Prognostic values of baseline, interim and end-of therapy ¹⁸F-FDG PET/CT in patients with follicular lymphoma

Figures & data

Table 1 Characteristics of FL patients

Characteristic	No. of patients (n=84)
Sex (male)	43 (51.19%)
Age median (range)	51 (25–80)
B symptoms (Yes)	29 (34.52%)
Ann Arbor stage (III/IV)	63 (75.00%)
Histologic grade
High	23 (27.38%)
Low	52 (61.90%)
Unknown	9 (10.71%)
ECOG >1	13 (15.48%)
BM (+)	21 (25.00%)
LDH (Increased)	21 (25.00%)
FLIPI
0–2	51 (60.71%)
3–5	33 (39.29%)
B-PET number	59
I-PET number	24
E-PET number	43

Abbreviations: ECOG, Eastern Cooperative Oncology Group; BM: bone marrow; FLIPI, Follicular Lymphoma International Prognostic Index.

Figure 1 The baseline ¹⁸F-FDG PET/CT (A) image showed hypermetabolic lesions with TLG of 2,366.61. I-PET (B) after four cycles of R-CHOP therapy, and E-PET (C) after end-of therapy showed no hyper-metabolic lesions. After 11 months of therapy, the patient experienced relapse. ¹⁸F-FDG PET/CT (D) showed increased ¹⁸F-FDG uptake in the liver, abdomen and right pelvic (arrows).

Figure 2 The baseline PET/CT (A) image showed hypermetabolic lesion in the left cervical lymph node (arrows) with a TLG of 65. E-PET (B) after end-of therapy did not show hypermetabolic lesions and no recurrence after the 49-month follow-up.

Table 2 Comparison between low and high tMTV, TLG and SUV_max groups

Clinical Factors (n=59)	tMTV			TLG			SUVmax
Low	High	p	Low	High	p	Low	High	p
Sex
Female (26)	17	9	0.151	22	4	0.152	19	7	0.417
Male (33)	16	17	23	10	26	7
Age
>60 (18)	9	9	0.372	13	5	0.431	12	6	0.205
≤60 (41)	24	17	32	9	33	8
B symptoms
Yes (18)	8	10	0.186	12	6	0.205	10	8	0.018*
NO (41)	25	16	33	8	35	6
Ann Arbor stage
I/II (18)	18	0	0.000*	18	0	0.003*	15	3	0.311
III/IV (41)	15	26	27	14	30	11
ECOG
0–1 (48)	29	19	0.133	38	10	0.236	40	8	0.015*
≥2 (11)	4	7	7	4	5	6
No. of extranodal sites
<1 (36)	27	9	0.000*	30	6	0.101	32	4	0.006*
≥1 (23)	6	17	15	8	13	10
BM
+ (18)	6	12	0.021*	10	8	0.018*	14	4	0.569
- (41)	27	14	35	6	31	10
LDH
Increased (16)	5	11	0.021*	8	8	0.007*	8	8	0.007*
- (43)	28	15	37	6	37	6
FLIPI
1–2 (36)	28	8	0.000*	34	2	0.000*	32	4	0.006*
3–5 (23)	5	18	11	12	13	10
LodLIN (cm)
>6cm (14)	4	10	0.020*	6	8	0.002*	9	5	0.196
<6cm (45)	29	16	39	6	36	9
No. of involved nodes
>4 (33)	10	23	0.000*	19	14	0.000*	23	10	0.152
≤4 (26)	23	3		36	0		22	4

Note: *Statistically significant.

Abbreviations: tMTV, total metabolic tumor volume; TLG, total lesion glycolysis; SUV_max, maximum standardized uptake value; ECOG, Eastern Cooperative Oncology Group; BM, bone marrow; LDH, lactate dehydrogenase; FLIPI, Follicular Lymphoma International Prognostic Index.

