Volumetric staging (VS) is superior to TNM and AJCC staging in predicting outcome of head and neck cancer treated with IMRT

Figures & data

Table I.  Patient characteristics in the assessed IMRT cohort (n = 172).SIB-IMRT = Intensity modulated radiation therapy using simultaneously integrated boost, NPC = nasopharyngeal cancer, PNS = paranasal sinus cancer, GTV = Gross Tumor Volume, FU = Follow-Up.

Characteristics	n patients	%
N patients	172	100
Sex (M:F)	139:33
Mean age (years)	59
WHO PS
0	133	77
1	35	20
2	4	2
SIB-IMRT	172	100
Chemotherapy	129	75
T stage
T1	12	7
T2	57	33
T3	35	20
T4	53	31
Recurrence	15	7
Nstage
N0	42	24
N1	24	14
N2a	8	5
N2b	47	27
N2c	47	27
N3	4	2
AJCC Stages
I	2	1
II	15	7
III	25	14
IVA	110	64
IVB	5	3
Recurrence	15	7
HNC entity
Oropharynx	69	40
Oral Cavity	19	11
Hypopharynx	38	22
NPC	23	13
PNS	8	5
Supraglottic	15	7
GTV mean, cc
Primary GTV	38
Nodal GTV	15
Total GTV	58
FU mean, months	17

Table IIa.  Three prognostic groups were defined for the volumetric staging (VS), the TN classification, and the AJCC (number of patients in parenteses). The cut-off values are the same when used for the primary gross tumor volumes (PGTV) as for the total gross tumor volumes (TGTV).

	Staging Systems
	VS (n PGTV, n TGTV)	T(n)	N(n)	AJCC(n)
Favourable	1–15 cc (54, 30)	T1/2 (69)	No (42)	I–III (42)
Intermediate	>15–70 cc (89, 100)	T3 (35)	N1-2b (79)	IVA (110)
Unfavourable	>70 cc (29, 42)	T4, rec (68)	N2c, 3 (51)	IVB, rec (20)

Table IIb.  Primary gross tumor volume (PGTV) and total gross tumor volume (TGTV) employed to predict local, nodal, distant disease free survival, and disease free survival, respectively. For both PGTV and TGTV the same two cut-off values (15 and 70 cm³) were used to define three prognostic groups.

Volumes	Outcome
PGTV (cut-off values 15 and 70 cc)	→ local control
TGTV (cut-off values 15 and 70 cc)	→ nodal and distant control, disease free survival

Table III.  Distribution of the T stages in the volumetric staging system (VS) based on primary gross tumor volume (PGTV).

T distribution	Volumetric staging system (PGTV based)
	favourable (54)	intermediate (89)	unfavourable (29)
T1	9	3	0
T2	33	23	1
T3	1	31	3
T4	5	24	24
Recurrence	6	8	1

Table IV.  Logrank (Mantel-Cox) p-values of Kaplan-Meier survival curves for local control (LC), disease free survival (DFS), distant control (DC), and nodal control (NC) in the tested subgroups, using the TNM classification, the AJCC staging, and the volumetric staging (VS) system.

	LC		DFS		DC		NC
Sub groups (n)	VS	T/AJCC	VS	T/AJCC	VS	T/AJCC	VS	N/AJCC
Retrospective (88/172)	0.016	NS	0.018	NS	–	–	–	–
Prospective (84/172)	0.006	NS	0.002	NS	–	–	–	–
Pooled (172)	0.0001	NS	0.007	NS	<0.0001	NS	0.04	0.027/NS
Oropharynx 85/172	0.0003	NS	0.01	NS	–	–	0.02	–
Loc advanced* (127/172)	0.002	–	0.04	–	0.007	NS	–	–

*subgroup with locally advanced tumors, including T3-4, and any T N2c-3 stages as well as patients with recurrent tumors.

Figure 1.  Actuarial disease free survival curves, based on the volumetric staging (VS; n = 172, 44 events, p = 0.007), using the total gross tumor volume (TGTV, volume of the primary and the nodes).

Figure 2.  Actuarial local disease free survival curves, based on the volumetric staging (VS; n = 172, 36 events, p = 0.0001), using the primary gross tumor volume (PGTV).

Figure 3.  Actuarial local disease free survival curves in oropharyngeal tumors, based on the volumetric staging (VS; n = 85, 11 events, p = 0.0003), using the primary gross tumor volume (PGTV).

Table V.  Approximative actuarial 2 year disease control rates for patients with favourable, intermediate and unfavourable tumor volumes. LC = local control, NC = nodal control, DC = distant control, DFS = disease free survival, OAS = overall survival.

