Spatial distribution of FMISO in head and neck squamous cell carcinomas during radio-chemotherapy and its correlation to pattern of failure

Figures & data

Figure 1. Local progression-free survival for patients categorized as hypoxic during therapy with TBR_max > 1.93 in FMISOw2 (n = 12).

Table I. Patients' characteristics.

No.	Age (years)	Sex	Region	TNM	TBRmax FMISOpre	TBRmax FMISOw2	Local failure (LF)	Time to LF months	Imaging modality of LF
1	54	M	Oropharynx	T3 N0 M0	2.47	2.38	Y	7	PET-CT
2	46	M	Hypopharynx	T4 N2c M0	2.53	1.96	N	-	†
3	59	M	Hypopharynx	T4 N2b M0	2.79	2.65	Y	12	PET-CT
4	54	M	Tongue	T3 N1 M0	2.83	2.02	N	-	-
5	55	M	Tongue	T4 N2 M0	3.86	3.06	Y	6	(clinical)
6	53	M	Gingiva	T4 N2c M0	2.11	2.43	Y	16	CT
7	60	M	Gingiva	T4 N2c M0	2.73	2.25	N	-	†
8	52	M	Oropharynx	T4 N2c M0	2.41	2.01	Y	(39)	PET-CT
9	54	W	Oropharynx	T4 N2c M0	1.69	2.48	N	-	†
10	45	M	Tongue	T3 N2c M0	3.18	2.75	N	-	†
11	64	M	Tongue	T3 N2b M0	2.27	3.41	Y	20	PET-CT
12	55	M	Hypopharynx	T4 N2c M0	3.19	2.82	Y	7	CT

Maximum tumour to background ratio (TBRmax) in FMISOpre and FMISOw2. The symbol † indicates patients who died before the first follow-up visit.

Figure 2. FMISO stability during treatment, boxplot showing 50% quartiles, whiskers showing whole range. (A) Dice index (Dice) with percentage of overlap, (B) bilateral mean contour distance (BMCD) and (C) distance of SUV_max between corresponding sequential FMISO scans.

Table II. Variations of FMISO hypoxic subvolumes during treatment.

	FMISOpre to FMISOw1				FMISOw1 to FMISOw2				FMISOw2 to FMISOw5
Patient no. #	Dice index	MaxU distance (mm)	BMCD (mm)	Δ vol (ml)	Dice index	MaxU distance (mm)	BMCD (mm)	Δ vol (ml)	Dice index	MaxU distance (mm)	BMCD (mm)	Δ vol (ml)
1	75%	11.1	3.4	− 2.4	28%	8.6	10.3	− 28.6	49%	4.1	4.3	− 1.8
2	75%	8.0	3.3	+ 1.9	17%	30.2	13.6	− 29.8
3	65%	7.0	3.8	− 0.6	70%	10.1	3.7	− 1.2
4	53%	12.2	5.1	− 9.1	28%	24.8	8.4	+ 5.1
5					73%^a	50.8^a	4.1^a	− 7.6^a	22%	4.9	11.6	− 52.3
6	60%	5.7	5.6	+ 33.4	73%	21.9	5.0	− 18.5	57%	8.9	6.3	− 12.5
7	62%	1.9	5.7	− 45.3	69%	25.9	4.4	+ 34.1	7%	27.6	21.4	− 103.3
8	17%	29.7	15.3	+ 175.8	30%	21.5	13.8	− 158.9
9	23%	4.3	5.5	+ 4.1	52%	5.9	4.5	+ 1.2
10	50%	7.0	5.6	+ 19.4	56%	19.4	5.4	− 6.9	50%	5.9	5.4	− 12.7
11	67%	10.0	4.1	+ 5.3	77%	4.9	3.0	− 0.3	29%	11.6	6.8	− 17.3
12	76%	5.9	3.3	+ 0.7	59%	4.1	4.7	− 25.4	9%	14.9	8.7	− 24.0
MED	62%	7.0	5.1	–	58%	20.5	4.9	–	29%	8.9	6.8	–
M	57%	9.3	5.5	–	53%	19.0	6.7	–	32%	11.1	9.2	–

BMCD, bilateral mean contour distance; MaxU distance, distance between sequential SUVmax localization, M, mean; MED, median; Δ vol, absolute volume change between sequential FMISO scans. ^aUsage of FMISOpre instead of FMISOw1 since FMISOw1 not available for Patient 5.

