1. Using PET in Cervical 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. Cervical Cancer Problem: Accounts for 6% of all malignancies in women
Estimated 16,000 new cases of invasive cancer of the cervix per year with ~ 5,000 annual deaths in the US
Overall mortality has decreased due to early detection and treatment of pre-invasive disease
Mortality of invasive cervical cancer has not changed in 30 years
Prognosis:
Determined by extent of disease at time of initial diagnosis
Affected by patient age at diagnosis, performance status, primary tumor size, presence of para-aortic & pelvic lymph node metastases

17. Cervical Cancer Diagnosis and Staging
Combination of physical exam
Palpation, biopsy, conization, colposcopy, cystoscopy, sigmoidoscopy
Conventional radiographic exams
Chest and bone radiographs, IVP, barium enema
Clinical tools have limited accuracy in more advanced disease
68 – 83% in Stage IB
33 – 50% in Stage II - IV

18. Cervical Cancer Diagnosis and Staging
CT and MRI
Useful in assessing tumor size, depth of stromal invasion, stage of disease, presence of lymph node metastasis
CT - overall staging accuracy of 58 – 88%
Sensitivity of only 44% for detection of nodal mets
Unreliable in evaluation of tumor size and identification of early parametrial invasion
MRI – most accurate imaging modality for assessing tumor size and level of invasion
Accuracy of 80-92%
Sensitivity for nodal mets similar to CT – 50%

19. Cervical Cancer Diagnosis and Staging
GYN Oncology Group Study evaluated detection of para-aortic lymph node mets by US, CT and lymphangiography at initial staging. Surgical confirmation of all imaging findings.
Lymphangiography – sensitivity 79%, specificity 73%
CT – sensitivity 34%, specificity 96%
US – sensitivity 19%, specificity 99%
Limitations of current imaging techniques - basis for expanded coverage by CMS for initial staging of newly diagnosed cervical cancer patients in whom conventional imaging is negative or equivocal – PET has high sensitivity for detection of nodal disease

20. Cervical Cancer Key indicators of Prognosis > Staging
> Volume of primary tumor
> Histopathological grade of primary tumor
> Presence of lymph node metastasis
Spread of lymph node metastasis- PelvicPara AorticDistal
Primary cervical cancer- Squamous cell carcinoma – High FDG avidity in primary and metastases

21. Cervical Cancer Role for PET and PET/CT
Diagnosis / Staging - squamous and non-squamous cell cervical cancers are FDG avid
May require modified imaging technique to reduce interference from physiologic activity in the urinary tract (post void images, use of diuretics, in some cases bladder catheterization)
Reported sensitivity of 86-91% for detection of primary cervical cancers
More accurate detection of lymph node metastasis
PET – sensitivity of 86%, specificity of 100%
Compared with surgical staging of para-aortic lymph nodes, PET demonstrated sensitivity of 75% and specificity of 92%
Sensitivity of PET in identification of pelvic lymph node disease was greater than para-aortic nodes
Sagawara Y., et al, J Nucl Med, Vol 40, No 7: p (1999)
Rose P., et al, J of Clin Oncool, Vol 17, No 1: p (1999)

22. Cervical Cancer Role for PET and PET/CT
Accurate staging of the para-aortic nodes allows modification of the radiation therapy fields to include the diseased nodes which are not routinely part of the treatment field
PET has a distinct advantage for restaging patients with distorted anatomy following surgery and/or radiation therapy
Since metabolic changes precede anatomic changes after effective therapies, PET could prove to be an early and reliable marker to assess treatment response
CT and MRI have difficulty in assessing treatment response after radiation therapy or radiation implants

23. Cervical Cancer Staging Primary
PET shows higher sensitivity than CT for detection of nodal mets
Accuracy of PET in detecting Para aortic node mets with - CT
50 pts with locally advanced Ca Cx & - Abd CT
FDG PET compared to surgical exploration FDG PET Sensitivity 85.7% Specificity 94.4% Accuracy 92%
Comparison of PET and CT for lymph node metastasis in CA Cervix
101 consecutive pts with Ca Cervix underwent PET and CT and f/up
> Pelvic node metastases- PET 67% CT 20%
> Para Aortic node mets- PET 21% CT 7%
> Supraclavicular mets PET 8% CT 0%
Presence of paraaortic node mets on PET most important prognostic indicator
Lin et al Gynecol Oncol 89:
Grigsby et al J Clin Oncol Sep 1;19(17):3745-9

24. Cervical Cancer Staging
Lymph node metastasis in patients with clinical early stage Cervical Cancer: Detection with integrated FDG PET/CT
47 consecutive Ca Cervix patients underwent FDG PET/CT before radical hysterectomy with PLND
32% pts had metastatic lymph nodes confirmed by histopathology
Sensitivity Specificity PPV NPV Accuracy
PET/CT % % % % %
(for all nodes)
PET/CT % % % % %
(for nodes>0.5cm)
PET/CT method of choice in primary staging of Cervical CA especially for pelvic and para-aortic nodal mets
Sironi et al Radiology 238 Jan 2006

