A total of 135 lesions were irradiated during the investigation period, and 27 sites in 12 patients who underwent PET-CT before and after treatment were included in the analysis. Patients with AML, acute lymphoblastic leukemia (ALL), and chronic myelocytic leukemia (CML) were included, of which eight received BMT before radiation therapy and four of them received TBI. Most of the patients had uncontrolled leukemia, and seven died during the follow-up period, of which five were recorded as related to infections. Table 1 lists the characteristics of the 12 patients. In the 27 irradiated sites (Table 2), soft tissue was the most common (14 patients, 51.9%), followed by bone (11 patients, 40.7%), and organs (2 patients, 7.4%).
Table 1
Patient characteristics (n = 12)
Characteristic
|
N
|
%
|
Sex
|
|
|
|
|
Male
|
8
|
66.7
|
|
Female
|
4
|
33.3
|
Age
|
|
Median 37.5 (14–52)
|
|
|
Adult
|
10
|
83.3
|
|
Children
|
2
|
16.7
|
Disease
|
|
|
|
|
AML
|
5
|
41.7
|
|
ALL
|
6
|
50.0
|
|
CML
|
1
|
8.3
|
Previous BMT
|
|
|
|
No
|
4
|
33.3
|
|
Yes
|
8
|
66.7
|
Previous TBI
|
|
|
|
No
|
4
|
33.3
|
|
Yes
|
4
|
33.3
|
|
Not-BMT
|
4
|
33.3
|
TBI dose
|
|
|
|
|
1200 cGy/6 fractions
|
1
|
8.3
|
|
1320 cGy/8 fractions
|
3
|
25.0
|
Leukemia controlled
|
|
|
|
No
|
10
|
83.3
|
|
Yes
|
2
|
16.7
|
Survival
|
|
|
|
|
Survival
|
5
|
41.7
|
|
Death
|
7
|
58.3
|
Cause of death
|
|
|
|
Infection
|
5
|
41.7
|
|
Disease progression
|
1
|
8.3
|
|
Treatment-related complication
|
1
|
8.3
|
AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; CML, chronic myelocytic leukemia; BMT, bone marrow transplantation; TBI; total body irradiation.
|
Table 2
Characteristics of the irradiated sites (n = 27)
Characteristic
|
N
|
%
|
Site
|
|
|
|
|
Soft tissue
|
14
|
51.9
|
|
Bone
|
11
|
40.7
|
|
Organ
|
2
|
7.4
|
Disease
|
|
|
|
|
ALL
|
12
|
44.4
|
|
AML
|
13
|
48.1
|
|
CML
|
2
|
7.4
|
RT volume
|
|
Median 43.06 (0.26-486.53)
|
|
|
< 40 cm3
|
13
|
48.1
|
|
≥ 40 cm3
|
14
|
51.9
|
PreRT SUVmax
|
Median 7.47 (1.81–21.38)
|
|
|
< 7.5
|
14
|
51.9
|
|
≥ 7.5
|
13
|
48.1
|
RT technique
|
|
|
|
3D-CRT
|
9
|
33.3
|
|
IMRT
|
18
|
66.7
|
RT fraction size
|
|
|
|
200 cGy/fraction
|
6
|
22.2
|
|
250 cGy/fraction
|
7
|
25.9
|
|
300 cGy/fraction
|
8
|
29.6
|
|
500 cGy/fraction
|
6
|
22.2
|
BED10
|
|
Median 3125 (2400–5000)
|
|
|
< 3000 cGy10
|
12
|
44.4
|
|
≥ 3000 cGy10
|
15
|
55.6
|
AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; CML, chronic myelocytic leukemia; RT, radiotherapy; SUVmax, maximum standardized uptake value; 3D-CRT, 3-dimensional conformal radiotherapy; IMRT, intensity-modulated radiotherapy; BED10, biologically effective dose (alpha/beta ratio = 10).
|
The SUVmax in PET-CT before radiotherapy was in the range of 1.81–21.38, with a median of 7.47, and the patients were classified into high and low SUVmax groups based on an SUVmax of 7.5. The radiation treatment dose was 200–500 cGy per fraction, and when converted to BED10, the median value was 3125 cGy10, ranging from 2400–5000 cGy10. The patients were classified into high and low irradiation groups based on a median BED10 of 3000.
