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
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
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.
Stablished
RT Planning.
Early detection of tumor response to therapy.
Disease prognostication.
Screening.
In Evolution
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
J Clin Oncol. 2003 Jul 1;21(13):2574-82.
Interobserver and intraobserver variability
in measurement of NSCLC lesions
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, SUVgluc, Ki, and Ki,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
Mismatch 2:
CT diaphgram
position higher
than PET
ACT
ACT
+57%
Pan, T et.al. J Nucl Med 2005;46:1481:1487
Hypothetical Relationship of Tumor
FDG Uptake to Clinical Outcome
Young H, et al. Eur J Cancer 1999; 35:1773
Yamane et al. J Nucl Med 2004; 11:1838
Large B-cell Diffuse
Lymphoma Response to R-CHOP
Baseline
SUVcor =
7.7
1 Day
SUVcor =
1.2
20 Days
SUVcor =
0.0
End
SUVcor =
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
17/9/2009
7/12/2009
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
BM involvement (+) BM involvement(-), GCSF(+)
Example
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 intra-hepatic 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
ABVD 2 cycles
doxorubicin, bleomycin, vinblastine, dacarbazine Baseline
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
FDG PET/CT 2 months after 131-I Bexxar
63 year old woman with recurrent follicular lymphoma
JNM May 2009 Supplement
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