annibale versari medicina nucleare – centro pet ao arcispedale s.maria nuova - irccs reggio emilia...
TRANSCRIPT
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Annibale Versari
Medicina Nucleare – Centro PETAO Arcispedale S.Maria Nuova - IRCCS
Reggio Emilia
Neoplasie della tiroide
Carcinoma scarsamente differenziato
Terapia radiorecettoriale
15 giugno 2011
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Background
• Metastases from differentiated thyroid carcinoma (DTC) can lose in time the capacity to concentrate radioiodine and the possibility to have a specific treatment.
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Background
• DTC may express somatostatin receptors;
this offers a further opportunity of diagnosis and treatment.
Tenenbaum F et al J Nucl Med 1995
Görges R et al Nuklearmedizine 1999
Forssell-Aronsson EB et al J Nucl Med 2000
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Nuclear Medicine Imaging
Somatostatin analogs
Target site:Somatostatin
receptors
Scintigraphy, SPECT, SPECT/CT • 111In-Octreoscan
PET/CT •68Ga-DOTATOC•68Ga-DOTANOC•68Ga-DOTATATE
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Physics properties (LET)
mean range in body tissue
177Lu 0.5-2mm
90Y 3-11 mm
•
•
β- (Mev)
γ (Kev)
T1/2 (days)
177Lu 0.49 110-210 6.7
90Y 2.27 2.7
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Results
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JJJ Teunissen et alJ Nucl Med 2005
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JJJ Teunissen et alJ Nucl Med 2005
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68Ga DOTATOC PET/CT
68Ge/68Ga Generator
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68Ge/68Ga Generator
68Ge (t1/2 : 270.8 d) 68Ga (t1/2 : 68 m)
EC
68Ga emissions
E(max) = 1.9 MeV 89%
electron capture 11%
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Ant Lat
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B.M. male, 75 year old 68Ga-DOTATOC PET/CT:Diffuse lung metastases (+ bone and lymph node mts)
Metastatic differentiated thyroid cancer Metastatic differentiated thyroid cancer negative at radioiodine scannegative at radioiodine scan
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P.M. female, 61 year old 68Ga-DOTATOC PET/CT: multiple bone metastases
Metastatic differentiated thyroid cancer Metastatic differentiated thyroid cancer negative at radioiodine scannegative at radioiodine scan
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Patients45 pts with non-radioiodine-avid DTC, metastatic or
suspicious metastatic underwent 68Ga-DOTATOC PET/CT
m/f 21/24age 23-82 yrs,mean 59 Results
Negative PET: 23 pts (51%)Positive PET: 22 pts (49%)
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Results
• Multivariate analysis does not show any significant association with a positive 68Ga-DOTATOC PET/CT
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From Diagnosis to Treatment
Diagnosis68Ga
Treatment90Y / 177Lu
DOTATOC
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Results
• 13/45 (28%) patients satisfied the criteria (high uptake in the lesions) to access PRRT with 90Y/177Lu-DOTATOC
• 11 pts underwent treatment (90Y: 9 pts - 177Lu: 2 pts)
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90Y-DOTATOC
90Ittrium
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Radiolabelled Somatostatin Analogs Therapy
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90Y/177Lu-DOTATOC Treatment
pts Cumulative Dose (GBq)
Cycles Interval (weeks)
Dosimetry
90 Y 9 5-15 2-6 8-12 111In-DOTATOC
177Lu 2 15-22 3-4 7-10 177Lu
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PET VCAR
Patient evaluation
RECIST evaluation68Ga-PET/CT evaluation
•functional volume •SUV•tumor/muscle SUV
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Response to the treatmentFollow up: 6-15 months
RECIST Response SUV max Response
PR SD PD PR SD PD
Patients (11) 2 4 4 (1 NA) 2 4 5
Lesions
Lymph node (23) 18% 78% 4% 34% 52% 14%
Bone (130) NA NA NA 27% 33% 40%
Lung (20) 5% 90% 5% 39% 36% 25%
PR - partial responseSD - stable diseasePD - progression disease
According to EORTC criteria modified by ourEthics Committee
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Before Before therapytherapy
Sept 2007
Mar 2009
After 4 cycles After 4 cycles
9090Y-DOTATOC Y-DOTATOC
(cumulative dose 268 mCi)
Severe dyspnea No dyspneaO2-therapy: 6-7 hours/day No O2-therapy
B.M. male, 75 year old
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SUVmax changes (%)
-80
-70
-60
-50
-40
-30
-20
-10
0
10
20
0 1 2 3 4 5 6 7
Treatment steps
SU
Vm
ax c
han
ges (%
)
Lung
Bone
Lymph node
B.M. male, 75 year old
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Pre-therapy Post-therapy P.M. female, 61 year old
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Pre-therapy Post-therapy
P.M. female, 61 year old
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MAX SUV
0
5
10
15
20
25
30
35
0 1 2 3 4 5 6 7 8
cicli di curaTreatment steps
pain no pain no pain pain
P.M. female, 61 year old
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MAX SUV(ref)
0
10
20
30
40
50
60
0 1 2 3 4 5 6 7 8
cicli di cura
Tumor/muscle SUV
Treatment steps
pain no pain no pain pain
P.M. female, 61 year old
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Patient Tg pre-
treatmentTg post-
treatment68Ga-PET
SUVRECIST
1 >1000 stable PR PR
2 300 stable PD PD
3 0.5 stable PR PR
4 <0.3 stable SD SD
5 >6000 stable PD PD
6 380 increased PD PD
7 7500 stable SD SD
8 385 increased PD PD
9 0.4 increased SD SD
10 227 stable SD SD
11 200.000 increased PD PD
Tireoglobulin in comparison with treatment response
PR - partial response SD - stable disease PD - progression disease
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Results
• The clinical response is superior to the PET/CT findings.
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Side effects
• Nausea (grade 1): 4/11
• Astenia (grade 1): 2/11
• Hematologic Toxicity: 4/11• (transient decreasing of platelets, WBC,
eritrocytes)
• Renal failure: 1/11
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Side effectsImpact on renal function
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Side effectsImpact on blood platelets
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Side effectsImpact on WBC
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Conclusions
• Labelled somatostatin analogs are very interesting for pts with progressive radioiodine-negative Differentiated Tyroid Cancer
• About 50% of these pts are positive at 68Ga-DOTATOC PET/CT
• The possibility to use the same peptide for therapy in PET positive pts is promising but needs further confirmation in larger number of pts.
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Grazie per l’attenzione
Ponte di CalatravaReggio Emilia