Transcript 18 F-BPA PET

The Role of BPA-PET in
Prediction of H&N Cancer
Treatment failure after
BNCT
Yu-Ming Liu, Yi-Wei Chen, Pin-Lun Li, Ko-Han Lin, YuWen Hu, Ling-Wei Wang
Div. of Radiation Oncology, Dept.of Oncology
Taipei Veterans General Hospital
Taiwan
Cancer of the Lip and Oral Cavity (C00-C08), World Age-Standardised
Incidence Rates, World Regions, 2008 Estimates, Cancer Research
UK
Mortality of Cancer in Taiwan (2010)
Liver
Lung
Colorectal
Oral, pharynx
Esophagus
Stomach
Prostate
Pancreas
non hodgkin lymphoma
Leukemia
Total
Treatment of head & neck cancer
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Surgery and radiation therapy with or
without chemotherapy, but despite therapy,
many cancers recur.
Further treatment for recurrent H & N cancer
after multi-disciplined treatment is not
uncommon
Photon beams re-irradiation is not
recommended because of high complication
and low successful rate.
LONG-TERM OUTCOME OF CONCURRENT CHEMOTHERAPY
AND REIRRADIATION FOR RECURRENT AND SECOND PRIMARY
HEAD-AND-NECK SQUAMOUS CELL CARCINOMA
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115 previously irradiated patients without overt metastases
Surgical resection, concurrent chemotherapy and re-irradiation
The median lifetime radiation dose was 131 Gy.
The median F/U for survival patients was 67.4 months (18.5–158.7).
The median OS and PFS was 11 and 7 months (range, 0.2–158.7)
The 3-year OS = 22 %
PFS = 33 %
Locoregional control = 51 %
Freedom from distant metastasis = 61 %
For recurrent and second primary head-and-neck cancer, trimodality
therapy with OP, C/T and re-RT for a full second dose offers potential
for long-term survival.
Owing to the substantial toxicity and lack of an optimal regimen, reirradiation of recurrent head-and-neck cancer should be limited to
clinical trials.
Salama et al., Int. J. Radiation Oncology Biol. Phys., Vol. 64, No. 2, pp. 382–391, 2006
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In theory, BNCT provides a means to selectively
eradicate malignant cells and spare normal cells.
To ensure success, a sufficient amount of 10B should
be selectively delivered to the tumor and an adequate
number of thermal neutrons should be absorbed in
order to sustain a lethal 10B(n,α) 7Li capture reaction
[Ono et al., IJROBP 34: 1081-1086, 1996].
For BPA-based BNCT, it is necessary to analyze the
actual distribution of BPA in vivo before determining
factors for its indication, as well as before planning
treatment and predicting outcome. For these purposes,
numerous authors have used 18F-BPA-PET prior to
employing BPA-based BNCT.
Trial in Taiwan
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A phase I/II trial of boron neutron capture therapy (BNCT)
for recurrent head and neck cancer at Tsing Hua OpenPool Reactor (THOR) ” was drafted at Taipei Veterans
General Hospital (TVGH) in 2008 and was approved by
Institution Review Board of TVGH and our Department of
Health in 2009.
The primary end points: treatment toxicities and tumor
response rate.
The secondary end points: time to tumor progression,
progression-free survival, overall survival, and change of
quality of life.
Web site: www. clinicaltr ials .gov; ID: N CT01173172.
August 2010 – Jan. 2014
Schema
Pt
1st
registration CT Sim
(D-14±3) (D-7)
1st
1st
18F-BPA PET
THOR
T/N
(D-12)
(D-3)
1st
BNCT
(D-1)
2nd
CT Sim
(D22±3)
2nd
18F-BPA
PET
T/N
(D21)
2nd
BNCT
(D29±3)
2nd
THOR
(D26±3)
FDG-PET/CT
or MRI
Evaluation
(D84±3)
•The BPA-uptake in ‘ ‘normal’’ tissue was measured in the subcutaneous connective
tissue several cm away from the tumors.
• 20– 25 Gy(Eq) to 80% of GTV/Fx for 2 Fx at interval of 30 days.
•BPA injection
- 1 st phase: 180 mg/kg/h for 2 h before neutron irradiation
- 2nd phase: 1.5 mg/kg/min concurrent with irradiation and stopped when beam was off.
•Response Evaluation Criteria in Solid Tumors (version 1.1).
