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PET Scanning for Solid Malignancies: What to Image, What Not Andrew Quon, M.D. MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Different Tumors have different affinities for glucose SUV is an approximation of Glucose Metabolism MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Hot, Medium Hot, Not so Hot SUV 15 10 Melanoma Hodgkin’s/NHL Colorectal CA Non-Small Cell Lung Cancer Esophageal CA Head/Neck CA 5 Hot Infiltrating ductal CA Poorly diff - thyroid Testicular CA Pancreas Bronchoalveolar CA Cervical CA Renal cell CA Medium Hot Lobular Breast CA Prostate CA Primary ovarian CA Well diff - thyroid Not So Hot Most Common Tumors Evaluated by FDG PET/CT 1. 2. 3. 4. 5. 6. Lung cancer Melanoma Esophageal cancer Colorectal cancer Head and neck cancer Lymphoma Cervical cancer Breast cancer Thyroid cancer GIST MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Lung Cancer • Diagnosis/Detection: Histologic type Pitfalls • Staging: Primary Tumor (T-staging) Mediastinal Lymph Nodes (N-staging) Extrathoracic metastases (M-staging) • Restaging/Treatment Monitoring: Evaluation of therapy response Detection recurrence & metastases MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Primary Detection of Lung Cancer Histology and pitfalls 1. Be wary of patients with prior history of granulomatous disease or active infection 2. Bronchioloalveolar Carcinoma and typical Carcinoid tumors have a higher false negative rate than other lung carcinomas Sensitivity >93%, specificity 80% MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology PET for T-Staging Lung Cancer n = 40 All cases were histopathologically correlated MIPS Imaging Method Correct T-Staging (%) CT alone 58% PET alone 40% Visual Correlation of PET and CT 65% Fusion PET-CT 88% Lardinois 2003 N Engl J Med Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology PET for Mediastinal Staging in NSCLCa Meta-analysis of 39 studies MIPS Gould 2003 Ann Intern Med Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Extrathoracic Metastases • PET detects an unexpected distant metastasis in 10-20% of lung cancer cases • PET is more accurate than CT for evaluating adrenal and liver metastases • Because of greater specificity, PET may be more accurate than bone scanning for metastases (~95% vs 85%) MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Melanoma • Detection: FDG avidity in Histologic types Size limitations • Staging: Comparison to SLN staging Staging in clinically advanced cases • Restaging/Treatment Monitoring: Detection recurrence & metastases MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Melanoma Primary Detection • Melanoma is amongst the most FDG avid malignancies - Also avid in Ocular and Mucosal Melanoma subtypes - Scarce data on Desmoplastic and Clear Cell Melanoma • A 2000 study on size and lesion detectability in melanoma: Size of Metastases (mm) % Metastases Found by PET (n=114) (23) (83) (100) (100) (100) (100) ≤5 6-10 11-15 16-20 21-25 > 25 • PET has limited role in primary melanoma detection/screening MIPS Crippa J Nucl Med 2000 Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology • 144 prospectively recruited patients with early stage melanoma • A direct comparison between using FDG PET initial staging versus SLN biopsy with complete histologic correlation • FDG PET sensitivity for local metastatic lymph nodes was 21% (PPV 67%) MIPS Wagner 2005 Cancer Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology PET for Initial Melanoma Staging • PET has a limited role in staging patients with early disease (i.e. patients negative for suspected adenopathy: Stage I and II) • Sentinel lymph node (SLN) dissection is superior to PET for detecting locoregional lymph node spread (particularly micrometastases) • PET is limited in detecting brain metastases and micrometastases • PET is used primarily for evaluating suspected distant metastases where it is superior to conventional imaging (patients with stage III and IV disease) MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Surveillance and Restaging Melanoma • High risk (Stage III and IV) patients should be evaluated periodically by PET imaging after treatment • Patients with established recurrence should have a restaging exam to evaluate additional