PET/CT for Therapy Assessment in Oncology Rodolfo Núñez Miller, M.D. Nuclear Medicine Section Division of Human Health International Atomic Energy Agency Vienna, Austria
Clinical Applications of PET/CT in Oncology Stablished Characterization of tumor massess (e.g. Solitary Pulmonary Nodule). Staging and re-staging. Assessment of tumor response to therapy. Investigation of the patient with elevated tumor markers. Follow up and early detection of tumor recurrence. In Evolution RT Planning. Early detection of tumor response to therapy. Disease prognostication. Screening.
Limitations in Cancer Treatment Chemotherapy is selected empirically Complete response rates 10-20% Response can be slow Treatment-associated costs and morbidity Assessing whether treatment is complete is difficult
Ideal Planning of Cancer Treatment Non-invasive assessment of cancer phenotype and likelihood of response before therapy Early assessment of drug efficacy soon after therapy has begun Monitoring of efficacy, so therapy can be changed or discontinued Distinguish residual tumor from treatment effect
Tumor Response to Anticancer Agents 1960 Zubrod J Chronic Dis;11:7-33. 1976 Moertel, Hanley Cancer : 38:388-394 PR - palapation 50% decrease in size 1979 WHO handbook - PR 2 perpendicular diameters, 50% or > reduction 2000 RECIST PR J Natl Cancer Inst. 2000;92:205 216 uni-dimensional, 30% decrease
Interobserver and intraobserver variability in measurement of NSCLC lesions J Clin Oncol. 2003 Jul 1;21(13):2574-82.
Inflammatory Breast Cancer Rare, aggressive, young, poor prognosis MRI was the most accurate imaging technique in detecting a primary breast parenchymal lesion Sonography can be useful in diagnosing regional nodal disease. PET/CT provides additional information on distant metastasis, and it should be considered in the initial staging of IBC. Yang WT et.al. Breast Cancer Res Treat. 2007 Jul 26;
Assessment of FDG uptake
Standardized Uptake Value tissue conc. (µci/gm) SUV = inj. dose (µci)/body weight (gm) SUV shows a strong positive correlation with patient body weight (i.e., overestimated in heavy patients) SUV-lean and SUV-bsa are less weight dependent
Measurement of Tumor FDG Uptake: Reproducibility Test/re-test in 16 patients with various cancers with no intervening treatment Standard deviation 10% for SUV, SUV gluc, K i, and K i,gluc Change > 20% can be used to define a metabolic response Weber et al., J Nucl Med 1999; 40:1771
Consensus Recommendations: FDG PET as an indicator of therapeutic response in NCI Trials FDG PET can be an important tool for assessing therapeutic efficacy in large, multicenter trials. Enacting these recommendations will determine when and for what indications FDG PET can serve as a surrogate measure of therapeutic efficacy. The result should be shorter clinical trials and improved therapy for patients with cancer. Shankar et.al. J Nucl Med 2006:47;6, 1059-1066
Consensus Recommendations: FDG PET as an indicator of therapeutic response in NCI Trials Fasting, low carb diet, FBS < 200mg/dL FDG dose, hydration, sedative, uptake time Acquisition or Reconstruction 2D or 3D Image analysis SUV max ROI determination Timing post therapy Shankar et.al. J Nucl Med 2006:47;6, 1059-1066
Quantifying the Effect of IV Contrast Media on PET/CT There is a significant increase in SUV in regions of high-contrast concentration when contrast-enhanced CT is used for attenuation correction This increase is clinically insignificant. Accordingly, in PET/CT, IV contrast-enhanced CT can be used in combination with the PET to evaluate patients with cancer. Mawlawi et.al.ajr Am J Roentgenol. 2006 Feb;186(2):308-19.
