1. Using PET in Breast 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. Using PET in Breast Cancer

17. Breast Cancer Role for PET and PETCT
Staging patients at initial diagnosis when distant metastases are suspected based on symptoms, labs or radiographic findings (staging a loco-regional advanced breast cancer)
Determining extent of disease at time of local recurrence, if information would affect choice of therapy (restaging a known recurrence)
Monitoring patients in chemotherapy or radiation therapy protocols (restaging at the completion of therapy, or response to therapy)

18. Breast Cancer Role for PET and PETCT
Increased use of breast conserving surgery requires
Close follow-up exams for early detection of recurrence:
Mammography has difficulty w/ implants or surgical scarring
And…only images breasts
Case example – recurrent breast cancer in lumpectomy scar, axillary & mediastinal mets, lung mets
Images courtesy of Macapinlac, UT MD Anderson Cancer Center

19. Breast Cancer Role for PET and PETCT
Restaging, evaluating extent of recurrent disease
39 yr old woman with Rt breast cancer (stage 2B ductal CA)
Treated w/ lumpectomy, chemo & XRT 10 months prior
PET performed to evaluate new palpable abnormality in surgical scar discovered by patient

20. Breast Cancer Role for PET and PETCT
Comparison of PET and conventional imaging in the evaluation of suspected recurrent breast cancer
Conventional imaging (combination of radiography, nm bone scan, CT, MRI, mammography & US – selected for each patient based on routine clinical management parameters)
PET sensitivity = 93% specificity = 84%
CI sensitivity = 79% specificity = 68%
PET NPV = 80% versus 59% for CI
PET also was a better predictor of disease free survival
Source: Vranjesevic, D. JNM :

21. Breast Cancer Restaging Suspected Recurrence
Case Study: Clinical History
50 year old with a history of infiltrating duct carcinoma of the left breast diagnosed 2001
Lumpectomy and left axillary dissection --thirteen lymph nodes were sampled, and none of them were involved with metastatic disease
Underwent adjuvant chemotherapy then adjuvant radiotherapy to the left breast.
Recently diagnosed with recurrent disease by a biopsy of a left supraclavicular node.
CT scan staging does not reveal any other areas of metastatic disease elsewhere.
Recommended radiation therapy to the left supraclavicular area.

22. Images courtesy of Todd Blodgett, MD, UPMC
Breast Cancer Restaging Suspected Recurrence
PET/CT Findings: Focal lesion posterior to the brachiocephalic vein consistent with mets. Intense area of focal FDG uptake in the left illiac crest. CT negative in correlative area. Consistent with metastatic bone disease.
Images courtesy of Todd Blodgett, MD, UPMC

23. Breast Cancer Restaging Suspected Recurrence
Management Change:
Her treatment was ultimately changed from local radiation to the supraclavicular area to systemic chemotherapy.
Added benefits of PET/CT:
Subtle abnormality detected posterior to the brachiocephalic vein that is barely visible on CT, but is certainly very compelling on the fused PET/CT image.
Large lesion in the right iliac crest that is not visible on the CT portion of the exam. It is not uncommon to find a lesion on PET, localize it to bone using PET/CT, but realize there is no bony destruction yet.

24. Breast Cancer Restaging Suspected Recurrence
Case Study: Clinical History
B mastectomies for breast CA
Treated with chemotherapy, tamoxifen, and radiation
Some shoulder pain but the bone scan does not show any uptake
Appears to be localized disease, parasternal nodal mass.
Her oncologist has recommended local radiation, is not recommending any additional chemotherapy aside from the hormonal therapy that she is receiving.
She is NOT a candidate for standard radiation due to prior radiation to this area.
Plan: stereotactic radio-surgery
Risk: damage to the aorta or the lung

25. Images courtesy of Todd Blodgett, MD, UPMC
Breast Cancer Restaging Suspected Recurrence
PET/CT identified a number of internal mammary lymph nodes that, although not enlarged, were involved with tumor.
Images courtesy of Todd Blodgett, MD, UPMC

26. Breast Cancer Restaging Suspected Recurrence
Management Change:
Therapy plan changed from local stereotactic radiosurgery to systemic chemo therapy.
Added benefits of PET/CT:
One of the benefits of combined PET/CT is the accurate identification of normal sized malignant lymph nodes.

27. Breast Cancer Response to Therapy
Neoadjuvant chemotherapy improves management of patients w/ locally advanced disease
Studies have shown that metabolic changes in breast cancer can be detected with PET as early as after the first cycle of chemotherapy, prior to any noticeable change in anatomic tumor size
Prediction of response supports the decision to continue dose-intensive preoperative or systemic therapies
Early recognition of ineffective therapy allows
A change to an alternative, more effective chemotherapy regime
Prevents prolonged treatment with ineffective drugs that have potent side effects

28. Breast Cancer Response to Therapy
22 patients studied – PET exam after first and second course of chemotherapy
FDG PET correctly identified all of the responders after the first course of chemotherapy. Response determined by 55% decrease in SUV (semi-quantified measure of uptake)
Sensitivity = 100%
Specificity = 85%
PET findings predicted histopathologic response
Accuracy of 88% s/p first course
Accuracy of 91% s/p second course
Source: Schelling M, el al, J Clin Oncology 2000; 18(8):

29. RTP and Breast Cancer

30. Why PET/CT in RTP? More precise anatomic localization
PET benefits from the anatomic framework provided by CT
Hypermetabolic lesions can be assigned to specific structures
Facilitate biopsy guidelines
Improves patient throughput – eliminates transmission scan for AC
Improves PET specificity
Improves interpretative confidence
More accurate staging results in:
More appropriate patient selection
More appropriate treatment course
Images courtesy of Todd Blodgett, UPMC

