1. Using PET in Lymphoma
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2. Oncology Imaging Computed Tomography (CT) Photon attenuation Anatomy
Magnetic Resonance (MR) Spin flip time Anatomy (blood flow)
Ultrasound (US) Sound attenuation Anatomy
Conventional Nuclear Radioactive tracer Function
Medicine (NM) uptake
Positron Emission Radioactive tracer Function
Tomography (PET) uptake
Function

3. 18F-FDG Pharmacokinetics
Plasma Cell
Glucose
FDG
Glucose-6-P
FDG-6-P
FDG participates in the first step of glucose metabolism, but cannot be further metabolized and is trapped inside the cell where it is retained in proportion to the rate of glycolosis.

4. Normal distribution pattern of 18F-FDG
After IV injection, FDG is distributed to all organs of the body in proportion to cellular glucose metabolism.
Normal biodistribution will demonstrate uptake in the brain, evidence of excretion via the urinary and GI systems, faint hepatic uptake, some bone & soft tissue uptake, and variable cardiac uptake
Cancer cells are highly metabolic and utilize glucose at 3-5x the rate of normal cells.

5. Oncology Imaging Clinical Applications of PET
Characterization of radiographic abnormalities
Detection of radiographically occult lesions
Staging – initial evaluation of the extent of disease
Restaging - evaluation of the extent of recurrent disease (resectability)
Evaluation of response to therapy 3

6. Characterization of Radiographic Abnormalities
66 yr old w/ ovarian cancer & brain mets treated w/stereotactic radiosurgery & chemotherapy; developed right hemiplegia 2 wks prior to PET. Treated w/steroids, symptoms resolved.
A new mass or nodule is identified by conventional imaging (x-ray, CT, MRI, US) and the physician needs to determine what it is.

7. Characterization of Radiographic Abnormalities
61 year old woman with ovarian cancer and brain metastases treated with whole brain and stereotactic radiation

8. Characterization of Radiographic Abnormalities
66 year old man with pancoast tumor of the right lung – new adrenal mass.
CT shows enlargement of the right adrenal gland, adenoma vs metastasis.

9. Accuracy of PET in characterizing adrenal masses
Differentiation of Benign from Malignant Adrenal Masses
Sensitivity Specificity
Yun % (18/18) 94% (30/32)
J Nucl Med 2001;42:1795
Erasmus % (23/23) 80% (8/10)
Am J Roentgenol 1997;168:1361
Maurea % (7/7) 100% (6/6)
Radiol Med 1996;92:782
Boland % (14/14) 100% (10/10)
Radiology 1995;194:131 3

10. Detection of a radiographically occult lesion
61 yr old man s/p partial colectomy for sigmoid cancer, rising CEA level to Negative CT, CEA scan, bone scan, colonoscopy. PET demonstrates FDG uptake; biopsy = adenocarcinoma.
Abnormal lab values or physical symptoms indicate possible cancer or cancer spread, but conventional imaging is normal

11. Staging after initial diagnosis of cancer
To determine extent of disease and select the most appropriate treatment course
Surgery
Induction chemo and/or radiation therapy prior to surgery
Systemic therapy
Palliative therapy
Images courtesy of Macapinlac, UT MD Anderson Cancer Center

12. Restaging a known or suspected recurrence
76 yr old with locally recurrent cervical cancer, CT shows pelvic adenopathy, scheduled for pelvic exenteration. PET positive for disease beyond pelvis.
To determine extent of disease, particularly if planned treatment is local/regional surgery or radiation therapy to confirm suspicion of recurrence

13. Restaging a known recurrence
Repeat positive right breast excisional biopsy.
Conventional imaging negative and pt scheduled for right mastectomy
PET results: Widespread liver metastases
7 cm abdominal mass (!)
Unsuspected left breast tumor
Bone metastases, left acetabulum
Impact: Mastectomy cancelled and chemotherapy initiated
Restaging a Known Recurrence
In this case, a patient with a history of Rt. Breast cancer, post wedge resection, chemo and radiation therapy, presented with elevated tumor markers and a new right breast mass. The excisional breast biopsy was positive for metastatic breast cancer. Restaging by conventional imaging was negative and she was scheduled for a mastectomy. Tumor markers remained elevated after the excisional biopsy (should have returned to zero if that were the sole metastatic lesion). PET was performed to confirm extent of disease prior to surgery. PET demonstrated widespread liver metastases, a 7 cm abdominal mass, unsuspected Lt breast tumor, and a bone lesion on the left acetabulum. Her mastectomy was cancelled and she received high dose chemotherapy.
Images courtesy of Landis K. Griffeth, MD, PhD, North Texas Clinical PET Institute

