1. Using PET in Ovarian Cancer
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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. Ovarian Cancer Problem
21,650 new cases diagnosed and 7,470 deaths annually
Accounts for 3% of all cancers in women
Tumors are symptomatic only at late stages
2/3 of patients present with stage III disease at initial diagnosis
Prognosis
Tumor stage, residual tumor mass s/p surgery, histology, cytology and CA 125
Overall 5 yr survival ranges between 45%
90% in stage I
30% in stage IV
Source: American Cancer Society. Cancer Facts and Figures 2008

17. Ovarian Cancer Diagnosis & Staging
No screening exams for early detection exist
Detected incidentally during ultrasound exam or during general physical
Clinical evidence of advanced tumor progression
Unspecific abdominal pain, uterine bleeding, weight loss, ascites
Preoperative staging includes detailed ultrasound, cystoscopy, sigmoidoscopy, barium enema, chest xray, tumor marker measurements
CT is important for detailed preoperative planning, initial staging accuracy is 70-90%
Grunwald et al, “Ovarian Cancer” from Wieler, H. PET in Clinical Oncology. Springer 2000

18. Ovarian Cancer Diagnosis & Staging
Anatomic imaging is unable to detect microscopic disease
Laparotomy is performed in all cases of suspected ovarian cancer
Extended surgery is required for tumor resection, debulking and accurate staging of regional lymph nodes
Goal, stage I: surgical removal of all malignant cells
Goal, stage II-IV: tumor debulking, confirmation of stage, chemotherapy
Role of PET in diagnosis & initial staging is under evaluation
Grunwald et al, “Ovarian Cancer” from Wieler, H. PET in Clinical Oncology. Springer 2000

19. Ovarian Cancer Diagnosis
56 yr old with severe abdominal pain, elevated CA-125
PET ordered to confirm diagnosis & evaluate extent of disease
PET demonstrates extensive metastatic disease in liver, abdomen and pelvis
Images courtesy of Northern California PET Imaging Center

20. Ovarian Cancer Recurrence
50% of ovarian cancer patients recur within 1st yr, an additional 25% recur in the 2nd yr following surgery
Ovarian cancer spreads along the surfaces rather than through direct infiltration of adjacent tissues
Peritoneal implants lead to silent, occult dissemination
Requires frequent, careful medical monitoring – ultrasound monthly during 1st yr, sensitivity of ~ 60-90%
Tumor markers, only if positive preoperatively
CT and MRI detect only 40-50% of recurrent tumors
Patients with negative findings receive second-look laparotomy for clinical restaging and possible tumor resection at 1 yr
Positive “second-look” patients receive additional chemotherapy and radiation therapy, or both – limited success
Hubner K, “Discussions in PET Imaging PET and Ovarian Cancer.”
Schweitzer S, Applied Radiol Oct 2000; 29(10)
Hubner K, Clin Pos Imag 1999; 2(6) 346
Jimenez-Bonilla J, Clin Pos Imag 2000; 3(6):

21. Ovarian Cancer Recurrence
Laparotomy – limitations
Associated with some morbidity
Expensive
Not always accurate at confirming presence or absence of disease – false negative rate of 35%
The mesentery, peritoneum and regions obscured by adhesions may be inaccessible – incomplete exams
Often leads to more extensive exploratory surgery
Hubner K, “Discussions in PET Imaging PET and Ovarian Cancer.”
Schweitzer S, Applied Radiol Oct 2000; 29(10)
Hubner K, Clin Pos Imag 1999; 2(6) 346
Jimenez-Bonilla J, Clin Pos Imag 2000; 3(6):

22. Ovarian Cancer Recurrence
Role of PET
Extremely sensitive in identification of recurrent tumor
Published studies demonstrate PET confirmed disease in over 80% of ovarian cancer patients
Identify patients who are not surgical candidates
Identify patients who should receive chemotherapy
Studies by Hubner, et al. recommend patients w/suspected recurrence based on CT, w/tumors < 2cm that are FDG positive would not require debulking surgery and could be treated with chemotherapy
Patients with positive PET and CT nodes < 1.5 cm could also forgo laparotomy and proceed directly to chemotherapy or intraperitoneal radionuclide treatment
Hubner K, “Discussions in PET Imaging PET and Ovarian Cancer.”
Schweitzer S, Applied Radiol Oct 2000; 29(10)
Hubner K, Clin Pos Imag 1999; 2(6) 346
Jimenez-Bonilla J, Clin Pos Imag 2000; 3(6):

23. Ovarian Cancer Recurrence
Role of PET
15-17% of patients, PET altered course of treatment by identifying whether to continue or change chemotherapy or recommend or negate second-look operations
Useful in detecting disease in patients with elevated tumor markers and negative conventional imaging
Useful in the evaluation initiate or change treatment
Gain valuable time when PET indicates treatment is ineffective
Of response to therapy
Source: Gambhir et al. JNM 2001; 42:1S-93S

24. Ovarian Cancer Recurrence
History: 60 yr old with history of ovarian CA, s/p resection, chemo and XRT. “Stable” soft-tissue density on CT over last year but rising tumor markers.
PET Findings: Focal para-aortic lymph node (1.5 cm). Focal uptake in abdominal wall (subtle soft tissue fullness). Hepatic focus of uptake. Confirmed metastatic disease
Images Courtesy of Todd Blodgett, MD, UPMC

25. Ovarian Cancer
64 year old female with remote history 16 years ago of ovarian cancer, s/p TAH / BSO / chemo and recurrence 10 years ago, monitored yearly by tumor marker. Now with elevated CA-125 and neg. CT scan 1 week prior to PET/CT.
The PET/CT scan revealed recurrent disease, and a follow-up scan 6 mos. later after completion of chemotherapy, showed complete resolution of the metastatic mesenteric implant.
Images Courtesy of Todd Blodgett, MD, UPMC

26. Ovarian Cancer Recurrence
55 year old female with a history of ovarian cancer, s/p resection and chemo found to have rising CA-125 levels but negative CT.
Findings: Focal area of intense FDG uptake not visualized on CT. Patient was sent for CT-guided biopsy w/o images. Radiologist unable to locate the tumor to biopsy. The patient left the hospital.
One year later the patient returned to hospital for PET/CT scan which revealed wide spread disease.
Images Courtesy of Todd Blodgett, MD, UPMC

27. Ovarian Cancer Baseline prior to Therapy
Images courtesy of Waxman, MD

28. Ovarian Cancer 8 months post therapy
Images courtesy of Waxman, MD

29. Ovarian Cancer PET Summary
Most cost-effective imaging procedure for detecting residual or recurrent ovarian cancer
May detect presence of disease better than laparotomy or laparoscopy
Combination of PET and CT/MRI provides the highest accuracy for identification and exclusion of disease
May miss microscopic tumor foci, but large bulky tumors & peritoneal carcinosis are rarely missed
Negative PET may avoid exploratory laparotomy
Assists physician in determining whether surgery of chemotherapy is the appropriate treatment

30. Does Insurance cover PET in Ovarian Cancer?
Medicare will cover, ONLY if the patient and the PET Provider are participating in the FDG registry.
More details will follow on this and the results of CMS proposed National Coverage Determination in April of 2009.
Private payers may cover on a case by case basis.

31. 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

32. 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

33. 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

34. 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

35. 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 prognostic power of PET following therapy is greater than CT

36. Questions?
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