Status of PET/CT in Oncology— Emphasis on Current and Emerging Clinical Applications:
Richard L. Wahl, M.D. Division of Nuclear Medicine Department of Radiology Johns Hopkins Medical Institutes Baltimore, MD
9th International SAC Seminar on New Trends in Positron Emissiong Tomography (PET):
Cancer Imaging: The Questions
• • • • • • • Is cancer present (detection)? Is a mass cancer or not? Is the cancer localized or spread? How should the cancer be treated? Is a treatment working? Is more treatment needed? What is the prognosis?
• Does my new agent reach the target? • Does my new agent perturb tumor physiology?
Cancer Imaging: 100 Years of ―Form‖
• Form=Anatomy • Anatomy is and has been cornerstone of cancer imaging for diagnosis, staging and follow up. • Form has served us very well, X-Ray, US, CT, MRI etc.
Limitations of Imaging Form or Anatomy I.
• Detect masses, does not characterize them to a significant extent (fat, water, air) as to contents • Show lymph nodes as present or absent but doesn’t reliably state what is within lymph nodes
– (45% sensitivity in colorectal ca. for ln involvement)
• Often difficult to detect small tumor foci, especially if surrounded by normal tissues. • If small lesions identified, cannot be specific as to cause • Performance less good in post operative state due to distortion of normal anatomy
Limitations of Imaging Form or Anatomy II.
• Does not predict response to a given therapy • Displays limited information re. Tumor biology (60% accurate for invasion) • Slow to display response to treatment • Difficult to measure cytostatic responses • New imaging techniques, especially PET have potential to address limitations of anatomic imaging.
Molecular and Functional Alterations in Cancer I.
• • • • • • • • Increased glucose metabolism Increased Amino acid transport Increased Protein and membrane synthesis Increased DNA synthesis Overexpression of receptors/antigens Increased blood flow or vessel density Decreased oxygen tension in lesions Increased apoptotic rates with effective Rx
What is PET/CT?
• • • • • • Hybrid Imaging Device/Modality CT scanner (high quality images of anatomy) PET scanner (high quality images of function) Computer and software to fuse/display images No patient motion between studies Displays Anatomy, Function and the parameters fused in a series of images • Look into the body, see what it is doing and where
What are the benefits of PET/CT?
• Accurate spatial localization of abnormalities detected on PET—which can be VERY difficult to locate on PET alone • Accurate determination of location of questionable abnormalities on PET—are they normal tissues with FDG uptake or tumor?
What are the benefits of PET/CT?
• More rapid scans, less motion of patient • Higher quality transmission counts/precision • Consolidation of visits to imaging specialist • Goal: Better Diagnostic Accuracy
CT scan protocol
• Patient is positioned head first and supine on the table • Scanning begins from meatus of ear to mid thigh • Shallow breathing during the CT
CT: What do I want to achieve?
• Attenuation Correction Only • Localization only • Moderately high quality but modulated radiation dose for clear organ/lesion localization • Diagnostic CT, non contrast • Diagnostic CT, i.v. contrast • How much of the body needs to be imaged? • What radiation dose will I give and is it appropriate? • Breathing management an issue
• • • • • • • • •
Oncology–specific PET indications approved by HCFA
Solitary pulmonary nodule (SPN) Non-small cell lung cancer (NSCLC) Colon cancer Hodgkin’s and non-Hodgkin’s lymphoma Melanoma Head and neck cancer Esophageal cancer Thyroid cancer (rising TG) Breast cancer, specific applications
Quantitation
• SUV (standardized uptake value)
= Tissue Concentration (KBq/g) Injected Dose (KBq) / Body Weight (g)
Strauss and Conti. J Nucl Med 1991.
• SUV shows a strong positive correlation with patient body weight (i.e., overestimated in heavy patients).
Zasadny and Wahl. Radiology 1993.
How Accurate are CT and PET in Mediastinal Staging ?
• • • • • • Meta Analysis 29 CT studies 14 PET studies PET significantly more accurate than CT CT sens/spec 60/77% (n=2236 pts) PET sens/spec 79/91% (n=514)
– Dwamena etal. Radiology 1999,213:530-536
Changes in Management due to PET
• Randomized Trial
– PET or CDM only groups
• CDM group had 41% incidence of ―futile‖ thoracotomies • PET group had 21% frequency of ―futile‖ thoracotomies
– Van Tinteren, Lancet 2002:359:1388-93
Figure 1a
Branstetter, B. F. et al. Radiology 2005;235:580-586
Copyright ©Radiological Society of North America, 2005
Normal Tissues with FDG Uptake
Normal Head and Neck: Tonsils Submandibular and Parotid Glands Cricoarytenoid muscles Minimize by NOT talking during uptake nor swallowing.
Female, age 65 Colon ca sigmoid resection, chemo & right liver lobe resection CEA is 2.4 CT is negative
PET – CT
Hodgkin’s Lymphoma
HISTORY
27 Female Stage IV Hodgkin’s Lymphoma s/p chemotherapy and BMT
Evaluation for possible recurrence
PET – CT
Hodgkin’s Lymphoma
FINDINGS
3 Focal Abnormalities Spleen
FINDINGS Intense FDG uptake 3 Foci within Spleen DIAGNOSIS Recurrent disease
CT
PET
FUSED
2.7 USA Fat
• 3.9% of all patients have abnormal activity fusing in fat • Unsuspected before PET-CT
• THE SUPRACLAVICULAR FDG «MUSCLE» UPTAKE ARTIFACT IS OFTEN NOT MUSCLE : EVALUATION WITH PET-CT. • C Cohade, M Osman, R L Wahl
Male, age 56 Right shoulder stage III melanoma s/p sentinel node dissection, neg pathology Mass in right axilla 4 months later
Female, age 64 Right breast cancer by FNA 1 cm lesion UOQ of right breast, 2 Lymph nodes in right axilla
40 yo female, hx 3C ovarian cancer 5 years prior to PET/CT. CT outside Showed 2 cm ant abdominal mass and sub cm nodes periaortic region. ? Other foci of tumor?
