Απεικονίζοντασ τη Φλεγμονθ του Καρκίνου? Νικόλαοσ Τςουκαλάσ MD, MSc, PhD Ογκολόγοσ - Παθολόγοσ, MSc Βιοπληροφορική Επιμελητήσ Α, Ογκολογικό Τμήμα Νοςηλευτικό Ίδρυμα Μετοχικοφ Ταμείου Στρατοφ (417 ΝΙΜΤΣ) Αθήνα
Major Infection-Associated Malignancies In 2002, 17.8% of the global cancer burden (1.9 million cases) were infection-attributable Malignancy (infection) Stomach cancer (Helicobactor pylori) Cervical cancer (human papillomavirus) Liver cancer (hepatitis B and C viruses) Burkitt s lymphoma and nasopharyngeal cancer (Epstein-Barr virus) Kaposi sarcoma and Non-Hodgkin lymphoma (HIV/HHV-8) Bladder and colon cancer (schistosomiasis) Adult T-cell leukemia/lymphoma (human T-cell lymphotropic virus type I)
Mechanisms of Infection-Induced Malignancy Chronic Inflammation and Carcinogenesis Chronic host-pathogen interaction Immunosuppression Chronic inflammation Oxidative Stress DNA damage and mutations Cell injury Cell division Infection inducing Cell proliferation Production of Oncogenic Proteins Genomic Instability from Viral Genomic Integration
Evolution of Technology CT PET/CT PET 2001 1973 2000
In vivo μοριακή απεικόνιζη με ΡΕΤ (Positron Emission Tomography) - Μνξηαθή απεηθόληζε: πνιινί δηαθνξεηηθνί βηνινγηθνί markers επηζεκαζκέλνη κε ξαδηνϊζόηνπα ΡΕΤ ρξεζηκνπνηνύληαη γηα απεηθόληζε δηαθνξεηηθώλ βηνινγηθώλ θαηλνκέλωλ in vivo - Επηζεκαζκέλε γιπθόδε: απεηθόληζε κεηαβνιηζκνύ γιπθόδεο - ΡΕΤ κε FDG: ε πην ζπρλά ρξεζηκνπνηνύκελε εμέηαζε ζε νγθνινγηθνύο αζζελείο - Πνιινί άιινη δηαζέζηκνη markers (ξαδηνθάξκαθα) γηα δηαθνξεηηθέο βηνινγηθέο δηεξγαζίεο
PET Tracer: FDG Glucose FDG Plasma Cell Glucose FDG Glucose-6-P FDG-6-P 18F-fluorodeoxyglucose (FDG) is taken up by cells proportionate to their metabolic rates
FDG PET signal - [18F]FDG is transported into the cell via glucose transporters (GLUT). Mainly used transporters are GLUT- 1 and GLUT-3. In the cell [18F]FDG is phosphorylated via hexokinase II (HKII). - Φαηλόκελν Warburg ζηα θαξθηληθά θύηηαξα - Απεηθόληζε κεηαβνιηζκνύ γιπθόδεο (αύμεζε έληαζεο γιπθόιπζεο)
Πξνεηνηκαζία αζζελνύο γηα PET/CT - Νεζηηθόο 6-8 ώξεο - Ο ζαθραξνδηαβεηηθόο πξέπεη λα έρεη ξπζκηζκέλν ζάθραξν θαη γιπθόδε αίκαηνο θάηω από 200 mg/dl. Όρη ηλζνπιίλε 6 ώξεο πξηλ ηε ρνξήγεζε. Δηαθνπή κεηθνξκίλεο γηα 48 ώξεο αλαιόγωο. - Αθξηβέο ηζηνξηθό λόζνπ θαη πξνζθάηωλ ινηκώμεωλ-θιεγκνλήο Είδος θεραπείας Χρονικό διάζηημα για ΡΕΤ μεηά ηη θεραπεία Χεηξνπξγηθή Χεκεηνζεξαπεία (ζπκπ. βηνινγηθώλ ζεξ.) Αθηηλνζεξαπεία (θαη ζε ζπλδπαζκό) ηνπιάρηζηνλ 4 εβδνκάδεο 4-8 εβδνκάδεο ηνπιάρηζηνλ 3 κήλεο
Display CT PET Fused PET/CT 3D
PET CT PET/CT H.S., 077-64-28 FDG15 mci Bed 1 min CT (1 min) KVs130 kv mas75 ma Slice 5 mm
STANDARD UPTAKE VALUE Τη είλαη ην SUV? ROI decay corrected activity (mci/ml) Injected dose decay to scan time (mci)/ Body wt (g) Πόζεο θνξέο πεξηζζόηεξε είλαη ε ζπγθέληξωζε ηνπ ξαδηνθαξκάθνπ ζηελ πεξηνρή ελδηαθέξνληνο ζε ζρέζε κε ην αλ θαηαλέκνληαλ νκνηόκνξθα ζην ζώκα Πρακηικά: Όζν κεγαιύηεξε ε ηηκή SUV, ηόζν εληνλόηεξα ζπγθεληξώλεηαη ην FDG * Δελ ππάξρεη cut-off value πνπ λα δηαρωξίδεη θαθνήζεηα από θαινήζεηα.
