IMRT dose fractionation for head and neck cancer: Variation in current approaches will make standardisation difficult

Figures & data

Figure 1.  Calculation of Acute Mucosal BED

Table I.  IMRT dose fractionation reported in survey.

			CTV1			CTV2			CTV3
Schedule type		Weeks	Dose (Gy)	Fraction	Gy per fraction	Dose (Gy)	Fraction	Gy per fraction	Dose (Gy)	Fraction	Gy per fraction
	Conventional 2Gy per fraction
1	Prof J Bernier, Switzerland	6.5–7	70–72	35–36	2	54–60	35	1.5–1.7	50	25	2
	Prof V Gregoire, Belgium	7	70	35	2	–	–	–	50	25	2
	Prof A Eisbruch, USA	7	72	35	2	64	35	1.8	60	35	1.7
	Modest Acceleration
2	Prof P Levendag, Netherland	6	70	35	2	–	–	–	46	23	2
	Prof K Ang/ Dr A Ahamad, USA	6	70	35	2	56	35	1.6	50	25	2
	Prof C Grau, Denmark	5.5	66–68	33–34	2	60	33–34	1.8	50	33–34	1.5
	Continuous Acceleration
3	Prof B Maciejewski, Poland #	6	72	40	1.8	70	40	1.8	50	40	1.25
	Concomitant Boost
4	Prof W Mendenhall, USA	6	72	42	1.5–1.8	–	–	–	49.5–54	30	1.7–1.8
	[11]>2Gy per fraction
5	Prof P Harari, USA	6.5	70	33	2.1	60–66	33	1.8–2	54	33	1.63
6	Dr C Nutting, UK #	6	65	30	2.2	–	–	–	54	30	1.8
7	Prof J Bourhis, France	7	70–75	35	2.1	–	–	–	50	25	2
	Dose Escalated Hypofractionation
8	Dr H Shirato, Japan	6	74	30	2.5	68	30	2.3	60	30	2
9	Prof W De Neve, Belgium	6.5	72.5–77.5	32	2.5–3.0	62–65.9	32	1.9–2.1	56	32	1.75
10	Dr C Nutting, UK #	5.5	63–67.2	28	2.3–2.4	–	–	–	51.8	28	1.85
11	Dr N Slevin, UK	5	62.5–65	25–26	2.5	55–57.5	25–26	2.2–2.3	50	25–26	2
	Hyperfractionation
12	Prof B Maciejewski, Poland #	4	64	40	1.6	–	–	–	50	40	1.25

# Uses 2 IMRT schedules.

Figure 2.  Two vs Three target volume delineation

Table II.  Radiobiological comparison of schedules.

	Mean Dose to CTV1	Tumour BED (Gy10)	Tumour Log10 cell kill	Acute Mucosal BED (<61Gy10)	Late Tissue BED (<117Gy3)	Systemic Concurrent Treatment
De Neve	77.5Gy/32f (DL2)	82.2	12.5	68.3	141.7	Cisplatin
Shirato	74Gy/30f	80.4	12.2	66.9	134.8	Cisplatin
Bourhis	70–75Gy/35f	74.6	11.3	60.2	128.6	Cisplatin
De Neve	72.5Gy/32f (DL1)	74.5	11.3	60.5	131.0	Cisplatin
Maciejewsk i#	72Gy/40f	73.1	11.1	58.8	115.2	None
Nutting #	67.2Gy/28f (DL2)	72.8	11.1	58.8	121	Cisplatin
Mendenhall	72Gy/42f	72.5	11.0	59.1	113.4	Cisplatin
Levendag	70Gy/35f	72.1	11.0	58.7	116.7	Cisplatin
Ang/Ahamad						Cisplatin+/− Cetuximab
Slevin	65Gy/26f (DL2)	72.0	10.9	59.1	119	Cetuximab
Maciejewski #	64Gy/40f	71.6	10.9	59.9	98.1	None
Slevin	62.5Gy/25f (DL1)	70.9	10.8	58.3	114.6	Cetuximab
Grau	68Gy/34f	70.4	10.7	57	113.3	Nimorazole/Cisplatin
Harari	70Gy/33f	69.7	10.6	55.5	119.5	Cisplatin
Bernier	72Gy/36f	67.9	10.3	53.1	120	Cisplatin
Gregoire	70Gy/35f	67.5	10.3	53.1	117	Carboplatin/ 5FU
Eisbruch						Carboplatin/ Paclitaxel
Nutting #	65Gy/30f	67.2	10.2	53.7	111.8	None
Nutting #	63Gy/28f (DL1)	66.6	10.1	53.4	110.3	Cisplatin

DL1: Dose Level 1.

DL2: Dose Level 2.

# Uses 2 IMRT schedules.

Table III.  Acute mucosal tolerance factors.

	Acute Mucosal BED (<59–61Gy10)	Systemic Concurrent Treatment	Intermediate target volume	Margin from GTV to CTV1
De Neve	68.3	Cisplatin	Yes	Compartment
Shirato	66.9	Cisplatin	Yes	5mm
Bourhis	60.2	Cisplatin	No	Variable
Maciejewski #	59.9	None	No	1–1.5cm
Mendenhall	59.1	Cisplatin	No	1cm
Slevin	59.1	Cetuximab	Yes	≥0.5cm
Maciejewski #	58.8	None	Yes	1–1.5cm
Nutting #	58.8	Cisplatin	No	1–2cm
Levendag	58.7	Cisplatin	No	5mm
Ang/Ahamad	58.7	Cisplatin +/− Cetuximab	Yes	1cm
Grau	57	Cisplatin/Nimorazole	Yes	Variable
Harari	55.5	Cisplatin	Yes	3mm
Nutting #	53.7	None	No	1–2cm
Bernier	53.1	Cisplatin	Yes	5mm
Gregoire	53.1	Carboplatin/5FU	No	Compartment
Eisbruch	53.1	Carboplatin/Paclitaxel	Yes	1–2cm

# Uses 2 IMRT schedules.