14. Restaging a known recurrence
Restaging at completion of therapy
The post treatment scan demonstrated complete resolution of her metastatic disease and confirmed the effectiveness of the chemotherapy.
Images courtesy of Landis K. Griffeth, MD, PhD, North Texas Clinical PET Institute

15. Evaluating response to therapy
To determine effectiveness of treatment and whether additional treatment is necessary
Testicular cancer patient with apparent complete response to chemotherapy
Images: Northern California PET Imaging Center

16. Lymphoma Hodgkin’s (HD) & non-Hodgkin’s (NHL)
Problem:
74,340 new U.S. cases in 2008 (HD = 8,220; NHL = 66,120)
20,510 cancer deaths in 2008 (HD = 1,350; NHL = 19,160)
HD 85% 5 yr survival rate: NHL 63% 5 yr survival rate
Most patients with newly diagnosed Hodgkin’s are curable w/ stage adjusted radiation therapy and/or combination chemotherapy regimens
Prognosis is dependent on histology, stage of disease at presentation and treatment response
Source: American Cancer Society. Cancer Facts and Figures Atlanta

17. Lymphoma Hodgkin’s (HD) & non-Hodgkin’s (NHL)
Differences between HD & NHL factor into diagnosis and treatment:
Hodgkin’s begins as a unifocal disease located in a single group of malignant lymph nodes and spreads via adjacent lymph node groups
Limited disease (stage I or II) is treated with radiation therapy & is curative for a high percentage of patients
Patients with advanced disease have poorer prognosis – treated with chemotherapy

18. Lymphoma Non-Hodgkin’s (NHL)
NHL is multifocal disseminated disease and is classified as low, intermediate or high grade based on histocytology
More likely to develop non-nodal metastases
Require a combination of chemo & radiation therapy
Often resistant or relapse and require high dose chemotherapy & bone marrow transplantation
Low grade NHL has a better prognosis if left untreated, does not respond well to chemo
High grade NHL is rapidly fatal if untreated – long remissions & cures can be induced with therapy

19. Lymphoma Hodgkin’s (HD) & non-Hodgkin’s (NHL)
Staging – physical examination
CT of the neck, chest, abdomen & pelvis
Limitations – lymph node evaluation by size, difficulty in evaluating spleen, liver or bone marrow
Gallium67 imaging
Limitations – noisy images, variable uptake by tumors, limited detection of abdominal disease, multi-day exam
Bone marrow biopsy
Limitations – invasive aspiration & biopsy w/ sensitivity limited by sampling error (disease may be present in the marrow, but not in the area sampled)

20. Lymphoma Hodgkin’s (HD) & non-Hodgkin’s (NHL)
Staging – Role for PET
Avid uptake by virtually all lymphomas (uptake does correlate with grade of tumor & degree of proliferation)
Higher sensitivity & specificity for detection of nodal & extranodal disease than anatomic imaging
Higher image quality allows improved detection of CNS, abdominal and pelvic lesions over Ga67
Detection of focal bone marrow disease
Evaluation of CNS lymphomas – differentiate inflammatory lesions & tumor extension (HIV + patients)
Degree of uptake is predictive of patient outcome

21. Lymphoma Staging
Pre
Post
PET provides information which can aid the physician in more accurately staging Lymphoma. Conventional staging modalities are useful, but have their limitations. Diagnostic criteria cannot be based on size alone. Small malignant nodules may be missed by conventional imaging, and enlarged lymph nodes may be benign. Conventional imaging may not detect involvement of the spleen, liver or bone marrow.
In this case, a 28 year old female was diagnosed with Hodgkin’s disease through a left cervical lymph node biopsy.
A PET•CT scan was recommended for initial staging, which revealed extensive lymphadenopathy with markedly increased FDG uptake consistent with the patient’s known history of Hodgkin’s disease.
Chemotherapy was implemented and the follow-up PET scan after completion of therapy showed that the treatment had been effective.
28 year old female with newly diagnosed Hodgkin’s disease through left cervical lymph node biopsy. PET•CT for initial staging. Extensive lymphadenopathy with markedly increased FDG uptake consistent with the patient’s known history of Hodgkin’s disease.
Images courtesy of Barry Siegel MD, Barnes Jewish Hospital, St. Louis, MO