•MRIs before and after BNCT were performed for tumor size evaluation
•High response rate with acceptable toxicity was obtained for this clinical
trial with BNCT at THOR.
•The decreased T/N ratios after first fraction of BNCT may indicate that
the second fraction is less efficient than the previous one.
Hypothesis & Aim
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The success of BNCT ultimately depends upon the
selective delivery of 10B-atoms to tumor cells.
Boron concentrations in surrounding normal structures as
well as in the tumor itself, for which 18F-BPA PET was
utilized.
To the best of our knowledge, treatment failure of local
recurrence and features of 10B uptake in tumors according
to 18F-BPA-PET images have yet to be adequately
assessed.
The present study therefore aimed to qualitatively and
quantitatively elucidate the features of 18F-BPA-PET
imaging in the outcome of BNCT therapy of recurrent head
and neck cancer patients.
T/N ratio by pre-treatment BPA-PET
After IV. 60 min, Tumor mean value =7.0;
Normal tissue mean value =1.6
T/N=4.37
Methods and Materials
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12 advanced recurrent head & neck tumor
patients who had received BNCT from 2010/8
to 2013/12 in Taiwan without distant failure
In-field failure vs. complete response.
The relationship between patient characters,
disease status, pre-BNCT RT, 1st T/N ratio,
treatment dosage, BPA-PET data, and
clinical response were analyzed.
BPA-PET scan for 10B uptake
BNCT Treatment GTV according to
pretreatment MR and 18F-PET/CT scan
Response Evaluation by 18F-PET/CT
Maxillary sinus carcinoma rT3, CR
Patient and tumor characters
Prior OP
Prior RT
Dose
(Gy/course)
Recurrent
Stage
Tumor
diameter (cm)
Squamous
Y
134.6/2
T1N2a
4.00
Gingiva
Squamous
Y
66
T4
7.50
49/F
Nasal Cavity
Sinonasal Ca
Y
120/2
T4
5.00
4
57/M
Tongue
Squamous
Y
70
T3
4.50
5
52/M
Tongue base
Squamous
Y
70
T4a
5.30
6
46/M
NPC
Undiff Ca
Y
136/2
T4
3.90
7
54/M
Maxillary sinus
Squamous
N
70
T3
8.90
8
48/M
Maxillary sinus
Spindle cell sarcoma
Y
107/2
T4b
6.00
9
58/F
NPC
Non-keratinizing Ca
Y
122/2
T3
2.50
10
59/M
NPC
Non-keratinizing Ca
N
136/2
T1
3.90
11
56/M
Oral
Squamous
Y
129.5/2
T1
0.88
12
62/M
Buccal
Squamous
Y
128/2
T4a
6.60
Pt No.
Age/Sex
Primary Site
1
68/M
Hypopharynx
2
71/M
3
Pathology
Prescription Dose, T/N ratio, tumor response and
survival status
Pt No.
Interval
(month)
1st T/N
1st Fx D80
(Gy-eq)
2nd T/N
2nd Fx D80
(Gy-eq)
Total Dose
(Gy-eq)
Tumor
Response
Survival
Status
Surv
(months)
1
9.97
3.00
19.1
2.60
12.50
31.60
PD
DOC
12.2
2
26.77
3.80
25.1
1.75
12.70
37.80
PD
DOC
6.3
3
13.93
4.46
31.1
2.78
17.30
48.40
CR
DOC
32.5
4
6.37
3.73
19.6
2.00
13.50
33.10
Response
DOC
13.3
5
6.50
3.33
13.7
2.09
9.30
23.00
Response
DOI
8.5
6
7.73
6.16
36.9
2.57
21.10
58.00
CR
alive
38.6
7
17.07
5.69
35.0
2.50
18.10
53.10
CR
alive
35.2
8
28.17
2.50
20.0
2.50
19.40
39.40
CR
alive
26.0
9
33.70
1.05
19.1
1.79
9.90
29.00
Response
alive
37.3
10
42.37
3.00
19.2
2.71
18.30
37.50
CR
alive
6.8
11
5.13
3.30
20.01
20.01
CR
alive
8.8
12
9.57
3.92
26.5
43.30
PD
alive
6.4
2.27
16.80
DOC: death of cancer; DOI: death of incurrent cause
PD: progression disease; CR: complete response; Response: partial response & stable disease
Measurement of BPA-PET
Parameter definition
BPA_max
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BPA_H
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BPA_L
BPA_min
Only 1st BPA-PET data were analysis
BPA-M: BPA uptake value inside GTV volume
Min BPA_M: min BPA uptake value inside GTV
Max BPA_M: max BPA uptake value inside GTV
BPA_H: BPA uptake value ≧ 30% of BPA_M
