1. Using PET in Colorectal 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-year-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. Colorectal Cancer Problem:
149,000 new cases annually in U.S. – 50,000 deaths
3rd most common cause of cancer death in both men and women
Primary treatment for colon cancer is surgery with a 50% 5-year survival
Adjuvant chemotherapy (prior to tumor removal) to treat micrometastases has become more common
Following “curative” resection for primary colorectal cancer, ~75% patients recur within 2 yrs
Sources: American Cancer Society. Cancer Facts & Figures 2008
Gambir, S. J Nucl Med 2001; 42:1S-93S

17. Colorectal Cancer Diagnosis:
Screen patients with positive fecal occult blood tests for the presence of polyps or masses with air contrast barium enema examination of colon
Complete colonoscopy with biopsy to confirm or exclude cancer
CT and transrectal ultrasound are used for the preoperative diagnostic work-up and initial staging evaluation
Surgery may be necessary, despite distant metastases to correct bleeding and/or obstruction

18. Colorectal Cancer Initial Staging
Accurate staging is necessary before surgery is
planned for assumed locoregional disease:
Avoid unnecessary operations & surgical risks
Identify patients who might benefit from preoperative therapies
Identify patients who might benefit from resection of an isolated metastasis at initial surgery
CT sensitivity = 85% for detecting liver metastases
CT sensitivity = 33-94% for detecting non-liver mets (lymph nodes or other organs)
Source: Abdel-Nabi H, Radiology 1998; 206(3):

19. Colorectal Cancer Initial Staging
Limitations of anatomic staging result in:
A significant number of patients, thought to be candidates for curative surgery, found to have nonresectable disease during surgical exploration
Addition of PET to preoperative staging evaluation:
Improves surgical candidate selection
Higher sensitivity for detecting liver mets = >95%
Higher sensitivity for detecting distant mets = 33-95%
Neither CT nor PET reliably detected lymph node metastases when compared with a surgical gold standard
Source: Abdel-Nabi H, Radiology 1998; 206(3):

20. Colorectal Cancer Staging
60 year old man, with a history of colorectal cancer with two stable low density lesions seen on a prior CT scan.
The hypodense lesions in the liver demonstrated marked FDG activity.
Also noted is a left retrocrural node with marked FDG activity. Multiple mediastinal nodes are identified with FDG activity: subcarinal, paratracheal, AP window, and prevascular.
This patient would have been a candidate for radiofrequency ablation, but management was subsequently changed from surgical considerations to chemotherapy.
MIU CO11R. This 60 year old man, with a history of colorectal cancer was referred for evaluation of possible metastatic disease. A previous CT, identified two small hypodensities in the liver, but these had been stable in appearance.
The PET/CT scan revealed that the hypodense lesions in the liver demonstrated marked FDG activity. Which were determined to be metastatic lesions (bottom).
However, in addition to the liver lesions, the patient was found to have multiple supraclavicular and mediastinal metastatic lymph nodes (top). The patient would have been a candidate for radiofrequency ablation or wedge resection of the liver lesions without the small distant lymph nodes. Hi treatment was subsequently changed from surgical consideration to chemotherapy.
Images courtesy of Todd Blodgett, MD, UPMC

21. Colorectal Cancer Restaging Recurrence
Problem:
55% of patients will recur in the first year after “curative” resection
75% will recur during the first 2 years
Long term survival is dependent on very early identification and treatment
Surgical excision of isolated metastases remains best option for cure
Sites for recurrence: liver (30%), anastamosis site, locally in colon/rectum, regional lymph nodes, or in other distant organs

22. Colorectal Cancer Restaging Recurrence
Role for PET:
Characterization of abnormal CT or US findings
Benign versus malignant liver lesions
Recurrent tumor versus surgical scar or radiation changes
Identify sites of disease in patients with abnormal tumor marker levels (CEA) and negative conventional imaging
Differentiate patients with nonresectable (wide spread) disease from patients with isolated, resectable recurrence
Monitoring response to therapy

23. Colorectal Cancer Restaging Recurrence
54 yr old man with adenocarcinoma of the sigmoid colon 6 years ago.
Presacral recurrence 4 years ago that was resected and treated with XRT post operatively.
CT 1 month ago showed an enlarging mass. PET scan demonstrated focal area of increased uptake, biopsy proven recurrent adenocarcinoma

24. Colorectal Cancer Restaging
70 year old man, with a history of colorectal cancer who underwent resection, chemotherapy, and radiation therapy. Presented with rising CEA level. CT scan was read as negative 2 weeks prior.
Intense focal area of FDG uptake in the left pelvis.
This is a good example of the ability of PET•CT to detect occult disease, when a patient has rising tumor markers and a negative or equivocal CT scan.
MIU CO 09R. 70 year old man, with a history of colorectal cancer who underwent resection, chemotherapy, and radiation therapy. Presented with rising CEA level. CT scan was read as negative 2 weeks prior.
Intense focal area of FDG uptake in the left pelvis.
This is a good example of the ability of PET•CT to detect occult disease, when a patient has rising tumor markers and a negative or equivocal CT scan. Often times, we will find small area of tumor involvement that either aren’t visible on CT or are equivocal findings on CT alone.
Images courtesy of Todd Blodgett, MD, UPMC

25. Colorectal Cancer Restage / Guide Biopsy
History: 70 year old male with a history of colorectal cancer status post resection, chemo and radiation therapy. The patient had rising CEA levels and a CT which showed equivocal presacral soft tissue that had been stable for over a year.
Findings: Abnormality that correlated with presacral soft tissue. Appeared only a focal area within the mass was metabolically active, which may account for the initial negative biopsy.
MIU CO 04A. 70 year old male with a history of colorectal cancer status post resection, chemo and radiation therapy. The patient had rising CEA levels and a recent CT which showed equivocal presacral soft tissue that had been stable for over a year and was thought to represent post treatment changes.
Because his CEA level started to rise, a CT guided biopsy was performed which was negative. The patient then was referred for a PET/CT scan. By looking at the PET portion of the exam, it was clear there was an abnormality and it appeared that it correlated with that presacral soft tissue. After inspecting the fused image, it was clear why the first biopsy might have been negative. It appeared that there wasn’t microscopic disease throughout the presacral mass, it appeared that only a focal area within the mass was metabolically active. In retrospect, there was a very subtle difference in attenuation, but this was not picked up prospectively.
This patient subsequently was sent for a CT-guided biopsy directed at the focal area of hypermetabolism. Fused images were printed and the radiologist took 4 samples with his needle as close to the metabolic abnormality as possible, which finally yielded the diagnosis of recurrence adenocarcinoma of the colon.
Images courtesy of Todd Blodgett, MD, UPMC

26. 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

27. 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

28. 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

29. 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

30. 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

31. Questions?
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