71-y/o NSCLC after pneumonectomy with nodal metastases SUV = 3.2 SUV = 3.7
Average CT to match with PET Average CT Helical CT Helical CT w/o thorax Helical CT w/o thorax plus average CT of thorax Pan et al, J. Nuc Med, 2005
Tumor Imaging Mismatch 1: CT diaphgram position lower than PET +57% ACT Mismatch 2: CT diaphgram position higher than PET Pan, T et.al. J Nucl Med 2005;46:1481:1487 ACT
Hypothetical Relationship of Tumor FDG Uptake to Clinical Outcome Young H, et al. Eur J Cancer 1999; 35:1773
Large B-cell Diffuse Lymphoma Response to R-CHOP Baseline SUV cor = 7.7 1 Day SUV cor = 1.2 20 Days SUV cor = 0.0 Yamane et al. J Nucl Med 2004; 11:1838 End SUV cor = 0.0
Metabolic Response EORTC Recommendations PD SUV by more than 25%, or visible increase in tumor size, or new lesions SD SUV by less than 25% or by less than 15%, and no visible increase in tumor size PR SUV by at least 15-25% after 1 cycle of chemorx or by at least 25% after more cycles CR Complete resolution of abnormal FDG uptake Young et al., Eur J Cancer 1999; 13:1773
Oncology Biomarker Qualification Initiative FDA, NCI, part of the NIH and CMS First project to be implemented will serve to validate and standardize the use of FDG-PET Trials of patients being treated for non-hodgkin's lymphoma, to determine if FDG-PET is a predictor of tumor response. Data resulting from this type of evidence-based study will help both FDA and CMS work with drug developers based on a common understanding of the roles of these types of assessments. http://www.cancer.gov/newscenter/pressreleases/obqi
PET/CT for the evaluation of response to theraphy Lymphoma NSCLC Head and neck ca. Colon ca. Breast ca. Ca of the esophagous. Cervical and Ovarian cancer
42 year old patient with Hodgkins Linforma stage 4B. Referred for assessment of response to therapy after 2 cycles of ABVD. January 13, 2006 2 cycles of ABVD March 10, 2006 Report of the CT scan done with iv contrast: improvement in the adnopathy, likelly reflecting response to therapy the slpenn is smaller, however, low density lesions remain, consistent with residual tumor in the spleen..
January 13, 2006 March 10, 2006
January 13, 2006 March 10, 2006
7/12/2009 17/9/2009
17/9/209 7/12/2009
17/9/209 7/12/2009
PET to Detect Residual Lymphoma High NPV Good prognosis Close follow up, relapse >1 year Can RT be omitted? High PPV Exclude False (+) Biopsy residual Consider further Rx
Example BM involvement (+) BM involvement(-), GCSF(+)
27-year-old female who noticed dark urine, and workup showed that she had jaundice with bilirrubin up to 16. CT scan showed porta hepatis lesions and also intrahepatic lesion with an intra-hepatic biliary duct dilatation. The patient was referred to M.D. Anderson Cancer Center for further evaluation and initially was seen by the GI medical oncology. A core needle biopsy of her liver lesion, however, showed Hodgkin's lymphoma.
27 year old w/ Hodgkin s lymphoma Baseline ABVD 2 cycles doxorubicin, bleomycin, vinblastine, dacarbazine
27 year old with HD 4 cycles of ABVD Developed cough Dyspnea on exertion
Patient had BAL (negative) Pulmonary function tests obtained showed moderate restriction and diffusion capacity was severely reduced. Patient became asymptomatic 4 weeks after last course of therapy Resumed on AVD chemotherapy 2 cycles, PET at end of therapy
Pulmonary drug toxicity: FDG-PET findings in patients with lymphoma. Kazama T. et. al. Ann Nucl Med. 2008 Feb;22(2):111-4. Epub 2008 Mar 3.
63 year old woman with recurrent follicular lymphoma
I-131 Bexxar SPECT/CT
63 year old woman with recurrent follicular lymphoma FDG PET/CT 2 months after 131-I Bexxar
JNM May 2009 Supplement
Thank You