PET/CT in Lymphoma Ur Metser, M.D. Division Head, Molecular Imaging Joint Department of Medical Imaging, UHN- MSH- WCH University of Toronto
Outline 1. Introduction: PET/CT, how does it work? 2.Current indications for use of PET/CT in lymphoma in Ontario 3. PET/CT: Special considerations
Introduction: What is PET/CT? PET/CT enables collection of anatomical and functional data in a single examination. Positron emitting compounds: carbon- 11, nitrogen- 13, oxygen- 15 and fluorine- 18.
*
PET/CT Patient in position #1 CT plane. Patient in position #2 PET plane
18 F-fluorodeoxyglucose (FDG) Increased FDG uptake in neoplastic cells: a. over- expression of transporter proteins (k1 ), b. high levels of hexokinase (k3 ), & lower levels of glucose- 6- phosphatase (k4 ). FDG effectively trapped in cells, allowing measurement of glucose metabolism.
Normal MIP
SUV: standardized uptake value SUV is a semiquantitative analysis of metabolism. Normalizes radiotracer concentration for injected activity and body weight. Factors influencing SUV s between scans (other than change in tumor): a. in serum glucose level, b. in body weight (due to uptake of FDG in fat), c. in time interval between injection and acquisition. d. inaccuracies in measured injected activity (e.g, extravasation)
Assessment of response to therapy: limitations of CT 1. At early surveillance, inaccurate in differentiating viable tumor from necrotic tissue (may underestimate response). 2. At end of therapy, cannot accurately separate residual viable tumor from fibrotic mass. 3. Interobserver variability in size measurements
CV= coefficients of variation
Insured indications for PET in lymphoma: current status in Ontario Evaluation of residual mass(es) following chemotherapy in patient with Hodgkin's or NHL when further potentially curative therapy (e.g radiation or stem cell transplantation) is being considered.
Residual mass post- chemotherapy
Residual mass post- chemotherapy
Post 6 cycles of ABVD for Hodgkin s Lymphoma
Does patient have residual viable disease?
Negative MIP
Complete metabolic response post 6 cycles of ABVD
Baseline CT and post 6 cycles of ABVD for HD
Does patient have residual viable disease?
Residual mass; residual disease Bx (guided by PET images): Classic HL à Pre transplant RT (30 Gy)
Stage 4B DLBCL (left iliac bone, liver) post R- CHOP with residual enlarged nodes in mediastinum and liver lesions on CT.
Hodgkin s Lymphoma Stage III: Residual nodes post therapy (ABVD x6)
Risk- adapted treatment regimen: Consolidative radiotherapy based on PET response German Hodgkin Study Group Preliminary data suggests that with a PET- CR after 6 8 cycles of BEACOPP radiotherapy can be omitted with no impact on early progression or relapse (awaiting 5 yr data). Kobe C, Dietlein M, Franklin J, et al. Positron emission tomography has a high negative predictive value for progression or early relapse for patients with residual disease after first- line chemotherapy in advanced- stage Hodgkin lymphoma. Blood. 2008;112(10):3989 3994.
Early response assessment of HD with FDG PET/CT Early assessment of response in early stage HD following 2 or 3 cycles of chemotherapy when chemotherapy is being considered as the definitive single modality therapy.
Early response assessment In HL and aggressive B- cell non- Hodgkin's lymphoma (NHL), PET performed after only 2 or 3 cycles of chemotherapy provides valuable prognostic information. Earlier identification of chemoresistant disease, prior to treatment completion, would facilitate an individualized, risk- adapted treatment strategy.