	Total Gross Tumor Volume (TGTV)
Actuarial	1–15cc	>15–70 cc	>70 cc
2-y LC*	95%*	70%*	50%*
2-y NC	95%	90%	75%
2-y DC	99%	99%	60%
2-y DFS	90%	70%	50%
2-y OAS	95%	90%	70%

Figure 4.  Actuarial nodal disease free survival curves, based on the volumetric staging (VS; n = 172, 20 events, p = 0.04), using the total gross tumor volume (TGTV).

Figure 5.  Actuarial distant disease free survival curves, based on the volumetric staging (VS; n = 172, 15 events, p < 0.0001), using the total gross tumor volume (TGTV).

Figure 6.  Actuarial local disease free survival in T3-4, or any T N2c-3, and recurrent patients, stratified according to the volumetric staging (VS, n = 127, 33 events, p = 0.002), using the primary gross tumor volume (PGTV).

Table VI.  On literature on head and neck cancer (HNC) outcome prediction based on volumetric classifications. N is the number of analysed HNC patients (soft pal = soft palate, ant/post tons pil = anterior/posterior tonsillar pillar, hypo = hypopharyngeal tumor, OC = oral cavity tumor, oro: oropharyngeal tumor, NPC = nasopharyngeal tumor, RT = radiotherapy, CT = chemotherapy, 3DCRT = three-dimensional conventional radiotherapy, IMRT = intensity modulated radiation therapy, PGTV = primary gross tumor volumes, NI: not indicated, “–“ = no value, TGTV = total gross tumor volume, LC = local control,OS = overall survival.

Author [ref]	year	HNC entity	N	Stages	Treatment	RT technique	mean PGTV (cc)	cut-off value	p-value LC	p-value OS
Mendenhall et al. [2]	2003	soft pal/ supragl/ glottic/ant tons pil	12/114/55/37	T1-4	RT(-CT)	3DCRT	5/12/8/3/12	6	<0.05
Mendenhall ∣2]	2003	hypo/BoT/tonsil + post tons pil	45/72/69	T1-4	RT(-CT)	3DCRT	6/24/18	6	NS
Pameijer et al. [3]	1998	pyrifrom sinus	23	T1/2	RT	3DCRT	N1	6.5	0.021
Keberle et al. [4]	2004	Hypo	45	pT1-4	S(-RT)	3DCRT	8.1	8.1	0.004
Plataniotis et al. [13]	2004	OC/Oro/Hypo/ Larynx	101	lll-IV	RT(-CT)	3DCRT	17/13/22.6/14.8 median TGTV	22.8		0.01
Grabenbauer et al. [14]	1998	OC/Oro/Hypo/ Larynx	87	lll-IV	RT(-CT	3DCRT	median 110ml	110		0.0001
Rudat et al. [19]	1999	OC/Oro/Hypo/ Larynx	68	T2-4	RT-CT	3DCRT	median 112 TGTV	112	0.0008
Mukherji et al. [5]	2000	supraglottic	37	pT1-4	S(-RT)	3DCRT	9.3	16	0.04
Freeman et al. [21]	1990	supraglottic	31	T1-4	RT	3DCRT	Nl	6	0.038
Gilbert et al. [6]	1987	Larynx	37	T2-4	RT	3DCRT	21.8* vs 8.9*	–		0.02
Lee et al. [7]	1993	glottic	29	T3	RT	3DCRT	Nl	3.5	0.02
Pameijer et al. [8]	1997	glottic	42	T3	RT	3DCRT	Nl	3.5	0.0002
Chua et al. [9]	1997	NPC	290	T1-3	RT(-CT)	3DCRT	6.9/18.8/52.4 in T1,2,3	20 / >60	<0.05
Nathu et al. [22]	2000	oro	114	T2-4	RT(-CT)	3DCRT	6.8/14.8/42.6 in T2,3,4	N1	NS
Keberle et al. [23]	2003	oro	80	PT1-4	S(-RT)	3DCRT	median 4.7	Nl	NS
Hermans et al. [10]	2001	oro	112	T1-4	RT	3DCRT	3.1/10.6/14.5/44.9 in T1-4	6/14.5/31	0.047	NS
Chao et al. [11]	2004	oro	31	l-IV	RT(-CT)	IMRT	30.5	Nl	0.05
Present study	2006	oro	85	T1-4	RT(-CT)	IMRT	34	15/70	<0.001
Present study	2006	all except larynx	172	T1-4	RT(-CT)	IMRT	37.7	15/70	<0.02
Doweck et al. [20]	2002	all	64	lll-IV	RT-CT	3DCRT	35.4	19.6		0.0018
Johnson et al. [15]	1995	all	51	advanced	RT	3DCRT	median 35 TGTV	35	0.0001
Kurek et al. [16]	2003	all	107	T1-4	RT(-CT)	3DCRT	median 32.5 and 44.4	Nl		0.02

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