Carcinoma scarsamente differenziato Terapia radiorecettoriale   Neoplasie della tiroide Carcinoma scarsamente differenziato Terapia radiorecettoriale Annibale Versari Medicina Nucleare – Centro PET AO Arcispedale S.Maria Nuova - IRCCS Reggio Emilia versari.annibale@asmn.re.it 15 giugno 2011 1

Background Metastases from differentiated thyroid carcinoma (DTC) can lose in time the capacity to concentrate radioiodine and the possibility to have a specific treatment.

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

Nuclear Medicine Imaging Target site: Somatostatin receptors Somatostatin analogs Scintigraphy, SPECT, SPECT/CT 111In-Octreoscan PET/CT 68Ga-DOTATOC 68Ga-DOTANOC 68Ga-DOTATATE

Physics properties (LET) β- (Mev) γ (Kev) T1/2 (days) 177Lu 0.49 110-210 6.7 90Y 2.27 2.7 mean range in body tissue 177Lu 0.5-2mm 90Y 3-11 mm

Results

JJJ Teunissen et al J Nucl Med 2005

JJJ Teunissen et al J Nucl Med 2005

68Ga DOTATOC PET/CT 68Ge/68Ga Generator

68Ge/68Ga Generator EC 68Ge (t1/2 : 270.8 d) 68Ga (t1/2 : 68 m) 68Ga emissions b+ E(max) = 1.9 MeV 89% electron capture 11%

Ant Lat

Metastatic differentiated thyroid cancer negative at radioiodine scan B.M. male, 75 year old 68Ga-DOTATOC PET/CT: Diffuse lung metastases (+ bone and lymph node mts)

Metastatic differentiated thyroid cancer negative at radioiodine scan P.M. female, 61 year old 68Ga-DOTATOC PET/CT: multiple bone metastases

Patients Results Negative PET: 23 pts (51%) Positive PET: 22 pts (49%) 45 pts with non-radioiodine-avid DTC, metastatic or suspicious metastatic underwent 68Ga-DOTATOC PET/CT m/f 21/24 age 23-82 yrs, mean 59 Results Negative PET: 23 pts (51%) Positive PET: 22 pts (49%)

Results Multivariate analysis does not show any significant association with a positive 68Ga-DOTATOC PET/CT

From Diagnosis to Treatment 68Ga DOTATOC Treatment 90Y / 177Lu

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)

90Y-DOTATOC 90Ittrium

Radiolabelled Somatostatin Analogs Therapy

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

Patient evaluation PET VCAR RECIST evaluation 68Ga-PET/CT evaluation functional volume SUV tumor/muscle SUV PET VCAR

Response to the treatment Follow up: 6-15 months RECIST Response SUV max Response PR SD PD Patients (11) 2 4 4 (1 NA) 5 Lesions Lymph node (23) 18% 78% 4% 34% 52% 14% Bone (130) NA 27% 33% 40% Lung (20) 5% 90% 39% 36% 25% PR - partial response SD - stable disease PD - progression disease According to EORTC criteria modified by our Ethics Committee

Severe dyspnea No dyspnea O2-therapy: 6-7 hours/day No O2-therapy Before therapy After 4 cycles 90Y-DOTATOC (cumulative dose 268 mCi) Sept 2007 Mar 2009 B.M. male, 75 year old

B.M. male, 75 year old

Pre-therapy Post-therapy P.M. female, 61 year old

Pre-therapy Post-therapy P.M. female, 61 year old

pain no pain no pain pain Treatment steps P.M. female, 61 year old

pain no pain no pain pain Tumor/muscle SUV Treatment steps P.M. female, 61 year old

Tireoglobulin in comparison with treatment response Patient Tg pre-treatment Tg post- treatment 68Ga-PET SUV RECIST 1 >1000 stable PR 2 300 PD 3 0.5 4 <0.3 SD 5 >6000 6 380 increased 7 7500 8 385 9 0.4 10 227 11 200.000 PR - partial response SD - stable disease PD - progression disease

Results The clinical response is superior to the PET/CT findings.

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

Side effects Impact on renal function

Side effects Impact on blood platelets

Side effects Impact on WBC

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.

Grazie per l’attenzione Ponte di Calatrava Reggio Emilia