Using PET in Ovarian Cancer Place your logo here

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

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.

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.

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

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.

Characterization of Radiographic Abnormalities 61 year old woman with ovarian cancer and brain metastases treated with whole brain and stereotactic radiation

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.

Accuracy of PET in characterizing adrenal masses Differentiation of Benign from Malignant Adrenal Masses Sensitivity Specificity Yun 2001 100% (18/18) 94% (30/32) J Nucl Med 2001;42:1795 Erasmus 1997 100% (23/23) 80% (8/10) Am J Roentgenol 1997;168:1361 Maurea 1996 100% (7/7) 100% (6/6) Radiol Med 1996;92:782 Boland 1995 100% (14/14) 100% (10/10) Radiology 1995;194:131 3

Detection of a radiographically occult lesion 61 yr old man s/p partial colectomy for sigmoid cancer, rising CEA level to 44.8. 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

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

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

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

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

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

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

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

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

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

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):231-236

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):231-236

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):231-236

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

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

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

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

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

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

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

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.

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

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

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

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

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

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