Timing of radiotherapy and chemotherapy start for patients treated with definitive concurrent chemoradiation for head and neck cancer

Figures & data

Table 1. Patient baseline characteristics by concordant day of start of chemo and radiation therapy or discordant.

(Median, IQR) for continuous data	Total N = 131	Same day N = 62	Different day N = 69	p Value
Age	58 (52, 64)	58.5 (53, 65)	58 (52, 63)	0.37
Gender				0.40
Female	29 (22.1)	16 (25.8)	13 (18.8)
Male	102 (77.9)	46 (74.2)	56 (81.2)
BMI	26.8 (24.0, 32.1)	26.6 (23.8, 32.4)	27.4 (24.1, 31.7)	0.98
ECOG				0.84
0	34 (25.9)	15 (24.2)	19 (27.5)
1	88 (67.2)	42 (67.7)	46 (66.7)
2	9 (6.9)	5 (8.1)	4 (5.8)
Charlson comorbidity index	2 (0, 3)	2 (0, 3)	1 (1, 3)	0.54
Charlson comorbidity index (collapsed)
0	36 (28.3)	20 (33.3)	16 (23.9)	0.14
1	27 (21.3)	8 (13.3)	19 (28.4)
2	24 (18.9)	14 (23.3)	10 (14.9)
3+	40 (31.5)	18 (30.0)	22 (32.8)
Smoking history				0.16
Never	30 (22.9)	10 (16.1)	20 (29.0)
Former	58 (44.3)	32 (51.6)	26 (37.7)
Current	43 (32.8)	20 (32.3)	23 (33.3)
Smoking history ≥ 10 pack-years				0.25
No	40 (31.5)	16 (26.2)	24 (36.4)
Yes	87 (68.5)	45 (73.8)	42 (63.6)
Alcohol use				0.86
No	79 (60.3)	38 (61.3)	41 (59.4)
Yes	52 (39.7)	24 (38.7)	28 (40.6)
Primary site				0.27
Nasopharynx	9 (6.9)	1 (1.6)	8 (11.6)
Oropharynx	84 (64.1)	41 (66.1)	43 (62.3)
Oral Cavity	2 (1.5)	1 (1.6)	1 (1.4)
Larynx	30 (22.9)	16 (25.8)	14 (20.3)
Hypopharynx	4 (3.1)	2 (3.2)	2 (2.9)
Unknown primary	2 (1.5)	1 (1.6)	1 (1.4)
Clinical T Stage (AJCC 7^th)				0.51
T0	2 (1.5)	1 (1.6)	1 (1.5)
T1	10 (7.6)	7 (11.3)	3 (4.3)
T2	46 (35.1)	19 (30.7)	27 (39.1)
T3	37 (28.2)	20 (32.3)	17 (24.6)
T4a	27 (20.6)	12 (19.3)	15 (21.7)
T4b	9 (6.9)	3 (4.8)	6 (8.7)
Clinical N Stage (AJCC 7^th)				0.22
N0	16 (12.2)	7 (11.3)	9 (13.0)
N1	16 (12.2)	5 (8.1)	11 (15.9)
N2	3 (2.3)	0	3 (4.3)
N2a	3 (2.3)	0	3 (4.3)
N2b	35 (26.7)	18 (29.0)	17 (24.6)
N2c	51 (38.9)	28 (45.2)	23 (33.3)
N3	6 (4.6)	3 (4.8)	3 (4.3)
N3b	1 (0.8)	1 (1.6)	0
HPV status (Oropharynx)				0.22
Positive	65 (83.3)	31 (81.6)	34 (85.0)
Negative	13 (16.7)	7 (18.4)	6 (15.0)

Data presented as number (%) unless otherwise specified. % may not total to 100 due to rounding.

Table 2. Summary of treatment characteristics.

(Median, range) on continuous variables	Total	Same day	Different day
	N = 131	N = 62	N = 69	p Value
RT dose	70 (64, 70)	70 (64, 70)	70 (64, 70)	0.43
RT fractions	35 (32, 35)	35 (32, 35)	35 (32, 35)	0.43
RT neck target				0.62
Unilateral	4 (3.1)	1 (1.6)	3 (4.4)
Bilateral	127 (96.9)	61 (98.4)	66 (95.6)
RT modality				0.87
IMRT/VMAT	120 (91.6)	56 (90.3)	64 (92.8)
3 D/IMRT	9 (6.9)	5 (8.1)	4 (5.8)
3 D	2 (1.5)	1 (1.6)	1 (1.4)
Chemotherapy regimen				0.60
Weekly cisplatin HDC	79 (60.3)	39 (62.9)	40 (58.0)
Every 3 weeks	52 (39.7)	23 (37.1)	29 (42.0)
Cumulative cisplatin dose (mg/m^2)	240 (40, 300)	245 (40, 300)	232 (40, 300)	0.34
Modality delivered first
RT first	80 (61.1)	28 (45.2)	52 (75.4)
Chemo first	51 (38.9)	34 (54.8)	17 (24.6)	0.0006

Data presented as number (%) unless otherwise specified. % may not total to 100 due to rounding.

Figure 1. Kaplan–Meier plot of locoregional control by chemotherapy first versus radiotherapy first (A) and by same day versus different day start (B).

Table 3. Univariable and multivariable proportional hazards on locoregional control.

	Univariable hazard ratio (95% CI)	Multivariable hazard ratio (95% CI)^a
Chemotherapy started first (versus radiation therapy)	0.33 (0.11, 0.998)	0.31 (0.10, 0.93)
Concurrent chemotherapy (bolus versus weekly)	1.73 (0.73, 4.08)	1.93 (0.81, 4.57)
Age (per 5 years)	1.08 (0.84, 1.39)	–
Gender (Female vs Male)	1.21 (0.47, 3.11)	–
ECOG	1.55 (0.64, 3.75)	–
Charlson comorbidity (per 1 unit)	0.97 (0.75, 1.25)	–
Stage IVA vs III	2.11 (0.49, 9.17)	–
IVB vs III	2.39 (0.33, 16.9)
Modalities started same day (Y vs N)	0.68 (0.28, 1.65)	–
Modalities started within 24 h (Y vs N)	1.28 (0.52, 3.18)	–
Chemoradiation started on M/TW (Y vs N)	0.90 (0.30, 2.70)	–

Variables entered in the univariable model included: age, gender, ECOG, Charlson comorbidity, stage, chemotherapy started first, modalities started same day, modalities started within 24 h, chemoradiation started on M/T/W (vs Th/F), concurrent chemotherapy (bolus vs weekly).

^aThese are the variables with p < 0.20 after stepwise elimination.

Figure 2. Kaplan–Meier plot of progression-free survival (A) and overall survival (B).

Data availability statement

The data that support the findings of this study are available from the corresponding author, Cole R Steber, upon reasonable request.