22. PET in Lymphoma PET imaging for initial staging of lymphoma:
Can alleviate numerous other tests that have lower accuracies like illiac bone marrow biopsies for lymphoma patients
Takes care of debate over residual lymph nodes
PET imaging for restaging of lymphoma:
Baseline and Post-Tx PET improves direct assessment of residual masses
Improves assessment of response to therapy (at end vs. interim)
Improves prognostic assessment (at end vs. interim)

23. Lymphoma Staging
Delbeke et al, used PET in initial staging 45 patients:
PET alone: staging accuracy = 91%
Combined conventional staging modalities accuracy = 84%
PET correctly changed the stage of 16% of patients, but under staged 7% (absent or low tumor uptake)
Major advantage was assessment of bone marrow involvement
Recommend PET in conjunction with conventional staging methods
Source: Delbeke, MIB Vol 4:1,

24. Lymphoma Restaging & Response to Therapy
Restaging & Response to therapy: Role for PET
Identification of recurrence
Identification of residual lymphoma after treatment
Differentiate viable tissue from fibrosis
Proven prognostic value – residual FDG uptake s/p treatment is a strong predictor or relapse or progression of disease as well as a predictor of survival
FDG PET CT
# of PTS Sens Spec Sens Spec
Source: Gambhir, JNM Vol 42:5, pp 16S-20S. 2001

25. Lymphoma Restaging 53 y/o female, history of HD, s/p
stem cell transplant
CT: adenopathy in the celiac and porta hepatis abdominal lymph nodes. ? active HD
PET: markedly abnormal, FDG uptake throughout the body consistent with active Hodgkin's disease
PET confirmed active disease, high dose chemotherapy treatment implemented.
Images courtesy of Landis K. Griffeth, MD, PhD, North Texas Clinical PET Institute

26. Lymphoma Summary Summary: Role for PET
Staging the disease before treatment
Monitoring response to therapy
Detecting recurrence
Correlation of uptake with prognosis

27. Problems and Pitfalls False negative: Size less than 10 mm
Diabetes fasting blood glucose level >150 mg/dl
Histology low grade glioma
low grade lymphoma
bronchoalveolar carcinoma
mucinous adenocarcinoma
thyroid, liver, kidney, prostate CA

28. Problems and Pitfalls Non-Malignant (false) positives:
Infection granuloma, abscess, pneumonia
Inflammation pneumonitis, wounds, arthritis, reactive nodes
Uncertain sarcoid
Benign tumors thyroid, parathyroid, carcinoid, colon
Autoimmune rheumatoid nodules, thyroiditis
Miscellaneous fractures, Paget’s disease

29. PET in Oncology Summary
Clinical Applications of PET
Characterization of radiographic abnormalities
Detection of radiographically occult lesions
Staging – initial evaluation of the extent of disease
Restaging - evaluation of the extent of recurrent disease (resectability)
Evaluation of response to therapy
Benefits of PET Imaging
Impact on patient mgmt (identifies most appropriate course of treatment for a specific patient)
Avoid unnecessary biopsies or surgeries
Reduce patient risk, improves patient outcome
Determine patient response to therapy

30. PET in Oncology Conclusions
Every patient does not need PET, but many will benefit from the addition of PET into their staging/restaging work up
The information provided by PET and CT is complementary
PET is not perfect - there are false negative and false positive results
PET often changes the treatment plan, usually by avoiding futile surgery

31. PET in Oncology Conclusions
A negative PET scan usually eliminates the need for biopsy or surgery – avoid complications associated with unnecessary invasive procedures
A negative PET scan rules out cancer with a high degree of confidence
A positive PET scan usually indicates malignancy, but should be confirmed with biopsy
PET should be used to determine the extent of malignancy any time surgery or local radiation therapy is considered as the definitive treatment
The predictive or prognositic power of PET following therapy is greater than CT

32. Questions?
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