Table III. Stability of hypoxic subvolume.

Patient no. #	Volume FMISOpre (ml)	Merged volume FMISO w1 + w2+ w5 (ml)	Volume outside FMISOpre (ml)	Geographic Miss index
1	36.9	34.9	7.7	22.1%
2	33.5	37.5	11.2	29.9%
3	19.8	18.8	6.5	34.6%
4	15.6	15.7	7.0	44.6%
5	62.3	60.3	14.6	24.2%
6	79.8	149.8	81.1	54.1%
7	118.3	118.1	31.2	26.4%
8	18.1	194.8	176.7	90.7%
9	0.8	8.2	7.4	90.2%
10	11.4	7.9	5.2	65.8%
11	16.6	26.9	12.9	47.9%
12	50.3	54.1	12.8	23.7%

Volume of FMISOpre and merged FMISO subvolumes during therapy (sequential w1,w2,w5). Geographic Miss Index, percentage of FMISO subvolume during therapy missed by planning on FMISOpre; Volume ouside FMISOpre, subtraction of the intersection volume of FMISOpre and FMISOw1 + w2+ w5 from the FMISOw1 + w2+ w5 volume.

Figure 3. (A) Co-registration of FMISO subvolumes (FMISOpre = black, FMISOw1 = white, FMISOw2 = red, FMISOw5 = green) as delineated by one observer (NA) and projection of the location of maximum FMISO uptake (#) in serial FMISO-scans during therapy. Shown are the planning CTs with fusion of the FMISOw2-PET for two representative patients (# 1 and #8). Please note that the longitudinal distance between SUV_max (not shown here) substantially contributes to calculated distances. (B) Rigid co-registration of planning CT and PET-CT of local recurrence for the same patients with contours of FMISOpre (black) and FMISOw2 (red), pre-RT FDG-PET (light blue) and volume of recurrence (green). FMISO delineations of one observer (NA).

Table IV. Overlap and distances between geometric centres of recurrent tumour volume and FDG/FMISO PETs before/during treatment.

	Overlap of Rec with					Min contour distance if 0% overlap with c-s subvol	Distance (mm) of geometric centres between Rec and
No.	FDG	consensual FMISOpre	consensual FMISOw1	consensual FMISOw2	c-s subvol		FDG	consensual FMISOpre	consensual FMISOw1	consensual FMISOw2	c-s subvol
1	13.2%	5.5%	5.7%	0.3%	0%	0.5 mm	23.6	31.0	29.5	39.9	36.2
3	10.1%	14.8%	18.9%	15.4%	7.4%	–	15.9	22.2	17.9	16.9	19.3
6	26.7%	0%	20.1%	3.7%	0%	14.4 mm	24.8	42.0	24.4	29.0	37.8
8	0%	0%	0.4%	0%	0%	22.2 mm	36.2	38.0	30.8	37.3	38.2
11	24.8%	15.2%	6.7%	20.0%	3.2%	–	27.2	27.0	32.7	33.0	30.2
12	38.1%	21.0%	19.4%	11.8%	3.8%	–	14.3	13.4	14.6	16.6	16.0
M	18.8%	9.4%	11.9%	8.5%	2.4%	–	23.7	28.9	25.0	28.8	29.6
MED	19.0%	10.1%	12.8%	7.8%	1.6%	–	24.2	29.0	27.0	31.0	33.2

consensual, intersection of different FMISO observers/algorithm; c-s subvol, consensual and stable subvolume (FMISOpre, FMISOw1, FMISOw2 intersection); FDG, pre-RT FDG-PET volume; M, mean; MED, median; Rec, volume of recurrence.