Παξάγνληεο πνπ επεξέαδνπλ ην SUV Biological Weight composition Body size measurement Blood glucose level Post-injection uptake time Respiratory motion Technological Interscanner variability Intrascanner variability Reconstruction parameters (TOF, matrix, iterations etc) Calibration error Timing mismatch (scanner-dose calibrator) Use of contrast material for CT Interobserver variability Acquisition type Injected radioactivity ROI of measurement
What Are the Advantages of PET/CT? Advantages of CT high spatial resolution Advantages of PET better lesion characterization enhanced lesion detection
Πιενλεθηήκαηα ΡΕΤ έλαληη αλαηνκηθήο απεηθόληζεο - Μνξηαθή απεηθόληζε vs. Αλαηνκηθή απεηθόληζε: δύν εληειώο δηαθνξεηηθέο γωλίεο πξνζέγγηζεο ηνπ θαξθίλνπ - Μεηαβνιηθή δξαζηεξηόηεηα ζπλδέεηαη κε grade θαθνήζεηαο, Ki67 - Μεηαβνιηθή δξαζηεξηόηεηα πξωηνπαζνύο λόζνπ έρεη πξνγλωζηηθή αμία - Μεηαβνιηθή αληαπόθξηζε ζηε ζεξαπεία πξνεγείηαη ηεο αλαηνκηθήο - Χαξαθηεξηζκόο κηθξώλ ιεκθαδέλωλ ή εζηηώλ - Οιόζωκε απεηθόληζε - Αλάδεημε εζηηώλ λόζνπ επί αξλεηηθνύ ζπκβαηηθνύ ειέγρνπ (CUP, peritoneal implants)
Applications of PET-CT epilepsy tumor dementia Brain 5% Heart 5% Body 90% 76 % perfusion viability 1.5 million exams performed annually tumor infection bone
SURGERY 30.3% HEMATOLOGY 16.4% RAD.ONC. 9% OTHER 5.7% ONCOLOGY 38.5% Participant's Specialty
PET - CT in Tumor Imaging Detect radiographically occult lesions Characterize radiographic abnormalities Evaluate extent of disease Evaluate response to therapy
Normal PET - CT Body Scan
Abnormal PET - CT Body Scan
National Comprehensive Cancer Network Practice Guidelines in Oncology Acute Myeloid Leukemia Bladder Cancer Bone Cancer Breast Cancer Central Nervous System Tumors Cervical Cancer Chronic Myelogenous Leukemia Colorectal Cancer Esophageal Cancer Gastric Cancer Head and Neck Cancer Hepatobiliary Cancer Hodgkin s Disease Kidney Cancer Melanoma Myelodysplastic Syndromes Multiple Myeloma Neuroendocrine Tumors Non Hodgkin s Lymphoma Non-Small Cell Lung Cancer Occult Primary Cancer Ovarian Cancer Pancreatic Cancer Prostate Cancer Soft Tissue Sarcoma Skin Cancer (except Melanoma) Small Cell Lung Cancer Testicular Cancer Thyroid Cancer Uterine Cancer
National Comprehensive Cancer Network Practice Guidelines in Oncology Bone Cancer Breast Cancer Cervical Cancer Multiple Myeloma Non Hodgkin s Lymphoma Non-Small Cell Lung Cancer Occult Primary Cancer Ovarian Cancer Colorectal Cancer Esophageal Cancer Head and Neck Cancer Hodgkin s Disease Soft Tissue Sarcoma Small Cell Lung Cancer Testicular Cancer Thyroid Cancer Melanoma
Lesion Characterization 47 year old man with multiple trauma from a MVA who was incidentally discovered to have a pulmonary nodule
Lesion Characterization 84 year old man with chronic cough found to have a 13 mm nodule on CXR
Enhanced Detection 73 year old woman s/p resection for colon cancer, rising CEA level and negative CT
Enhanced Detection
Enhanced Detection 70 y/o male with H&N cancer
Enhanced Detection I-131 FDG PET 47 year old man with biopsy proven recurrent thyroid cancer 3 months after thyroidectomy
Unknown Primary 68 year old man who presented with right neck mass
Staging 49 year old man with new lung cancer
Recurrent Disease 64 year old man s/p laryngectomy, now has dysphagia
Monitoring Response 63 year old man stage 3A lung cancer, has received 4 cycles of chemotherapy
CT + PET/CT vs PET/ CT MOST CASES SOME CASES Standard CT followed by PET/CT if needed PET/CT CT component can be low resolution or optimized
Problems and Pitfalls False negative findings Tumor histology Lesions smaller than 8 mm Diabetes/Non-fasting patients False positive findings Normal physiology Granulomas and other infections Adenomas
Standard CT PET/CT 56 year man with HCV, end stage liver disease, and presumed hepatoma
Physiologic Uptake: Brown Fat
Infection 68 year old man with solitary lung nodule. Biopsy: aspergillosis
Granulomatous Disease 62 year old man with hilar and mediastinal adenopathy. Biopsy: sarcoidosis
Adenoma 82 year old man with wt loss and liver masses
Adenoma 82 year old man with wt loss and liver masses
Clinical Impact of PET/CT More accurate diagnosis Avoidance of unnecessary tests, and (potentially) harmful procedures Better treatment or management
National Oncologic PET Registry http://www.cancerpetregistry.org 36.5% change in decision to treat or not treat
Conclusions 1. CT is the first imaging test of choice in most cases 2. PET - CT is more accurate than CT alone Characterizing lesions difficult to biopsy Detecting occult cancer Determining extent of cancer and response to therapy 3. PET - CT changes management 36%
Why PET-CT?