Table 3 Correlation between clinical characteristics with semi-quantitative parameters

	SUVmax		tMTV		TLG
r	p	r	p	r	p
Sex	0.109	0.410	−0.069	0.603	0.008	0.952
Age	−0.014	0.918	−0.059	0.656	−0.067	0.616
B symptoms	0.203	0.123	0.149	0.260	0.164	0.214
Ann Arbor stage	0.299	0.021*	0.738	<0.0001*	0.687	<0.0001*
ECOG	0.121	0.360	0.138	0.297	0.084	0.525
No. of extranodal sites	0.473	<0.0001*	0.453	<0.0001*	0.533	<0.0001*
BM	0.051	0.702	0.486	<0.0001*	0.400	0.002*
LDH	0.371	0.004*	0.296	0.023*	0.390	0.002*
FLIPI	0.315	0.015*	0.628	<0.0001*	0.618	<0.0001*
LodLIN (cm)	0.391	0.002*	0.380	0.003*	0.512	<0.0001*
No. of involved nodes	0.370	0.004*	0.761	<0.0001*	0.740	<0.0001*
SUVmax	-	-	0.393	0.002*	0.636	<0.0001*
tMTV	0.393	0.002*	-	-	0.927	<0.0001*
TLG	0.636	<0.0001*	0.927	<0.0001*	-	-

Note: *Statistically significant.

Abbreviations: tMTV, total metabolic tumor volume; TLG, total lesion glycolysis; SUV_max, maximum standardized uptake value; ECOG, Eastern Cooperative Oncology Group; BM, bone marrow; LDH, lactate dehydrogenase; FLIPI, Follicular Lymphoma International Prognostic Index.

Table 4 Baseline ¹⁸F-FDG PET/CT metabolic parameters

	PFS					OS
	AUC (95 %CI)	Sensitivity	Specificity	Cutoff	p	AUC (95 %CI)	Sensitivity	Specificity	Cutoff	p
tMTV	0.727 (0.570–0.884)	76.9%	65.2%	179.84	0.013	0.759 (0.508–1.0)	60%	87%	353.04	0.057
TLG	0.712 (0.553–0.872)	53.8%	84.8%	1364.60	0.020	0.696 (0.419–0.973)	60%	90.7%	2398.00	0.149
SUVmax	0.602 (0.427–0.777)	46.2%	80.4%	10.44	0.265	0.552 (0.233–0.812)	40%	81.5%	11.81	0.870

Abbreviations: tMTV, total metabolic tumor volume; TLG, total lesion glycolysis; SUV_max, maximum standardized uptake value.

Figure 3 Kaplan-Meier survival curves for the PFS (A, C, E) and OS (B, D, F) The baseline tMTV and TLG results were associated with PFS (A, C) and OS (B, D), and the baseline SUV_max result was associated with PFS (E), but not OS (F).

Table 5 Univariate analysis for survivals

	2-years PFS	χ^2	p	2-years OS	χ^2	p
B symptoms
Yes	83.33%	0.262	0.609	94.44%	0.116	0.773
No	87.80%	95.12%
Ann Arbor stage
I/II	100.00%	5.974	0.015*	92.68%	3.347	0.067
III/IV	80.49%	100.00%
SUVmax
High	64.29%	4.093	0.043*	83.33%	0.812	0.368
Low	93.33%	97.87%
tMTV
High	73.77%	7.878	0.005*	70.00%	9.139	0.003*
Low	96.97%	100.00%
TLG
High	57.14%	14.498	0.0001*	62.50%	16.319	<0.0001*
Low	95.56%	100.00%
FLIPI
1–2	91.67%	1.452	0.228	97.22%	0.103	0.748
3–5	78.26%	91.30%
ECOG
0–1 (48)	89.58%	1.897	0.168	97.92%	6.766	0.009*
≥2 (11)	72.73%	81.82%
No. of extranodal sites
<1	91.67%	4.431	0.035*	97.22%	1.306	0.253
≥1	78.26%	91.30%
BM
+	72.22%	5.460	0.019*	88.89%	3.827	0.050*
-	92.68%	97.56%
LDH
Increased	81.25%	0.275	0.600	87.5%	0.489	0.484
Normal	88.37%	97.67%
LodLIN (cm)
>6 cm	84.44%	1.153	0.283	92.86%	0.019	0.892
<6 cm	92.86%	95.56%
No. of involved nodes
>4	78.79%	2.656	0.103	90.91%	0.308	0.579
≤4	96.15%	100.00%
Histologic grade
High	70.59%	2.257	0.324	94.12%	0.425	0.809
Low	91.67%			94.44%
Unknown	100.00%	100.00%

Note: *Statistically significant.