Early Interim FDG PET Is Prognostically Superior to International Prognostic Score in Advanced- Stage HL: A Report From a Joint Italian- Danish Study Prospective evaluation of high- risk HL (n=260) after cycle 2 PET. * Estimated 2- year PFS: 95% if negative PET; 13% if positive interim PET. * On multivariate analysis, only cycle 2 PET and the presence of stage IV disease were independently associated with outcome. * Interim PET was prognostically superior to IPS and emerges as the single most important tool for planning of risk- adapted treatment in advanced HL Gallamini et al. JCO 2007
Highly significant associations between early interim FDG- PET and PFS (P <0.0001) and OS (P <0.03). All advanced- stage patients with positive interim FDG- PET relapsed within 2 years. Minimal residual uptake on PET behaved similarly to PET- negative patients
MRU= Minimal Residual Uptake Right pelvic mass: SUVmax = 3.2
Risk- adapted treatment regimen 79% of initial high risk patients (IPS > 3) were PET (- ) after 2 cycles of esc- BEACOPP. Interim PET- based treatment was effective and feasible, with 5- year event- free survival (EFS) and OS of 85% and 90%, respectively Dann EJ. Risk- adapted BEACOPP regimen can reduce the cumulative dose of chemotherapy for standard and high- risk Hodgkin lymphoma with no impairment of outcome Blood. 2007;109:905-909
How does interim PET assessment work? Early PET offers a window into the chemosensitivity of the tumor. Chemotherapy kills tumor by first- order kinetics: a given dose kills the same fraction of cells (not same number) regardless of tumor size. Cancers are usually not diagnosed until they reach a size of 10 10 to 10 11 cells.
100,000,000,000 10,000,000
Early response assessment Early achievement of a negative PET is prognostically favorable, whereas persistent abnormal FDG uptake on early PET, even in the context of a CT response, raises concern for treatment failure.
Nodular Sclerosing Hodgkin s Lymphoma Stage IIA, Early, unfavorable Interim PET after 2 cycles of ABVD
Registry Indications for PET in lymphoma: current status in Ontario * Periodic Program in Evidenced Base Care (PEBC) lit reviews.
Registry Indications for PET in lymphoma: current status in Ontario * Evidence to suggest impact of PET in staging of potentially curable lymphomas: - PET/CT modified management in 9-32% of cases across studies. - Majority upstaged * Lymphoma staging registry to obtain more robust data to support use of PET in staging of potentially curable lymphomas. * To REPLACE 67 Gallium Scans
Indication #1: Staging of Early stage HD or NHL * PET in HL or NHL being treated with curative intent for the staging of apparent limited disease (Stage I & II) as per CI, and/or when imaging is equivocal for differentiating between limited stage disease and advanced stage disease.
Staging DLBCL CT: Nodal disease above diaphragm
Hodgkin s Lymphoma (Nodular lymphocyte predominant): Staging
Indication #2: Staging of Follicular/ other Indolent NHL * PET for apparent limited stage follicular lymphoma and other indolent NHLs where curative radiation therapy is being considered for treatment.
Staging Follicular Lymphoma Grade II (excisional LN bx right groin)
Metabolic Imaging: Factors to be considered.
PET performed after 5 days of chemotherapy
Effect of therapy on metabolic imaging * Too close to chemotherapy à temporary metabolic shutdown or conversely may show metabolic activity despite response if not enough time for metabolism to decrease. * TIMING is of paramount importance in metabolic imaging.
Additional considerations Thymic rebound (typical pattern) Other therapies (e.g. G- CSF): increased metabolic activity in bone marrow.
Further considerations Elevated serum glucose, steroid therapy or immunosuppressants may also decrease FDG uptake. Exercise within 24 hours of FDG injection. Effect of Corticosteroids on 18F- FDG Uptake in Tumor Lesions After Chemotherapy Lieselot Brepoels, Sigrid Stroobants, Peter Vandenberghe, Karoline Spaepen, Patrick Dupont, Johan Nuyts, Guy Bormans, Luc Mortelmans, Gregor Verhoef, and Christiane De Wolf- Peeters J Nucl Med 48: 390-397
Timing Chemotherapy: IHP in Lymphoma recommendations: at least 3 weeks (preferably 6 weeks from completion). Radiation therapy: Radiation- induced inflammation - up to 6 mo post Rad. FDG is not tumor- specific and uptake of FDG is seen in inflammation (activated macrophages). Therefore, the recommendations of the IHP in Lymphoma are to perform PET at least 8 weeks from radiation therapy.
www.petscansontario.ca