40 yo female, hx 3C ovarian cancer 5 years prior to PET/CT. CT outside Showed 2 cm ant abdominal mass and sub cm nodes periaortic region. ? Other foci of tumor?
40 yo female, hx 3C ovarian cancer 5 years prior to PET/CT. CT outside Showed 2 cm ant abdominal mass and sub cm nodes periaortic region. ? Other foci of tumor?
PET – CT
Recurrent Thyroid Carcinoma I-131 negative
HISTORY
28 Female Papillary thyroid Carcinoma and metastases
Treated I-131 in 1993
Elevated TG and Negative I-131
FINDINGS Focal increased FDG
2 Right lower cervical LN 1 Left paratracheal LN DIAGNOSIS
Pathology – 4 positive LNs and positive midline LN papillary CA
54 yo male, hx 4A cholangiocarcinoma distal CBD. S/P Whipple 2 yr Prior to PET/Ct. Suspicious CT for recurrence. PET positive fu.
• Aggressive multimodality therapy (surgery, radiation, chemotherapy) standard care for many brain tumors • CT and MRI unable to distinguish post-treatment necrosis from recurrent tumor • FDG-PET shows hypometabolism with necrosis and maintained metabolism with tumor
– Sensitivity and specificity 80% (results best with coregistration)
FDG-PET: Radiation Necrosis vs. Recurrent Brain Tumor
• FDG uptake related to prognosis
– 2-4X longer survival with low vs. high metabolic activity
Where is FDG PET Less Effective?
• Hepatomas (half clear FDG activity rapidly) • Renal Cancers (frequently difficult to distinguish from renal cortex and excreted activity) • Prostate Cancers (majority lukewarm except some aggressive metastases) • Tumors near uroepithelium (primary lesions) due to background activity
Role of PET in Treatment Response Monitoring
• Experience Growing Rapidly • FDG is Most explored to date • Residual Mass Characterization data in Breast cancer, testicular cancer, lymphoma and lung cancer • High FDG uptake bad, low FDG better • Rapid decline in activity good and common with chemotherapy—predictive of outcome in breast, esophageal cancer, lung and lymphoma • RT may cause slower declines as reproductive deaths and inflammation
What are roles of PET in Radiation Oncology
• Precise delineation of location of tumor • With PET/CT or markers, definition of normal tissues • Potential assessment for hypoxia or other phenotypic features, proliferative rate etc. • Assessments post therapy for adequacy of treatment, however more work is needed to determine how long residual FDG signal persists in varying situations
Emerging Roles of PET and PET/CT
• Radiation Therapy Planning
– Biological Tumor Volume vs. Anatomic Tumor Volume – Differing field sizes common – Changes in GTV common especially if there is parenchymal lung disease Reductions in normal lung irradiated
Other Tracers for Clinical PET
• • • • • • • • C11 Choline, F18 Choline C11 Acetate C11 Methionine--FET C11 Thymidine, F18 FLT F18 Misonidazole Cu 62 ATSM O 15 water 18 F NaF
• •
FDG PET Prostate Cancer False negative in multiple metastases
C-11 Choline WB Scan with multiple metastases especially in pelvis
NOPR National Oncologic PET Registry
• Hundreds of thousands of people with cancer will now have their positron emission tomography (PET) scans covered by Medicare as a result of the launch of the National Oncologic PET Registry (NOPR) by The American College of Radiology (ACR) and the American College of Radiology Imaging Network (ACRIN).
• Previously, Medicare only reimbursed for PET scans for several common cancers, but the opening of the NOPR means that participating Medicare beneficiaries will now have PET scans covered for essentially all types of cancers including, but not limited to, brain, cervical, small cell lung, pancreatic, testicular, and ovarian cancers.
Clinical PET/CT Imaging at JHU
• • • • Cancer 90% Brain 4% Cardiac 4% Other 2%
Why has PET/CT grown so rapidly as a clinical imaging tool?
• FDG is a superb and process specific tracer of a very common physiological alteration in cancers • PET imaging is sensitive • PET/CT imaging is specific • Diagnostic accuracy of PET/CT is high • RELEVANT and PRACTICAL diagnostic information is provided • FDG PET/CT is a ―killer application for PET‖ • FDG PET/CT addresses UNMET medical needs
Summary: Clinical PET/CT
• Oncologic applications are currently dominant and have expanded with NOPR activation in the US • Higher quality Diagnostic CT scans with contrast more common as ―one stop‖ diagnostic tool with PET/CT • Earlier use of PET/CT soon after therapy is initiated to perform ―Risk Adaptive‖ treatment planning specific to the patient may become the norm • Additional tracers and technical improvements will drive clinical PET forward in oncology • Lowered reimbursement rates may somewhat slow the explosive growth of the technology in the near future in the US
Acknowledgements:
• • • • • • • • • • Christian Cohade Medhat Osman Cherry T. Thomas Terrance Teslow Jeff Leal Ron Rosen Bennett Chin Pavni Patel Rex Yung Rusty Lavely Stephanie Weiss Ted DeWeese Frank Bengel Heather Jacene Kent Friedman Eliot Fishman