Abbreviations: tMTV, total metabolic tumor volume; TLG, total lesion glycolysis; SUV_max, maximum standardized uptake value; FLIPI, Follicular Lymphoma International Prognostic Index; ECOG, Eastern Cooperative Oncology Group; BM, bone marrow; LDH, lactate dehydrogenase; PFS, progression- free survival; OS: Overall survival.

Table 6 Multivariate analysis for survivals

	PFS				OS
p	HR	95 %CI		p	HR	95 %CI
Ann Arbor stage	0.112	–	–	ECOG	0.028*	8.924	1.273–62.559
SUVmax	0.832	–	–	tMTV	0.615	-	-
tMTV	0.221	–	–	TLG	0.030*	19.291	2.689–137.947
TLG	0.001*	6.577	2.167–19.960	BM	0.096	-	-
BM	0.090	–	–
No. of extranodal sites	0.278	–	–

Note: *Statistically significant.

Abbreviations: tMTV, total metabolic tumor volume; TLG, total lesion glycolysis; SUV_max, maximum standardized uptake value; BM, bone marrow.

Table 7 Comparison of PFS between positive and negative groups using D-5PS and IHP criteria

			Relapse/progression, n (%)	2-years PFS
PFS	χ^2	p
I-PET (n=24)	D-5PS	4–5	4/10 (40.00%)	70.00%	3.552	0.059
	1–3	1/14 (7.14%)	92.86%
	IHP	Positive	4/12 (33.33%)	75.00%	1.747	0.186
Negative	1/12 (8.33%)	91.67%
E-PET (n=43)	D-5PS	4–5	10/14 (71.43%)	35.71%	15.470	<0.0001*
	1–3	4/29 (13.79%)	93.10%
	IHP	Positive	11/21 (52.38%)	57.14%	7.594	0.006*
Negative	3/22 (13.64%)	95.45%

Note: *Statistically significant.

Abbreviations: D-5PS, Deauville five-point scale; IHP, International Harmonization Project criteria.

Figure 4 Kaplan-Meier survival curves for the PFS of D-5PS criteria (A, B) and IHP criteria (C, D). The I-PET results according to D-5PS (A) and IHP criteria (C) were not associated with PFS; and the E-PET results according to D-5PS (B) and IHP criteria (D) were associated with PFS.

Figure 5 A patient with interim¹⁸F-FDG PET/CT showed increased ¹⁸F-FDG uptake in the neck, axilla, mediastinum, abdominal and pelvis. D-5PS and IHP criteria were considered positive for patient, and the patient experienced relapse after 7 months of follow-up. A patient with an interim¹⁸F-FDG PET/CT D-5PS (score 1) and negative IHP criteria did not show progression and survived at the end of the 28-month follow-up period (B).

Table 8 Predictive values of interim and end-of treatment PET/CT

		Sensitivity	Specificity	Accuracy	PPV	NPV	AUC (95% CI)
I-PET (n=24)	D-5PS	80.00%	68.42%	70.83%	40.00%	92.86%	0.742 (0.499–0.985)
IHP	80.00%	57.89%	62.50%	33.33%	91.67%	0.689 (0.436–0.943)
E-PET (n=43)	D-5PS	71.43%	86.21%*	81.40%*	71.43%*	86.21%	0.788 (0.629–0.947)
IHP	78.57%	65.52%	69.77%	52.38%	86.36%	0.720 (0.557–0.884)

Note: *Statistically significant.

Abbreviations: PPV, positive predictive value; NPV, negative predictive value.

Figure 6 Kaplan-Meier survival curves for the PFS of ΔSUV_max%. The I-PET results according to ΔSUV_max% (A) were not associated with PFS; and the E-PET results according to ΔSUV_max% (B) were associated with PFS.

Figure 7 A patient with end-of therapy ¹⁸F-FDG PET/CT showed increased ¹⁸F-FDG uptake in the abdomen (arrows). D-5PS and IHP criteria were considered positive for patient, and the patient experienced relapse after 7 months of follow-up (A). A patient with an end-of therapy ¹⁸F-FDG PET/CT D-5PS (score 1) and negative IHP criteria did not show progression and survived at the end of the 71-month follow-up period (B).