primary tumor site
Oral cavity	21 (61.8)	85 (80.2)	0.029
Pharynx/larynx	13 (38.2)	21 (19.8)

Note:

* P-value based on the chi-square test.

Abbreviation: Pre-op Hb, preoperative hemoglobin – hemoglobin within 1 week before operation.

Figure 1 Kaplan–Meier curve of overall survival according to pre-op Hb level (g/dL) (A), nadir Hb (g/dL) during CCRT (B), and RTT (C).

Abbreviations: pre-op, preoperative; Hb, hemoglobin; CCRT, concurrent chemoradiotherapy; RTT, radiation treatment time.

Table 3 Results of multivariate analysis with regard to overall survival, disease-free survival, and locoregional control rate

	Overall survival			Disease-free survival			Locoregional control rate
	Adj HR	95% CI	P-value*	Adj HR	95% CI	P-value*	Adj HR	95% CI	P-value*
Primary tumor site
Oral cavity	1.0	–		1.0	–		1.0	–
Pharynx/larynx	1.3	0.8–2.3	0.278	1.7	1.0–2.8	0.036	2.1	0.99–4.4	0.053
Pathological N stage
N0–N2a	1.0	–		1.0	–		1.0	–
≧N2b	2.1	1.2–3.7	0.010	1.5	0.9–2.5	0.116	1.1	0.5–2.5	0.867
LVI
No	1.0	–		1.0	–		1.0	–
Yes	1.1	0.6–1.8	0.831	1.3	0.8–2.1	0.314	1.8	0.8–3.9	0.156
RTT (weeks)
≦7	1.0	–		1.0	–		1.0	–
>7	1.9	1.1–3.3	0.022	1.9	1.1–3.2	0.015	3.0	1.2–7.5	0.016
Hb parameter (g/dL)
Pre-op Hb >13.0	1.0	–		1.0	–		1.0	–
Pre-op Hb ≦13.0	1.8	1.1–3.1	0.023	1.9	1.2–3.2	0.010	2.1	0.96–4.4	0.067
Nadir Hb >11.0	1.0	–		1.0	–		1.0	–
Nadir Hb ≦11.0	1.9	1.1–3.3	0.020	1.6	0.95–2.6	0.079	1.2	0.6–2.7	0.573

Note:

* P-value based on the Cox proportional hazards model.

Abbreviations: Adj HR, adjusted hazard ratio; CI, confidence interval; LVI, lymphovascular invasion; RTT, radiation treatment time; pre-op Hb, preoperative hemoglobin – hemoglobin within 1 week before operation; nadir Hb, the lowest hemoglobin concentration during concurrent chemoradiotherapy.

Figure 2 Adverse survival outcome interaction between lower nadir Hb (≦11 g/dL) and the presence of prolonged RTT (>7 weeks) during postoperative CCRT.

Abbreviations: Hb, hemoglobin; RTT, radiation treatment time; CCRT, concurrent chemoradiotherapy.