Evaluation of the response to PET-CT was performed at a median of 3.5 months (range, 1.9–7.3). The PET response after radiotherapy was classified as complete metabolic remission (CMR) at 24 sites (88.9%), partial metabolic remission (PMR) at one site (3.7%), and progressive metabolic disease (PMD) at two sites (7.4%). The change in SUVmax ranged from a decrease of 88.0% (-88.0%) to an increase of 263.0% (+ 263.0%), showing a median change of -70.9%. Figure 1 shows a waterfall plot of the maximum change in the SUVmax. The two sites showing PMD were both arm muscles, and the pretreatment SUVmax values were 2.35 and 1.81, respectively (Table 3). In one ALL patient with extramedullary relapse, the follow-up SUVmax values of two irradiated lesions in PET-CT 6.4 months after completion of radiotherapy increased to 6.66 and 6.57, respectively. There was no PET response, but the patient’s symptoms improved. PET achieved CMR with additional chemotherapy, but the patient died from an infection related to chemotherapy.
Table 3
Characteristics of progressive metabolic lesions after radiotherapy
Lesion number
|
1
|
2
|
RT site
|
Brachioradialis muscle
|
Flexor carpi ulnaris muscle
|
RT daily dose (cGy/fx)
|
200
|
200
|
RT fraction number
|
10
|
10
|
BED10 (cGy10)
|
2400
|
2400
|
RT technique
|
3D-CRT
|
3D-CRT
|
RT volume (cm3)
|
4.03
|
0.26
|
PTV margin (cm)
|
0.5
|
0.5
|
Pre-RT SUVmax
|
2.35
|
1.81
|
Post-RT SUVmax
|
6.66
|
6.57
|
Change of SUVmax (%)
|
+ 183.40
|
+ 262.98
|
Response EORTC
|
PMD
|
PMD
|
Symptom improvement
|
Yes
|
Yes
|
Salvage treatment
|
Further chemotherapy
|
Further chemotherapy
|
Survival
|
Death
|
Death
|
RT, radiotherapy; BED10, biologically effective dose (alpha/beta ratio = 10); 3D-CRT, three-dimensional conformal radiotherapy; PTV, planning target volume; SUVmax, maximum standardized uptake value; EORTC, The European Organization for Research and Treatment of Cancer, PMD, progressive metabolic disease.
|
During the follow-up period, there were recurrences in three sites, two sites with in-field recurrences and one site with marginal recurrence. The characteristics of the relapsed lesions are summarized in Table 4. The EORTC PET responses to radiotherapy were CMR in all three lesions and the decreases in the SUVmax after treatment ranged from 27.84–84.12. The relapse periods were 18.6, 8.7, and 6.7 months after the completion of radiotherapy. After recurrence, radiation therapy with a salvage aim was performed again, and the lesions were all controlled.
Table 4
Characteristics of recurrent lesions after radiotherapy
Lesion number
|
8
|
15
|
21
|
Diagnosis
|
AML
|
ALL
|
ALL
|
Age at diagnosis
|
52
|
49
|
14
|
Sex
|
Female
|
Female
|
Male
|
Previous BMT history
|
Yes
|
Yes
|
No
|
RT site
|
Left lower extremity
|
Abdominal wall
|
Lumbar spine
|
RT daily dose (cGy/fx)
|
300
|
250
|
200
|
RT fraction number
|
10
|
10
|
10
|
BED10 (cGy10)
|
3900
|
3125
|
2400
|
RT technique
|
IMRT
|
IMRT
|
3D-CRT
|
RT volume (cm3)
|
17.39
|
123.32
|
3.77
|
PTV margin (cm)
|
0.5
|
1
|
-
|
Pre-RT SUVmax
|
5.46
|
14.74
|
6.06
|
Post-RT SUVmax
|
3.94
|
2.34
|
3.26
|
Change of SUVmax (%)
|
-27.84
|
-84.12
|
-46.20
|
Response EORTC
|
CMR
|
CMR
|
CMR
|
Relapse period (months)
|
18.6
|
8.7
|
6.7
|
Pattern of recurrence
|
In-field
|
Marginal
|
In-field
|
Systemic disease at recurrence
|
Uncontrolled
|
Uncontrolled
|
Controlled
|
Survival
|
Survival
|
Survival
|
Survival
|
Salvage treatment
|
re-RT
|
RT
|
re-RT
|
AML, acute myeloid leukemia; ALL, acute lymphocytic leukemia; RT, radiotherapy; BED10, biologically effective dose (alpha/beta ratio = 10); IMRT, intensity-modulated radiotherapy; 3D-CRT, three-dimensional conformal radiotherapy; PTV, planning target volume; SUVmax, maximum standardized uptake value; EORTC, The European Organization for Research and Treatment of Cancer; CMR, complete metabolic response; re-RT, re-irradiation.