(min. BPA-M + 30% of max BPA-M)
BPA_L: BPA uptake < 30% of BPA_M
Vol_L/H (cm3): Volume ratio between BPA_L and
BPA_H according to BPA-PET
BPA_L/H: BPA uptake value ratio between
BPA_L and BPA_H according to BPA-PET
BPA_H
BPA_L
Results
CR(-)
CR(+)
p
Age
61±7
52±5
0.093
M/F
5/1
5/1
Pathology SqCC
5/6
2/6
0.099
Pre RT Dose (Gy)
92.5±33
108.3±28
0.284
Interval s/p EBRT
(months)
15.5±12
19.1±14
0.605
Recurrent T stage
0.639
T1
1
2
T3
2
1
T4
3
3
Tumor (cm)
5.1±1.8
4.8±2.7
0.801
1st T/N
3.1±1.1
4.2±1.5
0.211
33±7
42.7±13.6
0.16
Volume L/H
1.5±0.8
0.7±0.2
0.134
BPA L/H
0.6±0.1
0.6±0.1
0.396
Total Dose-eq (Gy)
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Tumors were easily identified as high uptake areas
in all cases. Areas of the dorsum tongue to
middle pharynx were expressed as high uptake
areas in all of the cases.
18F-BPA-PET is useful in demonstrating the
presence of a tumor. Thus, it is crucial high uptake
area corresponding to the dorsum area of the tongue
when diagnosing a tumor using this technique.
18F-BPA-PET
Right maxilla
Mucoepidermoid
carcinoma
 Brain parenchyma (a)
Parotid gland (b).
 The high uptake area:
- Tumor (arrows);
- Dorsum surface of the
tongue (arrowheads).
 Differentiation
between the two
structures was difficult
on the 18F-BPA-PET
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18F-BPA-PET
Aanterior maxilla
adenocarcinoma
 High uptake area:
- Tumor (arrow).
- Surface of the oral
tongue and tongue
base (arrowhead)
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Left maxilla squamous cell
carcinoma
High uptake area
- Jaw bone (arrows).
- Tumor (arrowheads).
Tumor to brain (T/B) ratio = radioactivity of tumor/brain.
Normal tissue to brain (N/B) ratio = radioactivity of normal tissue/brain.
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1st head and neck cancer patient treated with up-front
BNCT and conventional radiotherapy.
BNCT followed by chemoradiation as first-line therapy of
a patient diagnosed with large, inoperable head and
neck carcinoma
Case Report
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53 y/o woman
CC:: obstructed nose and headache.
Dx: Intranasal poorly differentiated
carcinoma,
A 7.4 × 6 .7 × 4 .4 cm tumour causing
exophthalmos and diplopia
BNCT, 400 mg/kg of L- BPA -fructose ivf.
GTV dose = 31 Gy (W), PTV dose = 28 Gy
(W), Optic chiasm = 4 Gy (W )
IMRT was given 6 weeks later with 44 Gy/17
Fx, followed by SBRT booster dose of 6 Gy.
Iv with cetuximab (250 mg/m 2) + cisplatin
(40 mg/m 2), weekly during IMRT.
A radiological complete response was
achieved one month after RT.
Summary
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Histology of squamous cell carcnoma, Total Dose-eq (Gy),
Volume BPA uptake heterogeneity data might be a prognostic
factor for clinic response though no statistic significance.
The volume BPA uptake heterogeneity data were 0.7±0.2
(0.44-1.0) in CR group and 1.5±0.8 (0.71-2.69) in non-CR
group, respectively
There is only 12 patients in this study.
F/U of 20 months (6.4 – 38.6 months).
The CR is depended on the FDG-PET 3 months after BNCT.
However, its predictive and prognostic value remains to be
clarified.
Conclusion
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BNCT is an effective treatment for advanced
local recurrent head and neck tumor with high
percentage image CR rate in 20 months followup (6.4 – 38.6 months).
Though no statistic significance noted, volume
of BPA uptake heterogeneity might be a
prognostic factor for clinic response.
The low BPA uptake volume might need further
RT boost for local control.
Thank you for your attention