metastatic disease • FDG PET is the single best diagnostic exam for this clinical scenario MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Esophageal Cancer Histologic type • Diagnosis/Detection Comparison to EUS Primary Tumor (vs. EUS)? • Staging Local Lymph Nodes Distant metastases • Restaging/Treatment Monitoring Evaluation of neoadjuvant therapy Detection recurrence & metastases MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Esophageal Cancer Primary Detection • Histology: Squamous cell carcinoma and adenocarcinoma perform equally well on FDG PET and moderate to high avidity • Be wary of false negative PET in adenocarcinoma with high mucin content • Current practice: The initial diagnosis of esophageal cancer remains the realm of endoscopy, endoscopic ultrasound and CT; PET may be used adjunctively MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology PET for Esophageal CA Initial Staging • For PET has no role in T-staging the primary tumor (Endoscopic Ultrasound) • The primary staging role of PET is to evaluate distant metastases and as an adjunct to EUS for locoregional lymph nodes • PET appears better than CT overall for detecting distant disease • Mixed results regarding FDG PET and evaluation of liver metastases MIPS Hustinx 2004 Rad Clin NA Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology FDG PET for Evaluation of Neoadjuvant Chemo • The goal of neoadjuvant treatment is to diminish primary tumor volume and extent of disease prior to surgical resection • PET is useful for evaluating chemotherapy response and selecting eligible candidates for subsequent surgery • Growing data that PET provides strong predictive data: PET responders may expect significantly longer overall survival vs. non-responders Weber J Clin Oncol 2004 Colorectal Cancer • Diagnosis/Detection: Histology Screening • Staging: Primary Tumor (T-staging)? Lymph Nodes (N-staging) Distant metastases (M-staging) • Restaging/Treatment Monitoring: Evaluation of therapy: Hepatic vs. Extrahepatic Detection of recurrence & metastases MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Colorectal Cancer Primary Detection • FDG PET is very avid for colorectal adenocarcinoma; - May be only 50% sensitive for mucinous subtype - Little data on squamous and signet ring subtypes • Some studies report PET is capable of detecting both pre-malignant and malignant lesions incidentally • However, the cost is still prohibitive and effectiveness is unclear in a screening population • Current practice: Periodic colonoscopy and evaluation through occult blood tests are still standard for primary detection MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology PET for Initial Staging Colorectal Cancer • Limited role in initial staging • Most patients undergo surgery for staging of the primary tumor • Not effective for T-staging colorectal cancer • Poor sensitivity for evaluating locoregional nodal spread • PET has good accuracy in evaluating liver metastases but liver ultrasound commonly performed preoperatively MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Primary Role of FDG PET in Colorectal CA: Restaging and Surveillance • Restaging: PET is more accurate than ultrasound for evaluating the liver and superior to CT for detecting abdominal metastases • PET particularly effective for detecting extrahepatic disease prior to resection of recurrent liver metastases • Surveillance: Pooled data shows PET has a sensitivity of greater than 90% and specificity of ~75% in detecting recurrence • PET particularly emphasized in patients at high risk for recurrence (by initial staging) and/or rising CEA levels MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Head and Neck Cancer Tumor types/histology • Diagnosis/Detection: Use for unknown primary H/N Primary Tumor (T-staging) vs. MRI? • Staging Mediastinal Lymph Nodes (N-staging) Distant metastases (M-staging) • Restaging/Treatment Monitoring Evaluation of therapy response Detection recurrence & metastases MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Tumor types/Histology • Most work has been done on squamous cell carcinoma (SCC) • Other pathologies – – – – – Thyroid carcinoma Lymphoma Mucosal melanoma Salivary gland tumors Sinonasal undifferentiated CA (SNUC)? MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Clinical