Bandung Hematology Oncology Meeting 2015

24-25 October 2015, Hotel Hyatt, Bandung

PERANAN PENCITRAAN F-18 FDG PET

DALAM DIAGNOSIS DAN TATALAKSANA
LIMFOMA MALIGNA

Basuki Hidayat
Dept. Ilmu Kedokteran Nuklir dan Pencitraan Molekuler
FK UNPAD/Dr. Hasan Sadikin
Bandung
 P ositron E mission T omography

PET is a noninvasive, three-dimensional, nuclear medicine imaging

technique.
The PET images result from the use of different substances of
biological interest (sugars, amino acids, metabolic precursors,
hormones) labelled with positron emitting radioisotopes (PET
radiopharmaceuticals).
PET is a sensitive imaging method for detecting metabolic changes in
cancer.
PET is a sensitive measure of real-time metabolism of the body.

Cleveland Clinic Journal of Medicine, Volume 73, Number 12, December 2006
Journal of the National Comprehensive Cancer Network , Volume 7 Supplement 2 , June 2009
Radiopharmaceuticals for PET
F-18 (T1/2 110 min):
• FDG • FET
• FLT • NaF, etc
C-11 (T1/2 20.4 min):
• C-11 methionine • C-11 thymidine,
N-13 (T1/2 10 min):
• N-13 Ammonia
O-15 (T1/2 122 sec)
• O-15 Water
Ga-68 (T1/2 67 min)
• DOTA-TATE • DOTA-NOC
• DOTA-TOC
 Evolution of Technology

CT

PET/CT

PET
2001

1973 2000
Courtesy of George Segall MD
Clinical Applications of FDG-PET

Cardiology
5%
Oncology
85%

Neurology
10%
 Clinical indications of FDG-PET In Oncology
1) Diagnosis of malignant lesions.
2) Evaluation of the extent of disease (staging/restaging).
3) Study of patients with biochemical evidence of recurrence
(increase in tumour marker levels) but no clinical features or
evidence of disease with morphological imaging.
4) Differentiation of recurrent or residual malignant disease from
therapy-induced changes.
5) Study of patients with metastases from unknown primary sites.
6) Grading of malignant lesions.
7) Determination of the most aggressive part of the tumor to
plan biopsy.
8) Evaluation of tumor response to chemo- or radio-therapy.
9) Planning of radiotherapy
 Clinical indications of FDG-PET In Oncology
1) Diagnosis of malignant lesions.
2) Evaluation of the extent of disease (staging/restaging).
3) Study of patients with biochemical evidence of recurrence
(increase in tumour marker levels) but no clinical features or
evidence
4) of disease with morphological
Differentiation imaging.or
of recurrent
4) Differentiation of recurrent
residual or residual
malignant malignant
disease fromdisease from
therapy-induced changes.
therapy-induced changes.
5) Study of patients with metastases from unknown primary sites.
6) Grading of malignant lesions.
7) Determination of the most aggressive part of the tumor to
plan biopsy.
8) Evaluation of tumor response to chemo- or radio-therapy.
9) Planning of radiotherapy
Assessment of Lymphoma by Integrated IWC PET
 The lower HR between the PR and CR designations by IWC is most likely related to the
apparent existence of two distinct subgroups within the PR by IWC category with respect to
outcome: a subgroup of PET-positive patients with poor outcome and another of PET-
negative patients with excellent outcome.
The biologic explanation of this finding: the residual radiographic abnormalities represented
necrosis and/or fibrosis in the vast majority of the PET- negative patients, whereas the
abnormalities represented viable tumor in the majority of PET-positive patients.
Conclusion:
Compared with IWC, the IWC PET-based assessment provides a more accurate
response classification in patients with aggressive NHL.
1. Use of PET for Response Assessment of Lymphoma at the Conclusion of Therapy
2. Requirement for Pretherapy PET Scan for Response Assessment of Lymphoma at
the Conclusion of Therapy
3. Timing of PET Performed for Response Assessment at the Conclusion of Therapy
4. Interpretation of PET Scans Performed for Response Assessment at the
Conclusion of Therapy
5. Use of PET for Response Assessment During Treatment
6. Use of CT and PET or PET/CT for Response Assessment in Lymphoma Clinical Trials
7. Standardization of PET and CT Imaging Parameters
8. Transfer of PET Images Between Various Institutions
 Consensus of the Imaging Subcommittee of IHP in Lymphoma
1. Use of PET for Response Assessment of Lymphoma at the Conclusion of Therapy
• Distinguish between viable tumor vs necrosis/fibrosis in residual masses
• Curable lymphomas: HL and DLBCL
• After first line therapy;
• HL : Sensitivity: 84% (95%CI, 71-92%), Specificity : 90% (95%CI, 84-94%)
• DLBCL: Sensitivity: 72% (95%CI, 61-82%), Specificity: 100% (95%CI, 97-100%)
2. Requirement for Pretherapy PET Scan for Response Assessment of Lymphoma at
the Conclusion of Therapy
• Mandatory for lymphoma with variably FDG avid: Other aggressive NHL (T-cell),
all subtype of indolent except FL
• Noted the PET (+) at all disease site > 1.5 in Ø by CT
• Strongly encouraged for HL, DLBCL, FL, MCL; it can be facilitate the
interpretation of post-therapy PET
3. Timing of PET Performed for Response Assessment at the Conclusion of Therapy
• 3 weeks after chemo.
• 8-12 weeks after radiotherapy
 Consensus of the Imaging Subcommittee of IHP in Lymphoma
4. Interpretation of PET Scans Performed for Response Assessment at the
Conclusion of Therapy
• Visual assessment. Generally: focal/diffuse FDG uptake above background
• Except:
• Mild & diffuse FDG uptake:
• > 2 cm higher than mediastinal blood pool (MBP)  indicative residual
• < 2 cm higher than background  considered
• New lung nodules
• Ø > 1.5 cm, uptake > MBP & no pulmo. Lymphoma at baseline  suggestive
• CR at all previously lession  negative
• Ø < 1.5 cm  residual can not be exclude
• Residual hepatic / splenic lesions:
• > 1.5 cm, uptake > liver/spleen  considered
• < 1.5 cm, uptake > liver/spleen  considered
• Diffuse increased splenic uptake > liver w/o cytokine adm.  considered
• Multi (focal) bone (marrow):
• Biopsy  standard procedure for assessment
• Should be interpreted as positive
• Diffuse  hyperplasia
Consensus of the Imaging Subcommittee of IHP in Lymphoma
5. Use of PET for Response Assessment During Treatment
• Performed as close as posible (i.e wihin 4 days) before subsequent cycle
6. Use of CT and PET or PET/CT for Response Assessment in Lymphoma
Clinical Trials
• Contrast no required if no liver/spleen involvement at initial
• PET/CT w/o contrast adequate for response assessment lymphomatous/
extralymphatic involvement
• It is critical to report size of lesions
7. Standardization of PET and CT Imaging Parameters
Shankar et al. NCI 2006: Consensus Recommendations for the Use of F-18
FDG PET as an Indicator of Therapeutic Responsein Patients in National
Cancer Institute Trials
8. Transfer of PET Images Between Various Institutions
Digital Imaging and Communications in Medicine (DICOM) format
MODIFICATIONS OF THE IWG CRITERIA
 MODIFICATIONS OF THE IWG CRITERIA

