1. Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, et al. Concurrent
cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med.
1999;340:1144-53.
2. Green JA, Kirwan JM, Tierney JF, Symonds P, Fresco L, Collingwood M, et al. Survival and
recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a
systematic review and meta-analysis. Lancet. 2001;358:781-6.
3. Collaboration CfCCM-A. Reducing uncertainties about the effects of chemoradiotherapy for
cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized
trials. J Clin Oncol. 2008;26:5802.
4. Toita T, Kitagawa R, Hamano T, Umayahara K, Hirashima Y, Aoki Y, et al. Feasibility and Acute
Toxicity of Concurrent Chemoradiotherapy (CCRT) With High–Dose Rate Intracavitary
Brachytherapy (HDR-ICBT) and 40-mg/m2 Weekly Cisplatin for Japanese Patients With Cervical
Cancer: Results of a Multi-Institutional Phase 2 Study (JGOG1066). Int J Gynecol Cancer.
2012;22:1420-6.
5. Gladwish A, Milosevic M, Fyles A, Xie J, Halankar J, Metser U, et al. Association of apparent
diffusion coefficient with disease recurrence in patients with locally advanced cervical cancer treated
with radical chemotherapy and radiation therapy. Radiology. 2015;279:158-66.
6. Markman M. Chemoradiation in the management of cervix cancer: current status and future
directions. Oncology. 2013;84:246-50.
7. Rose PG, Java J, Whitney CW, Stehman FB, Lanciano R, Thomas GM, et al. Nomograms
predicting progression-free survival, overall survival, and pelvic recurrence in locally advanced
cervical cancer developed from an analysis of identifiable prognostic factors in patients from NRG
oncology/gynecologic oncology group randomized trials of chemoradiotherapy. J Clin Oncol.
2015;33:2136-42.
8. Xue F, Lin LL, Dehdashti F, Miller TR, Siegel BA, Grigsby PW. F-18 fluorodeoxyglucose uptake
in primary cervical cancer as an indicator of prognosis after radiation therapy. Gynecol Oncol.
2006;101:147-51.
14
9. Nakamura K, Joja I, Kodama J, Hongo A, Hiramatsu Y. Measurement of SUVmax plus ADCmin
of the primary tumour is a predictor of prognosis in patients with cervical cancer. Eur J Nucl Med
Mol Imaging. 2012;39:283-90.
10. Onal C, Reyhan M, Parlak C, Guler OC, Oymak E. Prognostic value of pretreatment
18F-fluorodeoxyglucose uptake in patients with cervical cancer treated with definitive
chemoradiotherapy. Int J Gynecol Cancer. 2013;23:1104-10.
11. Marconi DG, Fregnani JHTG, Rossini RR, Netto AK, Lucchesi FR, Tsunoda AT, et al.
Pre-treatment MRI minimum apparent diffusion coefficient value is a potential prognostic imaging
biomarker in cervical cancer patients treated with definitive chemoradiation. BMC cancer.
2016;16:556.
12. Ho JC, Allen PK, Bhosale PR, Rauch GM, Fuller CD, Mohamed AS, et al. Diffusion-Weighted
Magnetic Resonance Imaging as a Predictor of Outcome in Cervical Cancer After Chemoradiation.
Int J Radiat Oncol Biol Phys. 2017;97:546-53.
13. World Medical Association. World Medical Association World medical association declaration of
Helsinki: ethical principles for medical research involving human subjects. Journal of the American
Medical Association. 2013;310:2191–2194.
14. Das S, Chandramohan A, Reddy JKR, Mukhopadhyay S, Kumar RM, Isiah R, et al. Role of
conventional and diffusion weighted MRI in predicting treatment response after low dose radiation
and chemotherapy in locally advanced carcinoma cervix. Radiother Oncol. 2015;117:288-93.
15. Somoye G, Harry V, Semple S, Plataniotis G, Scott N, Gilbert FJ, et al. Early diffusion weighted
magnetic resonance imaging can predict survival in women with locally advanced cancer of the
cervix treated with combined chemo-radiation. Eur Radiol. 2012;22:2319-2327.
16. Park JJ, Kim CK, Park BK. Prognostic value of diffusion-weighted magnetic resonance imaging
and 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography after concurrent
chemoradiotherapy in uterine cervical cancer. Radiother Oncol. 2016;120:507-11.
17. Ho KC, Lin G, Wang JJ, Lai CH, Chang CJ, Yen TC, et al. Correlation of apparent diffusion
coefficients measured by 3T diffusion-weighted MRI and SUV from FDG PET/CT in primary
cervical cancer. Eur J Nucl Med Mol Imaging. 2009;36:200-208.
15
Figures
Figure1
p<0.001
p=0.001
00
90
90
80
80
70
70
60
60
30
20
20
,0
Diseas
ease
ecu
ence(
) r
cu
e(
Disease
Disease
cu
enc
) r
ence(+)
%ADCi
%Volumer
Figure 1: Box plots of %ADC increase and %Volume reduction in patients with and without
disease recurrences
Box plots summarize (A) %ADC increase and (B) %Volume reduction in patients with and without
disease recurrences. ADC = apparent diffusion coefficient.