31. RTx Applications & Impact of PET Imaging
Radiation therapy plays an essential role in the interdisciplinary management of patients with breast malignancies
Accurate tumor staging is critical to determine appropriate treatment strategy (may not receive invasive surgical staging)
Curative radiation therapy requires
Absence of distant metastases
Locoregional lymph node metastases must be included in the radiation field
Optimized target volume & dose are critical when RT is main strategy for local or regional tumor control
RT will be futile if all tumors are not included within high-dose volume

32. Conventional anatomic imaging and RTP
Limitations of conventional imaging:
Requires a structural or morphologic change
Inability to identify disease in “normal” size lymph nodes
Evaluates a limited field of view, not entire body

33. Role of PET▪CT in RTP Improves accuracy of oncology staging
More appropriate patient selection for RTx
Fusion of PET & CT provides superior definition of the primary GTV, of nodal involvement & of distant metastases
Used to design more conformal radiation dose distributions based on functional tumor volumes
Ensure better dose delivery to gross tumor volume while avoiding critical normal tissues

34. Why PET▪CT for RTP? Change in GTV (>25%) PET/CT vs. CT
56% of cases, GTV was changed significantly if information from PET▪CT was used in RTP (202 patients)
Modification in GTV altered PTV (by > 20%) in 46% of cases
PET▪CT revealed distant mets in 16% of cases changing treatment from curative to palliative
Target volume
PTV
CTV
GTV
GTV: Gross tumor volume
CTV: Clinical target volume is the GTV and margin to include local sub clinical tumor spread.
PTV: planning target = CTV+ margin to ensure that CTV receives the prescribed dose.
Source: Ciernik, Dizendorf, et al, RTP w/ Integrated PET/CT. Int J. Rad Onc Biol Phys 2003;57(1):853

35. Impact of Whole Body FDG PET on Staging & Managing Patients for RTx
202 consecutive patients intended for RRT
Variety of malignant tumors
Radiation oncologists determined clinical stage of each patient’s tumor, proposed & documented initial management plan based on CI, surgical staging, clinical findings
Lymph nodes were considered positive if > 1cm
FDG PET scans were performed in all patients
All patients were assigned a post-PET tumor stage, discrepancies were biopsied or confirmed by additional imaging modalities
Radiation oncologists compared pre-PET and post PET tumor stages & determined changes in patient management
Source: Dizendorf et al, JNM 2003; 44(1):24-28

36. Impact of Whole Body FDG PET on Staging & Managing Patients for RTx
Diagnosis
Patients (N)
Patients with N
RX changes %
Head & Neck 55 18 33
GYN tumors 28 9 32
Breast CA 7 25
Lung CA 26 8 31
Lymphoma 24 5 21
GI tumors 4 22
Unknown 10 3 75
Melanoma 2 1 50
TOTAL
202 27
Source: Dizendorf et al, JNM 2003; 44(1):24-28

37. Impact of Whole Body FDG PET on Staging & Managing Patients for RTx
Pathologic Findings by PET in 202 patients
Over a broad range of clinical indications PET altered therapy planning in 55/202 patients (27%)
PET detected unknown nodal metastases in 25% of patients
PET detected unsuspected distant metastases in 12% of patients
Pathologic findings by PET
Newly detected disease by PET
Tumor
N = 120 25
12%
Lymph node metastases 50
Distant metastases 24
Source: Dizendorf et al, JNM 2003; 44(1):24-28

38. Proof Statements
Source: Ciernik, Dizendorf, et al, RTP with Integrated PET/CT. Int J. Rad Onc Biol Phys 2003;57(1):853

39. Breast Cancer PET/CT for RTP
Case Study: Clinical History
75 year old woman with a history of breast cancer 11 years ago and partial R mastectomy and ALND
Txd with initial XRT, Tamoxifen times five years
2002, she noticed what she describes as a parasternal lump
CT scan was done by her primary physician, that noted a nodular distention surrounding the sternun with soft tissue infiltrate
Patient underwent a needle biopsy which verified recurrence of breast cancer.
PET/CT done for RTP

40. Breast Cancer PET/CT for RTP
PET/CT Findings: Intense uptake within the R supraclavicular node, parasternal masses, R adrenal, posterior L thoracic rib, consistent with metastatic disease.
Images courtesy of Todd Blodgett, MD, UPMC

41. Breast Cancer PET/CT for RTP
Management Change:
Her treatment was ultimately changed from local radiation to the supraclavicular area to systemic chemotherapy.
Added benefits of PET/CT:
Identified several additional areas in the region not identified on CT.
Alters target volume for RT
Many radiation oncologists have been incorporating both the PET and CT data into their planning software to use both the metabolic and anatomic data to do their contouring.

42. Breast Cancer Conclusion: PET/CT for RTP
Metabolic imaging with FDG PET/CT improves accuracy of oncology staging/restaging over conventional imaging
FDG PET can be used to improve GTV calculations for radiation treatment planning
PET/CT can demonstrate changes to conventional treatment strategy resulting in improved cancer outcomes with pre- and post-RTx utilization

43. Breast Cancer Summary: Role of PET/CT
At initial staging when there is a high suspicion of advanced locoregional disease
At initial staging to clarify inconclusive findings on conventional imaging
Restaging – evaluation of suspicious or known recurrence (40% change in patient management)
Restaging – completion of therapy
Evaluation of treatment response

44. 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

45. 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

46. 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

47. 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

48. 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

49. Questions?
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