Timing of PET scans after therapy

PET scans should not be performed for at least 3 weeks, and preferably
6 to 8 weeks, after completion of therapy.

Definition of a positive PET scan

• A positive scan is defined as focal or diffuse FDG uptake above background in a
location incompatible with normal anatomy or physiology
• Other causes of false-positive scans should be ruled out.
• Exceptions
• Mild and diffusely increased FDG uptake at the site of moderate- or large-
sized masses with an intensity that is lower than or equal to the MBP,
• Hepatic or splenic nodules 1.5 cm with FDG uptake lower than the
surrounding liver/spleen uptake,
• Diffusely increased bone marrow uptake within weeksafter treatment.
REVISED RESPONSE CRITERIA
Statement 3 (interpretation).
• A visual analysis using a 5-point scale should first be applied.
• The preferable reference scale should be the mediastinum and the liver.
Statement 4 (scoring).
The 5-point scale.
1. No uptake.
2. Uptake < mediastinum.
3. Uptake > mediastinum but < liver.
4. Uptake moderately more than liver uptake, at any site.
5. Markedly increased uptake at any site and new sites of disease.
 • INITIAL EVALUATION
• RECOMMENDATION FOR REVISIONS TO STAGING CRITERIA
• PROGNOSTIC GROUPS AND TREATMENT ALLOCATION
Summary
• Excisional biopsy is preferred for diagnosis, although core-needle biopsy may
suffice when not feasible.
• Clinical evaluation includes careful history, relevant laboratory tests, and
recording of disease-related symptoms.
• PET-CT is the standard for FDG-avid lymphomas, whereas CT is indicated for
nonavid histologies.
• A modified Ann Arbor staging system is recommended; however, patients are
treated according to prognostic and risk factors.
• Suffixes A and B are only required for HL.
• The designation X for bulky disease is no longer necessary; instead, a recording
of the largest tumor diameter is required.
• If a PET-CT is performed, a BMB is no longer indicated for HL; a BMB is only
needed for DLBCL if the PET is negative and identifying a discordant histology
is important for patient management.
 • ASSESSMENT OF RESPONSE AFTER TREATMENT
• FOLLOW-UP EVALUATIONS
Summary
• PET-CT should be used for response assessment in FDG-avid histologies, using
the 5-point scale; CT is preferred for low or variable FDG avidity.
• A complete metabolic response even with a persistent mass is considered a
complete remission.
• A PR requires a decrease by more than 50% in the sum of the product of the
perpendicular diameters of up to six representative nodes or extranodal lesions.
• Progressive disease by CT criteria only requires an increase in the PPDs of a
single node by 50%.
• Surveillance scans after remission are discouraged, especially for DLBCL and HL,
although a repeat study may be considered after an equivocal finding after
treatment.
• Judicious use of follow-up scans may be considered in indolent lymphomas with
residual intra-abdominal or retroperitoneal disease.
Recommendations for overall initial workup (staging)

Patient with palpable nodal disease

Biopsy & Diagnosis

F-18 FDG PET/CT

CECT limited to the field/s of F-18 FDG PET (+)

lesions

Therapy

End-therapy F-18 FDG

F-18 FDG PET (-) No need CECT F-18 FDG PET (+) Need CECT
Recommendations for bone marrow evaluation
(staging)
 Concluding Remarks

• F-18 FDG PET is a sensitive imaging method for detecting

metabolic changes in cancer
• The advantage of F-18 FDG PET scan in oncology is the
capability to differente of recurrent or residual malignant
disease from therapy-induced changes
• F-FDG PET have significant role in management of lymphoma:
initial staging, treatment response prediction and evaluation
• Need standard procedure of acquisition and interpretation of
F-18 FDG PET in lymphoma
• Interpretation of F-18 FDG PET in lymphoma management
mainly based on visual analysis
NHL Imaging Using Ga-DOTA-SSR