1. Using PET in Malignant Melanoma
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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. Melanoma
Problem:
Continuous rising global incidence over recent years due to changing exposure of the population to UV light
Increased awareness, improvements in skin screening & early detection have resulted in decreased mortality despite the annual increased incidence
Characterized by aggressive metastatic spread through the lymph system, in an unpredictable pattern, at a very early point in the disease

17. Melanoma
Problem:
Only curative treatment – early detection & surgical removal of the primary tumor and any isolated metastases, followed by chemotherapy
Prognosis is highly correlated with depth of invasion in the skin, the thickness of the melanoma at resection, and the presence of lymph node or distant metastases
No curative approach exists for disseminated metastatic spread
- experimental trials with various immunotherapy drugs

18. Melanoma Staging Thin lesions = Breslow thickness of < 0.75mm
Very low incidence of nodal or distant metastases
Intermediate thickness melanomas = 0.76–4.0 mm
25-57% incidence of lymph node metastases
8-15% incidence of distant metastases
Thicker melanomas > 4mm
62% likelihood of nodal metastases
72% likelihood of distant metastases
The prognosis for patients with malignant melanoma is highly correlated with the depth of invasion in the skin, the thickness of the melanoma tumor at the time of resection, and the presence of lymph node or distant metastases. Melanomas with a Breslow thickness of less than 0.75 mm have a very low incidence of nodal and distant metastases and thus PET is not used for staging of these patients. Intermediate-thickness melanomas ( mm) have a 25-57% incidence of lymph node metastases and an 8% to 15% incidence of distant metastases. Melanomas thicker than 4 mm have a 62% likelihood of nodal metastases and a 72% likelihood of distant metastases.
Source: Ann Surg 1981; 193:

19. Melanoma Staging Early stage, thin melanomas:
Surgical resection and pathologic examination of the sentinel lymph node (first node of the lymphatic bed draining a malignant tumor)
If sentinel node is free of tumor, the remainder of the nodes in that basin are likely to be disease free
Sentinel node biopsy is highly sensitive
Surveillance for recurrence

20. Melanoma Staging Intermediate – thick melanomas:
PET – most effective staging tool for assessing nodal spread & distant metastases
Assess entire skin surface & all organ systems for tumor invasion
MRI brain
In multiple studies of over 200 patients:
PET sensitivity & specificity between 83% and 91%
Conventional imaging: sensitivity of 88%, specificity of 75%
PET routinely detected numerous, new, unsuspected metastatic lesions – better assessment of tumor burden
Case management change in 26% of patients
Source: Gambhir et all. JNM 2001; 42:1S-93S

21. Melanoma Staging Study of 100 high risk patients (lesions > 1.5mm)
compared the accuracy of PET to conventional
imaging:
PET = 92%
Conventional imaging = 77%
CT was better for small lung lesions (87% vs 69%)
PET was better in the abdomen (100% vs 27%)
PET was better for cervical node metastases (100 % versus 66%)
Source: Cancer 82:9, pp

22. Melanoma Staging 53 y/o female with a history of
right calf melanoma, local
excision and skin graft
placement. Positive sentinel
lymph node biopsy. Evaluated
for extent of metastatic disease.
CT: no evidence of abnormal mediastinal or hilar lymph nodes
PET: multiple lesions in the mediastinum suspicious for metastatic disease. Trapezius muscle uptake, bilaterally - artifact
Images courtesy of Landis K. Griffeth, MD, PhD, North Texas Clinical PET Institute

23. Melanoma Restaging & Response to Therapy
PET:
Evaluate palpable lymph nodes discovered on physical exam
Clarify questionable lymph node findings identified by CT or ultrasound
Evaluate other abnormal findings on conventional imaging studies
Determine full extent of disease when surgery is considered for an apparent isolated metastasis
Monitor response to new immunotherapy & biochemical treatments (interleukin-2, GCSF, tomoxifen)

24. Melanoma Evaluate Extent of Recurrence
39 year old man with history of melanoma, chest xray showed a possible left lung nodule

25. Melanoma Restaging
52 y/o female with history of Rt inguinal melanoma. S/P resection of lesions with chemotherapy. Patient presents with recurrence in the Rt groin.
CT: post surgical changes in anterior-medial aspect of Rt thigh. No adenopathy or soft tissue mass identified. Findings could be related to radiation changes
PET: intense FDG uptake in Rt inguinal region, diffuse liver metastases, single splenic mets, probably Rt sternal or parasternal mets.
Surgery cancelled, high dose chemo
Images courtesy of
Landis Griffeth, MD, PhD, North Texas Clinical PET Institute

26. Melanoma Summary
PET:
Determine the stage of thick melanoma lesions at presentation
Assess nodal spread from lesions of intermediate thickness
Confirm recurrence of disease
Monitor response to treatment
Restage for extent of disease before surgical removal of any isolated metastases
Surveillance for high risk patients

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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