Utility of PET: Unknown Primary Head and Neck Cancer • Some patients present with nodal SCC and the 1o site is unknown • Diagnostic work-up: - Cross-sectional imaging (MR) - Panendoscopy with “blind” bx of several sites + tonsillectomy • Empiric XRT to likely sites with neck dissection of no primary site is found • PET may be used adjunctively to identify primary site, best done prior to panendoscopy MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Sample Case: Unknown Primary • Multiple necrotic nodes on CT, FNA showed squamous cell carcinoma • No 1o site seen; no MR due to pacemaker • Endoscopy with biopsies 3 wks earlier was reported as negative, tonsillectomy had not been done MIPS Case courtesy of Nancy Fischbein, MD Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology FDG PET Nodal Staging: Studies Author Adams Benchaou Braams Kau Laubenbacher McGuirt Myers Pai Paulus Stoeckli Stokkel Stokkel Stuckensen Year 1998 1996 1995 1999 1995 1995 1998 1999 1998 2002 1999 2000 2000 Sens 90% 72% 91% 87% 90% 83% 78% 82% 50% 25% 100% 96% 70% Spec 94% 99% 88% 94% 96% 82% 100% 100% 100% 88% 90% 90% 82% No. pts 60* 48 12 70 22 45 14 7 25 12 20 54 106 Comment N0-N2c N0-N2 N0-N3 Neck sides evaluated N0-N3 N0-N2 N0 Mostly NPC Micromets in 5 FN All N0 patients Neck sides Dual head PET Prospective Sensitivity: ~90%; Specificity 82-100% MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology PET for Staging for Head/Neck Cancer • PET does not have enough anatomical detail for adequate T-staging of H/N cancer • PET is useful for detecting additional nodal and distant metastases • The sensitivity of PET for lymph node staging is remarkably variable: - Poor sensitivity in patients with clinically staged N0 disease - Excellent sensitivity in patients with established nodal disease - Good specificity overall • PET also valuable for detecting second primary lesions (e.g. lung) MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Strength of PET in Head/Neck Cancer: Post Treatment Evaluation of Residual/Recurrent Disease • Clinical and imaging follow-up are limited: tissue edema, fibrosis, distortion • FDG-PET sensitivity 80-100%, specificity 43-100% • High negative predictive value: disease is unlikely to be present if test is negative (very few false negatives) • Mixed evidence that PET may have considerably less accuracy (~70%) after XRT, particularly within 12 weeks (although some authors report 6 weeks) MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology Sample Case: PET post-treatment • Patient s/p XRT and chemotherapy for base of tongue cancer • Questionable residual disease on MRI • FNA biopsy confirmed all focal sites on PET Summary of Clinical Role of PET: Key Points for Each Tumor Type 1. Lung Cancer • Primary role: Initial staging (particularly N and M staging), evaluation of therapy, early prediction of prognosis, restaging/surveillance • Be wary of: Bronchioloalveolar CA (BAC) false negatives, granulomatous false positives 2. Melanoma • Primary role: Initial staging of patients with stage III & IV disease, restaging/surveillance • Weakness: Poorly evaluates locoregional lymph node spread, i.e. sentinel lymph node (SLN) dissection is better MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology 1. 2. 3. 4. i Summary of Clinical Role of PET (con’t): i Key Points for Each Tumor Type i Esophageal • Primary role: Initial staging of distant disease (M staging), evaluation of neoadjuvant chemotherapy response, restaging/surveillance, early prediction of prognosis • Note: Endoscopic ultrasound (EUS) likely better for initial staging of locoregional lymph nodes and the primary lesion 5. Colorectal • Primary role: Detection of recurrence (particularly in patients with rising CEA), restaging recurrent disease, • Note: PET mainly adjunctive role for initial T and N staging 6. Head and Neck • Primary role: Initial staging of patients with suspected nodal disease by physical exam & MRI, evaluation of therapy, restaging/surveillance • Be wary of: PET utility questionable for initial staging of patients with negative nodal disease (N0) by exam & MRI, poor T-staging, accuracy diminished after XRT MIPS Molecular Imaging Program at Stanford Stanford University School of Medicine Department of Radiology