Uso della PET nella valutazione della risposta

Transcription

1 La diagnostica per immagini e la radioterapia: una cooperazione nel nostro futuro Uso della PET nella valutazione della risposta Cagliari, 21 giugno 2008 Arturo Chiti Medicina Nucleare, Istituto Clinico Humanitas, Rozzano - Milano arturo.chiti@humanitas.it

2 FDG Uptake and Metabolism Glycogen 18 FDG-1-P 18 FDG K 1 K 2 Hexokinase K 3 18 FDG 18 FDG-6P K 4 Glucose-6- phosphatase 18 F-fru-6-P 18 FDG-6- phosphogluconolactone HMP shunt Glycolysis

3 Buerkle and Weber, Cancer Metastasis Rev, 2008

4 FDG compartment model Calibration Transmission Emission Young et al, Eur J Cancer 1999

5 Detection limit Fischer et al. EJNM 2005

6 Monitoring therapy response Objective and standardized criteria WHO Two perpendicular diameters, 50% decrease Moertel CG, Hanley JA. Cancer 1976 RECIST Largest diameter, 30% decrease One definition of response may not be adequate for prediction of response in all tumor types

7 Limits of morphologic imaging Radiologic criteria Reduction in tumor size may take time Scar tissue and edema may mask tumor regression Histopatologic criteria Regression score Close correlation with survival in some tumors Not useful to modify treatment

8 Monitoring response with FDG PET Visual interpretation Uptake is specific for viable tumor tissue Associated with a poor prognosis Quantitative assessment Baseline scan Tumor response Technical issues

9 Interpreting FDG uptake Young et al, Eur J Cancer 1999

10 Methods of Analysis Qualitative T/N ratio SUV Patlak plot Quantitative Non-linear regression

11 Standardized Uptake Value Single image No arterial input function required Plasma clearance is normal Steady state is reached Correction for plasma glucose level (?) Correction for: body weight body surface area (?) lean body mass (?)

12 Standardized Uptake Value SUV BW = A c, A tissue o BW A c,tissue : A o : BW: Activity concentration in a volume (tissue) of interest (VOI) injected activity body weight

13 Quantitative FDG measurement Acquisition time Partial volume effects Heterogeneous uptake Image processing smoothing / noise ROI definition Max value Mean value Plasma glucose level FDG is not glucose Pre Post

14 Common errors in SUV calculation Para-venous injection Residual activity in syringe No decay correction of activity Incorrect cross-calibration scanner/calibrator Variable uptake time

15 Interpreting SUV differences Tumors with sufficient baseline activity 20% changes can be considered significant Metabolic stunning Clinical context Correlation with outcome demonstrated in some tumors

16 EORTC criteria Progressive metabolic disease (PMD) SUV increase > 25% Visible increase in extent > 20% New lesions Stable metabolic disease (SMD) SUV increase < 25% or decrease < 15% No visible increase in extent Partial metabolic response (PMR) SUV reduction > 15-25% after one cycle SUV reduction > 25% after more than one cycle Complete metabolic response (CMR) Complete resolution of FDG uptake Young et al, Eur J Cancer 1999

17 When perform FDG PET? Chemo-sensitivity Chemo-resistance Chemotherapy Flare phenomenom Radiotherapy False positive?

18 Assessment of tumor response Chemo-resistance Chemo-sensitivity Weber and Wieder EJNMMI 2006

19 NHL - Early PET response Complete Censored PET- 0.8 Cumulative Proportion Surviving PET+ PFS Time Spaepen et al, Annals of Oncology, 2002 Cumulative Proportion Surviving Time PET- PET+ OS

20 PET predicts TF and PFS in HL Hutchings et al Blood 2006

21 Use of Positron Emission Tomography for Response assessment of Lymphoma: Consensus of the imaging subcommittee of International Harmonization Project in Lymphoma Malik Juweid, Sigrid Stroobants, Otto Hoekstra, Felix Mottaghy, Markus Dietlein, Ali Guermazi, Gregory Wiseman, Lale Kostakoglu, Klemens Scheidhauer,Andreas Buck, Ralph Naumann, Karoline Spaepen, Rodney Hicks, Wolfanf Weber, Sven Reske, Markus Schywaiger, Lawrence Schwartz, Josee Zijlstra, Barry Siegel and Bruce Cheson J. Clin. Oncol. 25: , 2007

22 Response evaluation in lung cancer: RT and CT/RT OS by PET response OS by CT response MacManus, JCO 2003

23 Evaluation of response to ChT in NSCLC TTP:163 vs 54 days p=.0003 OS:252 vs 151 days p=.005 Weber et al, JCO 2003

24 Mesothelioma Mesothelioma diffusely encases pleural cavity Mesothelioma causes morbidity and mortality through local disease rather than metastatic tumor burden Chemotherapy in mesothelioma is palliative however responding patients demonstrate improved symptoms, improved QOL and increased survival

25 Response assessment CT response assessment is challenging due to the rind-like pattern of tumor growth. Modified RECIST criteria (Byrne and Nowak, Annals Oncol 2004;15: ) - measurements perpendicular to pleural surface - 2 positions at 3 separate levels - measurements on f/up scans at same position and same level Limitations time consuming, subject to error, relatively insensitive, no account of viability of tissue, often require 3-4 cycles of chemotherapy to attain PR Mesothelioma is FDG-avid Studies showing emerging utility in staging and prognosis

26 Mesothelioma CT measurements Baseline Post chemotherapy

27 Patients with histologically proven MPM not candidates to curative surgery Evaluated with FDG at baseline and after 2 courses of chemotherapy CT scans at baseline and after every two cycles of chemotherapy CT response compared to PET metabolic response PET metabolic response = 25% SUVmax(bw) change

28 Early response in mesothelioma A patient classified as SD on CT and as PR on PET SUVmax 5.09 SUVmax 2.78

29 Sarcomatoid mesotelioma

30 Sarcomatoid mesotelioma

31 Sarcomatoid mesotelioma

32 Stage IV sarcomatoid mesotelioma

33 Stage IV sarcomatoid mesotelioma SUV max 7.7

34 Early response in mesothelioma Kaplan-Meier curve of time to disease progression by PET and CT proportion progressed (%) proportion progressed (%) time to progression (months) time to progression (months) PET response: p=0.02 CT response: p=0.57

35 Francis et al., JNM 2007 PET scan - coronal slices PET scan - region growing algorithm

36 After 1 cycle chemotherapy CT 10% change TGV 10% change SUVmax 10% change Survival Hazard ratio 0.71 ( ) 0.64 ( ) 0.65 ( ) p value Francis et al., JNM 2007

37 FDG PRE MET PRE MET POST

38 Conclusions There is evidence that FDG PET can be used to assess tumor response to chemo- and chemoradiotherapy The technique is of value for malignant lymphomas and for many solid tumors Visual interpretation of PET scans is sometime sufficient for assessment of tumor response after completion of therapy. Quantitative analysis of tumor uptake should be used in predicting tumor response early in the course of therapy In many cases SUVs seems to be adeguate to measure relative changes in tumor glucose use during therapy It is essential to follow a strict protocol for data acquisition, image reconstruction, and data analysis in order to reliably measure changes in tumor uptake with SUVs