25. Cervical Cancer Staging
37 year old with a history of recently diagnosed cervical cancer for staging PET and XRT planning. PET/CT revealed heterogenous uptake in the uterus,
intense uptake in the cervix and uptake in the R adnexal area (probable malignant node uptake). Surgical excision of adnexal node showed negative pathology. In view of PET/CT results, subsequent review of pathology taking fine cuts through the lymph node, showed positive for recurrence.
Images courtesy of Todd Blodgett, MD, UPMC

26. Cervical Cancer Restaging
Value of FDG PET in local recurrence & nodal metastases
20 pts underwent FDG PET for detection of local recurrence & nodal metastases.
PET Sensitivity Specificity
Overall % %
Local Recurrence % %
Pelvic node mets % %
Para aortic node mets % %
Distal metastases % %
Sun et al. Anticancer Res Jul-Aug;21(4B):

27. Cervical Cancer Restaging
PET in detection of recurrent cervical CA
Recurrence rate of cervical cancer- 6.5% after surgery & 26.2% after RT
60% of recurrences occur within two years of completion of primary therapy
249 pts with no evidence of disease at end of therapy evaluated retrospectively for detection of early recurrence with FDG PET
80 pts (32.1%) showed + lesions with FDG PET,
28 pts (11.2%) were confirmed as having recurrences.
FDG PET- Sensitivity 90% Specificity 76% for detection of early recurrence
Sensitivity higher for recurrence in spine, liver, mediastinal, hilar and scalene nodes
Ryu et al J Nucl Med Mar;44(3):
22 pts of cervical CA evaluated for recurrence with FDG PET
Tissue biopsy and clinical follow up indicator of true recurrence
PET True True – 13
PET False False – 2
PET Sens 85% Spec 86% PPV 85% NPV 86% for detection of recurrence
Havrilesky et al. Gynecol Oncol Jul;90(1):186-90

28. Cervical Cancer Restaging
PET vs CT in detection of recurrent Cervical CA
36 pts with clinically suspected recurrence underwent PET & CT
18 pts confirmed for recurrence by histopathology & follow up
TP FP FN TP Sens Spec Accu
CT % 83% %
PET % 94% %
False + CT due to radiation necrosis
False – CT due to metastatic nodes smaller than 1 cm
Park DH et al. Korean J Radiol Jan-Mar;1(1):51-5.

29. Cervical Cancer Restaging
76 yr old with locally recurrent cervical cancer, CT shows pelvic adenopathy,
scheduled for pelvic exenteration. PET positive for disease beyond pelvis.

30. Cervical Cancer Restaging Recurrent Disease
43 year old female, 9 mos. post hysterectomy for cervical cancer, restage.
Enhancing mass with abnormal glucose metabolism in the left pelvis consistent with recurrent cervical cancer involving the left aspect of the vaginal cuff and contiguously involving left ovary. Additional solitary left iliac chain nodal metastasis revealed on FDG PET images.
Left iliac chain nodal metastasis
Images courtesy of Dr. P. Shreve, Grand Rapids, MI

31. Cervical Cancer Restaging
42 year old female with a history of cervical cancer, s/p resection, for XRT planning. Staging clinical CT showed few paraaortic nodes.
PET/CT showed near complete resolution of the paraaortic nodes and complete resolution of L pelvic sidewall node.
Images courtesy of Todd Blodgett, MD, UPMC

32. Cervical Cancer Prognosis
PET in prediction of survival in cervical cancer
76 pt reviewed – all pre and post therapy FDG PET
Normal Post therapy FDG PET- 86% progression free 2 yr survival
Persistent FDG PET positive lesions – 40% progression free 2 yr survival
New hypermetabolic sites on FDG PET- 0% progression free 2 yr survival.
Grigsby et al. Int J Radiat Oncol Biol Phys 55:

33. Cervical Cancer Summary
PET increases accuracy for detecting lymph node metastasis in patients with advanced-stage cervical cancer
Fusion with anatomic images, CT and/or MRI, ensures accurate localization of increased uptake
Predicts both the presence and absence of pelvic and para-aortic nodal metastatic disease
Presence of nodal disease alters therapeutic management of patients – surgery, radiation therapy and/or chemotherapy – affects patient outcomes
PET uniquely valuable in evaluation of the response of primary cervical cancer and lymph node metastasis to radiation therapy and chemotherapy
May have value for surveillance of patients after initial therapy to detect asymptomatic recurrence
PET imaging approved 2005 for initial staging of cervical cancer when CI negative. Many commercial insurance companies approve PET for these cancers with documentation of medical necessity.

34. Cervical Cancer Conclusion
PET stages cervical cancer with high diagnostic accuracy
PET/CT is superior to any conventional imaging modality for staging and follow up
PET or PET/CT should be used to monitor the effects of treatment and the course of the disease
PET provides important prognostic information
PET/CT impacts patient management cost-effectively

35. 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

36. 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

37. 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

38. 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

39. 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

40. Questions?
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