|
The two lesions with disease progression and the three lesions with recurrence were defined as a treatment failure group, and the clinical factors were compared with the controlled groups and analyzed (Table 5). There was no significant difference in the radiation volume, site, and SUVmax before treatment, but the SUVmax after treatment showed a value of 2 or more in the treatment failure group, with a marginal statistical difference (P = 0.057). Although there was no significant difference between the radiation technique and the dose per fraction, the number of lesions irradiated with more than 3000 cGy10 based on BED10 was significantly greater in the treatment control group (P = 0.024).
Table 5
Comparison of clinical factors between treatment failure and controlled groups
Characteristic
|
Treatment failure group
|
Treatment controlled group
|
P-value
|
(n = 5)
|
(n = 22)
|
Site
|
|
|
|
0.296
|
|
Bone
|
1
|
10
|
|
|
Non-bone
|
4
|
12
|
|
RT volume
|
|
|
0.114
|
|
< 40 cm3
|
4
|
9
|
|
|
≥ 40 cm3
|
1
|
13
|
|
PreRT SUVmax
|
|
|
0.163
|
|
< 7.5
|
4
|
10
|
|
|
≥ 7.5
|
1
|
12
|
|
PostRT SUVmax
|
|
|
0.057
|
|
< 2
|
0
|
10
|
|
|
≥ 2
|
5
|
12
|
|
RT technique
|
|
|
0.161
|
|
3D-CRT
|
3
|
6
|
|
|
IMRT
|
2
|
16
|
|
RT fraction size
|
|
|
0.185
|
|
200–300 cGy/fraction
|
5
|
16
|
|
|
500 cGy/fraction
|
0
|
6
|
|
BED10
|
|
|
|
0.024
|
|
< 3000 cGy10
|
3
|
3
|
|
|
≥ 3000 cGy10
|
2
|
19
|
|
RT, radiotherapy; SUVmax, maximum standardized uptake value; 3D-CRT, three-dimensional conformal radiotherapy; IMRT, intensity-modulated radiotherapy; BED10, biologically effective dose (alpha/beta ratio = 10).
|
In this study, the median change in the SUVmax was − 70%, and binary logistic regression analysis was performed to predict the changes in the SUVmax. In the univariate analysis, a high SUVmax of 7.5 or more before radiotherapy (P = 0.017) and further chemotherapy after radiotherapy (P = 0.018) were found to be significant factors. In the multivariate analysis, both of these factors were significant (further chemotherapy after radiotherapy, P = 0.026; pretreatment SUVmax, P = 0.027). Changes in the SUVmax decreased by more than 70% in cases when chemotherapy was not administered after radiotherapy and the SUVmax before treatment was higher than 7.5. The results are described in Table 6.
Table 6
Binary logistic regression analysis predicting reductions in SUVmax of ≥ 70% after radiotherapy
Characteristic
|
Univariate
|
Multivariate analysis
|
P-value
|
Odds ratio
|
95% CI
|
P-value
|
RT site (Non-bone)
|
0.816
|
|
|
|
RT volume (40 cm3)
|
0.335
|
|
|
|
Further chemotherapy after RT (yes)
|
0.018
|
0.062
|
0.005–0.718
|
0.026
|
Pretreatment SUVmax (≥ 7.5)
|
0.017
|
13.862
|
1.350-142.341
|
0.027
|
RT dose (BED10) (≥ 3000 cGy10)
|
0.092
|
|
|
|
CI, confidence interval; RT, radiotherapy; SUVmax, maximum standardized uptake value; BED10, biologically effective dose (alpha/beta ratio = 10).
|