16
Figure2
(A)%ADCincrease,disease-freesurvival
(B)%ADCincrease,overallsurvival
%ADCinc「ease~median
100
88070605040302010
e>
ea>O
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﹄﹄,
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%ADCincrease~median
%ADCi
e<medi
an
Log
k,p<0
%ADCi
c「ease<median
,p=0.005
Follow-uptime(
years)
Follow-uptime(years)
sa
tr
~median 52
47
34
24
sa
tr
~median 52
51
36
24
<median51
24
<median 5
49
37
23
(C)%Volumereduction,disease-freesurvival
100
90
70
50
40
%Vol
umer
<median
30
ーa
,p=0
002
Log
“"“父“xt
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(D)%Volumereduction,overallsurvival
%Volumereduction~median
%Volumer
<median
,p=0.
08
Follow-uptime(years)
Follow-uptime(years)
sa
tr
sk
~median 52
45
34
23
sa
tr
~median 52
50
36
26
<median 51
33
24
14
<median 51
50
37
21
Figure 2: Kaplan-Meier curve analysis by %ADC increase and %Volume reduction
The figures (A) and (B) show Kaplan-Meier curves in patients stratified by the median (33%)
of %ADC increase for prediction of disease-free survival and overall survival, respectively. The
figures (C) and (D) show Kaplan-Meier curves in patients stratified by the median (72%)
of %Volume reduction for prediction of disease-free survival and overall survival, respectively.
ADC = apparent diffusion coefficient.
17
Figure3
1:mbs'!4~1eqo19
a」
P=0.
011
32
Pr
um
e+pre-ADC Pre-Volume+pre-ADC Pr
e-Vo
lume+pr
e-ADC
+%Vo
lumereduc
ton +%Vo
umer
+%A
DCi
crease
Figure 3: Global chi-square analysis
The figure shows a global chi-square analysis which puts focus on the incremental value
of %Volume reduction and %ADC increase.
ADC = apparent diffusion coefficient.
18
Figure4
A.
ADCbeforetreatment
.ADCduringtreatment
比's'
、¥
•••
/し
、7 .
ヽ 〒‘
‘ ¥、人
\*.'.
C.T2WIbeforetreatment D
.T2WIduringtreatment E
.T2WIa
rtreatment
Figure 4: A case of a patient who had no disease recurrences
The figures show images of a patient with FIGO stage IIIB who had no disease recurrences. The
figures (A) and (B) show ADCs of a tumor (red region of interest) before (0.89 mm2/sec) and during
(1.26 mm2/sec) treatment, respectively. Therefore, a %ADC increase was 42%, which was higher
than the median of %ADC increases. T2WIs before (Figure C) and during (Figure D) treatment
demonstrated decrease (%Volume reduction = 57%) of the tumor volume (white arrow). In a T2WI
after treatment (Figure E), a complete response to treatment was confirmed. During a follow up of 7
years, the patient had no disease recurrences.
ADC
apparent
diffusion
coefficient;
T2WI
International Federation of Gynecology and Obstetrics
T2
weighted
image;
FIGO
19
Supplementary Table 1. Imaging results
Parameter
ADC
Pre-ADC (mm2/sec)
Mid-ADC (mm2/sec)
%ADC increase (%)
Tumor volume
Pre-Volume (ml)
Mid-Volume (ml)
%Volume reduction (%)
ADC = apparent diffusion coefficient.
Value
0.95±0.12
1.27±0.13
35±18
63±57
19±20
69±19
20
SupplementaryFigure1
lcancerp
st
dw
hd
eCCRTor
ybetweenSeptember2007andJanuary2018
n=153
eI
,n=3
NoM
,n=38
sw
hstageI
Ac
lcancerwhohadMRI
sbeforeandd
gtreatment
n=112
sb
et
,n=4
wupl
,n=S
lstudyp
n=103
Supplementary Figure 1: Study flow chart
CCRT = concurrent chemoradiotherapy; MRI = magnetic resonance imaging.
21
SupplementaryFigure2
lbeamr
ntherapy:50-50.4Gy
r土 boost5.4-10.
8Gy
36
Brach
:12-24Gy
(Nob
n=5)
Day0
Pre-treatmentMRI
Day25士4.
Mid-treatmentMRI
Supplementary Figure 2: Treatment regimen
CDDP = cisplatin; PTX = paclitaxel; MRI = magnetic resonance imaging.
Ti
me(
da
22
SupplementaryFigure3
A.
ADCbeforetreatment
.ADCduringtreatment
.T2WIbeforetreatment
.T2WIduringtreatment
.T2WIa
rtreatment
.CT1yeara
rtreatment
Supplementary Figure 3: A case of a patient who had a disease recurrence
The figures show images of a patient with FIGO stage IIIB who had a disease recurrence. The
figures (A) and (B) show ADCs of a tumor (red region of interest) before (0.92 mm2/sec) and during
(1.07 mm2/sec) treatment, respectively. Therefore, a %ADC increase was 16%, which was lower
than the median of %ADC increases. T2WIs before (Figure C) and during (Figure D) treatment
demonstrated decrease (%Volume reduction = 53%) of the tumor volume (white arrow). A T2WI
after treatment (figure E) shows a complete response to treatment. In the figure (F), a CT image one
year after treatment reveals a disease recurrence (green arrow).
ADC = apparent diffusion coefficient; T2WI = T2 weighted image; FIGO = International Federation
of Gynecology and Obstetrics
...