Early volume variation of positive lymph nodes assessed by in-room mega voltage CT images predicts risk of loco-regional relapses in head and neck cancer patients treated with intensity-modulated radiotherapy

Figures & data

Table I. Main patient and tumor characteristics.

Number of patients	27
Sex	M: 18; F: 9
Age	Median: 53.7 y; range: 28.6–81.9
Tumor site	Nasopharynx: 8
	Oropharynx: 15
	Hypo pharynx: 3
	Paranasal sinus: 1
Chemotherapy	None: 2
	Adjuvant: 11
	Concomitant: 20
T stage	T1: 8; T2: 9; T3: 4; T4: 6
PNs volumes	Median: 1.76 cm^3; range: 0.13 – 2.08 cm^3
GTV PET volume	Median: 1.76 cm^3; range: 0.13 – 2.08 cm^3

Table II. Difference of PET positive volume variation between patient without (group 1) versus with (group 2) relapses in primary tumor (T), lymph node (N) or metastatic (M) location at different timing during treatment (i.e. fraction 10, 20, end of treatment). Mann-Whitney test (*p < 0.10) was used and volumes at different timing were normalized to volume at beginning of treatment (i.e. 1st fraction).

	p-value	Group 1: median (Interquartile range)	Group 2: median (Interquartile range)
Fraction 10
Relapse T	0.23	0.90 (0.65–1.06)	1.06 (0.77–1.68)
Relapse N	0.07*	0.86 (0.66–1.05)	1.35 (0.94–1.74)
Relapse M	0.63	0.91 (0.70–1.09)	0.67 (0.63–1.20)
Fraction 20
Relapse T	0.06*	0.56 (0.43–0.74)	1.07 (0.58–1.52)
Relapse N	0.08*	0.57 (0.43–0.72)	1.25 (0.75–1.60)
Relapse M	0.97	0.58 (0.43–0.85)	0.48 (0.42–1.25)
End of therapy
Relapse T	0.07*	0.36 (0.23–0.52)	0.69 (0.43–1.27)
Relapse N	0.09*	0.38 (0.25–0.53)	0.88 (0.41–1.48)
Relapse M	0.50	0.38 (0.21–0.61)	0.39 (0.22–1.27)

Figure 1. Absolute frequency distribution of patients with or without relapse in primary tumor (T) against the corresponding volume variation of PET-positive lymph nodes at fraction 20 (normalized to volume at 1st fraction and divided in classes of 50% variation).

Figure 2. Relapse-free survival curves for patients with large (solid line) and no/moderate (dotted line) positive nodes volume variation at fraction 10 for T (A) and N (B) relapses; p-values were 0.09 and 0.07, respectively (Cox proportional). Best cut-off values used to separate between responding and non-responding patients were 58% and 98% of the initial positive nodes volume for T and N relapses, respectively (Table III). Number of patients at risk are also indicated.

Table III. Actuarial analysis of primary tumor (T), lymph node (N) and metastatic (M) recurrences at different timing during treatment (i.e. fraction 10, 20, end of treatment). Patients were divided based on ROC curve best cut-off values evaluated for all different recurrences and timing. Hazard ratios (HR, 95% confidential interval) and p-value (*p < 0.10; **p < 0.05) of Cox proportional actuarial analysis are also reported.

	ROC curve	Cox proportional hazard ratio
	Best Cut-off value	p-value	HR	95% CI
Fraction 10
Relapse T	1.05	0.09*	6.0	0.6–57.6
Relapse N	1.05	0.07*	6.8	0.7–64.7
Relapse M	0.67	0.16	3.6	0.6–21.6
Fraction 20
Relapse T	0.58	0.12	5.2	0.5–49.4
Relapse N	0.98	0.01**	15.0	1.6–142.9
Relapse M	0.48	0.18	3.5	0.6–21.6
End of therapy
Relapse T	0.50	0.08*	6.5	0.7–61.3
Relapse N	0.68	0.01**	19.6	2.0–191.0
Relapse M	0.82	0.01**	11.9	1.7–84.4