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

Thank You